Regulations (Preambles to Final Rules) - Table of Contents Regulations (Preambles to Final Rules) - Table of Contents
• Record Type: Air Contaminants
• Section: 6
• Title: Section 6 - VI. Health Effects Discussion and Determination of Final PEL

VI. Health Effects Discussion and Determination of Final PEL

A. General Principles of Toxicology and Dose Response

Introduction

As long ago as the 16th century, people recognized that there is no such thing as an absolutely safe chemical. The Swiss physician Paracelsus, who lived from 1493 to 1541, said:

All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.

On the other hand, methods have been devised to permit any chemical, no matter how poisonous, to be handled safely; this is done either by limiting the dose or controlling the exposure. However, before the necessary degree of control can be determined for a particular exposure or situation, the toxicity of the substance in question must be known. The paragraphs that follow describe the methods used by scientists to measure the relative toxicity of substances and to select exposure limits that will prevent exposed individuals from suffering adverse effects from such exposures. As this discussion demonstrates, methods of choosing exposure limits must, because of the lack or inadequacy of dose-response information for many chemicals, rely on experience in the use of these substances and on scientific and professional judgment(1).


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  Footnote(1) The material in this section derives principally from the following sources: Klaasen, Amdur, and Doull 1986; National Research Council 1986; Cohen 1986a, b; and Tardiff and Rodricks 1987.


Chemicals range in inherent toxicity from those that are relatively harmless even after large doses have been administered to others that cause death if encountered even in small quantities. Toxicologists rank chemicals by categories that range from practically nontoxic (an adult human would have to consume a quart) to supertoxic (fewer than 7 drops would be lethal for most people).

In the occupational setting, it is the risk associated with a particular use of a chemical rather than its inherent toxicity that is important. Risk can be defined as the probability that a substance will produce harm under certain conditions of use. The converse of risk is safety, which is the probability that no harm will occur under specific circumstances.

The degree of hazard associated with exposure to a specific substance depends on the manner in which it is handled in a particular situation: a supertoxic chemical that is processed in a closed, isolated system may be less hazardous in actual use than a low-toxicity compound handled in an open batch process. Another factor affecting the ability of a chemical to elicit a toxic response is the susceptibility of the biological system or individual. For the relative degree of hazard to be known in a particular instance, this requires knowledge about the chemical agent, the exposure situation, and the exposed subject. In addition, the route of administration and the duration and frequency of exposure must be known.

Route of Exposure

There are four principal routes of exposure by which toxic substances can invade humans or animals. These are inhalation, ingestion, dermal absorption, and parenteral administration (i.e., administration through routes other than the intestinal canal). The route of administration of a toxin also affects the relative toxicity of the agent. For example, a chemical that can be detoxified in the liver will be less toxic if it is administered orally than if it is given systemically (i.e., inhaled). Studies that provide information about the relative toxicity of an agent via different routes of exposure can provide a considerable amount of information about the absorbability of the agent. For example, if exposure to a certain dose of a chemical via all routes of administration causes death within the same time period, it can be assumed that the substance in question is easily and rapidly absorbed. On the other hand, if the dermal dose of a chemical that is required to kill a subject is much higher than the dose required to produce the same effect when the chemical is ingested, one can deduce that the skin provides, to some degree, a barrier against that agent's toxicity. Other, less important, elements affecting the response to a toxic substance include the relative concentration of the substance, the volume of the vehicle used to administer the chemical, the chemical and physical properties of the vehicle, and the dose rate (i.e, the period of time over which the dose is administered).

Duration and Frequency of Exposure

Scientists conduct animal experiments that involve four different types of exposure: acute, subacute, chronic, and subchronic. Acute exposures are limited to periods of less than 24 hours and can involve either single or repeated exposures within that period. Subacute exposures are repeated exposures that last for one month or less, while subchronic exposures have a duration of one to three months. When a research project having a chronic regimen is conducted, the test animals are dosed repeatedly for a period lasting more than three months. Animals exposed acutely can have both immediate and delayed-onset responses. Similarly, chronic exposures can cause immediate reactions as well as long-term effects.

The frequency of dosing also has an important influence on the magnitude of the toxic effect: a large single dose of an acute toxin will usually have more than three times the effect of one-third the dose given at three different times, and the same dose administered in 10 or 15 applications might have no effect whatsoever. The pattern of dosing is important because it is possible for some of the substance to be excreted between successive administrations or because the lesion caused by the toxin has a chance to be partially or completely repaired between applications. Thus a chronic effect is said to occur: (1) if a toxic substance accumulates in the system of an exposed person or animal because the dose absorbed is greater than the body's ability to transform or eliminate the substance; (2) if it produces adverse effects that are not reversible; or (3) if it is administered in a manner that permits inadequate time for repair or recovery.

Variation in Response

Responses to toxic insults vary in a number of ways. For example, some toxicants have immediate effects, while others are associated with delayed symptom onset. The latency period for carcinogenic agents may be as long as 40 years for some types of cancer, and even some acute agents, such as some chemicals that have adverse ocular effects, may not cause overt symptoms until hours after exposure.

Another difference in type of response concerns the reversibility or irreversibility of the effect. Reversibility depends on the site of action as well as the magnitude of the insult. That is, some tissues of the body, such as the liver, have considerable ability to regenerate; others, like the kidney or central nervous system, do not.

The site of action associated with toxic substances also varies widely. Local effects are those lesions caused at the site of first contact between the agent and the organisms. Examples of localized effects are skin burns caused by contact with a caustic substance and site-of-contact tumors that develop at the locus of the injection of the carcinogen.

In contrast to localized effects, systemic effects involve the absorption and distribution of the toxic agent from the point of entry to a distant site; the toxic response is manifested at this distant point. An example of a systemic poison is mercury, which produces its toxic effect on the central nervous system. Often, the site of deposition for a chemical is not the organ system most affected by the toxin. For example, although lead is deposited and concentrated in the bone, it affects the central nervous system. Any sites that are adversely affected by the toxic effects of exposure to a substance, whether they are sites of contact or distal sites, are called the target organs of toxicity.

In cases of systemic poisoning, the system most often affected is the central nervous system (CNS); it is common for the CNS to be involved even when another target, such as the liver, is the primary target organ of toxicity. In descending order of frequency, the systems or organs most often involved in cases of systemic poisoning are the central nervous system, the circulatory system, the blood and hematopoietic system, the visceral organs (liver, kidneys, lungs), and the skin.

Dose-Response

The relationship that associates the dose of a chemical with the effects it causes is called the dose-response relationship. A single data point relating a dose to a response is sufficient to establish a dose-response relationship. As additional data become available, it is possible to expand our understanding of the dose-response relationship to cover a range of doses or exposures. Dose-response is an important principle in toxicology, and an understanding of dose-response is important in establishing occupational or other exposure limits. Knowing how toxic substances act makes it easier to predict the potential effects of exposure. (It is, of course, generally true that lowering dose reduces response, and data are often available to demonstrate that lower doses reduce responses, at least on the grossly observable level. However, data showing that more subtle responses (e.g., those at the subcellular level) have been reduced are rarely available.) To apply dose-response relationships, it is helpful if several types of data are available. First, it must be possible to relate a response to a particular chemical. Although basic data pointing toward causality may be available, it is often difficult to refine the dose-response relationship further. For example, epidemiological studies often identify an association between a disease and one or more causative agents. However, since information on the precise identity of the etiologic agent, the actual dose received, and the true site of the response is usually not available, it is often impossible to use data from epidemiological studies to establish a precise dose-response relation between a specific dose of a toxin and an effect.

The second condition to be met before dose-response can be established is that it must be possible to relate the response to the dose. It is relatively easy to determine that a large dose causes an obvious response. Refining the relationship, however, involves three other requirements: (1) that there be a receptor site; (2) that the response and the intensity of the response be related to the concentration of the toxin at the receptor site; and (3) that the concentration of the toxin at the site be related to the dose given.

The third principle underlying the concept of dose-response is that there must be a quantifiable means of measuring the toxicity of a substance and a method of expressing this measured toxicity. Although lethality in test animals is often used to measure toxicity, the best form of measurement would involve quantification of the sequence of molecular events occurring during the toxic response. In the absence of such endpoints, other good methods are available. For example, it is common to measure an effect believed to be related to the substance in question. The level of activity of an enzyme in the blood is often used as a measure of effect, e.g., serum glutamic-oxaloacetic transaminase (SGOT) levels are used to measure liver damage. Many different endpoints can be used to measure toxic effects, such as changes in muscle tone, heart rate, blood pressure, electrical activity of the brain, motor functioning, and behavior.

The most widely used endpoint, especially when a new substance is involved, is lethality in an animal test system. Lethality studies allow scientists to make comparative assessments of a chemical's toxicity as it relates to that of many other substances. Research of this type also permits the gathering of essential information on dose, duration, route of administration, site of action, and the target organ of toxicity.

Form of the Response

The classic form of dose-response is sigmoidal (Figure 1). This form characterizes the relationship between the amount of a toxin administered and the degree of response to that dose. The response is measured on the ordinate, and the dose is represented on the abscissa.
Dose-response can be thought of in two ways:
As exposure increases, the proportion of the population that manifests the response increases (quantal response); and

As exposure increases, the intensity of an individual's response increases (graded response).

A relatively flat dose-response curve means that a large change in dose is required before there is a significant change in response. A steep curve, on the other hand, means that a small change in dose will elicit a large increase in response. Although it is sometimes possible to generate a curve of the type shown in Figure 1, it is not necessary to do so to demonstrate that exposure at a given level is associated with a particular response. That is, it is not necessary to have sufficient data to define, in mathematical terms, the dose-response relationship to know that exposure at a given level is associated with adverse consequences.


Figure 1 - Diagram of Dose-Response Relationship

(For Figure 1,
Click Here)


In the regulatory context, it is most common to express dose-response relations in terms of the percentage of the population responding. However, before this information can be evaluated, the endpoint being considered must be known. For every substance, there are several dose-response relationships, depending on endpoint: a substance that produces irritation at low doses may cause more severe symptoms or even death at high doses and in other conditions. For example, many substances that are mucosal irritants at low doses will produce pulmonary edema and nervous system effects at high doses.

Plotting the cumulative percentage of individuals responding against dose produces the typical sigmoid curve. Such a curve reflects the fact that at the lowest dose, zero percent of the population responds, while 100 percent of the population will respond at the highest dose. However, if the percentage responding is plotted against incremental rather than total dose, the curve produced is a normal distribution (Figure 2). This curve says that a relatively small percentage of the population will manifest the response at the lowest dose and that a similarly small percentage of the population will exhibit the effect only at the highest dose. What this normal distribution of response reflects is individual and species variation in exposed populations. A wide degree of variation occurs even in inbred, homogeneous laboratory animals, and such variability increases dramatically when a heterogeneous population, such as workers, is involved. Individuals responding at the left end of the curve shown in Figure 2 are hypersusceptible, while those at the right end could be termed resistant.


Figure 2 - Diagram of Quantal Dose-Response Relationship

(For Figure 2,
Click Here)


Because the relationship between dose and response is sigmoidal, response approaches zero as dose approaches zero. However, because of the mathematical form used to express this relationship, a true zero response can never be achieved. In the strictest sense, therefore, a true threshold dose level (i.e., the dose with which a zero response is associated) can never be established on the basis of experimental research. Instead, scientists attempt to define the minimum dose associated with a specific endpoint, which is customarily termed the "threshold" dose for that particular endpoint. However, unless a specific endpoint (such as respiratory irritation, cholinesterase inhibition, the development of a tumor, or death) is specified, the concept of a threshold is essentially meaningless. In fact, a separate threshold could be said to exist for each of these endpoints.

The extent to which an experimentally derived "threshold" actually reflects the true threshold for a substance (i.e., the level above which a response will occur and below which no response will occur) depends on several factors, such as the number of animals used to determine the experimental threshold, the number of dose levels tested, and the degree of variation represented in the test subjects. For example, to determine an LD(50) (the lethal dose that will kill 50 percent of the animals tested) with a high degree of precision requires the use of a minimum of 50 test animals and five dose groups (10 animals in each group). Other factors that can influence the magnitude of the median lethal dose include the sources involved, the sex and age of the animals, the environmental conditions prevailing during the test conditions, diet, the health status of the subjects being tested, and the subjects' past exposure to other toxic substances.

In toxicological research, the experimentally observed threshold dose is called the low-observed-effect level (LOEL) or the low-observed-adverse-effect level (LOAEL). Alternatively, the threshold may be expressed as the highest no-observed-effect level (NOEL), i.e., the highest dose administered and found not to produce a given response. Determination of an accurate NOEL requires both a careful interpretation of the toxicological data and the use of an adequate number of test animals. The National Academy of Sciences (1985) has concluded that the chance of finding a no-adverse-effect level (that is, of missing an adverse effect) at a given dose is statistically greater in experiments having a small number of animals than in studies involving a large number of animals. Thus, the degree of confidence one has that a NOEL actually represents a "safe" dose, rather than a research design artifact, increases with the number of animals tested. The greatest degree of confidence is associated with studies involving a large number of animals that were tested at several doses that were administered at close intervals.

In a recent publication (Tardiff and Rodricks 1987), David W. Gaylor of the National Center for Toxicological Research explained that experimentally derived thresholds represent statistical limitations in study design rather than biological characteristics:

The existence of dose-response relationships might lead one to assume incorrectly the existence of threshold doses below which no toxic effects could occur. As dosage is decreased, the prevalence of an observable toxic effect...diminishes to zero. Eventually, a dosage is reached below which the experiment has essentially no resolving power to distinguish between the spontaneous background rate and small induced toxic effects....

If no toxic effects are detected at a specified dosage, this dosage is called the no-effect, or more correctly the no-observed-effect dosage. Because of the limitations of any given experiment, the no-observed-effect dosage is not a precise estimate of a true no-effect level. Lack of statistical significance is not equivalent to no toxic effect. It may or may not be, and further experimentation would be required to resolve this equivocal issue.... The no-observed-effect level is not a biological property, but, rather, a statistical property or operational threshold that is highly dependent on sample size.

The scientific issues surrounding the concept of no-observed-effect levels or experimentally derived thresholds have important implications for their use in establishing protective occupational exposure limits. Because the no-observed-effect level cannot represent the "true" threshold for an adverse effect, given the design of most toxicologic studies, regulators and others have used the concept of safety factors (also known as uncertainty factors) to aid them in setting permissible exposure limits; that is, the exposure limit is established at some interval below the no-observed-effect level to provide additional assurance that exposed populations are not likely to suffer harm.

The size of the interval between the permissible exposure limit and the no-observed-effect level depends on a professional judgment as to whether the no-observed-effect level is likely to represent a level that is not harmful to humans. Thus, if the available data include a NOEL derived from a well-conducted human study, a smaller safety factor might be used to establish an exposure limit than would be used if the data to be used to establish the limit consisted of a NOEL from an animal study; in the latter case, there is greater uncertainty regarding the relationship between the animal NOEL and human NOEL. Safety factors have also been used to recognize the fact that the human population is heterogeneous and that there may be a wide variation in individual responses to toxic substances (the wide range in the odor thresholds reported for some substances is a good illustration of individual variability in response).

The use of NOELs, LOAELs, and safety factors to develop permissible exposure limits is not a recent development:

For more than half a century, evaluation of the safe use of chemicals has been focused mainly on the development of toxicity data and on the application of professional judgment to the ad hoc interpretation of such data to derive acceptable levels of exposure for humans. Generally, this practice has taken the form of identifying from studies in laboratory animals the no-observed-effect level and dividing it by a safety factor (usually 100 for NOELs derived from chronic studies) reflecting the uncertainties of relating data to humans under their conditions of exposure and the quality and appropriateness of the data base....

Safety factors are usually chosen prospectively to address the uncertainties of interspecies extrapolation. Although safety factors as small as 2 and as large as 2000 have been used...the safety factor of 100 is used most commonly, at least for NOELs derived from chronic toxicity studies, and incorporates adjustments for interspecies variability (usually 10) and intrahuman variability (usually 10).... The resulting value is equivalent to a NOEL in humans (Tardiff and Rodricks 1987, pp. 391, 421).

Tardiff and Rodricks caution, however, that the use of safety factors has been questioned because these factors "often create the impression that human population thresholds have been identified and that there is virtually no risk below that level of exposure" (Tardiff and Rodricks 1987, p. 421).

Although safety factors have traditionally been used to establish exposure limits for chronic or lifetime exposure situations, they have also been applied to establish limits for acute effects resulting from short-term exposure. The National Academy of Sciences' Committee on Toxicology has been using a safety-factor approach to establish emergency exposure guidance levels (EEGLs), which are exposure levels judged to be acceptable for military personnel performing tasks during emergency situations. An EEGL is not considered to be a safe exposure level for routine or normal operations, but these levels are considered acceptable when tasks must be performed to prevent greater risks (e.g., death or injury caused by fires or explosions). In developing EEGLs, safety factors are generally applied to account for uncertainties in the use of animal data and when extrapolating between different dose routes. The NAS also develops short-term public emergency exposure guidance levels (SPEGLs) to apply to the exposures of the general public to contaminants during airborne chemical releases; SPEGLs are generally set at a level of 0.1 to 0.5 times the EEGL (i.e., an additional safety factor of from 2 to 10) (Criteria and Methods for Preparing Emergency Exposure Guidance Level (EEGL), Short-Term Public Emergency Guidance Level (SPEGL), and Continuous Exposure Guidance Level (CEGL) Documents. Washington, D.C.: National Academy Press, National Academy of Sciences 1986).

The use of the safety factor approach in establishing occupational exposure limits was addressed by many rulemaking participants (Exs. 3-744, 3-1095, 8-16, 8-47, 116, and 144; Tr. 1-221, Tr. 2-163 to 2-164). NIOSH (Ex. 8-47) stated that safety factors cannot be used to estimate human risk and are therefore not related to the magnitude or significance of a risk; instead, NIOSH believes that safety factors are intended to reflect uncertainty in the available data. This comment echoes the observation made by Tardiff and Rodricks, i.e., that safety factors do not necessarily identify a human population threshold. NIOSH (Ex. 8-47) also endorsed the use of safety factors as a "pragmatic method" of developing standards (except when a nonthreshold process, such as the induction of cancer, is the outcome of concern). NIOSH also believes that "standards based on a margin of safety...as well as standards derived from a case-by-case evaluation, [should] be periodically reviewed to determine what new information is available" (Ex. 8-47).

Dr. Marcus Key, Professor of Occupational Medicine at the University of Texas School of Public Health, also testified on the appropriateness of using safety factors to establish occupational exposure limits:

We seldom, if ever, know with any precision where a significant risk level begins or ends; hence, the need for safety factors. Safety factors depend on several considerations,...mainly on toxicity and the nature of the health effects, but also on the availability of scientific evidence of effects at lower levels.

Professional judgment must be relied on in selecting safety factors, with one to three orders of magnitude being commonly used for serious effects, and 50 percent, or [a] safety factor of 2, [being used] for acute, less harmful effects (Tr. 1-221).

Both Dr. Key (Tr. 1-221) and Dr. Ernest Mastromatteo, Chairman of the ACGIH TLV Committee (Tr. 2-163 to 2-164) testified that safety factors are frequently used by the ACGIH to develop recommended exposure limits.

Some commenters (Exs. 8-16, 116, and 144; Tr. 7-121) were of the opinion that OSHA should adopt a uniform system of assigning safety factors to establish permissible exposure limits. For example, the Workers' Institute for Safety and Health (WISH) (Ex. 116, p. 13) commented that OSHA should review the toxicology profiles prepared by the Agency for Toxic Substances and Disease Registry (ATSDR), in which Reference Doses (RfD) are computed. The RfD, as described by WISH, is "an estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious effects during a lifetime" (Ex. 116, p. 13). The RfD is derived by applying uncertainty factors to experimentally derived NOAELs in a consistent manner. The uncertainty factors used by ATSDR include factors of 10 to account for each of the following:
* Human variation in response;
* Extrapolation from animals to humans;
* Extrapolation of effects associated with lifetime exposure from less-than-lifetime studies; and
* Additional uncertainty in relying on a LOAEL rather than a NOAEL.
In addition, ATSDR applies a factor of from 1 to 10 to account for the overall quality of the scientific evidence.

EPA uses the same approach to develop RfDs for noncarcinogens; EPA's application of this approach is described in a concept paper presented by the EPA Reference Dose Work Group (Ex. 144, Appendix A). As explained by the Work Group:

The RfD is useful as a reference point for gauging the potential effects of other doses. Usually, doses that are less than the RfD are not likely to be associated with any health risks, and are therefore less likely to be of regulatory concern ....Nonetheless, a clear conclusion cannot be categorically drawn that all doses below the RfD are "acceptable" and that all doses in excess of the RfD are "unacceptable" (Ex. 144, Appendix A, p. A-10).

The EPA has been compiling dose-response data and information on RfDs for almost 2,000 chemicals in a database called the Integrated Risk Information System (IRIS). The system is described by Dr. Rebecca T. Zagraniski, Assistant Commissioner of the Division of Occupational and Environmental Health, New Jersey Department of Health (Exs. 144 and 144A). In her posthearing submission, Dr. Zagraniski presents an analysis in which EPA RfDs from the IRIS system are converted to Workday Ambient Air Concentrations (WACs) for 43 of the substances included in this rulemaking. These WACs were then compared to OSHA's proposed PELs for the same substances. After converting the RfDs to equivalent lifetime occupational exposure levels, Dr. Zagraniski found that all but three of the resulting WACs were lower than 1 mg/m(3) and that the WACs for noncarcinogens were generally 100 to 1,000 times lower than the PELs being proposed by OSHA in this rulemaking. Dr. Zagraniski commented on these findings as they relate to OSHA's proposal:

The WACs are not recommended exposure limits because they do not take into account numerous significant considerations including feasibility, anecdotal reports of effects following human exposure, routes of exposure other than inhalation, and other critical information. Also, the WACs for non-carcinogens are based primarily on oral exposure studies. In some cases, there may be inhalation studies which are more appropriate for use in setting an occupational exposure guideline, but which were not discussed in IRIS due to their focus on the oral exposure route. In spite of these constraints, the WACs may be considered preliminary health-based guidelines which are useful as indicators that current PELs and TLVs may need reevaluation (Ex. 144A, p. 4).

In response to Dr. Zagraniski's comments, OSHA notes that the approach suggested by this commenter is new and was not supported by other participants. It is also inconsistent with the recommendations of most expert organizations in this field and would require extensive analysis by OSHA before its merit could be ascertained. Accordingly, OSHA finds this approach inappropriate for use in the present rulemaking.

In this rulemaking, OSHA has evaluated the efficacy of the final rule's limits on a case-by-case basis; although the initial evaluation presented in the NPRM relied heavily on analyses conducted by the ACGIH and NIOSH, the limits promulgated in the final rule are based on an expanded toxicologic assessment using information contained in the rulemaking record. OSHA believes that, at this time, this case-by-case assessment is the best way to establish new and revised limits for the numerous substances addressed in this rulemaking.

Types of Toxicological Evidence

The evidence available to scientists wishing to evaluate the toxicity of a substance can be derived from studies in laboratory animals, in vitro studies in cell or tissue systems, reports of clinical observations, studies of exposed human populations, or from intervention studies conducted with human volunteers. The preceding paragraphs have described animal studies (or "bioassays"). The following section discusses the two most common types of human evidence: data derived from clinical observations and information from epidemiological studies.

Clinical observations. Much of the data on the toxic effects associated with human exposures have come from industrial accidents, fatal poisonings, or other such tragedies. This information is generally more useful in delineating broad categories of pathological effects than in refining a specific dose-response relationship, because the exposure levels causing the accident are known to be high but cannot be quantified with precision.

Epidemiological studies. Studies conducted by epidemiologists are designed to reveal the patterns of disease or mortality prevailing in certain groups of people (usually workers) exposed to a single toxin or to a group of substances. One of the advantages of epidemiological studies is that they involve humans and their responses to actual situations. The interpretation of the results of epidemiological studies is complicated by the inevitable presence of confounding variables that occur whenever human populations are involved. Ideally, the populations being studied (i.e., the study population and the control population) should be fully comparable with regard to every variable except the single characteristic under study. Because it is rarely possible to achieve this degree of comparability, statistical techniques are often used to attempt to adjust for this lack of comparability. In addition, if the measured effect is relatively large, it is unlikely that confounding factors will obscure the true picture.

Broadly speaking, epidemiological studies can have two possible outcomes: they can report an effect or they can report no effect; in the former case, the study is termed a positive study, and in the latter, a negative one. Within each of these categories, it is possible for the study to be correct (that is, to give a true-positive or true-negative result) or to be incorrect (that is, to give a false-positive or a false-negative result). A false-positive result reports that there is an increased risk when in fact there is not, and a false-negative study reports that there is no increased risk when in fact there is.

The probability that a study will detect a statistically significant effect if that effect is actually present is called the power of the study. As the power of a study increases, the likelihood of producing a false-negative error decreases. Power is dependent on two factors: the level of relative risk being evaluated and the number of cases of the effect (i.e., disease) that are expected in the population being studied. The number of expected cases depends both on the sample size and the expected disease frequency in the comparison population. For example, a study involving a small population and a common disease can have the same power as a study of a rare disease in a large population. Consequently, studies of larger samples have sufficient power to detect smaller increases in risk, and studies of smaller samples will be able only to detect large increases in relative risk.

Because epidemiological studies have limitations, it is essential that the power of such studies, particularly of negative studies, be examined to ensure that their sample sizes are adequate to detect the absence of increased risk with validity. When the power of a study is not adequate, negative studies cannot be said either to contradict or to support the conclusion that increased risk exists. Essentially, a negative epidemiologic study identifies a NOAEL, which, as discussed above, reflects the statistical limitations of a study more than the "true" population threshold for an effect. However, a study with a positive result may indicate a relationship if the excess risk is high, even if the study's sample size is small and the effects of some factors are not controlled for.

Quality of Evidence

Dose-response models have often been used in the quantitative assessment of the risks associated with exposures to carcinogenic substances. However, less scientific effort has been devoted to models to be used with non-carcinogenic substances. Mathematically precise methods to establish the true no-effect level or to define the dose-response curves have not been developed for most of the more than 400 substances involved in this rulemaking.

Most of the scientific work that has been done was designed to identify lowest observed effect or no-effect levels for a variety of acute effects.

As described above, experts in industrial hygiene and occupational health have developed factors to be used to offset, at least to some extent, the insensitivity of NOELs and LOELs to such factors as subcellular effects, sensitive individuals, and chronic effects. It is possible to use these data, combined with professional judgment and OSHA's expertise and experience, to determine that significant risk exists at current levels of exposure and that a reduction in these levels will substantially reduce this risk of material impairment of health. OSHA is also confident that it is not attempting in this rulemaking to reduce exposures to insignificant levels. However, additional analysis may well reveal that the levels being established in the final rule can be refined further in the future.

B. Historical Development of Occupational Exposure Limits Early Limits

Until the development of occupational health standards, the occurrence of adverse health effects resulting from exposures to hazardous substances or conditions in the workplace could only be determined ex post facto - after impairment had already occurred to the health and welfare of exposed employees. In her 1910 studies of lead poisoning, Dr. Alice Hamilton was forced to rely on "personal observations of working conditions and the illness and deaths of workers to demonstrate the existence of harmful exposures" (Paull 1984/Ex. 1-255). The concept of occupational exposure limits thus represents a dramatic breakthrough in the battle against occupational disease and remains "one of the most useful and indispensable tools yet devised for safeguarding the health and well-being of industrial workers" (Thomas 1979/ Ex. 1-96).

Occupational exposure limits are air quality values that apply in workplaces, and they are derived by studying the correlation between the amount of a toxic substance absorbed by the body and its effects on health. Within the context of occupational exposure, knowledge of this relationship permits quantification of the etiology "of a large number of occupational health impairments, [evaluation of] the risk of such impairments and, if necessary, [consideration of] the effectiveness of preventive measures" (Parmeggiani 1973/Ex. 1-229). More specifically, an understanding of the levels at which disease or other health effects occur can be used to establish limits of occupational exposure below which health hazards are unlikely to occur in most workers.

The historical development of occupational exposure limits began with the published reports of a German scientist whose investigations in 1883 into the effects on experimental animals (and on himself) of carbon monoxide in known air concentrations caused him to conclude that "the boundary of injurious action of carbon monoxide lies at a concentration in all probability of 500 parts per million, but certainly [not less than] 200 parts per million" (Cook 1987/Ex. 1-187). Shortly after the appearance of this first documented dose-response value, another German researcher, K. N. Lehmann, published a series of reports on a number of chemical substances under the title "Experimental Studies on the Effect of Technically and Hygienically Important Gases and Vapors on the Organism." This series culminated in 1936 with a comprehensive paper on chlorinated hydrocarbons, published as Volume 116 of Archiv fur Hygiene.

In 1912, Rudolf Kobert published a table of exposure limits, based on animal studies, for 20 compounds. One of the first tables of hazardous air concentrations to originate in the United States was a technical paper published in 1921 by the U.S. Bureau of Mines. The 33 substances included in this table were those frequently encountered in the workplace. In addition to limits based on acute toxic effects, this table provided some information on the least detectable odor concentration and the lowest airborne concentration required to cause irritation (Paull 1984/Ex. 1-255; Cook 1987/Ex. 1-187).

Throughout the 1920s and 1930s, data became available that correlated concentrations of harmful substances with observed effects on worker health for such materials as lead and mercury compounds, benzene, and granite dusts. These early occupational health studies, which were based on animal experiments and on findings in exposed workers, provided the kind of data needed to link human exposures "to concentrations that were capable of producing not only acute, but chronic health effects" (Paull 1984/Ex. 1-255).

After 1935, the emphasis of researchers had shifted, for the most part, from the reporting of a series of values for a range of acute effects to results that yielded a single limit based on studies of repeated exposures. Over the years, a sizable amount of data about the levels of exposure that would not produce injurious effects had been amassed for a considerable number of substances. "By the early 1940s, control of the occupational environment to prevent the harmful absorption of toxic materials was becoming an accepted principle, and the practical problem of defining what was `harmful' was beginning to be met by employing maximum allowable concentrations" (Paull 1984/Ex. 1-255). In 1943, Sterner (Ex. 1-806) explained the meaning of the term maximum allowable concentrations as "the upper limit of concentration of an atmospheric contaminant which will not cause injury to an individual exposed continuously during his working day and for indefinite periods of time" (Paull 1984/Ex. 1-255).

The first lists of maximum allowable concentrations of airborne toxic substances were issued between 1933 and 1938. The Union of Soviet Socialist Republics (U.S.S.R.) was the first country to make occupational exposure limits a statutory obligation; in 1933 it published a list that included 14 substances (although health standards for some air pollutants apparently were used in the Soviet Union during the 1920s). The first American list was published four years later by the State of Massachusetts, and in 1938 Germany issued occupational health standards for a number of organic solvents (Holmberg and Winell 1977/Ex. 1-141). Additionally, the United States "imposed limited occupational safety and health requirements on certain contractors with the Federal government" when the Walsh-Healey Act was passed in 1936 (Mintz 1984/Ex. 1-840).

Standards Developed by Professional Organizations

During the 1940s, American organizations led in the development of occupational health standards, beginning with the American Standards Association (now the American National Standards Institute, or ANSI) list of "maximum acceptable concentrations" (MACs), which appeared in 1941. This list represented a consensus of opinion by the ASA and a number of industrial hygienists who had formed the American Conference of Governmental Industrial Hygienists (ACGIH) in 1938 (Baetjer 1980/Ex. 1-223). Originally conceived of as a time-weighted concentration to be maintained as an average over the working shift, the MAC was redefined in 1957 to mean an upper level (ceiling level) that should never be exceeded (Turner 1976/Ex. 1-79).

An important contribution to occupational health standard-setting was made in 1945 by Warren Cook (Ex. 1-726), who published a list of maximum allowable concentrations for 132 industrial atmospheric contaminants. These limits had been developed by six states, the U.S. Public Health Service, and the American Standards Association, and included Cook's own list of "accepted or tentative values" based on industrial experience, animal experimentation, human sensory response, or a combination of these factors. This table was followed by:

Documentation supported by 187 specific references, indicating the basis and reliability of each value. Cook was the first investigator to codify all of the available data on MAC's and present it in one publication. His list of recommended values was incorporated, practically without changes, by the ACGIH in establishing the TLVs. In support of Cook's inferences, it should be noted that 50 of the...values that he recommended in 1945 were subsequently adopted as federal standards, and are still in use today (Paull 1984/Ex. 1-255).

The American Conference of Governmental Industrial Hygienists Subcommittee on Threshold Limits presented its second report at the Eighth Annual Meeting of the ACGIH in 1946. The report included values for 131 gases, vapors, dusts, fumes, mists, and 13 mineral dusts "compiled from the list reported by this subcommittee...in 1942, from the list published by Warren Cook in...1945, and from published values of the Z-37 Committee of the American Standards Association" (Cook 1987/Ex. 1-87). The Committee's report noted that:

Considerable difficulty attends the fixing of satisfactory values for maximal allowable concentrations of chemicals in respirable atmospheres because of the lack of a uniform definition of the maximum allowable concentration concept. One concept is that the M.A.C. value should represent as accurately as possible that concentration at which a worker exposed for a sufficient period of time will just escape physiological or organic injury and occupational disease.

A second concept is that the M.A.C. should represent some fraction of that concentration which will injure the worker in order to allow a margin of safety in the design of protective equipment and guard against possible synergistic effects in the case of multiple exposures. A third concept is that the M.A.C. should perform the functions of the former concepts and in addition provide a work environment free of objectionable but non-injurious concentrations of smokes, dusts, irritants and odors. Obviously all of these concepts cannot be fulfilled with the establishment of a single value. M.A.C. values in use at the present time represent examples of all of these concepts. The committee feels that the establishment of dual lists or a single definition is not possible at the present time (ACGIH 1946).

The report concluded by stressing that the 1946 list of M.A.C. values was presented "with the definite understanding that it be subject to annual revision" (ACGIH 1946).

Papers presented at both the Ninth International Congress on Industrial Medicine in London (1948) and at the Fifteenth International Congress of Occupational Health in Vienna (1966) also dealt with maximum acceptable concentrations. The first of these proposed that zones of toxicity be set up to facilitate an understanding of the relative hazards of substances, "since the boundaries of MAC values were not sharp lines of demarcation" (Cook 1987/Ex. 1-87). At the 1966 meeting, discussion took place on the advantages of the concept of a "peak level" of exposure - an extension of the "ceiling level" notion inherent in the definition of a MAC since 1957.

A "peak level" was defined as one "that can be applied to certain substances for brief designated periods and for a strictly limited number of times during the work shift, with a designated time interval between peaks. The 'peak' concept places a limit on the intermittent higher exposures that occur in many industrial operations. The time-weighted average exposure limit is of course to be observed [even when a peak has also been assigned to a substance]" (Cook 1987/Ex. 1-87).

Terminology and definitions throughout this early period were ambiguous and imprecise, reflecting uncertainty as to exactly what needed to be and could be done in the realm of occupational health standard setting. Initially, the ACGIH designated its recommended limits as "maximum allowable concentrations," although this term was often used interchangeably with "threshold limit values." Confusion about the meaning, interpretation, and relative significance of the terms being employed during this embryonic period was common. After 1953, the ACGIH defined the concept of threshold limit values in the preface to its annual published list of occupational health standards as "maximum average atmospheric concentrations...for an eight-hour day." This definition of the TLVs as average concentrations differed from the general understanding of the original term "maximum allowable concentrations," which were essentially ceiling values (Stokinger 1962/Ex. 1-998).

Documentation for the 238 substances included in the TLV list for 1956 was provided by Smyth (Ex. 1-759) in a separate paper in which the author:

Recommended that the TLV's include references to the underlying data, and that the concepts represented by the values be restated in more realistic toxicological terms. In his analysis of the TLVs, he [Smyth] concluded that nine categories of objectionable action were guarded against: chronic toxicity, acute toxicity, narcosis, irritation, asphyxiation, fume fever, eye pigmentation, allergic response, and cancer (Paull 1984/Ex. 1-255).

At about the same time, Stokinger stated that, in his opinion, the Threshold Limits Committee had avoided grappling with the issue of developing a method for establishing limits for industrial carcinogens and noted that, with the exception of nickel carbonyl, limits had not been assigned for potential carcinogens (Paull 1984/Ex. 1-255). In 1962, however, the TLV Committee included three carcinogens as additions to the TLV list, although these were listed separately in an appendix and did not have assigned TLVs. Despite the fact that the ACGIH had stressed early on that TLVs were intended as guides and not as rigidly enforceable limits, the American Standards Association's MAC values (or, where none was available, the TLV) were included as mandatory limits in the Safety and Health Standards for Federal Supply Contracts, which were published in 1960 under the Walsh-Healey Act. Following this action, the ACGIH issued a statement on the definitions and interpretations of TLVs and MACs (Stokinger 1962/Ex. 1-998). At the same time, the ACGIH announced the production of the first edition of the Documentation for Threshold Limit Values (ACGIH 1962); this was followed by another paper in which the work and intentions of the Threshold Limits Committee were reviewed. Turner states that:

[a]t this time the concept of ceiling values and excursion factors around the timeweighted average values was introduced in order to reduce conflict or confusion with the "maximal" values in the American [ANSI] Standards. A "C" (ceiling value) listing was to be given to those fast-acting substances thought likely to be injurious if the concentration exceeded the limit value by more than a designated factor for a relatively short period (about 15 min.). The factor varied between 3 and 1.25, depending inversely upon the magnitude of the TLV. A corollary was that the factor would also indicate the limit of permissive excursion of the concentration above the TLV for a substance not given a "C" listing, always provided that the time-weighted average concentration did not exceed the TLV. This rule of thumb approach to limiting exposure is no doubt appropriate to certain substances when they are used routinely throughout the working day. It seems to have little relevance in other instances where exposure is irregular or where the basis for fixing the TLV is on grounds other than toxicity (Turner 1976/Ex. 1-79).

Several commenters (Tr. pp. 6-30 to 6-31, 7-119, 8-139 to 8-141, and 8-167) were of the opinion that the ACGIH's procedures for establishing TLVs were not open to comment and that its reasons for selecting certain TLVs were not clear. Dr. Ernest Mastromatteo, Chairman of the ACGIH's TLV Committee, explained the organization's limit-setting process at the hearing (Tr. pp. 2-113 to 2-128). He stated that the Committee's minutes have recently been made public and explained that the committee often invited industry or union consultants to help the committee in its work on the TLVs (however, these consultants do not vote on the recommended limits). In addition, Dr. Mastromatteo described the ACGIH's process of placing new or revised limits on an "Intended" list for a period of two years, during which time comments on the proposed limits are invited, and considered.

Permissible Exposure Limits in the Era of OSHA

The enactment of the Occupational Safety and Health Act of 1970 marked the first "comprehensive and serious attempt...to protect the health and safety of American workers" (Mintz 1984/Ex. 1-840); it also greatly extended the use of MACs and TLVs by authorizing the newly established Occupational Safety and Health Administration (OSHA) to adopt as its own standards "national consensus standards" and established federal standards (29 USC 655(a)). Mintz notes that "in addition to the safety standards adopted under Section 6(a), OSHA also adopted permissible exposure limits for approximately 400 toxic substances. These [start-up] health standards, now appearing in 29 CFR 1910.1000,...were derived from both national consensus and established federal standards. The national consensus standards had been issued by ANSI, while the established federal standards had been adopted under the Walsh-Healey Act from the TLVs... recommended by the...ACGIH" (Mintz 1984/Ex. 1-840).

Since OSHA's large-scale adoption of the ANSI consensus standards and the 1968 ACGIH TLVs, the Agency has promulgated standards under Section 6(b) of the OSH Act to regulate the industrial use of 24 substances, most of which have been identified as occupational carcinogens, but the ANSI and ACGIH start-up standards continue to comprise the major part of the Agency's occupational health and safety program.

In the interval since the establishment of OSHA and the adoption of the ACGIH and ANSI limits by the Agency, the ACGIH has continued to revise, update, and document the recommended limits that appear in its annual list of TLVs. Since 1968, annual revisions have been made to these limits by the ACGIH. During this time, the TLVs have been "accepted on an international basis as the best available guides for providing healthful occupational environments, and at least 18 countries, including the United States, have either adopted them as legal standards or as guides to legal action, thus verifying their efficacy in accomplishing this purpose" (Paull 1984/Ex. 1-255).

The action OSHA takes today initiates the process of updating the Agency's Z-table permissible exposure limits. That these limits were seriously out of date is attested to by the fact that the ACGIH has found it necessary to revise or add nearly 400 limits to its list in the 20 years since the limits that were later adopted by OSHA were initially published. Recognition that OSHA's Z-table limits need updating to reflect recent developments in toxicology and new data on the health effects associated with exposure to these substances is widespread throughout industry: for example, OSHA's Hazard Communication standard (29 CFR 1910.1200) requires organizations that develop Material Safety Data Sheets (MSDSs) to include on these MSDSs the ACGIH's current TLV values as well as OSHA's limits.

The following section describes the methodology used by OSHA in selecting the limits it is promulgating today. The Agency believes that promulgation of these limits will address a broad range of significant risks now prevalent in industry. As many industrial hygienists and occupational safety and health professionals have noted, the use of permissible exposure limits continues to be the single most efficacious way of protecting the health, functional capacity, and well-being of the American worker.

C. Description of the Substances For Which Limits Are Being Established

In this rulemaking, OSHA considered revising 428 substances, and the final rule is revising existing or adding new limits for several hundred toxic substances currently being manufactured, used, or handled in workplaces throughout general industry. This section of the preamble identifies the PELs being established, describes the available toxicological data, and explains the Agency's rationale for selecting the final permisible exposure limits for these substances.

The universe of substances included in this rulemaking is bounded by the substances for which the American Conference of Governmental Industrial Hygienists (ACGIH) has established a Threshold Limit Value (TLV) for exposures in the work environment. That is, OSHA is not at this time establishing exposure limits for any hazardous substance that is not included in the ACGIH's 1987-88 List of TLVs. In addition, where the limit included in the current ACGIH list was identical to OSHA's existing Z-table limit for the same substance, OSHA did not consider revising its existing limit.

Although new limits are not being established for chemicals excluded from the ACGIH's 1987-88 list, OSHA has not limited its initial consideration of appropriate limits to those levels established by the ACGIH. The Agency has also carefully evaluated the exposure limits recommended by the National Institute for Occupational Safety and Health (NIOSH), OSHA's sister agency. In instances where both NIOSH and the ACGIH have recommended substantially different limits for the same substance, OSHA has thoroughly analyzed the evidence presented by each organization and has made its own judgment of the appropriate level at which to establish the PEL. In addition OSHA has fully considered levels recommended by commenters and levels supported by evidence. For all substances addressed in this rulemaking, OSHA has also evaluated the extensive record evidence. The limits being established today thus represent, in the Agency's professional judgment, those levels found to be most consistent with the best available toxicological data, OSHA's mandate, and the case law that has subsequently developed to interpret that mandate. (For a discussion of the relevant legislative and judicial principles, see the sections of this preamble entitled Pertinent Legal Authority, History and Need for Revision of the PELs, and Approach).

For ease of analysis and presentation, the substances included in the scope of this rulemaking have been grouped into 18 separate sub-sections. In general, these groupings reflect the primary basis underlying the ACGIH or NIOSH recommended limits for these substances. In addition, three additional sections cover substances for which the ACGIH has increased its limits, substances for which OSHA is adding short-term limits, and those for which the Agency is adding skin notations.
The following sections are included:
1. Substances for which Limits Are Based on Avoidance of Neuropathic Effects
2. Substances for which Limits Are Based on Avoidance of Narcotic Effects
3. Substances for which Limits Are Based on Avoidance of Sensory Irritation
4. Substances for which Limits Are Based on Avoidance of Liver or Kidney Effects
5. Substances for which Limits Are Based on Avoidance of Ocular Effect
6. Substances for which Limits Are Based on Avoidance of Respiratory Effects
7. Substances for which Limits Are Based on Avoidance of Cardiovascular Effects
8. Substances for which Limits Are Based on Avoidance of Systemic Toxicity
9. Substances for which Limits Are Based on Observed-No-Adverse-Effect Levels
10. Substances for which Limits Are Based on Avoidance of Physical Irritation and Other Effects
11. Substances for which Limits Are Based on Avoidance of Odor Effect
12. Substances for which Limits Are Based on Analogy to Related Substances
13. Substances for which Limits Are Based on Avoidance of Biochemical/Metabolic Effects
14. Substances for which Limits Are Based on Avoidance of Sensitization Effects
15. Substances for which Limits Are Based on Avoidance of Cancer
16. Substances for Which Current ACGIH TLVs Are Less Stringent than Former OSHA PELs
17. Substances for Which OSHA Is Establishing Short-Term Exposure Limits
18. Substances for Which OSHA Is Adding Skin Notations.

A list of the references that OSHA relied on in evaluating the toxicological evidence pertaining to these chemicals appears in Section VI-D.

1. Substances for Which Limits Are Based on Avoidance of Neuropathic Effects

Introduction

Many industrial chemicals have been shown to cause severe neurological effects in exposed workers, and in many cases these effects are irreversible. Limits have been set on the basis of avoidance of neuropathic effects for 20 substances. Table C1-1 lists the former, proposed, and final rule limits, CAS number, and OSHA HS number for each of these substances. The table shows time-weighted averages (TWAs), ceiling limits, and short-term exposure limits (STELs). For this group of 20 substances, OSHA is lowering its former TWA - PEL for three substances; adding a STEL to a former or a revised TWA for four substances; changing a ceiling to a TWA or a TWA to a ceiling for four substances; establishing permissible exposure limits for seven substances not formerly regulated by OSHA; retaining an existing TWA but changing its accompanying ceiling to a STEL for one substance; and lowering the former TWA and changing its accompanying ceiling to a STEL for one substance.

Description of the Health Effects

The human nervous system comprises the central nervous system (CNS) and peripheral nervous system (PNS). The CNS is made up of the brain and spinal cord, while the PNS consists of a network throughout the body of nerves that communicate with the CNS via connections to the spinal cord. The brain and spinal cord are bathed in cerebrospinal fluid, which supplies nutrients to the CNS and also acts as a barrier against some foreign substances. This barrier protects the central nervous system. In general, fat-soluble substances readily diffuse across this barrier and water soluble substances do not.

    TABLE C1-1.  Substances for Which Limits Are Based on Avoidance of
                 Neuropathic Effects
NOTE: Because of its width, this table has been divided;
              see continuation for additional columns.
_____________________________________________________________________
H.S. Number/
Chemical Name                   CAS No.         Former PEL
_____________________________________________________________________
1051 n-Butyl alcohol             71-36-3        100 ppm TWA
1078 Chlorinated camphene      8001-35-2        0.5  mg/m(3) TWA,
                                 Skin
1114 Decaborane               17702-41-9        0.05 ppm TWA,
                                                Skin
1116 Di-sec-octyl-phthalate     117-81-7        5 mg/m(3) TWA
1123 Dichloroacetylene         7572-29-4         --
1149 Dipropylene glycol       34590-94-8        100 ppm TWA,
methyl ether                                    Skin
1200 n-Hexane                   110-54-3        500 ppm TWA
1202 2-Hexanone                 591-78-6        100 ppm TWA
1216 Iron pentacarbonyl       13463-40-6         --
       (as Fe)
1236A Manganese, fume          7439-96-5        5 mg/m(3)
        (as Mn)                                 Ceiling
1237 Manganese                12079-65-1         --
       cyclopentadienyl
       tricarbonyl (as Mn)
1238 Manganese tetroxide       1317-35-7         --
       (as Mn)
1240 Mercury (aryl and         7439-97-6        0.1 mg/m(3) TWA
       inorganic compounds)
       (as Hg)
1241 Mercury, vapor            7439-97-6        0.1 mg/m(3) TWA
       (as Hg)
1242 Mercury, (organo)         7439-97-6        0.01 mg/m(3) TWA
       alkyl compounds                          0.04 mg/m(3)
       (as Hg)                                  Ceiling
1251 Methylacrylonitrile        126-98-7         --
1253 Methyl bromide              74-83-9        20 ppm Ceiling,
                                                 Skin
1304 Pentaborane              19624-22-7        0.005 ppm TWA
1316 Phenyl mercaptan           108-98-5         --
1342 1,2-Propylene glycol      6423-43-4         --
     dinitrate
_______________________________________________________________________


  TABLE C1-1.  Substances for Which Limits Are Based on Avoidance of
                 Neuropathic Effects (Continuation)
_______________________________________________________________________
H.S. Number/
Chemical Name                   Proposed PEL        Final Rule PEL(1)
_______________________________________________________________________
1051 n-Butyl alcohol            50 ppm Ceiling      50 ppm Ceiling
                                Skin
1078 Chlorinated camphene       0.5  mg/m(3) TWA,   0.5  mg/m(3) TWA,
                                1 mg/m(3) STEL,     1 mg/m(3) STEL,
                                Skin                Skin
1114 Decaborane                 0.05 ppm TWA, Skin  0.05 ppm TWA, Skin
                                0.15 ppm STEL       0.15 ppm STEL
1116 Di-sec-octyl-phthalate     0.5 mg/m(3) TWA     0.5  mg/m(3) TWA,
                                10 mg/m(3) STEL     10 mg/m(3) STEL
1123 Dichloroacetylene          0.1 ppm Ceiling     0.1 ppm Ceiling
1149 Dipropylene glycol         100 ppm TWA, Skin   100 ppm TWA, Skin
methyl ether                    150 ppm STEL        150 ppm STEL
1200 n-Hexane                   50 ppm TWA          50 ppm TWA
1202 2-Hexanone                 5 ppm TWA           5 ppm TWA
1216 Iron pentacarbonyl         0.1 ppm TWA         0.1 ppm TWA
       (as Fe)                  0.2 ppm STEL        0.2 ppm STEL
1236A Manganese, fume           1 mg/m(3) TWA       1 mg/m(3) TWA
     (as Mn)                    3 mg/m(3)           3 mg/m(3) STEL
1237 Manganese                  0.1 mg/m(3) TWA,    0.1 mg/m(3) TWA,
   cyclopentadienyl             Skin                Skin
   tricarbonyl (as Mn)
1238 Manganese tetroxide        1 mg/m(3) TWA       1 mg/m(3) TWA
      (as Mn)
1240 Mercury (aryl and          0.1 mg/m(3) Ceil.   0.1 mg/m(3) Ceil.
   inorganic compounds)             Skin                   Skin
      (as Hg)
1241 Mercury, vapor             0.05 mg/m(3) TWA    0.05 mg/m(3) TWA
      (as Hg)                        Skin               Skin
1242 Mercury, (organo)          0.01 mg/m(3) TWA    0.01 mg/m(3) TWA
 alkyl compounds                0.03 mg/m(3) STEL   0.03 mg/m(3) STEL
       (as Hg)                        Skin              Skin
1251 Methylacrylonitrile        1 ppm TWA, Skin     1 ppm TWA, Skin
1253 Methyl bromide             5 ppm TWA, Skin     5 ppm TWA, Skin
1304 Pentaborane                0.005 ppm TWA       0.005 ppm TWA
1316 Phenyl mercaptan           0.5 ppm TWA         0.5 ppm TWA
1342 1,2-Propylene glycol       0.05 ppm TWA        0.05 ppm TWA
 dinitrate                        Skin
_______________________________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures; its STELs are
for 15 minutes unles otherwise specified; and its ceilings are peaks not
to be exceeded for any period of time.

Chemicals that affect the central nervous system may manifest their toxic effects peripherally. An example of this is the tremor associated with elemental and organic mercury poisoning. Exposure to some chemicals (for example, n-hexane) is associated with axonal degeneration of the nerves in both the central and peripheral nervous systems. Baker (1983/ Ex. 1-230) refers to this dual-system effect as centralperipheral distal axonopathy.

Nervous system toxicants can affect motor function, sensory function, or integrative processes, and they can also cause changes in the behavior of exposed persons. Substances that cause demyelination or neuronal damage can produce motor dysfunction that is expressed as muscular weakness or unsteadi-ness of gait, while exposures to chemicals that are associated with loss of sensory function may result in alterations in touch, pain, or temperature sensation or damage to sight or hearing. Other neuropathic chemicals affect the way in which information is processed in the brain and can interfere with learning and memory. All of the health effects described above constitute material impairments of health within the meaning of the Act.

Although mature neurons cannot divide and be replaced, the nervous system has considerable ability to restore function lost as a result of exposure to toxic chemicals. This capability to restore function even after neurons have been killed is achieved by two mechanisms: plasticity of organization and redundancy of function. That is, when some neurons die, other cells that perform the same function may be able to maintain an adequate level of functioning, or other neurons may be able to "learn" how to perform the lost function. However, even when one of these mechanisms comes into play to compensate for neuronal damage, the overall reserve capacity of the nervous system will have been diminished. The loss of this reserve could be critical in a situation in which additional demands are placed on the nervous system. Thus, even so-called reversible neuropathic effects should be seen as toxic effects causing alterations in and material impairment of the normal functioning of the nervous system.

The neurological effects potentially associated with chemical exposures are numerous, and it is not always easy to identify the precise target site. However, recent medical advances have made tests available that can detect neurological damage that was not detectable several years ago. For example, electrophysiological methods have been developed to measure damage to the visual pathway caused by such exposures. Because of the variation in individual responses to chemical exposures, exposure limits should be set with a view toward this range of susceptibility and the avoidance of any neuropathic effects.

Peripheral Nervous System Effects

The pathological mechanisms associated with peripheral neuropathies result from segmental demyelination or axonal degeneration. Segmental demyelination destroys the myelin sheath but leaves the axon intact; this causes a slowing in nerve conduction velocity. Muscle weakness is often the first sign of such segmental demyelination, and this effect can progress to a decline in motor function or paralysis. Although remyelination may occur within weeks after injury, even a temporary loss in motor or sensory function places the affected worker or others at risk of injury.

Axonal degeneration is a more serious effect in that recovery is often slow or incomplete. It causes demyelination secondary to the degeneration of the distal portion of the nerve. This effect occurs when a chemical interferes with the physiologic dynamics of the nerve, e.g., when it decreases the transport of nutrients to the nerve. The axon will degenerate (die back) sufficiently to accommodate the cell's capacity to supply it with nutrients. Axonal degeneration can also occur as a result of biochemical or metabolic derangement of the central nervous system. Alkyl mercury and elemental mercury are examples of chemicals causing this type of effect (Cavanaugh 1977/Ex. 1-202).

Central Nervous System Effects

The mechanism of action of central nervous system toxins is not well understood but is believed to be associated with neurochemical alteration in the brain. Seizures, Parkinsonism, intellectual impairment, narcosis, dementia, cranial neuropathy, and visual disturbances are all examples of effects that can occur after overexposures to neuropathic chemicals. The more serious CNS effects, such as Parkinsonism, dementia, intellectual impairment, and cranial neuropathy, are generally irreversible (Baker 1983/Ex. 1-230). Before these effects are manifested, subtle changes in behavior may occur; if these subtle signs are interpreted correctly, exposure can be stopped before irreversible damage occurs.

Dose-Response Relationships and Neuropathic Effects

The development of chemically induced neurological effects is believed to follow a dose-response pattern. At an exposure intensity or duration below the no-effect level, detectable effects are unlikely to be evident. As exposure intensity/ duration increases to and beyond this level, the toxin begins to interfere with the normal cellular processes of the neurological system. At this early stage, transient signs and symptoms may appear. Overt effects become more severe as exposure continues and finally progress to serious loss of neurological function and possible permanent damage to neural tissue. Increases in our ability to detect neurological changes at lower levels of exposure have shown that neurobehavioral changes or impairment may occur at levels previously thought to be innocuous. These early effects can be important indicators of potential functional impairment at exposure levels below those that produce either transient or permanent damage. Heavy metals, solvents, and pesticides are examples of chemicals that can cause symptoms that include nausea, sensory and motor function impairments, depression, sleep disturbances, cognitive impairment, and sexual dysfunction. Limits for substances in this group are generally designed to maintain worker exposures below the level associated with such symptoms. This approach ensures that employees will not be likely to suffer these material impairments of health and provides a margin of safety against the risk of more severe or permanent neurological impairment.

The following discussions describe the record evidence and OSHA's findings for all of the substances in this group and illustrate the material impairments of health faced by workers exposed to these toxicants.


n-BUTYL ALCOHOL
CAS: 71-36-3; Chemical Formula: CH(3)CH(2)CH(2)CH(2)OH
H.S. No. 1051


OSHA's former PEL for n-butyl-alcohol was a 100-ppm 8-hour TWA; the ACGIH limit is a 50-ppm ceiling, with a skin notation. The proposed and final rule PEL is a 50-ppm ceiling, with a skin notation. NIOSH (Ex. 8-47, Table N1) concurs that these limits are appropriate. n-Butyl alcohol is a colorless, highly refractive liquid with a mild vinous odor that has long been known to cause irritation of the eyes and headaches in occupational settings.

Systemic effects in the form of vestibular and auditory nerve injuries have been reported in workers in France and Mexico (Seitz 1972 and Velasquez 1964, both as cited in ACGIH 1986/Ex. 1-3, p. 76; Velasquez, Escobar, and Almaraz 1969/Ex. 1-1174). Contact dermatitis of the hands may occur due to the defatting action of liquid n-butyl alcohol, and toxic amounts can be absorbed through the skin. Based on data describing the rate of n-butyl alcohol uptake through the skin of dogs, DiVincenzo and Hamilton (1979, as cited in Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2C, pp. 4571-78, Clayton and Clayton 1982) suggested that direct contact of human hands with n-butyl alcohol for one hour results in an absorbed dose that is four times that resulting from inhalation of 50 ppm for one hour.

The former OSHA limit of 100 ppm (TWA) was based on the studies of Tabershaw, Fahy, and Skinner (1944, as cited in ACGIH 1986/Ex. 1-3, p. 76) and of Smyth (1956/Ex. 1-759). These studies indicated that workers experienced no narcotic or systemic effects at levels lower than 100 ppm. However, irritation has been reported in humans exposed to 24 ppm; this irritation became uncomfortable and was followed by headaches at 50 ppm (Nelson, Enge, Ross et al. 1943/Ex. 1-66).

More recent data reported by Seitz (1972, as cited in ACGIH 1986/Ex. 1-3, p. 76), Velasquez (1964, as cited in ACGIH 1986/Ex. 1-3, p. 76), and Velasquez, Escobar, and Almaraz (1969/Ex. 1-1174) indicate serious exposure-related long-term systemic effects on the auditory nerve and hearing loss (hypoacusia); the magnitude of the hearing loss was related to length of exposure. Nine of 11 workers exposed without hearing protection to 80 ppm for periods of from 3 to 11 years displayed impaired hearing. This phenomenon was particularly evident in younger workers (Velasquez 1964, as cited in ACGIH 1986/Ex. 1-3, p. 76; Velasquez, Escobar, and Almaraz 1969/Ex. 1-1174).

Three commenters, ConAgra (Ex. 3-635), the Motor Vehicle Manufacturers Association (MVMA) (Ex. 3-902), and ARCO (Tr. p. 3-237) submitted comments on n-butyl alcohol. ConAgra (Ex. 3-635) misinterpreted OSHA's discussion of a 1964 study (Velasquez, as cited in ACGIH 1986/Ex. 1-3, p. 76) to mean that OSHA attributed all hearing loss found in the workers in this study to n-butyl alcohol exposure. ARCO (Tr. p. 3-237) also questioned n-butyl alcohol's effect on hearing. In response to these commenters, OSHA notes that n-butyl alcohol has been shown in many studies to damage the auditory nerve and further, that workplace noise may also have contributed to the hearing loss observed in these studies. The MVMA comment (Ex. 3-902) lists n-butyl alcohol as a substance for which rulemaking should be delayed, but provides no other details.

OSHA finds that the former PEL of 100 ppm is not sufficiently protective against the acute effects associated with exposure to n-butyl alcohol; in addition, the possibility of auditory nerve damage from exposures below the 100-ppm level makes the former PEL inadequate. A skin notation is necessary because data in beagle dogs suggest that dermal contact with n-butyl alcohol can result in a systemic dose greater than that obtained by inhalation (DiVincenzo and Hamilton 1979). The Agency is establishing a permissible exposure limit of 50 ppm as a ceiling, with a skin notation, for n-butyl alcohol. OSHA concludes that this limit will protect workers against the significant risks of possible vestibular and auditory nerve injury as well as of headaches and irritation, which constitute material impairments of health and are associated with exposure to this substance at levels above the new limit.


CHLORINATED CAMPHENE (60 Percent)
CAS: 8001-35-2; Chemical Formula: C(10)H(10)Cl(8)
H.S. No. 1078


Previously, OSHA had a limit of 0.5 mg/m(3), with a skin notation, for chlorinated camphene. The ACGIH has a TLV-TWA limit of 0.5 mg/m(3) and a TLV-STEL of 1 mg/m(3) for chlorinated camphene (60 percent), with a skin notation, and these were the limits proposed. The final rule retains the 0.5-mg/m(3) 8-hour TWA and the skin notation, and adds a 1-mg/m(3) STEL for chlorinated camphene, an amber waxy solid with a pleasant, pine-like odor.

Chlorinated camphene has demonstrated a moderately high acute toxicity in animal studies (ACGIH 1986/Ex. 1-3, p. 115). Toxic doses cause varied central nervous system effects, including nausea, muscle spasms, confusion, and convulsions (Hayes 1963/Ex. 1-982). Data indicate that rats and guinea pigs show no significant effects at dietary levels of 800 ppm daily for a six-month period (Alderson Reporting Co., as cited in ACGIH 1986/Ex. 1-3, p. 115). Monkeys tolerate daily feeding at 10 ppm but show toxic symptoms after two weeks' feeding at the 60-ppm level (Sosnierz, Szczurek, Knapek, and Kolodziejczyk 1972/Ex. 1-760). Although chlorinated camphene may accumulate in fatty tissues, it clears quickly when ingestion is terminated (Sosnierz, Szczurek, Knapek, and Kolodziejczyk 1972/Ex. 1-760).

In humans, the acute lethal dose of chlorinated camphene is between 2 and 7 grams, and a dose of 10 mg/kg causes nonfatal convulsions in some exposed individuals. The ACGIH (1986/Ex. 1-3, p. 115) concludes that the acute toxicity of chlorinated camphene is equivalent to that of chlordane, for which the fatal human dose is estimated to be around 6 grams; the ACGIH TLV-TWA for chlordane is 0.5 mg/m(3). One study of 25 human volunteers failed to reveal toxic responses to daily 30-minute exposures to 500 mg/m(3) for 10 consecutive days, followed by similar exposures for three consecutive days three weeks later (Shelansky 1947, as cited in ACGIH 1986/Ex. 1-3, p. 115). There are no reports of occupational poisonings, and a review of the medical records of employees engaged in the manufacture and handling of chlorinated camphene showed no ill effects in workers exposed for an average of 3.7 years (Frawley 1972, as cited in ACGIH 1986/Ex. 1-3, p. 115).

NIOSH does not concur with OSHA's PELs for this substance; NIOSH believes that chlorinated camphene is a potential occupational carcinogen and should have lower exposure limits (Ex. 8-47, Table N6B; Tr. pp. 3-97, 3-98). No other comments on the health effects of this substance were submitted to the record.

OSHA is retaining the 8-hour TWA PEL of 0.5 mg/m(3) TWA and adding a 15-minute STEL of 1.0 mg/m(3) for this insecticide. The Agency's skin notation is retained. OSHA concludes that both a TWA and a STEL are required to protect exposed workers against the significant risks of bioaccumulation and neuropathic and systemic effects; the Agency finds that these effects constitute material impairments of health. The STEL ensures that TWA exposures will be maintained under good industrial hygiene control.


DECABORANE
CAS: 17702-41-9; Chemical Formula: B(10)H(14)
H.S. No. 1114


OSHA's former limit for decaborane was 0.05 ppm TWA, with a skin notation. The ACGIH has a TLV-TWA of 0.05 ppm and a TLV-STEL of 0.15 ppm, also with a skin notation. The proposal retained the 8-hour TWA of 0.05 ppm and added a 0.15-ppm STEL, with a skin notation, and the final rule establishes these limits. NIOSH (Ex. 8-47, Table N1) concurs that these limits are appropriate. Decaborane forms colorless crystals that are stable at ordinary temperatures and have a pungent odor.

The acute toxicity of decaborane is extremely high for small laboratory animals. The 40-hour LC(50)s for rats and mice are 46 and 12 ppm, respectively (Schechter 1958/ Ex. 1-363). Dermal LD(50)s for rabbits and rats are 71 and 740 mg/kg, respectively (Svirbely 1954a/Ex. 1-385). Acute exposures to decaborane cause loss of coordination, convulsions, weakness, tremors, and hyperexcitability. Decaborane's primary effects are on the kidneys and liver. Studies of repeated exposures to this substance suggest that the toxicity of decaborane is intermediate between that of pentaborane and diborane. The ability of decaborane to penetrate the skin is particularly notable, as is its toxicity to the central nervous system in some species, e.g., rats and rabbits (Svirbely 1954a/Ex. 1-385, 1954b/Ex. 1-530, and 1955/Ex. 1-386). Monkeys showed decreased ability for certain operant behaviors when injected with doses of 3 to 6 mg/kg decaborane (Reynolds et al. 1964, as cited in ACGIH 1986/Ex. 1-3, p. 169).

Central nervous system toxicity has been observed in humans exposed occupationally (Krackow 1953/Ex. 1-344). No comments other than NIOSH's were received on the health effects of decaborane.

OSHA is retaining its 8-hour TWA PEL of 0.05 ppm TWA and skin notation, and adding a 15-minute STEL of 0.15 ppm for decaborane. The Agency concludes that these limits will provide protection against the significant risks of material health impairment in the form of neuropathy and kidney and liver damage possible in the absence of a short-term limit for decaborane.


Di-sec-OCTYL PHTHALATE
CAS: 117-81-7; Chemical Formula: C(24)H(38)O(4)
H.S. No. 1116


OSHA formerly had a limit of 5 mg/m(3) TWA for di-sec-octyl phthalate. The ACGIH has a TLV-TWA of 5 mg/m(3) and a TLV-STEL of 10 mg/m(3), and these are the limits that were proposed. In the final rule, OSHA is retaining the 8-hour TWA limit of 5 mg/m(3) and adding a 15-minute STEL of 10 mg/m(3) for this light-colored, viscous, odorless, combustible liquid.

Di-sec-octyl phthalate (DEHP) is not acutely toxic in small laboratory animals via the oral route. The oral LD(5)0 reported for mice is 26.3 g/kg; for rats, it is 33.8 g/kg (Krauskopf et al. 1973/Ex. 1-495). No skin irritation or sensitization potential has been demonstrated in either animals or humans, and the lethal dermal dose in rabbits is about 25 ml/kg (Singh, Lawrence, and Autian 1972/Ex. 1-436). Shaffer, Carpenter, and Smyth (1945/Ex. 1-369) and Lawrence (unpublished data, as cited in ACGIH 1986/Ex. 1-3, p. 223) have reported deaths in rats and chronic diffuse inflammation of the lung in mice exposed to DEHP at unspecified levels.

Long-term dietary toxicity studies in rats, guinea pigs, and dogs have established a no-effect dose level of about 60 mg/kg/day, and no carcinogenic or histologic abnormalities were observed at this level (Gesler 1973/Ex. 1-481). Higher doses were associated with growth retardation and increased liver and kidney weights but not histologic abnormalities. Metabolic studies have demonstrated that laboratory animals do not appreciably metabolize DEHP (Dillingham and Autian 1973/ Ex. 1-477). Teratogenicity studies in pregnant rats indicated that fertility is unaffected at doses of 0.1, 0.2, or 0.33 percent of the acute intraperitoneal LD(50) dose for rats, although slight effects on embryonic and fetal development were observed in these animals; skeletal deformities were the most common teratogenic effects observed (Dillingham and Autian 1973/Ex. 1-477). Mutagenic effects were observed at intravenous doses of one-third, one-half, and two-thirds of the acute LD(50); these effects are consistent with DEHP's ability to produce dominant lethal mutations (Dillingham and Autian 1973/Ex. 1-477).

A study of workers exposed to a mixture of the vapors of diethyl phthalate, dibutyl phthalate, and di-2-ethylhexyl phthalate reported that exposures to 1 to 6 ppm caused no peripheral polyneuritis (Raleigh, as cited in ACGIH 1986/Ex. 1-3, p. 223). However, Russian investigators examined male and female workers exposed to between 1.7 and 66 mg/m(3) of various combinations of airborne phthalates (including butyl phthalate, higher aryl phthalates, dioctyl phthalate and others) and noted complaints of pain, numbness, and spasms in the upper and lower extremities after six to seven years of exposure. Polyneuritis was observed in 32 percent of the workers studied, and 78 percent of these workers showed depression of vestibular receptors (Milkov, Aldyreva, Popova et al. 1973/Ex. 1-646).

OSHA received a comment from the Chemical Manufacturers Association Phthalate Esters Program Panel (Ex. 3-900). Although the Panel did not oppose the proposed PEL for di-sec-octyl phthalate, it objected to this substance's categorization as a neuropathic agent on the grounds that (1) confounding exposures to tricresyl phosphate and vinyl chloride, which are known neurotoxicants, occurred in the study referenced in the NPRM; and (2) other studies (in humans or animals) have not substantiated that this substance is neuropathic:

Including [di-sec-octyl phthalate] in this category of compounds [i.e., neuropathic agents] is not justified and could lead to improper labeling of the material or unwarranted regulations, and restrictions on the use of the material based on unfounded conclusions (Ex. 3-900, p. 1).

In response to this comment, OSHA notes that the classification scheme used in the preamble to the proposed and final rules is not intended to have regulatory implications. As explained earlier in the preamble, OSHA is using this scheme simply to facilitate generic rulemaking; the various categories reflect the health endpoint used by the ACGIH or NIOSH as the point of reference in setting a limit. Most of the substances included in this rulemaking produce multiple health effects and could be classified in more than a single health effects category. Di-sec-octyl phthalate is no exception, and exposure to this substance has been associated with liver damage, testicular injury, and teratogenic and carcinogenic effects in experimental animals, as well as with possible neuropathic effects.

Another commenter, Lawrence H. Hecker of Abbott Laboratories, feels that the STEL for di-sec-octyl phthalate is unwarranted (Ex. 3-678, p. 8). OSHA disagrees with Dr. Hecker and finds that, for substances posing serious health hazards, such as those associated with di-sec-octyl phthalate exposure, the STEL further protects workers from the significant adverse effects that could occur in the short-term excursions above the TWA limit permitted in the absence of a STEL.

NIOSH concurs in OSHA's selection of limits for di-sec-octyl phthalate but believes it should be designated as a potential occupational carcinogen (Ex. 8-47, Table N6A). On the other hand, the Chemical Manufacturers Association's (Ex. 140) analysis of the evidence for DEHP's carcinogenicity led the CMA to conclude that this substance is not a carcinogen. OSHA is aware of di-sec-octyl phthalate's carcinogenic effects in experimental animals and notes that IARC has determined that sufficient evidence exists to designate it as an animal-positive carcinogen. However, adequate data are not available to evaluate the risk of cancer to humans. The Agency will continue to monitor the scientific evidence for di-sec-octyl phthalate and will re-evaluate this substance in the future if such evidence suggests that this is appropriate.

In the final rule, OSHA is retaining the 8-hour PEL of 5 mg/m(3) and adding a 15-minute STEL of 10 mg/m(3) for di-sec-octyl phthalate. The Agency concludes that these limits together will protect workers from the significant risks of neuropathic, hepatic, and other systemic injuries, which constitute material health impairments and are associated with exposure to this substance.


DICHLOROACETYLENE
CAS: 7572-29-4; Chemical Formula: ClC - CCl
H.S. No. 1123


OSHA previously had no limit for dichloroacetylene. The ACGIH has a TLV-ceiling of 0.1 ppm for this liquid, which explodes upon boiling. OSHA proposed a ceiling limit of 0.1 ppm, and this is the limit established by the final rule.

In preliminary inhalation exposure studies, guinea pigs demonstrated a 4-hour LC(50) of 20 ppm; death occurred two or three days after exposure and was caused by pulmonary edema. In rats, similar exposures to dichloroacetylene in the presence of 330 ppm of trichloroethylene indicated an LC(50) of 55 ppm (Siegel 1967, as cited in ACGIH 1986/Ex. 1-3, p. 177). When dichloroacetylene was mixed with 9 parts of ether, the 4-hour LC(50) in rats was 219 ppm; in combination with 7 parts of trichloroethylene, the 4-hour LC(50) in rats was 55 ppm; and exposure to dichloroacetylene with 10 parts of trichloroethylene caused a 4-hour LC(50) in guinea pigs of 15 ppm (Siegel, Jones, Coon, and Lyon 1971/Ex. 1-371).

In humans, dichloroacetylene exposure causes headache, loss of appetite, extreme nausea, and vomiting; it affects the trigeminal nerve and facial muscles and exacerbates facial herpes. Disabling nausea was experienced by approximately 85 percent of individuals exposed for prolonged periods of time (not further specified) at concentrations from 0.5 to 1 ppm (Saunders 1967/Ex. 1-361). A number of occupational fatalities have been attributed to exposure to dichloroacetylene (Humphrey and McClelland 1944/Ex. 1-491; Firth and Stuckey 1945, as cited in ACGIH 1986/Ex. 1-3, p. 177). Humphrey and McClelland (1944/Ex. 1-491) reported 13 cases of cranial nerve palsy, nine of which had labial herpes, following exposure to dichloroacetylene. These patients also had symptoms of nausea, headache, jaw pain, and vomiting. Autopsies of two of these fatalities revealed edema at the base of the brain (Humphrey and McClelland 1944/Ex. 1-491).

NIOSH concurs with OSHA's limit for dichloroacetylene but believes that this substance should be designated as a potential occupational carcinogen (Ex. 8-47, Table N6A). However, as explained elsewhere in the preamble, OSHA has decided not to designate substances specifically as carcinogens since so many other organizations already do so. OSHA received no other comments regarding the health effects of dichloroacetylene.

In the final rule, OSHA is establishing a ceiling limit of 0.1 ppm for dichloroacetylene. The Agency concludes that this limit will substantially reduce the significant risks of disabling nausea and serious systemic effects posed to workers exposed to dichloroacetylene at the levels formerly permitted by the absence of any OSHA limit. OSHA finds that these health effects constitute material impairments of health.


DIPROPYLENE GLYCOL METHYL ETHER
CAS: 34590-94-8; Chemical Formula: CH(3)OC(3)H(6)OC(3)H(6)OH
H.S. No. 1149


OSHA formerly had an 8-hour TWA limit of 100 ppm for dipropylene glycol methyl ether (DPGME), with a skin notation. The ACGIH recommends a TLV-TWA of 100 ppm and a TLV-STEL of 150 ppm, with a skin notation, for this colorless liquid with a mild, pleasant, ethereal odor and a bitter taste. OSHA proposed to retain the 8-hour permissible exposure limit of 100 ppm TWA, to add a 150-ppm STEL, and to retain the skin notation for dipropylene glycol methyl ether. NIOSH (Ex. 8-47, Table N1) concurs that these limits are appropriate, and the final rule establishes these limits.

Intact dogs receiving intravenous injections of DPGME exhibited central nervous system depression and died as a result of respiratory failure (Shideman and Procita 1951/Ex. 1-667). Rowe and associates (1954/Ex. 1-435) reported a single acute oral LD(50) for rats of 5.4 ml/kg. Even at the highest levels tested (not further specified), no single application of DPGME to the skin of rabbits was lethal, although some narcosis and transient weight loss did occur. However, a significant number of deaths occurred in a group of rabbits treated with 65 repeated dermal applications containing DPGME concentrations of 3 ml/kg or higher during a 90-day period. Four animal species, including the monkey, were exposed repeatedly to seven-hour daily inhalation exposures of between 300 and 400 ppm DPGME; the animals exhibited narcosis and changes in the lung and liver (Rowe, McCollister, Spencer et al. 1954/Ex. 1-435).

Humans inhaling DPGME concentrations of 300 to 400 ppm judged this level to be very disagreeable, but 100 ppm was tolerable and, in the opinion of the authors, was unlikely to produce organic injury (Rowe, McCollister, Spencer et al. 1954/Ex. 1-435). Patch tests on the skin of 250 human subjects produced neither irritation nor sensitization (ACGIH 1986/Ex. 1-3, p. 221). Humans exposed to DPGME vapor concentrations at levels between 50 to 2000 ppm experienced eye, nose, and throat irritation before the onset of CNS impairment, which occurred at 1000 ppm in one of two subjects (Stewart, Baretta, Dodd, and Torkelson 1970/Ex. 1-379).

NIOSH (Ex. 150, Comments on Dipropylene Glycol Monomethyl Ether) reported that it is developing a criteria document on the glycol ethers; NIOSH submitted recent toxicity data on DPGME, including the following: rats and mice inhaling concentrations of 50, 140, or 330 ppm DPGME six hours/day for nine days showed increased liver weights (at 50 and 140 ppm for the rat and at 330 ppm for the mouse), but no effects were observed when rats inhaled 15, 50, or 200 ppm DPGME six hours/day, five days/week for 13 weeks (Landry and Yano 1984, as cited in Ex. 150). NIOSH also reported results of a 1985 study by Miller et al. indicating that DPGME is metabolized via the same routes to the same types of metabolites - propylene glycol, and sulfate and glucuronide conjugates of DPGME - as previously identified for PGME (1-methoxy-2-propanol) (Miller, Hermann, Calhoun et al. 1985, as cited in Ex. 150). The Landry and Yano study (1984, as cited in Ex. 150) further indicated that at the concentrations tested, DPGME exerted no teratogenic or reproductive effects (NIOSH/Ex. 150, Comments on Dipropylene Glycol Monomethyl Ether).

The ARCO Chemical Company (Ex. 3-740) questioned the appropriateness of a skin notation for this substance. In response to ARCO, the Agency notes that DPGME, applied essentially according to the Draize method, is absorbed in sufficient quantities through rabbit skin to cause transient narcosis, although the absorption rate was not considered acutely dangerous (Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2C, p. 3990, Clayton and Clayton 1982). Topical administration of 10 mg/kg DPGME five times per week for 13 weeks to shaved rabbit skin caused six deaths among seven animals (Chemical Hazards of the Workplace, 2nd ed., p. 221, Proctor, Hughes, and Fischman, 1988). To date, there are no human data demonstrating that dermal contact with DPGME is without a significant adverse health risk; therefore, in accordance with the policy described in Section VI.C.18, OSHA finds that the available evidence does not meet the criterion for deleting an existing skin notation.

In the final rule, OSHA is retaining a PEL of 100 ppm TWA and adding a STEL of 150 ppm for dipropylene glycol methyl ether; the skin notation is retained. The Agency concludes that this combined limit will substantially reduce the significant risks of central nervous system effects and irritation, which constitute material health impairments, that exist when workers are exposed to DPGME for short periods above the 100-ppm PEL.


n-HEXANE
CAS: 110-54-3; Chemical Formula: CH(3)(CH(2))(4)CH(3)
H.S. No. 1200


OSHA's former PEL for n-hexane was 500 ppm. The ACGIH has a 50-ppm TWA limit for this substance, and the NIOSH REL is 100 ppm as a 10-hour TWA. OSHA proposed a limit of 50 ppm TWA for n-hexane, and the final rule establishes this limit. NIOSH (Ex. 8-47, Table N1) concurs that a PEL of 50 ppm is appropriate for n-hexane. Normal hexane is a clear, volatile liquid.

n-Hexane has been shown to produce distal axonopathy in both experimental animals and humans; it is metabolized to 2,5-hexanedione (2,5-HD), which is thought to be the causative agent of most of the adverse neurological effects observed after exposure to hexane (Schaumburg, Spencer, and Thomas 1983/ Ex. 1-228).
In the preamble to the proposed rule, OSHA asked:
Does the most current scientific information generally support acceptance of the hypothesis that the C(5-8) alkanes are not equally toxic because a metabolite of n-hexane exhibits unique neurotoxic properties?

Several commenters (Exs. 3-593, 3-1246, and 124; Tr. III, pp. 109-110) responded to this question, and their detailed responses are discussed in Section V of this preamble, Summary of Commenters' Responses to NPRM Questions.

The C(5)-(8) alkanes include pentane, n-hexane, the hexane isomers, n-heptane, octane, and the refined petroleum solvents. Whether all of these alkanes exhibit the same degree of toxicity or whether one (or more) is uniquely toxic has a direct bearing on the appropriate exposure limits for these substances. Based on a thorough review of the chemical and toxicological literature and the responses of these commenters, OSHA has determined that n-hexane is uniquely toxic to the peripheral nervous system. The Agency finds that 2,5-hexanedione (2,5-HD), a metabolite of n-hexane, is likely to be responsible for this unique toxicity, and the American Petroleum Insitute (Ex. 124) agrees with this finding. NIOSH (Tr. III, pp. 109-110), on the other hand, is of the opinion that any ketone or related chemical that can be metabolized to a gamma diketone has the potential to cause peripheral neuropathy. However, representatives of the Texaco Company (Ex. 3-1246) agree with OSHA that n-hexane is uniquely toxic because its toxicity is mediated by 2,5-HD.

The ACGIH established a TLV of 50 ppm for this substance, based primarily on studies (Miyagaki 1967/Ex. 1-198; Inoue, Takeuchi, Takeuchi et al. 1970/Ex. 1-75) showing peripheral neuropathies at exposure levels as low as 210 ppm. NIOSH based its 100-ppm REL on the same studies as those cited by the ACGIH (Miyagaki 1967/Ex. 1-198; Inoue, Takeuchi, Takeuchi et al. 1970/Ex. 1-75). NIOSH reasoned as follows:

The absence of definitive epidemiologic or toxicologic evidence makes it difficult to determine how much lower the environmental limit should be. Professional judgment suggests [that] a TWA concentration of 350 mg/m(3) (100 ppm) offers a sufficient margin of safety to protect against the development of chronic nerve disorders in workers (NIOSH 1977a/ Ex. 1-233, p. 74).

The adverse neurological effects of hexane exposure are manifested as both sensory and motor dysfunctions. Initially, there is a symmetric sensory numbness of the hands and feet, with loss of pain, touch, and heat sensation. Motor weakness of the toes and fingers is often present; as the neuropathy becomes more severe, weakness of the muscles of the arms and legs may also be observed (Schaumburg, Spencer, and Thomas 1983/Ex. 1-228). There are no known conditions that predispose an individual to hexane neurotoxicity (Schaumburg, Spencer, and Thomas 1983/Ex. 1-228). The onset of neurological symptoms may not be evident for several months to a year after the beginning of exposure. Recovery may be complete, but severely exposed individuals often retain some degree of sensorimotor deficit.

OSHA received comments on n-hexane from several participants, including NIOSH, the National Cotton Council, the American Petroleum Institute, the Corn Refiners Association, the AFL-CIO, and the United Auto Workers. Two commenters, the National Cotton Council (Tr. pp. 9-45 to 9-47) and the Corn Refiners Association (Ex. 177), stated that the revised PEL for n-hexane would impact their members, but did not provide further detail.

Some commenters (Exs. 194 and 197: Tr. pp. 3-290 to 3-293) urged OSHA to regulate all of the refined petroleum solvents on the basis of neurotoxicity. For example, the AFL-CIO recommended a 10-ppm PEL for all such solvents, and Dr. Franklin Mirer of the United Auto Workers described feasible controls that could be used, in his opinion, to achieve this level. Dr. Philip Landrigan (Tr. pp. 3-290 to 3-293) described the neurotoxic effects of exposure to any of the refined petroleum solvents. In response to these commenters, OSHA notes that it is reducing the limits for a number of these solvents in this rulemaking; however, the scale of this undertaking is such that OSHA was unable to perform the detailed analysis necessary to evaluate the health effects, risks, and feasibility for all of the solvents in this large group of substances.

The dose-response relationship for n-hexane exposure in humans is not well defined, although it is clear that the severity of the resulting neuropathy increases as the exposure level of n-hexane increases. A number of studies have shown a consistent relationship between exposure levels of 500 ppm (OSHA's former exposure limit) to 2000 ppm and the development of characteristic peripheral neuropathies (Yamamura 1969, as cited in ACGIH 1986/Ex. 1-3, p. 305; Yamada 1967/Ex. 1-192). Neuropathic effects have also been shown to occur at levels between 210 and 500 ppm (Takeuchi, Maluchi, and Takagi 1975/Ex. 1-217).

Reports of effects occurring at levels of 210 to 500 ppm indicate that the former OSHA PEL of 500 ppm was not adequate to protect exposed workers from adverse sensorimotor neuropathic effects, and exposure at this level thus represents a significant risk to workers. The decreased sensitivity to pain, touch, and temperature associated with n-hexane exposure can also make a worker more susceptible to injuries and accidents. Further, the delayed onset of a clinical response, which is typical of hexane exposure, increases the probability that exposure will continue until irreversible effects occur.

Both the presence of peripheral neuropathies at 210 ppm and the delay in onset of neurological symptoms indicate that workers exposed at levels above the new limit are at significant risk of developing these symptoms. OSHA therefore establishes a PEL of 50 ppm TWA for n-hexane. The Agency concludes that this PEL will substantially reduce the significant risk of peripheral neurophathies and other adverse neuropathic effects, which constitute material impairments of health and are associated with the exposures permitted at levels above the new limit.


2-HEXANONE (METHYL n-BUTYL KETONE)
CAS: 591-78-6; Chemical Formula: CH(3)CO - CH(2)CH(2)CH(2)CH(3)
H.S. No. 1202


OSHA's former PEL for 2-hexanone was 100 ppm TWA; the NIOSH REL is a 1 ppm (10-hour) TWA; and the ACGIH recommends a TLV-TWA of 5 ppm. The Agency proposed, and the final rule establishes, a permissible exposure limit of 5 ppm as an 8-hour TWA for 2-hexanone. 2-Hexanone is a colorless, volatile liquid with a characteristic acetone-like odor that is more pungent than that of acetone.

Industrial exposure to 2-hexanone causes distal neuropathy manifesting as interference with motor and sensory function; even in cases characterized by minimal intensity, electrodiagnostic abnormalities were seen (ACGIH 1987/Ex. 1-16). In animals, exposure to 2-hexanone causes axonal swelling and thinning of the myelin sheath. A metabolite of 2-hexanone, 2,5-hexanedione, appears to be responsible for the neural damage; this same metabolite is formed when n-hexane (discussed above) is metabolized. Exposures of rats, cats, dogs, monkeys, hens, and guinea pigs to 2-hexanone have resulted in peripheral neuropathies (O'Donoghue 1985). Krasavage, O'Donoghue, and Terhaar (1978) reported that 2,5-hexanedione is 3.3 times more neurotoxic than 2-hexanone and 38 times more neurotoxic than n-hexane in rats. Thus, 2-hexanone would be approximately eleven times more neurotoxic than n-hexane in rats.

The limit of 5 ppm TWA for 2-hexanone recommended by the ACGIH is based on the results of several studies. These include studies showing evidence of peripheral neuropathy at levels of 50 ppm and above after exposures lasting six months or more (Johnson, Anger, Setzer et al. 1979/Ex. 1-984; Streletz, Duckett, and Chambers 1976/Ex. 1-1067). Another study identified 2,5-hexanedione (the metabolite believed responsible for neurotoxic effects) in the serum of humans after a one-day exposure to 50 ppm (DiVincenzo, Kaplan, and Dedinas 1976/Ex. 1-1049).

The NIOSH REL for 2-hexanone of 1 ppm (10-hour TWA) is based on an epidemiologic study describing an outbreak of neurologic disease among workers in a plant that manufactures printed fabrics (Allen, Mendall, Billmaier et al. 1975/ Ex. 1-80). This study reported that a screening of 1,157 exposed workers revealed 86 verified cases of distal neuropathy. 2-Hexanone was suspected of being the neurotoxicant because it had only recently been introduced into the process (Allen, Mendall, Billmaier et al. 1975/Ex. 1-80). When recommending its limit, NIOSH relied on an industrial hygiene survey of the plant conducted by Billmaier, Yee, Allen et al. (Ex. 1-76) in 1974, which showed that 2-hexanone concentrations near the textile printing machines ranged from 1 to 156 ppm (10-minute area samples). After reviewing this evidence, NIOSH concluded that 1 ppm could not be considered a no-effect level for 2-hexanone-induced neuropathy, and NIOSH (Ex. 8-47, Table N2; Tr. p. 3-86) continues to recommend a limit of 1 ppm TWA for 2-hexanone. The AFL-CIO (Ex. 194) also supports the adoption of the lower NIOSH REL. Dr. Franklin Mirer of the AFL-CIO (Ex. 197) described controls for use in workplaces where solvents present exposure problems.

The ACGIH (1987/Ex. 1-16) stated that interpretation of the results of the Billmaier, Yee, Allen et al. (1974/Ex, 1-76) study was complicated because the exposure measurements reported in the study had been taken after the outbreak of neuropathic effects had occurred. In addition, the ACGIH pointed out that Billmaier and colleagues (1974/Ex. 1-76) found poor work practices at the plant (gloves were rarely used, employees washed their hands with solvent, etc.); thus, dermal exposure may have contributed substantially to the outbreak.

Both human and animal studies show the development of disease at exposure levels well below the former 100-ppm PEL, clearly indicating the need to reduce this significant risk. In the final rule, OSHA is establishing a 5-ppm (8-hour TWA) PEL for 2-hexanone. The Agency concludes that this limit will substantially reduce the significant risk of distal neuropathy, which constitutes a material impairment of health and has been demonstrated to occur at concentrations above the new limit.


IRON PENTACARBONYL
CAS: 13463-40-6; Chemical Formula: Fe(CO)(5)
H.S. No. 1216


OSHA previously had no exposure limit for iron pentacarbonyl. The ACGIH has a TLV-TWA of 0.1 ppm with a TLV-STEL of 0.2 ppm, measured as iron, for this highly flammable, oily, colorless to yellow liquid. The Agency proposed, and the final rule establishes, permissible exposure limits of 0.1 ppm TWA and 0.2 ppm STEL for iron pentacarbonyl, measured as Fe. NIOSH (Ex. 8-47, Table N1) concurs that these limits are appropriate.

In studies of rats, iron pentacarbonyl has been reported to have approximately one-third the acute toxicity of nickel carbonyl (for which the ACGIH has recommended a TLV of 0.05 ppm TWA) (Sunderman, West, and Kincaid 1959/Ex. 1-384). In 1970, Gage found that a 5.5-hour exposure at 33 ppm caused fatalities in three of eight rats; four of eight animals died after two 5.5-hour exposures at 18 ppm. At 7 ppm, no ill effects were observed in rats exposed 18 times in 5.5 hours (Gage 1970/ Ex. 1-318). There are no reports of long-term dose-response exposure studies in laboratory animals, and no evidence exists that iron pentacarbonyl is carcinogenic in either humans or animals (ACGIH 1986/Ex. 1-3, p. 327).

Immediate symptoms of acute exposure to high concentrations of iron pentacarbonyl include headache and dizziness, followed in 12 to 36 hours by fever, cyanosis, cough, and shortness of breath. Another clinical effect of overexposure to this substance is lung injury, and degenerative changes in the central nervous system have also been reported (ACGIH 1986/Ex. 1-3, p. 327). No comments (other than NIOSH's) on the health effects of iron pentacarbonyl were submitted to the rulemaking record.

In the final rule, OSHA establishes a permissible exposure limit of 0.1 ppm TWA and a STEL of 0.2 ppm for iron pentacarbonyl. The Agency concludes that these limits will protect workers from the significant risks of material health impairment in the form of headache, dizziness, fever, dyspnea, cyanosis, pulmonary injury, and central nervous system effects, which are potentially associated with exposures at levels above the new limits.


MANGANESE FUME
CAS: 7439-96-5; Chemical Formula: MnO
H.S. No. 1236a


OSHA previously had a ceiling limit of 5 mg/m(3) for manganese fume, measured as manganese. Because of this substance's potential for damage to the lungs and central nervous system, the ACGIH recommends an 8-hour TWA of 1 mg/m(3) and a 3-mg/m(3) STEL for manganese fume. These limits were proposed and are now established by the final rule. NIOSH (Ex. 8-47, Table N1) concurs that these limits are appropriate.

Symptoms of manganese poisoning range from sleepiness and weakness in the legs (Fairhall 1957a, as cited in ACGIH 1986/ Ex. 1-3, p. 354) to difficulty in walking and uncontrolled laughter (Fairhall and Neal 1943, as cited in ACGIH 1986/ Ex. 1-3, p. 354). Health surveys of employees exposed to manganese fume have demonstrated a high incidence of pneumonia in these workers (Davies 1946, as cited in ACGIH 1986/Ex. 1-3, p. 354). Tanaka and Lieben (1969/Ex. 1-388) found seven cases of pneumonia and 15 borderline cases of pneumonia among 144 workers exposed to manganese dust or fume concentrations greater than 5 mg/m(3); three of these cases were associated with fume rather than dust exposure. Those workers exposed to fume levels below 5 mg/m(3) exhibited no signs of pneumonia. In a separate study by Smyth, Ruhf, Whitman, and Dugan (1973/Ex. 1-990), three cases of manganese poisoning were detected among 71 employees exposed to levels of 13.3 mg/m(3) manganese fume.

OSHA received several comments on manganese fume and dust (Exs. 3-189, 3-673, 3-675, 3-829, 8-22, and 129). Some commenters stated that reducing the PEL for manganese fume would have a large impact on their industries but did not provide any details (Exs. 3-673, 3-675, and 8-22). Chemetals, Inc., a manufacturer of manganese products, supports the reduction in the PEL for manganese fume from a ceiling of 5 mg/m(3) to an 8-hour TWA of 1 mg/m(3) and a STEL of 3 mg/m(3). According to Chemetals:

[We] agree that the fumes of metals and their compounds have higher toxicities than the dusts....and that a time-weighted average is more appropriate for manganese (Ex. 3-189, p. 2).

However, Chemetals urged OSHA to also revise the Agency's limit for manganese dust from a ceiling to an 8-hour TWA (Ex. 3-189). OSHA did not propose a change to its existing 5-mg/m(3) ceiling limit for manganese dust. In response to this comment, OSHA notes that manganese dust is not a substance that is included in this rulemaking; the Agency did not propose to regulate manganese dust and is not revising its limits for this substance in the final rule (see the preamble section entitled "Boundaries to the Regulation").

One other commenter, the Specialty Steel Industry of the United States (Ex. 3-829), stated that, in its opinion, there was no basis for reducing OSHA's former PEL for manganese fumes or for supplementing this limit with a STEL. OSHA does not agree with the views of this commenter, because exposures to these fumes have been demonstrated to cause toxic effects in both humans and animals. Workers exposed to manganese fumes developed pneumonia (Tanaka and Lieben 1969/Ex. 1-388), and Stokinger (1981f, in Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2A, p. 1767) reports that the 1-mg/m(3) limit "is supported by the finding in animals that the higher oxides are more toxic, and the report of an occasional case of Mn poisoning in susceptible workers exposed to ferro Mn fumes around the 1-mg/m(3) limit."

Based on a review of all of the record evidence, the final rule establishes a 1-mg/m(3) TWA and a 3-mg/m(3) STEL for manganese fume. The Agency concludes that both a TWA limit and a STEL are required to protect employees from the significant risks of manganese poisoning, lung damage, and pneumonia, all of which constitute material health impairments, associated with exposure to these fumes.


MANGANESE CYCLOPENTADIENYL TRICARBONYL
CAS: 12079-65-1; Chemical Formula: C(5)H(5) - Mn(CO)(3)
H.S. No. 1237


OSHA formerly had no limit for exposure to manganese cyclopentadienyl tricarbonyl (MCT). The ACGIH has a TLV-TWA of 0.1 mg/m(3) (measured as manganese), with a skin notation. The Agency proposed, and the final rule establishes, a permissible exposure limit of 0.1 mg/m(3) TWA (measured as manganese), with a skin notation, for this substance. NIOSH (Ex. 8-47, Table N1) concurs that these limits are appropriate.

A Russian study reported that a single two-hour exposure to MCT at 120 mg/m(3) was fatal to 80 percent of albino rats, although rabbits, guinea pigs, and rats survived a single two-hour exposure at 20 to 40 mg/m(3). Chronic exposure of rats for 11 months at levels averaging 1 mg/m(3) for four hours daily showed delayed effects (seven months from onset of exposure) of neuromuscular excitability, evidence of kidney damage, and decreased resistance to infection (Arkhipova, Tolgskaya, and Kochetkova 1965/Ex. 1-1046). The tails of 10 white mice were dipped in a gasoline mixture containing 1 gram MCT per 100 ml; a second group of mice had their tails immersed in gasoline without MCT. An equal number of fatalities were observed in the gasoline plus MCT and gasoline only groups after four or five two-hour applications, and all tails exhibited necrosis. The authors concluded that these effects were caused by the gasoline and not by the MCT (Arkhipova, Tolgskaya, and Kochetkova 1965/Ex. 1-1046). Further studies in rabbits showed that MCT applied dermally as an oil emulsion caused irritation of the skin. These authors also investigated the dermal toxicity of MCT solutions in tetrahydrofuran versus solutions of tetrahydrofuran in oil. All animals whose tails had been dipped in the hydrofuran solution of MCT died within an hour, while animals whose tails had been dipped in pure tetrahydrofuran did not (Arkhipova, Tolgskaya, and Kochetkova 1965/Ex. 1-1046). The same authors concluded that MCT is toxic at low concentrations, has cumulative properties, affects the nervous system, is irritating to the skin, and causes early histological changes in the respiratory tract.

More recent reports describe MCT-induced pulmonary edema and convulsions in the rat (Penney, Hogberg, Traiger, and Hanzlik 1985/Ex. 1-431). The ED(50s) for convulsions were 32 mg/kg orally and 20 mg/kg intraperitoneally; LD(50s) were 24 mg/kg orally and 14 mg/kg intraperitoneally. Necrosis of the bronchiolar tissue and pulmonary parenchymal damage were seen in mice and rats given intraperitoneal doses (Haschek, Hakkinen, Witschi et al. 1982/Ex. 1-1083). No comments other than NIOSH's were received on MCT.

OSHA has concluded that occupational exposure to MCT poses a risk of neuropathic effects, kidney damage, skin irritation, pulmonary edema, and tissue damage, which together constitute material health impairments. The Agency is therefore establishing an 8-hour TWA PEL of 0.1 mg/m(3) for manganese cyclopentadienyl tricarbonyl, with a skin notation, to protect workers against the significant risk of these effects, which have been shown to occur at levels above the new standard.


MANGANESE TETROXIDE
CAS: 1317-35-7; Chemical Formula: Mn(3)O(4)
H.S. No. 1238


OSHA previously had no exposure limit for manganese tetroxide (compound and fume). The ACGIH recommends a TLV-TWA of 1 mg/m(3), measured as manganese, for this brownish-black powder and its dust and fume. The Agency proposed a PEL of 1 mg/m(3) TWA for manganese tetroxide, measured as Mn, and the final rule establishes this limit. Ferromanganese fume has been determined by X-ray diffraction analysis to consist primarily of manganese tetroxide.

Findings from a Russian study indicated that intratracheal suspensions of manganese oxide, manganese dioxide, and manganese tetroxide particles (particle size less than 3 um) produced pneumonitis and other similar pulmonary effects in rats (Levina and Robachevskiau 1955/Ex. 1-1041). These investigators also determined that manganese tetroxide has a greater toxicity than do the lower oxides of manganese and that freshly prepared oxides were more potent than those stored for six months to one year.

Two cases of manganese fume poisoning were reported in a plant where concentrations were between 2.7 and 4.7 mg/m(3) (Whitlock, Amuso, and Bittenbender 1966/Ex. 1-455), but other investigators have questioned these air sampling results and believe that exposures to manganese tetroxide concentrations of 5 mg/m(3) or less cause no harmful effects (Whitman and Brandt 1966/Ex. 1-1103). In a seven-year study, Smyth and co-workers (1973/Ex. 1-990) investigated chronic manganese poisoning in workers exposed to both ferromanganese fumes and dust. Five of 71 employees suffered from chronic manganism; of these five cases, three resulted from fume exposure and two from dust exposure. Two of the three fume-exposure victims were exposed over a five-year period to an estimated average ferromanganese concentration of 13.3 mg/m(3); however, the third victim worked in an operation where air concentrations of manganese were less than 1 mg/m(3), which suggests that certain individuals may be hypersusceptible to manganese poisoning. The dust-exposed victims worked in areas where air concentrations were in the range of 30 to 50 mg/m(3) throughout the study period (Smyth, Ruhf, Whitman, and Dugan 1973/Ex. 1-990).

Martonik (1976, as cited in ACGIH 1986/Ex. 1-13, p. 357) reported that the fume of manganese has greater toxicity than does the dust. During a two-year period, at least one case of acute manganese poisoning was documented at a fume concentration level of 7.5 mg/m(3), and another case at the same welding operation may also have involved manganism.
OSHA received two comments on this substance, one from NIOSH (Ex. 8-47;
Tr. p. 3-86), and one from Chemetals, a manganese manufacturer (Ex. 3-189). NIOSH (Ex. 8-47, Table N2) does not concur with the limits being established by OSHA. NIOSH (Ex. 8-47, Table N2) notes that, based on the results of the Smyth and co-workers study (1973/Ex. 1-990), the 1-mg/m(3) PEL being established by OSHA "may not be protective, especially to the potentially sensitive individual." In response to this NIOSH comment, OSHA states that the Agency intends to monitor the literature on manganese tetroxide closely in the future to determine whether the new limit for this substance is adequately protective.

Chemetals (Ex. 3-189) asked OSHA to promulgate separate limits for the dust and fume of manganese tetroxide based on the relative toxicities of these two particulate forms. OSHA recognizes that some information in the literature (including some discussed above) points to the greater toxicity of the fume and that fumes are generally the more toxic form of particulate. However, the Agency notes that intratracheal suspensions of manganese tetroxide dust caused pneumonitis and other pulmonary effects in Russian workers (Levina and Robachevskiau 1955/Ex. 1-1041) and that several cases of manganism have been caused by dust exposure (Smyth, Ruhf, Whitman, and Anger 1973/Ex. 1-990). The Agency believes it prudent not to distinguish at this time between the dust and the fume but to set the TWA PEL at a level that will protect against the effects of exposure to both forms of particulate.

OSHA is establishing a 1-mg/m(3) 8-hour TWA for manganese tetroxide (compound and fume). The Agency concludes that this limit will provide protection against the significant risks of material health impairment in the form of chronic manganese poisoning, pneumonitis, and other respiratory effects that are associated with exposure to manganese tetroxide at levels above 1 mg/m(3).


MERCURY (ARYL AND INORGANIC COMPOUNDS)
CAS: 7439-97-6; Chemical Formula: Hg
H.S. No. 1240


The former OSHA limit for all inorganic forms of mercury (Hg) was 0.1 mg/m(3) as a ceiling limit, as indicated on Table Z-2; this limit was adopted from ANSI standard Z37.8 (1943). In a compliance directive issued in 1978 (OSHA Instruction CPL 2-2.6), however, the Agency stated that the PEL for inorganic mercury should be expressed as an 8-hour TWA of 1 mg/10 m(3) (0.1 mg/m(3)) rather than as a ceiling. The ACGIH has a 0.1-mg/m(3) TLV-TWA for aryl and inorganic mercury compounds. NIOSH (1973b, as cited in ACGIH 1986/Ex. 1-3, p. 358) has recommended a 0.05-mg/m(3) limit as an 8-hour TWA. OSHA proposed to return to its 0.1-mg/m(3) ceiling limit (measured as mercury) and this limit is being established, together with a skin notation, in the final rule. This action cancels the 1978 compliance directive.

In 1971, shortly after OSHA had adopted the 0.1-mg/m(3) ceiling, the ACGIH reduced the TLV-TWA for all forms of mercury, including the inorganic compounds, to 0.05 mg/m(3). ANSI also reduced its standard to 0.05 mg/m(3) in 1972, and NIOSH recommended the same limit in 1973. The 0.05-mg/m(3) limit was based largely on the study of Smith, Vorwald, Patil, and Mooney (1970/ Ex. 1-373) of workers exposed to mercury levels ranging from less than 0.1 to 0.27 mg/m(3) in chlor-alkali plants. The authors reported a significant dose-related increase in the incidence of weight loss, tremors, abnormal reflexes, nervousness, and insomnia among workers exposed to concentrations of 0.1 mg/m(3) or more. There were slight increases in incidences of insomnia and loss of appetite among workers exposed to 0.1 mg/m(3) or less. Smith, Vorwald, Patil, and Mooney (1970/Ex. 1-373) concluded that a limit of 0.1 mg/m(3) contained little or no margin of safety. Other studies (Bidstrup, Bonnell, Harvey, and Locket 1951/Ex. 1-1014; Turrian, Grandjean, and Turrian 1956, as cited in ACGIH 1986/ Ex.1-3, p. 358) have also reported symptoms of mercury poisoning among workers exposed below 0.1 mg/m(3). The 0.05-mg/m(3) limit established by the ACGIH, ANSI, and NIOSH also follows the 1968 recommendation of an international committee (Permanent Commission & International Association on Occupational Health 1968, as cited in ACGIH 1986/Ex. 1-3, p. 358).

In 1980, the ACGIH revised its recommended TLV for aryl and inorganic mercury compounds to 0.1 mg/m(3). In revising this limit, the ACGIH cited discrepancies in the literature regarding the ratio of blood and urinary mercury levels to airborne concentrations of mercury (Bell, Lovejoy, and Vizena 1973/Ex. 1-1078; Stopford et al. 1978/Ex. 1-1100). These studies reported lower ratios of mercury body burden to airborne concentration when personal sampling is used rather than area sampling. According to Bell, Lovejoy, and Vizena (1973/Ex. 1-1078), the lower ratio results because mercury exposure measurements are generally found to be higher when personal sampling is conducted, presumably as a consequence of contamination of clothing. The ACGIH argued that the 0.05-mg/m(3) limit may be too stringent to apply when personal sampling is conducted. The ACGIH also stated that, in contrast to the effects of elemental or alkyl mercury, little mercury is deposited in the brain following exposure to aryl or inorganic mercury compounds. Based on this reasoning, the ACGIH adopted the higher 0.1-mg/m(3) TLV-TWA for aryl and inorganic compounds of mercury. However, the ACGIH (1986/Ex. 1-3, p. 358) also noted that, although central nervous system effects are less likely to occur from exposure to mercury salts than from other forms of mercury, the risk of renal and oral effects would "presumably be just as great." Therefore, they cautioned that the higher limit for mercury salts "may be subject to debate" (ACGIH 1986/Ex. 1-3, p. 358).

Robert G. Smerko, President of the Chlorine Institute (Ex. 3-828; Tr. pp. 10-171 to 10-177), reviewed the pharmacologic evidence on the various forms of mercury. He concluded that, contrary to the statement by the ACGIH, there is little difference in brain deposition between elemental mercury and mercury compounds:

The ACGIH differentiated between aryl mercury and inorganic salts of mercury in comparison with elemental mercury vapor.... While this is true for large doses of mercury, it overlooks the fact that absorbed elemental mercury is rapidly oxidized in the blood as reported by Clarkson et al. (1967)....

Only when the rate of absorption exceeds the rate at which the body can oxidize mercury between the point of absorption and the brain does elemental mercury behave differently than aryl mercury and inorganic salts of mercury at the blood-brain barrier (Ex. 3-828, p. 7).

Mr. Smerko requested that OSHA retain its 0.1-mg/m(3) limit as an 8-hour TWA, but supplement the limit with requirements for monitoring of urinary mercury levels; Dr. James Melius of the New York State Department of Health (Tr. pp. 11-105, 11-106, 11-109 to 11-111) also stressed the importance of biological monitoring for mercury. This issue is discussed below, for mercury vapor.

In light of this information, which counters the basis for the 0.1-mg/m(3) ACGIH TLV, and given the caution expressed by the ACGIH (1986/Ex. 1-3, p. 358) that the 0.1-mg/m(3) TWA limit "may be subject to debate," OSHA concludes that the PEL for aryl and inorganic mercury should be 0.1 mg/m(3) as a ceiling limit, as indicated in Table Z-2. The health studies cited above indicate that reducing the limit for these forms of mercury will ensure that employees are not at significant risk of adverse neuropathic effects from exposure to these forms of mercury and their compounds. Accordingly, OSHA is establishing a 0.1-mg/m(3) ceiling limit (measured as mercury) for aryl and inorganic mercury and compounds. Dr. Grace Ziem (Ex. 46) supported lowering the mercury limit in the final rule, and the Workers Institute for Safety and Health urged OSHA to restore the ceiling (Ex. 116). OSHA is also adding a skin notation to alert employers to the fact that mercury readily penetrates the skin, causing systemic poisoning; several cases of poisoning from this route have been reported (NIOSH 1973b, as cited in ACGIH 1986/Ex. 1-3, p. 358; Ex. 3-828).

One commenter, Stuart B. Cooper, Manager of Regulatory Affairs for Cosan Chemical Corporation (Ex. 3-1162), expressed concern that establishing different PELs for inorganic mercury and elemental mercury vapor would confuse the interpretation of monitoring results in cases in which more than one form of mercury is present. He suggested that, where one form of mercury is present to a greater extent than another form, only the PEL for the predominant form should apply. OSHA agrees that, for some workplaces, such an approach may be reasonable; however, since the limits for inorganic mercury and mercury vapor differ, both in numerical value and required sampling duration, OSHA believes that employers may wish to conduct both ceiling and full-shift air sampling in cases where both forms of mercury are present.

In the final rule, OSHA is establishing a PEL of 0.1 mg/m(3) as a ceiling for aryl mercury and the inorganic compounds of mercury, along with a skin notation. The Agency concludes that these limits are necessary to protect exposed workers from the significant risks of neuropathy and systemic toxicity (both of which constitute material impairments of health) that are associated with exposure to these substances at higher levels.


MERCURY (VAPOR)
CAS: 7439-97-6; Chemical Formula: Hg
H.S. No. 1241


OSHA formerly had a TWA limit of 0.1 mg/m(3) for mercury (including vapor). The ACGIH recommends a TLV-TWA of 0.05 mg/m(3) for mercury vapor, measured as mercury, and a skin notation. NIOSH has a REL of 0.05 mg/m(3) as an 8-hour TWA. The Agency proposed a PEL of 0.05 mg/m(3) TWA for mercury and its vapor, measured as Hg, and the final rule establishes this limit, also with a skin notation. NIOSH (EX. 8-47, Table N1) concurs that this limit is appropriate. Elemental mercury is a silvery, odorless, heavy liquid.

Inhalation of high concentrations of mercury vapor for relatively brief periods can cause pneumonitis, bronchitis, chest pain, dyspnea, coughing, stomatitis, gingivitis, salivation, and diarrhea (NIOSH 1973b, as cited in ACGIH 1986/Ex. 1-3, p. 359; Ashe, Largent, Dutra et al. 1953/ Ex. 1-502). Chronic mercurialism is manifested by central nervous system effects, including tremor, a variety of neuropsychiatric disturbances, and loss of appetite (Kazantzis 1968, as cited in ACGIH 1986/Ex. 1-3, p. 359; Smith, Vorwald, Patil, and Mooney 1970/Ex. 1-373).

Severe organ damage occurred in rabbits exposed for four hours to an average vapor concentration of 28.8 mg/m(3). Damage was observed in the kidneys, liver, brain, heart, lungs, and colon (Ashe, Largent, Dutra et al. 1953/Ex. 1-502). A study by Smith, Vorwald, Patil, and Mooney (1970/Ex. 1-373) of 567 male workers exposed to a mean exposure level of 0.065 mg/m(3) (S.D. + 0.085) showed a significant dose-related increase in the incidence of weight loss, tremors, abnormal reflexes, nervousness, and insomnia among workers exposed to0.1 mg/m(3) or higher. There were slight increases in the incidence of insomnia and loss of appetite among workers exposed to 0.1 mg/m(3) or less. Smith, Vorwald, Patil, and Mooney (1970/Ex. 1-373) concluded that a limit of 0.1 mg/m(3) contained little or no margin of safety. Six of 75 workers regularly exposed to 0.05 to 0.1 mg/m(3) of mercury vapor in a glassware manufacturing plant reported insomnia, and one was found to have tremors (Danziger and Possick 1973/Ex. 1-504). One of 11 workers employed in a mercury mine or refining plant and exposed at vapor concentrations below 0.1 mg/m(3) had sore gums, loose teeth, or excess salivation (Rentos and Seligman 1968/Ex. 1-523).

NIOSH (1973b, as cited in ACGIH 1986/Ex. 1-3, p. 358) has recommended a 10-hour TWA limit of 0.05 mg/m(3) for inorganic mercury and concluded that hyperactivity, rather than tremor, may be the most typical symptom of chronic mercurialism. Two studies report no evidence of mercury vapor poisoning in industrial settings where characteristic exposures ranged between 0.05 and 0.1 mg/m(3) (Danziger and Possick 1973/Ex. 1-504; McGill, Ladd, Jacobs, and Goldwater 1964/Ex. 1-520).

In workers exposed levels above 0.1 mg/m(3), toxic symptoms were seen (Rentos and Seligman 1968/Ex. 1-523). Turrian, Grandjean, and Turrian (1956, as cited in ACGIH 1986/Ex. 1-3, p. 358) found that 33 percent of workers exposed to the vapor at levels above 0.05 mg/m(3) exhibited hyperexcitability, while only 8 percent of those exposed below that level manifested this symptom. About 20 percent of workers in both groups exhibited tremor. The ACGIH notes that, after exposure to the vapor, "a relatively high percentage of the absorbed mercury remains in the brain," compared with the amount deposited in the brain after exposure to the aryl and inorganic compounds (ACGIH 1986/Ex. 1-3, p. 359). The ACGIH accordingly recommends a higher TLV-TWA for aryl and inorganic mercury than for mercury vapor (see, however, the discussion of aryl and inorganic mercury above).

Robert G. Smerko, President of the Chlorine Institute (Ex. 3-828), and the Laboratory Products Association (Ex. 135) urged OSHA to retain its 0.1-mg/m(3) PEL and to require urinary mercury analysis in lieu of a reduced PEL because dermal contact with mercury may contribute substantially to its toxicity (Ex. 3-828; Tr. pp. 10-171 to 10-177). Mr. Smerko cited several reports of such effects in his testimony and submission, including reports of poisoning resulting from contact with contaminated clothing. Because dermal contact is a significant route of exposure for mercury, Mr. Smerko commented:

There is a large probability that air measurements of mercury concentrations (aryl mercury, inorganic salts, or elemental mercury vapor) either overestimate or underestimate the extent of exposure to mercury. The extreme accuracy and precision of the urinary mercury analysis and the amount of work that has been done in correlating urinary mercury concentrations with the presence or absence of effects from exposure to mercury warrant the proposal that a biological standard, or a comprehensive standard that includes an air concentration and urinary mercury concentration, be established for aryl mercury, inorganic salts of mercury, and elemental mercury vapor (Ex. 3-828, p. 9).

Mr. Robert F. Adams, Senior Industrial Hygienist for Occidental Chemical Corporation (Ex. 3-1174), supported the position of the Chlorine Institute on this issue. Dr. James Melius of the New York State Department of Health supported both environmental and biological monitoring but agreed with the PEL proposed by OSHA. (Tr. pp. 11-105, 11-106, 11-109 to 11-111).

OSHA agrees that prevention of mercury contamination of skin and clothing, as well as the proper handling of contaminated clothing, are essential elements of a program to protect employees from the health hazards of mercury. OSHA also believes that mercury presents one of the rare instances in which a biological-monitoring-based standard may represent an effective and reasonable approach for ensuring worker protection. Margaret Seminario, Associate Director of Occupational Safety, Health, and Social Security for the AFL-CIO, also supported provisions for biological monitoring of mercury as well as supporting the OSHA proposed airborne level (Ex. 194, Appendix 1, p. 3). However, developing such a standard is beyond the scope of this rulemaking, which is being conducted solely to revise OSHA's air contaminant limits.

Despite some of the uncertainties in the studies described above regarding the relationship between airborne exposure levels and health effects, OSHA concludes that the data suggest that the former PEL of 0.1 mg/m(3) is not sufficiently protective. Given the severity of the neuropathic effects caused by mercury poisoning, OSHA finds that a reduction in the airborne limit is necessary to ensure that workers are not at significant risk of mercury-related neuropathic effects. Therefore, OSHA is revising its PEL for elemental mercury vapor to 0.05 mg/m(3) as an 8-hour TWA. In addition, because skin absorption is a significant route of exposure and leads to systemic poisoning, as evidenced by Mr. Smerko's written testimony, OSHA is including a skin notation in the final rule.

OSHA is establishing an 8-hour TWA PEL of 0.05 mg/m(3) TWA for mercury vapor, with a skin notation. The Agency concludes that this limit will substantially reduce the significant risks of acute and chronic mercury poisoning (which constitute material health impairments) that have been demonstrated to occur at exposure levels above 0.05 mg/m(3). The skin notation is added because the vapors of elemental mercury can be readily absorbed through the skin.


MERCURY, (ORGANO) ALKYL COMPOUNDS
CAS: 7439-97-6
H.S. No. 1242


OSHA had a former 8-hour PEL of 0.01 mg/m(3) TWA and a ceiling limit of 0.04 mg/m(3) for the alkyl compounds of mercury. The ACGIH has a TLV-TWA of 0.01 mg/m(3) and a TLV-STEL of 0.03 mg/m(3), with a skin notation, for these compounds, measured as mercury. The Agency proposed, and the final rule is establishing, permissible exposure limits of 0.01 mg/m(3) as an 8-hour TWA and 0.03 mg/m(3) as a STEL, with a skin notation, for the alkyl compounds of mercury (measured as Hg). NIOSH (Ex. 8-47, Table N1) concurs with these limits. Alkyl mercury compounds include volatile liquids, such as dimethyl and diethyl mercury, as well as many complex salts, which are usually solids.

Alkyl mercury compounds pose greater health hazards than do the inorganic compounds of mercury because they can penetrate the blood-brain barrier and the placenta very quickly. The primary toxic effects associated with exposure to the organic compounds of mercury are injuries to the central and peripheral nervous systems and to the kidneys (Casarett and Doull 1975/ Ex. 1-1144). In addition, data concerning mouse and rat exposures to alkyl mercury compounds have demonstrated toxicity to the gastrointestinal system, pancreas, liver, gonads, and cardiovascular system. Suppression of the immune system and impairment of the endocrine system have also been observed (Shakbazyan, Shevchenko, Borisenko et al. 1977/Ex. 1-933). Fatalities in mice have been reported following exposures of 10 to 30 mg/m(3) for 3 to 5 hours (Trakhtenberg 1950/Ex. 1-447).

Methyl mercury is among the most damaging of the alkyl compounds to humans because it accumulates in the body and causes developmental effects (Wilson 1977/Ex. 1-457). A three-month exposure to approximately 1 mg/m(3) diethyl mercury caused death in two individuals (Hill 1943/Ex. 1-786). Another fatal case of alkyl mercury poisoning has also been described (Hook, Lundgren, and Swensson 1954/Ex. 1-333). On the basis of his work with laboratory animals, Trakhtenberg (1950/Ex. 1-447) stated that even a concentration as low as 0.00001 mg/m(3) could not be tolerated by humans on a continuing basis. However, a later study reported no consistent, acute effects of mercury poisoning at air concentrations between 0.01 and 0.1 mg/m(3), despite the fact that brief excursions considerably above this range occurred (Dinman, Evans, and Linch 1958/Ex. 1-311). Organic mercury compounds can be absorbed through the skin (Dangerous Properties of Industrial Materials, 7th ed., Sax and Lewis 1989).

Lawrence H. Hecker, representing Abbott Laboratories (Ex. 3-678), objected to the inclusion of a STEL for the alkyl mercury compounds, stating that there is no health basis for such a limit. OSHA believes that both the seriousness of the neurological effects caused by exposure to low levels of alkyl mercury and the ability of alkyl mercury to accumulate in the body necessitate the establishment of a STEL to ensure that the PEL is not exceeded. As discussed in Section VI.C.17 of this preamble, OSHA has determined that a STEL is warranted in instances where extremely hazardous substances are involved.

OSHA is retaining its 8-hour TWA PEL of 0.01 mg/m(3) and adding a 15-minute STEL of 0.03 mg/m(3) for the alkyl compounds of mercury (measured as Hg), with a skin notation. The Agency concludes that exposure to the alkyl mercury compounds poses significant risks of severe neuropathic and other systemic injuries, which constitute material health impairments, and that both the short-term and 8-hour limits are necessary to reduce these risks. OSHA has added the skin notation to protect against the dermal absorption possible in the absence of a skin notation.


METHYLACRYLONITRILE
CAS: 126-98-7; Chemical Formula: CH(2)=C(CH(3))C=N
H.S. No. 1251


OSHA previously had no standard for methylacrylonitrile. The ACGIH recommends a 1-ppm TLV-TWA with a skin notation to protect workers who are occupationally exposed to methyl acrylonitrile. The Agency proposed, and the final rule establishes, a permissible 8-hour TWA exposure limit of 1 ppm, with a skin notation, for methylacrylonitrile, which is a colorless liquid. NIOSH (Ex. 8-47, Table N1) concurs that these limits are appropriate.

Methylacrylonitrile has been shown to be extremely toxic in animals, both by inhalation and dermal absorption. The dermal LD(50) in rabbits is 0.35 ml/kg (280 mg/kg) (ACGIH 1986/Ex. 1-3, p. 370). Beagles exposed for 90 days to 13.5 ppm convulsed and lost motor control in their hind limbs. Microscopic brain lesions were detected in one of the dogs. The level at which no effects were detected was determined to be between 3.2 and 8.8 ppm (ACGIH 1986/Ex. 1-3, p. 370) No comments (other than NIOSH's) on the health effects of methyl acrylonitrile were submitted to the rulemaking record.

OSHA is establishing a 1-ppm 8-hour TWA PEL and a skin notation for this substance. The Agency concludes this limit will substantially reduce the significant risk of neurological damage (which constitutes a material health impairment) that formerly existed in the absence of an OSHA exposure limit for this substance.


METHYL BROMIDE
CAS: 74-83-9; Chemical Formula: CH(3)Br
H.S. No. 1253


OSHA's former PEL for methyl bromide was a 20-ppm ceiling with a skin notation, while the ACGIH limit is 5 ppm as an 8-hour TWA, with a skin notation. NIOSH recommends that the REL for this substance be set at the lowest feasible level. The Agency proposed, and the final rule establishes, a permissible exposure limit of 5 ppm (8-hour TWA), with a skin notation, for methyl bromide. Methyl bromide is a colorless, nonflammable gas with no taste and no odor at low temperatures. At levels above 5 ppm, it has a sweetish odor.

Acute poisoning from methyl bromide is characterized by lung irritation, pulmonary edema, convulsions, and coma. Chronic exposure to low concentrations of methyl bromide generally produces central nervous system effects, including muscle weakness and pain, incoordination, inability to focus one's eyes, and behavioral changes (ACGIH 1986/Ex. 1-3, p. 376; Craft 1983/Ex. 1-196). The onset of neurological signs and symptoms may be delayed for from several hours to a few days after exposure.

Methyl bromide is a gas and is predominantly an inhalation hazard, although there are suggestions that it can also be absorbed through the skin (Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2B, p. 3443, Clayton and Clayton 1981). A report by Hine (1969/Ex. 1-70) notes that methyl bromide has been responsible for more deaths among occupationally exposed workers in California than have the organophosphates. It is hypothesized that methyl bromide has a greater potential for toxicity than do other organic bromides because its greater lipophilicity provides increased access to the brain.

Various studies demonstrate methyl bromide's toxicity in humans. Ingram (1951/Ex. 1-175) reported ill effects (symptoms not specified) after exposure to methyl bromide at concentrations of 100 ppm. Similar exposure concentrations were also reported by Hine (1969/Ex. 1-70) in a case study of two date packers in California. Johnson, Setzer, Lewis, and Anger (1977/Ex. 1-87) indicated that 34 packers became sick when exposed to an average methyl bromide concentration of 50 ppm, although concentrations in the packing room may have been as high as 100 to 150 ppm during the purging of a fumigation chamber.

Watrous (1942/Ex. 1-275) described nausea, vomiting, and headache in 90 workers who were exposed for two weeks to concentrations "generally below" 35 ppm. These symptoms emphasized the need to create a TLV to protect workers from the nausea, vomiting, and headaches (which together constitute material impairments of health) associated with lower levels of exposure. This need is strengthened by the fact that, since these symptoms are usually delayed in onset, workers may not have sufficient warning of this substance's potential neurotoxicity.

The AFL-CIO (Ex. 194, p. A-12) supports the inclusion of methyl bromide in this rulemaking, but notes that it is a potential occupational carcinogen. NIOSH takes the same position and believes that methyl bromide should be addressed in a full Section 6(b) rulemaking (Ex. 8-47, Table N6B; Tr. pp. 3-97, 3-98). OSHA shares the concerns of these commenters and intends to monitor the scientific evidence on methyl bromide's toxicity in the future. The Workers Institute for Safety and Health (WISH) (Ex. 116) is of the opinion that a ceiling limit is more appropriate than an 8-hour TWA for methyl bromide. OSHA finds, however, that the 5-ppm TWA will provide protection against the levels shown to produce poisoning in humans (generally in the 50- to 150-ppm range).

The presence of neurologic symptoms at levels below 35 ppm indicates that the former ceiling limit of 20 ppm is not adequate to protect workers from the effects of methyl bromide poisoning. OSHA is establishing a PEL of 5 ppm TWA, with a skin notation, to protect workers more adequately against these incapacitating symptoms. The Agency concludes that these limits will reduce this significant risk substantially.


PENTABORANE
CAS: 19624-22-7; Chemical Formula: B(5)H(9)
H.S. No. 1304


OSHA's former limit for pentaborane was 0.005 ppm as an 8-hour TWA. The ACGIH has the same 8-hour TWA but additionally recommends a 15-minute STEL of 0.015 ppm. The Agency proposed, and the final rule establishes, permissible exposure limits of 0.005 ppm as an 8-hour TWA and 0.015 ppm as a 15-minute STEL for pentaborane. NIOSH (Ex. 8-47, Table N1) concurs that these limits are appropriate. Pentaborane is a colorless liquid with a strong and penetrating odor.

In both humans and animals, inhalation of pentaborane vapor causes central nervous system effects (Svirbely 1954a/ Ex. 1-385; Rozendaal 1951/Ex. 1-525; Lowe and Freeman 1957/ Ex. 1-518; Cordasco, Cooper, Murphy, and Anderson 1962/ Ex. 1-545).
The 5-minute LC(50) for rats and mice is 67 and 40 ppm, respectively;
for 60 minutes, these values are 10 and 6 ppm for rats and mice, respectively (Weir, Bath, and Weeks 1961, as cited in ACGIH 1986/Ex. 1-3, p. 459). Rats exposed repeatedly to 3 ppm pentaborane by inhalation exhibited tremors, hyper-excitability, belligerence, and weight loss (Svirbely 1954a/ Ex. 1-385). Rats, rabbits, monkeys, and dogs exposed repeatedly to pentaborane vapor at concentrations of 1 ppm for four weeks or 0.2 ppm for six months lost weight (Levinskas, Paslian, and Bleckman 1958/Ex. 1-517). In the same experiments, rats and rabbits exposed at 1 ppm showed reduced activity and impaired locomotor ability, respectively, and monkeys and dogs exhibited apathy, loss of appetite, insensitivity to pain, loss of mobility, tremor, and impaired coordination. The ACGIH (1986/Ex. 1-3, p. 459) notes that the 0.2-ppm concentration reported in the Levinskas, Paslian, and Bleckman (1958/Ex. 1-517) study was a calculated rather than measured value and that the actual exposure level was probably closer to 0.01 ppm.

Humans accidentally overexposed to pentaborane experienced tremors, convulsions, behavioral changes, loss of memory, impaired judgment, and other symptoms of central nervous system intoxication (Svirbely 1954a/Ex. 1-385; Rozendaal 1951/ Ex. 1-525; Lowe and Freeman 1957/Ex. 1-518; Cordasco, Cooper, Murphy, and Anderson 1962/Ex. 1-545). No comments other than those from NIOSH were received on the health effects associated with pentaborane exposure.

OSHA is establishing an 8-hour TWA PEL of 0.005 ppm and a 15-minute STEL of 0.015 ppm for pentaborane. The Agency concludes that these limits will protect workers against the significant risk of central nervous system effects, such as tremors and convulsions, behavioral changes, and loss of judgment, potentially associated with exposure to pentaborane at levels only slightly above those formerly permitted by the 8-hour TWA alone. OSHA finds that these neuropathic effects constitute material health impairments within the meaning of the Act.


PHENYL MERCAPTAN
CAS: 108-98-5; Chemical Formula: C(6)H(5)SH
H.S. No. 1316


OSHA previously had no exposure limit for phenyl mercaptan. The ACGIH has a TLV-TWA of 0.5 ppm. NIOSH recommends a 15-minute ceiling limit of 0.1 ppm for phenyl mercaptan (benzenethiol). The Agency proposed a permissible exposure limit of 0.5 ppm as an 8-hour TWA, and the final rule establishes this limit. Phenyl mercaptan is a colorless liquid with an offensive, garlic-like odor.

The primary acute hazards of exposure to phenyl mercaptan are central nervous system stimulation followed by post-convulsive CNS depression, severe eye and skin irritation, systemic toxicity to spleen, kidney, lung, and liver tissues, and narcotic effects (ACGIH 1986/Ex. 1-3, p. 478).

Phenyl mercaptan has been reported to have 4-hour inhalation LC(50) values of 33 and 28 ppm for rats and mice, respectively (Doull and Plzak 1962, as cited in ACGIH 1986/Ex. 1-3, p. 478; Fairchild and Stokinger 1958/Ex. 1-415). The oral LD(50) for the rat is reported to be 46 mg/kg (McCord and Witheridge 1949/Ex. 1-882; Robles 1975, as cited in ACGIH 1986/Ex. 1-3, p. 478). For the rabbit and rat, the dermal LD(50) values are 134 mg/kg and 300 mg/kg, respectively (Doull and Plzak 1962, as cited in ACGIH 1986/Ex. 1-3, p. 478; Fairchild and Stokinger 1958/Ex. 1-415); Schafer 1972/Ex. 1-362). The responses of animals to phenyl mercaptan exposure were uniform regardless of species, and progressed from CNS stimulation to incoordination, skeletal and muscular paralysis, and respiratory depression, followed at high concentrations by coma and death. High doses (not further specified) administered via inhalation produced lung, liver, and kidney changes in mice (Doull and Plzak 1962, as cited in ACGIH 1986/Ex. 1-3, p. 478; Fairchild and Stokinger 1958/ Ex. 1-415); Schafer 1972/Ex. 1-362). In rabbits, phenyl mercaptan is a severe eye and skin irritant (McCord and Witheridge 1949/Ex. 1-882; Robles 1975, as cited in ACGIH 1986/ Ex. 1-3, p. 478; Schafer 1972/Ex. 1-362).

In humans, phenyl mercaptan is a moderately toxic skin irritant and causes severe dermatitis, headaches, and dizziness at unspecified levels (Fairchild and Stokinger 1958/Ex. 1-415; McCord and Witheridge 1949/Ex. 1-882). NIOSH (Ex. 8-47, Table N7; Tr. p. 3-99) believes that the limit for phenyl mercaptan is better expressed as a ceiling than as a time-weighted average; however, OSHA believes that a TWA limit set at 0.5 ppm will protect against phenyl mercaptan's toxic effects. No other comments on the health effects of phenyl mercaptan were submitted to the rulemaking record.

OSHA is establishing an 8-hour TWA limit of 0.5 ppm for phenyl mercaptan. The Agency concludes that this limit will protect workers from the significant risks of CNS effects, skin irritation, and systemic injury, all material impairments of health that are potentially associated with exposure to phenyl mercaptan at the uncontrolled levels formerly permitted by the absence of any OSHA limit.


PROPYLENE CLYCOL DINITRATE
CAS: 6423-43-4; Chemical Formula: C(3)H(6)N(2)O(6)
H.S. No. 1342


OSHA previously had no exposure limit for propylene glycol dinitrate. The ACGIH recommends a TLV-TWA of 0.05 ppm, with a skin notation. The Agency proposed a permissible exposure limit of 0.05 ppm TWA, with a skin notation, for this substance, and NIOSH (Ex. 8-47, Table N1) concurred with the proposed limit. The final rule establishes a PEL of 0.05 ppm but does not include the proposed skin notation. When freshly prepared, propylene glycol dinitrate is a colorless liquid with a disagreeable odor.

Exposure to this substance affects blood pressure, causes methemoglobinuria and respiratory toxicity, injures liver and kidney tissues, and distorts vision. Propylene glycol dinitrate can also cause headache and incoordination.

The oral LD(50) value for the rat is between 480 and 250 mg/kg (Clark and Litchfield 1969/Ex. 1-543; Andersen and Mehl 1973/Ex. 1-536), and the subcutaneous LD(50) is 530 mg/kg (Andersen and Mehl 1973/Ex. 1-536). Mice are reported to be somewhat more resistant, with a subcutaneous LD(50) of slightly more than 1200 mg/kg; however, cats appear to be even more susceptible to propylene glycol dinitrate and exhibit a subcutaneous LD(50) of between 200 and 300 mg/kg (Clark and Litchfield 1969/Ex. 1-543). In all species studied, death occurs by anoxia, which is caused by almost complete conversion of hemoglobin to methemoglobin (Clark and Litchfield 1969/Ex. 1-543). Skin tests in albino rabbits did not produce irritation, but ocular instillation caused transient conjunctival redness (Jones, Strickland, and Siegel 1972/ Ex. 1-742). Twenty-day skin exposures in rabbits at 1 g/kg caused minor irritation, and at 2 g/kg, rabbits became weak and cyanotic; one of five rabbits died, and this animal's hemoglobin and hematocrit values had decreased. When the dose was increased to 4 g/kg, the rabbits' methemoglobin values rose to 34.5 percent at death (Jones, Strickland, and Siegel 1972/ Ex. 1-742). Continuous 90-day inhalation exposures at 10 ppm caused kidney and liver changes in dogs; exposures at 35 ppm caused heavy iron deposits in the liver, spleen, and kidneys. Female (but not male) rats showed a drop in blood pressure within 30 minutes after injection of doses above 5 mg/kg. Rhesus monkeys displayed mydriasis in 90-day exposures at 35 ppm but no change in avoidance behavior during a visual discrimination and acuity threshold test (Jones, Strickland, and Siegel 1972/ Ex. 1-742).

In humans, eight-hour exposures to 0.2 ppm or higher concentrations of propylene glycol dinitrate resulted in visual distortion and headache (Stewart, Peterson, Newton et al. 1974, as cited in ACGIH 1986/Ex. 1-3, p. 502). Although subjects developed a tolerance for the headache response, the visual effects were cumulative. Impaired balance occurred after 6.5 hours of exposure to 0.5 ppm, and a 40-minute exposure to 1.5 ppm caused eye irritation. Subjects exposed at 0.5 ppm for 8 hours experienced a consistent elevation in diastolic pressure but no pulmonary irritation. At concentrations of 0.03 to 1.5 ppm, no hematologic effects were observed (Stewart, Peterson, Newton et al. 1974, as cited in ACGIH 1986/Ex. 1-3, p. 502). Studies of human exposures to levels below 0.1 ppm do not report chronic neurotoxicity (Horvath, Ilka, Boyd, and Markhan 1981/Ex. 1-557).

The skin notation included in the proposal for this substance is not included in the final rule because evidence demonstrates that the dermal LD(50) in rabbits is even greater than 2 g/kg (see the discussion in Section VI.C.18 for OSHA's policy on skin notations). No comments except those from NIOSH were received on the health effects of propylene glycol dinitrate.

OSHA is establishing an 8-hour TWA limit of 0.05 ppm for propylene glycol dinitrate. The Agency concludes that this limit will protect workers against the significant risks of hepatotoxic, hematologic, and central nervous system effects (all of which constitute material health impairments) that exist from workplace exposure at the levels permitted in the absence of any OSHA PEL.

Conclusions

OSHA concludes that significant risks are associated with occupational exposure to the group of neuropathic toxicants shown in Table C1-1. The effects caused by such exposures include brain lesions, nausea, vomiting, general depression of the central nervous system, interference with sensory and motor functions, and alterations in the ability of the brain to process information. Affected workers may experience drowsiness, dizziness, loss of ability to concentrate, mood changes, reduced awareness, learning difficulty, unsteadiness, and auditory and visual disturbances. In addition, employees experiencing these effects are imperiled and are likely to hurt themselves or others in accidents caused by their reduced functional capacities. The final rule's promulgation of new or revised exposure limits for these neurotoxins substantially reduces such risks and affords protection to workers against these material health impairments.

2. Substances for Which Limits Are Based on Avoidance of Narcotic Effects

Introduction

OSHA is establishing new or revised limits for 19 substances based primarily on evidence showing that occupational exposure to these substances causes narcosis. The narcotic effects of exposure to such substances as the alcohols, aliphatic hydrocarbons, and chlorinated hydrocarbons have been recognized as serious for many years. Table C2-1 lists these chemicals, their CAS and HS numbers, and their former, proposed, and final rule limits. For seven of these substances, the Agency is lowering the 8-hour TWA permissible exposure limit and revising or adding a STEL. In five additional cases, OSHA is retaining its former 8-hour TWA permissible exposure limit and adding a STEL. Eight-hour TWAs and/or STELs are being established for four previously unregulated substances, and in three other cases, OSHA is lowering its 8-hour TWA permissible exposure limit.

Description of the Health Effects

Narcosis is caused by a general depression of central nervous system (CNS) function. When the CNS becomes sufficiently depressed, the awareness or consciousness of affected persons is diminished. Initial symptoms of narcosis include drowsiness, difficulty in concentration, and mood changes; these effects may progress to slurred speech, dizziness, loss of coordination, and, in more severe cases, loss of consciousness, coma, and death. Except in more serious cases, CNS depression is reversible if the exposure ceases. However, because narcosis adversely affects the concentration and coordination of affected workers, these workers and their co-workers are at increased risk of injuries and accidents caused by slowed reaction times, incoordination, and mistakes and errors in judgment. Moreover, these effects constitute material impairments of health or functional capacity within the meaning of the Act, even if they are not permanent.

TABLE C2 - 1.  Substances for Which Limits Are Based on Avoidance of
                                Narcosis

NOTE: Because of its width, this table has been divided;
              see continuation for additional columns.
_____________________________________________________________________
H.S. Number/                                 Former
Chemical Name                CAS No.         PEL
_____________________________________________________________________
1044 Butane                  106-97-8         --

1049 sec-Butyl alcohol        78-92-2        150 ppm TWA

1050 tert-Butyl alcohol       75-65-0        100 ppm TWA

1111 Cyclopentane            287-92-3         --

1163 Ethyl bromide            74-96-4        200 ppm TWA

1185 Gasoline               8006-61-9         --

1194 Heptane                 142-82-5        500 ppm TWA

1201 Hexane isomers       Varies with         --
                             compound

1218 Isoamyl alcohol         123-51-3        100 ppm TWA
 (primary and secondary)

1221 Isophorone               78-59-1        25 ppm TWA

1254 Methyl chloride          74-87-3        100 ppm TWA
                                             200 ppm Ceil.
                                             (5 min/3 hrs)
                                             300 ppm Peak

1255 Methyl chloroform        71-55-6        350 ppm TWA
 (1,1,1-Trichloroethane)

1296 Octane                  111-65-9        500 ppm TWA

1306 Pentane                 109-66-0        1000 ppm TWA

1307 2-Pentanone             107-87-9        200 ppm TWA
 (Methyl propyl ketone)

1371 Stoddard solvent       8052-41-3        500 ppm TWA

1372 Styrene                 100-42-5        100 ppm TWA
                                             200 ppm Ceil.
                                             (5 min/3 hrs)
                                             600 ppm Peak

1397 Toluene                 108-88-3        200 ppm TWA
                                             300 ppm Ceil.
                                             (10 min/8 hrs)
                                             500 ppm Peak

1406 Trichloroethylene        79-01-6        100 ppm TWA
                                             200 ppm Ceil.
                                             (5 min/2 hrs)
                                             300 ppm Peak
______________________________________________________________________


TABLE C2 - 1.  Substances for Which Limits Are Based on Avoidance of
Narcosis (Continuation)
______________________________________________________________________
H.S. Number/                 Proposed         Final Rule
Chemical Name                    PEL             PEL(1)
______________________________________________________________________
1044 Butane                  800 ppm TWA      800 ppm TWA

1049 sec-Butyl alcohol       100 ppm TWA      100 ppm TWA
                             150 ppm STEL

1050 tert-Butyl alcohol      100 ppm TWA      100 ppm TWA
                             150 ppm STEL     150 ppm STEL

1111 Cyclopentane            600 ppm TWA      600 ppm TWA

1163 Ethyl bromide           200 ppm TWA      200 ppm TWA
                             250 ppm STEL     250 ppm STEL

1185 Gasoline                300 ppm TWA      300 ppm TWA
                             500 ppm STEL     500 ppm STEL

1194 Heptane                 400 ppm TWA      400 ppm TWA
                             500 ppm STEL     500 ppm STEL

1201 Hexane isomers          500 ppm TWA      500 ppm TWA
                             1000 ppm STEL    1000 ppm STEL

1218 Isoamyl alcohol         100 ppm TWA      100 ppm TWA
  (primary and secondary)    125 ppm STEL     125 ppm STEL

1221 Isophorone              4 ppm TWA        4 ppm TWA

1254 Methyl chloride         50 ppm TWA       50 ppm TWA
                             100 ppm STEL     100 ppm STEL

1255 Methyl chloroform       350 ppm TWA      350 ppm TWA
(1,1,1-Trichloroethane)      450 ppm STEL     450 ppm STEL

1296 Octane                  300 ppm TWA      300 ppm TWA
                             375 ppm STEL     375 ppm STEL

1306 Pentane                 600 ppm TWA      600 ppm TWA
                             750 ppm STEL     750 ppm STEL

1307 2-Pentanone             200 ppm TWA      200 ppm TWA
     (Methyl propyl ketone)  250 ppm STEL     250 ppm STEL

1371 Stoddard solvent        100 ppm TWA      100 ppm TWA

1372 Styrene                 50 ppm TWA       50 ppm TWA
                             100 ppm STEL     100 ppm STEL

1397 Toluene                 100 ppm TWA      100 ppm TWA
                             150 ppm STEL     150 ppm STEL

1406 Trichloroethylene       25 ppm TWA       50 ppm TWA
                                              200 ppm STEL
______________________________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures; its STELs are
for15 minutes unless otherwise specified; and its ceilings are peaks not
to be exceeded for any period of time.

The mechanism by which exposure to substances induces narcosis is poorly understood. It is believed that CNS depressants may have the same mechanism of action as general anesthetics, which appear to produce a reversible effect on electrically excitable neuronal membranes.

Dose-Response Relationship and Narcotic Effects

The induction of narcosis following exposure to narcotic agents is expected to follow the classical S-shaped (sigmoidal) dose-response relationship. As exposure level increases, both the percent of exposed persons affected and the severity of the effect increase. Although it is not known whether a true threshold exists for the occurrence of the molecular events leading to narcosis (i.e., disruption of electrical impulses in neurons), there is usually a level at which most exposed individuals will manifest the onset of symptoms associated with narcosis. The no-effect level for a particular substance is determined largely by individual susceptibility, the extent to which the material is absorbed, and the rate at which it is metabolized and eliminated.

The following discussion describes the record evidence and OSHA's findings for the substances in this group and illustrates the material health impairments associated with workplace exposure to these substances.


BUTANE
CAS: 106-97-8; Chemical Formula: C(4)H(10)
H.S. No. 1044


Previously, OSHA had no limit for butane. The ACGIH has a TLV-TWA of 800 ppm for this colorless, flammable gas. The proposed PEL was 800 ppm as an 8-hour TWA, and NIOSH (Ex. 8-47, Table N1,) concurs with this limit. The final rule promulgates an 8-hour TWA of 800 ppm.

The primary risk of exposure to butane is narcosis, which occurs at high exposure levels. Exposure to 10,000 ppm butane for 10 minutes causes drowsiness, but there are no reports of systemic toxicity or irritation at this level (Gerarde 1963a, as cited in ACGIH 1986/Ex. 1-3, p. 10).

In rats, the 4-hour LC(50) for butane is 658 g/m(3), or about 280,000 ppm (NIOSH 1977i/Ex. 1-1182). Humans exposed to 1000 ppm for a single eight-hour day, or to 500 ppm for two-week periods of eight-hour workdays, showed no harmful subjective or abnormal physiological responses but did show a reduced visual evoked response (VER) wave amplitude during the second week (Stewart, Herrman, Baretta et al. 1977/Ex. 1-575). OSHA received no comments, other than NIOSH's, on butane.

In the final rule, OSHA is establishing a permissible exposure limit of 800 ppm TWA for butane. The Agency concludes that this limit will protect workers against the significant risks of drowsiness and other narcotic effects, which together constitute material health impairments and are associated with exposures at the uncontrolled levels permitted in the past by the absence of an OSHA limit.


sec-BUTYL ALCOHOL
CAS: 78-92-2; Chemical Formula: CH(3)CH(2)CHOHCH(3)
H.S. No. 1049


OSHA's former limit for sec-butyl alcohol was 150 ppm as an 8-hour TWA. The proposed PELs were 100 ppm as an 8-hour TWA and 150 ppm as a 15-minute STEL, and NIOSH (Ex. 8-47) concurred with these limits. In the final rule, OSHA is establishing an 8-hour TWA of 100 ppm but is not adding a STEL (see the discussion of the Agency's policy on STELs for this rulemaking in Section VI.C.17). sec-Butyl alcohol is a colorless liquid with a strong, wine-like odor.

The acute toxicity of sec-butyl alcohol is reported to be lower than that of n-butanol, for which OSHA is establishing a ceiling of 50 ppm. The oral LD(50)s in rats for these two substances are 6.5 g/kg for sec-butyl alcohol and 4.4 g/kg for n-butanol, respectively (Smyth, Carpenter, and Weil 1951/Ex. 1-439). Liquid sec-butyl alcohol is less injurious to the eyes than liquid n-butanol (ACGIH 1986/Ex. 1-3, p. 77). Occupational exposures to sec-butyl alcohol at levels of about 100 ppm were reported not to be associated with difficulties (Banks 1966, as cited in ACGIH 1986/Ex. 1-3, p. 77).

OSHA received a comment on this substance from the American Industrial Hygiene Association (AIHA) (Ex. 8-16). The AIHA noted that there was no evidence to support a STEL for this substance and reported that the ACGIH intends to delete this STEL. OSHA has arrived at the same conclusion, and the final rule thus has no STEL for sec-butyl alcohol.

OSHA is reducing the permissible exposure limit for sec-butyl alcohol to 100 ppm TWA to afford protection against the significant risks of narcosis and irritation, which are material health impairments that are caused by exposures to sec-butyl alcohol at concentrations above the revised PEL. The Agency concludes that this limit will substantially reduce this risk.


tert-BUTYL ALCOHOL
CAS: 75-65-0; Chemical Formula: (CH(3))(3)COH
H.S. No. 1050


OSHA formerly had a limit of 100 ppm for tert-butyl alcohol. The ACGIH has a TLV-TWA of 100 ppm, with a TLV-STEL of 150 ppm. OSHA proposed to retain the 8-hour TWA limit of 100 ppm and to add a STEL of 150 ppm for tert-butyl alcohol, and NIOSH (Ex. 8-47, Table N1) concurs. These limits are established by the final rule. At ordinary temperatures and pressures, tert-butyl alcohol exists in the form of colorless, hygroscopic crystals (ACGIH 1986/Ex. 1-3).

Although similar to the other butyl alcohols in many respects, tert-butyl alcohol is more volatile and has a greater potential for narcotic effects than other butyl alcohols (Weese 1928/Ex. 1-1073). Mice exposed to tert-butyl alcohol exhibit a stronger narcotic response than they show when exposed to normal or isobutyl alcohol (Weese 1928/Ex. 1-1073). Repeated daily doses of tert-butyl alcohol that produced narcosis were not fatal in animals (Schaffarzick and Brown 1952/Ex. 1-868). In humans, contact with t-butyl alcohol produces erythema and hyperemia (Oettel 1936/Ex. 1-921). Except for NIOSH's submittal, OSHA received no comments on tert-butyl alcohol.

In the final rule, OSHA is retaining the 8-hour TWA PEL of 100 ppm and adding a 15-minute STEL of 150 ppm for tert-butyl alcohol. The Agency concludes that this combination of limits will protect against the significant risk of narcosis, which constitutes a material health impairment that potentially occurs at levels above the 8-hour TWA PEL.


CYCLOPENTANE
CAS: 287-92-3; Chemical Formula: CH(2)CH(2)CH(2)CH(2)CH(2)
H.S. No. 1111


Previously, OSHA had no limit for cyclopentane. The proposed PEL was 600 ppm as an 8-hour TWA, and NIOSH concurred with this limit (Ex. 8-47, Table N1). The final rule promulgates this limit, which is consistent with that of the ACGIH. Cyclopentane is a mobile, colorless, and flammable liquid.

The existing animal data indicate that cyclopentane is a narcotic agent. As with other alicyclic hydrocarbons, exposure to high concentrations causes excitement, loss of equilibrium, stupor, coma, and, rarely, respiratory failure (Gerarde 1963a, as cited in ACGIH 1986/Ex. 1-3, p. 164). No major animal studies on the effects of cyclopentane exposure have been reported, and evaluations of the toxic properties of this substance have therefore relied on the animal data for n-pentane. n-Pentane has been shown to cause narcosis in animals at exposures of 90,000 to 120,000 ppm for 5 to 60 minutes (Abbritti, Siracusa, Cianchetti et al. 1976/ Ex. 1-406). Swann, Kwon, and Hogan (1974/Ex. 1-124) reported that a concentration of 130,000 ppm is fatal. Almost no data are available concerning the chronic effects of cyclopentane exposure.

Abbritti, Siracusa, Cianchetti et al. (1976/Ex. 1-406) reported that petroleum solvents used in the Italian shoe industry contain up to 18 percent cyclopentane. Workers exposed to these solvents have developed polyneuropathy, and Oettel (1936/Ex. 1-921) reported that skin exposure to such solvents caused burning and skin blistering after 15 minutes of confined contact. It has not been determined whether the irritation was caused by cyclopentane or by cyclopentane and other substances, such as n-hexane, in the solvent. OSHA received no comments other than those from NIOSH.

In the final rule, OSHA is establishing a PEL of 600 ppm as an 8-hour TWA for cyclopentane. OSHA concludes that occupational exposure to cyclopentane poses a significant risk of irritation and narcosis, which constitute material impairments of health that occur at levels somewhat above the PEL established in the final rule.


ETHYL BROMIDE
CAS: 74-96-4; Chemical Formula: C(2)H(5)Br
H.S. No. 1163


OSHA formerly had an 8-hour TWA limit of 200 ppm for ethyl bromide. The ACGIH also has a limit of 200 ppm as an 8-hour TWA and 250 ppm as a 15-minute STEL. The proposal retained the PEL of 200 ppm and added a STEL of 250 ppm; these limits are established by the final rule. Ethyl bromide is a colorless, highly volatile, flammable liquid with an ether-like odor; it becomes yellow when exposed to light and air.

The concentrations of ethyl bromide reported as lethal to guinea pigs are 3200 ppm for 9 hours and 1700 ppm for 12.5 hours (Sayers, Yant, Thomas, and Berger 1929/Ex. 1-803). von Oettingen (1955/Ex. 1-876) reported the minimal lethal concentration of this substance for mice as 3500 ppm.
Ethyl bromide acts as a central nervous system depressant (narcotic);
additionally, exposure causes irritation of the lungs and congestion and fatty degeneration of the liver, intestinal hemorrhage, and kidney swelling. Several deaths have been reported from the use of ethyl bromide as a general anesthetic (von Oettingen 1955/Ex. 1-876). The record contains no submissions on the health effects of ethyl bromide exposure other than a submission from NIOSH (Ex. 8-47, Table N2; Tr. 3-86) indicating its nonconcurrence. NIOSH noted that one study (Karimullna and Gizatullina 1969) demonstrated liver injury and disrupted liver function in rats exposed 4 hours daily for 6 months to 540 ppm ethyl bromide. NIOSH also reported that an NTP inhalation bioassay to assess the carcinogenicity of ethyl bromide in rats and mice exposed at 100, 200, or 400 ppm was scheduled for peer review in October 1988. OSHA will review this study and any others that become available on this substance to determine whether further action is warranted.

In the final rule, OSHA is retaining its PEL of 200 ppm as an 8-hour TWA and adding a 15-minute STEL of 250 ppm for ethyl bromide. The Agency concludes that these limits will work together to reduce the significant risks of narcosis, kidney and liver damage, and respiratory irritation, all material impairments of health that are associated with occupational exposure to elevated levels of ethyl bromide.


GASOLINE
CAS: 8006-61-9; Chemical Formula: None
H.S. No. 1185


Previously, OSHA had no PEL for gasoline. The ACGIH has a 300-ppm 8-hour TWA and a 500-ppm 15-minute STEL for this substance. OSHA proposed a TWA PEL of 300 ppm and a STEL of 500, and these limits are established in the final rule.

Studies have shown that exposure to 2000 ppm of gasoline for 30 minutes produces mild anesthesia, while exposure to concentrations between 500 and 900 ppm for one hour produces dizziness (Gerarde 1963a and Runion 1975, both as cited in ACGIH 1986/Ex. 1-3, p. 283). However, these authors also found that people exposed to gasoline at concentrations of 160 to 270 ppm for several hours do not experience any symptoms of narcosis but may, as Dr. Liem (Ex. 46) points out, experience eye and throat irritation.

Several commenters noted that gasoline, or specific types of gasoline (i.e., unleaded), may cause kidney and liver damage and cancer, in addition to CNS effects (Exs. 3-746, 8-47, 194, 197; Tr. VII, pp. 70-76). Dr. Franklin Mirer, Director of the Health and Safety Department of the United Auto Workers, made the following statement, which is typical of the views of this group of commenters:

The crucial study in redefining the toxicity of aliphatic hydrocarbons is an inhalation bioassay of unleaded gasoline conducted by the American Petroleum Institute in 1984. The study found increased kidney tumors in male rats and liver tumors in female mice.

The rat portion of the study gave definitely clear evidence of carcinogenic activity. Kidney tumors appeared in a group of rats exposed at 292 parts per million, although a statistical analysis was not documented in the published report. Of greater concern to me than the carcinogenic effect was that male rats also suffered a characteristic toxic kidney effect[s]. Indications of this toxicity appeared as early as three to six months in rats exposed at 47 parts per million (Tr. VII, pp. 70-71).

NIOSH shares these concerns and commented (Ex. 8-47, Table N6B) that gasoline would be an appropriate candidate for a full Section 6(b) rulemaking.

OSHA is aware that there is a recent and rapidly developing body of evidence about other health effects associated with exposure to gasoline and other petroleum materials and that this is an active area of toxicological research. However, the Agency agrees with the American Petroleum Institute (Ex. 124, p. 4) that complex and difficult scientific questions remain to be answered before conclusions can be drawn about these other potentially toxic effects of gasoline exposure. OSHA believes that it would be inappropriate to delay action on this substance at the present time. NIOSH representatives at the hearing (Tr. pp. 3-130, 3-131) agreed that, in the absence of a NIOSH REL for gasoline, promulgation of the proposed limits would constitute an appropriate first step in affording exposed workers protection against these health effects.

OSHA is establishing an 8-hour TWA of 300 ppm, supplemented with a STEL of 500 ppm, to ensure that workplace exposure levels to gasoline do not exceed the TWA level for any length of time; these limits are intended to protect against narcosis. OSHA concludes that the 8-hour TWA and STEL being promulgated in the final rule will substantially reduce the significant risks posed to workers exposed to gasoline in their places of work. These exposure-related health effects, which include narcosis and liver and kidney damage, clearly constitute material impairments of health within the meaning of the Act.


HEPTANE
CAS: 142-82-5; Chemical Formula: CH(3)(CH(2))(5)CH(3)
H.S. No. 1194


The former OSHA limit for heptane was 500 ppm as an 8-hour TWA. The ACGIH TLVs for heptane are 400 ppm as a TWA and 500 ppm as a STEL. NIOSH (1977a/Ex. 1-233) has recommended that workplace exposures to heptane not exceed 85 ppm as a full-shift TWA or 440 ppm as a 15-minute ceiling limit. The proposed PEL and STEL were 400 and 500 ppm, respectively, and these limits are established by the final rule. Heptane is a clear, flammable liquid which is highly volatile.

Patty and Yant (1929, as cited in ACGIH 1986/Ex. 1-3, p. 297) reported that exposure to 1000 ppm of heptane for 6 minutes caused slight dizziness in humans; exposures to higher levels caused vertigo, incoordination, and inappropriate behavior. These authors also reported that a four-minute exposure to 5000 ppm produced complaints of loss of appetite and nausea. Based on this information, as well as on animal data showing 10,000 to 15,000 ppm to be an effect level for heptane-induced narcosis (Fuhner 1921, as cited in ACGIH 1986/Ex. 1-3, p. 297), the ACGIH concluded that heptane was more acutely toxic than hexane. The ACGIH therefore recommended limits for heptane that are somewhat lower than the limits for the hexane isomers.

As discussed in connection with pentane and the hexane isomers, NIOSH (1977a/Ex. 1-233) has recommended the same occupational exposure limits for all of the C(5) - C(8) alkanes (i.e., 350 mg/m(3) TWA and 1800 mg/m(3) as a 15-minute ceiling). This recommendation is based on NIOSH's belief that all C(5) - C(8) alkanes possess a potential neurotoxic capability similar to that of n-hexane. OSHA disagrees with this concept (see the discussion of this issue in Section V of the preamble); the Agency finds that the neurotoxicity caused by exposure to n-hexane is the result of the action of a unique metabolite, 2,5-hexanedione; the majority of record commenters agreed with OSHA that n-hexane is uniquely toxic (Exs. 3-593, 3-896, and 3-1246).

NIOSH does not concur with the limits being established for heptane (Ex. 8-47, Table N2) because NIOSH believes that "it would be incorrect to conclude that the neurotoxic properties ascribed to n-hexane are unique to this compound [n-hexane]. Other alkanes or related chemicals [such as heptane] that are ultimately metabolized to gamma diketone may have similar toxicity" (Tr. III, p. 110). However, OSHA does not agree with NIOSH that all of the C(5) - C(8) alkanes have equal toxicity (see the discussion in Section V of the preamble); OSHA believes that n-hexane is uniquely toxic.

The AFL-CIO (Ex. 194, p. A-7) reiterated its position that OSHA should promulgate a 10-ppm limit for all of the petroleum solvents, including heptane. However, OSHA has determined (see Section IV.D) that it would be inappropriate at this time to enlarge the scope of this already extensive regulation. The United Auto Workers (Ex. 197) described engineering controls that could be used to achieve the lower levels the unions advocate for all petroleum solvents; these are discussed in Section VII.

Because heptane is considered to be more acutely toxic than hexane, OSHA concludes that it is appropriate to revise its limit for heptane to a level below that established for the hexane isomers to reduce the significant risk of narcosis, which is a material health impairment. Therefore, OSHA is revising its limit for heptane to 400 ppm as an 8-hour TWA and 500 ppm as a 15-minute STEL. The Agency concludes that the TWA and STEL together will substantially reduce this significant occupational risk.


HEXANE ISOMERS
CAS: None; Chemical Formula: (CH(3))(3)C(3)H(5); n(CH(3))(4)C(2)H(2)
H.S. No. 1201


Previously, OSHA had no limit for the hexane isomers. The ACGIH TLVs for the hexane isomers are 500 ppm as an 8-hour TWA and 1000 ppm as a 15-minute STEL. NIOSH has a recommended TWA limit for these isomers of 100 ppm, supplemented with a 510-ppm 15-minute ceiling. The proposed and final rule PELs are an 8-hour TWA of 500 ppm and a 15-minute STEL of 1000 ppm. The hexanes are clear, highly volatile liquids with a mild gasoline-like odor.

A study by Drinker, Yaglou, and Warren (1943/Ex. 1-730) shows that humans exposed to 1400 to 1500 ppm of hexane experienced nausea and headache. Patty and Yant (1929, as cited in ACGIH 1986/Ex. 1-3, p. 307) found that a 10-minute exposure to 5000 ppm caused giddiness and dizziness in exposed subjects. A study by Nelson, Enge, Ross et al. (1943/Ex. 1-66) showed no effects in unacclimated subjects exposed to hexane isomers in concentrations of 500 ppm, but narcotic effects have often been seen in subjects exposed at levels above 1000 ppm (Elkins 1959d, as cited in ACGIH 1986, Ex. 1-3, p. 307). The ACGIH based its limit primarily on the Nelson, Enge, Ross et al. (1943/Ex. 1-66) study.

NIOSH recommends limits for the hexane isomers of 100 ppm as a 10-hour TWA and 510 ppm as a 15-minute short-term limit. These recommendations are based on human and animal evidence showing that exposure to n-hexane below concentrations of 500 ppm is associated with the development of polyneuropathy (Inoue, Takeuchi, Takeuchi et al. 1970/Ex. 1-75; Miyagaki 1967/Ex. 1-198); NIOSH (1977a/Ex. 1-233) did not distinguish between n-hexane and other hexane isomers when making its recommendation for an exposure limit. NIOSH concluded that all of the C5-C8 alkanes are potential neuropathic agents and should have the same PELs as those established for n-hexane.

OSHA disagrees with NIOSH that all C(5)-C(8) alkanes are potential neuropathic agents. As discussed in Section V of the preamble, OSHA believes that a metabolite of n-hexane (2,5-hexanedione) is responsible for the unique neurotoxic properties of n-hexane (see also the discussion of n-hexane in Section VI.C.1 of the Preamble). Thus OSHA agrees with the ACGIH that "it seems unlikely that all the hexanes would follow the same metabolic route in the body [as n-hexane], in view of the marked variations in structure of the molecule" (ACGIH 1986/Ex. 1-3, p. 307). The majority of commenters supported OSHA's conclusion that n-hexane is uniquely toxic because of the presence of 2,5-hexanedione and that the other alkanes are not toxic in this way (Exs. 3-593, 3-896, and 3-1246). However, the AFL-CIO (Ex. 194, p. A-7) argued for a lower limit for the hexane isomers and all petroleum solvents (see the discussion for heptane, above), and the UAW (Ex. 197) noted that controls are available to reduce exposures (see Section VII for a discussion of feasibility).

After reviewing the evidence cited by the ACGIH (1986/Ex. 1-3), NIOSH (1977a/Ex. 1-233), and commenters to the record, OSHA finds that workers exposed to hexane isomers are at significant risk of experiencing narcosis and of developing neuropathy at exposure levels above the new PELs. The Agency concludes that establishing an 8-hour TWA of 500 ppm and a 15-minute STEL of 1000 ppm will substantially reduce these risks. OSHA finds that both narcosis and neuropathy constitute material health impairments.

ISOAMYL ALCOHOL (PRIMARY AND SECONDARY)
CAS: 123-51-3; Chemical Formula:  (CH(3))(2)CHCH(2)CH(2)OH - Primary;
                                   (C(2)H(5))(2)CHOH - Secondary
H.S. No. 1218

OSHA's former limit for the isoamyl alcohols was 100 ppm as an 8-hour TWA. The ACGIH has established an 8-hour TLV-TWA of 100 ppm and a 15-minute STEL of 125 ppm for these substances, which are colorless liquids that have pungent tastes and an alcoholic odor that causes coughing. OSHA proposed to retain the 8-hour TWA limit of 100 ppm and to add a 125-ppm 15-minute STEL; NIOSH (Ex. 8-47, Table N1) concurs with these limits. The final rule retains the 100-ppm 8-hour TWA and adds a 125-ppm STEL for isoamyl alcohol.

In rats, the oral LD(50) for the primary isoamyl alcohol is 7.07 ml/kg (Smyth, Carpenter, Weil et al. 1969/Ex. 1-442). Haggard, Miller, and Greenberg (1945/Ex. 1-956) determined that isoamyl alcohol's anesthetic toxicity was approximately 12 times higher than that of ethyl alcohol, which has a TLV-TWA of 1000 ppm. Exposure to isoamyl alcohol is not associated with chronic effects.

Smyth (1956/Ex. 1-759) reported that the principal effect of inhalation exposure to this substance is narcosis, and that a 100-ppm level would protect exposed workers against significant narcosis but not against some irritation. Nelson, Enge, Ross, and co-workers (1943/Ex. 1-66) stated that unacclimatized human volunteers reported upper respiratory tract irritation after brief exposures to an isoamyl alcohol concentration of 100 ppm, and objectionable eye and mucous membrane irritation at short-term exposures to 150 ppm. With the exception of NIOSH's submittal, OSHA received no comments on isoamyl alcohol.

In the final rule, OSHA is retaining the 8-hour TWA of 100 ppm and adding a 15-minute STEL of 125 ppm for the isoamyl alcohols (primary and secondary). OSHA concludes that a short-term limit is necessary because the chemically induced eye and throat irritation associated with exposure to the isoamyl alcohols is an acute effect that occurs at concentrations only slightly higher than the 100-ppm 8-hour TWA; in addition, significant narcosis occurs at the levels permitted by the absence of a STEL. The Agency concludes that both the TWA and STEL limits are necessary to ensure that workers are protected against the material impairments represented by significant narcosis, as well as the eye, nose, and upper respiratory tract irritation known to be associated with brief exposures to isoamyl alcohol at levels above 100 ppm.


ISOPHORONE
CAS: 78-59-1; Chemical Formula: C(9)H(14)O
H.S. No. 1221


The former OSHA limit for isophorone was 25 ppm as an 8-hour TWA. The ACGIH has established a 5-ppm TLV as a ceiling limit, and NIOSH recommends a workplace standard of 4 ppm as an 8-hour TWA for isophorone. Isophorone is a colorless liquid at room temperature, and it has a camphor-like odor. The proposed limit was 4 ppm as an 8-hour TWA; NIOSH (Ex. 8-47, Table N1) concurs. This is the limit promulgated by the final rule.

Studies in animals and with human volunteers indicate that exposures to high concentrations of isophorone cause nephrotoxic and other adverse effects. A paper by Smyth, Seaton, and Fischer (1942/Ex. 1-378) reported that guinea pigs and rats exposed to 550 ppm isophorone for six weeks demonstrated degenerative changes in the kidneys and liver. At an exposure level of 25 ppm, no adverse effects were noted, but at 50 ppm, the liver of one animal and the kidneys of four others were damaged. The entire group of 20 animals exposed at 50 ppm survived, but 2 of 16 animals died after this level was raised to 100 ppm (Smyth, Seaton, and Fischer 1942/Ex. 1-378). Volunteers exposed for a few minutes to isophorone vapor at concentrations between 40 and 400 ppm experienced eye, nose, and throat irritation; several subjects exposed at the 200-ppm level developed headache, nausea, faintness, dizziness, and a feeling of suffocation (Smyth and Seaton 1940a/Ex. 1-377). Silverman, Schulte, and First (1946/Ex. 1-142) reported that volunteers exposed to 25 ppm isophorone, the former OSHA PEL, complained of irritation of the eyes, nose, and throat. Another study conducted by the Western Electric Company (Ware 1973, as cited in ACGIH 1986/Ex. 1-3, p. 333) reported that workers exposed for a one-month period to levels of 5 to 8 ppm isophorone demonstrated fatigue and malaise. When the workplace level was reduced to between 1 and 4 ppm, there were no complaints of adverse effects. The NIOSH criteria document for the ketones (1978f, as cited in ACGIH 1986/Ex. 1-3, p. 333) notes that all of the ketones are central nervous system depressants and that workplace exposures to more than one ketone may produce additive effects.

A comment from the New Jersey Department of Public Health (Ex. 144) urged OSHA to use EPA's IRIS data to set a limit for isophorone. The use of IRIS data is discussed in Section VI.A.

In the final rule, OSHA is reducing its 8-hour TWA PEL of 25 ppm to an 8-hour TWA of 4 ppm to protect workers against the significant risk of fatigue, nausea, and headaches, which together constitute material health impairments that have been demonstrated to occur at isophorone levels between 5 and 8 ppm. The Agency concludes that this limit will substantially reduce these occupational risks.


METHYL CHLORIDE
CAS: 74-87-3; CHEMICAL FORMULA: CH(3)Cl
H.S. No. 1254


OSHA's former limits for methyl chloride were 100 ppm as an 8-hour TWA, 200 ppm as a ceiling (not to be exceeded for more than five minutes in any three-hour period), and 300 ppm as a peak. The ACGIH has a 50-ppm 8-hour TLV-TWA limit and a 100-ppm 15-minute STEL for this substance, and NIOSH recommends the lowest feasible limit because it considers methyl chloride a potential occupational carcinogen. The proposed PELs were 50 ppm as an 8-hour TWA and 100 ppm as a 15-minute STEL; the final rule establishes these limits. Methyl chloride is a colorless, sweet-smelling gas.

There is considerable evidence in humans and some in animals demonstrating that exposure to methyl chloride by inhalation or dermal absorption produces narcosis and other central nervous system effects, including respiratory failure and death (ACGIH 1986/Ex. 1-3, p. 380). In animals, repeated exposures to 500 ppm or to higher concentrations can be life-threatening, but exposures to 300 ppm for 64 weeks caused no apparent effects (Smith and von Oettingen 1947/Ex. 1-527).

Reports in the earlier literature described by Fairhall (1969a/Ex. 1-848) indicate that moderate (not further specified) exposure causes ocular symptoms that may persist for weeks, while high (not further specified) exposure has severe effects on the central nervous system. Patty (1963a/Ex. 1-855) states that serious exposure causes central nervous system, liver and kidney, and bone marrow effects, with symptoms of ataxia, staggering gait, weakness, tremors, vertigo, speaking difficulty, and blurred vision. Symptoms may be of several weeks' duration or may even be permanent (Patty 1963a/Ex. 1-855).

The Dow Chemical Company (as cited in ACGIH 1986/Ex. 1-3, p. 380) studied the methyl chloride exposures of employees in 54 job classifications over a four-month period. Exposures ranged from 5 to 78 ppm methyl chloride (8-hour TWAs), averaged 30 ppm over the work shift, and occasionally included peaks as high as 440 ppm. Medical examination of these workers revealed no detectable effects of methyl chloride exposure. However, average eight-hour exposures in the range of 195 to 475 ppm caused symptoms of weakness, drowsiness, staggering gait, thickness of the tongue, and memory lapses in some of the exposed employees (Dow Chemical Company, as cited in ACGIH 1986/Ex. 1-3, p. 380).

In a study of six cases of industrial methyl chloride poisoning, workers chronically exposed to levels between 200 and 400 ppm developed neurotoxic symptoms after two or more weeks of exposure (Scharnweber, Spears, and Cowles 1974/Ex. 1-664). Symptoms included drowsiness, dizziness, mental confusion, clouded vision, staggering gait, and slurred speech, and symptoms sometimes recurred after apparent recovery and in the absence of renewed exposure.

Repko and co-workers (1976/Ex. 1-1165) found that workers exposed to concentrations of methyl chloride ranging from 7.4 to 70 ppm but averaging 33.6 ppm displayed a significant performance decrement, and that exposures below 100 ppm produced significant but transitory changes in functional capacity. OSHA will continue to monitor the toxicological evidence for methyl chloride and will re-evaluate the substance if this evidence suggests that this is appropriate.

OSHA received comments on methyl chloride from NIOSH and the Methyl Chloride Industry Association. NIOSH believes that methyl chloride is an appropriate substance for a Section 6(b) rulemaking because, in NIOSH's view, methyl chloride is a potential occupational carcinogen (Ex. 8-47; Tr. 3, pp. 97-98). The AFL-CIO (Ex. 194) agrees with NIOSH on this point. The Methyl Chloride Industry Association (MCIA) indicated its support of OSHA's proposed PELs for this substance and submitted material suggesting that methyl chloride may not be a potential occupational carcinogen (Ex. 148, pp. 2-4). MCIA submitted to the record a copy of the IARC monograph and recent supplement on methyl chloride, which conclude that the evidence for the carcinogenicity of methyl chloride is inadequate in both animals and humans.

In the final rule, OSHA is establishing an 8-hour TWA of 50 ppm and a 15-minute STEL of 100 ppm for methyl chloride. The Agency concludes that these two limits together will substantially reduce the significant risk of neurotoxic effects, including functional impairment, performance decrements, headaches, dizziness, slurred speech, and staggering gait, which together constitute material impairments of health. These effects have been associated with exposure to this substance at the levels permitted by OSHA's former PEL. OSHA will continue to monitor the literature on the toxicity of methyl chloride to determine whether other action is appropriate.


METHYL CHLOROFORM (1.1.1-TRICHLOROETHANE)
CAS: 71-55-6; Chemical Formula: CH(3)CCl(3)
H.S. No. 1255


Previously, OSHA had an 8-hour TWA limit of 350 ppm for methyl chloroform. The ACGIH has established the same TWA limit in addition to a TLV-STEL of 450 ppm; NIOSH recommends a 15-minute ceiling limit of 350 ppm. The Agency proposed to retain its 8-hour TWA limit and to add a STEL of 450 ppm; NIOSH concurs that these limits are appropriate but would express them as ceilings rather than as TWAs (Ex. 8-47, Table N7). The final rule retains an 8-hour TWA of 350 ppm and adds a STEL of 450 ppm for methyl chloroform, which is a clear, nonflammable liquid.

The primary health effects associated with exposure to methyl chloroform are anesthesia and cardiac sensitization. The oral toxicity of methyl chloroform is low, with LD(50) values ranging from 5.7 to 12.3 g/kg for rats, mice, rabbits, and guinea pigs. This substance does, however, defat the skin on contact, causing redness and scaling (Torkelson, Oyen, McCollister, and Rowe 1958/Ex. 1-768). Skin absorption is relatively insignificant: the acute percutaneous LD(50) in rabbits is greater than 16 g/kg, and slight, reversible irritation was observed from applications of 0.5 g/kg to rabbit skin for 90 days (Torkelson, Oyen, McCollister, and Rowe 1958/Ex. 1-768). Repeated exposures of animals to concentrations between 1000 and 10,000 ppm for three months produced anesthesia and lung and liver damage in some species, but exposure to 500 ppm of methyl chloroform vapor for seven hours daily, five days/week for six months caused no toxic changes in guinea pigs, rabbits, or monkeys (Torkelson, Oyen, McCollister, and Rowe 1958/Ex. 1-768). Other animal studies (Gehring 1968/Ex. 1-637; Plaa, Evans, and Hine 1958/Ex. 1-754; Rowe, Wujkowski, Wolf et al. 1963/Ex. 1-687) have reported that methyl chloroform has low hepatotoxicity, but cardiac sensitization has occurred at high doses (5000 to 10,000 ppm)(Rennick, Malton, Moe, and Seevers 1949/Ex. 1-864; Trochimowicz, Reinhardt, Mullin et al. 1976/Ex. 1-992). Tests in rats and mice for teratogenicity and carcinogenicity have demonstrated negative results (Schwetz, Leong, and Gehring 1975/Ex. 1-757; NIOSH 1976m, as cited in ACGIH 1986/Ex. 1-3, p. 382; Weisberger 1977/Ex. 1-694).

In humans, it has been reported that anesthetic effects may begin to occur at methyl chloroform concentrations approaching 500 ppm (Stewart, Gay, Schaffer et al. 1969/Ex. 1-529). Deaths from anesthesia and/or cardiac sensitization have been noted in employees working in confined areas (Patty 1963d/Ex. 1-856). Kramer and co-workers (1978/Ex. 1-515) conducted an epidemiological study of men and women exposed for periods ranging from several months to six years to methyl chloroform at levels that occasionally exceeded 200 ppm; when compared to matched-pair controls, no adverse exposure-related effects were found (Kramer, Ott, Fulkerson et al. 1978/Ex. 1-515).

Commenters supplied conflicting evidence to the record on the toxicity of methyl chloroform. The Workers Institute for Safety and Health (WISH) (Ex. 116, Tr. pp. 7-134, 135) noted that there is an extensive amount of recent information on this substance. In particular, WISH mentioned three recent studies (McLeod et al. 1987, Karlsson et al. 1987, and Mackay et al. 1987) that demonstrate that methyl chloroform causes chronic cardiac toxicity on long-term exposure, may have toxic effects on brain cells, and may cause behavioral changes after 3.5-hour exposures to 175 to 350 ppm. WISH believes that these studies and others warrant a further reduction in the PELs for methyl chloroform. However, the Halogenated Solvents Industry Alliance (Ex. 186) criticized these studies and believes that the PELs for methyl chloroform are appropriate.

In the final rule, OSHA is retaining its PEL of 350 ppm as an 8-hour TWA and adding a STEL of 450 ppm for methyl chloroform. The Agency concludes that this combined PEL-STEL limit will protect workers against the significant risk of narcotic and cardiac-sensitizing effects, which constitute material health impairments that are potentially associated with exposure to methyl chloroform at the elevated short-term levels permitted by an 8-hour TWA limit alone.


OCTANE
CAS: 111-65-9; Chemical Formula: CH(3)(CH(2))(6)CH(3)
H.S. No. 1296


OSHA's former limit for octane was 500 ppm as an 8-hour TWA. The ACGIH has a 300-ppm TWA and a 375-ppm STEL; NIOSH (1977a/Ex. 1-233) recommends a 75-ppm 10-hour TWA and a 385-ppm 15-minute ceiling limit. The proposed PELs were an 8-hour TWA of 300 ppm and a 15-minute STEL of 375 ppm, and these are the limits promulgated in the final rule. n-Octane is a colorless, flammable liquid with an odor like that of gasoline.

Mice exposed to octane concentrations of 6600 to 13,700 ppm developed narcosis within 30 to 90 minutes (Fuhner 1921, as cited in ACGIH 1986/Ex. 1-3, p. 448). Flury and Zernik (1931h, as cited in ACGIH l986/Ex.l-3, p. 448) believed the narcotic concentration in humans to be 5000 ppm; Patty and Yant (1929, as cited in ACGIH 1986/Ex. 1-3, p. 448) placed the narcotic concentration at 8000 ppm. Based on this information, the ACGIH concluded that octane was 1.2 to 2 times more toxic than heptane, and recommended TLVs of 300 ppm TWA and 375 ppm STEL.

As discussed in more detail in Section V of the preamble and in the discussions above for the other C(5)-C(8) alkanes, the NIOSH (1977a/Ex. 1-233) recommended limits for octane are based on NIOSH's belief that all C(5)-C(8) alkanes present a neurotoxic hazard similar to that of n-hexane.

OSHA disagrees with this conclusion and has found instead that the neurotoxic properties of n-hexane are unique among the substances in the alkane series. NIOSH continues to recommend these lower limits for all of the C(5)-C(8) alkanes, including octane (Ex. 8-47, Table N2; Tr. 3-86 to 122). The AFL-CIO (Ex. 194) and the UAW (Ex. 197) made the same comments for octane as for heptane (see the discussion, above).

The Chevron Corporation (Ex. 3-896) objected to the proposed short-term exposure limit for octane on the grounds that studies showing narcosis at concentrations of 5000 and 8000 ppm do not provide a justification for a STEL. In addition, Chevron stated that, "as a practical matter, a STEL that is only 25 percent greater than the TWA value suggests a level of precision that simply does not exist in exposure assessment techniques. Variations in sampling and analytical methodologies combined with normal statistical variability in exposure patterns make it impossible to reliably distinguish between exposures that differ by only 20 to 25 percent. Intuitively, it is not reasonable to conclude that a concentration that is slightly above an acceptable 8-hour exposure level would be unsafe for a 15-minute exposure" (Ex. 3-896, p. 3).

In response to Chevron, OSHA notes that octane is considered more toxic than heptane, for which OSHA is establishing limits of 400 ppm as an 8-hour TWA and 500 ppm as a 15-minute STEL. Short-term effects have been observed in humans and animals exposed to the hexane isomers at levels below 500 ppm (Nelson, Enge, Ross et al. 1943/Ex. 1-66), and OSHA finds it appropriate to establish a STEL for octane and several other alkanes to protect against these narcotic effects. OSHA disagrees with Chevron that it is not possible to distinguish between octane exposures of 300 ppm and those of 375 ppm; although a + 25-percent level of precision may be difficult to achieve at very low contaminant concentrations, there should be no sampling and analytical difficulty at the levels being considered here. Finally, OSHA notes that a theoretically possible, although unlikely, exposure scenario that could occur with an 8-hour TWA limit of 300 ppm alone would be an excursion of up to 9600 ppm; such an exposure could produce serious CNS effects in exposed workers. Thus, the purpose of the 375-ppm STEL is to ensure that the TWA limit is not exceeded for any substantial period of time and that exposures are effectively controlled.

In the final rule, OSHA is revising its limits for octane to 300 ppm as an 8-hour TWA and 375 ppm as a 15-minute STEL. The Agency concludes that these limits will protect workers from the significant risks of narcosis, a material health impairment that is associated with octane exposures. OSHA believes that these limits will substantially reduce these significant risks.


PENTANE
CAS: 109-66-0; Chemical Formula: C(5)H(12)
H.S. No. 1306


Previously, OSHA's limit for pentane was 1000 ppm TWA. In 1976, the ACGIH adopted a 600-ppm TLV-TWA and a 750-ppm TLV-STEL. NIOSH (1977a/Ex. 1-233; Ex. 8-47, Table N2) has recommended that workplace exposures to pentane not exceed 120 ppm as a 10-hour TWA and 610 ppm as a 15-minute short-term limit. The proposed and final rule PELs are 600 ppm as an 8-hour TWA and 750 ppm as a 15-minute STEL. Pentane, a colorless, flammable liquid with a gasoline-like odor, is usually encountered in volatile petroleum fractions, some of which are used as solvents. Pure pentane is used as a blowing agent for plastics, in solvent extraction, and in ice manufacture.

Fairhall (1957c/Ex. 1-184) stated that narcosis and mucous membrane irritation were the only reported toxic effects resulting from exposure to pentane. The reported lethal concentration in humans is 130,000 ppm (Flury and Zernik 1931j/Ex. 1-994; Swann, Kwon, and Hogan 1974/Ex. 1-124). According to Patty and Yant (1929, as cited in ACGIH 1986/Ex. 1-3, p. 463), humans exposed for 10 minutes to 5000 ppm did not complain of any adverse symptoms.

In a report by Gaultier, Rancurel, Piva, and Efthymioc (1973/Ex. 1-123), five cases of polyneuropathy occurred among employees exposed to a solvent containing 80 percent pentane, 14 percent heptane, and 5 percent hexane. Based largely on this report, NIOSH (1977a/Ex. 1-233) recommended the same occupational limit for all C(5) - C(8) alkanes as for the neuropathic agent n-hexane (350-mg/m(3) TWA and 1800-mg/m(3) 15-minute short-term limits; these limits are equal to about 120-ppm TWA and 610-ppm 15-minute short-term limits for pentane).

OSHA points out that the rationale used by NIOSH in setting a limit for pentane ignores the theory that n-hexane is uniquely neuropathic via metabolism to 2,5-hexanedione, which is the same metabolite that is formed during exposure to another neuropathic agent, methyl butyl ketone (see the discussion in Section V of this preamble). OSHA finds that all C(5) - C(8) alkanes are not equally toxic; the Agency concludes that a metabolite of n-hexane exhibits unique neurotoxic properties. In OSHA's view, the Gaultier, Rancurel, Piva, and Efthymioc (1973/Ex. 1-123) study does not provide specific isomer exposure data supporting the NIOSH RELs of 120 ppm (TWA) and 610 ppm (STEL).

The Chevron Corporation (Ex. 3-896) objected to the proposed STEL for pentane because, in Chevron's opinion, the health evidence did not justify this addition. However, OSHA finds that the STEL is needed to protect workers from the significant neurotoxic effects of pentane exposure by ensuring that the high short-term excursions possible in the absence of a STEL do not occur. The Workers Institute for Safety and Health (Ex. 116) and the UAW (Ex. 197) submitted the same comments on pentane as on heptane (which see).

In the final rule, the Agency is establishing an 8-hour TWA of 600 ppm and a 15-minute STEL of 750 ppm as the permissible exposure limits for pentane. OSHA concludes that these limits will protect exposed workers from the narcosis long known to be associated with pentane exposure; the Agency finds that narcosis constitutes a material health impairment within the meaning of the Act.


2-PENTANONE (METHYL PROPYL KETONE)
CAS: 107-87-9; Chemical Formula: CH(3)COC(3)H(7)
H.S. No. 1307


The former OSHA limit for 2-pentanone was 200 ppm as an 8-hour TWA. The ACGIH has a 200-ppm TLV-TWA and a 250-ppm TLV-STEL; NIOSH (1978k, as cited in ACGIH 1986/Ex. 1-3, p. 408) has recommended a 150-ppm limit as a 10-hour TWA. The proposed PELs were 200 ppm as an 8-hour TWA and 250 ppm as a 15-minute STEL, and these limits are established in the final rule. 2-Pentanone is a clear, flammable liquid with a strong odor resembling acetone and ether.

Both the ACGIH- and NIOSH-recommended limits are based on a study by Specht, Miller, Valaer, and Sayers (1940/Ex. 1-1179), which found that guinea pigs exhibited irritation and weakness on exposure to 2500 ppm, and that exposure to 5000 ppm produced narcosis and coma. The authors concluded that 2-pentanone is considerably less toxic than methyl butyl ketone but is more toxic than methyl ethyl ketone, and, in addition, is likely to be more irritating than either methyl ethyl ketone or acetone. The ACGIH-recommended limits are based on a judgment that the 200-ppm TLV-TWA and 250-ppm TLV-STEL are low enough to prevent narcosis and irritation.

NIOSH (1978k, as cited in ACGIH 1986/Ex. 1-3, p. 408) applied the findings of the Specht, Miller, Valaer, and Sayers (1940/Ex. 1-1179) study to the results of the Nelson, Enge, Ross et al. study (1943/Ex. 1-66); these latter authors reported that volunteers complained of slight irritation on exposure to 100 ppm methyl ethyl ketone. Because 2-pentanone was found by Specht, Miller, Valaer, and Sayers (1940/Ex. 1-1179) to be at least as irritating as methyl ethyl ketone, NIOSH (1978k, as cited in ACGIH 1986/Ex. 1-3, p. 408) stated that a "slight reduction" in the standard was warranted for 2-pentanone. Therefore, NIOSH recommended a 150-ppm limit for 2-pentanone, and NIOSH reiterates this recommendation in the present rulemaking (Ex. 8-47, Table N2; Tr. 3-86). No other comments were submitted regarding the health effects of 2-pentanone.

OSHA has concluded that the combination of a 200-ppm TWA and a 250-ppm STEL will work together to ensure that workplace levels are maintained at levels that will prevent the occurrence of the adverse health effects associated with exposures to this chemical. In the final rule, OSHA is establishing these limits to reduce the significant risks of narcosis, a material impairment of health, which is associated with exposures to 2-pentanone at elevated short-term levels.


STODDARD SOLVENT
CAS: 8052-41-3; Chemical Formula: C(9)H(20)
H.S. No. 1371


OSHA's former limit for Stoddard solvent was 500 ppm as an 8-hour TWA. The ACGIH has established a TLV-TWA of 100 ppm, and NIOSH (1977g, as cited in ACGIH 1986/Ex. 1-3, p. 537) recommends limits of 350 mg/m(3) as a 10-hour TWA and 1800 mg/m(3) as a 15-minute ceiling for all refined petroleum solvents; these limits correspond approximately to a 60-ppm TWA and a 310-ppm STEL, respectively. Stoddard solvent is a refined petroleum solvent having a flash point in the range of 102 to 110 deg. F, a boiling point in the range of 154 to 202 deg. C, and containing 65 percent or more C10 and higher-molecular-weight hydrocarbons. OSHA proposed to reduce its 8-hour TWA to 100 ppm, and the final rule promulgates this limit. NIOSH (Ex. 8-47, Table N1) agreed with the Agency's selection of this PEL.

The former OSHA limit of 500 ppm (equivalent to the limit in the 1968 ACGIH TLV list) was based largely on analogy to the irritant and narcotic effects of gasoline vapor in humans (ACGIH 1966/Ex. 1-13, pp. 176-177). The revised ACGIH limit of 100 ppm was based on a report by Carpenter, Geary, Myers et al. (1978/Ex. 1-301), which found slight kidney damage among rats exposed to 330 ppm Stoddard solvent for 65 days. The ACGIH TLV for Stoddard solvent was calculated from the TLVs for nonane and trimethyl benzene, the major components of Stoddard solvent (ACGIH 1986/Ex. 1-3); the TLV for nonane is 200 ppm, based on the Carpenter, Geary, Myers et al. (1978/Ex. 1-301) study's findings of a no-effect level for nonane in rats of 590 ppm, while the TLV for trimethyl benzene is 25 ppm, because there is evidence that humans exposed to the isomers of trimethyl benzene exhibited central nervous system effects (ACGIH 1986/Ex. 1-3).

The ACGIH (1986/Ex. 1-3, p. 537) notes that guinea pigs exposed for 30 eight-hour days to 290 ppm Stoddard solvent developed congestion and emphysema of the lungs. The eye irritation threshold in humans is approximately 150 ppm for 15 minutes (ACGIH 1986/Ex. 1-3, p. 537).

The NIOSH limits of a 350-mg/m(3) (60-ppm) TWA and an 1800-mg/m(3) (310-ppm) 15-minute short-term limit are derived from NIOSH's recommended limits for all of the C(5)-C(8) alkanes; NIOSH recommended the same limit for Stoddard solvent as for all C(5)-C(8) alkanes both because of the lack of scientific data on Stoddard solvent's chronic effects and because of a report of polyneuropathy occurring among workers exposed to jet fuels containing mixtures of kerosene and gasoline. NIOSH reasoned that, although the C(5)-C(8) alkanes present in jet fuel may have been implicated, it was possible that the heavier hydrocarbon components may also have been responsible. Thus, the NIOSH recommended limits for Stoddard solvent reflect a concern that higher-molecular-weight hydrocarbons may be neuropathic. However, no evidence exists that the C(10) and higher molecular weight hydrocarbons cause neuropathies. NIOSH has re-examined the health evidence for Stoddard solvent in this rulemaking and concurs with OSHA that the 100-ppm 8-hour TWA limit is appropriate for this substance (Ex. 8-47, Table N1). Several commenters (Tr. 7-70 to 7-95; Exs. 46, 116, 194, 197) urged OSHA to reevaluate the final rule's limits for this substance because recent evidence points to hepatic and hematopoietic effects. OSHA is aware of the emerging literature and will monitor developments in the future. In the final rule, OSHA is establishing an 8-hour TWA of 100 ppm to reduce the significant risk of eye irritation, narcosis, polyneuropathy, and kidney damage, all of which constitute material health impairments that have been demonstrated to occur in either humans or animals at levels well below the former PEL. OSHA finds that the study of Carpenter and co-workers (1978/Ex. 1-301) in animals and the study reported by the ACGIH showing that exposed workers develop eye irritation at levels of 150 ppm and above clearly indicate that a reduced PEL is needed for Stoddard solvent to diminish these significant occupational risks.


STYRENE
CAS: 100-42-5; Chemical Formula: C(6)H(5)CHCH(2)
H.S. No. 1372


OSHA's former exposure limits for styrene (listed in 29 CFR 1910.1000, Table Z-2) were 100 ppm as an 8-hour TWA, 200 ppm as a STEL, not to be exceeded for more than 5 minutes in any 3-hour period, and 600 ppm as a ceiling limit. OSHA proposed revising these limits to 50 ppm as an 8-hour TWA and 100 ppm as a 15-minute STEL, based on both the ACGIH TLVs and the NIOSH RELs, which are identical. NIOSH (Ex. 150, Comments on Styrene) concurs that these limits are appropriate for styrene, and they are established in the final rule. Styrene monomer is a colorless, oily liquid with an aromatic odor.

In the proposal, styrene was located in the cancer category; in the final rule, it has been moved into the narcotics section, for the reasons discussed below. According to the generic methodology used by OSHA to group the 428 substances included in this rulemaking, substances were grouped according to the guidelines given by the ACGIH for assigning an appropriate exposure limit for a particular substance. In other words, if the ACGIH noted that a particular TLV was designed to protect against irritant effects, that substance was classified by OSHA in the sensory irritant category. This classification scheme was chosen by OSHA because it facilitated the rulemaking process (made unusually complex by the broad scope of the issues addressed) and made the discussion of hundreds of substances easier. However, as is often the case with classification schemes, this methodology oversimplifies the issues, particularly in those situations where a substance has more than one serious health effect.

Styrene is a case in point. This widely used substance is an irritant, a narcotic, and a neuropathic agent; some studies also show that animals exposed to styrene vapor develop tumors. The ACGIH Documentation (1986/Ex.1-3) for styrene states:

[A] time-weighted average TLV of 50 ppm, one-tenth the lowest concentration possibly causing lymphoid or hematopoietic tumors in female rats, and a STEL of 100 ppm are suggested as reasonable limits [for styrene] (emphasis added) (ACGIH 1986/Ex. 1-3, p. 539).

Because the ACGIH limit had been set with reference to tumorigenicity (notwithstanding the lack of an A1 or A2 cancer designation), styrene fell into the category of carcinogens for the purposes of the proposal (53 FR 21202).

Many commenters objected to the proposal's classification of styrene as a carcinogen (Exs. 3-741, 3-742, 3-1059, L3-1312B, 8-12, 8-32, 8-48, 8-54, 34, 36, 103, 155, and 187; Tr. 8/3/88, pp. 5-9 to 5-127; Tr. pp. 11-265, 11-266). For example, the Styrene Information and Research Council (SIRC) stated:

Regarding the long-term animal studies on styrene...there have been nine...seven of which were via the oral route and two via inhalation....All of these studies showed either no evidence of cancer or gave inconclusive results due to study limitations, e.g., faulty study design, high background tumor incidence and/or high morbidity in test and control groups of animals (Ex. 3-742, p. 10).

Other commenters echoed the view of the SIRC. For example, a paper prepared by the Epidemiology Department of the Dow Chemical Company and reported on in Dow's prehearing submission (Ex. 3-741, p. 55) concludes: "[O]verall these data do not support a causal link between lymphatic and hematopoietic cancer and styrene." Dr. Gregory Bond (Ex. 103 and testimony) also criticized the epidemiology studies relied on by OSHA in the proposal, as did the Chemical Manufacturers Association (Ex. 8-54). J. Roger Crawford, Director of Environmental Control for the Outboard Marine Corporation, a manufacturer of outboard and inboard engines, lawn care equipment, and marine products, commented that OSHA's conclusion in the proposal about the carcinogenicity of styrene "is clearly outside the mainstream of most scientific opinion" (Ex. 8-12, p. 3).

In posthearing testimony on behalf of the SIRC, Dr. Robert G. Tardiff, Director of Versar, Incorporated's Risk Focus Division, described the comments of EPA's Science Advisory Board (SAB) on a draft EPA Water Criteria Document on Styrene. Dr. Tardiff reported that the SAB had advised EPA to consider styrene a "possible human carcinogen (Category C) at best" (Ex. 34, p. 4). Dr. Tardiff further commented that the Category C classification "would generally lead EPA to regulate the compound based on protection against non-cancer pathology" (Ex. 34, pp. 4-5).

However, EPA's Guidelines for Carcinogen Risk Assessment (51 FR 33992) interpret the meaning of a Category C designation somewhat differently than does Dr. Tardiff. In a letter dated March 9, 1988 from the SAB to EPA's Administrator, Lee M. Thomas (Attachment to Ex. 124), the SAB makes clear that factors other than category are important to consider for regulatory purposes:

From a scientific point of view, it seems inappropriate for EPA and other agencies to regulate substances that are classified as B2 [probable human carcinogens] and not to consider regulation of compounds classified as C.... A substance classified as C (limited evidence in animals) for which human exposure is high may represent a much greater potential threat to human health [than substances with classifications of B2, B1, or A where exposures are lower].

EPA and other agencies...may, therefore, wish to take steps to reduce high exposures to substances in the C category whenever there appears to be a potentially significant threat to human health (in the sense [where risk estimates are]...above the threshold where regulation may be judged appropriate) (Attachment to Ex. 124).

Several animal and human studies have suggested that styrene may be a carcinogen. A nested case-control study conducted by McMichael, Spirta, Gamble, and Tousey (1976/Ex. 1-206) found significantly increased risks of lymphatic and hematopoietic cancer, lymphatic leukemia, and stomach cancer among workers exposed to both styrene and butadiene. A retrospective cohort mortality study by Meinhardt, Lemen, Crandall, and Young (1982/Ex. 1-199), also among workers exposed concurrently to styrene and butadiene, reported an excess risk of leukemia and aleukemia. In a study sponsored by the Chemical Manufacturers Association (Dow 1978, as cited in EPA 1987/Ex. 1-836), male and female Sprague-Dawley rats were exposed to styrene vapor at concentrations of 600 to 1200 ppm, six hours per day, five days per week, for 18 or 20 months. The higher exposure level was reduced to 1000 ppm after the first two months of exposure because of excessively reduced weight in the male rats. A statistically significant increased incidence of mammary tumors was reported in low-dose female rats (7 of 87) compared with controls (1 of 85); no increase in mammary tumors was reported among high-dose female rats. The authors questioned the significance of this response, since historical control animals from the same laboratory showed a higher background incidence of mammary tumors than did the controls used in this study.

In a 1979 NCI study (NCI 1979b/Ex. 1-948), male and female B6C3F1 mice and Fischer 344 rats were treated by gavage five days per week for 78 weeks (low-dose rat groups were treated for 103 weeks). The study was terminated at 91 weeks for mice and at 104 to 105 weeks for rats. Dose-related increases in alveolar/bronchiolar adenomas and carcinomas were observed only in the low-dose (150 mg/kg) and high-dose (300 mg/kg) male mice; the incidence of tumors for vehicle controls, low-dose, and high-dose male mice was 0/20, 6/44, and 9/43, respectively. Although the historical incidence of tumors among untreated controls was 12 percent (32/271), the historical incidence of vehicle controls was 0/40.

However, the human studies cannot be used to definitely demonstrate styrene's carcinogencity because there were confounding exposures in these cohorts to butadiene, a substance identified by the NTP as carcinogenic. The animal studies also have limitations, such as high background rates of cancer in the controls and non-treatment-related mortality in some of the test animals.

Thus, at this time, OSHA believes that the current evidence on styrene's carcinogenicity does not support its classification in the final rule as a carcinogen. OSHA has reviewed additional evidence and has determined that the most appropriate basis for classifying styrene in this rulemaking is the substance's demonstrated narcotic effects. In its criteria document (1983a), NIOSH agrees that styrene is primarily a narcotic and central-nervous-system toxin:

The principal health effects due to styrene exposure involve the central nervous system. These effects include subjective complaints of headache, fatigue, dizziness, confusion, drowsiness, malaise, difficulty in concentrating, and a feeling of intoxication....There have also been reports of liver injury, peripheral nervous system dysfunction, abnormal pulmonary function, chromosomal changes, reproductive effects, and carcinogenicity related to styrene expo-sures. Although data concerning these latter adverse effects are not well defined at this time, they do provide cause for concern (NIOSH 1983a, p. 150).

Accordingly, OSHA has placed the health-effects discussion for styrene in the preamble section labeled "Narcotic Effects" in this final rule.

OSHA proposed to reduce its former exposure limits for styrene to 50 ppm as an 8-hour TWA and 100 ppm as a 15-minute STEL. The Agency finds clear evidence, based on styrene's narcotic effects, to support these limits. Richard Olsen, representing the Dow Chemical Company, agrees, and stated at the hearing that 50 ppm is likely to be the most "appropriate" limit for styrene (Tr. 3, pp. 250, 251). There is a considerable body of health-effects information in humans for styrene in the toxicological literature. Subjects exposed at 800 ppm for four hours experienced eye and throat irritation and also reported listlessness, drowsiness, and impaired balance (NIOSH 1983a, p. 150). At a concentration of 376 ppm, five human volunteers experienced eye and respiratory tract irritation within 20 minutes and demonstrated decrements in motor function (NIOSH 1983a, p. 150). Three subjects exposed to 100 ppm of styrene for 90 minutes had slower reaction times; on repeated exposure, sleepiness, fatigue, headache, difficulty in concentration, malaise, nasal irritation, and nausea occurred in another group of subjects (NIOSH 1983a, p. 150).

Effects attributable to central nervous system depression were seen in a six-week study involving human subjects exposed to 20, 100, or 125 ppm styrene; the authors of the study reported visual-evoked-response and electroencephalogram changes in these subjects (NIOSH 1983a, p. 150). Other studies report irritation of the eyes and throat at concentrations ranging from 1 to 100 ppm (NIOSH 1983a, p. 151).

Workers in reinforced plastics (RP) facilities in many countries have also evidenced narcotic effects as a consequence of styrene exposure. Swedish, Dutch, and Czechoslovakian workers in RP plants complained of headache, fatigue, drowsiness, giddiness, and dizziness at exposure levels in the range of 4 to 195 ppm (NIOSH 1983a, p. 151).

Respiratory effects were observed in U.S. RP workers exposed to from 9 to 111 ppm styrene; symptoms included wheezing, shortness of breath, and chest tightness. Another study showed a significantly greater number of RP workers with abnormal pulmonary function when compared with workers from a nonstyrene facility (NIOSH 1983a, p. 154).

NIOSH concluded, based on its extensive review of the health-effects literature for styrene, that an 8-hour TWA exposure limit of 50 ppm was appropriate to protect against the health effects observed in workers exposed to styrene at levels of 100 ppm and below. NIOSH also recommends a STEL of 100 ppm for styrene to prevent acute eye and upper-respiratory-tract irritation (NIOSH 1983a, p. 156). The State of New Jersey's Department of Public Health (Ex. 144) urged OSHA to derive a PEL for styrene on the basis of EPA's IRIS data, but this approach was criticized by other commenters (Ex. 187). The use of IRIS data for limit-setting purposes is addressed in Section VI.A of the preamble. At the hearing, representatives of the International Chemical Workers Union urged OSHA to adopt a lower PEL because considerable risk remains at the 50-ppm level (Tr. 9, p. 216). However, the AFL-CIO (Ex. 194) agrees with NIOSH that the 50-ppm and 100-ppm TWA and STEL limits are appropriate.

OSHA finds that workplace exposures to styrene are associated with health effects ranging from narcosis to neuropathies and irritation, which together constitute material impairments of health. The Agency finds that an 8-hour TWA of 50 ppm and a STEL of 100 ppm are necessary to protect against these significant risks of material health impairment. The Agency also notes that large chemical companies (for example, Rohm and Haas and the Dow Chemical Company) have already established internal corporate limits of 25 or 50 ppm (8-hour TWAs) for styrene to protect their workers from the range of serious health effects associated with exposure to this substance (Ex. 25, Appendix II, pp. 1-3).

Some commenters (Ex. 155; Tr. p. 10-111) pointed to the fact that the State of Washington has not yet adopted a 50-ppm limit for styrene as evidence of this limit's infeasibility; however, OSHA notes that Stephen Cant, for the State of Washington's Department of Public Health, stated that his department was monitoring the health evidence for styrene and considered the State's 100-ppm limit an "incremental improvement" (Tr. 2, pp. 105, 106).

OSHA notes that, with the exception of two operations in a single industry (i.e., the boat-building industry), these limits have been found to be achievable with engineering and work-practice controls in all styrene-using operations, including styrene manufacture and other reinforced-plastics operations. OSHA finds that general dilution ventilation, local exhaust ventilation, and process enclosure can be used effectively in tub, shower, and diving board manufacturing because the size and configuration of these items lend themselves to effective control. However, in two operations, manual layup and sprayup, in the boat-building industry, there is insufficient data in this record to indicate that compliance can generally be achieved with engineering and work-practice controls. For these boat-building operations, employers may use any combination of engineering controls, work practices, and respiratory protection to achieve these limits (see the discussion in Section VII of this preamble). For these operations, engineering controls and work practices will only be required to achieve full compliance with the final rule's PELs in cases where the Assistant Secretary can demonstrate that engineering controls and work practices can generally achieve these limits. In the absence of such a finding, the employer must nonetheless use engineering controls and work practices to achieve compliance with the Agency's former PELs for styrene.


TOLUENE
CAS: 108-88-3; Chemical Formula: C(6)H(5)CH(3)
H.S. No. 1397


The former OSHA standard for toluene was 200 ppm as an 8-hour TWA limit, with a 300-ppm ceiling (not to be exceeded for more than 10 minutes in any eight-hour period), and a 500-ppm peak. The ACGIH has an exposure limit for toluene of 100 ppm as an 8-hour TWA and 150 ppm as a 15-minute STEL; NIOSH recommends a 100-ppm 8-hour TWA and a 10-minute ceiling of 200 ppm. The proposed PELs were 100 ppm as an 8-hour TWA and 150 ppm as a STEL; NIOSH (Ex. 8-47, Table N1) concurs with these limits, which are established in the final rule. Toluene is a flammable, colorless liquid with an aromatic hydrocarbon odor.

The acute toxicity of toluene in animals is greater than that of benzene. Patty (1963b, as cited in ACGIH 1986/Ex. 1-3, p. 578) reports that the lethal doses of toluene and benzene in mice are 10,000 and 14,000 ppm, respectively. The oral LD(50) for toluene in rats is 7.53 ml/kg (Smyth, Carpenter, Weil et al. 1969/Ex. 1-442). Exposure of rats to 2500 or 5000 ppm of toluene caused a temporary decrease in white cell count but no evidence of damage to the blood-forming organs or the liver. Fairhall (1957d, as cited in ACGIH 1986/Ex. 1-3, p. 578) stated that severe toluene exposure can cause a marked drop in the red blood cell count and partial destruction of the blood-forming elements of the bone marrow, but other researchers report that numerous animal studies indicate that toluene is not a bone marrow toxin (Gerarde 1960c, as cited in ACGIH 1986/Ex. 1-3, p. 578).

A study by Greenberg, Mayers, Heinmann, and Moskowitz (1942/Ex. 1-325) reported that painters exposed to toluene levels of 100 to 1100 ppm exhibited enlarged livers, a moderate decrease in red blood cell counts, enlarged red blood cells, and absolute lymphocytosis, but no leukopenia. Wilson (1943/Ex. 1-403) observed 1,000 workers exposed to toluene at levels ranging from 50 ppm to 1500 ppm for periods of one to three weeks. One hundred of these workers developed symptoms severe enough to require hospitalization. At levels less than 200 ppm, 60 of these employees experienced headache, fatigue, and lack of appetite. Those workers exposed to 200 to 500 ppm toluene experienced headache, nausea, bad taste in the mouth, lassitude, temporary amnesia, impaired coordination, and anorexia. Levels of exposure from 500 to 1500 ppm resulted in nausea, headache, dizziness, anorexia, marked loss of coordination, diminished reaction time, pronounced weakness, and heart palpitations. Red cell counts were also decreased, and two cases of aplastic anemia required lengthy hospital treatment; however, the author noted that he could not rule out the possibility that benzene contamination of the toluene was the cause of these effects. Aplastic anemia (including one fatal case) has been noted in six glue sniffers; toluene was the base solvent in the glue (Powars 1965/Ex. 1-433). A man who had inhaled toluene regularly at unspecified levels for 14 years developed permanent encephalopathy (Knox and Nelson 1966/Ex. 1-421).

von Oettingen, Neal, Donahue et al. (1942/Ex. 1-875) exposed human volunteers to toluene levels ranging from 50 ppm to 800 ppm for 8 hours/day. These authors report that exposures to 50 ppm cause drowsiness and headaches and that exposures at 100 ppm result in sleepiness, moderate fatigue, and headaches. At 200 ppm, effects included impairment of coordination and reaction times. Later studies by Ogata, Tomokuni, and Takatsuka (1970/Ex. 1-352) showed an increase in reaction time, a decrease in pulse rate, and a decrease in systolic blood pressure in humans exposed to 200 ppm toluene for seven hours.

The Chevron Corporation (Ex. 3-896) objected to the short-term exposure limit for toluene as being unjustified by either the discussion in the preamble or that in the ACGIH Documentation (1986/Ex. 1-3). Chevron also urged OSHA to clarify the proposal's discussion of blood dyscrasias occurring as a result of toluene exposure because, according to Chevron:

[T]he majority of later studies show no such evidence [of blood dyscrasias]. Due to the tighter specifications for benzene contamination of toluene, we question whether blood dyscrasias will occur (Ex. 3-896, p. 14).

As discussed above in connection with octane and pentane, OSHA finds that a short-term exposure limit is necessary to ensure that workers are not exposed at the elevated levels possible with a TWA limit alone. Levels only slightly above the 8-hour TWA may cause incoordination and amnesia. For example, workers could be exposed to toluene at levels as high as several hundred ppm if the 8-hour TWA limit was promulgated alone. In addition, OSHA notes that the Agency has always had a short-term and ceiling limit for toluene, to protect against this substance's narcotic and neuropathic effects; OSHA continues to find a short-term limit necessary to ensure that workers do not experience the effects seen at levels only slightly above 100 ppm. On the question of blood dyscrasias, OSHA noted in the preamble to the proposal that the author of the study in question (Wilson 1943/Ex. 1-403) himself noted that benzene contamination may have been the cause of these blood effects; OSHA agrees that this may have been the case.

NIOSH (Ex. 150, Comments on Toluene) reports that "[s]everal recent studies indicate measurable biological changes in liver function" as a consequence of exposures to 100 ppm (Seiji et al. 1987) but not at 46 ppm (Yin et al. 1987). NIOSH also states that volunteers' performance on psychological test scores was reduced during 100-ppm exposures to toluene and that these volunteers expressed exposure-related complaints. NIOSH also notes that there is some evidence that toluene causes reproductive effects at levels currently being experienced in the workplace (NIOSH, Ex. 150, Comments on Toluene). NIOSH concluded that "there are significant health effects at the ...[former] PEL of 200 ppm which will be reduced by the ... [final rule] PEL of 100 ppm." The New Jersey Department of Health, represented by Dr. Rebecca Zagriniski, also notes that there are more recent studies on toluene (Tr. 11-266).

In the final rule, OSHA is establishing an 8-hour TWA PEL of 100 ppm and a STEL of 150 ppm for toluene. The Agency concludes that studies clearly indicate that a significant risk of hepatotoxic, behavioral, and nervous system effects exists at toluene levels substantially at or only slightly above the Agency's former PEL. OSHA finds that the new limits will protect workers against the significant risk of serious health effects that have been demonstrated to occur even during less than full-shift exposures to toluene.


TRICHLOROETHYLENE
CAS: 79-01-6; Chemical Formula: CCl(2) = CHCl
H.S. NO. 1406


OSHA's former limit for trichloroethylene, adopted from the American National Standards Institute, was 100 ppm TWA, 200 ppm as a ceiling limit not to be exceeded for more than five minutes every two hours, and 300 ppm as a peak limit. The proposed PEL for trichloroethylene was 25 ppm as an 8-hour TWA, and NIOSH (Ex. 8-47, Table N1) supported the proposed limit, which is consistent with the NIOSH REL. The ACGIH has a 50-ppm TLV-TWA and a 200-ppm TLV-STEL for trichloroethylene. Based on its review of the record evidence, OSHA has determined that a 50-ppm TWA PEL and 200-ppm STEL are appropriate limits for trichloroethylene; the final rule establishes these limits. Trichloroethylene is a colorless, nonflammable, noncorrosive liquid with the sweet odor characteristic of some chlorinated hydrocarbons.

The ACGIH (1986/Ex. 1-3) cited several studies establishing that trichloroethylene primarily affects the central nervous system and liver; some of these studies have indicated that chronic exposure to less than 100 ppm trichloroethylene is associated with a variety of nervous disturbances. Haas (1960, as cited in ACGIH 1986/Ex. 1-3, p. 595) and Grandjean, Muchinger, Turrian et al. (1955/Ex. 1-324) reported nervous symptoms among workers exposed for five years or more to trichloroethylene concentrations ranging from 1 to 335 ppm; the frequency of complaints increased when average exposures exceeded 40 ppm. Bardodej and Vyskocil (1956/Ex. 1-461) also reported symptoms of trichloroethylene poisoning, including tremors, giddiness, anxiety, and alcohol intolerance, among workers exposed above 40 ppm. In contrast, controlled laboratory experiments with human subjects exposed for up to several days to 100 or 200 ppm have generally reported no behavioral or subjective responses. The ACGIH concluded that, although the symptoms reported by workers are subjective and commonly found among individuals having no chemical exposure, the consistency of the reports "suggests the possibility of some subjective complaints as concentrations exceed about 50 ppm" (ACGIH 1986/Ex. 1-3, p. 596). Therefore, the ACGIH recommended a TLV-TWA of 50 ppm and a TLV-STEL of 200 ppm for trichloroethylene to minimize symptoms of headache, fatigue, and irritability.

The ACGIH (1986/Ex. 1-3) also reviewed some of the carcinogenicity data on trichloroethylene. In an NCI bioassay (1976b/Ex. 1-168), mice given trichloroethylene by gavage developed hepatocellular carcinomas, but rats did not. The species difference in response was attributed to a difference in the way trichloroethylene is metabolized between the mouse and rat (Stott, Quast, and Watanabe 1982/Ex. 1-833). An inhalation study in mice, rats, and Syrian hamsters (Henschler, Romen, Reichert et al. 1980/Ex. 1-330) found only an increase in the occurrence of malignant lymphomas in mice, which the authors attributed to the strain of mouse used (NMRI). The ACGIH also cited a number of epidemiologic investigations having cohorts as large as 7,688 workers, in which no correlation between cancer mortality and exposure to trichloroethylene was found (Novotna, David, and Malek 1971, as cited in ACGIH 1986/Ex. 1-3, p. 595; Axelson, Andersson, Hogstedt et al. 1978/Ex. 1-713; Tola, Vilhunen, Jarvinen, and Korkala 1980/Ex. 1-391).

After reviewing all of the available health data, NIOSH (1978m/Ex. 1-1121) concluded that the results of the NCI (1976b/ Ex. 1-168) gavage study indicate trichloroethylene (TCE) to be a potential human carcinogen, although NIOSH noted that TCE was "not considered to be a potent carcinogen." NIOSH also stated that a 100-ppm limit would not protect against the neuropathic symptoms, such as headache and fatigue, caused by exposure to trichloroethylene. In support of this conclusion, NIOSH (1978m/Ex. 1-1121) cited three health hazard evaluations conducted in facilities using trichloroethylene as a degreasing agent. In all three facilities, employees consistently experienced symptoms of dizziness, fatigue, nausea, headache, sensory irritation, and difficulty in breathing. Personal TWA exposures to trichloroethylene ranged from 37 to 112 ppm in one plant, 10 to 100 ppm in the second plant, and 10 to 95 ppm in the third plant. NIOSH (1978m/Ex. 1-1121) concluded that these reports documented the presence of adverse effects caused by acute exposure to trichloroethylene at levels of one-fourth to one-half the 100-ppm OSHA limit, at 25 to 50 ppm.

NIOSH recommended a 25-ppm TWA limit for trichloroethylene based on the health hazard reports described above as well as on a NIOSH evaluation of several NIOSH industrial hygiene reports showing that degreasing operations, including those using open-top tanks, are able to achieve 25 ppm uniformly by the use of engineering controls. NIOSH reasoned that these open-tank operations would be among the most difficult of all TCE-using operations to control.

Since publication of the NIOSH (1978m/Ex. 1-1121) report, several recent bioassays on trichloroethylene have been published and are currently being reviewed by EPA. Fukuda, Takemoto, and Tsuruta (1983/Ex. 1-1109) exposed female rats and mice to 50, 150, or 450 ppm trichloroethylene for 103 weeks and reported an increased incidence of lung tumors among mice only. Maltoni, Lefemine, and Cotti (1986/Ex. 1-1160) exposed rats and mice to 100, 300, or 600 ppm trichloroethylene and reported a significant increase of renal adenocarcinomas and Leydig cell tumors in rats, as well as a significant increase in hepatomas and lung tumors in mice. In 1986, the NTP reported an increase in the incidence of kidney tumors in rats given trichloroethylene by gavage; however, the NTP considered the tumor response to be weak (3 of 49 animals) and reported that the results were only statistically significant after corrections for high mortality were made.

Based on the information discussed above, OSHA proposed to revise the PEL for trichloroethylene to 25 ppm as an 8-hour TWA. The proposed limit was supported by NIOSH (Ex. 8-47) and by the AFL-CIO (Ex. 194), which consider trichloroethylene a potential carcinogen. However, the Dow Chemical Company objected to this proposed limit on the grounds that:

OSHA does not provide justification for reduction of the PEL to 25 ppm based on CNS effects. Although NIOSH (1978m/Ex. 1-1121) mentions [the] CNS effects of trichloroethylene, the 25-ppm REL was not based on concern for these effects....After reviewing the data on the reported [CNS and subjective response] effects of TCE, ACGIH concluded [that] a 50-ppm TWA protects workers from potential adverse effects (Ex. 3-741, pp. 61-62).

Dow also pointed out that neither the ACGIH nor IARC has classified trichloroethylene as a potential carcinogen and that EPA's Science Advisory Board concluded that the weight of evidence for TCE's carcinogenicity "lies on a continuum between their categories B2 [probable human carcinogen] and C [possible human carcinogen]" (Ex. 3-741, p. 62). Dow concluded:

Since justification for reduction of the PEL below that recommended by ACGIH has not been provided, based on either CNS effects or carcinogenicity, we recommend adoption of the ACGIH TWA of 50 ppm with a 200-ppm STEL...(Ex. 3-741, p. 63).

The Halogenated Solvents Industry Alliance (Ex. 8-89, pp. 3-18) expressed an opinion similar to that of Dow Chemical.

In its posthearing submission, Dow submitted the written findings of the EPA's Science Advisory Board (SAB) on trichloroethylene (letter dated March 9, 1988 to Lee M. Thomas, Administrator of EPA, Ex. 106D). In this letter, the SAB concluded that "[t]richloroethylene has the potential to cause cancer in humans, but its potency is low." The Science Advisory Board also stated:

The endpoints with the most biological plausibility, based upon what is known about the effects of structurally related compounds, are liver and lung tumors in mice and renal tumors in rats....While [the incidence of these tumors] is clearly in excess, [it does]...not approach the incidence of 100 percent that occurred for chloroform, for example. This suggests a lower or more moderate potency for trichloroethylene (Ex. 106D).

OSHA believes that the evidence described above supports OSHA's preliminary conclusion in the NPRM (53 FR 21013) that the former 100-ppm TWA PEL for trichloroethylene is insufficiently protective against CNS effects and, further, that exposure to trichloroethylene may present a possible carcinogenic hazard. However, OSHA concludes that the evidence for adverse CNS effects below concentrations of 50 ppm is equivocal; exposures exceeding 50 ppm were found in each of the facilities studied by NIOSH in which symptoms of CNS disturbances were reported. Furthermore, OSHA finds that it is premature to establish a PEL for trichloroethylene based on evidence of its carcinogenicity, given the uncertainties in the evidence. Therefore, OSHA concludes that it is appropriate at this time to establish a TWA PEL of 50 ppm and a STEL of 200 ppm to reduce the signficant risk of adverse CNS effects that are associated with exposure to trichloroethylene at the former OSHA limits. The Agency considers the adverse effects resulting from exposure to trichloroethylene to be material impairments of health. Accordingly, the Agency is establishing a 50 ppm TWA PEL and 200 ppm STEL for trichloroethylene in the final rule.

Conclusions for This Group of Narcotic Agents

OSHA concludes that workers exposed to these narcosis-causing substances in the workplace are at significant risk of experiencing a broad range of narcotic effects, including loss of consciousness, uncoordinated movements, inability to concentrate, drowsiness, irritability, poor judgment, and inappropriate behavior. These highly undesirable and potentially serious health effects, which are viewed by OSHA as material impairments of health, additionally have the potential to cause serious workplace accidents and injuries because they interfere with reaction times, muscle coordination, and the ability to make good decisions and excercise good judgement. The new or revised exposure limits being established by OSHA in the final rule will protect employees from experiencing these significant risks in their places of work and will contribute to a substantial reduction in these risks.

3. Substances for Which Proposed Limits Are Based on Avoidance of Sensory Irritation

Introduction

Exposure to many chemical agents is associated with the development of sensory irritation, which is initiated when these substances come into contact with mucous membranes or skin. Limits have been set for a large group of chemicals on the basis of their sensory irritant effects. These substances, which number 79, are shown in Table C3-1, along with their former OSHA limits, the limits proposed by OSHA in the June 7, 1988 NPRM, and the final exposure limits being promulgated today. For five of these chemicals, OSHA is reducing the 8-hour TWA and for an additional eight, the Agency is both reducing the 8-hour limit and adding a STEL. In 21 cases, the 8-hour limit remains unchanged but a STEL is being added. In eight instances, a ceiling is being deleted, and this limit is being replaced by an 8-hour TWA and/or STEL value; in five instances, a TWA limit is being deleted and a ceiling value added in its place. For one chemical, methyl n-amyl ketone, OSHA is retaining its existing PEL. Thirty-one of these substances were previously unregulated by OSHA, and for these, the Agency is establishing 8-hour limits, 8-hour limits supplemented by a STEL, or ceiling limits.

      TABLE C3-1.  Substances for Which Limits Are Based on
                       Avoidance of Irritant Effects

NOTE: Because of its width, this table has been divided;
           see continuation for additional columns.
______________________________________________________________________
H.S. Number/                                   Former
Chemical Name                     CAS No.      PEL
______________________________________________________________________
1001 Acetaldehyde                 75-07-0      200 ppm TWA
1002 Acetic acid                  64-19-7      10 ppm TWA
1004 Acetone                      67-64-1      1000 ppm TWA
1007 Acrolein                    107-02-8      0.1 ppm TWA
1010 Allyl alcohol               107-18-6      2 ppm TWA, Skin
1012 Allyl glycidyl ether        106-92-3      10 ppm Ceiling
1013 Allyl propyl disulphide    2179-59-1      2 ppm TWA
1021 Ammonia                    7664-41-7      50 ppm TWA
1022 Ammonium chloride fume    12125-02-9       --
1036 Borates, tetra,            1330-43-4       --
       Na (anhydrous)
1037 Borates, tetra,            1303-96-4       --
       Na (decahydrate)
1038 Borates, tetra,           12179-04-3       --
       Na (pentahydrate)
1042 Bromine                    7726-95-6      0.1 ppm TWA
1045 2-Butanone (MEK)             78-93-3      200 ppm TWA
1047 n-Butyl acetate             123-86-4      150 ppm TWA
1053 n-Butyl lactate             138-22-7       --
1054 n-Butyl mercaptan           109-79-5      10 ppm TWA
1064 Caprolactam (dust)          105-60-2       --
1065 Caprolactam (vapor)         105-60-2       --
1077 Cesium hydroxide          21351-79-1       --
1079 Chlorine                   7782-50-5      1 ppm Ceiling
1083 Chloroacetyl chloride        79-04-9       --
1084 o-Chlorobenzylidene        2698-41-1      0.05 ppm TWA
       malononitrile
1105 Cyanogen                    460-19-5       --
1106 Cyanogen chloride           506-77-4       --
1119 Dibutyl phosphate           107-66-4      1 ppm TWA
1122 1,3-Dichloro-5,5-di-        118-52-5      0.2 mg/m(3) TWA
     methylhydantoin
1127 Dichloroethyl ether         111-44-4      15 ppm Ceiling,
                                               Skin
1130 2,2-Dichloropro-             75-99-0       --
       pionic acid
1137 Diethylamine                109-89-7      25 ppm TWA
1140 Diisobutyl ketone           108-83-8      50 ppm TWA
1158 Epichlorohydrin             106-89-8      5 ppm TWA, Skin
1162 Ethyl benzene               100-41-4      100 ppm TWA
1164 Ethyl ether                  60-29-7      400 ppm TWA
1165 Ethyl mercaptan              75-08-1      10 ppm Ceiling
1169 Ethylene glycol             107-21-1       --
1171 Ethylidene                16219-75-3       --
       norbornene
1183 Furfural                     98-01-1      5 ppm TWA, Skin
1184 Furfuryl alcohol             98-00-0      50 ppm TWA
1187 Glutaraldehyde              111-30-8       --
1196 Hexachlorocyclo-             77-47-4       --
       pentadiene
1204 Hexylene glycol             107-41-5       --
1206 Hydrogen bromide          10035-10-6      3 ppm TWA
1208 Hydrogen fluoride          7664-39-3      3 ppm TWA
1211 2-Hydroxypropyl             999-61-1       --
       acrylate
1217 Iron salts (soluble)     Varies with       --
                              compound
1224 Isopropyl acetate           108-21-4      250 ppm TWA
1225 Isopropyl alcohol            67-63-0      400 ppm TWA
1228 n-Isopropylamine             75-31-0      5 ppm TWA
1243 Mesityl oxide               141-79-7      25 ppm TWA
1248 Methyl 2-cyano-             137-05-3       --
       acrylate
1261 Methyl isobutyl             108-11-2      25 ppm TWA,
       carbinol                                Skin
1263 Methyl mercaptan             74-93-1      10 ppm Ceiling
1264 Methyl n-amyl ketone        110-43-0      100 ppm TWA
1267 alpha-Methyl styrene         98-83-9      100 ppm Ceiling
1270 o-Methylcyclo-              583-60-8      100 ppm TWA,
       hexanone                                Skin
1298 Osmium tetroxide          20816-12-0      0.002 mg/m(3) TWA
1302 Paraffin wax fume          8002-74-2       --
1322 Phosphoric acid            7664-38-2      1 mg/m(3) TWA
1325 Phosphorus trichloride     7719-12-2      0.5 ppm TWA
1334 Potassium hydroxide        1310-58-3       --
1343 Propylene glycol            107-98-2       --
       monomethyl ether
1350 Rosin core solder                 --       --
       pyrolysis products,
       as formaldehyde
1365 Sodium bisulfite           7631-90-5       --
1367 Sodium hydroxide           1310-73-2      2 mg/m(3) TWA
1368 Sodium metabisulfite       7681-57-4       --
1376 Sulfur monochloride       10025-67-9      1 ppm TWA
1377 Sulfur pentafluoride       5714-22-7      0.025 ppm TWA
1387 Tetrahydrofuran             109-99-9      200 ppm TWA
1389 Tetrasodium                7722-88-5       --
       pyrophosphate
1392 Thioglycolic  acid           68-11-1       --
1405 1,2,4-Trichloro-            120-82-1       --
        benzene
1408 Triethylamine               121-44-8      25 ppm TWA
1421 Vanadium (V205,            1314-62-1      0.5 mg/m(3)
       respirable dust)                        Ceiling
1422 Vanadium (V205,            1314-62-1      0.1 mg/m(3)
       fume)                                   Ceiling
1424 Vinyl acetate               108-05-4       --
1429 VM & P Naphtha             8032-32-4       --
1431 Xylenes                    1330-20-7      100 ppm TWA
       (o-, m-, and p-
       isomers)
1435 Zinc chloride fume         7646-85-7      1 mg/m(3) TWA
______________________________________________________________________


TABLE C3-1.  Substances for Which Limits Are Based on
             Avoidance of Irritant Effects (Continuation)
______________________________________________________________________
H.S. Number/                   Proposed            Final Rule
Chemical Name                  PEL                 PEL(1)
______________________________________________________________________
1001 Acetaldehyde              100 ppm TWA         100 ppm TWA
                               150 ppm STEL        150 ppm STEL
1002 Acetic acid               10 ppm TWA          10 ppm TWA
                               15 ppm STEL
1004 Acetone                   250 ppm TWA         750 ppm TWA
                                                   1000 ppm STEL
1007 Acrolein                  0.1 ppm TWA         0.1 ppm TWA
                               0.3 ppm STEL        0.3 ppm STEL
1010 Allyl alcohol             2 ppm TWA, Skin     2 ppm TWA, Skin
                               4 ppm STEL          4 ppm STEL
1012 Allyl glycidyl ether      5 ppm TWA           5 ppm TWA
                               10 ppm STEL, Skin   10 ppm STEL
1013 Allyl propyl disulphide   2 ppm TWA           2 ppm TWA
                               3 ppm STEL          3 ppm STEL
1021 Ammonia                   25 ppm TWA          35 ppm STEL
                               35 ppm STEL
1022 Ammonium chloride fume    10 mg/m(3) TWA      10 mg/m(3) TWA
                               20 mg/m(3) STEL     20 mg/m(3) STEL
1036 Borates, tetra,           1 mg/m(3) TWA       10 mg/m(3) TWA
       Na (anhydrous)
1037 Borates, tetra,           5 mg/m(3) TWA       10 mg/m(3) TWA
       Na (decahydrate)
1038 Borates, tetra,           1 mg/m(3) TWA       10 mg/m(3) TWA
       Na (pentahydrate)
1042 Bromine                   0.1 ppm TWA         0.1 ppm TWA
                               0.3 ppm STEL        0.3 ppm STEL
1045 2-Butanone (MEK)          200 ppm TWA         200 ppm TWA
                               300 ppm STEL        300 ppm STEL
1047 n-Butyl acetate           150 ppm TWA         150 ppm TWA
                               200 ppm STEL        200 ppm STEL
1053 n-Butyl lactate           5 ppm TWA           5 ppm TWA
1054 n-Butyl mercaptan         0.5 ppm TWA         0.5 ppm TWA
1064 Caprolactam (dust)        1 mg/m(3) TWA       1 mg/m(3) TWA
                               3 mg/m(3) STEL      3 mg/m(3) STEL
1065 Caprolactam (vapor)       5 ppm TWA           5 ppm TWA
                               10 ppm STEL         10 ppm STEL
1077 Cesium hydroxide          2 mg/m(3) TWA       2 mg/m(3) TWA
1079 Chlorine                  0.5 ppm STEL        0.5 ppm TWA
                                                   1.0 ppm STEL
1083 Chloroacetyl chloride     0.05 ppm TWA        0.05 ppm TWA
1084 o-Chlorobenzylidene       0.05 ppm Ceiling,   0.05 ppm Ceiling,
       malononitrile           Skin                Skin
1105 Cyanogen                  10 ppm TWA          10 ppm TWA
1106 Cyanogen chloride         0.3 ppm Ceiling     0.3 ppm Ceiling
1119 Dibutyl phosphate         1 ppm TWA           1 ppm TWA
                               2 ppm STEL          2 ppm STEL
1122 1,3-Dichloro-5,5-di-      0.2 mg/m(3) TWA     0.2 mg/m(3) TWA
methylhydantoin                0.4 mg/m(3) STEL    0.4 mg/m(3) STEL
1127 Dichloroethyl ether       5 ppm TWA           5 ppm TWA
                               10 ppm STEL, Skin   10 ppm STEL, Skin
1130 2,2-Dichloropro-          1 ppm TWA           1 ppm TWA
       pionic acid
1137 Diethylamine              10 ppm TWA          10 ppm TWA
                               25 ppm STEL         25 ppm STEL
1140 Diisobutyl ketone         25 ppm TWA          25 ppm TWA
1158 Epichlorohydrin           2 ppm TWA, Skin     2 ppm TWA, Skin
1162 Ethyl benzene             100 ppm TWA         100 ppm TWA
                               125 ppm STEL        125 ppm STEL
1164 Ethyl ether               400 ppm TWA         400 ppm TWA
                               500 ppm STEL        500 ppm STEL
1165 Ethyl mercaptan           0.5 ppm TWA         0.5 ppm TWA
1169 Ethylene glycol           50 ppm Ceiling      50 ppm Ceiling
1171 Ethylidene                5 ppm Ceiling       5 ppm Ceiling
       norbornene
1183 Furfural                  2 ppm TWA, Skin     2 ppm TWA, Skin
1184 Furfuryl alcohol          10 ppm TWA          10 ppm TWA
                               15pm STEL, Skin     15 ppm STEL, Skin
1187 Glutaraldehyde            0.2 ppm Ceiling     0.2 ppm Ceiling
1196 Hexachlorocyclo-          0.01 ppm TWA        0.01 ppm TWA
       pentadiene
1204 Hexylene glycol           25 ppm Ceiling      25 ppm Ceiling
1206 Hydrogen bromide          3 ppm Ceiling       3 ppm Ceiling
1208 Hydrogen fluoride         3 ppm TWA           3 ppm TWA
                               6 ppm STEL          6 ppm STEL
1211 2-Hydroxypropyl           0.5 ppm TWA,Skin    0.5 ppm TWA, Skin
       acrylate
1217 Iron salts (soluble)      1 mg/m(3) TWA       1 mg/m(3) TWA
1224 Isopropyl acetate         250 ppm TWA         250 ppm TWA
                               310 ppm STEL        310 ppm STEL
1225 Isopropyl alcohol         400 ppm TWA         400 ppm TWA
                               500 ppm STEL        500 ppm STEL
1228 n-Isopropylamine          5 ppm TWA           5 ppm TWA
                               10 ppm STEL         10 ppm STEL
1243 Mesityl oxide             15 ppm TWA          15 ppm TWA
                               25 ppm STEL         25 ppm STEL
1248 Methyl 2-cyano-           2 ppm TWA           2 ppm TWA
       acrylate                4 ppm STEL          4 ppm TWA
1261 Methyl isobutyl           25 ppm TWA          25 ppm TWA
       carbinol                40 ppm STEL, Skin   40 ppm STEL, Skin
1263 Methyl mercaptan          0.5 ppm TWA         0.5 ppm TWA
1264 Methyl n-amyl             100 ppm TWA         100 ppm TWA
       ketone
1267 alpha-Methyl styrene      50 ppm TWA          50 ppm TWA
                               100 ppm STEL        100 ppm STEL
1270 o-Methylcyclo-            50 ppm TWA          50 ppm TWA
       hexanone                75 ppm STEL, Skin   75 ppm STEL, Skin
1298 Osmium tetroxide          0.002 mg/m(3) TWA   0.002 mg/m(3) TWA
                               0.006 mg/m(3) STEL  0.006 mg/m(3) STEL
1302 Paraffin wax fume         2 mg/m(3) TWA       2 mg/m(3) TWA
1322 Phosphoric acid           1 mg/m(3) TWA       1 mg/m(3) TWA
                               3 mg/m(3) STEL      3 mg/m(3) STEL
1325 Phosphorus                0.2 ppm TWA         0.2 ppm TWA
        trichloride            0.5 ppm STEL        0.5 ppm STEL
1334 Potassium hydroxide       2 mg/m(3) Ceiling   2 mg/m(3) Ceiling
1343 Propylene glycol          100 ppm TWA         100 ppm TWA
       monomethyl ether        150 ppm STEL        150 ppm STEL
1350 Rosin core solder         0.1 mg/m(3) TWA     0.1 mg/m(3) TWA
       pyrolysis products,
       as formaldehyde
1365 Sodium bisulfite          5 mg/m(3) TWA       5 mg/m(3) TWA
1367 Sodium hydroxide          2 mg/m(3) Ceiling   2 mg/m(3) Ceiling
1368 Sodium metabisulfite      5 mg/m(3) TWA       5 mg/m(3) TWA
1376 Sulfur monochloride       1 ppm Ceiling       1 ppm Ceiling
1377 Sulfur pentafluoride      0.01 ppm Ceiling    0.01 ppm Ceiling
1387 Tetrahydrofuran           200 ppm TWA         200 ppm TWA
                               250 ppm STEL        250 ppm STEL
1389 Tetrasodium               5 mg/m(3) TWA       5 mg/m(3) TWA
       pyrophosphate
1392 Thioglycolic  acid        1 ppm TWA, Skin     1 ppm TWA, Skin
1405 1,2,4-Trichloro-          5 ppm Ceiling       5 ppm Ceiling
        benzene
1408 Triethylamine             10 ppm TWA          10 ppm TWA
                               15 ppm STEL         15 ppm STEL
1421 Vanadium (V205,           0.05 mg/m(3) TWA    0.05 mg/m(3) TWA
       respirable dust)        Ceiling
1422 Vanadium (V205,           0.05 mg/m(3) TWA    0.05 mg/m(3) TWA
       fume)                   Ceiling
1424 Vinyl acetate             10 ppm TWA          10 ppm TWA
                               20 ppm STEL         20 ppm STEL
1429 VM & P Naphtha            300 ppm TWA         300 ppm TWA
                               400 ppm STEL        400 ppm STEL
1431 Xylenes                   100 ppm TWA         100 ppm TWA
       (o-, m-, and p-         150 ppm STEL        150 ppm STEL
       isomers)
1435 Zinc chloride fume        1 mg/m(3) TWA       1 mg/m(3) TWA
                               2 mg/m(3) STEL      2 mg/m(3) STEL
______________________________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures; its STELs
are for 15 minutes unless otherwise specified; and its ceilings are
peaks not to be exceeded for any period of time.

Description of the Health Effects

Irritant effects are readily perceived by affected individuals. The symptoms of sensory irritation include stinging, itching, and burning of the eyes, tearing (or lacrimation), a burning sensation in the nasal passages, rhinitis (nasal inflammation), cough, sputum production, chest pain, wheezing, and dyspnea (breathing difficulty). In the majority of cases, the onset of symptoms occurs rapidly upon exposure to the irritant; it is therefore easy to associate the causative agent with the irritant effect.

These effects may cause severe discomfort and be seriously disabling, as is the case with dyspnea or wheezing. The tearing and eye irritation associated with exposure to sensory irritants are often severe and can be as disabling as the weeping caused by exposure to tear gas. In addition to these primary effects, workers distracted by material irritant effects are more likely than nonexposed workers to have accidents and thus to endanger both themselves and others. (These adverse health effects also clearly have substantial productivity impacts.) The eye irritation caused by exposure to irritants is believed to result from stimulation of the sensory nerve endings in the cornea. There is little information available on the relationship between the severity of the effect and the physical or chemical properties of the irritating substance. In addition, the mechanism of action underlying this irritant effect is not well understood. Mechanisms that have been suggested include physical action of the irritant on nerve endings, binding of the irritant to sulfhydryl groups of protein, inhibition of cellular respiration, and cholinesterase inhibition (Grant 1986/Ex. 1-975). The symptoms of eye irritation are usually transient and do not generally persist after cessation of exposure; however, exposure to concentrations of lacrimators that exceed the levels associated with transient eye irritation may produce corneal or conjunctival injury that requires medical treatment (Grant 1986/Ex. 1-975).

Sensory irritation of the pulmonary system primarily affects the upper respiratory tract and causes an increase in sputum production; inflammation of the nasal passages, trachea, and upper bronchial tree; and decreased cilial clearance. These effects produce a burning sensation in the nasal passages and throat; coughing; sneezing; and acute bronchitis. The development of bronchitis indicates that the cilial clearance mechanism has been compromised, and the resulting mucous retention increases the risk of secondary bacterial infection. Wheezing may also be apparent, particularly if the affected individual has a history of hyperreactive airway disease. If exposure is sufficiently intense, the irritant may reach the lower portion of the bronchial tree, causing a chemical burn of the parenchyma and the sudden collection of fluid in interstitial spaces and alveoli (pulmonary edema). Irritation-induced edema may have a delayed onset (12 hours or more) and can cause hypoxia and difficulty in breathing. All of the effects described above are considered to constitute material impairment of health or functional capacity within the meaning of the Act.

For the great majority of substances in this group, current limits are derived from human evidence that exposure to the chemical agent at a particular airborne concentration will be associated with sensory irritation. For a few substances in this group, animal evidence provided the basis for limit setting. Several general types of evidence may be used to revise existing limits:
* Consideration of new human evidence;

* Reinterpretation of human data that formed the basis for setting the 1968 TLV;

* Consideration of evidence from industrial experience showing that employees are not experiencing irritation; and

* Evaluation of new animal evidence.
The studies that provide the basis for the sensory irritant levels being proposed by OSHA are generally controlled-exposure experiments using human volunteers or reports of employee complaints arising in industrial settings.

Dose-Response Relationships and Sensory Irritation

The onset of sensory irritation is considered a "threshold" or NOE level; that is, for any sensory irritant, there is an exposure level below which very few, if any, individuals will experience sensory irritation. As exposure increases above this level, a larger proportion of exposed individuals will notice the effect and the effect will become increasingly severe. At some level above this NOEL, all exposed persons will experience sensory irritation, although the intensity of the response may vary.

The risk of experiencing irritation that is associated with exposures below the NOEL will be minimal (except in the hypersensitive individual), while the risk of experiencing the irritant effect will increase directly as exposure increases. At some point above the NOE level (i.e., at some dose of the substance) the response will be 100 percent, and all exposed persons will experience irritation. According to general toxicologic principles, the shape of the curve that describes responses above the NOEL is sigmoidal, and the steepness of the curve is a function of the variability in individual responses to the particular irritant. For example, if nearly all persons exposed to the substance will experience a response at approximately the same concentration (dose), the curve will be steep; if, on the other hand, the percentage of people responding increases only slowly as concentration rises, the curve will be considerably flatter.

In addition to the relationship between increasing dose and increasing proportion of exposed persons being affected, the intensity of the response also increases with increasing exposure level. Slightly above the NOE level, affected individuals will experience itching and burning of the eyes, nose, and throat; this is a transient effect and disappears upon removal from exposure. For some substances, workers may become inured to the sensations and higher exposure levels are necessary to elicit a subjective response. As exposure levels increase, the irritant effects become more severe to the point where objective signs of mucous membrane irritation are apparent (i.e., redness of the eyes, rhinitis, coughing, and lacrimation).

During the rulemaking, the question arose as to the level of irritation that constitutes a significant risk of material health impairment; OSHA posed this question in the NPRM and a discussion of the responses received appears earlier in this preamble (see Section V, Question 21). Some commenters (Exs. 3-744 and 3-896) were of the opinion that transient irritant effects should not be considered material impairment of health. For example, the U.S. Borax and Chemical Corporation (Ex. 3-744) stated that transient "rhinitis, cough, sputum production, chest pain, wheezing, and dyspnea" do not constitute material impairments of health.

Most commenters, however, recommended that these signs and symptoms be regarded as material health impairments (see, for example, Exs. 8-47, 3-1095, 3-660, and 3-593). For example, NIOSH stated:

The recognition of sensory irritation as potentially being "material impairment of health" is consistent with the current scientific consensus related to health effects of environmental agents.

Mucous membrane irritants can cause increased blink frequency and tearing; nasal discharge, congestion, and sneezing; and cough, sputum production, chest discomfort, sneezing, chest tightness, and dyspnea. Work environments often require levels of physical and mental performance considerably greater than encountered in daily living. Even in the absence of any permanent impairment, the symptoms listed can interfere with job performance and safety.

Mucous membrane irritation can result in inflammation, which may lead to increased susceptibility to nonspecific irritants and infectious agents. For example, experimental ozone exposure in humans results in increased airway reactivity. Also, studies of exposure to environmental tobacco smoke have shown irritative symptoms and evidence of increased frequency of respiratory tract illnesses in young children and decreased pulmonary function in adults....

Mucous membrane irritation is associated with respiratory illnesses, depending on the composition of specific exposure and on the dose, duration, and frequency of exposure. No universally applicable conclusion can be drawn at this time regarding the association between irritative symptoms and permanent injury or dysfunction. Where certain individuals show no measurable impairment after an exposure, even when experiencing irritative symptoms, others may develop identifiable dysfunction.

Aside from the effects of irritation, mucous membrane exposure may result in absorption of a substance, with resultant systemic toxicity. An inflamed mucous membrane may be an even more effective route of absorption, either for the irritant or for other substances. Furthermore, injury to bronchopulmonary membranes can impair removal of particulates from the respiratory system (Ex. 8-47, pp. 38-40).

Thus, according to NIOSH, sensory irritants interfere with job performance and safety, cause inflammation, may increase the victim's susceptibility to other irritants and infectious agents, lead to permanent injury or dysfunction, or permit greater absorption of hazardous substances (Ex. 8-47).

Another commenter, E.L. DeWitt, an occupational health consultant for the du Pont Company, remarked:

Irritation takes many forms...with the effect being perhaps no more than transient, slight to mild discomfort. Again, this type of irritation needs to be prevented but the `safety factor' [applied] might be somewhat less in this case. There are also situations where `irritation' is perceived but is without any accompanying manifestations. In these cases, there may be no real need to modify the exposure limit. The exposure conditions required to produce these findings need to be considered also (Ex. 3-660, p. 4).

OSHA concludes that exposure limits are needed for those substances for which PELs are being established in this rulemaking to protect against sensory irritant effects that result in objective signs of irritation, such as coughing, wheezing, conjunctivitis, and tearing. Such levels of mucous membrane irritation may require medical treatment, adversely affect the well-being of employees, and place the affected individual at risk from increased absorption of the substance and decreased resistance to infection. Exposing workers repeatedly to irritants at levels that cause subjective irritant effects may cause workers to become inured to the irritant warning properties of these substances and thus increase the risk of overexposure. In addition, the long-term effects of repeated low-level sensory irritation have not been well studied.

Therefore, OSHA finds that the sensory irritation caused by exposure to those substances for which PELs are being established in this rulemaking constitutes a material impairment of health and functional well-being and has established exposure limits for these substances at levels that will protect workers from the significant risk of experiencing this material impairment of health.

Analyses of the toxicologic data for the substances in this group of chemicals and OSHA's findings in each case are presented below.


ACETALDEHYDE
CAS: 75-07-0; Chemical Formula: CH(3)CHO
H.S. No. 1001


OSHA's previous PEL for acetaldehyde was 200 ppm as an 8-hour TWA. In its NPRM, OSHA proposed revising its limit for acetaldehyde to 100 ppm as an 8-hour TWA and supplementing this with a STEL of 150 ppm; these are the limits currently recommended by the ACGIH. OSHA is establishing permissible exposure limits of 100 ppm as an 8-hour TWA and 150 ppm as a 15-minute STEL in the final rule. Acetaldehyde is a colorless liquid with a pungent, fruity odor.

The 200-ppm 1968 TLV established by the ACGIH for acetaldehyde was based on a sensory irritation study conducted by Silverman, Schulte, and First (1946/Ex. 1-142) that showed that unacclimatized individuals experienced eye irritation at 50 ppm, but that a level of 200 ppm was tolerable for an 8-hour day. Reexamination of the data reported by Silverman, Schulte, and First (1946/Ex. 1-142) reveals that, at 200 ppm of acetaldehyde, all exposed persons experienced inflammation of the conjuctivae of the eyes, which manifested as redness. OSHA therefore concluded that its previous PEL of 200 ppm placed exposed employees at risk of conjunctivitis and other irritation and that a reduction to 100 ppm was necessary to reduce this risk. OSHA also proposed a STEL of 150 ppm to supplement the 8-hour limit because, without a STEL, workers could be exposed to levels many times those that have been shown to cause corneal injury, sensitization, and respiratory tract irritation. NIOSH (Ex. 8-47, Table N6B; Tr. pp. 3-97 to 3-98) indicated that acetaldehyde might be a candidate for an individual 6(b) rulemaking. As pointed out by the Workers Institute for Safety and Health (WISH) (Tr. 7-117, Ex. 116, p. 8), IARC has classified acetaldehyde as a possible human carcinogen based an animal data. There is also evidence that acetaldehyde is teratogenic and fetotoxic in animals (Ex. 116). The Agency will continue to monitor the scientific evidence for this substance to examine whether a further reduction in the PEL is warranted.

OSHA concludes that employees are placed at significant risk of conjunctivitis and irritation at the current 8-hour TWA limit of 200 ppm. The Agency has determined that conjunctivitis and sensory irritation represent material impairments of health or functional capacity. Therefore, OSHA is revising the limit for acetaldehyde to 100 ppm as an 8-hour TWA and 150 ppm as a 15-minute STEL to substantially reduce this risk.

ACETIC ACID CAS: 64-19-7; Chemical Formula: CH(3)COOH H.S. No. 1002

The former OSHA PEL for acetic acid was a 10-ppm 8-hour TWA. OSHA proposed to retain the TWA limit and to supplement it with a 15-ppm STEL, based on the acute irritant properties of acetic acid. These limits are consistent with the ACGIH recommended TLVs (1986/Ex. 1-3). NIOSH (Ex. 8-47, Table N1) concurred with these proposed limits. However, OSHA's review of the evidence for acetic acid has demonstrated that there is no basis at this time for a STEL, and the final rule thus retains the 8-hour TWA PEL. Acetic acid is a clear, colorless, flammable liquid with a pungent odor.

Sterner (1949/Ex. 1-1207) reported that exposures to concentrations of acetic acid ranging from 800 to 1200 ppm cannot be tolerated by humans for longer than three minutes. The AIHA (Ex. 8-16) stated that unacclimatized workers experience eye and nasal irritation at acetic acid levels in excess of 26 ppm, and that exposure to 50 ppm is intolerably irritating. The ACGIH also reported that acclimatized workers are sometimes able to tolerate exposure to concentrations as high as 30 ppm. Guinea pigs exhibited minor changes in respiration after exposure to 5 ppm; exposure to 100 ppm produced a significant increase in pulmonary flow resistance and a decrease in breathing rate and minute volume, which suggests that bronchial constriction is the primary irritant action of acetic acid (Amdur 1961/Ex. 1-601).

The 10-ppm TWA was established on the basis of studies indicating that industrial exposure to acetic acid at 10 ppm was nonirritating (Sterner 1943/Ex. 1-806). However, conjunctival irritation has been reported in humans exposed below 10 ppm (duration not specified) (Baldi 1953/Ex. 1-602), and workers exposed to concentrations of 60 ppm during the workshift, plus one hour daily at 100 to 260 ppm, for 7 to 12 years developed respiratory irritation, conjunctivitis, bronchitis (which was asthma-like in some workers), pharyngitis, erosion of exposed teeth, and gastritis (Parmeggiani and Sassi 1954/Ex. 1-753). Vigliani and Zurlo (1955/Ex. 1-164) observed respiratory, gastrointestinal, and skin irritation in the same group of workers.

In a prehearing comment, Eastman Kodak (Ex. 3-661) argued that there was no toxicologic basis for a 15-ppm STEL, citing Vigliani and Zurlo (1955/Ex. 1-164), who reported that exposure to 20 to 30 ppm is without danger. In addition, Kodak stated that irritation has only been observed "with prolonged and repeated exposures" above the 10-ppm TWA PEL. Eastman Kodak concluded that "[no] significant irritation or other ill effects have been reported by employees that periodically are exposed to levels of acetic acid in excess of the proposed 15-ppm STEL" (Ex. 3-661, p. 4).

OSHA has carefuly reviewed the toxicologic evidence in the record and has determined that the evidence supporting a STEL for acetic acid is equivocal. Because information on exposure durations is lacking in the studies cited above (Baldi 1953/Ex. 1-602; Parmeggiani and Sassi 1954/Ex. 1-753), it is not known whether the conjunctival irritation found among exposed workers was due to short-term or prolonged exposure to acetic acid. Eastman Kodak (Ex. 3-661) has maintained that prolonged exposure to acetic acid at levels above the 10 ppm TWA PEL is necessary to cause irritant responses among exposed workers. Therefore, in the final rule, OSHA is retaining its 10 ppm TWA PEL for acetic acid, but is not supplementing this limit with a STEL.


ACETONE
CAS: 67-64-1; Chemical Formula: CH(3)COCH(3)
H.S. No. 1004


OSHA's previous Z-table limit for acetone was 1000 ppm as an 8-hour TWA. In the NPRM, the Agency proposed to lower this limit to 250 ppm as an 8-hour TWA. This proposed limit was derived from the NIOSH-recommended limit, which was based on a number of industrial and human volunteer studies reporting irritant and central nervous system effects resulting from exposure to acetone concentrations at levels below 1000 ppm; NIOSH (Ex. 8-47, Table N1) and the AFL-CIO (Ex. 194) concurred with the proposed limit. The ACGIH TLVs for acetone are 750 ppm as an 8-hour TWA and 1000 ppm as a 15-minute STEL. OSHA has carefully reviewed the scientific evidence and comments in the record and has determined that it is appropriate to revise the acetone PEL in the final rule to 750 ppm as an 8-hour TWA and to add a short-term limit of 1000 ppm. Acetone is a colorless, highly volatile, flammable liquid with an aromatic odor.

OSHA's proposed 250-ppm TWA limit for acetone was largely based on controlled human studies conducted by Nelson, Enge, Ross et al. (1943/Ex. 1-66) and Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191), as well as studies in workers conducted by Vigiliani and Zurlo (1955/Ex. 1-164) and Parmeggiani and Sassi (1954/Ex. 1-753). OSHA's reliance on these studies to establish a revised limit for acetone was criticized by Dr. William C. Thomas, Manager of Toxicology for the Hoechst Celanese Corporation, who testified on behalf of the Ketones Program Panel of the Chemical Manufacturers Association (CMA) (Ex. 8-54; Tr. 8/4/88, pp. 6-114 to 6-127; Exs. 149A, 149C). The National Marine Manufacturers Association (Ex. 181) agreed with Dr. Thomas' remarks. Summaries of each of these studies and of OSHA's response to Dr. Thomas' remarks follow.

In a controlled-exposure experiment, Nelson, Enge, Ross et al. (1943/Ex. 1-66) exposed an average of 10 human subjects (both male and female) to a variety of solvents, including acetone, for three to five minutes. Subjects were asked to judge the level of sensory irritation as absent, slightly irritating, or very irritating. Tests were conducted in a 1200-cubic-foot gas cabinet equipped with an anemostat to distribute the air uniformly. Acetone was reported to produce slight irritation on exposure to 300 ppm, but a concentration of 500 ppm produced a degree of eye, nose, and throat irritation that was still described by a majority of the subjects as "tolerable."

Dr. Thomas expressed five criticisms of the Nelson, Enge, Ross et al. (1943/Ex. 1-66) study. These were: (1) the short duration of exposure used; (2) the study's failure to account for adaptation because "naive" subjects who had not had previous acetone exposure were used; (3) the authors' reliance on subjective responses rather than on objective medical examination; (4) the use of nominal (calculated) exposures rather than measured exposures; and (5) the introduction of potential bias because students who were involved in the experiment were used as test subjects (Tr. 8/4/88, pp. 6-114 to 6-117; Exs. 149A, 149C).

NIOSH addressed some of these issues in its criteria document for ketones (NIOSH 1978f, as cited in ACGIH 1986/Ex. 1-3, p. 6). In its analysis of the Nelson, Enge, Ross et al. (1943/Ex. 1-66) study, NIOSH (1978f) concluded:

The concentrations of ketones in the exposure chamber were calculated (nominal) rather than measured analytically, so the true concentration may have been lower than reported....

[T]he use of experimenters as subjects was a possible source of bias, and the exposure periods of 3-5 minutes were not long enough to show if adaptation would occur.... The fact that exposure duration did not approach that of a normal workshift is a major limitation of...[this study]. However, the data are useful as a guide to the relative irritating properties of ketones and the concentrations at which these [properties] appear (NIOSH 1978f, p. 31).

Thus, despite these experimental limitations, NIOSH concluded that the Nelson, Enge, Ross et al. (1943/Ex. 1-66) study was useful in identifying ketone concentrations that are irritating, and it relied on this study, at least in part, when recommending a 250-ppm TWA limit for acetone (NIOSH 1978f, as cited in ACGIH 1986/Ex. 1-3, p. 6).

The second paper discussed by Dr. Thomas is the report by Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191). In this study, the authors exposed 25 healthy male subjects to 0, 100, 250, 500, or 1000 ppm acetone. Subjects were exposed for three hours in the morning and three hours in the afternoon, with a 45-minute period between exposures. Irritant responses were scored on a scale from 0 to 12, with a score of 12 representing severe irritation.

Most of the subjects exposed to 500 or 1000 ppm acetone reported irritation (scored between 4 and 5 in severity) during the first 90 minutes of exposure in the morning and the first 60 minutes of exposure in the afternoon. Subjects ceased to report irritation at the 90-minute mark during the afternoon exposure. A lesser degree of irritation was reported to occur among subjects exposed to 100 or 250 ppm acetone; however, this irritation subsided after the first 90 minutes of exposure in each of the two exposure periods. Subjects exposed to 250 ppm or higher reported feeling general weakness and a sense of tension even as long as 24 hours after exposure. Blood and urine samples taken during and after exposure showed increasing blood and urinary acetone levels among subjects exposed to 250 ppm or higher. Following the exposure period, these levels fell to normal values within about 25 to 35 hours after exposure was terminated. The authors also reported an increased leukocyte count in subjects exposed to 500 or 1000 ppm acetone; the increased white cell count persisted for about 24 hours after the cessation of exposure. The authors attributed this increased leukocyte count to acetone's irritant properties (Matsushita, Yoshimune, Inoue et al. 1969/Ex. 1-191).

Dr. Thomas criticized this study because it did not describe the methods used by its authors for measuring acetone exposures, and the blood acetone levels reported by Matsushita and colleagues (1969/Ex. 1-191) were about 2.5 times higher than those reported after similar exposures conducted by DiVincenzo, Yanno, and Astill (1973, as cited in ACGIH 1986/Ex. 1-3, p. 6). After a two-hour exposure to 500 ppm acetone, Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191) found a blood acetone level of 25 mg/L, compared to a level of 10 mg/L reported by DiVincenzo, Yanno, and Astill (1973, as cited in ACGIH 1986/Ex. 1-3, p. 6). Dr. Thomas suggested that the actual exposure levels employed by Matsushita and associates (1969/Ex. 1-191) may actually have been substantially higher than reported by these authors (Tr. 8/4/88, pp. 6-118 to 6-119; Exs. 149A, C).

OSHA has reviewed the report by DiVincenzo, Yanno, and Astill (1973, as cited in ACGIH 1986/Ex. 1-3, p. 6) and finds that the blood acetone results reported in this paper cannot be directly compared, as Dr. Thomas has done, with those reported by Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191), for a number of reasons. First, the subjects studied by DiVincenzo, Yanno, and Astill fasted for eight hours prior to exposure; it is not clear that the subjects studied by Matsushita, Yoshimune, Inoue et al. fasted before they were exposed. Second, the blood acetone values reported by DiVincenzo, Yanno, and Astill were corrected for endogenous acetone (i.e., acetone levels that existed prior to exposure). The authors reported that endogenous acetone levels ranged from 0 to 10 mg/L of blood, or about as high as would occur after a two-hour exposure to 500 ppm of acetone. Whether Matsushita, Yoshimune, Inoue et al. corrected for endogenous blood acetone levels is uncertain; if they did not, their reported blood acetone levels may be as much as two times overstated. The third consideration is that the studies used different methods to measure blood acetone levels. Matsushita, Yoshimune, Inoue et al. used a colorimetric method, while DiVincenzo, Yanno, and Astill used a gas chromatographic approach. The use of different analytical methods by the two investigative groups complicates any comparison of their blood acetone results. Thus, OSHA does not agree that the results by DiVincenzo, Yanno, and Astill (1973, as cited by ACGIH 1986/Ex. 1-3, p. 6) demonstrate that the exposure levels used by Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191) are necessarily understated.

In addition to the two controlled-exposure studies discussed above, two industry studies were relied on by OSHA to support the reduction in the acetone PEL. One report by Parmeggiani and Sassi (1954/Ex. 1-759) indicated that six employees exposed to 307 to 918 ppm acetone in a rayon acetate plant experienced eye and throat irritation, dizziness, and inebriation. Five of the employees showed objective signs of pharyngeal irritation, four had lung irritation, and three had conjunctivitis. Although the authors attribute the observed CNS effects to excessive concomitant exposure to carbon disulfide, the irritant effects are more likely to have been the result of exposure to acetone, because carbon disulfide is not a primary irritant by vapor inhalation (Chemical Hazards of the Workplace, 2nd ed., Proctor, Hughes, and Fischman 1988, pp. 120-121). The other report, by Vigliani and Zurlo (1955/Ex. 1-164), found that acetone production workers exposed to 700 ppm acetone for three hours daily for 7 to 15 years experienced inflammation of the respiratory tract, stomach, and duodenum; giddiness; and loss of strength.

Dr. Thomas (Exs. 8-54, 149A, 149C; Tr. 8/4/88, pp. 6-114 to 6-127) criticized these two studies on the basis that the urinary acetone levels reported by Parmeggiani and Sassi (1954/Ex. 1-759) and by Vigliani and Zurlo (1955/Ex. 1-164) indicated that airborne exposures were much higher than the reported values. He stated that, based on these values, the employees observed in both of these studies were likely to have been exposed to acetone levels approximating 5000 ppm. OSHA is not convinced that the exposure levels reported in these two studies are understated. The studies by Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-191) and DiVincenzo, Yanno, and Astill (1973, as cited in ACGIH 1986/Ex. 1-3, p. 6) clearly demonstrate that blood and urinary acetone levels can increase with continued, daily exposure. Furthermore, in its criteria document, NIOSH (1978f, as cited in ACGIH 1986/Ex. 1-3, p. 6) cites a number of studies that demonstrate that skin absorption of acetone can result in elevated blood and urinary acetone levels. OSHA believes that the high urinary acetone levels reported in the workers studied by Parmeggiani and Sassi (1954/Ex. 1-759) and by Vigiliani and Zurlo (1955/Ex. 1-164) were most likely the result of an accumulated body burden of acetone brought about by long-term exposure and dermal absorption. Given these considerations, it does not appear appropriate to approximate airborne exposure levels on the basis of the urinary acetone levels reported in these two studies.

To summarize, OSHA finds that the studies discussed above show that acetone is capable of producing sensory irritation at concentrations below 1000 ppm and that long-term exposure to acetone at levels below 1000 ppm can cause CNS disturbances. In addition, the ACGIH (1986/Ex. 1-3, p. 6) reports that chronic exposure to acetone causes respiratory irritation and headaches. Despite the methodological shortcomings of all of these studies, OSHA is impressed with the consistency of their findings. Both the Nelson, Enge, Ross et al. (1943/Ex. 1-66) and the Matsushita, Yoshimune, Inoue et al. (1969/Ex. 1-91) studies demonstrate that exposure to concentrations of acetone below 1000 ppm are associated with eye, nose, and throat irritation. Both industry studies (Parmeggiani and Sassi 1954/Ex. 1-759; Vigliani and Zurlo 1955/Ex. 1-164) report similar signs and symptoms of irritation and CNS disturbances in workers exposed to concentrations of acetone between 700 and 1000 ppm. OSHA is not persuaded by Dr. Thomas' arguments that exposure levels are understated in these reports; OSHA believes that the quantitative relationship between long-term exposure to acetone and urinary acetone levels is not sufficiently established to draw this conclusion. Therefore, OSHA concludes that the findings of these four studies are consistent in demonstrating the acute and long-term effects of acetone exposure at levels below 1000 ppm.

The Ketones Panel of the CMA (Tr. 8/4/88, pp. 6-100 to 6-113; Exs. 149A, 149B, and 179) also presented testimony by Dr. Robert Raleigh, Adjunct Professor of Medicine at the University of Rochester School of Medicine. Dr. Raleigh testified on a study he conducted among filter press operators who were exposed exclusively to acetone (Raleigh and McGee 1972, as cited in Ex. 8-54). In this study, 13 workers were asked about symptoms and were medically examined over a one-week period. Using grab bags, acetone samples were taken at random periods during each workshift. Subjective symptoms were recorded with each grab sample. Samples were analyzed by gas chromatography.

Over the period studied, TWA exposures to acetone varied from 950 to 1060 ppm. Of the 13 workers studied, nine (69 percent) reported eye irritation, five (38 percent) reported nasal irritation, and five (38 percent) reported throat irritation. Three (23 percent) employees reported experiencing lightheadedness. Some employees reported these symptoms more than once during the study period. There were four cases of eye irritation following short-term exposures to acetone concentrations below 1000 ppm. Eye irritation that was reported to be "strong" occurred following short-term exposures to approximately 1800 ppm. Physical examination revealed a few instances of redness of the nasal mucosa and slight infection of the mucosa of the nose and throat.
In his written testimony regarding this study, Dr. Raleigh concluded:
Considering the number of samples taken, the variability of human response, the slight to mild nature of the response, and the lack of objective evidence of eye irritation as noted by the examining physician, I do not believe... [instances of irritation occurring below 1000 ppm] indicate the need for a safe level being set below 1000 parts per million (Ex. 8-54, p. 9).

Dr. Raleigh also testified that the occurrence of transient dizziness was no cause for concern:

[T]his symptom is usually very transient and in my experience I have never noted any adverse consequences from an occasional person...who complains of dizziness (Tr. 8/4/88, p. 6-103).

OSHA does not agree with Dr. Raleigh's interpretation of his study or with his view that dizziness, irritation and mild infections of the mucous membranes of the respiratory tract do not constitute material impairments of health. After reviewing the Raleigh and McGee report (1972, as cited in Ex. 8-54), OSHA notes that more than half the workers studied experienced sensory reactions from exposure to acetone at TWA levels equal to the former 1000-ppm OSHA limit. Furthermore, some of these reactions were characterized as "strong." OSHA believes that this study further demonstrates that the Agency's former 1000-ppm 8-hour TWA limit is insufficiently protective and does not prevent workers from experiencing these sensory effects. In addition, in contrast to Dr. Raleigh, OSHA characterizes transient dizziness in and of itself as an "adverse consequence." Dizziness connotes an effect on the central nervous system; in addition, dizziness is a serious safety hazard in the workplace. For the reasons stated earlier in this section, OSHA finds that such effects constitute material impairments of health. Thus, OSHA finds that the Raleigh and McGee study (1972, as cited in Ex. 8-54) is a recent, well-conducted study that provides additional support for the need to lower the former 1000-ppm TWA limit for acetone. Furthermore, OSHA finds the evidence that adverse effects can result from short-term exposures to levels of acetone at or near 750 ppm convincing; two controlled human studies (Nelson, Enge, Ross et al. 1943/Ex. 1-66; Matsushita, Yoshimune, Inoue et al. 1969/Ex. 1-191) reported sensory irritant effects upon short-term exposure to such levels of acetone, and two industry studies (Parmeggiani and Sassi 1954/Ex. 1-759; Vigliani and Zurlo 1955/Ex. 1-164) reported irritation and CNS effects among employees exposed to acetone levels ranging from 307 to 918 ppm in one instance and about 700 ppm in the other. In addition, two studies (Matsushita, Yoshimune, Inoue et al. 1969/Ex. 1-191; DiVincenzo, Yanno, and Astill 1973, as cited in ACGIH 1986/Ex. 1-3, p. 6) suggest that chronic exposure to acetone on a daily basis leads to the bioaccumulation of acetone.

In light of the studies discussed above, OSHA concludes that it is necessary to reduce the limit for acetone to 750 ppm as an 8-hour TWA and 1000 ppm as a STEL to protect workers from the acute and chronic effects of acetone exposure. OSHA finds that the chemically induced sensory irritation associated with acute exposures to acetone can occur at levels only slightly above the 750-ppm level being established as an 8-hour TWA. In the absence of a STEL, the 750-ppm limit would permit excursions to levels as high as 12,000 ppm for brief periods. Such levels "depress the central nervous system, causing dizziness, weakness, and loss of consciousness" (Proctor, Hughes, and Fischman 1988, p. 49). An 8-hour TWA of 750 ppm is necessary to protect workers against the bioaccumulation of acetone, chronic irritation of the respiratory tract, and headaches associated with long-term acetone exposures. OSHA considers both the short-term sensory irritation associated with brief exposures to acetone and the increased blood and urinary accumulation and chronic respiratory irritation characteristic of long-term acetone exposures to be material impairments of health. Accordingly, OSHA is establishing in the final rule an 8-hour TWA PEL of 750 ppm and a STEL of 1000 ppm for acetone.


ACROLEIN
CAS: 107-02-8; Chemical Formula: CH(2) = CHCHO
H.S. No. 1007


OSHA formerly had an 8-hour TWA PEL of 0.1 ppm (0.25 mg/m(3)) for acrolein. OSHA proposed the addition of a 0.3-ppm STEL to this TWA limit, and the final rule adopts this short-term limit. NIOSH (Ex. 8-47, Table N1) concurred with these proposed limits. These limits for acrolein are the same as those recommended by the ACGIH (1986/Ex. 1-3). Acrolein is a colorless or yellowish flammable liquid with a disagreeable, choking odor.

In early inhalation studies of cats (Iwanoff 1911, as cited in ACGIH 1986/Ex. 1-3, p. 11), exposure to 10 ppm acrolein for 3.5 hours was found to have only transient effects, including salivation, lacrimation, respiratory irritation, and mild narcosis. However, later studies reported that an exposure to 1 ppm of acrolein produced marked nose and eye irritation in five minutes or less (Cook 1945/Ex. 1-726). Over longer periods, studies have demonstrated fatalities in one of six rats exposed for four hours to airborne concentrations of acrolein at 8 ppm; at 16 ppm, the mortality was 100 percent (Smyth 1956/Ex. 1-759). Irritation of the upper respiratory tract is the primary symptom of acrolein inhalation, but lung edema can occur after exposure to high concentrations (Henderson and Haggard 1943a/Ex. 1-881). In addition, skin contact with acrolein causes skin burns and severe injury to the cornea.

No comments (other than NIOSH's) were received on OSHA's proposed 8-hour time-weighted-average limit or its 15-minute short-term limit of 0.3 ppm. OSHA concludes that, in the absence of a STEL, the current 0.1-ppm TWA limit would not protect employees from short-term exposures to airborne concentrations in excess of 1 ppm, the level found by Cook (1945/Ex. 1-726) to cause severe eye and nose irritation. OSHA considers these adverse effects to represent material impair-ments of health or functional capacity. Therefore, OSHA finds that the 0.3-ppm STEL is necessary to protect employees from the significant risk associated with mucous membrane irritation, and the Agency is revising the exposure limit for acrolein to 0.1 ppm as an 8-hour TWA and 0.3 ppm as a 15-minute STEL.


ALLYL ALCOHOL
CAS: 107-18-6; Chemical Formula: CH(2) = CHCH(2)OH
H.S. No. 1010


OSHA previously had a PEL of 2 ppm TWA for allyl alcohol, with a skin notation. OSHA proposed to supplement this TWA limit with a STEL of 4 ppm and to retain the existing skin notation. NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The final rule establishes a 2-ppm TWA limit, a 4-ppm STEL, and a skin notation for allyl alcohol, which is consistent with the ACGIH (1986/Ex. 1-3) recommendation. Allyl alcohol is a colorless liquid with a pungent, mustard-like odor.

The most important adverse effects of occupational exposures to allyl alcohol are upper-respiratory-tract irritation and burns of the eyes. In a controlled human sensory response study (Dunlap, Kodama, Wellington et al. 1958/Ex. 1-630), a five-minute exposure to 25 ppm resulted in severe eye irritation. Milder irritation has been reported to occur at 5 ppm (McCord 1932, as cited in ACGIH 1986/Ex. 1-3, p. 18). Necrosis of the cornea and temporary blindness occurred in one individual exposed to allyl alcohol at a level irritating to the eyes and nose (Smyth 1956/Ex. 1-759). Skin absorption may lead to serious systemic injury (visceral congestion, periportal congestion of the liver, hematuria, and nephritis); in addition, when evaporation from the skin is prevented or reduced, skin contact causes burns (ACGIH 1986/Ex. 1-3, p. 18).

Exposure to airborne concentrations of allyl alcohol causes a series of characteristic effects, including lacrimation, photophobia, blurred vision, and retrobulbar pain (Dunlap, Kodama, Wellington et al. 1958/Ex. 1-630). Exposed individuals do not develop a tolerance for this substance, and they also do not become sensitized (Kodama and Hine 1958/Ex. 1-1088).

The New Jersey Department of Public Health (Ex. 144, 144A) urged OSHA to set its limits for allyl alcohol on the basis of EPA's IRIS data. The use of such an approach is discussed in Section VI.A of the preamble.

In a prehearing comment, Dr. Lawrence Hecker of Abbott Laboratories (Ex. 3-678) stated that a STEL did not appear to be warranted for allyl alcohol, based on his review of the literature. However, Dr. Hecker did not specifically discuss the evidence or rationale underlying this contention. In reviewing the evidence for allyl alcohol, OSHA notes that severe eye irritation has been reported to occur in human subjects exposed to 25 ppm for as short an interval as five minutes (Dunlap, Kodama, Wellington et al. 1958/Ex. 1-630); such an exposure would be permitted under the current limit of 2 ppm as an 8-hour TWA. OSHA also notes that short-term exposure to allyl alcohol produces characteristic effects more severe than those caused by other sensory irritants; these effects include photophobia and blurred vision. OSHA considers the effects of sensory irritation and disturbed vision to constitute material impairments of health or functional capacity. Sax and Lewis (1989) report that the dermal LD(50) in rabbits is 53 mg/kg, indicating that allyl alcohol readily permeates the skin and causes systemic toxicity.

OSHA concludes that the scientific evidence clearly shows a significant health risk associated with short-term exposure to the levels of allyl alcohol that would be permitted under the former standard; accordingly, the Agency is establishing a 4-ppm 15-minute STEL to supplement its 8-hour TWA limit of 2 ppm. The final rule retains the skin notation for this substance to protect workers from dermal absorption.


ALLYL GLYCIDYL ETHER
CAS: 106-92-3; Chemical Formula: C(6)H(10)O(2)
H.S. No. 1012


OSHA's former PEL for allyl glycidyl ether (AGE) was 10 ppm (45 mg/m(3)) as a ceiling. OSHA proposed to revise this limit to a TWA of 5 ppm, and to add a 15-minute STEL of 10 ppm and a skin notation, consistent with the recommended limits of the ACGIH (1986/Ex. 1-3). NIOSH (Ex. 8-47, Table N1) concurred with this proposal. In the final rule, OSHA is establishing the air contaminant limits as proposed, but is not establishing a skin notation for this substance (see Section VI.C.18 for a discussion of the Agency's policy on skin notations). Allyl glycidyl ether is a colorless liquid of characteristic, but not unpleasant, odor.

In limited human exposure studies, AGE has been demonstrated to cause dermatitis and eye irritation; the substance produces moderate primary skin irritation and severe eye irritation in animals (Hine, Kodama, Wellington et al. 1956/Ex. 1-331). At 260 ppm, animals experienced irritation of the eyes and respiratory distress; at higher levels (e.g., 400, 600, and 900 ppm), corneal opacities and severe respiratory difficulties occurred (Hine, Kodama, Wellington et al. 1956/Ex. 1-331). The percutaneous LD(50) for rabbits is 2.55 g/kg. Intragastric administration of AGE in mice, rats, and rabbits has also been demonstrated to cause depression of the central nervous system (Hine, Kodama, Wellington et al. 1956/Ex. 1-331).

In humans, skin sensitization occurs readily (Hine and Rowe 1963a, as cited in ACGIH 1986/Ex. 1-3, p. 20). In addition to primary irritation and sensitization, the potential exists for cross-sensitization with other epoxy agents (ACGIH 1986/ Ex. 1-3, p. 20).

Sax and Lewis (Dangerous Properties of Industrial Materials, 7th ed., 1989) report the dermal LD(50) in rabbits to be 2.25 g/kg; there is no other evidence of systemic poisoning occurring from skin absorption in humans or other animal species. Therefore, in accordance with the general policy described in Section VI.C.18 of this preamble, OSHA is not establishing a skin notation for AGE. Other than those submitted by NIOSH, OSHA received no comments on its proposed revision of the exposure limit for AGE.

In the final rule, OSHA is establishing PELs of 5 ppm (8-hour TWA) and 10 ppm (15-minute STEL) for allyl glycidyl ether. OSHA concludes that these combined limits will reduce the significant risks of sensitization and primary irritation to which employees could otherwise be exposed. OSHA considers these adverse effects material impairments of health and functional capacity.


ALLYL PROPYL DISULFIDE
CAS: 2179-59-1; Chemical Formula: CH(2) = CHCH(2)S(2)C(3)H(7)
H.S. No. 1013


The previous OSHA PEL for allyl propyl disulfide was 2 ppm (12 mg/m(3)) as an 8-hour TWA. OSHA proposed to supplement this limit with a 3-ppm (18-mg/m(3)) 15-minute STEL, and NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The final rule establishes a 2-ppm TWA limit and 3-ppm STEL for this substance; these limits are the same as those recommended by the ACGIH (1986/Ex. 1-3). Allyl propyl disulfide is a liquid with a pungent, irritating odor.

Nearly all occupational exposures to allyl propyl disulfide, the primary volatile constituent of onion oil, occur in the processing of onions and onion products. Allyl propyl disulfide's irritative effects on the human eye, nose, and upper respiratory tract are well recognized. The most severe irritation effects have occurred when workers were exposed to allyl propyl disulfide in the vicinity of onion slicing machines, where average concentrations of 3.4 ppm have been measured (Feiner, Burke, and Baliff 1946/Ex. 1-604).

No rulemaking participants other than NIOSH commented on the addition of a STEL to the current TWA limit for allyl propyl disulfide. OSHA concludes that, in the absence of a STEL, the 2-ppm TWA limit would not prevent employees from being exposed to short-term concentrations of sufficient magnitude to cause acute irritant effects. The Agency considers this effect to constitute material impairment of health and functional capacity. Accordingly, OSHA finds that a limit on short-term exposure is necessary to protect workers from significant acute irritation and is supplementing its current 2-ppm TWA limit with a 3-ppm 15-minute STEL in the final rule.


AMMONIA
CAS: 7664-41-7; Chemical Formula: NH(3)
H.S. No. 1021


OSHA's former exposure limit for ammonia was 50 ppm as an 8-hour TWA. OSHA proposed to revise this limit to 25 ppm TWA and to add a 35-ppm 15-minute STEL, based on the limits established by the ACGIH. NIOSH indicated its agreement with these proposed limits (Ex. 8-47, Table N1). However, in the final rule, the Agency has determined that it is not appropriate to establish a 25-ppm TWA limit for ammonia; the final rule does revise OSHA's exposure limit to 35 ppm as a 15-minute STEL. Ammonia is principally used as a feedstock in the manufacture of fertilizers and other chemical substances and is also used as a refrigerant.

Ammonia is a primary eye and upper respiratory tract irritant. An unpublished study conducted by the Detroit Department of Health and cited by the ACGIH (1986/Ex. 1-3, p. 27) reports that ammonia concentrations in the range of 20 to 25 ppm elicited complaints of discomfort from workers engaged in blueprinting and copying operations. In addition, a study of pigs conducted by Stombaugh et al. (1969) apeared to demonstrate that exposure to ammonia also causes systemic effects. Thus the ACGIH established both a full-shift TWA of 25 ppm to protect against chronic effects and a 35-ppm STEL to protect against ammonia's irritant effects.

OSHA also considered NIOSH's recommended 5-minute ceiling limit for ammonia of 50 ppm. When making this recommendation, NIOSH relied on several reports that ammonia concentrations as low as 50 ppm are moderately irritating (Vigliani and Zurlo 1955/Ex. 1-164; Mangold 1971; Industrial Bio-test Laboratories 1973, all as cited in NIOSH 1974a/Ex. 1-238; MacEwen, Theodore, and Vernot 1970/Ex. 1-827; Pagnotto 1973, as cited in ACGIH 1986/Ex. 1-3, p. 27). NIOSH concluded that the "irritating or annoying effects...[of exposure to ammonia are] more dependent upon concentration than length of exposure," and that "a standard expressed as a time-weighted average is inappropriate since it would permit fluctuations to concentrations considerably higher than 50 ppm" (NIOSH 1974a/Ex. 1-238, p. 69). In the proposal, OSHA preliminarily concluded that NIOSH's recommended 50-ppm ceiling limit was above the effect level reported in the Detroit Department of Health studies (1965-1970, as cited in ACGIH 1986/Ex. 1-3, p. 27) for sensory irritation.

Several rulemaking participants objected to a reduction in the current 50-ppm TWA limit (Exs. 3-375, 3-582, 3-756, 3-869, 3-888, 3-902, 3-939, 3-1012, 3-1118, 8-25, 8-29, 8-62, 8-68, 8-123, Tr. VIII 121-136). At the rulemaking hearing, Lucas Seeman, Technical Advisor for the Association of Reproduction Materials Manufacturers (ARMM), testified that there was no basis for the proposed revision since the effects associated with exposure to 50 ppm of ammonia did not, in his opinion, constitute impairment of health:

The Detroit Health Department studies, which make reference to "worker complaints" of ammonia exposures, appear to be based on subjective reactions of workers and not any manifestation of health impairment or physical evidence of severe irritation.

None of the reference data added [by the ACGIH] in 1980...made reference to any health impairment at the 25-ppm TWA or 35-ppm STEL levels of exposure. References added in 1980 did indicate that at 50 ppm workers reported no irritation, or minor to moderate irritation, and that they quickly became accustomed to the ammonia exposure up to that level (Tr. VII, pp. 222-224).

In reviewing the record evidence, OSHA finds that the 50-ppm 5-minute ceiling limit recommended by NIOSH is not sufficiently protective against ammonia's irritant effects. The evidence discussed by NIOSH (Ex. 150) and the testimony presented by Mr. Seeman (Tr. VII, pp. 222-224) show that, at levels below 50 ppm, some workers experience eye and upper respiratory tract irritation. This view is supported by Proctor, Hughes, and Fischman (Chemical Hazards of the Workplace, 2nd ed., 1988, p. 71), who report that even 5-minute exposures to 32 ppm caused nasal dryness in 10 percent of exposed volunteers, and that 5-minute exposures to 50 ppm ammonia caused nasal irritation and dryness in 20 percent of exposed volunteers. Deborah Berkowitz of the AFL-CIO testified that two companies in the meat packing industry evacuate the work place if airborne concentrations of ammonia reach 25 ppm (Tr. pp. 6-310 to 6-311).

OSHA finds that sensory irritation, such as that experienced by volunteers exposed to ammonia (Proctor, Hughes, and Fischman, 1988) constitutes material impairment of health. OSHA also finds that the fact that some workers may become acclimatized to ammonia exposures at concentrations as high as 50 ppm may account for the belief expressed by Mr. Seeman and others that 50 ppm is an acceptable exposure level. However, OSHA does not agree with this view of acclimatization because the long-term consequences of a continual assault on the sensory nerves are not known. In addition, acclimatization lessens the ability of workers to discern airborne concentrations of other hazardous materials.

The ACGIH (1986/Ex. 1-3) believes that an 8-hour TWA limit is necessary for ammonia because a study by Stombaugh, Teague, and Roller (1960/Ex. 1-29) reports that pigs exposed continuously to 103 to 145 ppm ammonia reduced their consumption of food and lost weight. The ACGIH interprets this study to mean that systemic toxicity occurs as a result of chronic exposure to ammonia. However, OSHA interprets this study differently, believing instead that it shows a secondary effect of the irritation traditionally associated with ammonia exposure. That is, in OSHA's view, these pigs stopped eating because they were experiencing too much respiratory and eye irritation to be interested in their food.

Thus, OSHA does not find it necessary in the final rule to establish an 8-hour TWA limit for ammonia to protect against chronic effects. Instead, the Agency concludes that a 15-minute STEL of 35 ppm will protect against this substance's irritant effects, which have been demonstrated to occur in workers exposed to ammonia at and below 50 ppm. OSHA concludes that the eye and upper respiratory tract irritation associated with ammonia exposure constitute material impairments of health and pose a significant risk to exposed workers.


AMMONIUM CHLORIDE (FUME)
CAS: 12125-02-9 Chemical Formula: NH(4)C(1)
H.S. No. 1022


No previous OSHA PEL had been established for ammonium chloride fume. Based on the ACGIH recommendation, OSHA proposed a TWA limit of 10 mg/m(3) and a 20-mg/m(3) STEL, and NIOSH (Ex. 8-47, Table N1) concurred with these proposed limits, and they are established in the final rule. Ammonium chloride is a white crystalline solid, somewhat hygroscopic, with a cool, saline taste.

Ammonium chloride fume is an irritant to the skin and respiratory passages when inhaled and produces mild systemic toxicity when ingested (Sax 1968a/Ex. 1-867). Although exposure-response data are lacking for this substance, the ACGIH (1986/Ex. 1-3) judged that these workplace limits would be sufficient to prevent workers from experiencing respiratory irritation.

OSHA received no comments on the proposed addition of exposure limits for ammonium chloride fume to the Z tables, other than those submitted by NIOSH. OSHA finds that, in the absence of any limit on airborne exposure, employees are at significant risk of respiratory irritation caused by exposure to high concentrations of ammonium chloride fume. OSHA concludes that the respiratory irritation caused by exposure to ammonium chloride fume constitutes a material impairment of health. To substantially reduce this risk, OSHA is establishing an 8-hour TWA limit of 10 mg/m(3) and a 15-minute STEL of 20 mg/m(3) in the final rule.

BORATES, TETRA, SODIUM SALTS (ANHYDROUS, PENTAHYDRATE, AND DECAHYDRATE) CAS: 1303-96-4 (Decahydrate); Chemical Formula:
Na(2)B(4)O(7) 10H(2)O 1330-43-4 (Anhydrous); Chemical Formula:
Na(2)B(4)O(7)
12179-04-3 (Pentahydrate); Chemical Formula:
Na(2)B(4)O(7) 5H(2)O H.S. Nos. 1036, 1038, and 1037

OSHA formerly had no exposure limits for the anhydrous or hydrated forms of sodium tetraborate. Based on the ACGIH-recommended TLVs for these substances, OSHA proposed a 1-mg/m(3) 8-hour TWA PEL for the anhydrous and pentahydrate forms of sodium tetraborate and a 5-mg/m(3) TWA PEL for the decahydrate form. NIOSH (Ex. 8-47, Table N1) concurred with these proposed limits. However, during the rulemaking proceeding, OSHA received several comments on the proposed limits and obtained information on a large health survey currently being conducted by the U.S. Borax and Chemical Corporation. Based on this evidence, the Agency has determined that it is appropriate at this time to establish a 10-mg/m(3) 8-hour TWA limit for all forms of the sodium tetraborates. Anhydrous sodium tetraborate is a light gray, odorless solid; the pentahydrate and decahydrate forms are white, odorless, and crystalline.

OSHA's proposed limits were based on some early studies cited by the ACGIH (1986/Ex. 1-3) and on observation that the anhydrous and pentahydrate forms of sodium tetraborate present a greater irritant hazard than does the decahydrate form. These early studies reported that exposure to the tetraborates produces irritation of the skin, eyes, and upper respiratory tract and can cause shortness of breath and nosebleeds. These studies were criticized at the hearings by John Middleton, Manager of Product Safety for the U.S. Borax Research Corporation, because they did not have sufficient exposure data to define a dose-response relationship (Tr. p. 9-113).

During the rulemaking, commenters discussed two NIOSH health hazard evaluations (HHEs) relevant to the borates. The first study (HHE 75-059-496, NIOSH 1978o) was conducted at the Kerr-McGee Chemical Corporation plant in Trona, California. NIOSH performed clinical examinations of nine employees exposed to tetraborates and collected total dust samples for each employee. Clinical examination revealed symptoms of eye irritation in five employees, nose irritation with bleeding in three workers, throat irritation in three employees, and chapping of the hands in four workers. Four of the nine dust samples exceeded 10 mg/m(3), with the highest being 29.9 mg/m(3). In testimony before the Occupational Safety and Health Standards Board in California in 1985, Dr. Charles Hine of Kerr-McGee stated that dust exposures at the California plant were probably well above the 10-mg/m(3) level because employees commented that dust from "frequent windstorms" was the main problem at the plant. Dr. Hine also noted that the NIOSH HHE reported that dust levels at the plant were excessive and that the visibility of employees was impaired (Ex. 3-744, Attachment I).

The second NIOSH HHE (conducted in 1980) reported on a walk-through survey of the U.S. Borax and Chemical Corporation's Boron, CA Operation. This HHE identified health complaints among employees, and its findings led to a larger, more comprehensive health survey in 1981 (HETA 80-109), a report of which was subsequently published in a peer-reviewed journal (Garabrant, Bernstein, Peters et al. 1985). Data on employees' respiratory symptoms were obtained by questionnaire, and total dust measurements were collected from historical data obtained between 1977 and 1981. The authors found no evidence of X-ray abnormalities or declines in pulmonary function among the 629 active employees examined. There was a dose-related and statistically significant increase in the frequency of reported symptoms, which included eye irritation, dry cough, nosebleeds, sore throat, shortness of breath, and chest tightness. Over 10 percent of employees having mean TWA exposures of 8.6 mg/m(3), measured as total tetraborate dust, reported experiencing nosebleeds, dry cough, eye irritation, and dryness of the mouth, nose, or throat. At a mean exposure level of 14.6 mg/m(3), between 15 and 30 percent of the employees examined reported these symptoms. The authors concluded that borax dust appears to act as a simple respiratory irritant and may cause small changes in pulmonary function among smokers who are also heavily exposed to borate dust.

U.S. Borax submitted to the record the written testimony of Dr. David Heilbron, a biostatistician (Ex. 3-744, Attachment 2), and of Dr. Ralph C. Smith, Professor of Occupational and Environmental Health, School of Public Health, University of Michigan (Ex. 3-744, Attachment 3), both of whom were of the opinion that the Garabrant et al. (1985) study's treatment of exposure data was biased. For example, Dr. Heilbron objected to the grouping of employees into three exposure categories, commenting that such aggregation "can seriously distort a dose-response relationship and particularly, the estimation of an effect threshold..." (Ex. 3-744, Attachment 2, p. 4). Dr. Heilbron also took issue with these authors' use of geometric means to describe the tetraborate exposure data; in the opinion of Dr. Heilbron, there was no statistical justification for the use of geometric means because of the heterogeneity of jobs within each exposure group.

OSHA believes that it is not possible to determine whether arithmetic or geometric means are appropriate without having access to the raw data. OSHA notes further that Garabrant and his co-authors (1985) both gathered and analyzed the data and that neither Dr. Heilbron nor Dr. Smith had access to these data.

Dr. Smith (Ex. 3-347, Attachment 3) believes that the exposure data in the Garabrant et al. (1985) study substantially underreported the actual exposures of the workers comprising the study group. According to Dr. Smith, when the data are reanalyzed using arithmetic means, the observed health effects would be associated with exposures to much higher dust levels than those presented in the report (Ex. 3-744, Attachment 3, p. 13).

Because the raw exposure data from the study were not available to Dr. Smith, he based his reanalysis of the exposure data on an assumption that all individuals in a job category had exposures equal to the mean exposure level for the job category as a whole. For example, according to Dr. Smith, if "four laborers in the fusing building had average exposures of 49.2 mg/m(3)...[it was assumed] that all four had the same exposure" (Ex. 3-744, Attachment 3, p. 8). OSHA believes that Dr. Smith's approach provides less information about the actual exposures of the members of the cohort than does Dr. Garabrant's because Dr. Garabrant took two factors (representative data by job category as well as subjective self-reporting of exposure levels by employees) into account, while Dr. Smith only considered a single factor (job category). That is, Dr. Smith assumes that all workers in a job category have the same exposure, while Dr. Garabrant's approach recognizes the impact of such factors as individual differences in work practices, differences in control effectiveness at different workstations, etc., on the exposures of individuals in the same job category. OSHA is therefore unpersuaded by Dr. Smith's reanalysis; the Agency finds Dr. Garabrant's analysis convincing and believes that it more accurately reflects the true exposures of members of this cohort.

Largely because of questions raised concerning the dose-response relationship for tetraborates, U.S. Borax has been conducting a large epidemiologic study at its facility. This study, described at the informal hearing by Mr. Middleton (Tr. pp. 9-114 to 9-115, Ex. 120), will span a three- to four-year period and will obtain about 400 measurements of workplace tetraborate dust. The test protocols have been reviewed by representatives of OSHA, the U.S. Bureau of Mines, NIOSH, the ACGIH TLV Committee, and the Mine Safety and Health Administration. The final report is expected to be released in mid-1989. At the hearing, Mr. Middleton stated the position of U.S. Borax:

Based on the fact that the present data does not support the establish[ment] of PEL's for these compounds and that U.S. Borax is presently collecting data that could be meaningful in establishing PEL's, we request that OSHA delay action on these compounds until these data are available and can be analyzed by OSHA and MSHA (Tr. p. 9-115).

OSHA commends U.S. Borax for undertaking this effort to study the relationship between exposure to tetraborates and respiratory effects. OSHA believes that such data are essential to inform employees properly about hazards present in their workplaces and to guide employers in the development of effective occupational health programs. However, OSHA does not agree that the evidence currently available is inadequate to serve as a basis for establishing a PEL for the tetraborates at the present time. The study by Garabrant et al. (1985) does demonstrate a dose-response relationship for respiratory symptoms and exposure to sodium borates. OSHA finds that employees should be protected from experiencing the symptoms that have been reported. These symptoms, which have been reported in the more recent Garabrant et al. (1985) and NIOSH (1978o; 1980b) studies, as well as in the older literature, include nosebleeds, upper respiratory tract irritation, dermatitis, and dyspnea. OSHA believes that this evidence clearly indicates that the tetraborates act as primary respiratory and skin irritants, and that a 10-mg/m(3) PEL is clearly warranted. In light of the research currently being conducted by U.S. Borax, however, OSHA notes that the Agency will consider new evidence as it becomes available and will revise its limits if such action appears to be appropriate.

OSHA agrees with U.S. Borax that, at this time, there are insufficient data upon which to establish different PELs for the different hydrated forms of tetraborate. OSHA believes that current sampling and analytical procedures cannot distinguish among the various hydrated forms of tetraborate (Ex. 3-744, Attachment 3, pp. 4 - 5) and therefore that separate standards of 5 mg/m(3) and 1 mg/m(3) are not feasible at this time.

OSHA concludes that an 8-hour TWA of 10 mg/m(3) is appropriate for the tetraborates, and the final rule establishes this limit. OSHA finds that, in the absence of any limit on exposure, employees are at significant risk of experiencing acute eye, skin, and respiratory irritation effects, and that a 10-mg/m(3) PEL will substantially reduce these risks. The Agency considers the eye, skin, and upper respiratory tract irritation caused by exposure to all forms of sodium tetraborates to be material impairments of health.


BROMINE
CAS: 7726-95-6; Chemical Formula: Br(2)
H.S. No. 1042


OSHA's previous exposure limit for bromine was 0.1 ppm as an 8-hour TWA. OSHA proposed to supplement this TWA limit with a STEL of 0.3 ppm, the same limit recommended by the ACGIH, and NIOSH (Ex. 8-47, Table N1) concurred with this proposal. In the final rule, the Agency is establishing a 0.1-ppm TWA limit and a 0.3-ppm STEL for bromine. Bromine is a dark, reddish-brown, noncombustible, diatomic liquid that has irritating vapors.

Early studies of bromine exposure indicated that workers exposed to 0.75 ppm for 6 hours exhibited no symptoms (Flury and Zernik 1931a, as cited in ACGIH 1986/Ex. 1-3, p. 65). Later studies reported physiological responses to different concentrations of bromine and used these findings to make the following recommendations: the maximum allowable concentration for prolonged exposures should be 0.1 to 0.15 ppm, and the maximum allowable concentration for short-term exposures (i.e., 30 minutes to one hour) should be 4 ppm (Henderson and Haggard 1943b, as cited in ACGIH 1986/Ex. 1-3, p. 65). These investigators found levels of 40 to 60 ppm dangerous for short-term exposures, and a level of 1000 ppm proved rapidly fatal even during short exposures. These authors reported that the effects of exposure to bromine include respiratory irritation and lung edema. Elkins (1959a/Ex. 1106) reported that workers exposed to 1 ppm in a plant handling liquid bromine found this level excessively irritating.

OSHA received no comments on its proposed STEL for bromine, other than the NIOSH concurrence statement. The Agency finds that both the TWA and the short-term limits are necessary to substantially reduce the risk of respiratory irritation and lung damage that could occur following short-term exposures to concentrations of bromine that would be permitted by the 8-hour TWA limit alone. OSHA considers the effects related to bromine exposure material impairments of health. Therefore, OSHA is revising the limit for bromine to 0.1 ppm as an 8-hour TWA and 0.3 ppm as a 15-minute STEL.


2-BUTANONE (METHYL ETHYL KETONE)
CAS: 78-93-3; Chemical Formula: CH(3)COCH(2)CH(3)
H.S. No. 1045


OSHA's former exposure limit for 2-butanone was 200 ppm TWA. OSHA proposed to supplement this limit with a STEL of 300 ppm, based on the ACGIH (1986/Ex. 1-3) recommendation. NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The final rule establishes a 200-ppm TWA limit and a 300-ppm STEL for 2-butanone. 2-Butanone is a colorless, flammable liquid with an objectionable odor.

2-Butanone is an ocular and upper respiratory tract irritant. One study (Nelson, Enge, Ross et al. 1943/Ex. 1-66) reported that exposures to 200 ppm for 3 to 5 minutes caused mild eye irritation in some subjects and that others experienced slight nose and throat irritation at concentrations of 100 ppm. Exposure to 350 ppm caused eye and nasal irritation in a majority of subjects tested. Studies conducted in the 1940s noted low-grade intoxication resulting from exposure to 300 to 600 ppm (Smith and Mayers 1944, as cited in ACGIH 1986/Ex. 1-3, p. 395). Later studies have shown that approximately 50 percent of trained panelists experienced eye and nose irritation at 200 ppm (as reported in ACGIH 1986/Ex. 1-3, p. 395).

In the preamble discussion on 2-butanone, OSHA noted that a number of studies indicate that the proposed limits may not be sufficient to fully protect workers from the irritant effects of this substance (ACGIH 1986/Ex. 1-3; Nelson, Enge, Ross et al. 1943/Ex. 1-66). The ACGIH also cited a manufacturer's publication that stated that 200 ppm was the highest concentration judged by human subjects to be "satisfactory" for eight hours. In addition, another study cited by the ACGIH (1986/Ex. 1-3) reported that exposure to 200 ppm was associated with a 50-percent response rate for eye and nasal irritation (the degree of irritation was not specified).

OSHA specifically requested comment on whether its proposed limits for 2-butanone were sufficiently protective. The New Jersey Department of Public Health (Exs. 144, 144A) urged OSHA to set its limits for 2-butanone based on EPA's IRIS data. The use of such an approach is discussed in Section VI.A of the preamble. The AFL-CIO (Ex. 194) supported the establishment of a STEL for butanone.

OSHA has determined that its previous 8-hour TWA limit of 200 ppm was not sufficient to protect workers from experiencing the significant irritation and narcotic effects that are associated with short-term exposures to high concentrations of 2-butanone. After reviewing the available reports describing human sensory responses to short-term exposures to 2-butanone, the Agency concludes that a 300-ppm STEL is also necessary to reduce the significant risk of sensory irritation; exposure to 350 ppm for three to five minutes was reported to cause eye, nose, and throat irritation in a majority of subjects (Nelson, Enge, Ross et al. 1943/Ex. 1-66). Accordingly, OSHA is establishing a 200-ppm TWA limit and a 300-ppm 15-minute STEL for 2-butanone to protect employees from the significant risk of sensory irritation; OSHA considers the irritation caused by 2-butanone to be a material impairment of health or functional capacity.


n-BUTYL ACETATE
CAS No. 123-86-4; Chemical Formula: CH(3)COO(CH(2))(3)CH(3)
H.S. No. 1047


The previous OSHA exposure limit for n-butyl acetate was 150 ppm, measured as an 8-hour TWA. OSHA proposed the adoption of a 15-minute STEL of 200 ppm to supplement the TWA limit. NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The final rule establishes limits of 150 ppm as an 8-hour TWA and 200 ppm as a 15-minute STEL for this substance; these are the same limits as those recommended by the ACGIH (1986/Ex. 1-3). n-Butyl acetate is a colorless liquid with a fruity odor.

n-Butyl acetate is an irritant to the eyes, skin, and respiratory system. In a study involving cats exposed for six hours to 6100 ppm, slight narcotic effects were noted (Flury and Wirth 1933, as cited in ACGIH 1986/Ex. 1-3, p. 72). When exposed to 4200 ppm n-butyl acetate for six days at six hours per day, cats experienced slight irritation of the respiratory passage; at 3100 ppm, changes in blood cell morphology were recorded. At exposures of 1600 ppm, these cats exhibited slight irritation of the eyes and increased salivation (Flury and Wirth 1933, as cited in ACGIH 1986/ Ex. 1-3, p. 72). Air concentrations of 10,000 ppm n-butyl acetate proved fatal to rats after eight hours; four hours of exposure at the same level produced no deaths (Smyth 1956/Ex. 1-759). A paper by Sayers, Schrenk, and Patty (1936/Ex. 1-802) reported that guinea pigs demonstrated eye irritation effects at 3300 ppm, became unconscious after nine hours of exposure to 7000 ppm, and died after four hours of exposure to 14,000 ppm.

Human volunteers complained that throat irritation, which began at an exposure level of 200 ppm n-butyl acetate, worsened and became quite severe at 300 ppm (Nelson, Enge, Ross et al. 1943/Ex. 1-66). NIOSH was the only commenter to the record in response to OSHA's proposed STEL for n-butyl acetate.

OSHA finds that workers are at significant risk of experiencing the severe eye, skin, and respiratory irritation, in addition to narcotic effects, that are associated with short-term exposures to this substance at levels above the 8-hour limit. The Agency considers the irritant and narcotic effects resulting from exposure to n-butyl acetate to be material impairments of health and functional capacity. OSHA concludes that a STEL is necessary to reduce this risk, and the Agency is therefore revising its limit for n-butyl acetate to 150 ppm as an 8-hour TWA and 200 ppm as a 15-minute STEL.


n-BUTYL LACTATE
CAS: 138-22-7; Chemical Formula: C(7)H(14)O(3)
H.S. No. 1053


OSHA previously had no limit for n-butyl lactate but proposed a 5-ppm 8-hour TWA limit, based on the ACGIH recommendation. NIOSH (Ex. 8-47, Table N1) concurred with the proposed 5-ppm TWA limit, and this limit is established in the final rule. Butyl lactate is a colorless liquid ester of lactic acid.

In humans, prolonged exposures to n-butyl lactate at approximately 7 ppm, with brief peak excursions to 11 ppm, caused headache, irritation of the pharyngeal and laryngeal mucosa, and coughing in all workers, and occasional nausea, vomiting, and sleepiness in some (Zuidema and Pel 1969, as cited in ACGIH 1986/Ex. 1-3, p. 82). Headache, coughing, and irritation of the pharynx were sometimes related to n-butyl lactate concentrations of 4 ppm; however, no adverse effects were observed at a concentration of 1.4 ppm. Studies employing improved sampling and analytic methods have subsequently concluded that, although the odor of n-butyl lactate is discernible at the 7-ppm level, this concentration does not produce objectionable or injurious effects (Turner 1972/as cited in ACGIH 1986/Ex. 1-3, p. 82).

In the preamble discussion of the proposed limit for this substance, OSHA noted that some studies reported acute adverse effects associated with exposure levels below the proposed 5-ppm TWA limit. This was also pointed out by Dr. Grace Ziem, an independent physician (Ex. 46). Based on the study by Turner (1972, as cited in ACGIH 1986/Ex. 1-3, p. 82), which employed improved sampling and analytical techniques as compared to earlier studies, OSHA judges that promulgation of a 5-ppm 8-hour TWA limit will effectively protect workers from the significant risks of irritation, headache, and nausea caused by exposure to higher concentrations of n-butyl lactate. OSHA considers these adverse effects to represent material impairments of health. Therefore, OSHA is establishing a 5-ppm 8-hour TWA limit for n-butyl lactate.


n-BUTYL MERCAPTAN
CAS: 109-79-5; Chemical Formula: CH(3)CH(2)CH(2)CH(2)SH
H.S. No. 1054


n-Butyl mercaptan is a colorless, flammable liquid and has a strong, obnoxious, garlic-like odor. It is used as a solvent, a chemical intermediate, and an odorant for natural gas. OSHA's previous limit for n-butyl mercaptan was 10 ppm as an 8-hour TWA. OSHA proposed a lower limit of 0.5 ppm TWA, based on the ACGIH recommendation, and the final rule establishes this limit.

Humans exposed to concentrations of n-butyl mercaptan report that the "readily noticeable" odor level for this substance is between 0.1 and 1 ppm, although the odor threshold is significantly below this level (ranging from 0.001 to 0.0001 ppm). Gobbato and Terribile (1968/Ex. 1-178) have reported that symptoms of CNS toxicity occurred in humans exposed for one hour to concentrations of n-butyl mercaptan believed to lie in the range of 50 to 500 ppm. These same authors reported that mucosal irritation occurred in human volunteers exposed to 4 ppm of ethyl mercaptan, a closely related substance. Irritation did not occur at exposures to 0.4 ppm. The ACGIH established the TLV for n-butyl mercaptan at 0.5 ppm, to protect against the intolerable odor effects, mucosal irritation, and CNS toxicity that occur on exposure to higher concentrations of this substance.

The current PEL of 10 ppm is between 10 and 100 times higher than the concentration of n-butyl mercaptan that is readily detected by smell and is more than twice the concentration reported as causing mucosal irritation for a closely related substance. OSHA finds that workers are at risk of significant acute effects in the absence of a more stringent limit.

In its prehearing comments, NIOSH (Ex. 8-47, Table N7) pointed out that it has recommended a 0.5-ppm ceiling limit for n-butyl mercaptan, rather than a TWA limit, for this substance. No other comments were submitted to the record. In accordance with the criteria in its June 7, 1988 NPRM (53 FR 20977), OSHA is establishing the 0.5-ppm TWA limit for n-butyl mercaptan. The Agency concludes that this PEL will substantially reduce the risks of irritation, CNS toxicity, and intolerable odor effects, which together constitute material health impairments.


CAPROLACTAM (DUST)
CAS: 105-60-2; Chemical Formula: C(6)H(11)NO
H.S. No. 1064

OSHA had no previous permissible exposure limit for caprolactam dust;
however, a 1-mg/m(3) 8-hour TWA and a 3-mg/m(3) STEL were proposed, based on the recommended limits adopted by the ACGIH, and NIOSH (Ex. 8-47, Table N1) concurred with these limits. The final rule establishes these limits. Caprolactam is a white crystalline solid with an unpleasant odor.

In humans, caprolactam has been shown to be a convulsant, a dermal and respiratory irritant, and a dermal sensitizer; however, dosage levels in humans are ill-defined (Ferguson and Wheeler 1973/Ex. 1-1108; Tuma, Orson, Fossella, and Waidhofer 1981/Ex. 1-1071). In animals, exposure to caprolactam by several routes can cause convulsions, tremors, mydriasis, opisthotonus (Elison, Lien, Zinger et al. 1971/Ex. 1-1050; Lien, Lien, and Tong 1971/Ex. 1-1089) and salivation (Goldblatt, Farquharson, Bennett, and Askew 1954/Ex. 1-1044). Cardiovascular and respiratory effects have been reported in rabbits and cats, with an initial increase in blood pressure followed by a decrease in blood pressure and an increased respiratory rate (Goldblatt, Farquharson, Bennett, and Askew 1954/Ex. 1-1044). Weight loss and initial growth depression occurred in rats and mice (Morrison, Ross, and Ruth 1980/Ex. 1-1062).

One animal study observed that caprolactam's convulsant effects on rats, rabbits, and cats occur at injection doses above 100 mg/kg (Goldblatt, Farquharson, Bennett, and Askew 1954/Ex. 1-1044). Results of studies in guinea pigs were consistent with these findings (Hohensee 1951, as cited in ACGIH 1986/Ex. 1-3, p. 95). In a 90-day feeding study of dogs, Burdock, Kolwick, Alsakor, and Marshall (1984, as cited in ACGIH 1986/Ex. 1-3, p. 95) reported that dogs given dietary dose levels of 0.1, 0.5, or 1.0 percent caprolactam showed weight losses at both the 1.0-percent and 0.5-percent levels. Hematologic and ophthalmologic changes did not occur. In a two-year bioassay of rats and mice, caprolactam was not observed to be carcinogenic (NCI/NTP 1982, as cited in ACGIH 1986/Ex. 1-3, p. 95). A Polish study observed hematologic and systemic changes, increased mortality, kidney and liver damage, and growth inhibition in animals given daily doses of 50 or 100 mg/kg (Zwierzchowski, Kowalski, Szendzikowski, and Slusarczyk-Zalobna 1967, as cited in ACGIH 1986/Ex. 1-3, p. 96.1). The results of early studies of caprolactam's teratogenicity in rats and rabbits indicate that it is not teratogenic even at doses as high as 1000 mg/kg/day (Gad, Powers, Robinson et al. 1984, as cited in ACGIH 1986/Ex. 1-3, p. 96.1).

Studies of industrial exposures to caprolactam dust in Germany report severe irritation on inhalation of 10 percent caprolactam in dust (Hohensee 1951, as cited in ACGIH 1986/Ex. 1-3, p. 95). Workers experienced a bitter taste, nervousness, epistaxis, upper respiratory tract irritation, and dry and splitting skin on the lips and nose (Hohensee 1951, as cited in ACGIH 1986/Ex. 1-3, p. 95). Direct contact with the solid form of caprolactam produces primary skin irritation (Ferguson 1972, as cited in ACGIH 1986/Ex. 1-3, p. 96.1). Brief (1972, as cited in ACGIH 1986/Ex. 1-3, p. 96.1) also reports that the dust produces skin irritation.

OSHA received no comments, other than NIOSH's, on its proposed limits for caprolactam dust. Based on its review of the health evidence, OSHA concludes that, in the absence of any limit on employee exposure to caprolactam dust, workers are at significant risk of respiratory irritation, adverse nervous system effects, and possible cardiovascular effects; the Agency considers these effects to be material impairments of health. OSHA finds that promulgation of the 1-mg/m(3) TWA and 3-mg/m(3) STEL limits for caprolactam dust will substantially reduce this risk.


CAPROLACTAM (VAPOR)
CAS: 105-60-2; Chemical Formula: C(6)H(11)NO
H.S. No. 1065


OSHA had no previous permissible exposure limit for caprolactam as vapor. The Aency proposed a TWA of 5 ppm (20 mg/m(3)) for the vapor, supplemented by a STEL of 10 ppm (40 mg/m(3)), based on the limits adopted by the ACGIH. These limits are established in the final rule. Caprolactam is a white crystalline solid at room temperature; thus, high vapor levels occur only at elevated temperatures.

The health effects of exposure to caprolactam vapor are identical to those described for caprolactam dust, except that contact with the vapor is reported to be even more irritating (Hohensee 1951, as cited in ACGIH 1986/Ex. 1-3, p. 95). Workers exposed to the vapor at approximately 12 ppm complained of a bitter taste in the mouth, nervousness, epistaxis, upper respiratory tract congestion, and dry and splitting skin; other workers reported experiencing heartburn, flatulence, and a heavy feeling in the stomach (Hohensee 1951, as cited in ACGIH 1986/Ex. 1-3, p. 95).

In another report of industrial exposure to the vapor, Ferguson and Wheeler (1973/Ex. 1-1108) reported that workers routinely exposed to unspecified levels and occasionally to concentrations as high as 100 ppm for 18 years reported severe discomfort from burning nose, throat, and eyes. This irritation response was dose-related, with no workers reporting effects at 7 ppm or below, some experiencing transient upper respiratory tract irritation at levels above that, and others reporting eye irritation at concentrations of 25 ppm and above (Ferguson and Wheeler 1973/Ex. 1-1108). Ferguson (1972, as cited in ACGIH 1986/Ex. 1-3, p. 96.1) noted that a group of 143 workers, some of whom were exposed for as long as 17 years to vapor concentrations of 5 to 10 ppm, showed no evidence of adverse effects. At higher vapor exposures (13 to 130 ppm), all subjects experienced eye irritation (Ferguson 1972, as cited in ACGIH 1986/Ex. 1-3, p. 96.1). Human volunteers exposed at low relative humidities to concentrations of the vapor in the range of 10 to 100 ppm showed a dose-related response, but at higher relative humidities, no irritation was observed below a concentration of 14 ppm (Ferguson and Wheeler 1973/Ex. 1-1108).

NIOSH (Ex. 8-47, Table N2; Tr. p. 3-86) did not concur with the Agency's proposal to establish an 8-hour TWA exposure limit of 5 ppm (20 mg/m(3)) and a 10-ppm (40-mg/m(3)) STEL for caprolactam vapor. NIOSH (Ex. 8-47) noted that the 1986 ACGIH Documentation (Ex. 1-3) lists a TLV-TWA of 1 mg/m(3) for the combined vapor and aerosol of caprolactam and 0.22 ppm if the substance is present only as a vapor. The proposed change in the 1986 TLV was recommended to prevent early signs of irritation in some workers. NIOSH observed that "the proposed PEL does not appear to provide a sufficient margin of safety to caprolactam vapor," based on available human exposure responses. No other comments on this substance were submitted to the rulemaking record.

As explained in Section IV.D. of this preamble, which discusses the boundaries of today's rulemaking, the Agency confined its attention to the substances and exposure limits listed in the 1987-1988 edition of ACGIH's Threshold Limit Values and Biological Exposure Indices (ACGIH 1987/Ex. 1-16). Caprolactam vapor is listed on ACGIH's Notice of Intended Changes but new limits have neither been reviewed nor adopted by that organization to date. Under these circumstances, OSHA believes it prudent to promulgate the limits as proposed for caprolactam vapor. The Agency is establishing an 8-hour TWA limit of 5 ppm (20 mg/m(3)) and a 15-minute STEL of 10 ppm (40 mg/m(3)) for this previously unregulated substance. OSHA concludes that these PELs will substantially reduce the significant risk of eye, upper respiratory tract, and skin irritation that are permitted in the absence of any exposure limit for caprolactam vapor. OSHA considers the irritant effects resulting from exposure to caprolactam vapor to be material impairments of health. The Agency will continue to monitor the health evidence for this substance to determine whether further action is warranted.


CESIUM HYDROXIDE
CAS: 21351-79-1; Chemical Formula: C(s)OH
H.S. No. 1077


OSHA formerly had no limit for cesium hydroxide; however, based on the ACGIH recommendation, OSHA proposed the establishment of a 2-mg/m(3) limit as an 8-hour TWA. NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposed limit for this substance, and the Agency is establishing this limit for cesium hydroxide in the final rule. Cesium hydroxide is a colorless or yellowish fused crystalline mass; it is the strongest base known and is highly soluble in both water and alcohol.

Animal studies indicate that cesium hydroxide has an acute oral toxicity of about one-third that of potassium hydroxide, which causes lesions of the nasal septum and irritation of the eyes and respiratory tract (Karpov 1971/Ex. 1-1115). The oral LD(50) for cesium hydroxide in rats is 1016 mg/kg. Although a concentration of 5 percent cesium hydroxide did not produce skin irritation, contact with this concentration did result in severe eye irritation. Cesium hydroxide does not cause skin sensitization (Johnson, Lewis, and Perone 1972, as cited in ACGIH 1986/Ex. 1-3, p. 113).

No rulemaking participants other than NIOSH commented on the proposed 2-mg/m(3) TWA limit for cesium hydroxide.

In the final rule, the Agency is promulgating an 8-hour TWA PEL of 2 mg/m(3) for cesium hydroxide and concludes that this limit will protect workers from the significant risk of severe eye irritation associated with exposure to this substance at levels above the new PEL. The Agency considers the severe eye irritation caused by exposure to cesium hydroxide a material impairment of health and functional capacity.


CHLORINE
CAS: 7782-50-5; Chemical Formula: Cl(2)
H.S. No. 1079


The previous OSHA limit for chlorine was 1 ppm as a ceiling limit. OSHA proposed to revise this limit to 0.5 ppm measured over 15 minutes, which was the limit recommended by NIOSH (1976b/Ex. 1-276) in its criteria document; NIOSH (Ex. 8-47, Table N1) concurred with the proposed limit. However, the final rule establishes a PEL of 0.5 ppm TWA with a 15-minute short-term exposure limit of 1 ppm for chlorine. Chlorine is a greenish-yellow, noncombustible gas at atmospheric pressure; it has a suffocating odor. At -35 C, it condenses to an amber liquid.

Exposure to chlorine at concentrations around 5 ppm has been associated with respiratory symptoms, erosion of the teeth, and inflammation of the mucous membranes (Flury and Zernik 1931c/Ex. 1-1199; Patty 1963c/Ex. 1-854). Ferris, Burgess, and Worcester (1967/Ex. 1-316) reported slight effects on the respiratory system in workers exposed to chlorine concentrations ranging from negligible to 7 ppm. Rupp and Henschler (1967/Ex. 1-1122) reported burning of the eyes among human subjects exposed to 0.5 ppm; an unspecified number of these subjects reported painful eyes after 15 minutes' exposure to this level. In a separate test, subjects reported respiratory irritation on exposure to 0.5 ppm, and a concentration of 1 ppm was described as being uncomfortable.

At the time of OSHA's proposal, the limits adopted by the ACGIH were a 1-ppm TLV-TWA and a 3-ppm TLV-STEL; these limits were based on the reports described above and were established to "minimize chronic changes in the lungs, accelerated aging, and erosion of the teeth" (ACGIH 1986/Ex. 1-3, p. 117). NIOSH (1976b/Ex. 1-276) reviewed these studies, as did others (Matt 1889, as cited in Flury and Zernick 1931c/Ex. 1-1199; Beck 1959, as cited in NIOSH 1976b/Ex. 1-276) that reported ocular and respiratory irritation associated with exposure to chlorine levels of around 1 ppm for 30 minutes or less. NIOSH (1976b/Ex. 1-276) recommended a 15-minute 0.5-ppm limit to prevent possible eye and respiratory tract irritation.

The United Paperworkers International Union (UPIU) (Ex. 8-37) cited the NIOSH Criteria Document (Ex. 1-276) and ACGIH Documentation (Ex. 1-3) as evidence that exposure to 0.5 ppm chlorine causes respiratory irritation. The UPIU also submitted several studies indicating that decrements in pulmonary function may persist for several days or weeks following acute exposure to concentrations of chlorine requiring medical treatment. In addition, the UPIU cited a number of studies indicating that pulp mill workers and chlorine production plant workers experience declines in pulmonary function as a result of chronic exposure to low levels of chlorine (Ex. 8-37); however, interpretation of many of these studies is complicated by a lack of exposure data or the presence of confounding exposure to other respiratory toxins, such as sulfur dioxide. The UPIU (Ex. 8-37) supported the promulgation of a 0.2 ppm limit for chlorine.

In 1986, the ACGIH proposed revising the TLVs for chlorine to 0.5 ppm as an 8-hour TWA and 1 ppm as a 15-minute STEL. This proposal was based on a review of two recent studies. One study, a 1981 doctoral dissertation by Anglen (Ex. 108A), was sponsored by the Chlorine Institute and was conducted on 29 human subjects. This study reported statistically significant changes in pulmonary function and subjective irritation resulting from exposure to 1 ppm chlorine for eight hours. No significant ocular effects were noted at this exposure level and duration. Exposure to 0.5 ppm for eight hours was not associated with significant declines in pulmonary function, and subjective irritation was also less severe at this level than at 1 ppm (Anglen 1981, Ex. 108A). During the eight-hour exposure to 1 ppm, sensory responses of itching or burning of the throat were reported to be "just perceptible" or "distinctly perceptible." A short-term (30-minute) exposure to 2 ppm produced no increase in subjective irritation compared with controls.

These findings were confirmed in a study of eight healthy volunteers exposed to 0.5 or 1 ppm chlorine concentrations (Rotman, Fliegelman, Moore et al. 1983/Ex. 108B). Significant declines in pulmonary function were associated with exposure to 1 ppm but not to 0.5 ppm.

The Chlorine Institute (Ex. 3-828) described a recent animal study conducted by the Chemical Industry Institute of Toxicology (CIIT). In this study, groups of 20 rats were exposed to 1, 3, or 9 ppm chlorine for six hours/day, five days/week, for six weeks. Exposure to the two highest levels resulted in significant decreases in body weight. Inflammation of the upper and/or lower respiratory tract was observed in the 9-ppm group and, to a lesser extent, in the 3- and 1-ppm groups. Pathological and clinical changes were not observed in the 1-ppm group, but were seen in the 3- and 9-ppm groups.

Several rulemaking participants urged OSHA to adopt the more recent ACGIH limits of 0.5 ppm TWA and 1 ppm STEL (Exs. 3-677, 3-741, 3-828, and 3-1150; Tr. pp. 10-165 to 10-170; Tr. pp. 10-178 to 10-180). For example, the Chlorine Institute commented as follows:

The imposition of an instantaneous ceiling PEL is inappropriate. The Chlorine Institute's University of Michigan and CIIT studies demonstrate conclusively that sensory effects and adverse pulmonary function effects are directly related to prolonged chlorine exposures and are correctly controlled by a PEL expressed as a Time Weighted Average (TWA).... The Chlorine Institute supports...[the ACGIH limits] as the correct PEL for adoption by OSHA, and we submit that the evidence is conclusive that such a PEL is totally protective of worker health in chlorine-producing and chlorine-using industries (Ex. 3-828, p. 3).

In its posthearing comment, NIOSH (Ex. 150) reaffirmed its recommended TWA of 0.5 ppm as a 15-minute limit, based on the findings of Rupp and Henschler (1967/Ex. 1-1122):

The studies of Anglen (1981) and Rotman (1983), as summarized by the ACGIH, if considered alone, would support the ACGIH TWA TLV of 0.5 ppm with a STEL of 1 ppm. However, in the studies of Rupp and Henschler (1967), exposure to chlorine at concentrations of approximately 0.5 ppm resulted in conjunctival pain in several subjects after 15 minutes; in their second study, subjects reported respiratory irritation after exposure to 0.5 ppm for 25 minutes....

The Rupp and Henschler study (1967), although it has been criticized for lack of a control group (Ex. 3-685) confirms the Anglen (1981), Rotman et al. (1983), and CIIT studies (Ex. 3-828) that there is a significant risk of irritation and a risk of respiratory inflammation at the present PEL of 1 ppm ceiling. Reduction of the current PEL to 0.5 ppm ceiling will reduce the risk of respiratory irritation and pulmonary function changes, and minimize the subjective complaints of irritation (Ex. 150, Comments on Chlorine).

The Dow Chemical Company submitted a critical review of the NIOSH (1976b/Ex. 1-276) criteria document on chlorine and the Rupp and Henschler (1967/Ex. 1-1122) study that was prepared in 1979 by Dr. Ralph G. Smith, who directed the University of Michigan (Anglen 1981) study (Ex. 3-741, Appendix B; Tr. pp. 10-165 to 10-170). In his review, Dr. Smith criticized the Rupp and Henschler (1967/Ex. 1-1122) study because the design of the exposure facility led to uncertainties in determining actual exposure levels present in the test room. He also remarked that the chlorine was passed through "liquid paraffin," which may have produced chlorinated hydrocarbons. In addition, Dr. Smith felt that the air compressor used may have caused contamination of the air in the test room by carbon monoxide and other impurities. Dr. Smith believed these observations were important "because one of the effects allegedly resulting from short exposures to low levels of chlorine was headaches, a symptom which we have never had reported to us by a subject in the University of Michigan (Anglen 1981) exposures" (Ex. 3-741, Appendix B, pp. 9-10).

After reviewing the evidence and testimony presented in the record on the effects of exposure to chlorine gas, OSHA concludes that there is clearly a significant risk of pulmonary function impairment and sensory irritation at the current 1-ppm ceiling PEL; such effects have been demonstrated by the Anglen (1981/Ex. 108A) and Rotman, Fliegelman, Moore et al. (1983/Ex. 108B) studies in human subjects exposed to 1 ppm for 8 hours, an exposure level and duration that would be permitted by the former PEL. In addition, pulmonary inflammation has been observed in rats exposed daily for six weeks to 1 ppm chlorine. Therefore, OSHA finds that it is necessary to revise its current limit for chlorine.

The human studies by Anglen (1981/Ex. 108A) and by Rotman, Fliegelman, Moore et al. (1983/Ex. 108B) also indicate that exposure to 0.5 ppm chlorine for as long as 8 hours is not associated with impairment of pulmonary function or significant sensory irritation; these findings are in contrast to the earlier German reports upon which the NIOSH REL of 0.5 ppm (15 minutes) is based. However, the German studies, in particular those of Rupp and Henschler (1967/Ex. 1-1122), appear to have had methodological shortcomings that call into question the finding that exposure to 0.5 ppm chlorine is associated with significant acute effects. Therefore, OSHA judges, based on the more recent University of Michigan study, that an exposure limit of 0.5 ppm TWA with a 1-ppm 15-minute STEL will reduce the risk of irritation and pulmonary function decline in workers, and is today revising its limit for chlorine to these values. OSHA considers the effects of respiratory irritation and the declines in pulmonary function associated with chlorine exposure to be material impairments of health.


CHLOROACETYL CHLORIDE
CAS: 79-04-9; Chemical Formula: ClCH(2)COCl
H.S. No. 1083


No previous exposure limit existed for chloroacetyl chloride. OSHA proposed a 0.05-ppm 8-hour TWA limit for this substance, based on the ACGIH recommendation, and NIOSH (Ex. 8-47, Table N1) concurred with this proposal. This limit is established in the final rule. Chloroacetyl chloride is a colorless liquid with a pungent odor.

The oral LD(50) in rats fed this substance is between 0.12 and 0.25 g/kg. Chloroacetyl chloride is corrosive to the skin and eyes, and skin absorption of this substance can be lethal. Inhalation of 4 ppm for five to ten minutes caused respiratory problems in rats; however, no effect was observed in these animals when they inhaled 2.5 ppm for a period of seven hours (Dow Chemical Company 1977a, as cited in ACGIH 1986/Ex. 1-3, p. 122). Thirty-day inhalation studies with rats, mice, and hamsters showed eye and respiratory irritation at 2.5 ppm and no effect at 0.5 ppm (Dow Chemical Company 1977a, as cited in ACGIH 1986/Ex. 1-3, p. 122).

Reports of the acute effects associated with exposure to chloracetyl chloride in humans include mild to moderate skin burns and erythema, eye burns and tearing, cough, dyspnea, and cyanosis, as well as mild gastrointestinal effects. Eye and respiratory irritation occurred in an industrial setting characterized by an exposure level of 0.009 to 0.017 ppm, with excursions as high as 0.140 ppm (Dow Chemical Company 1977a, as cited in ACGIH 1986/Ex. 1-3, p. 122). An accidental drenching with a mixture containing chloroacetyl chloride resulted in extensive first- and second-degree burns, pulmonary edema, and three episodes of cardiac arrest, followed by coma and anoxia-induced brain damage (Pagnotto 1978, as cited in ACGIH 1986/Ex. 1-3, p. 122). Other ingredients of the mixture involved in the accident included xylidine, benzene, and sodium carbonate. Rescuers of this victim experienced hand blisters, chest tightness, and nausea for two days. OSHA received no comments other than NIOSH's on the proposed 0.05-ppm TWA limit for chloroacetyl chloride.

The Agency concludes that an 8-hour TWA limit of 0.05 ppm for chloracetyl chloride is necessary to protect employees from the significant risk of eye, skin, and respiratory irritation; gastrointestinal effects; and severe systemic effects, including life-threatening coma, cardiac arrest, and pulmonary edema, to which they could otherwise be exposed in the absence of any OSHA limit; the Agency considers each of these exposurerelated adverse effects to be material impairments of health and functional capacity. Accordingly, OSHA is establishing an occupational limit of 0.05 ppm as an 8-hour TWA for chloroacetyl chloride.


o-CHLOROBENZYLIDENE MALONONITRILE
CAS: 2698-41-1; Chemical Formula: ClC(6)H(4)CH = C(CN)(2)
H.S. No. 1084


OSHA's previous PEL for o-chlorobenzylidene malononitrile (OCBM) was 0.05 ppm as an 8-hour TWA. The Agency has proposed revising this limit to 0.05 ppm as a ceiling, with a skin notation, based on the ACGIH (1986/Ex. 1-3) recommendation. This revision is incorporated in the final rule. NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposed limit for this substance. o-Chlorobenzylidene malononitrile is a white crystalline solid with a pepper-like odor.

OCBM has extremely irritating properties. It causes intense eye and skin irritation, coughing, difficulty in breathing, chest tightness, running nose, dizziness, nausea, and vomiting. These effects are evident on exposure to concentrations between 12 and 20 mg/m(3) (1.5 to 2.5 ppm), and they become incapacitating within 20 seconds of exposure; the effects persist for approximately 5 to 10 minutes after the victim has been removed to fresh air (Military Chemistry and Chemical Agents 1963, as cited in ACGIH 1986/Ex. 1-3, p. 124).

OCBM is only slightly toxic to laboratory animals when they are exposed intravenously, subcutaneously, or through inhalation (Punte, Weimer, Ballard, and Wilding 1962/ Ex. 1-354). In animals, it has been demonstrated that OCBM is metabolized by the body into cyanide (Frankenberg and Sorbo 1973/Ex. 1-480). Short-term exposures to high levels of OCBM did not cause carcinogenic, teratogenic, or embryolethal effects in animals (McNamara et al. 1973, as cited in ACGIH 1986/Ex. 1-3, p. 124).

Three of four human volunteers exposed to a 1.5-mg/m(3) (0.19-ppm) concentration of OCBM aerosol dispersed from a 10-percent solution of methylene chloride for 90 minutes developed headaches, and one showed mild eye and nose irritation. Headache persisted for 24 hours in two subjects. At 4 to 5 mg/m(3) (0.5 to 0.6 ppm), subjects' problem-solving abilities were affected and they showed eye irritation, conjunctivitis, lacrimation, and skin burning (Punte, Owens, and Gutentag 1963/Ex. 1-353). Other researchers observed no persistent clinical abnormalities in seven subjects exposed to OCBM at concentrations ranging from 1 to 13 mg/m(3) (0.13 to 1.6 ppm) over a 15-day period; however, none of these subjects developed a tolerance for the compound. Severe skin sensitization has also been reported in workers handling OCBM (Shmunes and Taylor 1973/Ex. 1-370). No comments, except those submitted by NIOSH, were received on OSHA's proposed revision of the limit for OCBM.

In the final rule, OSHA is establishing a PEL of 0.05 ppm as a ceiling, with a skin notation, to reduce the risks associated with elevated short-term exposures to OCBM. The Agency concludes that workers are at significant risk of experiencing the severe eye and upper respiratory tract irritation, skin sensitization, dyspnea, nausea, lacrimation, vomiting, and performance decrements that are associated with brief exposures to this substance at the former 8-hour TWA PEL. Furthermore, OSHA considers the effects related to exposure to OCBM to represent material impairments of health.


CYANOGEN
CAS: 460-19-5; Chemical Formula: (CN)(2)
H.S. No. 1105


OSHA previously had no limit for cyanogen. The Agency proposed a limit of 10 ppm as an 8-hour TWA for this colorless gas, which has a pungent, almond-like odor. NIOSH (Ex. 8-47, Table N1) concurred with this proposal, and the final rule establishes the 10 ppm TWA limit, which is the same as that recommended by the ACGIH (1986/Ex. 1-3).

The acute toxicity for cyanogen in various animal species is high (Flury and Zernik 1931d, as cited in ACGIH 1986/Ex. 1-3, p. 154). One hundred ppm was fatal to cats in two to three hours, and 400 ppm was fatal to rabbits in less than two hours. However, rabbits exposed to 100 ppm for four hours showed practically no effects. Cats exposed to 50 ppm were severely affected but recovered (Flury and Zernik 1931d, as cited in ACGIH 1986/Ex. 1-3, p. 154). Investigations in the rat suggest that cyanogen is approximately 10 times less acutely toxic than is hydrogen cyanide (McNerney and Schrenk 1960/Ex. 1-426).

Human tests showed that subjects experienced almost immediate eye and nasal irritation at exposures of 16 ppm (McNerney and Schrenk 1960/Ex. 1-426).

The New Jersey Department of Public Health (Exs. 144, 144A) urged OSHA to set a limit for cyanogen on the basis of EPA's IRIS data. The use of such an approach is discussed in Section VI.A of the preamble.

In the final rule, OSHA is establishing an 8-hour TWA limit for cyanogen. The Agency concludes that this limit is necessary to protect against the significant risk of irritation and systemic effects associated with exposure at the levels permitted in the absence of any OSHA limit. OSHA considers the irritant and systemic effects caused by exposure to cyanogen to be material impairments of health.


CYANOGEN CHLORIDE
CAS: 506-77-4; Chemical Formula: ClCN
H.S. No. 1106


OSHA previously had no limit for cyanogen chloride; however, a ceiling limit of 0.3 ppm was proposed for this colorless liquid or gas, which has a pungent odor. NIOSH (Ex. 8-47, Table N1) concurred with this proposal. In the final rule, OSHA is establishing a 0.3-ppm ceiling limit, which is the same as that recommended by the ACGIH.

The chronic effects of exposure to cyanogen chloride, which include hoarseness, conjunctivitis, and edema of the eyelid, have long been recognized (Reed 1920/Ex. 1-355). Flury and Zernik (1931d, as cited in ACGIH 1986/Ex. 1-3, p. 155) observed the effects of exposure to cyanogen chloride in five animal species. In mice, a concentration of approximately 500 ppm was fatal within three minutes; in cats, 120 ppm was fatal in 3.5 minutes; 48 ppm was fatal to dogs in six hours; in goats, a 1000-ppm exposure for three minutes caused death after 70 hours; and 1200 ppm was fatal to the rabbit. Several other studies have demonstrated that animals exposed to cyanogen chloride exhibit pulmonary edema and interference with cellular metabolism (Jandorf and Bodansky 1946/Ex. 1-334; Aldridge and Evans 1946/Ex. 1-708).

Human data indicate that 1 ppm is the lowest irritant concentration that can be tolerated for a 10-minute exposure; 2 ppm was intolerable for this time period, and 48 ppm was fatal in 30 minutes (Prentiss 1937/Ex. 1-1164). The Michigan Department of Health (1977, as cited by ACGIH 1986/Ex. 1-3, p. 155) reported that a concentration of about 0.7 ppm caused severe eye and nasal irritation, forcing workers to evacuate the area. NIOSH submitted the only comment received by OSHA on its proposed ceiling limit of 0.3 ppm for cyanogen chloride.

OSHA is establishing this 0.3-ppm ceiling limit for cyanogen chloride in the final rule. The Agency concludes that a ceiling limit is necessary to protect workers from the significant risks of severe irritation, metabolic effects, and pulmonary edema associated with short-term exposures to this substance at levels above the former PEL. The Agency considers the irritant, metabolic, and respiratory effects associated with exposure to cyanogen chloride to be material impairments of health and functional capacity.

DIBUTYL PHOSPHATE CAS: 107-66-4; Chemical Formula: (n-C(4)H(9)O)(2)(OH)PO H.S. No. 1119

OSHA previously had an 8-hour TWA PEL of 1 ppm for dibutyl phosphate. The Agency proposed to supplement this limit with a 2-ppm STEL, based on the ACGIH recommendation. NIOSH (Ex. 8-47, Table N1) concurred with this proposal, and the final rule establishes a 1-ppm TWA limit with a 2-ppm STEL for this substance.

There are no published reports of toxic reactions caused by exposure to dibutyl phosphate. However, in a personal communication to the ACGIH, Mastromatteo reported that workers exposed to relatively low levels of dibutyl phosphate developed respiratory tract irritation and headache (Mastromatteo 1964a, as cited in ACGIH 1986/Ex. 1-3, p. 236). No additional data or health effects comment was introduced into the record during the rulemaking proceeding.

OSHA concludes that both a TWA and a STEL are necessary to protect workers from the risk of respiratory tract irritation and headaches reported to occur at low levels of exposure. OSHA judges it likely that, in the absence of a STEL, short-term exposure permitted by the 1-ppm TWA limit alone may be sufficiently high to present a significant risk of respiratory tract irritation and headache to workers; the Agency considers these exposure-related effects to be material impairments of health. Therefore, the Agency is supplementing its 1-ppm 8-hour TWA limit with a 2-ppm 15-minute STEL in the final rule.


1,3-DICHLORO-5,5-DIMETHYL HYDANTOIN
CAS: 118-52-5; Chemical Formula: C(5)H(6)Cl(2)N(2)O(2)
H.S. No. 1122


OSHA previously had a limit of 0.2 mg/m(3) TWA for 1,3-dichloro-5,5-dimethyl hydantoin (DCDMH). Based on the ACGIH (1986/Ex. 1-3) recommendation, the Agency proposed a TWA limit of 0.2 mg/m(3) and a STEL of 0.4 mg/m(3) for this white powder, which has a mild odor similar to that of chlorine. NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposed limits for this substance, and they are established in the final rule.

1,3-Dichloro-5,5-dimethyl hydantoin produces systemic toxicity in laboratory animals. The acute oral LD(50) in rats of both sexes is 542 + 84 mg/kg when DCDMH is administered as a 10-percent aqueous suspension. Rats dying within 48 hours of administration showed gastrointestinal hemorrhage at necropsy. The animals tolerated aqueous solutions of DCDMH maintained at 20 ppm available chlorine (Industrial Bio-Test Laboratories 1961 and 1962, as cited in ACGIH 1986/Ex. 1-3, p. 183).

Limited human exposure data have been provided by Baier, who reported that individuals experienced extreme respiratory irritation at an average level of 1.97 mg/m(3), but that some experienced this degree of irritation even at 0.7 mg/m(3) (Baier 1964, as cited in ACGIH 1986/Ex. 1-3, p. 183). Other than the NIOSH submission, OSHA received no comments on its proposal to revise the limit for DCDMH.

The 0.2-mg/m(3) TWA and 0.4-mg/m(3) STEL limits that were proposed are based on evidence of systemic toxicity in laboratory animals and respiratory irritation at low exposure levels in human subjects. The Agency concludes that both a TWA and a STEL are required to protect exposed workers from the risk of respiratory irritation that has been shown to occur at levels only slightly above the level specified by the 8-hour TWA limit. OSHA considers the respiratory irritant effects associated with exposure to DCDMH to represent material impairment of health and functional capacity. OSHA also concludes that the combined TWA-STEL limits will reduce this risk substantially and is therefore establishing a 0.2-mg/m(3) TWA and a 0.4-mg/m(3) STEL for DCDMH.


DICHLOROETHYL ETHER
CAS: 111-44-4; Chemical Formula: (CH(2)ClCH(2))(2)O
H.S. No. 1127


OSHA previously had a 15-ppm ceiling limit, with a skin notation, for dichloroethyl ether. The Agency proposed to revise its limit for dichloroethyl ether to 5 ppm as an 8-hour TWA, with a 10-ppm STEL, and to retain the skin notation. NIOSH (Ex. 8-47, Table N6A; Tr. pp. 3-96 to 3-97) concurred with the proposed limits but indicated that a carcinogen designation should be added to the PEL. The final rule establishes the proposed limits, which are consistent with the ACGIH recommendation. Dichloroethyl ether is a colorless, flammable liquid with a nauseating odor.

The primary health hazards associated with exposure to this substance are irritation of the eyes and respiratory system and pulmonary damage. Schrenk, Patty, and Yant (1933/Ex. 1-665) reported that guinea pigs exposed to the vapor of dichloroethyl ether at 500 ppm experienced immediate and severe eye and nose irritation, respiratory disturbances after 1.5 to 3 hours, and death after five to eight hours. Lung, kidney, liver, and brain damage were also observed in these animals; exposure to a reduced level of 105 ppm caused eventual death after 10 hours of continuous exposure. A one-hour exposure to 105 ppm caused irritation only (Carpenter, Smyth, and Pozzani 1949/Ex. 1-722). At 35 ppm, for an unspecified duration, irritation but no other adverse effects were observed (Schrenk, Patty, and Yant 1933/Ex. 1-665). Rats responded similarly, with four-hour exposures to 250 ppm proving lethal (Carpenter, Smyth, and Pozzani 1949/Ex. 1-722).

Repeated exposures to 69 ppm (seven hours/day, five days/week for 130 days) caused no serious injury in rats or guinea pigs; only mild stress-related effects were noted (Kosyan 1967/Ex. 1-914). However, other studies of guinea pigs have shown mild primary irritative effects on the skin, and fatalities occurred when 300 mg/kg was applied dermally as a pure liquid for 24 hours (Smyth and Carpenter 1948/Ex. 1-375). Direct contact of dichloroethyl ether with the eye causes moderate pain, conjunctival irritation, and transient corneal injury (Carpenter and Smyth 1946/Ex. 1-859). A sufficient amount of dichloroethyl ether can be absorbed through the skin to be lethal: Sax and Lewis (Dangerous Properties of Industrial Materials, 7th ed., 1989) report the dermal LD(50) in rabbits as 720 mg/kg. Mice have been reported to develop hepatomas after prolonged oral administration (80 weeks) of dichloroethyl ether at 300 mg/kg (Innes, Ulland, Valerio et al. 1969/Ex. 1-270).

Humans exposed briefly to dichloroethyl ether at concentrations above 550 ppm experienced intolerable eye and nasal irritation, with coughing, nausea, and retching. Concentrations between 100 and 260 ppm were irritating but tolerable; however, the odor of dichloroethyl ether was still nauseating at 35 ppm (Schrenk, Patty, and Yant 1933/ Ex. 1-665). Eye irritation has been reported from industrial exposure to a concentration of dichloroethyl ether of 2.5 ppm (Bell and Jones 1958/Ex. 1-714). A single fatality, presumably from inhalation of the vapor, has been reported but not documented (Elkins 1959c, as cited in ACGIH 1986/Ex. 1-3, p. 186). NIOSH submitted the only comments on OSHA's proposed revision of the PEL for dichloroethyl ether.

In the final rule, OSHA is establishing a 5 ppm TWA and 10 ppm STEL for this substance. The Agency concludes that a 5-ppm TWA and a 10-ppm STEL will protect workers against the significant risk of irritation, lung injury, and nausea associated with occupational exposure to elevated levels of dichloroethyl ether, and these limits are established in the final rule. OSHA considers the eye and nasal irritation, lung injury, and other symptoms associated with exposure to dichloroethyl ether to be material impairments of health and functional capacity. The skin notation is retained because dichloroethyl ether can cause systemic toxicity if percutaneously absorbed.


2,2-DICHLOROPROPIONIC ACID
CAS: 75-99-0; Chemical Formula: CH(3)CCl(2)COOH
H.S. No. 1130


OSHA previously had no limit for 2,2-dichloropropionic acid; however, the Agency proposed a 1-ppm 8-hour TWA limit for this liquid, based on the ACGIH (1986/Ex. 1-3) recommendation. NIOSH (Ex. 8-47, Table N1) concurred with the proposed 1-ppm TWA limit, and the final rule establishes it.

In a communication to the ACGIH, the Dow Chemical Company (1977b, as cited in ACGIH 1986/Ex. 1-3, p. 190) reported that 2,2-dichloropropionic acid is corrosive to the skin and can cause permanent injury to the eye. The oral LD(50) in rats is between 0.7 and 1 g/kg. Seven-hour exposures to a saturated atmosphere of the acid vapor caused no ill effects in rats, and a 120-day study of dietary exposure in rats showed a no-effect level of 15 mg/kg/day (Dow Chemical Company 1977b, as cited in ACGIH 1986/Ex. 1-3, p. 190). Dr. Grace Ziem, an independent occupational physician (Ex. 46), commented that Dow's material safety data sheet on 2,2-dichloropropionic acid reports that the liver and kidneys are target organs in rats fed higher dietary levels.

Acute human exposures have been reported to cause mild to moderate skin, eye, respiratory, and gastrointestinal irritation. Minimal respiratory irritation was observed in workers exposed at concentrations of between 2 and 7 ppm (ACGIH 1986/Ex. 1-3, p. 190).

The Agency concludes that a 1 ppm TWA limit for 2,2-dichloropropionic acid will protect workers from the significant risk of eye, respiratory, and gastrointestinal irritation, and possible liver or kidney injury, at exposure levels permitted in the absence of any OSHA limit. The Agency considers the irritant and adverse organ effects associated with exposure to this substance to be material impairments of health and functional capacity. Therefore, OSHA is establishing a 1-ppm 8-hour TWA limit for 2,2-dichloropropionic acid.


DIETHYLAMINE
CAS: 109-89-7; CHEMICAL FORMULA: (C(2)H(5))(2)NH
H.S. No. 1137


OSHA's previous limit for diethylamine was 25 ppm as an 8-hour TWA. The Agency proposed to lower this limit to an 8-hour TWA of 10 ppm and to add a 15-minute STEL of 25 ppm, based on the ACGIH (1986/Ex. 1-3) recommendation. NIOSH (Ex. 8-47, Table N1) concurred with these proposed limits, which are established in the final rule. Diethylamine is a colorless liquid with an ammonia-like odor.

Diethylamine is a strong irritant of the eyes, skin, and mucous membranes, and chronic sublethal exposures cause tracheitis, bronchitis, pneumonitis, and pulmonary edema (ACGIH 1986/Ex. 1-3, p. 197). In rabbits, the dermal LD(50) is 0.82 ml/kg, and instillation of solutions of 1 percent or greater into the eyes of rabbits caused corneal opacity (Sutton 1963/Ex. 1-1101). Direct contact of the skin with diethylamine causes necrosis (ACGIH 1986/Ex. 1-3, p. 197). Rabbits exposed seven hours/day, five days/week for six weeks to 50 or 100 ppm diethylamine survived; those exposed to 50 ppm showed marked lung and corneal irritation, and, occasionally, degeneration of the heart muscle (Brieger and Hodes 1951/Ex. 1-408). In the animals exposed to 100 ppm, these changes were more severe, and the parenchymatous degeneration of the heart muscle was marked (Brieger and Hodes 1951/Ex. 1-408).

OSHA finds that its previous limit of 25 ppm as an 8-hour TWA is only one-half the level found to cause marked lung and corneal irritation in animals exposed for six weeks. The Agency concludes that the 25-ppm limit is not sufficient to protect workers from the significant risk of skin burns, corneal injury, pulmonary irritation, and skin, eye, and upper respiratory tract irritation potentially associated with more prolonged exposures to this substance. OSHA considers the exposure-related effects of diethylamine on the eyes, skin, and respiratory tract to be material impairments of health. To afford workers greater protection from these adverse effects, OSHA is revising its limit for diethylamine to 10 ppm as an 8-hour TWA and 25 ppm as a 15-minute STEL; these limits are established in the final rule.


DIISOBUTYL KETONE
CAS: 108-83-8; Chemical Formula: [(CH(3))(2)CHCH(2)](2)CO
H.S. No. 1140


OSHA previously had an 8-hour limit of 50 ppm TWA for diisobutyl ketone. The Agency proposed to reduce this limit to 25 ppm TWA, based on both the ACGIH and NIOSH recommendations. NIOSH (Ex. 8-47, Table N1) concurred with this proposal, and the final rule revises OSHA's limit for diisobutyl ketone to 25 ppm as an 8-hour time-weighted average.

The primary health effects associated with exposure to diisobutyl ketone are eye, nose, and throat irritation, although experimental animals have shown some systemic effects. Diisobutyl ketone has a uniformly low acute toxicity by all routes of exposure. Rats and guinea pigs survived single exposures of from 7.5 to 16 hours to essentially saturated vapor (McOmie and Anderson 1949/Ex. 1-918). Smyth, Carpenter, and Weil (1949/Ex. 1-528) reported that five of six rats died after exposure to 2000 ppm for eight hours; these investigators also reported a percutaneous LD(50) for rabbits of greater than 20 ml/kg. Direct application of diisobutyl ketone to rabbit skin was only mildly irritating, and no eye irritation was reported after instillation of this substance into the rabbit eye. The oral toxicity for the rat was reported as 5.8 g/kg (Smyth, Carpenter, and Weil 1949/ Ex. 1-528). Carpenter and Smyth (1946/Ex. 1-859) reported a no-effect level for diisobutyl ketone of 125 ppm in rats and guinea pigs given 30 seven-hour exposures. At 250 ppm, the liver and kidney weights of female rats increased, and the liver weights of male guinea pigs decreased; at levels of 530 and 920 ppm, rats showed increased liver and kidney weights; and at 1650 ppm, increased mortality was noted (Carpenter and Smyth 1946/Ex. 1-859).

Silverman, Schulte, and First (1946/Ex. 1-142) reported eye irritation and complaints of objectionable odor in volunteer human exposures to concentrations above 25 ppm. No worker illnesses have been linked to diisobutyl ketone exposure (ACGIH 1986/Ex. 1-3, p. 203).

NIOSH (Ex. 150, Comments on Diisobutyl Ketone) concurred with OSHA's proposal to reduce the limit for diisobutyl ketone and reported that there are no new toxicological data beyond those described above; no other comments on this substance were received. The Agency concludes that the previous 50-ppm TWA limit is inadequate to protect workers against the significant risk of irritation associated with workplace exposures to diisobutyl ketone levels greater than 25 ppm. The Agency has determined that the irritation associated with exposure to diiso-butyl ketone constitutes a material impairment of health and functional capacity. Therefore, OSHA is revising its limit for diisobutyl ketone to 25 ppm as an 8-hour TWA.


EPICHLOROHYDRIN
CAS: 106-89-8; Chemical Formula: C(3)H(5)C10
H.S. No. 1158


OSHA previously had a limit of 5 ppm TWA, with a skin notation, for epichlorohydrin. OSHA proposed to reduce this limit to 2 ppm TWA, also with a skin notation, based on the ACGIH (1986/Ex. 1-3) recommendation, and the final rule establishes an 8-hour TWA limit of 2 ppm and retains the skin designation. Epichlorohydrin is an unstable liquid with an odor like that of chloroform.

In animals, epichlorohydrin is irritating and systemically toxic by all routes of exposure (Shell Chemical Corporation 1958, as cited in ACGIH 1986/Ex. 1-3, p. 233). Fatalities are caused by central nervous system and respiratory tract effects resulting from exposure to high concentrations.

In mice, single 30-minute exposures to 8300 ppm of epichlorohydrin vapor caused muscular paralysis and death from respiratory failure; similar results have been reported for dermal application of the liquid at 0.5 ml/kg in rats, and repeated oral administration at 0.1 mg/kg in mice (Shell Chemical Corporation 1958, as cited in ACGIH 1986/Ex. 1-3, p. 233). At 32 ppm (seven hours/day, five days/week) for 91 days, rats failed to show normal weight gain, and at 16 ppm they showed increased kidney size (ACGIH 1986/Ex. 1-3, p. 233). Gage (1959/Ex. 1-1052) confirmed these findings and demonstrated lung, liver, and kidney injury in rats from repeated six-hour exposures at concentrations ranging from 17 to 120 ppm. No effects were observed by this author at 9 ppm. The oral LD(50) in rats is reported as 260 mg/kg, and the dermal LD(50) in rabbits is reported as 755 mg/kg (Lawrence, Malik, Turner, and Autian 1972/Ex. 1-1058). A four-hour exposure at a level of 250 ppm was fatal to rats (Carpenter, Smyth, and Pozzani 1949/Ex. 1-722).

NIOSH (Ex. 8-47, Table N6B) did not concur with OSHA's proposed limit for epichlorohydrin, and considers this substance a potential human carcinogen and a likely candidate for a 6(b) rulemaking. There have been reports of carcinogenicity in mice resulting from both dermal application and subcutaneous injection of epichlorohydrin (Van Duuren, Goldschmidt, Katz et al. 1974/Ex. 1-969), as well as indications of reproductive effects resulting from ingestion; in addition, mutagenic effects have been observed in microbial systems and in the fruit fly (NIOSH 1976c/Ex. 1-972).

In humans exposed to concentrations above 100 ppm for brief periods, lung edema and kidney lesions have been reported (NIOSH 1976c/Ex. 1-972). Exposure at 20 ppm caused burning of eyes and nasal mucosa (Wexler 1971, as cited in NIOSH 1976c/Ex. 1-972). Another exposure to an unknown concentration caused eye and throat irritation, nausea, dyspnea, bronchitis, and an enlarged liver (Schultz 1964/Ex. 1-1064). Painful irritation of subcutaneous tissues follows skin contact in humans (ACGIH 1986/Ex. 1-3. p. 233). The New Jersey Department of Public Health (Exs. 144, 144A) urged OSHA to establish a PEL for epichlorohydrin on the basis of EPA's IRIS data. The use of such an approach is discussed in Section VI.A of the preamble.

OSHA is establishing an 8-hour TWA limit of 2 ppm, with a skin notation, for epichlorohydrin. The Agency concludes that this limit will protect workers from the significant risk of dermal, respiratory, liver, and kidney effects that are potentially associated with exposure to epichlorohydrin at elevated concentrations. OSHA has determined that the respiratory, liver, kidney, and dermal effects associated with exposure to epichlorohydrin represent material impairments of health. The skin notation is retained because of this substance's capacity to penetrate the skin and cause toxicity; according to Lawrence, Malik, Turner, and Autian 1972/ Ex. 1-1058, the dermal LD(50) of epichlorohydrin in rabbits is 755 mg/kg.


ETHYL BENZENE
CAS: 100-41-4; Chemical Formula C(8)H(10)
H.S. No. 1162


OSHA's former limit for ethyl benzene was 100 ppm as an 8-hour TWA. Based on the skin and mucous membrane irritant properties associated with exposure to ethyl benzene, OSHA proposed permissible exposure limits for this substance of 100 ppm as an 8-hour TWA and 125 ppm as a 15-minute STEL. NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The final rule establishes limits of 100 ppm TWA and 125 ppm STEL for ethyl benzene; these limits are consistent with the ACGIH recommendation. Ethyl benzene is a colorless, flammable liquid with an aromatic odor.

The Agency's decision to add a STEL to the existing time-weighted average limit reflects evidence that transient eye irritation occurs in humans at vapor concentrations of 200 ppm; the short-term limit is necessary to protect exposed workers from the risk of such irritation as a result of even brief excursions above the 100-ppm level.

Written comments submitted by ARCO Chemical Company (ACC) (Ex. 3-638) include a detailed discussion of ethyl benzene's toxicity in animals, as reported in several recent studies (ECETOC 1986; Dynamac Corporation 1986) and in a personal communication from the National Toxicology Program's Chemical Manager for Ethyl Benzene. The findings of these investigators include: moderate dermal irritation on intact and abraded rabbit skin after a 24-hour application; mild conjunctival irritation (without corneal effects) from direct instillation of undiluted ethyl benzene in rabbit eyes; erythema and edema with superficial necrosis, resulting in exfoliation of large patches of skin, following repeated and prolonged application of the undiluted material to rabbit skin; "a slight, cloudy swelling of hepatocytes" in animals subchronically exposed to the vapor as a "result of an increase in the endoplasmic reticulum (SER), which is an adaptive process responsible for increased microsomal enzyme activity and, presumably, increased metabolism of ethyl benzene"; congestion of the lungs, nasal mucosa, liver, and kidneys in mice and rats exposed six hours/day for four consecutive days to ethyl benzene concentrations of 2360 ppm and in mice exposed to 1190 ppm; and lacrimation and salivation in rats exposed at 400 and 800 ppm for six hours/day, five days/week (ECETOC 1986 and Dynamac Corporation 1986, both as cited in Ex. 3-638). ACC stressed the fact that, except at very high concentrations, significant systemic toxicity does not appear to be a manifestation of ethyl benzene exposure.

In addition to providing the results of these up-to-date studies on the health effects in animals of ethyl benzene exposure, the ACC indicated its support for both the retention of the current 100-ppm TWA limit and the adoption of a 125-ppm 15-minute STEL for ethyl benzene. Both concentrations, according to the ACC, "provide a wide safety margin for eye irritation compared to the concentration which can be tolerated in the workplace (1000 ppm)."

The New Jersey Department of Health (Exs. 144, 144A) urged OSHA to set a PEL for ethyl benzene on the basis of EPA's IRIS data. The use of such an approach is discussed in Section VI.A of the preamble.

OSHA concludes that workers exposed to concentrations of ethyl benzene above the 100-ppm level, even briefly, are at significant risk of experiencing irritation; the Agency considers this to be a material impairment of health. Accordingly, the Agency is establishing a short-term limit of 125 ppm for a 15-minute period to supplement the existing 100-ppm time-weighted-average limit for ethyl benzene.


ETHYL ETHER
CAS: 60-29-7; Chemical Formula: C(2)H(5)OC(2)H(5)
H.S. No. 1164


OSHA's previous limit for ethyl ether was a 400-ppm TWA. The Agency proposed the same time-weighted-average TWA limit, with the addition of a 15-minute STEL of 500 ppm. These limits are established in the final rule and are consistent with those recommended by the ACGIH. Ethyl ether is a colorless, volatile, mobile liquid with a distinct odor and a burning, sweet taste. It is extremely flammable and is a severe fire and explosion hazard when exposed to heat or flame.

Ethyl ether causes narcosis and general anesthesia. Concentrations of 3.6 to 6.5 volumes percent in air are anesthetic to humans; 7- to 10-percent concentrations cause respiratory arrest, and concentrations greater than 10 percent are fatal (ACGIH 1986/Ex. 1-3, p. 259). Repeated workplace exposures deliberately induced to produce the so-called "ether jag" have caused narcosis, exhaustion, headache, dizziness, sleepiness, excitation, and other psychic disturbances (Hake and Rowe 1963a/Ex. 1-1152). In women, albuminuria and polycythemia may result (Browning 1965a/Ex. 1-1017). Repeated exposure may cause skin desiccation; irritation of the mucous membranes and eyes occurs on contact with the liquid or after exposure to high concentrations of the vapor (Hake and Rowe 1963a/Ex. 1-1152). Nelson and co-workers (1943/Ex. 1-66) reported that workers began to experience nasal irritation at 200 ppm (Nelson, Enge, Ross et al. 1943/Ex. 1-66). Henderson and Haggard (1943c, as cited in ACGIH 1986/Ex. 1-3, p. 259) calculated that the amount of ether absorbed by a man of average height at a concentration of 400 ppm would not cause intoxication. Armor (1950, as cited in ACGIH 1986/Ex. 1-3, p. 259) observed that exposure effects occur only at levels of 500 ppm and above.

NIOSH (Ex. 8-47, Table N2; Tr. pp. 3-86 and 3-89) did not concur with OSHA's proposed limits and noted that some individuals may experience sensory irritation upon exposure to these levels, as evidenced by the Nelson, Enge, Ross et al. (1943/Ex. 1-66) study. However, this finding was not supported by Armor (1950, as cited in ACGIH 1986/Ex. 1-3, p. 259). OSHA received no other comments on its proposed limits. The Agency concludes that both of these limits are necessary to protect exposed workers against the significant risk of narcosis and irritation potentially associated with excursions above the 8-hour TWA level, and OSHA is establishing PELs of 400 ppm as an 8-hour TWA and 500 ppm as a 15-minute STEL for ethyl ether in today's rule. The Agency has determined that irritation and narcosis caused by excessive exposure to ethyl ether constitute material impairments of health and functional capacity.


ETHYL MERCAPTAN
CAS: 75-08-1; Chemical Formula: C(2)H(5)SH
H.S. No. 1165


OSHA previously had a ceiling limit of 10 ppm for ethyl mercaptan. An 8-hour TWA limit of 0.5 ppm was proposed for this substance, based on the ACGIH (1986/Ex. 1-3) recommendation; NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposal. The final rule establishes a PEL of 0.5 ppm as an 8-hour TWA for ethyl mercaptan. Ethyl mercaptan is a colorless liquid with a persistent and penetrating leek-like odor.

Acute animal toxicity data concerning ethyl mercaptan are taken from a single study that reports the following findings. The 4-hour inhalation LC(50) values in rats and mice are 2770 ppm and 4420 ppm, respectively. In the rat, the intraperitoneal LD(50) is reported to be approximately 450 mg/kg. One drop applied to rabbit eyes caused only slight irritation, but high concentrations of vapor caused considerable irritation within 15 minutes. Maximal sublethal intraperitoneal doses have been reported to induce deep sedation, with higher exposures causing restlessness, muscular incoordination, skeletal muscular paralysis, cyanosis, respiratory depression, coma, and death. Although inhalation tests showed no noteworthy pathology in rats, intraperitoneal injection caused lymphatic infiltration of the liver with occasional necrosis (Fairchild and Stokinger 1958/Ex. 1-415). In chronic inhalation studies of rabbits, rats, and mice, a five-month exposure to 40 ppm caused minimal cardiovascular and other systemic effects (Blinova 1965/Ex. 1-603).

Studies of human volunteers, exposed at 4 ppm for three hours daily for 5 to 10 days, have reported adverse effects. At this level, all subjects experienced altered taste and olfactory reactions, periodic nausea, mucous membrane irritation, and fatigue. Exposure to 0.4 ppm produced no unpleasant symptoms (ACGIH 1986/Ex. 1-3, p. 262).

The Workers Institute for Safety and Health (WISH) (Ex. 116) was critical of OSHA's proposal to establish an 8-hour TWA limit rather than a STEL or ceiling for ethyl mercaptan. OSHA believes that the health evidence on ethyl mercaptan shows that a 0.5 ppm TWA limit will be sufficient to reduce the adverse acute effects associated with exposure to this substance; for example, a 3-hour exposure to 4 ppm, which caused adverse acute effects in human volunteers (ACGIH 1986/Ex. 1-3, p. 262), would exceed 0.5 ppm as an 8-hour TWA. The health evidence discussed above demonstrates that, at the previous PEL of 10 ppm (ceiling), employees were at risk of nausea, fatigue, and irritation; these effects have been demonstrated to occur on exposure to 4-ppm concentrations of this substance for just a few days. OSHA considers these exposure-related effects of nausea, fatigue, and irritation to be material impairments of health. The Agency concludes that the revised limit of 0.5 ppm will substantially reduce this significant risk. Therefore, OSHA is lowering its limit for ethyl mercaptan to 0.5 ppm as an 8-hour TWA.


ETHYLENE GLYCOL
CAS: 107-21-1; Chemical Formula: CH(2)OHCH(2)OH
H.S. No. 1169


OSHA previously had no limit for ethylene glycol and proposed a ceiling limit of 50 ppm (approximately 125 mg/m(3)) for this clear, colorless, odorless, hygroscopic liquid. The final rule establishes a limit of 50 ppm as a ceiling, which is consistent with the limit recommended by the ACGIH for ethylene glycol. Ethylene glycol poses virtually no exposure risk at room temperature because of its low vapor pressure; at elevated temperatures, however, exposures are possible and adverse effects have been reported as a result of exposure to mists.

In studies of rats, guinea pigs, rabbits, dogs, and monkeys, Coon and colleagues (1970/Ex. 1-84) reported that animals exposed over a 30-day period to concentrations of 10 or 57 mg/m(3) for eight hours daily, five days per week, showed no adverse effects. Moderate to severe eye irritation did occur in rats and rabbits exposed at 12 mg/m(3) for 24 hours per day for 90 days (Coon, Jones, Jenkins, and Siegel 1970/Ex. 1-84). Wiley and co-workers (1936/Ex. 1-600) reported no ill effects in animals exposed to approximately 350 to 400 mg/m(3), eight hours per day, for 16 weeks (Wiley, Hueper, and von Oettingen 1936/Ex. 1-600).

Rowe (1963/Ex. 1-865) concluded that daily exposure to 100 ppm of the vapor did not cause systemic or eye injuries, although Troisi (1949/Ex. 1-598) described nystagmus in overexposed workers (concentrations not reported). In a human inhalation study, Wills and colleagues (1974/Ex. 1-582) reported that volunteers exposed to the aerosol from 20 to 22 hours per day for four weeks, at an average concentration of 12 ppm, complained of throat irritation, mild headache, and lower back pain. Complaints were more pronounced when the concentration was raised to 140 mg/m(3) (50 ppm) for part of a day. Average concentrations of 80 ppm were found intolerable by the subjects, who reported a burning sensation in the throat and respiratory passages; irritation was also common at 60 ppm (Wills, Coulston, Harris et al. 1974/Ex. 1-582). Based primarily on this study, NIOSH (Ex. 8-47, p. 6; Tr. p. 3-86) suggested that OSHA reconsider its proposed 50-ppm ceiling limit; however, NIOSH acknowledged that the exposure concentrations used by Wills et al. (1974/Ex. 1-582) were "significantly erratic." NIOSH also described recent evidence that ethylene glycol may be a potential teratogen. OSHA will continue to monitor the toxicologic literature on this substance to evaluate ethylene glycol's potential teratogenicity.

Gary L. Melampy, counsel for the Independent Lubricant Manufacturers Association (ILMA)(Ex. 3-830), commented that OSHA should apply the 50-ppm ceiling limit only to those workplaces where ethylene glycol is used at elevated temperatures. In the final rule, OSHA has not restricted the application of any new or revised PEL to a particular industry segment or industrial process. OSHA recognizes that industrial processes vary in characteristics that affect the degree of risk to which workers are exposed; these characteristics include the amount of material processed or handled, the frequency with which a substance is present, the extent to which a process is open or closed, and the temperatures and pressures at which materials are used. OSHA's policy, which is reflected in all of its previous health standards, has been to base its permissible exposure limits on scientific evidence that exposure to a substance at a given concentration or dose is associated with a health risk and that promulgating a PEL will reduce that risk. Thus, a relationship between exposure level and degree of risk is established and is deemed applicable in all situations where a substance is present. If the characteristics of a process are such that employee exposure to a substance is nonexistent or is well below the levels associated with a health risk, the promulgation of a limit on employee exposure will have little or no effect on the operation or process and imposes no additional burden on the employer. Therefore, in the specific case of ethylene glycol, OSHA sees no reason to limit application of the 50-ppm ceiling limit to those processes where exposure to airborne ethylene glycol is most likely.

Based on evidence of an occupational risk of severe throat and respiratory irritation associated with exposure to the vapor and mist, OSHA is promulgating a ceiling limit of 50 ppm for ethylene glycol; this level is just below the level at which clinical symptoms have been noted in humans. OSHA considers these symptoms, which include throat and respiratory irritation and headache, to be material impairments of health. The Agency concludes that this limit will substantially reduce the significant risk associated with exposures to higher levels that would be permitted in the absence of a PEL.


ETHYLIDENE NORBORNENE
CAS: 16219-75-3; Chemical Formula: C(9)H(12)
H.S. No. 1171


OSHA had no previous limit for ethylidene norbornene. The Agency proposed a ceiling limit of 5 ppm, based on the ACGIH recommendation, and is establishing this limit in the final rule. NIOSH (Ex. 8-47, Table N1) agreed with the selection of this limit. Ethylidene norbornene is a colorless liquid which reacts with oxygen.

In a range-finding study, five of six rats died following a 4-hour exposure to 4000 ppm 5-ethylidene-2-norbornene (Smyth, Carpenter, Weil et al. 1969/Ex. 1-442). Other studies of longer duration have reported that exposures to 237 ppm for seven hours per day, five days per week, for 88 days resulted in death for 21 of 24 rats. No deaths resulted from repeated exposures at 90 ppm, but renal lesions and enlarged livers were observed; liver lesions, testicular atrophy, and hydrothorax occurred only at the 237-ppm level (Kinkead, Pozzani, Geary, and Carpenter 1971/Ex. 1-606). Beagle dogs similarly exposed to 93 ppm for 89 days survived but exhibited such effects as testicular atrophy, hepatic lesions, and slight blood changes. Less pronounced effects were seen after exposures to 61 ppm, and no effects were seen at 22 ppm (Kinkead, Pozzani, Geary, and Carpenter 1971/Ex. 1-606).

Human volunteers exposed for 30 minutes to ethylidene norbornene concentrations of 11 ppm experienced eye and nose irritation; at 6 ppm, transient eye irritation occurred (ACGIH 1986/Ex. 1-3, p. 261). Other than the comments submitted by NIOSH, OSHA received no comments on its proposal to establish a ceiling limit of 5 ppm for ethylidene norbornene.

In the final rule, OSHA is establishing a 5-ppm ceiling for this substance. The Agency finds that this limit is necessary to minimize the risk of irritation that has been documented to occur in occupational exposures to concentrations as low as 6 ppm for 30-minute periods. OSHA has determined that the eye and nasal irritation associated with exposure to ethylidene norbornene constitute material impairments of health. The Agency concludes that this limit will reduce this risk substantially.


FURFURAL
CAS: 98-01-1; Chemical Formula: C(5)H(4)O(2)
H.S. No. 1183


OSHA's previous exposure limit for furfural was an 8-hour TWA limit of 5 ppm, with a skin notation. The Agency proposed reducing this limit to 2 ppm TWA and retaining the skin notation, based on the ACGIH recommendation; these limits are established in the final rule. Furfural is a colorless, oily liquid that turns rust-colored when exposed to air and light.

An inhalation exposure to 260 ppm of furfural was fatal to rats but not to mice or rabbits. A four-week exposure of dogs to 130 ppm for six hours a day caused liver damage, but no adverse effects were observed at 63 ppm (AIHA 1965, as cited in ACGIH 1986/Ex. 1-3, p. 280).

Bugyi and Lepold (1949/Ex. 1-1077) described numbness of the tongue and oral mucosa, absence of a sense of taste, and labored breathing in workers exposed to furfural (at unspecified levels) in a poorly ventilated facility. Korenman and Resnik (1930, as cited in ACGIH 1986/Ex. 1-3, p. 280) stated that inhalations of from 1.9 to 14 ppm furfural caused headaches, itching throat, and eye irritation; Kuhn (1944/Ex. 1-883) reported that exposure to furfural damages the eyesight in some individuals. NIOSH (1975e/Ex. 1-1183) described widespread eye and respiratory tract irritation in workers at a grinding wheel plant exposed to furfural vapor at levels ranging from 5 to 16 ppm. NIOSH (Ex. 8-47, Table N2; Tr. p. 3-86) did not concur with the proposed limit on the basis of these findings and, in addition, urged the Agency to follow up on a recent NTP assay with regard to a possible carcinogenic response in animals exposed to furfural. OSHA notes that Dunlop and Peters (1953/Ex. 1-1189) report that a 15-year study of furfural use in the synthetic resin industry revealed that this substance is not hazardous to employee health in facilities that are adequately ventilated, and that only occasional individual sensitivity was found. The Agency will carefully monitor the results of the NTP Study, currently in peer review, as well as any other scientific evidence pertaining to the health effects of furfural. NIOSH was the only commenter on this substance in the rulemaking record.

After reviewing the evidence above, OSHA concludes that its former 5-ppm TWA limit is not sufficient to protect workers from eye and respiratory tract irritation; this is evidenced by the NIOSH study (1975e/Ex. 1-1183), in which widespread irritation was reported to occur among workers exposed to 5 to 16 ppm. OSHA considers the eye and respiratory tract irritation caused by exposure to furfural to be material impairment of health. Therefore, to protect workers from eye and respiratory tract irritation, OSHA is revising its limit for furfural to 2 ppm as an 8-hour TWA; this limit is established in today's rule. OSHA is also retaining its skin notation; Sax and Lewis (Dangerous Properties of Industrial Materials, 7th ed., 1989) reported the dermal LD(50) in rabbits to be 620 mg/kg, indicating that furfural penetrates the skin and can cause systemic effects.


FURFURYL ALCOHOL
CAS: 98-00-0; Chemical Formula: C(6)H(6)O(2)
H.S. No. 1184


OSHA's previous limit for furfuryl alcohol was 50 ppm as an 8-hour TWA. In the NPRM, OSHA proposed revising its limit to 10 ppm as an 8-hour TWA and 15 ppm as a 15-minute STEL, and adding a skin notation, based on the ACGIH recommendation. NIOSH (Ex. 8-47, Table N1) concurred with this proposal, and these limits are established in the final rule. Furfuryl alcohol is a colorless liquid which turns red or brown on exposure to light and air.

The bases for the proposed OSHA limits, which were derived from ACGIH-recommended limits, are two foundry studies in which furfuryl alcohol was released during core preparation. Apol (1973/Ex. 1-1180) reported no discomfort among workers exposed to 10.8 ppm furfuryl alcohol, but severe lacrimation occurred at 15.8 ppm. Formaldehyde was also present at a concentration of 0.33 ppm. Burton and Rivera (1972/Ex. 1-944) found no irritation, headache, or dizziness among workers exposed to 8-hour TWA concentrations of 5 and 6 ppm, with excursions up to 16 ppm.

In its criteria document, NIOSH (1979a/Ex. 1-236) also reviewed these studies but concluded that it was unknown whether the lacrimation reported by Apol (1973/Ex. 1-1180) was caused by furfuryl alcohol, formaldehyde, or both combined. NIOSH also noted that the current OSHA limit (50 ppm) is five times lower than the concentration reported to cause no adverse effects in monkeys (Woods and Seevers 1954-1956, as cited in NIOSH 1979a/Ex. 1-236). At the time, NIOSH (1979a/Ex. 1-236) recommended that the 50-ppm limit should remain, since no information existed that showed that this limit offered inadequate protection.

Mr. H.K. Thompson, Corporate Industrial Hygiene Manager of Caterpillar, Inc. (Ex. 3-349), commented that formaldehyde probably contributed more than furfuryl alcohol to the lacrimation observed by Apol (1973/Ex. 1-1180). He also agreed that the 50-ppm PEL was too high, since his personal experience has indicated that eye irritation occurs between 25 and 30 ppm furfuryl alcohol. Mr. Thompson recommended that OSHA revise its limit to 25 ppm TWA and add a 50 ppm STEL.

In its final rule for formaldehyde, OSHA analyzed extensively the dose-response data on formaldehyde's irritant effects. In that analysis, OSHA concluded that severe irritation and lacrimation occur in most individuals when the formaldehyde levels reach 3 ppm or above; at levels between 0.1 and 0.5 ppm, slight eye irritation may occur in some individuals (52 FR 46235). In the foundry study by Apol (1973/Ex. 1-1180), formaldehyde was present at a concentration of 0.33 ppm, about 10 times below the level associated with severe eye irritation. Therefore, OSHA believes that exposure to furfuryl alcohol levels of about 16 ppm was most likely the cause of the lacrimation reported by Apol (1973/Ex. 1-1180).

NIOSH (Ex. 150, Comments on Furfuryl Alcohol) concurred with OSHA's proposal to revise the limits for this substance to 10-ppm TWA and 15-ppm STEL. In its posthearing submission, NIOSH cited a study by Cockcroft et al. (1980, as cited in Ex. 150), who reported that a 50-year-old moldmaker developed asthma after working with a mixture containing furfuryl alcohol, paraformaldehyde, xylene, and a catalyst containing sulfuric acid, phosphoric acid, and butyl alcohol. The patient's bronchial response to inhaled histamines was two to three times more severe following exposure to furfuryl alcohol mixed with butyl alcohol.

OSHA finds that the additional evidence submitted by NIOSH further justifies the proposed limits. This evidence indicates that exposure to furfuryl alcohol may potentiate asthmatic responses that are suggestive of an allergic or hypersensitive condition. Individuals that are so affected frequently respond adversely to exposure levels below those that affect most other persons, and the asthmatic response is much more severe than that of respiratory tract irritation.

Therefore, OSHA concludes that the Apol (1973/Ex. 1-1180) study shows that severe eye irritation is associated with exposure to about 16 ppm furfuryl alcohol, and that furfuryl alcohol is capable of inducing more serious asthmatic responses in at least some workers. OSHA has determined that the severe eye irritation and asthma caused by exposure to furfuryl alcohol represent material impairments of health and functional capacity. The Agency is establishing PELs for this substance of 10 ppm as an 8-hour TWA and 15 ppm as a 15-minute STEL, with a skin notation, to reduce these significant risks among exposed employees. The skin notation is added to alert employers that excessive exposure may result from dermal contact; according to Proctor, Hughes, and Fischman (1988, p. 263), furfuryl alcohol is readily absorbed through the skin of animals in sufficient quantity to be lethal.


GLUTARALDEHYDE
CAS: 111-30-8; Chemical Formula: OCH (CH(2))(3)CHO
H.S. No. 1187


OSHA previously had no limit for glutaraldehyde and proposed establishing a ceiling limit of 0.2 ppm, based on the ACGIH (1986/Ex. 1-3) recommendation. NIOSH (Ex. 8-47, Table N1) concurred with this proposal, and the final rule establishes this limit. Glutaraldehyde is an aliphatic dialdehyde that forms colorless crystals.

Glutaraldehyde is strongly irritating to the nose, eyes, and skin (Human Sensory Irritation Threshold of Glutaraldehyde Vapor 1976, as cited in ACGIH 1986/Ex. 1-3, p. 285) and can cause allergic contact dermatitis from occasional or incidental occupational exposure (Jordan, Dahl, and Albert 1972/ Ex. 1-1056). The rat oral LD(50) has been variously reported as 250, 820, and 2380 mg/kg (Stonehill, Krop, and Borick 1963/Ex. 1-1066; Smyth 1963 and NIOSH 1975f, both as cited in ACGIH 1986/Ex. 1-3, p. 285). The dermal LC(50) in the rabbit is 2560 mg/kg, and the 4-hour inhalation LD(50) in the rat is 5000 ppm (NIOSH 1975f, as cited in ACGIH 1986/Ex. 1-3, p. 285).

Mice exposed to alkalinized glutaraldehyde at 8 and 33 ppm for 24 hours have shown marked nervous behavior with panting and compulsive washing of the face and limbs; those exposed to 33 ppm exhibited signs of toxic hepatitis at autopsy (Varpela, Otterstrom, and Hackman 1971/Ex. 1-1072).

In a study of a cold-sterilizing operation in which the operator was exposed for 12 minutes to an activated 2-percent aqueous solution, a measurement of 0.38 ppm glutaraldehyde was taken in the operator's breathing zone; the operator and the investigators experienced severe eye, nose, and throat irritation as well as sudden headache at the end of this procedure (Schneider and Blejer 1973, as cited in ACGIH 1986/Ex. 1-3, p. 285). Another study employing very precise methods of airborne concentration measurement reported the irritation response level for glutaraldehyde to be 0.3 ppm and the odor recognition threshold to be 0.04 ppm (Colwell 1976, as cited in ACGIH 1986/Ex. 1-3, p. 285).

Other than the NIOSH submission, OSHA received no comments on its proposal to establish a ceiling level of 0.2 ppm for glutaraldehyde. The Agency finds that the human evidence cited above clearly demonstrates a significant risk of irritation to the eyes, nose, and throat associated with short-term exposures to glutaraldehyde at concentrations of 0.3 ppm or above. OSHA consides the irritation effects associated with exposure to glutaraldehyde to be material impairments of health. Therefore, OSHA is establishing a 0.2-ppm ceiling limit for this substance in the final rule.


HEXACHLOROCYCLOPENTADIENE
CAS: 77-47-4; Chemical Formula: C(5)Cl(6).
H.S. No. 1196


No previous OSHA limit existed for hexachlorocyclopentadiene. The Agency proposed to establish a 0.01-ppm 8-hour TWA limit for this substances, based on the ACGIH (1986/Ex. 1-3) recommendation; NIOSH (Ex. 8-47, Table N1) concurred with this proposal, and the final rule adds this limit to the Z table. Hexachlorocyclopentadiene is a yellow to amber-colored, nonflammable liquid with a pungent odor.

Hexachlorocyclopentadiene has a high order of acute toxicity in laboratory animals. Rabbits, mice, rats, and guinea pigs died from inhaling 89.5 percent of the vapor in air (Treon, Cleveland, and Cappel 1955/Ex. 1-497). In 150 daily exposures of seven hours each, rabbits, rats, and guinea pigs survived concentrations of 0.15 ppm, but a similar exposure was fatal to four of five mice. At approximately twice this concentration, mice, rats, and most rabbits died by or before the 25th exposure, but guinea pigs survived 30 exposures. The hexachlorocyclopentadiene vapors caused tearing, labored respiration, and, at high concentrations, tremors. Treon and associates (1955/Ex. 1-497) observed degenerative changes in the brain, heart, liver, adrenal glands, and kidneys, and pulmonary irritation occurred in all species, even at the lowest concentration of 0.15 ppm. At higher concentrations, pulmonary edema, hyperemia, necrotizing bronchitis, and bronchiolitis were observed (Treon, Cleveland, and Cappel 1955/Ex. 1-497).

In humans, there are few data concerning hexachlorocyclo-pentadiene's toxicity. Irritation is known to occur, but the intolerable odor and eye irritation associated with exposure to this substance have discouraged prolonged exposures (McGilvray 1971, as cited in ACGIH 1986/Ex. 1-3, p. 300).

The New Jersey Department of Public Health (Exs. 144, 144A) urged OSHA to establish a PEL for hexachlorocyclopentadiene on the basis of EPA's IRIS data. The use of this approach is discussed in Section VI.A of the preamble.

The proposed TWA PEL of 0.01 ppm for this severely toxic substance is about 10 times below the level associated with systemic damage and pulmonary irritation in experimental animals. In the absence of any limit on exposure, OSHA finds that employees are at significant risk of intense eye and pulmonary irritation and multiple organ damage; the Agency considers these effects to be material impairments of health and functional capacity. To substantially reduce these risks, OSHA is establishing an 8-hour TWA limit of 0.01 ppm for hexachlorocyclopentadiene.


HEXYLENE GLYCOL
CAS: 107-41-5; Chemical Formula: (CH(3))(2)-COHCH(2)-CHOH-CH(3)
H.S. No. 1204


OSHA previously had no limit for hexylene glycol. Based on the ACGIH recommendation, OSHA proposed a ceiling limit of 25 ppm for this liquid, which has a mild, sweetish odor. NIOSH (Ex. 8-47, Table N1) concurred with this proposed limit, and the final rule establishes it.

In mice, the LD(50) for hexylene glycol is reported to be 3.8 ml/kg, and it is reported to be 4.79 g/kg in rats. A single dose of 2.0 ml/kg induced hypnosis in mice. Undiluted hexylene glycol instilled into the rabbit eye caused irritation and corneal injury (Smyth and Carpenter 1948/Ex. 1-375).

The Shell Chemical Corporation has reported that oral administration of hexylene glycol can cause nervous system depression that is manifested by an initial state of excitation, followed by deep depression (Shell Chemical Corporation, as cited in ACGIH 1986/Ex. 1-3, p. 309). When the liquid is applied to the skin, mild to moderate irritation occurs, although skin absorption does not. At high concentrations, hexylene glycol vapors evoke a strong sensory response: a five-minute exposure at 1000 ppm produced eye irritation and throat and respiratory discomfort. At concentrations of 50 ppm for 15 minutes, slight eye irritation was reported (ACGIH 1986/Ex. 1-3, p. 309).

Mr. Melampy, Counsel to the ILMA, commented that the proposed 25-ppm ceiling limit "is far below the hazard levels found to exist...," given that exposures to hexylene glycol concentrations of 50 ppm for brief periods of time cause only slight eye irritation. OSHA does not agree with the assessment that a 25-ppm ceiling limit is too low. As discussed earlier in this section, OSHA has determined that no employee should be subjected to mucous membrane or respiratory irritation caused by exposure to toxic agents and that this effect represents material impairment of health and adversely affects the well-being and functional capacity of employees. For hexylene glycol, 50 ppm represents an adverse-effect level, and estab-lishing the limit at this level would not be sufficiently protective. OSHA also concludes that 25 ppm is a reasonable level at which to establish the PEL; this level provides some margin against this substance's irritant effects. Therefore, OSHA finds that establishing a 25-ppm ceiling limit for hexylene glycol is necessary to reduce the risks of eye and respiratory irritation, which occur at exposure levels above the new PEL.


HYDROGEN BROMIDE
CAS: 10035-10-6; Chemical Formula: HBr
H.S. No. 1206


The previous OSHA PEL for hydrogen bromide was 3 ppm as an 8-hour TWA. The Agency proposed revising this limit to 3 ppm as a ceiling limit not to be exceeded at any time during the working day; NIOSH (Ex. 8-47, Table N1) concurred with this proposal. In the final rule, OSHA is establishing this ceiling limit, which conforms to the recommendation made by the ACGIH. Hydrogen bromide (HBr) is a colorless, corrosive, nonflammable gas with an acrid odor.

Animal studies have demonstrated that hydrogen bromide has a considerably higher acute toxicity than hydrogen chloride (HCl) in mice and a somewhat higher acute toxicity than this chemical in rats (NIOSH 1977i/Ex. 1-1182). In mice, the LC(50) is 800 ppm HBr in air for 60 minutes (and 2500 ppm HCl in air for 30 minutes); in rats, the LC(50) is 2800 ppm HBr in air for 60 minutes (and 5000 ppm HCl in air for 30 minutes).

The chief toxic effect of hydrogen bromide in humans is primary irritation of the nose and throat. Irritation begins within several minutes at levels of between 3 and 6 ppm. At 2 ppm, the odor of HBr is detectable, but no irritation is experienced (Connecticut State Department of Health 1955, as cited in ACGIH 1986/Ex. 1-3, p. 312). No chronic effects have been associated with exposure to hydrogen bromide. No comments, other than NIOSH's, were received on this substance.

OSHA finds that, under its previous 3-ppm TWA limit, workers were at significant risk of experiencing irritant effects due to short-term exposures to levels of hydrogen bromide exceeding 3 ppm. The Agency considers the irritant effects of exposure to hydrogen bromide to be material impairments of health. Therefore, OSHA is establishing a 3-ppm ceiling limit for this substance in the final rule to limit short-term exposures to hydrogen bromide and reduce this risk.


HYDROGEN FLUORIDE
CAS: 7664-39-3; Chemical Formula: HF
H.S. No. 1208


The previous OSHA standard for hydrogen fluoride was 3 ppm as an 8-hour TWA. OSHA proposed supplementing its 3-ppm TWA with a 15-minute STEL of 6 ppm. These limits are established in the final rule and are the same as those recommended by NIOSH (1976f, as cited in ACGIH 1986/Ex. 1-3, p. 315). In its posthearing comments, NIOSH (Ex. 150, Comments on Hydrogen Fluoride) concurred with OSHA's proposed limits for hydrogen fluoride. The ACGIH (1986/Ex. 1-3) recommends a 3 ppm TLV-ceiling for hydrogen fluoride. Hydrogen fluoride is a fuming, colorless liquid; at temperatures above 19 deg. C (66 deg. F), it becomes a colorless gas.

Guinea pigs and rabbits survived 40-ppm hydrogen fluoride concentrations for 41 hours, but exposure to 300 ppm for two hours or more was fatal (Machle, Thamann, Kitzmiller, and Cholak 1934/Ex. 1-519). Animals exposed to 3 ppm hydrogen fluoride for 30 days showed no adverse effects (Ronzani 1909, as cited in ACGIH 1986/Ex. 1-3, p. 315). Stokinger (1949a, as cited in ACGIH 1986/Ex. 1-3, p. 315) reported that animals repeatedly exposed to 7 ppm on a daily basis exhibited mild respiratory tract irritation. One study by Largent (1961/Ex. 1-1158) demonstrated kidney, liver, and lung damage in laboratory animals repeatedly exposed to 17 ppm hydrogen fluoride. At 8.6 ppm, the pathologic changes seen in exposed animals were minor, except for lung damage in one dog (Largent 1961/Ex. 1-1158).

In studies with humans, Largent (1960/Ex. 1-516; 1961/Ex. 1-1158) reported that volunteers exposed repeatedly to concentrations of hydrogen fluoride as high as 4.7 ppm for six hours/day for 10 to 50 days experienced irritation and burning of the eyes and nose, in addition to reddening of the skin, at concentrations above 3 ppm. Industrial experience has shown that direct contact of the skin with hydrogen fluoride results in severe burns that may have a delayed onset but later develop into ulcers that eventually scar (Stokinger 1981b/Ex. 1-1127). A report by Eagers (1969, as cited in Stokinger 1981b, above) described several industrial accidents in which workers died in a matter of hours after accidental splashing from ruptured containers of hydrogen fluoride (the cause of death was respiratory failure and cardiac arrest). Kleinfeld (1965/Ex. 1-514) reported a fatal case of hydrogen fluoride poisoning that caused death from pulmonary edema.

NIOSH (1976f, as cited in ACGIH 1986/Ex. 1-3, p. 315), in its criteria document, cites numerous studies that consistently show that long-term occupational exposures to hydrogen fluoride lead to fluorosis in workers. The NIOSH limit is based in part on a study by Derryberry, Bartholomew, and Fleming (1963/Ex. 1-506) showing that the threshold limit for minimal increases in bone density caused by fluoride (fluorosis) is below 4.3 ppm of hydrogen fluoride. The limits proposed by OSHA are the current NIOSH-recommended limits for this substance, and NIOSH's concurrence statement was the only comment received in the record.

Because of hydrogen fluoride's potential to cause respiratory irritation, OSHA finds that a STEL is necessary to reduce the risk associated with elevated, short-term exposures, which would be permitted under the 3 ppm TWA limit alone. The Agency has determined that the irritation caused by exposure to hydrogen fluoride constitutes a material impairment of health. Therefore, OSHA is revising the limits for hydrogen fluoride to 3 ppm as an 8-hour TWA and 6 ppm as a 15-minute STEL; these limits are established in the final rule.


2-HYDROXYPROPYL ACRYLATE
CAS: 999-61-1; Chemical Formula: CH(2)CHCOOCH(2)CHOHCH(3)
H.S. No. 1211


OSHA previously had no limit for 2-hydroxypropyl acrylate. A limit of 0.5 ppm as an 8-hour TWA, with a skin notation, was proposed, based on the ACGIH recommendation. NIOSH (Ex. 8-47, Table N1) concurred with the proposal, and this limit is established in the final rule. 2-Hydroxypropyl acrylate (HPA) is a colorless liquid at room temperature.

In experimental animals, 2-hydroxypropyl acrylate has a high acute toxicity. The Dow Chemical Company (1977c, as cited in ACGIH 1986/Ex. 1-3, p. 320) has reported an oral LD(50) for the rat of 0.25 to 0.5 g/kg, and a dermal LD(50) for the rabbit of approximately 0.25 mg/kg. In guinea pigs, direct contact with HPA caused severe eye burns and skin corrosion and sensitized some of the experimental animals. Rats exposed to a concentration of 650 ppm HPA in air for seven hours survived. Longer-term inhalation studies (30 days for two hours/day, six days/week) in rats, dogs, rabbits, and mice resulted in some irritation at 5 ppm (Dow Chemical Company 1977c, as cited in ACGIH 1986/Ex. 1-3, p. 320).

OSHA received no comment (other than NIOSH's) on its proposed 0.5-ppm TWA limit and skin notation for this substance. The Agency finds that this limit is necessary to protect workers from the risks of irritant effects, skin and eye burns, and sensitization effects associated with exposure to 2-hydroxypropyl acrylate; OSHA considers these effects material impairments of health. Therefore, OSHA is promulgating a TWA limit of 0.5 ppm, which is below the effect level for irritation found in experimental animals. OSHA is also adding a skin notation to the limit because 2-hydroxypropyl acetate readily penetrates the skin to cause systemic effects; the dermal LD(50) in rabbits has been reported to be 0.25 mg/kg (ACGIH 1986/Ex. 1-3).


IRON SALTS (SOLUBLE)
CAS: Varies with compound; Chemical Formula: Varies with compound
H.S. No. 1217


OSHA previously had no limit for the soluble iron salts and proposed establishing the ACGIH-recommended limit of 1 mg/m(3), measured as iron, for these substances. NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposed limit for the soluble salts of iron, and the final rule establishes an 8-hour TWA PEL of 1 mg/m(3).

When injected into the bloodstream of experimental animals, iron salts (especially the ferric salts) are highly toxic (ACGIH 1986/Ex. 1-3, p. 328). The acute intravenous dose of ferric chloride that is lethal to rabbits is about 7.2 mg/kg (Drinker, Warren, and Page 1935/Ex. 1-315). The ACGIH (1986/Ex. 1-3, p. 328) considers the salts to be irritants to the respiratory tract when inhaled as dusts and mists. Stewart and Faulds (1934/Ex. 1-764) described the ferric salts as skin irritants. The oral toxicities of iron salts are considered to be moderate to low, although marked gastrointestinal irritation results from ingestion (U.S. Department of Labor 1941, as cited in ACGIH 1986/Ex. 1-3, p. 328); 30 grams is the estimated fatal dose for humans (Smyth 1956/Ex. 1-759).

NIOSH was the only commenter on OSHA's proposed 8-hour TWA PEL of 1 mg/m(3), measured as iron, for the soluble salts of iron. The Agency concludes that, in the absence of any limit, employees are at risk of skin and mucous membrane irritation associated with exposure to high concentrations of these salts. OSHA considers these effects to be material impairments of health and deems this risk to be significant. Therefore, OSHA is establishing a 1-mg/m(3) 8-hour TWA PEL for the soluble iron salts.


ISOPROPYL ACETATE
CAS: 108-21-4; Chemical Formula: CH(3)COOCH(CH(3))(2)
H.S. No. 1224


OSHA previously had a 250-ppm 8-hour TWA limit for isopropyl acetate. The Agency proposed supplementing this limit with a 15-minute STEL of 310 ppm, based on the ACGIH (1986/Ex. 1-3) recommendation. OSHA is establishing these limits for this substance in the final rule. Isopropyl acetate is a colorless liquid and has a fruity odor.

The oral LD(50) for rats is reported to be 6.75 g/kg; five of six rats died after a four-hour exposure to 32,000 ppm, and one of six rats died after a four-hour exposure to 16,000 ppm (Smyth, Carpenter, Weil, and Pozzani 1954/Ex. 1-440).

The primary problems in occupational exposures to isopropyl acetate are eye and mucous membrane irritation. In humans, exposure to 200 ppm isopropyl acetate for 15 minutes caused eye irritation, with nose and throat irritation occurring at higher concentrations (Silverman, Schulte, and First 1946/Ex. 1-142). NIOSH (Ex. 8-47, Table N2) notes that the majority of subjects exposed to 200 ppm in the Silverman, Schulte, and First (1946/ Ex. 1-142) study experienced eye irritation and that the authors of this study recommended an 8-hour TWA of 100 ppm to prevent sensory irritation. OSHA agrees with NIOSH that this substance presents a hazard at elevated short-term levels and has accordingly added a STEL to ensure that worker exposures are maintained under good industrial hygiene control.

OSHA concludes that, in the absence of a short-term limit on exposure, the 250-ppm TWA limit alone will not protect employees from experiencing the irritant effects associated with elevated short-term exposures to isporopyl acetate. OSHA has determined that the irritant effects related to exposure to isopropyl acetate are material impairments of health. Therefore, to reduce the risk of irritation among exposed employees, the Agency is establishing a 250-ppm 8-hour TWA limit and a 310 ppm STEL for this substance.


ISOPROPYL ALCOHOL
CAS: 67-63-0; Chemical Formula: CH(3)CHOHCH(3)
H.S. No. 1225


The previous PEL for isopropyl alcohol was 400 ppm as an 8-hour TWA. OSHA proposed adding a 15-minute STEL of 500 ppm to this TWA, based on the ACGIH recommendation, and the final rule establishes these limits. In its posthearing comment, NIOSH (Ex. 150, Comments on Isopropyl Alcohol) endorsed OSHA's proposal, stating that a STEL is necessary to reduce the risks of irritation and narcosis that can occur on short-term exposure to elevated concentrations of isopropyl alcohol. Isopropyl alcohol is a colorless, flammable liquid with a slight odor resembling that of rubbing alcohol.

Rats exposed at isopropyl alcohol concentrations of 12,000 ppm for four hours survived, but extending the duration of exposure to eight hours killed the animals (Smyth 1937-1955, as cited in ACGIH 1986/Ex. 1-3, p. 337).

Isopropyl alcohol has been demonstrated to be irritating to the eyes, nose, and throat in humans exposed for brief periods to 400 ppm (Nelson, Enge, Ross et al. 1943/Ex. 1-66); at 800 ppm, these symptoms were more intense. In addition, isopropyl alcohol has narcotic and irritative acute effects at higher concentrations. Weil and associates have reported that an excess of paranasal sinus cancers has been observed among workers manufacturing isopropyl alcohol (Weil, Smith, and Nale 1952/Ex. 1-453). However, it has been established that the cancers associated with isopropyl alcohol manufacture were caused by isopropyl oil and not by the isopropyl alcohol itself (NIOSH 1976g, as cited in ACGIH 1986/Ex. 1-3, p. 337).

No comments, other than NIOSH's, were received on this substance. The irritant effects associated with exposure to isopropyl alcohol occur at concentrations only twice as high as the 8-hour TWA limit, even when the exposure lasts only for a brief period; exposures at this level clearly cause irritation, as documented by the study by Nelson et al. (1943/Ex. 1-66).

OSHA concludes that, in the absence of a STEL, workers are at significant risk of experiencing the narcotic and irritative effects associated with short-term exposures to isopropyl alcohol above the 8-hour TWA PEL of 400 ppm. Therefore, the Agency is retaining its 400 ppm 8-hour TWA limit for isopropyl alcohol and adding a 500 ppm 15-minute STEL to substantially reduce this significant risk. OSHA has determined that the narcosis and eye and mucous membrane irritation associated with chronic and acute exposures to isopropyl alcohol constitute material impairments of health and that a STEL is needed to protect workers from experiencing these harmful effects.


n-ISOPROPYLAMINE
CAS: 75-31-0; Chemical Formula: (CH(3))(2)CHNH(2)
H.S. No. 1228


OSHA's previous limit for n-isopropylamine was 5 ppm as an 8-hour TWA. The Agency proposed retaining this TWA limit and adding a 10-ppm 15-minute STEL, based on the ACGIH recommendation. NIOSH (Ex. 8-47, Table N1; Tr. p. 3-86) concurred with this proposal, and these limits are established in the final rule. This substance is a flammable, volatile, colorless liquid that has an odor similar to that of ammonia.

The most serious effect of n-isopropylamine in laboratory animals is respiratory tract irritation, which can be severe enough to cause lung edema (Smyth 1956/Ex. 1-759). Rats survived a four-hour inhalation at 4000 ppm, but an 8000-ppm exposure resulted in fatalities (Smyth, Carpenter, and Weil 1951/Ex. 1-439). Proctor and Hughes (1978/Ex. 1-1136) have reported that the odor of n-isopropylamine becomes strong and unpleasant at the 10- to 20-ppm level; nose and throat irritation is experienced even as a result of brief exposures.

Except for NIOSH, no rulemaking participants commented on OSHA's proposal to issue a 5-ppm TWA and 15-minute STEL of 10 ppm for this substance. The Agency concludes that both a TWA and STEL are required to protect exposed workers from the significant risk of upper respiratory tract irritation that is known to occur even at brief excursions above the 8-hour PEL. The Agency considers upper respiratory tract irritation resulting from exposure to this substance to be a material impairment of health. Therefore, OSHA is revising the PEL for n-isopropylamine to 5 ppm as an 8-hour TWA and 10 ppm as a 15-minute STEL; these limits are established in the final rule.


MESITYL OXIDE
CAS: 141-79-7; Chemical Formula: (CH(3))(2)C = CHCOCH(3)
H.S. No. 1243


OSHA's previous limit for mesityl oxide was 25 ppm as an 8-hour TWA. The Agency proposed revising this limit to 15 ppm as an 8-hour TWA and 25 ppm as a 15-minute STEL, based on the ACGIH (1986/Ex. 1-3) recommendation. NIOSH has a 10-ppm REL for mesityl oxide. The final rule establishes a 15-ppm 8-hour TWA and a 25-ppm 15-minute STEL for mesityl oxide, which is an oily, colorless liquid with a peppermint odor.

Silverman, Schulte, and First (1946/Ex. 1-142) found that a majority of test subjects experienced eye irritation on exposure to 25 ppm mesityl oxide and nasal irritation at 50 ppm. A toxicity data sheet published by the Shell Chemical Corporation (1957, as cited in ACGIH 1986/Ex. 1-3, p. 361) confirms 25 ppm as the maximum comfort level. Smyth, Seaton, and Fischer (1942/Ex. 1-378) reported liver and kidney damage among rats and guinea pigs exposed to 100 ppm mesityl oxide for six weeks; no adverse effects were reported for animals exposed to 50 ppm. After reviewing these data, the ACGIH (1986/Ex. 1-3, p. 361) concluded that the former TLV of 25 ppm should be reduced to 15 ppm TWA and 25 ppm as a 15-minute STEL because of the greater systemic toxicity of mesityl oxide compared with that of other saturated ketones. NIOSH (1978f, as cited in ACGIH 1986/Ex. 1-3, p. 361), relying on the same data, recommended a limit of 10 ppm as a 10-hour TWA.

Studies indicate that eye irritation occurs following brief exposure to 25 ppm of mesityl oxide, and nasal irritation is experienced at the 50-ppm level. Animal studies show liver and kidney damage in experimental animals exposed to 100 ppm. NIOSH's comment (Ex. 8-47, Table N2; Tr. p. 3-86) was the only one received by the Agency on its proposal to revise the limits for mesityl oxide. NIOSH based its lower recommended limit on a belief that the eye irritation caused by exposure to mesityl oxide might be more severe than the irritation caused by exposure to the other ketones because mesityl oxide has a higher molecular weight than the lower ketones. OSHA is not persuaded by this argument because the evidence that brief exposure to 25 ppm mesityl oxide causes eye irritation is based on actual human exposures to mesityl oxide at that level; that is, NIOSH's argument would be reasonable if the 25 ppm short-term limit were being established by analogy to the effects of another (lower-molecular-weight) ketone.

After reviewing the health evidence for this substance, OSHA finds that the proposed 15-ppm TWA and 25-ppm STEL limits are protective against both the acute and chronic effects demonstrated to be caused by exposure to this substance. In the final rule, OSHA concludes that a TWA PEL of 15 ppm and a STEL of 25 ppm are necessary to protect employees both from the possible liver and kidney damage associated with chronic exposures and the eye irritation resulting from elevated short-term exposures to mesityl oxide. The Agency considers both the systemic and the irritant effects of exposure to mesityl oxide material impairments of health and functional capacity. To reduce these risks, OSHA is establishing limits for mesityl oxide of 15 ppm as an 8-hour TWA and 25 ppm as a 15-minute STEL.


METHYL 2-CYANOACRYLATE
CAS: 137-05-3; Chemical Formula: CH(2)=C(C=N)COOCH(3)
H.S. No. 1248


No previous limit existed for methyl 2-cyanoacrylate. OSHA proposed establishing a limit of 2 ppm as an 8-hour TWA and 4 ppm as a STEL, based on the ACGIH recommendation, and the final rule establishes these limits. NIOSH (Ex. 8-47, Table N1) concurred with the selection of these limits. Methyl 2-cyanoacrylate is a colorless, viscous liquid.

In a personal communication to the ACGIH TLV Committee in 1985, Eastman Kodak reported on the toxicity of methyl 2-cyanoacrylate in experimental animals. The oral LD(50) in rats is reported to be 1.6 to 3.2 g/kg, and the dermal LD(50) in guinea pigs is 10 ml/kg. The adverse effects reported in laboratory animals are slight irritation of the skin and corneal damage. An inhalation LC(50) of 101 ppm has been reported in rats exposed for six hours to methyl 2-cyanoacrylate. Repeated exposures (six hours/day for five days/week) to 31.3 ppm for a total of 12 exposures caused only a slight decrease in the rate of weight gain in rats and no nasal or tracheal lesions or systemic toxicity. No changes were observed in rats similarly exposed to 3.1 ppm (Eastman Kodak 1985, as cited in ACGIH 1986/Ex. 1-3, p. 383).

In a simulated workbench exposure, McGee and co-workers reported nasal irritation in humans at 3 ppm and eye irritation at 5 ppm (McGee, Oglesby, Raleigh, and Fassett 1968/Ex. 1-424). There are no reports of occupational poisonings. No comments, other than NIOSH's, were received on OSHA's proposed PELs for this substance.

The report by McGee et al. (1968/Ex. 1-424) clearly establishes that employees are at risk of nasal irritation on exposure to 3 ppm or above and of eye irritation at 5 ppm or above. The Agency has determined that these adverse effects constitute material impairment of health and should be avoided in the workplace. Therefore, to substantially reduce these significant risks, OSHA is establishing a 2-ppm 8-hour TWA limit and a 4-ppm STEL for methyl 2-cyanoacrylate in the final rule.


METHYL ISOBUTYL CARBINOL
CAS: 108-11-2; Chemical Formula: CH(3)CHOHCH(2)CH(CH(3))(2)
H.S. No. 1261


OSHA previously had an 8-hour TWA limit of 25 ppm, with a skin notation, for methyl isobutyl carbinol. OSHA proposed supplementing these limits with a STEL of 40 ppm, based on the ACGIH (1986/Ex. 1-3) recommended limits, and NIOSH (Ex. 8-47, table N1) concurred with this proposal. The final rule estab-lishes a TWA limit of 25 ppm and a STEL of 40 ppm for this substance, with a skin notation. Methyl isobutyl carbinol is a colorless, stable liquid.

In rabbits, a 24-hour skin application of 3.56 ml/kg (2.9 g/kg) was lethal to half the animals (Smyth, Carpenter, and Weil 1951/Ex. 1-439). Rats exposed by inhalation to 2000 ppm of methyl isobutyl carbinol vapor died, and the same authors report that the oral LD(50) for rats is 2.6 g/kg (Smyth, Carpenter, and Weil 1951/Ex. 1-439).

Human volunteers exposed to methyl isobutyl carbinol reported eye irritation upon 15-minutes' exposure to 50 ppm (Silverman, Schulte, and First 1946/Ex. 1-142). Other than NIOSH's, OSHA received no comments regarding the basis for its proposed limits for methyl isobutyl carbinol.

In view of the finding that exposure to 50 ppm can result in eye irritation in as little as 15 minutes, OSHA has determined that a risk of eye irritation exists in the absence of a limit on short-term exposure. The Agency considers the eye irritation caused by exposure to this substance to be a material impairment of health. Therefore, to reduce this risk, OSHA is establishing a 15-minute STEL of 40 ppm, while retaining the 25-ppm 8-hour TWA PEL and skin notation for this substance.


METHYL MERCAPTAN
CAS: 74-93-1; Chemical Formula: CH(3)SH
H.S. No. 1263


OSHA previously had a ceiling limit of 10 ppm for methyl mercaptan. Based on the ACGIH recommendation, the Agency proposed revising this limit to an 8-hour TWA of 0.5 ppm, and OSHA is establishing this limit in the final rule. Methyl mercaptan is a flammable, water-soluble gas with a disagreeable odor like that of rotten cabbage.

Methyl mercaptan acts on the respiratory center, producing death by respiratory paralysis. DeRekowski (1893, as cited in ACGIH 1986/Ex. 1-3, p. 405) and Frankel (1927/Ex. 1-1033) have reported that the acute toxicity of methyl mercaptan is similar to but somewhat lower than that of hydrogen sulfide; however, Ljunggren and Norberg (1943/Ex. 1-916) have concluded that the two substances exhibit toxicities of the same magnitude. Pulmonary edema results from exposures to lower, less acute concentrations of methyl mercaptan (Fairchild, personal communication, as cited in ACGIH 1986/Ex. 1-3, p. 405).

Inhalation of (an unspecified concentration of) methyl mercaptan produced coma and death in one worker; acute hemolytic anemia and methemoglobinemia developed after this exposure (Schultz, Fountain, and Lynch 1970, as cited in ACGIH 1986/Ex. 1-3, p. 405). A 1918 report by Pickler (as cited by E.E. Sandmeyer in Clayton and Clayton 1981) describes the accidental exposure (for several hours) of 28 students to a concentration of methyl mercaptan estimated at 4 ppm. The individuals had headache and nausea, and one student showed some liver involvement, demonstrated by the appearance of epithelial cells, protein, and erythrocytes, in the excretion fluid. This condition subsided in six weeks (Sandmeyer 1981).

John L. Festa, Director of Chemical Control and Health Programs at the American Paper Institute, Inc. (Ex. 3-685) objected to OSHA's proposal for methyl mercaptan, stating that the basis for the ACGIH TLV, from which the OSHA proposal was derived, was not to reduce irritant effects but to limit odor intensity. He commented further that regulating substances on the basis of "unpleasant sensory stimuli...embarks upon a new precedent" (Ex. 3-685, p. 3). Mr. Festa reported that the odor of methyl mercaptan is relatively faint at 0.05 ppm, although the substance may be mildly irritating over long periods of exposure to concentrations of 4 to 5 ppm.

OSHA does not agree with the suggestion made by Mr. Festa that the effects associated with exposure to methyl mercaptan below 10 ppm (the previous OSHA limit) do not warrant attention. First, Mr. Festa acknowledges that prolonged exposure to 4 to 5 ppm causes irritation; as discussed earlier in this section, OSHA has determined that sensory irritation constitutes material impairment of health. Furthermore, a single inhalation exposure to 7.9 ppm has been reported to result in nauseating odor (NIOSH 1978b, as cited in ACGIH 1986/Ex. 1-3 p. 405); clearly, this effect adversely affects the performance and functional capacity of employees. OSHA is also concerned about the possible liver effects that were reported from a single exposure to approximately 4 ppm methyl mercaptan (Pickler 1918, as cited by E.E. Sandmeyer in Clayton and Clayton 1981). Although this report is dated, OSHA has found no evidence that comprehensive studies have been undertaken in humans to examine the potential for liver or other organ damage as a result of long-term exposure to low levels of methyl mercaptan. Liver and other organ defects have been reported to occur in animals exposed to 50 ppm for only 90 days. Because of these considerations, OSHA concludes that a significant risk of acute sensory effects, as well as possible organ damage, exists at the former 10-ppm ceiling, and that a 0.5-ppm limit is necessary to ensure that these significant risks are adequately reduced. NIOSH (Ex. 8-47, Table N7) recommends a ceiling limit at the same 0.5 ppm level. OSHA is revising its limit for methyl mercaptan to 0.5 ppm as an 8-hour TWA, and this limit is promulgated in today's rule.


METHYL n-AMYL KETONE
CAS: 110-43-0; Chemical Formula: CH(3)COC(5)H(11)
H.S. No. 1264


The current OSHA limit for methyl n-amyl ketone is 100 ppm TWA. OSHA did not propose a revision to its current limit of 100 ppm, and this limit is being retained in the final rule. NIOSH (Ex. 150) agreed that the 100-ppm PEL was sufficiently protective.

Johnson et al. (1978/Ex. 1-335) found no neurologic impairment in rats and monkeys exposed to 131 ppm or 1025 ppm methyl n-amyl ketone for nine months. No gross or histopathologic changes were found (Johnson, Setzer, Lewis, and Hornung 1978/Ex. 1-335). Because of the absence of any human data indicating the concentration of methyl n-amyl ketone that produces sensory irritation, ACGIH (1986/Ex. 1-3, p. 374) believed it prudent to reduce the TLV-TWA from 100 ppm to 50 ppm. NIOSH (1978f, as cited in ACGIH 1986/Ex. 1-3, p. 374) concluded that there was no basis for revising the 100-ppm OSHA limit, since the evidence showed methyl n-amyl ketone's irritant effects to be equivalent to those of 2-pentanone, which had a recommended limit of 150 ppm.

No neurological or histopathological effects were observed at 131 ppm. The ACGIH's 50-ppm TLV applies an additional factor of safety to this no-observed-effect level, while the NIOSH REL is based on a judgment that such a reduction is unnecessary. In the NPRM, OSHA requested additional information on the health effects of methyl n-amyl ketone; however, no information was received into the record.

OSHA notes that the current 100-ppm PEL is well below the highest level (1025 ppm) reported to be associated with any adverse effects. Because histopathological examination was conducted on the organs of the rats and monkeys tested, OSHA is confident that the existing 100-ppm limit is not likely to be associated with adverse affects and that further reducing this limit would not result in a substantial reduction in risk. Therefore, OSHA is not revising its 100-ppm TWA limit for methyl n-amyl ketone at this time.


alpha-METHYL STYRENE
CAS: 98-83-9; Chemical Formula: C(6)H(5)C(CH(3))=CH(2)
H.S. No. 1267


OSHA previously had a ceiling limit of 100 ppm for alpha-methyl styrene. The Agency proposed revising this limit to 50 ppm TWA with a STEL of 100 ppm, and NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposed limits for this substance, which are established in the final rule. alphaMethyl styrene is a polymerizable, colorless liquid.

OSHA's former ceiling limit of 100 ppm is based on data developed in 1955 by the Dow Chemical Company (as cited in ACGIH 1986/Ex. 1-3, p. 410) and by Wolf, Rowe, McCollister et al. (1956/Ex. 1-404). These data demonstrated that seven-hour-per-day, five-day-per-week exposures to 200 ppm alpha-methyl styrene for six months produced no ill effects in rats, guinea pigs, rabbits, or monkeys.

In humans, however, these authors reported that a two-minute exposure to 200 ppm caused eye irritation and complaints about this substance's unpleasant odor. OSHA received no comments, other than NIOSH's, on its proposal to revise the limit for alpha-methyl styrene.

Therefore, to ensure that workers are protected against the acute irritant effects of this substance, OSHA is establishing a 50-ppm 8-hour TWA limit and a 100-ppm 15-minute STEL in the final rule. The Agency concludes that these combined limits will substantially reduce the exposure-related risk of irrita-tion and odor effects, which together constitute material impairments of health.


o-METHYLCYCLOHEXANONE
CAS: 583-60-8; Chemical Formula: CH(3)C(5)H(9)CO
H.S. No. 1270


OSHA's former limit for o-methylcyclohexanone was 100 ppm as an 8-hour TWA, with a skin notation. The Agency proposed revising this limit to 50 ppm as a TWA and 75 ppm as a STEL, and to retain the skin notation; NIOSH (Ex. 8-47, Table N1) concurred with this proposal. These limits are established in the final rule and are consistent with the limits recommended by the ACGIH. ortho-Methylcyclohexanone is a somewhat viscous liquid with an acetone-like odor.

o-Methylcyclohexanone has both irritative and narcotic effects at relatively low concentrations. The commercial product contains a mixture of isomers; however, toxicity data describe the effects of the ortho isomer only. Gross (as cited in Lehman and Flury 1943a/Ex. 1-962) reported that 450 ppm had irritative effects on the eyes and respiratory systems of rabbits, and 2500 ppm produced narcotic effects (Gross, as cited in Lehman and Flury 1943a/Ex. 1-962). Treon et al. (1943a/Ex. 1-393) reported the oral LD(50) to be between 1 and 1.25 g/kg for rabbits. Eye problems were observed at about 500 ppm, but exposure to 182 ppm produced no adverse effects (Treon, Crutchfield, and Kitzmiller 1943a/Ex. 1-393).

Rowe and Wolf (1963, as cited in ACGIH 1986/Ex. 1-3, p. 386) reported that concentrations of 100 ppm had no narcotic effects in humans but could cause irritation. No comments, other than NIOSH's, were received on OSHA's proposal to revise the limit for this substance.

Because a level of 100 ppm may represent an effect level for irritation in humans (Rowe and Wolf 1963, as cited in ACGIH 1986/Ex. 1-3, p. 386), OSHA finds that a reduction in its 100-ppm PEL is warranted. The Agency considers the irritation caused by exposure to this substance to be a material impairment of health. Therefore, OSHA is revising its limit for o-methylcyclohexanone to 50 ppm as an 8-hour TWA and 75 ppm as a 15-minute STEL. OSHA is also retaining its skin notation for this substance.


OSMIUM TETROXIDE
CAS: 20816-12-0; Chemical Formula: O(s)O(4)
H.S. No. 1298


OSHA previously had an 8-hour TWA limit of 0.002 mg/m(3) for osmium tetroxide. Based on the ACGIH recommendation, OSHA proposed to revise this limit to 0.002 mg/m(3) as a TWA and to add a STEL of 0.006 mg/m(3); NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The final rule establishes these limits for this substance. Osmium tetroxide is a noncombustible, colorless to pale yellow solid with a disagreeable, chlorine-like odor.

Exposure to osmium tetroxide is known to produce ocular effects and respiratory irritation. In 1933, Brunot (Ex. 1-776) reported that rabbits died from pulmonary edema four days after a 30-minute exposure to osmium tetroxide at 130 mg/m(3) or higher. Visual problems (e.g., delayed lacrimation and "halo" effects) were reported by this investigator after a brief exposure to osmium tetroxide at a significantly lower concentration (Brunot 1933/Ex. 1-776). A four-hour LC(50) value of 40 ppm has been reported in rats and mice (NIOSH 1977i/Ex. 1-1182). Toxic effects to bone marrow have been reported in guinea pigs (Hamilton and Hardy 1974a/ Ex. 1-957).

Industrial experience indicates that concentrations in a precious metal refining plant ranged from 0.1 to 0.6 mg/m(3); intermittent exposures produced symptoms (sometimes delayed) of lacrimation, vision disturbances, headache, conjunctivitis, and cough (McLaughlin, Milton, and Perry 1946/Ex. 1-749). Complaints of persistent and severe nose and throat irritation have been reported (Hamilton and Hardy 1974a/Ex. 1-957). Fairhall (1949d, as cited in ACGIH 1986/Ex. 1-3, p. 450) reported a human fatality resulting from inhalation exposure to OsO4. Flury and Zernik (1931i, as cited in ACGIH 1986/Ex. 1-3, p. 450) reported that 0.001 mg/m(3) is the highest concentration of osmium tetroxide that can be tolerated for six hours without harmful effects.

Except for NIOSH, no rulemaking participants commented on the proposed addition of a STEL for osmium tetroxide. The study by McLaughlin, Milton, and Perry (1946/Ex. 1-749) used a calibrated, calorimetric procedure, together with well-described case reports, to assess the dose-response relation-ship. OSHA finds this study superior to the report by Flury and Zernik (1931i, as cited in ACGIH 1986/Ex. 1-3, p. 450), which is more anecdotal. The McLaughlin et al. (1946/ Ex. 1-749) study demonstrates serious, acute effects resulting from intermittent and short-term exposure. OSHA concludes that, in the absence of a limit on short-term exposures, the 0.002-mg/m(3) 8-hour TWA PEL alone is not sufficient to protect employees from experiencing these effects, which are deemed to constitute material impairments of health. Therefore, to reduce the risk from short-term elevated exposures to osmium tetroxide, OSHA is establishing a 15-minute STEL of 0.006 mg/m(3) to supplement the 0.002-mg/m(3) TWA limit.


PARAFFIN WAX FUME
CAS: 8002-74-2; Chemical Formula: C(n)H(2)(n)+(2)
H.S. No. 1302


OSHA previously had no limit for paraffin wax fume and proposed establishing an 8-hour TWA limit of 2 mg/m(3); NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The final rule establishes this limit, which is the same as the limit recommended by the ACGIH. Paraffin is a white or slightly yellow, odorless solid that is derived from petroleum.

Paraffin is considered nontoxic in its solid state, but fume generated when it is in the molten state may cause discomfort and nausea (Queries and Minor Notes, JAMA 1938/ Ex. 1-308). In the most recent report of industrial exposure effects, paraffin fume is reported to cause no discomfort in most cases when the concentration is maintained at or below 2 mg/m(3), although one instance of mild discomfort was reported at concentrations between 0.6 and 1 mg/m(3) (Massachusetts Division of Occupational Hygiene 1970, as cited in ACGIH 1986/Ex. 1-3, p. 455).

Dr. William Zeiler, President of the College of American Pathologists (Ex. 3-976), objected to OSHA's inclusion of paraffin wax fume in the final rule, stating that the scientific basis for the limit was lacking. Specifically, Dr. Zeiler commented that the JAMA article (1938/Ex. 1-308) reported "vague and nonspecific" symptoms and that the reference from the Massachusetts Division of Occupational Hygiene was unpublished. He also reported that a literature search dating back to 1965 produced no references on the toxicology of paraffin wax fume. Dr. Zeiler expressed concern that, if a final limit is promulgated for paraffin wax fume, "nonspecific complaints about the workplace environment may implicate this substance as the cause" (Ex. 3-976).

OSHA is aware that the dose-response data for paraffin wax fume are dated; nevertheless, OSHA finds it notable that two different sources (cited by ACGIH 1986/Ex. 1-3, p. 455) report acute adverse effects associated with the use of molten paraffin. OSHA also believes that promulgation of a PEL for paraffin wax fume will present little problem for pathology laboratories, since Dr. Zeiler commented that most clinical laboratories already comply with the ACGIH TLVs and that the services of certified industrial hygienists are used when new laboratories are designed or old ones are remodeled. OSHA is more concerned about workplaces in which paraffin is used in large quantities, such as the food industry, and a greater degree of exposure control is needed. To protect employees in these industries from experiencing acute adverse effects, such as discomfort and nausea, OSHA believes that a PEL for paraffin wax fume is necessary. The Agency has determined that the adverse effects associated with excessive exposure to paraffin wax fume constitute material impairments of health. The limit of 2 mg/m(3) has been shown to be effective in reducing this risk (ACGIH 1986/Ex. 1-3, p. 455); therefore, OSHA is establishing this limit for paraffin wax fume.


PHOSPHORIC ACID
CAS: 7664-38-2; Chemical Formula: H(3)PO(4)
H.S. No. 1322


OSHA's former limit for phosphoric acid was 1 mg/m(3) as an 8-hour TWA. The Agency proposed adding a 15-minute STEL of 3 mg/m(3) based on the ACGIH recommendation, and NIOSH (Ex. 8-47, Table N1) concurred with this proposal. In the final rule, the Agency is establishing a 1-mg/m(3) TWA and a 3-mg/m(3) STEL for this substance. Phosphoric acid is a colorless, odorless solid at temperatures below 21 deg. C but becomes a viscous, clear liquid at higher temperatures.

In humans, there have been reports of respiratory irritation from exposure to phosphorus pentoxide fume at concentrations of between 3.6 and 11.3 mg/m(3); concentrations of 100 mg/m(3) were unendurable except to workers who had developed a tolerance to the fume over time (Rushing 1957, as cited in ACGIH 1986/Ex. 1-3, p. 483). The AIHA Hygiene Guide for phosphoric acid reports that this substance is less hazardous than either nitric or sulfuric acid (AIHA 1957/ Ex. 1-709).

To protect unacclimatized workers from the risk of respiratory irritation, OSHA proposed a TWA limit of 1 mg/m(3), with a STEL of 3 mg/m(3), for phosphoric acid. No comments, other than NIOSH's, were received on this proposal. The Agency concludes that the combined 8-hour TWA and STEL limits are necessary to reduce this significant risk of irritation, which is considered by OSHA to be material impairment of health and which has been shown to occur at levels only slightly above those permitted by the TWA alone. Therefore, OSHA is establishing a 15-minute STEL of 3 mg/m(3) to supplement its 8-hour TWA PEL of 1-mg/m(3) TWA PEL for phosphoric acid.


PHOSPHORUS TRICHLORIDE
CAS: 7719-12-2; Chemical Formula: PCl(3)
H.S. No. 1325


OSHA's former limit for phosphorus trichloride was 0.5 ppm as an 8-hour TWA. The Agency proposed revising this limit to 0.2 ppm as an 8-hour TWA with a STEL of 0.5 ppm; NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The final rule establishes these limits, which are consistent with the limits recommended by the ACGIH. Phosphorus trichloride is a fuming, colorless, noncombustible liquid.

The primary occupational hazards associated with exposure to phosphorus trichloride are respiratory irritation and intoxication involving cough, bronchitis, pneumonia, and conjunctivitis (Henderson and Haggard 1943e/Ex. 1-1086; International Labour Office 1934b, as cited in ACGIH 1986/ Ex. 1-3, p. 486; Sassi 1954/Ex. 1-931).

Early studies indicate that severe symptoms did not occur in cats and guinea pigs until concentration levels reached 50 to 90 ppm for exposures lasting one hour, although slight illness was observed at 0.7 ppm after an exposure of six hours (Butjagin 1904, as cited in ACGIH 1986/Ex. 1-3, p. 486). However, by 1934, the effects of phosphorus trichloride were considered to be 5 to 10 times as intense as those of hydrolyzed hydrochloric acid (International Labour Office 1934b, as cited in ACGIH 1986/Ex. 1-3, p. 486). More recently, Weeks, Musselman, Yevich et al. (1964, as cited in ACGIH 1986/Ex. 1-3, p. 486) reported studies in which 4-hour LC(50) values of 104 ppm for rats and 50 ppm for guinea pigs were obtained.

OSHA received comments only from NIOSH on its proposal to establish a PEL of 0.2 ppm TWA and a STEL of 0.5 ppm for phosphorus trichloride. Because of the acutely irritating effects of this substance, the Agency concludes that both a TWA and a STEL are required to reduce the risk of respiratory and eye irritation that exists for workers exposed to this substance. OSHA considers these effects to be material impairments of health. Therefore, OSHA is revising its limit for phosphorus trichloride to 0.2 ppm as an 8-hour TWA and 0.5 ppm as a 15-minute STEL; these PELs are promulgated in the final rule.


POTASSIUM HYDROXIDE
CAS: 1310-58-3; Chemical Formula: KOH
H.S. No. 1334


OSHA had no former limit for potassium hydroxide. A ceiling limit of 2 mg/m(3) was proposed by the Agency based on the ACGIH recommendation, and NIOSH (Ex. 8-47, Table N1) concurred with this proposal. OSHA has concluded that this limit is necessary to afford workers protection from irritant effects and is establishing the 2-mg/m(3) ceiling limit for potassium hydroxide in the final rule. Potassium hydroxide is a white, deliquescent material that occurs in the form of pellets, sticks, lumps, or flakes.

Potassium hydroxide is corrosive to tissues. The health hazards of potassium hydroxide are similar to those of the other strong alkalies, such as sodium hydroxide. These substances gelatinize tissue on contact, causing deep, painful lesions. Dust or mist exposures may cause eye or respiratory system irritation and nasal septum lesions (Karpov 1971/ Ex. 1-1115).

Mr. Gary Melampy of the Independent Lubricant Manufacturers Association (ILMA) (Ex. 3-830) commented that there was no basis for establishing an occupational limit for potassium hydroxide. OSHA disagrees and notes that the irritant effects of potassium hydroxide dusts, mists, and aerosols have been documented (ACGIH 1986/Ex. 1-3, p. 495; Karpov 1971/ Ex. 1-1115). Although dose-response data are lacking for this substance, it is reasonable to expect potassium hydroxide to exhibit irritant properties similar to those of sodium hydroxide, a structurally related strong alkali. In its criteria document, NIOSH (1976k/Ex. 1-965) cites a personal communication (Lewis 1974), which reported that short-term exposures (2 to 15 minutes) to 2 mg/m(3) sodium hydroxide caused "noticeable" but not excessive upper respiratory tract irritation. Therefore, OSHA finds that the 2-mg/m(3) ceiling limit will provide workers with an environment that minimizes respiratory tract irritation, which the Agency considers to be material impairment of health. To reduce these risks, OSHA is establishing a ceiling limit of 2 mg/m(3) for potassium hydoxide.


PROPYLENE GLYCOL MONOMETHYL ETHER
CAS: 107-98-1; Chemical Formula: CH(3)OCH(2)CHOHDCH(3)
H.S. No. 1343


OSHA had no former limit for propylene glycol monomethyl ether (PGME). The ACGIH recommends a TWA of 100 ppm and a STEL of 150 ppm, and these were the limits proposed. NIOSH has no REL for this substance but concurred (Ex. 8-47, Table N1; Ex. 150, Comments on PGME) with OSHA's proposed limits. The final rule promulgates an 8-hour TWA of 100 ppm and a STEL of 150 ppm for PGME, which is a colorless liquid.

Propylene glycol monomethyl ether is an irritant, neurotoxin, teratogen, and nasal tumorigen (Sax and Lewis 1989, p. 2904). Exposure causes anesthesia at a level of approximately 1000 ppm and eye tearing at levels above 100 ppm; at 100 ppm, PGME also has an objectionable odor (Stewart, Baretta, Dodd, and Torkelson 1970/Ex. 1-379). Ingestion of 3 g/kg in a 35-day period caused changes in the livers and kidneys of rats, and repeated dermal applications of 7 to 10 ml/kg/day caused death in rats treated over a 90-day period (Rowe, McCollister, Spencer et al. 1954/Ex. 1-435). Sax and Lewis (1989) causes nausea, and that inhalation has induced nasal tumors.

Unlike many other members of the glycol ethers family, PGME has been shown not to cause testicular effects at levels below 3000 ppm (NIOSH 1988/Ex. 150). However, Sax and Lewis (1989) note that PGME is an experimental teratogen. Rats exposed by inhalation to 3000 ppm for six hours on days 6 through 15 of gestation produced offspring with delayed skeletal ossification (Sax and Lewis 1989; Proctor, Hughes, and Fishman 1988).

The final rule PELs for PGME of 100 ppm TWA and 150 ppm STEL are designed to protect workers from experiencing the acute effects of exposure to PGME, which include eye and skin irritation and nausea, and the chronic effects of exposure, which include possible liver and kidney changes. Because PGME was not formerly regulated by OSHA, previous workplace exposures could attain essentially uncontrolled levels, and OSHA has determined that an 8-hour TWA of 100 ppm and a STEL of 150 ppm are necessary to protect against these significant occupational risks, which constitute material impairments of health. The Agency finds that the new limits will substantially reduce these significant risks.

ROSIN CORE SOLDER PYROLYSIS PRODUCTS, AS FORMALDEHYDE CAS: None; Chemical Formula: None H.S. No. 1350

OSHA previously had no limit for rosin core solder pyrolysis products. Based on the ACGIH TLV, the Agency proposed an 8-hour TWA of 0.1 mg/m(3) for these compounds, measured as formaldehyde. OSHA has determined that a TWA limit of 0.1 mg/m(3) is necessary to prevent workers from experiencing severe irritant reactions, and the Agency is including this limit in its final rule. This limit applies to the thermal decomposition products of gum rosin soldering flux (3 to 6 percent rosin and 30 to 70 percent tin-lead solder)(Lozano and Melvin, unpublished data, as cited in ACGIH 1986/Ex. 1-3, p. 514).

A two-week exposure of guinea pigs and rats to these products at average concentrations of 0.96 mg/m(3) caused reduction in rate of weight gain in male guinea pigs, abnormal liver-to-body-weight ratios in guinea pigs of both sexes, and abnormal heart-to-body-weight ratios in male rats (Industrial Bio-test Lab, Inc., as cited in ACGIH 1986/Ex. 1-3, p. 514). Lungs of the animals exposed in this same study were hyperemic.

In humans, slight bronchial irritation has been reported at 1 mg/m(3) (Industrial Bio-test Laboratories, Inc. 1967, as cited in ACGIH 1986, p. 514). Several workers who were chronically exposed to levels as high as 0.15 mg/m(3) had to be removed from exposure because of intractable upper respiratory tract irritation; when concentrations were kept below 0.1 mg/m(3), such irritation was not reported (Christy 1965, as cited in ACGIH 1986/Ex. 1-3, p. 514). In a study designed to quantify dose-response levels for irritation in human volunteers, subjects were exposed for 15 minutes to these products at aldehyde concentrations (measured as formaldehyde, which is the best indirect measure of rosin pyrolysis products) of 0.04 to 0.2 mg/m(3) (U.S. Public Health Service 1965, as cited in ACGIH 1986/Ex. 1-3, p. 514). Subjects detected the odor at 0.07 mg/m 3, and 80 percent of subjects reported moderate to severe irritation of the eyes, nose, and throat at concentrations of 0.12 mg/m(3) or above. At levels below 0.05 mg/m(3), fewer than 10 percent of subjects experienced irritation. Mucous membrane irritation occurred in 30 percent of subjects exposed at 0.07 mg/m(3) (U.S. Public Health Service 1965, as cited in ACGIH 1986/Ex. 1-3, p. 514).

NIOSH (Ex. 8-47, Table N6B; Tr. p. 3-97 to 3-98) did not concur with OSHA's selection of a TWA limit of 0.1 mg/m(3) and recommended a ceiling limit of 0.1 ppm for a 15-minute period. In addition, NIOSH (the only commenter to the rulemaking record) considers these thermal decomposition products to be likely candidates for a separate 6(b) rulemaking.

OSHA is establishing an 8-hour TWA limit of 0.1 mg/m(3), measured as formaldehyde, for rosin core solder pyrolysis products. OSHA concludes that this limit will protect employees from the significant risk of respiratory tract irritation, which is a material impairment of health, that exists at levels above the new PEL.

SODIUM BISULFITE CAS: 7631-90-5; Chemical Formula: NaHSO(3) H.S. No. 1365

OSHA's Z tables previously included no exposure limit for sodium bisulfite. The Agency proposed to establish a limit of 5 mg/m(3) as an 8-hour TWA, and it is establishing this PEL in the final rule. NIOSH (Ex. 8-47, Table N1) agrees with the selection of this limit, which is the same as that recommended by the ACGIH. Sodium bisulfite is a white crystalline powder and has an odor like that of sulfur dioxide.

The oral LD(50) in rats fed this substance is 2 g/kg (Dow Chemical Company 1977d, as cited in ACGIH 1986/Ex. 1-3, p. 534), and the intraperitoneal LD(50) for rats is 115 mg/kg (Hoppe and Goble 1951/Ex. 1-490). The ACGIH reports that sodium bisulfite is an eye, skin, and mucous membrane irritant; acute exposures have resulted in mild eye and respiratory effects (ACGIH 1986/Ex. 1-3, p. 534).

One rulemaking participant, Mr. Gary Melampy of the Independent Lubricant Manufacturers Association (ILMA), remarked that OSHA's discussion of the proposed limit for sodium bisulfite in the preamble failed to demonstrate an adequate basis for the limit. OSHA notes that dose-response data to demonstrate a no-effect level are lacking. The 5-mg/m(3) limit was proposed because it represents a limit below that established for physical irritant particulates, and this limit reflects the irritant properties of sodium bisulfite. In the professional judgment of the ACGIH (1986/Ex. 1-3, p. 534), "inhalation of or contact with the dust would result in high local concentrations [of sodium bisulfite] in contact with high local concentrations of sensitive tissue." The ACGIH further states that an occupational limit below that for physical irritant particulates "seems definitely in order." OSHA concurs with this assessment.

Dr. Grace Ziem, an independent occupational physician (Ex. 46), expressed concern about the adverse effects of sodium bisulfite on sensitized individuals. Although cases of severe, and even lethal, allergic reactions to this material have been documented from the use of sodium bisulfite as a food additive, OSHA does not believe that there is sufficient information to use as a basis for an exposure limit to protect against inhalation-induced allergic reactions.

OSHA finds that exposure to this substance presents a significant risk of irritant effects at high concentrations, and that these effects constitute material impairments of health. Accordingly, to substantially reduce this risk, OSHA is establishing a 5-mg/m(3) 8-hour TWA for sodium bisulfite.

SODIUM HYDROXIDE CAS: 1310-73-2; Chemical Formula: NaOH H.S. No. 1367

The former OSHA limit for sodium hydroxide (also known as caustic soda or lye) was 2 mg/m(3) as an 8-hour TWA. OSHA proposed a 2-mg/m(3) ceiling limit for sodium hydroxide, based on the ACGIH- and NIOSH-recommended limits. NIOSH (Ex. 8-47, Table N1) concurred with the proposed limit, and this limit is established in the final rule. Sodium hydroxide is a white, deliquescent solid.

Sodium hydroxide is a severe irritant of the eyes, mucous membranes, and skin. Exposure to sodium hydroxide in the form a caustic dust irritates the upper respiratory tract and may cause ulceration of the nasal passages (ACGIH 1986/Ex. 1-3, p. 535). Although inhalation of sodium hydroxide is usually of secondary importance in industrial exposures, the effects of inhaling the dust or mist vary from mild irritation of the nose, which occurs on brief exposure to 2 mg/m(3), to severe pneumonitis, which occurs at very high exposures. The greatest industrial hazard is rapid tissue destruction of the eyes or skin upon contact either with the solid or with concentrated solutions (Chemical Hazards of the Workplace, 2nd ed., p. 444, Proctor, Hughes, and Fischman 1988).

Contact with the eyes causes disintegration and sloughing of conjunctival and corneal epithelium, corneal opacification, marked edema, and ulceration; after 7 to 13 days, either gradual recovery begins or there is a progression to ulceration and corneal opacification. Complications of severe eye burns are symblepharon with overgrowth of the cornea by a vascularized membrane, progressive or recurrent corneal ulceration, and permanent corneal opacification (Proctor, Hughes, and Fischman 1988, p. 444). Grant (1986/Ex. 1-975) states that sodium hydroxide causes "some of the most severe, blinding injuries of the eye. Because it may be considered public enemy number one for causing chemical burns of the eye, sodium hydroxide has been the chemical caustic most extensively studied in animal and clinical investigations." Clinically, the worst features of sodium hydroxide burns of the eye are the great rapidity with which extreme damage can be done to the anterior segment of the eye and the tendency for the cornea to ulcerate and perforate or to become densely vascularized and opaque.

On the skin, solutions of 25 to 50 percent sodium hydroxide cause the sensation of irritation within about three minutes; with solutions of 4 percent, the sensation of burning does not occur until several hours later. If not removed from the skin, sodium hydroxide causes severe burns with deep ulcerations. Exposure to the dust or mist of sodium hydroxide may cause multiple small burns with temporary loss of hair (Proctor, Hughes, and Fischman 1988, p. 445). Nagao and co-workers (1972) examined skin biopsies from volunteers who had had a 1 N solution (equal to a 4-percent solution) of sodium hydroxide applied to their arms for 15 to 180 minutes. Progressive changes, beginning with dissolution of the cells in the horny layer and progressing through edema to total destruction of the epidermis, occurred within 60 minutes (Nagao, Stroud, Hamada et al. 1972).

Rats were exposed to an aerosol of 40 percent aqueous sodium hydroxide whose particles were less than 1 um in diameter. Exposures lasted for 30 minutes and were administered twice a week. The experiment was terminated after three weeks because two of the 10 rats died. Histopathological examination showed mostly normal lung tissue with foci of enlarged alveolar septae, emphysema, bronchial ulceration, and enlarged lymph adenoidal tissues (Wands 1981b, in Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., vol. 2B, p. 3062).

OSHA received only one comment on sodium hydroxide, from NIOSH (Ex. 150, Comments on Sodium Hydroxide); NIOSH supported OSHA's proposed limit and reported that no new information on the health effects of sodium hydroxide had become available since the publication of the NIOSH criteria document (NIOSH 1976k/Ex. 1-965).

The irritant effect of sodium hydroxide and its markedly corrosive action on all body tissue can result even from brief (one minute or more) exposures to airborne concentrations above the 2-mg/m(3) level; the acute nature of these effects is evident in the studies described above. Therefore, OSHA concludes that establishing a ceiling of 2 mg/m(3) is necessary to reduce the significant risks of eye and skin burns and respiratory irritation that occur as a result of very brief exposures to the higher levels of sodium hydroxide that would be permitted with an 8-hour TWA PEL alone. OSHA considers the irritant effects resulting from exposure to sodium hydroxide material impairments of health. In the final rule, OSHA is accordingly revising its former 8-hour TWA limit for sodium hyroxide to a ceiling limit of 2 mg/m(3).

SODIUM METABISULFITE CAS: 7681-57-4; Chemical Formula: Na(2)S(2)O(5) H.S. No. 1368

OSHA previously had no exposure limit for sodium metabisulfite. The Agency proposed a 5-mg/m(3) limit as an 8-hour TWA, based on the ACGIH recommendation, and is establishing this limit in the final rule. NIOSH (Ex. 8-47, Table N1) concurred with the selection of this limit. Sodium metabisulfite can occur either in the form of a solid or as white crystals; this substance smells like sulfur dioxide.

A two-year study at the Dow Chemical Company (1977e, as cited in ACGIH 1986/Ex. 1-3, p. 535), in which rats ingested 0.215 percent sodium metabisulfite, demonstrated no adverse effects in the rats. Other animal studies show a median lethal dose of 192 mg/kg for rabbits and 115 mg/kg for rats when sodium metabisulfite is injected intravenously (NIOSH 1973c, as cited in ACGIH 1986/Ex. 1-3, p. 535). Inhalation of sodium metabisulfite dust is irritating to the lungs, nose, and throat (ACGIH 1986/Ex. 1-3, p. 535).

Dr. Grace Ziem, an independent physician (Ex. 46), expressed concern that sensitized individuals may experience severe allergic reactions on exposure to sodium metabisulfite dust. Cases of severe, and even fatal, reactions have ben documented in individuals exposed by consuming food items containing metabisulfite additive. At this time, OSHA believes there is insufficient data on oral toxicity to use as a basis to extra-polate to the airborne concentration likely to cause sensitization.

OSHA proposed an 8-hour TWA of 5 mg/m(3) for sodium metabisulfite. The Agency concludes that establishing this limit is necessary to reduce the risk of skin and eye irritation associated with exposure to high concentrations of sodium metabisulfite dust. OSHA has determined that these effects constitute material impairments of health. Accordingly, OSHA is promulgating a 5-mg/m(3) limit as an 8-hour TWA for this substance.

SULFUR MONOCHLORIDE CAS: 10025-67-9; Chemical Formula: S(2)Cl(2) H.S. No. 1376

OSHA's former PEL for sulfur monochloride was 1 ppm as an 8-hour TWA. Based on the ACGIH recommendation, the Agency proposed revising this limit to 1 ppm as a ceiling limit. NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposed limit for this substance, and the final rule establishes it. Sulfur monochloride is an amber, oily, nonflammable, fuming liquid, and has a penetrating odor.

Sulfur monochloride is a primary irritant that affects the upper respiratory tract by releasing hydrochloric acid (HCl) on contact with moisture (Henderson and Haggard 1943g, as cited in ACGIH 1986/Ex. 1-3, p. 545). This same study noted that "undecomposed vapor [of sulfur monochloride] might reach the lungs, in which case it would be more toxic than an equivalent quantity of HCl." The ACGIH (1986/Ex. 1-3, p. 545) considers these data indicative of a far greater acute toxicity for sulfur monochloride than for hydrochloric acid. Animal toxicity studies revealed that a dose of 150 ppm sulfur monochloride resulted in death to mice exposed for one minute (Flury and Zernik 1931k/Ex. 1-979). Cats exposed to 60 ppm sulfur monochloride for 15 minutes all died within a few days, but concentrations of 12 ppm for 15 minutes were tolerated (Henderson and Haggard 1943g, as cited in ACGIH 1986/Ex. 1-3, p. 545).

A study by Elkins (1959g, as cited in ACGIH 1986/Ex. 1-3, p. 545) of workers in the rubber industry found that concen-trations of 2 to 9 ppm sodium monochloride were mildly irri-tating; however, the concentrations to which these workers were exposed may have included a high proportion of hydrochloric acid. NIOSH was the only commenter on sulfur monochloride.

The Agency concludes that the former TWA PEL of 1 ppm is inadequate to protect exposed workers against the risk of primary irritation that could occur upon short-term exposure to elevated concentrations of sulfur monochloride. Since 2 ppm was reported to be an effect level for mild irritation, OSHA finds that revising its limit to 1 ppm as a ceiling limit is a reasonable and necessary action to protect workers from the significant risk associated with lung irritation, which constitutes a material impairment of health. Therefore, OSHA is establishing a ceiling limit for sulfur monochloride of 1 ppm.

SULFUR PENTAFLUORIDE CAS: 5714-22-7; Chemical Formula: S(2)F(10) H.S. No. 1377

The previous OSHA limit for sulfur pentafluoride was 0.025 ppm as an 8-hour TWA. OSHA proposed revising this limit to 0.01 ppm as a ceiling, and NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The Agency is establishing this limit in the final rule. This limit is consistent with the ACGIH (1986/Ex. 1-3) recommended limit. Sulfur pentafluoride is a colorless gas or liquid with a sulfur-dioxide-like odor.

Sulfur pentafluoride's toxic effects include lung congestion and lesions, and pulmonary edema. In a study in which rats were exposed to sulfur pentafluoride for 16 to 18 hours, levels of 0.1 ppm caused lung irritation, 0.5 ppm resulted in severe pulmonary lesions, and 1 ppm proved fatal (Greenberg and Lester 1950/Ex. 1-590). One-hour exposures to 10 ppm sulfur pentafluoride resulted in diffuse hemorrhagic lesions in the lungs of rats, while rats exposed to 1 ppm for one hour had severe congestion of the lungs. Rats exposed for one hour to 0.1 ppm showed no effects. Subsequent examination of rats surviving the 10- and 1-ppm exposures revealed that the lungs had returned to normal after 24 hours (Greenberg and Lester 1950/Ex. 1-590). Saunders, Shoshkes, DeCarlo, and Brown (1953/Ex. 1-610) established that the LD(50) for sulfur penta-fluoride in rabbits is 5.8 mg/kg, and that death was due to fulminant pulmonary edema. According to this study, sulfur pentafluoride does not injure the columnar epithelium of the respiratory tract, and exposure is not followed by bronchopneumonia.

Other than NIOSH's submission, OSHA received no comments on its proposal to revise the sulfur pentafluoride limit to 0.01 ppm as a ceiling. The 0.01-ppm ceiling was selected on the basis of evidence showing that even brief exposures to 1 ppm caused pulmonary effects in animals and prolonged exposures to 0.1 ppm caused lung irritation in animals. OSHA concludes that this limit for sulfur pentafluoride will reduce the risks of irritation and pulmonary effects to which workers could be exposed in the absence of a ceiling limit. The Agency considers these effects material impairments of health. Therefore, OSHA is promulgating a ceiling limit for sulfur pentafluoride of 0.01 ppm.

TETRAHYDROFURAN CAS: 109-99-9; Chemical Formula: (C(2)H(4))(2)O H.S. No. 1387

OSHA's former PEL for tetrahydrofuran was 200 ppm as an 8-hour TWA. The Agency proposed revising this limit to 200 ppm TWA with a 15-minute STEL of 250 ppm and is establishing these limits, which are consistent with those recommended by the ACGIH, in the final rule. NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposal to add a STEL for this substance. Tetrahydrofuran is a colorless liquid with an odor like that of ether.

This proposed limit was selected on the basis of extensive data from experimental animal studies. Lehmann and Flury (1943c/Ex. 1-879) reported irritation of the upper respiratory tract as well as kidney and liver injury in a number of animals exposed by inhalation to more than 3000 ppm tetrahydrofuran for 20 days, eight hours daily. Aqueous solutions exceeding a concentration of 20 percent tetrahydrofuran proved irritating to the skin of rabbits. One study (Stoughton and Robbins 1936/Ex. 1-597) found that tetrahydrofuran concentrations in excess of 25,000 ppm were needed to anesthetize dogs. The anesthesia process in these animals showed a delayed induction period and poor recovery. In other studies with dogs (Zapp 1971, as cited in ACGIH 1986/Ex. 1-3, p. 564), 200 ppm tetrahydrofuran in daily six-hour inhalation exposures produced an observable effect on the pulse pressure of these animals within three to four weeks; despite an exposure of nine weeks at this dosage level followed by three weeks at nearly twice this concentration, no histopathologic changes were observed in the critical organs. Studies (Jochmann 1961/Ex. 1-1021) in which tetrahydrofuran was given orally and peritoneally to a variety of laboratory animals resulted in both liver and kidney damage; however, some of the effects observed by this author may have been caused by peroxide contamination of the tetrahydrofuran. Oettel (as cited in ACGIH 1986/Ex. 1-3, p. 564) observed no kidney or liver damage in cats, rabbits, rats, or mice exposed repeatedly by inhalation to tetrahydrofuran at concentrations of 3400 to 17,000 ppm for as long as six hours. Technicians involved in the experiment of Stoughton and Robbins (1936/Ex. 1-597, described above) experienced severe headaches when conducting these experiments.

Dr. Larry Hecker, Director of Corporate Industrial Hygiene and Toxicology for Abbott Laboratories, commented that there was no toxicological basis to justify a STEL for tetrahydrofuran (Ex. 3-678). However, OSHA believes that the severe headaches experienced by researchers conducting animal experiments (Stoughton and Robbins 1936/Ex. 1-597) are indicative of an acute effect that constitutes material impairment of health and is best avoided by establishing a short-term limit. OSHA also notes that the ACGIH (Threshold Limit Values and Biological Exposure Indicies for 1988-1989, ACGIH 1988b) has not proposed to delete its recommended STEL for this substance. Therefore, OSHA finds that both a 200-ppm 8-hour TWA and a 250-ppm STEL are necessary to reduce the risk of long-term systemic and acute effects associated with exposure to tetrahydrofuran and is establishing these limits in the final rule.

TETRASODIUM PYROPHOSPHATE CAS: 7722-88-5; Chemical Formula: Na(4)P(2)O(7) H.S. No. 1389

The OSHA Z tables previously included no limit for tetrasodium pyrophosphate. OSHA proposed a PEL of 5 mg/m(3) as an 8-hour TWA, and NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposed limit for this substance. This limit is established in the final rule and is consistent with the ACGIH recommendation. Tetrasodium pyrophosphate may occur as either a white powder or a crystalline substance.

Tetrasodium pyrophosphate is an alkaline dust and therefore causes irritation to the eyes and the respiratory tract (ACGIH 1986/Ex. 1-3, p. 567). For this reason, the ACGIH recommended a time-weighted average TLV of 5 mg/m(3), which is one-half the value recommended for irritant dusts. NIOSH's comment was the only one submitted on OSHA's proposal to issue a 5-mg/m(3) 8-hour TWA for this substance.

The Agency concludes that this previously unregulated chemical poses a significant risk of eye and respiratory tract irritation to workers potentially exposed to high concentrations. OSHA has determined that these irritant effects represent material impairments of health. Accordingly, OSHA is promulgating a 5-mg/m(3) 8-hour TWA limit for tetrasodium pyrophosphate in the final rule.

THIOGLYCOLIC ACID CAS: 68-11-1; Chemical Formula: C(2)H(4)O(2)S H.S. No. 1392

OSHA had no former PEL for thioglycolic acid. The Agency proposed a 1-ppm 8-hour TWA, with a skin notation, for this colorless liquid, which has an unpleasant odor; NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The 1-ppm TWA limit and the skin notation, which are the same limits as recommended by the ACGIH, are established in the final rule.

A study by the Dow Chemical Company (1973b, as cited in ACGIH 1986/Ex. 1-3, p. 571) in which thioglycolic acid was instilled into the eyes of rabbits resulted in severe conjunctival inflammation and pain, dense opacity of the cornea, and severe inflammation of the iris. These effects had not improved 14 days after exposure and washing immediately after exposure did not modify the severity of this ocular response. A single dermal application of thioglycolic acid to rabbit skin caused necrosis within five minutes and was accompanied by hyperemia and edema. The LD(50) for a 10-percent solution applied percutaneously was 848 mg/kg for rabbits (ACGIH 1986/Ex. 1-3); further studies by Dow (1973b, as cited in ACGIH 1986/Ex. 1-3, p. 571), in which female rats were fed a single oral dose of a 10-percent solution of thioglycolic acid, showed that this dose resulted in death at the level of 125 mg/kg. Autopsy revealed damage to the liver and gastrointestinal tract. Fassett (1963b, as cited in ACGIH 1986/Ex. 1-3, p. 571) reported that the oral LD(50) for undiluted thioglycolic acid in rats was 50 mg/kg, and that a 10-percent solution applied to the skin of guinea pigs caused fatalities at doses of less than 5 ml/kg. Symptoms prior to death included gasping, convulsions, and weakness.

No rulemaking participants, other than NIOSH, commented on OSHA's proposal to establish a 1-ppm 8-hour TWA limit for thioglycolic acid. The evidence described above clearly demonstrates that this substance is a potent irritant; accordingly, OSHA finds that a limit on airborne exposure is necessary to protect workers from the risk of eye and skin irritation and systemic effects, which constitute material impairments of health. Therefore, OSHA is establishing a 1-ppm 8-hour TWA limit for this substance. In addition, the animal evidence shows that thioglycolic acid solutions readily penetrate the skin in lethal quantities (the dermal LD(50) in rabbits is 848 mg/kg). Thus, OSHA finds that a skin notation is necessary to limit dermal contract and is adding this notation to its limit for thioglycolic acid.

1,2,4-TRICHLOROBENZENE CAS: 120-82-1; Chemical Formula: C(6)H(3)Cl(3) H.S. No. 1405

OSHA formerly had no limit for 1,2,4-trichlorobenzene and proposed to establish a limit of 5 ppm as a ceiling for this substance. NIOSH (Ex. 8-47, Table N1) concurred with this proposal. The final rule establishes this limit, which is consistent with the ACGIH recommendation. 1,2,4-Trichloro-benzene is a colorless, stable liquid at room temperature, with an odor similar to that of o-dichlorobenzene.

The inhalation toxicity of 1,2,4-trichlorobenzene was studied by Treon (1950, as cited in ACGIH 1986/Ex. 1-3, p. 593), who determined that the target organs of exposure in cats, dogs, rats, rabbits, and guinea pigs included the liver, kidneys, ganglion cells at all brain levels, and mucous membranes. Irritation of the lungs and changes in respiration were seen in animals that later died as a result of exposure. Brown, Muir, and Thorpe (1969/Ex. 1-537) reported that 1,2,4-trichlorobenzene's single-dose oral LD(50) is 756 mg/kg for rats and 766 mg/kg for mice. The acute percutaneous LD(50) for rats was 6139 mg/kg. Sublethal doses administered repeatedly to guinea pigs caused liver damage; acute and short-term (15 six-hour exposures to 70 to 200 ppm) inhalation studies failed to kill these animals (Gage 1970/Ex. 1-318). In a separate study reported on by Rowe (1975, as cited in ACGIH 1986/Ex. 1-3, p. 593), 20 male rats, 4 rabbits, and 2 dogs were exposed at levels of 30 or 100 ppm 1,2,4-trichlorobenzene for seven hours/day, five days/week, for a total of 30 exposures in 44 days. No adverse effects were detected in exposed animals belonging to 30 species as a result of exposure to 30 ppm, with the exception of an elevation of urinary porphyrins in the rats at days 15 and 30 of exposure. A second inhalation study was performed with 1,2,4-trichlorobenzene administered seven hours/day, five days/week for 26 consecutive weeks (Coate, Schoenfisch, Busey, and Lewis 1977, as cited in ACGIH 1986/Ex. 1-3, p. 593). Thirty rats, 16 rabbits, and 9 monkeys, all males, were exposed at 0, 25, 50, or 100 ppm. Microscopic changes were seen in the parenchymal cells of the livers and kidneys of all rats after weeks 4 and 13 of exposure to 1,2,4-trichlorobenzene, but no adverse effects were seen in any of the other species.

In workers, exposure to 1,2,4-trichlorobenzene caused dermal irritation, which may have been attributable to the defatting action of this chemical (Powers, Coate, and Lewis 1975/Ex. 1-658), and in some cases, exposure levels of 3 to 5 ppm caused eye and throat irritation (Rowe 1975, as cited in ACGIH 1986/Ex. 1-3, p. 593). NIOSH was the only rulemaking participant to submit comments on 1,2,4-trichlorobenzene.

The Agency concludes that the PEL being established today will protect workers from the risk of eye, throat, and dermal irritation associated with exposure to this substance; these adverse effects represent material impairments of health. To afford workers this protection, OSHA is promulgating a ceiling limit of 5 ppm for 1,2,4-trichlorobenzene.

TRIETHYLAMINE CAS: 121-44-8; Chemical Formula: (C(2)H(5))(3)N H.S. No. 1408

OSHA previously had a limit of 25 ppm TWA for triethylamine. Based on the ACGIH recommendation, the Agency proposed revising this limit to 10 ppm as a TWA and 15 ppm as a 15-minute STEL for this colorless liquid with a strong, ammonia-like odor. NIOSH (Ex. 8-47, Table N1) concurred with this proposal, and OSHA is establishing these limits for triethylamine.

Exposure to triethylamine is associated with pulmonary, skin, and eye irritation and central nervous system effects. Guinea pigs exposed for 30 minutes to a concentration of 2000 ppm triethylamine survived, but four of six animals died when exposed to this level for two hours; two of six guinea pigs died during a four-hour exposure to a concentration of 1000 ppm, but all survived similar exposures at the 250- and 500-ppm levels (Carpenter, Smyth, and Shaffer 1948/Ex. 1-892). The single-dose oral LD(50) value in rats is 0.46 g/kg (range: 0.25 to 0.85) (Smyth, Carpenter, and Weil 1951/Ex. 1-439). These investigators also reported that triethylamine readily penetrated rabbit skin on contact, with an LD(50) value of 0.57 ml/kg (range: 0.36 to 0.90); skin irritation and eye injury were also noted from contact with the liquid. One of six rats died from an acute four-hour inhalation exposure to 1000 ppm triethylamine (Smyth, Carpenter, and Weil 1951/ Ex. 1-439). Rabbits exposed repeatedly to a level of 50 ppm exhibited marked irritation of the cornea and of pulmonary tissue (Brieger and Hodes 1951/Ex. 1-408; Carpenter and Smyth 1946/Ex. 1-859). The effects of repeated triethylamine exposure correspond to those of ethylamine and diethylamine (Brieger and Hodes 1951/Ex. 1-408). Triethylamine was also found to inhibit monoamine oxidase activity, resulting in central nervous system stimulation (De Bruin 1976/Ex. 1-895).

OSHA received a comment on its proposal to revise the limit for triethylamine from Mr. H.K. Thompson, Corporate Industrial Hygienist for Caterpillar, Inc. (Ex. 3-349), who agreed that the 25-ppm PEL is too high, but recommended that OSHA establish a 15-ppm TWA and a 25-ppm STEL. He stated that, in his experience, where triethylamine is used as a catalyst in the making of foundry cores, 16 ppm "produces no irritation or 'halo' effect."

OSHA appreciates the suggestion made by Mr Thompson; however, the Agency is concerned that his suggested STEL of 25 ppm is not sufficiently protective, given that rabbits exposed repeatedly to 50 ppm exhibited marked irritation of the cornea and pulmonary tissue. OSHA judges that a somewhat greater margin of safety is called for to protect employees who may regularly be exposed to short-term elevated concentrations of triethylamine. Therefore, OSHA is establishing the limits originally proposed for trimethylamine, which are 10 ppm as an 8-hour TWA and 15 ppm as a 15-minute STEL. The Agency believes that these limits are necessary to reduce the significant risk of irritation, which constitutes a material impairment of health that is associated with exposure to this substance.

VANADIUM (V(2)O(5)) DUST, RESPIRABLE CAS: 1314-62-1; Chemical Formula: V(2)O(5) H.S. No. 1421

The former OSHA PEL for vanadium pentoxide dust was a ceiling of 0.5 mg/m(3). The Agency proposed a limit of 0.05 mg/m(3) as an 8-hour TWA for the respirable dust of vanadium, as vanadium pentoxide, and is establishing this limit today in its final rule. This limit is the same as that recommended by the ACGIH. Vanadium pentoxide is a yellow to rust brown crystalline compound.

Several studies indicate that OSHA's current exposure limit is insufficient to protect exposed workers against vanadium dust's respiratory effects, which include bronchitis, emphysema, tracheitis, pulmonary edema, and bronchial pneumonia. According to Hudson (1964/Ex. 1-880), vanadium is poisonous to all animals by all routes of administration. The LD(50) in rabbits injected intravenously was 1.5 mg/kg, and rats fed 25 ppm demonstrated toxic responses within a short time (Hudson 1964/Ex. 1-880).

Seven cases of upper respiratory tract irritation were reported in boiler cleaners exposed to concentrations ranging from 2 to 85 mg/m(3) vanadium pentoxide dust (Sjoberg 1951/Ex. 1-437). Williams (1952/Ex. 1-456) reported eight cases of vanadium poisoning in workers cleaning boilers in an atmosphere ranging from 30 to 104 mg/m(3). Gul'ko (1956, as cited by Hudson 1964/Ex. 1-880) observed eye and bronchial irritation in workers exposed to 0.5 to 2.2 mg/m(3). A study by Lewis (1959/Ex. 1-345) indicated that workers exposed to levels of 0.2 to 0.5 mg/m(3) experienced a higher incidence of respiratory symptoms than did controls. Tebrock and Machle (1968/Ex. 1-446) reported that workers exposed to average concentrations of 1.5 mg/m(3) vanadium pentoxide in a mixed dust developed conjunctivitis, tracheobronchitis, and dermatitis. A single average eight-hour exposure to 0.2 mg/m(3) respirable vanadium dust caused severe upper respiratory tract irritation in five human volunteers, and two other subjects exposed to a 0.1-mg/m(3) concentration also developed delayed cough and an increase in mucous production (Zenz and Berg 1967/Ex. 1-405).

NIOSH (Ex. 8-47, Table N7; Tr. p. 3-99) recommended a ceiling limit of 0.05 mg/m(3) for a 15-minute period for this substance. The Workers Institute for Safety and Health (WISH) (Ex. 116, pp. 53) supported NIOSH's recommendation.

In the final rule, OSHA is establishing a limit of 0.05 mg/m 3 as an 8-hour TWA for respirable vanadium dust, measured as vanadium pentoxide. The Agency concludes that this limit will prevent or substantially reduce the risks of eye and bronchial irritation, respiratory symptoms, conjunctivitis, and coughing seen in workers exposed at levels ranging from 0.1 to 2.2 mg/m(3). OSHA considers these exposure-related effects material impairments of health.

VANADIUM (V(2)O(5)) FUME CAS: 1314-62-1; Chemical Formula: V(2)O(5) H.S. No. 1422

OSHA's former PEL for vanadium pentoxide fume was 0.1 mg/m(3) as a ceiling limit. The Agency proposed to revise this limit to 0.05 mg/m(3) as an 8-hour TWA, based on the ACGIH recommendation. OSHA is establishing this limit in the final rule.

Vanadium pentoxide fume's chief toxic effects are manifested in the respiratory passages: bronchitis, emphysema, tracheitis, pulmonary edema, and bronchial pneumonia can result from exposure. According to Hudson (1964/Ex. 1-880), vanadium is poisonous to all animals by all routes of administration. The LD(50) in rabbits injected intravenously is 1.5 mg/kg, and rats fed 25 ppm demonstrated toxic responses within a short time (Hudson 1964/Ex. 1-880).

Seven cases of upper respiratory tract irritation were reported in boiler cleaners exposed to concentrations of from 2 to 85 mg/m(3) vanadium pentoxide fume (Sjoberg 1951/Ex. 1-437). Williams (1952/Ex. 1-456) reported eight cases of vanadium poisoning in workers cleaning boilers in an atmosphere ranging from 30 to 104 mg/m(3). Gul'ko (1956, as cited by Hudson 1964/Ex. 1-880) observed eye and bronchial irritation in workers exposed to 0.5 to 2.2 mg/m(3). A study by Lewis (1959/Ex. 1-345) indicated that workers exposed to levels of 0.2 to 0.5 mg/m(3) experienced a higher incidence of respiratory symptoms than did controls. Tebrock and Machle (1968/Ex. 1-446) reported that workers exposed to average concentrations of 1.5 mg/m(3) vanadium pentoxide in a mixed dust developed conjunctivitis, tracheobronchitis, and dermatitis. A single average eight-hour exposure to 0.2 mg/m(3) respirable vanadium dust caused severe upper respiratory tract irritation in five human volunteers, and two other subjects exposed to a 0.1-mg/m(3) concentration also developed delayed cough and an increase in mucous production (Zenz and Berg 1967/Ex. 1-405).

NIOSH (Ex. 8-47, Table N7) recommended a 15-minute ceiling limit of 0.05 mg/m(3) for vanadium fume as vanadium pentoxide. However, OSHA is concerned about cumulative exposures below the former 0.1 mg/m(3) ceiling, and the Agency concludes that the TWA limit originally proposed will protect workers from the significant risks of eye, skin, and upper respiratory tract irritation; conjunctivitis; pulmonary damage; and systemic poisoning associated with exposure to vanadium pentoxide fume at even brief excursions to higher levels. The Agency considers these irritant and systemic effects to be material impairments of health. Accordingly, OSHA is establishing a PEL of 0.05 mg/m(3) as an 8-hour TWA for this substance in today's rule.

VINYL ACETATE CAS: 108-05-4; Chemical Formula: CH(3)COOCH = CH(2) H.S. No. 1424

There was no previous OSHA limit for vinyl acetate. OSHA proposed establishing a 10-ppm TWA and a 20-ppm STEL for this substance, based on the ACGIH recommendation, and the final rule establishes these limits. Vinyl acetate is a volatile liquid that polymerizes in light to a colorless, transparent mass and usually contains an inhibitor, such as hydroquinone.

The basis for the proposed limits is an epidemiologic report by Deese and Joyner (1969/Ex. 1-412) describing 15 years of industrial experience with vinyl acetate production. These authors reported that vinyl acetate is not a significant irritant at exposure levels of 5 to 10 ppm but causes cough and hoarseness at around 22 ppm. They also found no evidence of adverse chronic effects resulting from exposure to 5 to 10 ppm, as determined from medical records and examinations. While conducting air sampling for the study, the primary author (Deese) experienced hoarseness at concentrations of 4.2 to 5.7 ppm, and eye irritation at 5.7 to 6.8 ppm. Three chemical operators and one technician did not report any subjective responses at these levels. The ACGIH (1986/Ex. 1-3, p. 621) also cited a personal communication from the Mellon Institute (1968) stating that vinyl acetate concentrations of less than 5 ppm are detectable by odor, although some individuals may detect the odor at concentrations of 0.5 ppm (Mellon Institute 1968, as cited by ACGIH 1986/Ex. 1-3, p. 621).

NIOSH (1978i, as cited in ACGIH 1986/Ex. 1-3, p. 621) reviewed these data and concluded that the recommended exposure limit be designed to protect even the most sensitive individuals from sensory irritant effects. Since the lowest level reported to cause upper respiratory tract irritation was 4.2 ppm (Deese and Joyner 1969/Ex. 1-412), NIOSH recommended that workplace exposures not exceed 4 ppm measured over a 15-minute period. In its prehearing submission (Ex. 8-47, Table N2), NIOSH continued to recommend its earlier limit.

The NIOSH REL of 4 ppm (ceiling) relies on a report concerning the experience of a single individual; in contrast, the limits being established today are based on a 15-year epidemiology study that suggests that a 10-ppm TWA and a 20-ppm STEL will provide protection against the risk of irritation associated with exposure to vinyl acetate at higher levels. OSHA considers the irritation caused by exposure to vinyl acetate a material impairment of health. Therefore, the Agency is promulgating this 8-hour TWA and STEL combination as the revised limits for vinyl acetate.

VM & P NAPHTHA CAS No. 8032-32-4; Chemical Formula: none H.S. No. 1429

OSHA formerly had no PEL for VM & P (Varnish Makers' and Printers') naphtha. The Agency proposed to establish an 8-hour TWA of 300 ppm and a STEL of 400 ppm for this substance. NIOSH (Ex. 8-47, Table N1) concurred with these limits, which are based on the ACGIH TLVs. These limits are established in the final rule. VM & P naphtha, also known as ligroin, is a colorless, flammable liquid.

A study in which rats and beagles received inhalation doses of 500 ppm VM & P naphtha for 30 hours per week for 13 weeks resulted in no chronic or latent effects (Carpenter, Kinkead, Geary et al. 1975a/Ex. 1-302). These authors also noted that the acute toxicity of VM & P naphtha for rats and other species was four times greater than that of rubber solvent naphtha, which has a limit of 400 ppm. Carpenter and associates (1975a/Ex. 1-302) also reported on an experiment in which rats lost coordination and went into convulsions within 15 minutes during exposures to saturation concentrations at ambient room temperature. The 4-hour inhalation LC(50) was 3400 ppm, and the acclimated rats survived 5800 ppm for six hours.

Seven human volunteers exposed to 880 ppm VM & P naphtha for 15 minutes reported upper respiratory tract, eye, and nose irritation, in addition to olfactory fatigue (ACGIH 1986/ Ex. 1-3, p. 631). Elkins (1959d, as cited in ACGIH 1986/ Ex. 1-3, p. 631) noted one case of a worker, exposed to levels of VM & P naphtha averaging 800 ppm, who developed unspecified chronic effects. Elkins also reported that the VM & P naphtha level producing significant irritation in human volunteers was about half as great for this form of naphtha as for rubber solvent naphtha.

The Agency concludes that the 300-ppm TWA is necessary to protect workers against the risk of possible chronic effects associated with naphtha exposure. In addition, OSHA finds that a STEL is necessary to prevent upper respiratory tract and eye irritation, which are considered by OSHA to be material impairments of health that have been demonstrated to occur on short-term exposure to 880 ppm VM & P naphtha (ACGIH 1986/Ex. 1-3, p. 631); the proposed 300-ppm TWA limit alone would permit such excursions. Therefore, OSHA is establishing both a 300-ppm 8-hour TWA and a 400-ppm STEL for VM & P naphtha in the final rule.

XYLENES, (o-,m-, AND p-ISOMERS) CAS: 1330-20-7; Chemical Formula: C(6)H(4)(CH(3))(2) H.S. No. 1431

The previous OSHA limit for the xylenes was 100 ppm as an 8-hour TWA. Based on the ACGIH recommendation, OSHA proposed to revise this limit to a TWA of 100 ppm and a 15-minute STEL of 150 ppm. NIOSH (Ex. 8-47, Table N1) as well as the AFL-CIO (Ex. 194) concurred with these limits, and they are established in the final rule. The xylene isomers are clear, flammable liquids with an aromatic hydrocarbon odor.

Rats and rabbits exposed to a mixture of xylene isomers at a concentration of 690 ppm for eight hours daily, six days per week showed no blood abnormalities, but rabbits exposed on the same regimen at 1150 ppm for 55 days showed a decrease in red and white blood cell counts and an increase in platelet count (Fabre and Truhaut 1954, as cited in ACGIH 1986/Ex. 1-3, p. 637).

Studies of workers exposed to xylene revealed headache, fatigue, lassitude, irritability, and gastrointestinal disturbances as the most common symptoms (Gerarde 1960d/Ex. 1-738a). At unspecified exposure levels, Browning (1965b/Ex. 1-1016) also noted gastrointestinal disturbances, in addition to kidney, heart, liver, and neurological damage; blood dyscrasias, some of which resulted in death, were also reported in these workers. A study by Nelson, Enge, Ross et al. (1943/Ex. 1-66), in which human volunteers were exposed to 200 ppm xylene, found eye, nose, and throat irritation in the subjects at this level of exposure.

NIOSH developed a criteria document for xylene in 1975 (NIOSH 1975; as cited in ACGIH 1986/Ex. 1-3, p. 637), in which the work of Morley, Eccleston, Douglas, and colleagues (1970/Ex. 1-794) was discussed. These authors observed liver dysfunction and renal impairment in three workers overexposed to xylene (estimated concentration of 10,000 ppm). One of these workers died, but the others recovered slowly. Furniture polishers were reported by Matthaus (1964/Ex. 1-830) to have suffered corneal damage as a result of exposure to xylene at unknown concentrations.

One other commenter, Stanley L. Dryen of Chevron Corporation (Ex. 3-896, p. 15), objected to OSHA's issuing of a STEL, stating that there was no basis for one. OSHA disagrees and points out that a 100-ppm TWA limit alone would permit short-term exposure to several hundred ppm xylene, well above the 200-ppm level reported to be irritating as a result of short-term exposures. OSHA notes that NIOSH also recommends a short-term limit to supplement the TWA.

After reviewing this evidence, OSHA concludes that both a TWA and a STEL are necessary to prevent the risks of narcosis, blood effects, and irritant effects at the elevated levels possible at the current exposure limit. The Agency considers the effects of narcosis, irritation, and blood effects to constitute material impairments of health and functional capacity. Therefore, to reduce the risk of irritation to workers exposed to the xylenes, OSHA is establishing a 150-ppm STEL and a 100-ppm TWA for xylene isomers in the final rule.

ZINC CHLORIDE (FUME) CAS: 7646-85-7; Chemical Formula: ZnCl(2) H.S. No. 1435

OSHA's former PEL for zinc chloride was 1 mg/m(3) as an 8-hour TWA. The Agency proposed a TWA of 1 mg/m(3), with a STEL of 2 mg/m(3), for this substance, based on the ACGIH recommendation. NIOSH (Ex. 8-47, Table N1) concurred with this proposal, and these limits are established in the final rule. Zinc chloride fume is white and has an acrid odor.

Zinc chloride fume is highly caustic and damages the mucous membranes of the nasopharynx and respiratory tract. Exposure to the fumes of zinc chloride may result in a severe pneumonitis that is caused by irritation of the respiratory tract (Gafafer 1964/Ex. 1-1149). One instance in which a worker inhaled zinc chloride fumes resulted in advanced pulmonary fibrosis that ended in death (Milliken, Waugh, and Kadish 1963/Ex. 1-751), and 10 deaths and 25 nonfatal cases of pneumonitis occurred in workers caught in a tunnel when 79 smoke generators caught fire and generated zinc chloride fumes (Hunter 1955/Ex. 1-853). Other studies have shown that zinc chloride exposures cause skin ulceration (Sax 1957/ Ex. 1-1095). It has also been suggested that zinc chloride exposure may have chronic effects (Hamilton and Hardy 1974b/Ex. 1-958). In an investigation of the adverse effects of zinc chloride fume exposures, Ferry (1966, as cited in ACGIH 1986/Ex. 1-3, p. 643) reported that no sensory effects occurred when 30-minute exposures were limited to 0.07 and 0.4 mg/m(3); however, this researcher noted that these levels did corrode metal. Other than NIOSH's submission, no comments were received by OSHA on the proposed limits for zinc chloride fume.

OSHA concludes that the risk of damage to the eyes, skin, and respiratory tract associated with short-term exposure to zinc chloride fume, which are considered by OSHA to be material impairments of health, should be substantially reduced by establishing both a STEL and a TWA. Therefore, in the final rule, OSHA is promulgating a 1-mg/m(3) TWA limit and 2-mg/m(3) STEL for this substance.

Conclusions for the Group of Sensory Irritants

OSHA finds that sensory irritation poses an occupational health risk to workers exposed to these substances at the Agency's former exposure limits. Among the adverse health consequences of exposure to sensory irritants are acute breathing difficulty, eye tearing, conjunctivitis, sensitization, persistent coughing, and upper respiratory tract irritation. OSHA has determined that these effects constitute material impairments of health and functional capacity within the meaning of the Act. In addition to the pain and suffering associated with these signs and symptoms, workers experiencing irritant effects find it difficult if not impossible to concentrate on the job at hand; they therefore work less safely and less productively than nonexposed employees. Reducing exposures from levels that have been associated with these effects to levels where such consequences are substantially less likely to occur will reduce the significant risk posed to workers at current levels. Furthermore, many of the substances in this group have been demonstrated to have adverse effects on other organ systems, including the cornea, lungs, kidney, liver, central nervous system, and gastrointestinal tract. OSHA finds that promulgation of the new or revised limits for the substances in this group will also further reduce the possibility of harm to these organ systems.

OSHA concludes that the health evidence for these substances forms a reasonable basis for establishing revised or new limits, and that establishing these limits is necessary to reduce the risk of sensory irritation effects to exposed workers. OSHA concludes that sensory irritation constitutes a material impairment of health and functional capacity.

4. Substances for Which Limits Are Based on Avoidance of Liver or Kidney Effects

Introduction

The liver or the kidneys are the primary target organs affected by toxic exposures to a number of industrial chemicals. In recognition of this target organ toxicity, OSHA is establishing new or revised limits for 17 hepato- or nephrotoxic compounds (12 hepatotoxins and five nephrotoxins). For these substances, the liver or kidney appears to be the organ most sensitive to the effects of exposure. Thus, establishing permissible exposure limits that are low enough to prevent toxicity to these target organs generally also protects other organ systems.

For seven of the 12 substances for which limits were based on liver toxicity, OSHA is lowering the PEL, and for three substances, OSHA is adding a short-term exposure limit. For two substances, OSHA is adding a PEL where none previously existed. For three kidney toxins, OSHA is establishing new PELs; in one case, it is reducing an existing TWA-PEL, and, in another case, it is reducing its current PEL and adding a STEL. The sections below discuss liver and kidney toxins separately. Table C4-1 shows these hepatotoxic substances and their former, proposed, and final rule limits, CAS, and HS numbers; Table C4-2 provides the same information for the nephrotoxins in this group.

Table C4-1.  List of Substances For Which Limits Are Based
             Primarily on Avoidance of Liver Toxicity

NOTE: Because of its width, this table has been divided;
            see continuation for additional columns.
_________________________________________________________________________
H.S. Number/
Chemical Name                 CAS No.   Former PEL      Proposed PEL
_________________________________________________________________________
1011 Allyl chloride        107-05-1   1 ppm TWA         1 ppm TWA
                                                        2 ppm STEL
1072 Carbon tetrabromide   558-13-4   --                0.1 ppm TWA
                                                        0.3 ppm STEL
1089 o-Chlorostyrene      2039-87-4   --                50 ppm TWA
                                                        75 ppm STEL
1108 Cyclohexanone         108-94-1   50 ppm TWA        25 ppm TWA,
                                      Skin              Skin
1145 Dioxane               123-91-1   100 ppm TWA,      25 ppm TWA,
                                      Skin              Skin
1168 Ethylene dichloride   107-06-2   50 ppm TWA        1 ppm TWA
                                      100 ppm STEL      2 ppm STEL
                                      (5 min/3 hrs)
                                      200 ppm Ceiling
1205 Hydrazine             302-01-2   1 ppm TWA,        0.1 ppm TWA,
                                      Skin              Skin
1269 Methylcyclohexanol  25639-42-3   100 ppm TWA       50 ppm TWA
1295 Octachloro-          2234-13-1   0.1 mg/m(3) TWA,  0.1 mg/m(3) TWA
       naphthalene                    Skin              0.3 mg/m(3) STEL,
                                      Skin               Skin
1341 Propylene dichloride   78-87-5   75 ppm TWA         75 ppm TWA
                                      110 ppm STEL
1385 1,1,2,2-Tetrachloro-   79-34-5   5 ppm TWA,         1 ppm TWA,
       ethane                         Skin               Skin
1407 1,2,3-Trichloro-       96-18-4   50 ppm TWA,        10 ppm  TWA,
       propane                                           Skin
________________________________________________________________________


Table C4-1.  List of Substances For Which Limits Are Based
             Primarily on Avoidance of Liver Toxicity (Continuation)
_____________________________________________
H.S. Number/
Chemical Name               Final Rule PEL(1)
______________________________________________
1011 Allyl chloride         1 ppm TWA
                            2 ppm STEL
1072 Carbon tetrabromide    0.1 ppm TWA
                            0.3 ppm STEL
1089 o-Chlorostyrene        50 ppm TWA
                            75 ppm STEL
1108 Cyclohexanone          25 ppm TWA,
                            Skin
1145 Dioxane                25 ppm TWA,
                            Skin
1168 Ethylene dichloride    1 ppm TWA
                            2 ppm STEL
1205 Hydrazine              0.1 ppm TWA,
                            Skin
1269 Methylcyclohexanol     50 ppm TWA
1295 Octachloro-            0.1 mg/m(3) TWA
       naphthalene          0.3 mg/m(3) STEL,
                            Skin
1341 Propylene dichloride   75 ppm TWA
                            110 ppm STEL
1385 1,1,2,2-Tetrachloro-   1 ppm TWA,
       ethane               Skin
1407 1,2,3-Trichloro-       10 ppm  TWA,
       propane              Skin
________________________________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures and its STELs
are for 15 minutes only unless otherwise specified.



Table C4-2.  List of Substances For Which Limits Are Based Primarily
             on Avoidance of Liver Toxicity

NOTE: Because of its width, this table has been divided;
see continuation for additional columns.
_________________________________________________________________________
H.S. Number/
Chemical Name                 CAS No.   Former PEL      Proposed PEL
_________________________________________________________________________
1129 1,3-Dichloropropene     542-75-6   --              1 ppm TWA,
                                                        Skin
1132 Dicyclopentadiene        77-73-6   --              5 ppm TWA
1166 Ethyl silicate           78-10-4  100 ppm TWA      10 ppm TWA
1195 Hexachlorobutadiene      87-68-3   --               0.02 ppm TWA,
                                                         Skin
1203 Hexone (Methyl           108-10-1  100 ppm TWA      50 ppm TWA
     isobutyl ketone)                                    75 ppm STEL
________________________________________________________________________



Table C4-2.  List of Substances For Which Limits Are Based Primarily
             on Avoidance of Liver Toxicity (Continuation)
__________________________________________________
H.S. Number/
Chemical Name                 Final Rule PEL(1)
__________________________________________________
1129 1,3-Dichloropropene       1 ppm TWA, Skin
1132 Dicyclopentadiene         5 ppm TWA
1166 Ethyl silicate            10 ppm TWA
1195 Hexachlorobutadiene       0.02 ppm TWA,
1203 Hexone (Methyl            50 ppm TWA
     isobutyl ketone)          75 ppm STEL
___________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures and its
STELs are for 15 minutes unless otherwise specified.

Liver Toxicity

Description of the Health Effects

Although the precise mechanisms by which these compounds cause liver damage are only partly understood, the development and manifestation of liver toxicity are similar for all of them. In general, liver toxicity is a graded response (i.e., the severity of the lesion is directly proportional to the intensity/duration of exposure). Although many of the effects caused by exposure to these substances are reversible, some are not.

Liver damage is not a single entity; the manner in which it is manifested depends upon the dose, duration, and particular chemical agent involved. For example, acute exposures may cause lipid accumulation in the hepatocytes, cellular death, and hepatobiliary dysfunction. In contrast, chronic exposures may lead to cirrhotic changes and the development of neoplasms. Fatty accumulation and necrosis can be either localized or widespread, and chemically induced lesions resulting from chronic exposures can cause marked changes of the entire liver (Plaa 1986/Ex. 1-183).

Typically, the earliest and most sensitive indicators of liver toxicity are alterations in biochemical liver functions, such as changes in specific enzyme activities. These may be accompanied by changes in the morphology of specific organelles in hepatocytes. For example, relatively low doses of halo-genated aliphatic hydrocarbons, such as allyl chloride, carbon tetrabromide, and ethylene dichloride, cause an increase in the activity of microsomal mixed-function oxidase enzymes. This increase is ordinarily accompanied by proliferation of the endoplasmic reticulum.

Many compounds that damage the liver, such as 1,1,2,2-tetrachloroethane, also cause an abnormal accumulation of fat, especially of triglycerides, in liver cells. In experimental animals, this effect is manifested as an accumulation of microscopic vacuoles in liver cells. In humans, however, the only grossly detectable manifestation of this effect is increased liver size, which is an indication of severe fat accumulation in the liver.

At sufficiently high doses, most substances that damage the liver cause cell death that leads to tissue necrosis or gangrene. This necrosis may initially be localized, but, at higher or more sustained exposure levels, the entire liver may be involved. Moderate to severe liver necrosis is usually accompanied by increased concentrations of marker enzymes such as glutamate-pyruvate transaminase or glutamate-oxaloacetate transaminase in the serum; the detection of these substances in the serum of exposed individuals can thus be a useful diagnostic tool.

Dose-Response Characteristics

The development of liver and other organ damage in humans and animals is progressive; it begins with subcellular changes, progresses to the cellular level, and is finally manifested as whole-organ damage. This progression is related to the intensity/duration of dose (i.e., as dose increases, cellular death becomes widespread and eventually causes liver dysfunction). The extent to which liver damage is reversible follows a similar continuum; since the liver can regenerate, minor cellular damage or transient disease states are usually reversible if exposure ceases. However, if exposure continues, the capacity of the liver to regenerate is exceeded and permanent damage results. As is the case for some chemically induced toxic effects, there appears to be a NOE level below which hepatotoxic effects do not occur.

The following paragraphs describe OSHA's findings for all of the substances in this group of hepatotoxins and discuss the record evidence and the nature of the material health impairments experienced by exposed workers.


ALLYL CHLORIDE
CAS: 107-05-1; Chemical Formula: CH(2) = CHCH(2)Cl
H.S. No. 1011


The former OSHA PEL for allyl chloride was a 1-ppm (3-mg/m(3)) 8-hour TWA; the proposed PEL was also 1 ppm, with a 15-minute STEL of 2 ppm. NIOSH (Ex. 8-47, Table N1) concurred with the proposed limits. In the final rule, OSHA is establishing an 8-hour TWA limit of 1 ppm and a STEL of 2 ppm for this substance; these limits are consistent with those of the ACGIH. Allyl chloride is a colorless liquid with an unpleasant, pungent odor.

Studies of animal exposures to allyl chloride indicate that this chemical is among the most toxic of the halogenated aliphatic hydrocarbons, producing mucous membrane irritation, mild narcosis, and, at higher concentrations, histologic lesions of the lungs and kidneys (Adams, Spencer, and Irish 1940/Ex. 1-584). Even single exposures lasting only a few minutes at concentrations between 1 and 100 mg/liter (332 to 32,000 ppm) caused mucous membrane irritation in various laboratory animals; at 8-ppm concentrations for five weeks, kidney and liver damage were observed (Adams, Spencer, and Irish 1940/Ex. 1-584). Further animal studies have confirmed liver and kidney pathology in many species (Torkelson, Wolf, Oyen, and Rowe 1959/Ex. 1-691), and female rats exhibited kidney pathology after exposure to 3 ppm for six months.

Exposures of 50 to 100 ppm for five minutes in humans caused eye and nose irritation, and five-minute exposures below 25 ppm have been associated with pulmonary irritation (Shell Chemical Corp. 1974, as cited in Ex. 150). Humans exposed to concentrations of 1 to 113 ppm showed abnormal liver test results (Hausler and Lenich 1968/Ex. 1-1035).

In a posthearing comment (Ex. 150, Comments on Allyl Chloride), NIOSH reported the results of a recent National Cancer Institute monograph (Santodonato et al. 1985, as cited in Ex. 150) showing that allyl chloride is a tumor initiator in mice and a mutagen in bacterial test systems. NIOSH (Ex. 150) and Drs. Grace Ziem and Barry Castleman (Ex. 114A) discussed recent epidemiological and clinical studies from the People's Republic of China (He et al. 1985, as cited in Exs. 114A and 150), which also found toxic polyneuropathy in workers exposed to between 2.6 and 6650 mg/m(3) allyl chloride for durations ranging from 2.5 months to 6 years; in contrast, workers at another facility with allyl chloride exposures below 25 mg/m(3) for 1 to 4.5 years had few neurological disorders, but 50 percent showed abnormal electroneuromyographic results. Animal studies confirm this substance's neuropathic potential (Ex. 114A and Ex. 150, Comments on Allyl Chloride).

The final rule establishes an 8-hour TWA limit of 1 ppm and a STEL of 2 ppm for allyl chloride. The Agency concludes that both TWA and STEL limits are necessary to protect workers from the significant risk of kidney and liver damage and neuropathic effects which constitute material health impairments and are potentially associated with the elevated short-term exposures to allyl chloride currently permitted by the 8-hour TWA alone.


CARBON TETRABROMIDE
CAS: 558-13-4; Chemical Formula: CBr(4)
H.S. No. 1072


OSHA formerly had no limit for exposure to carbon tetrabromide. The proposed limits were 0.1 ppm as an 8-hour TWA and 0.3 ppm as a 15-minute STEL; the final rule establishes these limits, which are consistent with those of the ACGIH. NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposed limits for carbon tetrabromide. At room temperature, pure carbon tetrabromide is a colorless, nonflammable solid. However, samples are usually yellow-brown in color.

Carbon tetrabromide's hepatotoxic effects include both fatty infiltration and necrosis. The 0.1-ppm and 0.3-ppm TWA and STEL levels were selected based on an observed no-effect level of 0.1 ppm; this finding derives from a study in which rats were exposed to carbon tetrabromide by inhalation for seven hours per day, five days per week for six months (Torkelson and Rowe 1981a/Ex. 1-974). Dr. Grace Ziem (Ex. 46) submitted information to OSHA showing that exposure to 0.07 ppm has caused sensory irritation in rats.

The final rule establishes limits of 0.1 ppm as an 8-hour TWA and 0.3 ppm as a 15-minute STEL for carbon tetrabromide. OSHA concludes that establishing these limits for this previously unregulated chemical will protect workers against the significant risk of hepatotoxic effects, which constitute material health impairments.

o-CHLOROSTYRENE CAS: 2039-87-4; Chemical Formula: C(8)H(7)Cl H.S. No. 1089

OSHA formerly had no limit for o-chlorostyrene. The proposed limits were an 8-hour TWA of 50 ppm and a STEL of 75 ppm, and NIOSH (Ex. 8-47, Table N1) concurred with these limits. The final rule establishes a 50-ppm TWA PEL and a 75-ppm STEL, limits that are consistent with those of the ACGIH. o-Chlorostyrene is a colorless liquid at room temperature.

In an unpublished report, the Dow Chemical Company (1973a, as cited in ACGIH 1986/Ex. 1-3, p. 136) describes the results of an o-chlorostyrene inhalation study in rats, rabbits, guinea pigs, and dogs. Dow exposed the animals to an average concentration of 101 ppm for seven hours daily, five days per week, for a total of 130 exposures in 180 days. No adverse effects were observed in any species in terms of appearance, growth, behavior, mortality, hematology, BUN, alkaline phosphatase, SGPT, BSP, organ weights, or gross pathology (Dow Chemical Company 1973a, as cited in ACGIH 1986/Ex. 1-3, p. 136). Microscopic examination of animal tissue revealed a somewhat higher incidence of pathological changes in the liver and kidneys. There is evidence indicating that the warning properties of o-chlorostyrene do not permit workers to be aware of o-chlorostyrene concentrations of 100 ppm. Based on o-chlorostyrene's structural analogy to styrene, for which short-term exposures of 100 ppm have been demonstrated to produce neuropathic and narcotic effects (Stewart, Dodd, Baretta, and Schaffer 1968/Ex. 1-380), OSHA finds that a short-term limit is necessary. OSHA received no comments (other than NIOSH's) on this substance.

The final rule establishes a PEL of 50 ppm as an 8-hour TWA and a 15-minute STEL of 75 ppm for o-chlorostyrene. The Agency concludes that both of these limits will protect workers from the significant risks of liver and kidney damage, narcosis, and neuropathy to which they could potentially be exposed in the absence of any OSHA limit. OSHA finds that these health effects constitute material health impairments and that the TWA and STEL limits will substantially reduce these significant occupational risks.

CYCLOHEXANONE CAS: 108-94-1; Chemical Formula: C(6)H(10)O H.S. No. 1108

OSHA's former limit for cyclohexanone was 50 ppm as an 8-hour TWA. The Agency proposed to reduce this limit to 25 ppm and to add a skin notation for this substance. NIOSH (Ex. 8-47, Table N1) concurred with this proposed limit. The final rule establishes an 8-hour TWA PEL of 25 ppm and includes a skin notation. Both the ACGIH and NIOSH recommend a time-weighted average for cyclohexanone of 25 ppm, and the ACGIH also recommends a skin notation. Cyclohexanone is a white to pale yellow, oily liquid with an odor similar to that of acetone and peppermint.

Cyclohexanone has been studied in several experimental animal species. A concentration of 2000 ppm inhaled for four hours was lethal to one of six rats; at 4000 ppm, all of the exposed animals died. In rabbits, the dermal LD(50) was 1000 mg/kg (Smyth, Carpenter, Weil et al. 1969/Ex. 1-442). Rabbits showed marked irritation and some corneal injury when undiluted cyclohexanone was instilled in the eye (Carpenter and Smyth 1946/Ex. 1-859). Guinea pigs exposed to 4000 ppm for six hours showed narcotic symptoms, lacrimation, salivation, depression of body temperature and heart rate, and corneal opacity (Specht, Miller, Valaer, and Sayers 1940/Ex. 1-1179). Rabbits exhibited degenerative changes of the liver and kidneys after 50 daily six-hour inhalation exposures to 190 ppm (Treon, Crutchfield, and Kitzmiller 1943b/Ex. 1-394). Exposures to 309 ppm cyclohexanone on the same regimen caused conjunctival congestion, while exposures to 3000 ppm were lethal to some of the exposed animals (Treon, Crutchfield, and Kitzmiller 1943b/Ex. 1-394).

In humans, Nelson and co-workers (1943/Ex. 1-66) reported that irritation caused by exposure to cyclohexanone was intolerable at 50 ppm; however, 25 ppm was not objectionable to most subjects in three- to five-minute exposures (Nelson, Enge, Ross et al. 1943/Ex. 1-66).

OSHA is adding a skin notation for cyclohexanone based on this substance's ability to cause systemic toxicity through dermal absorption. L.H. Hecker, Director of Corporate Industrial Hygiene and Toxicology at Abbott Laboratories, commented that, in his opinion, there was no evidence for cyclohexanone's dermal toxicity, and thus that no skin notation was necessary (Ex. 3-678). However, OSHA has determined, based on a review of the evidence for this substance, that cyclohexanone has a dermal LD(50) of 1000 mg/kg in rabbits ( Dangerous Properties of Industrial Materials, 7th ed., p. 997, Sax and Lewis 1989). The Agency believes it appropriate to establish a skin notation for substances posing a percutaneous hazard, which OSHA is defining as any substance having a dermal LD(50) in rabbits of 1000 mg/kg or less. Accordingly, the Agency is including a skin notation for cyclohexanone in the final rule (see Section VI.C.18 for a full discussion of the Agency's policy on skin notations).

In the final rule, OSHA is establishing an 8-hour TWA for cyclohexanone of 25 ppm, with a skin notation. The Agency has determined that these limits will protect workers from the significant risks of liver and kidney damage, skin and respiratory-tract irritation, and percutaneous absorption associated with exposure to this substance. OSHA finds that skin and respiratory-tract irritation and liver and kidney damage all constitute material health impairments.

DIOXANE CAS: 123-91-1; Chemical Formula: O(CH(2)CH(2))(2)O H.S. No. 1145

OSHA's former PEL for dioxane was 100 ppm as an 8-hour TWA, with a skin notation. The Agency proposed a 25-ppm 8-hour TWA PEL for this substance, with retention of the skin notation; these limits, which are consistent with those of the ACGIH, are established in the final rule. NIOSH (Ex. 8-47, Table N6A) agreed with the selection of this PEL. Dioxane is a colorless liquid with an ethereal odor.

A two-year drinking water study conducted by the Dow Chemical Company (1972b, as cited in ACGIH 1986/Ex. 1-3, p. 217), in which male and female rats were given water containing 1.0, 0.1, or 0.01 percent dioxane, showed that animals given the highest dose developed liver and nasal tumors, in addition to pathological changes in the liver and kidney. Rats in the 0.1-percent group showed renal tubular sloughing and hepatocellular degeneration but no significant increase in neoplasms. Because this study demonstrated hepatoand nephrotoxic effects at doses 10 times lower than the dose causing cancer in animals, the permissible exposure limit has been set at a level that will prevent dioxane's liver and kidney effects. A study by Torkelson et al. (1974/Ex. 1-111) in four species of animals exposed to multiple daily airborne exposures of dioxane at 50 ppm showed no gross or histopatho-logic organ changes; this study demonstrates that the 25-ppm level should protect against the risk of liver and kidney effects in exposed workers. Dioxane has been shown in several studies to readily penetrate the skin of humans and animals and cause liver and kidney damage (NIOSH 1977n, p. 151, as cited in ACGIH 1986/Ex. 1-3, p. 218).

NIOSH (Ex. 8-47, Table N6A; Tr. 3-96 to 3-97) concurs with OSHA's exposure limit for dioxane, but notes its cancer potential. The AFL-CIO (Ex. 194, p. A12) also urged OSHA to designate dioxane as a carcinogen, as did the International Chemical Workers Union (Tr. 9-217 to 9-218). IARC (1987) has classified dioxane as a Group 2B (possible human) carcinogen based on a finding of sufficient evidence in animals. OSHA is aware of the emerging literature on dioxane's carcinogenic potential and intends to monitor this substance in the future.

Thomas Robinson, representing Vulcan Chemicals, stated that it was "most appropriate" for OSHA to adopt a TWA limit of 25 ppm for dioxane (Ex. 3-677), and the Halogenated Solvents Industry Alliance also supported OSHA's proposed PELs.

OSHA finds that the evidence for dioxane indicates that it is a liver and kidney toxin at levels substantially lower than those at which it produces a carcinogenic response. The Agency concludes that an 8-hour TWA of 25 ppm for dioxane, with a skin notation, is necessary to protect exposed workers against the significant risks of kidney and liver damage and cancer, all material health impairments that are associated with exposure at levels above the new PELs. OSHA has determined that the 25-ppm TWA limit will substantially reduce this risk.

ETHYLENE DICHLORIDE CAS: 107-06-2; Chemical Formula: ClCH(2)CH(2)Cl H.S. No. 1168

The former OSHA standard for ethylene dichloride (EDC) was 50 ppm as an 8-hour TWA, with a 100-ppm STEL (maximum duration of five minutes in any three hours) and a 200-ppm ceiling; these limits were derived from limits recommended by the American National Standards Institute in 1969. In 1980, the ACGIH reduced its TLV for ethylene dichloride to 10 ppm as an 8-hour TWA. NIOSH (1978q/Ex. 1-1120 and Ex. 8-47, Table N6A) has concluded that ethylene dichloride should be considered a potential human carcinogen and has recommended a 1-ppm TWA REL and a 2-ppm 15-minute short-term limit. OSHA proposed an 8-hour TWA of 1 ppm and a STEL of 2 ppm, and the final rule establishes these limits. Ethylene dichloride is a colorless liquid with an odor typical of the chlorinated hydrocarbons.

Several studies indicate that the former OSHA PELs are insufficient to protect workers against the hepatotoxic and carcinogenic effects of exposure to EDC. A paper by Kozik (1957/Ex. 1-182) reported that workers generally exposed to ethylene dichloride at levels of 10 to 15 ppm but occasionally exposed to levels of 40 ppm experienced increased morbidity, diseases of the liver and bile ducts, and nervous system effects. In addition, Brzozowski and associates (1954/ Ex. 1-63) reported abnormal changes in the blood of 50 percent of workers (8 of 16) exposed to EDC levels of 10 ppm and above (Brzozowski, Czajka, Dutkiewicz et al. 1954/Ex. 1-63).

Many commenters submitted information to the docket on ethylene dichloride (Exs. 3-624, 3-677, 3-678, 3-741, 3-874, 3-1174, 8-47, and 150). Most commenters were of the opinion that a permissible exposure limit of 10 ppm, rather than the proposed 1-ppm limit, would provide adequate protection against EDC's hepatoxic, central nervous system, and hematopoietic effects (Exs. 3-624, 3-677, 3-678, 3-741, 3-874, and 3-1174). Several of these participants also expressed concern about the feasibility of the 1-ppm limit (Exs. 3-624, 3-741, and 3-874). The comments of Richard Olson, representing the Dow Chemical Company, were typical of those of this group of commenters. According to Mr. Olson, OSHA's proposed limit was based on two outdated studies (Kozik 1957/Ex. 1-182 and Brzozowski, Czajka, Dutkiewicz et al. 1954/Ex. 1-63) that are incomplete, reflect outdated work practices, and present results that are based on effects caused by dermal as well as airborne exposures (Ex. 3-741, p. 52). The Chemical Manufacturers Association Ex. 3-874) pointed out that the jobs being performed by the workers monitored in the Brzozowski et al. (1954/Ex. 1-63) study are no longer permitted because EPA has prohibited the use of EDC as a fumigant (Ex. 3-874).

In response to these commenters, OSHA notes that there are many studies reporting serious EDC-related effects among workers exposed to airborne concentrations in the 10- to 15-ppm range. For example, the aircraft workers in the Kozik (1957/Ex. 1-182) study (average 8-hour TWA exposures of 10 to 15 ppm) experienced increased morbidity and lost more workdays than did non-EDC-exposed workers at the same factory. These workers experienced high rates of gastrointestinal disease and liver and gallbladder diseases; these symptoms and diseases are typical EDC exposure effects. Another study (Cetnarowicz 1959) examined refinery workers exposed to EDC at levels ranging from 10 to 200 ppm and found that these workers experienced many of the same symptoms as those seen in the aircraft workers. Clinical analyses confirmed that the liver and gastrointestinal tract were the principal target organs affected by EDC exposure. Rosenbaum (1947) also reported that EDC exposures below 25 ppm (not further specified) caused functional nervous system disorders, including headache, insomnia, and fatigue, and also slowed the heartbeat rate in affected workers.

OSHA finds the evidence presented in these studies consistent, biologically plausible, and convincing. Although specific exposure levels and precise industrial hygiene measurements are not available for some of these studies, the weight of the evidence presented demonstrates that occupational exposures to EDC at levels of 10 ppm or somewhat higher (i.e., in the 14- to 15-ppm range) cause severe health effects in specific target organ systems (i.e., the liver and gastrointestinal tract). The symptoms and signs of EDC's effects have been confirmed both clinically (palpitation of enlarged livers, X-ray evidence of pyloric spasms) and by laboratory analysis (elevated urobilinogen levels, positive Takata-Ara liver function tests, negative glucose tolerance tests). Thus, OSHA finds that EDC's hepatotoxic and gastrointestinal effects clearly warrant a reduction in the PEL to levels substantially below the level (10 ppm) shown to cause toxic liver and other effects. In response to the CMA, OSHA agrees that EPA's ban has eliminated the fumigant exposures described in the Brzozowski et al. (1954/Ex. 1-63) study, which involved concomitant dermal exposures. However, OSHA notes that the dermal LD(50) in rabbits is in the range of 2.8 to 4.9 g/kg, indicating that EDC is not readily absorbed through the skin in toxic quantities. OSHA therefore finds that, although dermal exposure undoubtedly contributed somewhat to the toxic effects seen in the workers in the Brzozowski et al. (1954/ Ex. 1-63) study, airborne exposure was the predominant contributor to these effects.

Some commenters also took issue with OSHA's reference in the proposal to EDC's carcinogenicity. According to these commenters (Exs. 3-677, 3-741, and 3-874), because the NCI bioassay (1978d/Ex. 1-947) in mice and rats involved the use of corn oil as a vehicle, carcinogenic responses may have been enhanced. In addition, because EDC gavage produced greater amounts of the potentially genotoxic glutathione conjugate than did equivalent inhalation doses of EDC, these commenters believe that route of administration may play a critical role in the carcinogenicity of EDC, and thus, that occupational exposures, which are predominantly via inhalation, may not be carcinogenic.

OSHA is aware that inhalation bioassays of EDC did not produce a statistically significant increase in tumors in rats or mice. However, the NCI gavage study (1978d/Ex. 1-947) was positive in rats and mice, and intraperitoneal administration of EDC produced an elevated increase in lung adenomas in strain A mice (Health Assessment Document (HAD) for 1,2-Dichloroethane (Ethylene Dichloride), EPA/600/8-84/006F, p. 1-5, EPA 1985a). Dermal application caused a statistically significant increase in benign lung tumors in mice, although this route did not cause a significant increase in skin tumors. EPA (1985a) concludes that the direct and supporting evidence for the carcinogenicity of EDC includes:
(1) Multiple tumor types in oral bioassays in two species;

(2) Suggestive evidence in two other animal bioassays;

(3) Demonstrated evidence of reactive metabolites and formation of a DNA adduct; and

(4) Evidence that EDC is also a mutagen (EPA 1985a, p. 1-5). In posthearing comments, NIOSH (Ex. 150, Comments on Ethylene Dichloride) emphasized that the NCI bioassay (NCI 1978d/Ex. 1-947) demonstrated EDC-induced lung neoplasms and lymph system cancers in mice of both sexes, liver cancer in males, and mammary and uterine cancers in females. The AFL-CIO also emphasized EDC's carcinogeneity (Ex. 194). In rats, it produced cancers of the forestomach in males, mammary neoplasms in females, and hemangiosarcomas in animals of both sexes. NIOSH (Ex. 150, Comments on Ethylene Dichloride) concluded its comments by quoting the summary of the IARC (1979b, as cited in Ex. 150) monograph on EDC:
There is sufficient evidence that ethylene dichloride is carcinogenic in mice and rats. In the absence of adequate data in humans, it is reasonable for practical purposes to regard ethylene dichloride as if it presented a carcinogenic risk to humans.

In regard to the technological feasibility of achieving a 1-ppm limit for EDC, the Chemical Manufacturers Association (CMA) states that:

uniform compliance with the proposed PEL will not be achieved. Manufacturing operations appear to be able to meet a 10-ppm, 8-hour TWA PEL for many routine operations. However, maintenance tasks, sampling, and loading operations will have difficulty meeting a 10-ppm PEL (Ex. 3-874, p. 3).

Both the Vinyl Institute (Ex. 3-624) and the Dow Chemical Company (Ex. 3-741) share the CMA's view on the feasibility of achieving the 1-ppm limit. However, OSHA notes that ethylene dichloride is manufactured and used in closed systems (Ex. 3-874) and that 90 percent of all EDC produced in this country is used captively by the producers themselves (84 percent of all EDC produced in the United States is used to make vinyl chloride monomer) (EPA 1985a, p. 1-1). Emissions from closed systems, which include fugitive emissions from process equipment such as pumps, seals, and flanges; emissions during process sampling; emissions during loading operations; and emissions during maintenance operations, are all readily amenable to control through the use of engineering methods or improved work practices. For example, implementation of a rigorous schedule of manual leak detection and repair, the use of sampling bombs or ventilated sampling ports, the use of loading arms for closed-hatch loading of EDC into railcars and tank trucks, installation of vapor return lines or vapor recovery systems on loading docks, and installation of improved maintenance procedures are all inexpensive and effective methods of controlling fugitive emissions from process machinery. In addition, because of the intermittent, nonroutine, and varied nature of maintenance operations, OSHA typically permits the use of respirators during the performance of maintenance tasks. OSHA is also cognizant of the potential for feasibility problems in loading and sampling operations. The Agency will consider the use of respirators for these operations on a case-by-case basis or, as appropriate, on a sector-by-sector basis. However, OSHA finds that EDC producers will generally be able to achieve the 1-ppm 8-hour TWA and the 2-ppm short-term limit by using readily available control technologies and implementing additional work practices.

The Agency concludes that an 8-hour TWA of 1 ppm and a 15-minute STEL of 2 ppm are necessary to protect workers against the significant risks of liver damage, gastrointestinal toxicity, and cancer, all material health impairments that are associated with exposure to ethylene dichloride. OSHA further concludes that the revised limits will substantially reduce these significant occupational risks.

HYDRAZINE CAS: 302-01-2; Chemical Formula: H(2)N - NH(2) H.S. No. 1205

The former OSHA limit for hydrazine was 1 ppm as an 8-hour TWA, with a skin notation. OSHA proposed an 8-hour TWA PEL of 0.1 ppm, also with a skin notation, and the final rule establishes this limit. Hydrazine is an odorless, fuming, oily liquid with an ammonia-like odor. Because of hydrazine's potential carcinogenic hazard, NIOSH (1978e/Ex. 1-263; Ex. 8-47) has recommended that workplace exposures to hydrazine not exceed 0.03 ppm, as determined by a two-hour air sample; this level represents the lowest detectable concentration over this sampling period.

A hepatotoxic response in mice and anemia and weight loss in dogs were reported to occur following a six-month exposure to 1 ppm of hydrazine for six hours per day, five days per week, or to 0.2 ppm continuously (Haun and Kinkead 1973/Ex. 1-824). The ACGIH has assigned an A2 designation (suspect human carcinogen) to hydrazine, based on a study by MacEwen, Vernot, and Haun (1979/Ex. 1-193) showing significant increases in nasal tumors in rats exposed to 1 or 5 ppm hydrazine, in thyroid adenocarcinomas in rats exposed to 5 ppm, and in lung adenomas among mice exposed to 1 ppm. NIOSH (1978e/Ex. 1-263) cites studies that demonstrate the carcinogenicity of hydrazine in rodents by a variety of dose routes. NIOSH (Ex. 8-47, Table N6B) believes that hydrazine should be labelled a potential occupational carcinogen. Based on sufficient evidence of hydrazine's carcinogenicity in animals, IARC (1987) classified hydrazine as a Group 2B (possible human) carcinogen.

The animal studies conducted by Haun and Kinkead (1973/ Ex. 1-824) and by MacEwen, Vernot, and Haun (1979/Ex. 1-193) clearly demonstrate that exposure to hydrazine at the former 1-ppm PEL presents a significant risk of respiratory cancer, liver disease, and adverse blood effects; animals exposed to airborne concentrations at this level have exhibited all of these responses. Reported dermal LD(50)s in rabbits and dogs were 91 and 90 mg/kg, respectively, showing that hydrazine can readily penetrate the skin and cause systemic effects.

Some commenters (Ex. 8-16, 194, Tr. 9-218; Tr. 3-309) misunderstood the classification scheme used by OSHA to group substances in the proposal and commented that, in their opinion, hydrazine should have been classified as a carcinogen rather than a hepatotoxin. However, as discussed in other sections of the preamble, OSHA did not intend this classification scheme to have regulatory implications but to facilitate generic rulemaking. OSHA's approach was to classify substances in accordance with the health effect on which the ACGIH has based its TLV. In response to the American Industrial Hygiene Association's question about a risk assessment for hydrazine, OSHA notes that, in this rulemaking, OSHA has performed risk assessments only for some of the substances classified in Section VI.C.15 of the preamble.

The Agency is establishing an 8-hour TWA PEL of 0.1 ppm, with a skin notation, for hydrazine. OSHA concludes that this limit will substantially reduce the significant risks of cancer, liver disease, and hematopoietic effects, all clearly material impairments of health, that have been demonstrated to occur in animals at exposures above the revised PEL.

METHYLCYCLOHEXANOL CAS: 25639-42-3; Chemical Formula: CH(3)C(6)H(10)OH H.S. No. 1269

OSHA formerly had an 8-hour TWA limit of 100 ppm for methylcyclohexanol. The Agency proposed a limit of 50 ppm TWA for this substance, and is establishing this limit in the final rule. NIOSH (Ex. 8-47, Table N1) concurred with OSHA's proposed limits for methylcyclohexanol. Methylcyclohexanol is a colorless, viscous liquid with an aromatic odor, and usually exists as a mixture of isomers in which the meta and para forms predominate.

Exposure to methylcyclohexanol produces liver and kidney impairment, narcotic effects, and eye and respiratory irritation. Treon, Crutchfield, and Kitzmiller (1943a/ Ex. 1-393) have reported the oral LD(50) in rabbits to be between 1.25 and 2 g/kg; liver damage was observed in surviving animals. Repeated inhalation exposures to the vapor caused salivation, eye irritation, and lethargy in rabbits exposed at 500 ppm, but exposures to 230 ppm caused no observable effects. Fifty 6-hour exposures at a level of 120 ppm caused microscopic changes in the liver and kidney tissue of rabbits (Treon, Crutchfield, and Kitzmiller 1943b/Ex. 1-394).

In humans, headaches and eye and respiratory irritation have been reported to occur following prolonged exposures to high concentrations of methylcyclohexanol (Fillipi 1914, as cited in ACGIH 1986/Ex. 1-3, p. 385). Smyth (1956/Ex. 1-759) considered an exposure limit of 100 ppm to be sufficiently low to prevent narcotic effects and, perhaps, significant liver or kidney damage. OSHA received no comments (other than NIOSH's) on this substance.

The Agency is establishing an 8-hour TWA of 50 ppm for methylcyclohexanol. OSHA concludes that this limit will protect workers against the significant risks of hepatic and renal damage and narcosis, which constitute material health impairments and are associated with exposures to this substance at levels above the revised PEL. The Agency finds that the revised limit will substantially reduce these risks.

OCTACHLORONAPHTHALENE CAS: 2234-13-1; Chemical Formula: C(10)Cl(8) H.S. No. 1295

OSHA formerly had a limit of 0.1 mg/m(3) TWA, with a skin notation, for octachloronaphthalene. The Agency proposed to obtain the 8-hour TWA and to add a STEL of 0.3 mg/m(3), also with a skin notation, for this substance, and NIOSH (Ex. 8-47, Table N1) concurred. These limits are established in the final rule. Octachloronaphthalene is a nonflammable, pale yellow, waxy solid containing 70 percent chlorine.

Inhalation toxicity data for octachloronaphthalene fumes or dust are lacking, but exposure to the chloronaphthalenes causes acne-like lesions that itch severely. Repeated exposures to the fumes of molten chlorinated naphthalenes can cause severe and sometimes fatal systemic poisoning and are especially damaging to the liver (Patty 1963g/Ex. 1-845). Ingestion studies of cattle have shown different toxicities for different naphthalenes, with toxicity increasing with the compound's degree of chlorination (Sikes, Wise, and Bridges 1952/Ex. 1-804). However, these data are controverted by another report in which octachloronaphthalene was found to be less toxic than the hexachloro derivative (Bell 1953/Ex. 1-951). This divergence in the data may be due to differing methods of administration (suspension versus solution), or may reflect the soluble form's greater capacity for absorption (ACGIH 1986/ Ex. 1-3, p. 447). NIOSH was the only submitter of comments specifically relating to octachloronaphthalene.

In the final rule, OSHA is retaining the 8-hour TWA PEL of 0.1 mg/m(3) and adding a STEL of 0.3 mg/m(3), with a skin notation, for octachloronaphthalene. The Agency concludes that this combined limit will protect workers against the significant risks of serious liver damage and dermal lesions, which constitute material health impairments and are associated with exposure to this substance at the elevated levels permitted by an 8-hour limit alone. The skin notation is retained because of octachloronaphthalene's demonstrated ability to cause systemic toxicity by percutaneous absorption.

PROPYLENE DICHLORIDE CAS: 78-87-5; Chemical Formula: CH(3)CHClCH(2)Cl H.S. No. 1341

OSHA's former limit for propylene dichloride was 75 ppm as an 8-hour TWA. The proposal retained the 75-ppm TWA and added a STEL of 110 ppm, and these are the limits being promulgated in the final rule. Propylene dichloride is a colorless, flammable, mobile liquid with an odor like that of chloroform.

The primary hazards associated with exposure to propylene dichloride are inhalation-induced toxicity to liver tissue and skin and eye irritation. Repeated inhalation exposures to 1000 ppm have been reported to kill dogs (after 24 exposures), guinea pigs (after 22 exposures), and rats (in some cases after only seven exposures); however, some animals survived more than 100 seven-hour exposures. Necropsy showed severe liver damage; the hepatotoxicity of propylene dichloride appears to be greater than that of carbon tetrachloride and less than that of ethylene dichloride (Heppel, Neal, Highman, and Porterfield 1946/Ex. 1-510). Animals of these same species (rats, dogs, and guinea pigs) survived 128 to 140 seven-hour exposures to 400 ppm propylene dichloride for five days/week without histologic effects, while mice died from similar exposures; surviving mice displayed hepatomas (Heppel, Highman, and Peake 1948/Ex. 1-605). The oral LD(50) for rats has been reported as 1.19 ml/kg (Smyth, Carpenter, Weil et al. 1969/Ex. 1-442); the acute 8-hour inhalation LC(50) for rats is 3000 ppm (Pozzani, Weil, and Carpenter 1959/Ex. 1-608). NIOSH (Ex. 150A, Comments on Propylene Dichloride) noted that an NTP (1986c) bioassay showed some evidence that propylene dichloride was carcinogenic in mice and caused an increased incidence of hepatocellular adenomas; NIOSH indicated (Ex. 8-47, Table N6B) that a separate 6(b) rulemaking might be appropriate for this substance. The finding of tumors was not reproduced in rats, in that female rats showed only a marginally increased incidence of mammary adenocarcinomas, and male rats showed no response. NIOSH was the only commenter on propylene dichloride.

In the final rule, OSHA is retaining the 8-hour TWA PEL for propylene dichloride of 75 ppm and adding a 15-minute STEL of 110 ppm. The Agency concludes that this combined limit will protect workers against the significant risks of serious hepatotoxic effects, which constitute material impairments of health, that are associated with exposures at the elevated levels permitted by the absence of a short-term limit. OSHA finds that the TWA and short-term PELs will act together to reduce this risk substantially.

1,1,2,2-TETRACHLOROETHANE CAS: 79-34-5; Chemical Formula: CHCl(2)CHCL(2) H.S. No. 1385

OSHA's former PEL for 1,1,2,2-tetrachloroethane was 5 ppm as an 8-hour TWA, with a skin notation; a 1-ppm 8-hour TWA, also with a skin notation, was the level proposed by OSHA. NIOSH considers 1,1,2,2-tetrachloroethane to be a potential carcinogen but concurred with the limit proposed (Ex. 8-47, Table N6A). The final rule establishes a PEL of 1 ppm TWA and retains the skin notation for this colorless, nonflammable, heavy, mobile liquid with a sweet, chloroform-like odor.

One study by Jeney, Bartha, Kondor, and Szendrei (1957, as cited in ACGIH 1986/Ex. 1-3, p. 561) revealed identifiably adverse effects on the liver, including hepatitis, in humans exposed to concentrations of tetrachloroethane ranging from 1.5 to 247 ppm; liver damage was still evident after exposures were reduced to 15 ppm. An animal study by Schmidt, Binnewies, Gohlke, and Rothe (1972/Ex. 1-222) found "barely detectable" fatty infiltration of the liver in rats exposed to 2 ppm tetrachloroethane for 11 months.

The ACGIH (1986/Ex. 1-3, p. 561) cites some early studies that show that tetrachloroethane penetrates human skin; one fatality has been attributed to excess skin absorption. The New Jersey Department of Public Health (Ex. 144) urged OSHA to set the PEL for this substance on the basis of EPA's IRIS data. The use of IRIS data is discussed in Section VI.A.

Based on this evidence, OSHA concludes that the former permissible exposure limit does not protect exposed workers against fatty infiltration of the liver or against more serious liver damage; these health consequences clearly constitute material health impairments and thus pose a significant occupational risk. OSHA finds that reducing the 8-hour TWA for 1,1,2,2-tetrachloroethane to 1 ppm will substantially reduce this significant risk, and in the final rule, OSHA is therefore establishing a 1-ppm 8-hour TWA, with a skin notation, for 1,1,2,2-tetrachloroethane.

1,2,3-TRICHLOROPROPANE CAS: 96-18-4; Chemical Formula: CH(2)ClCHClCH(2)Cl H.S. No. 1407

OSHA's former PEL for 1,2,3-trichloropropane was 50 ppm as an 8-hour TWA, and the proposed limit was a 10-ppm TWA with a skin notation. NIOSH (Ex. 8-47, Table N6A) concurred with the proposed limit but indicated that it considers this substance to be a potential human carcinogen. The final rule establishes the 10-ppm TWA but does not include a skin notation. 1,2,3-Tri-chloropropane is a colorless to straw-colored, combustible liquid with an odor similar to that of chloroform.

1,2,3-Trichloropropane is not irritating to intact skin; it is also not readily absorbed through the skin. The dermal LD(50) in rabbits is 1770 mg/kg (Dangerous Properties of Industrial Materials, 7th ed., p. 173, Sax and Lewis 1989). However, 1,2,3-trichloropropane is highly irritating to the eyes (Smyth, Carpenter, Weil et al. 1962/Ex. 1-441). Five of six rats exposed to 1000 ppm died after four-hour exposures. Rats and guinea pigs exposed at 800, 2100, or 5000 ppm for 30 minutes showed central nervous system depression, which progressed, at the higher exposure levels, to narcosis and convulsions (Lewis 1979, as cited in ACGIH 1986/Ex. 1-3, p. 601). Several mice exposed for 20 minutes to 5000 ppm died, some as long as several days later, from liver damage. Daily 10-minute exposures at 2500 ppm for 10 days killed 7 of 10 mice (McOmie and Barnes 1949, as cited in ACGIH 1986/Ex. 1-3, p. 601). Animals exposed once for four hours to 1,2,3-trichloropropane at concentrations of 125, 340, 700, or 2150 ppm showed dose-related signs of irritation, which included, at 700 or 2150 ppm, labored respiration, inactivity, and eye and nose irritation; at autopsy, however, no organ or other damage was apparent (McOmie and Barnes 1949, as cited in ACGIH 1986/Ex. 1-3, p. 601).

Drew, Patel, and Lin (1978/Ex. 1-313) noted changes in liver enzymes after a single four-hour exposure to 500 ppm, and Russian studies indicate that morphologic changes and metabolic lesions of the liver, kidney, and lungs occurred in mice exposed continuously to 1,2,3-trichloropropane concentrations of 0.007 to 0.3 ppm (Sidorenko, Tsulaya, Bonashevskaya, and Shaipak 1979/Ex. 1-669; Sidorenko, Tsulaya, Koreneveskaya, and Bonashevskaya 1976/Ex. 1-668; Tsulaya, Bonashevskaya, Zykova et al. 1977/Ex. 1-450).

A National Toxicology Program (NTP) prechronic study, in which rats were gavaged daily with 1,2,3-trichloropropane at 8, 16, 32, 63, 125, and 250 mg/kg body weight for 120 days, showed good survival in all but the highest dose group (NTP 1983a, as cited in ACGIH 1986/Ex. 1-3, p. 602). Statistically significant changes in the liver and kidneys, as well as necrosis and irritation of the nasal passages, occurred in the 63- and 125-mg/kg dose groups. Decreases in red blood cell counts and hematocrits were also seen, even in the 16-mg/kg dose group. 1,2,3-Trichloropropane did not affect testicular weight, sperm count, or morphology. The NTP found this substance to be genetically active in three bioassays. Hardin, Bond, Sikov et al. (1981/Ex. 1-699) did not find 1,2,3-trichloropropane to be fetotoxic or teratogenic.

Human volunteers found exposure to 1,2,3-trichloropropane objectionable because of eye and upper respiratory tract irritation, and many found 50 ppm an unacceptable level for a full-shift exposure (Silverman, Schulte, and First 1946/Ex. 1-142).

The Agency has determined that 1,2,3-trichloropropane's dermal toxicity is not such as to warrant a skin notation; OSHA's reasoning in regard to skin notations is discussed in Section VI.C.18 of this preamble.

In the final rule, OSHA is establishing an 8-hour PEL of 10 ppm for 1,2,3-trichloropropane. The Agency concludes that the 10-ppm 8-hour TWA limit is necessary to protect workers against the significant risks of liver and kidney damage and eye and throat irritation, all of which constitute material health impairments that are potentially associated with exposures to this substance at levels above the revised PEL.

Kidney Toxicity

Introduction

Kidney damage is the basis for revising the PELs for five of the compounds in this group. These compounds, their CAS and HS numbers, and their former, proposed, and final rule PELs, are shown in Table C4-2. Three of these substances will be regulated by OSHA for the first time, and in the other two cases, the 8-hour TWA will be reduced. In one of the latter cases, a STEL will also be added.

Description of the Health Effects

The precise mechanism by which these chemicals damage the kidneys is unknown. Typically, these compounds are selectively toxic to cells in the renal tubules, perhaps because impaired transport causes the chemical to collect in these cells. In addition to its function in the excretion of wastes, the kidney plays an important role in the regulation of total body homeostasis. This organ regulates extracellular volume, controls electrolyte and acid-base balance, and forms several hormones that control systemic metabolism. Depending on their particular site of action, nephrotoxicants can interfere with hydration, the proper excretion of the body's wastes, electrolytic balance, metabolism, or the maintenance of correct acid-base balances.

Like the hepatotoxic effects previously described, the least severe lesions caused by nephrotoxic compounds are graded and reversible. The earliest changes are usually alterations in the activities of specific enzymes in the tubular cells. These changes may be accompanied by minor morphological alterations of the cells that are visible only with an electron microscope. Higher doses or more sustained exposures are required to cause cellular necrosis that might be visible with light microscopy. Because of the reserve capacity of the kidneys, a significant degree of tubular cell necrosis must occur before it is reflected by measurable alterations in kidney function. Thus, indicators of impaired renal function that can be measured in humans, such as proteinuria, glucosuria, and increased BUN, are relatively insensitive indicators of kidney damage. Other indicators of significant kidney damage include increased kidney weight, swelling of the tubular epithelium, fatty degeneration of tubular epithelium, and the presence of tubular casts in the urine.

Dose-Response Characteristics

Kidney damage, like liver damage, is progressive; only at the earlier stages are nephrotoxic effects reversible. With continued exposure, the damage becomes more extensive, until it reaches the point at which it cannot be repaired. The toxicity of the kidney-damaging chemicals included in this group also increases as dose increases. For most nephrotoxins, there appears to be a NOEL. Workplace exposures to concentrations of these substances at levels at or below the revised limits are unlikely to cause kidney effects in most workers. OSHA has determined that the nephrotoxic risks being protected against are significant at the former PELs; kidney damage constitutes a material health impairment within the meaning of the Act.

1,3-DICHLOROPROPENE CAS: 542-75-6; CHEMICAL FORMULA: CHCl=CH-CH(2)Cl H.S. No. 1129

OSHA formerly had no limit for 1,3-dichloropropene. The Agency proposed an 8-hour TWA of 1 ppm, with a skin notation, for this straw-colored, clear liquid with a chloroform-like odor. NIOSH (Ex. 8-47, Table N6A) concurred with the proposed limit, which is established in the final rule. This compound occurs in two forms: cis- and trans-isomers.

In male and female rats, the acute oral LD(50)s for a 92-percent mixture of the cis- and trans-isomers of 1,3-dichloropropene were 713 and 470 mg/kg, respectively; postmortem examination showed liver and kidney damage and evidence of possible lung injury (Torkelson and Oyen 1977/Ex. 1-532). The dermal LD(50) in rabbits for a 92-percent undiluted mixture was 504 mg/kg, but a 10-percent solution administered by gavage at a dose of 125 or 250 mg/kg was lethal to some of the animals (Torkelson and Oyen 1977/Ex. 1-532). Contact with the liquid was irritating to the eyes and skin of rabbits (Torkelson and Oyen 1977/Ex. 1-532).

Inhalation exposures to 1,3-dichloropropene vapor concentrations above 2700 ppm produced eye and nasal irritation and severe lung, nasal, kidney, and liver damage in rats (Torkelson and Oyen 1977/Ex. 1-532). Exposure to 1000 ppm caused eye and nasal irritation, lacrimation, and, if prolonged, unconsciousness; rats exposed to 1000 ppm for two hours died, but those exposed for one hour survived (Torkelson and Oyen 1977/Ex. 1-532). Guinea pigs exposed to 400 ppm for a single seven-hour period died, while rats exposed similarly survived but had obvious lung congestion (Torkelson and Oyen 1977/Ex. 1-532). Rats, rabbits, guinea pigs, and dogs were exposed seven hours/day, five days/week for six months to 1-ppm or 3-ppm concentrations of 1,3-dichloropropene (Torkelson and Oyen 1977/Ex. 1-532). No adverse effects were observed in any of the animals exposed at 1 ppm. Of the animals exposed at 3 ppm, only male rats showed adverse effects; these animals had reversible cloudy swelling of the renal tubular epithelium (Torkelson and Oyen 1977/Ex. 1-532).

In humans, acute exposures to 1,3-dichloropropene cause skin, eye, and respiratory irritation (Torkelson and Oyen 1977/Ex. 1-532). There are no data on the effects in humans of chronic exposure to this substance. NIOSH (Ex. 8-47, Table N6A; Tr. 3-96 to 3-97) concurs with the limits being established by OSHA but notes that 1,3-dichloropropane could be classified as a potential occupational carcinogen. The new Jersey Department of Public Health urged OSHA to derive a PEL for this substance based on EPA's IRIS data. The use of such data is discussed in Section VI.A.

OSHA is establishing an 8-hour TWA limit of 1 ppm, with a skin notation, for 1,3-dichloropropene. The Agency concludes that this limit will protect workers against the significant risks of eye and mucous membrane irritation and lung, kidney, and liver damage, all of which constitute material health impairments that are associated with exposure to this substance. A skin notation is established to protect against 1,3-dichloropropene's ability to cause systemic toxicity when absorbed through the skin.

DICYCLOPENTADIENE CAS: 77-73-6; Chemical Formula: C(10)H(12) H.S. No. 1132

OSHA had no former limit for dicyclopentadiene (DCPD); the proposed limit was a TWA of 5 ppm, and NIOSH (Ex. 8-47, Table N1) concurred with this limit. The final rule establishes a 5-ppm 8-hour TWA PEL for this substance, which is consistent with the ACGIH's limit. DCPD is a solid at room temperature and has a disagreeable odor.

The health effects associated with exposure to DCPD include mild eye, skin, and respiratory irritation, as well as renal damage and possible pulmonary damage. By the oral and intraperitoneal routes, DCPD is extremely toxic, with an oral LD(50) value of 0.35 ml/kg and an intraperitoneal LD(50) value of 0.31 ml/kg in rats; rat fatalities occurred within 60 minutes of exposure to an unspecified concentration of the saturated vapor (Kinkead, Pozzani, Geary, and Carpenter 1971/Ex. 1-606). However, Gage (1970/Ex. 1-508) regards approximately 660 ppm as the 4-hour LC(50) in rats and reports that 10 six-hour daily exposures to DCPD at a concentration of 250 ppm were survived only by three of four rats; when the animals were subjected to a concentration of 100 ppm for 15 similar exposures, all survived (Gage 1970/Ex. 1-318). Although other species were less susceptible than mice to the effects of DCPD exposure, they exhibited eye irritation, incoordination, and convulsions preceding death (Kinkead, Pozzani, Geary, and Carpenter 1971/Ex. 1-606).

Kinkead and associates (1971/Ex. 1-606) report that rats exposed repeatedly for 10 days survived concentrations of 72 or 146 ppm but succumbed at the 332-ppm level, with convulsions, lung hemorrhage, and blood in the intestines; female rats also suffered hemorrhage of the thymus. Mice similarly exposed succumbed at all three concentration levels (Kinkead, Pozzani, Geary, and Carpenter 1971/Ex. 1-606). Chronic exposures of seven hours/day for 89 days produced kidney damage and some pulmonary effects in rats exposed at levels of 35 and 74 ppm; the no-effect level for these endpoints in rats was determined to be below 19.7 ppm. Dogs exposed at concentrations of 9, 23, or 32 ppm on the same regimen exhibited only minimal effects (Kinkead, Pozzani, Geary, and Carpenter 1971/Ex. 1-606).

Human sensory response tests resulted in findings of mild eye and throat irritation within seven minutes' exposure to 1 ppm DCPD vapor, and of olfactory fatigue within 24 minutes; a 30-minute exposure to 5.5 ppm produced no olfactory fatigue (ACGIH 1986/Ex. 1-3, p. 194). Subjective complaints of headache during the first two months of occupational exposure disappeared during the following three months of exposure, suggesting a developed tolerance for this substance (ACGIH 1986/Ex. 1-3, p. 194). No comments (other than NIOSH's) on this substance were received.

OSHA is establishing an 8-hour TWA PEL of 5 ppm TWA for dicyclopentadiene. The Agency concludes that this limit will protect workers against the significant risks of kidney injury, pulmonary effects, and irritation, which constitute material health impairments that are associated with workplace exposure to DCPD at levels above the new PEL.

ETHYL SILICATE CAS: 78-10-4; Chemical Formula: Si(OC(2)H(5))(4) H.S. No. 1166

OSHA's former permissible exposure limit for ethyl silicate was 100 ppm as an 8-hour TWA. The proposal included a limit of 10 ppm TWA for this colorless, flammable liquid with a faint odor; NIOSH (Ex. 8-47, Table N1) agreed with the selection of this limit. In the final rule, a PEL of 10 ppm is established for ethyl silicate; this limit is consistent with that of the ACGIH.

Ethyl silicate has been reported to cause both irritation and systemic toxicity. In guinea pigs and rats, a 60-minute exposure of 2000 ppm was reported as the maximal duration/concentration that did not cause serious disturbances; 500 ppm was the maximal no-effect exposure level for an exposure of several hours' duration (Smyth and Seaton 1940b/Ex. 1-376). Thirty-day exposures to 400 ppm ethyl silicate for seven hours/day caused significant mortality in rats and damage to the lungs, liver, and kidney in the surviving animals. Exposures of rats, guinea pigs, and mice to 88, 50, or 23 ppm for 90 days (seven hours/day, five days/week) resulted only in decreased kidney weights in mice exposed at the 88-ppm level (Pozzani and Carpenter 1951/Ex. 1-166). In another study, Kasper, McCord, and Fredrick (1937/Ex. 1-1155) showed that animals exposed to 164 ppm ethyl silicate for 17 eight-hour days showed less weight gain than did controls. Rowe and associates (1948/Ex. 1-359) reported that three 7-hour exposures at 1000 ppm were fatal to 4 of 10 rats; similar exposures to 500 ppm caused pronounced kidney changes and slight lung irritation. Four to 10 similar exposures at 250 ppm caused slow weight loss and some lung and renal changes; at 125 ppm, slight to moderate kidney damage was observed (Rowe, Spencer, and Bass 1948/Ex. 1-359). Smyth and Seaton (1940b/Ex. 1-376) reported that exposure to a concentration of 1200 ppm causes lacrimation in humans and that 250 ppm causes eye and nose irritation. Only NIOSH submitted comments to the rulemaking record on ethyl silicate.

OSHA is establishing a PEL for ethyl silicate of 10 ppm as an 8-hour TWA. The Agency concludes that this limit is required to protect workers from the significant risk of renal damage, which constitutes material health impairment, that is associated with exposures to this substance at concentrations above the revised PEL. OSHA finds that this reduced limit will substantially reduce this risk.

HEXACHLOROBUTADIENE CAS: 87-68-3; Chemical Formula: CCl(2)=CCl-CCl=CCl(2) H.S. No. 1195

OSHA had no former limit for hexachlorobutadiene (HCBD); the proposal included a PEL of 0.02 ppm and a skin notation for this substance. NIOSH (Ex. 8-47, Table N6A) supported the selection of this limit. The ACGIH recommends a TLV-TWA of 0.02 ppm with a skin notation and classifies this substance as a suspected human carcinogen (A2). The final rule establishes an 8-hour TWA of 0.02 ppm but does not include a skin notation. Hexachlorobutadiene is a heavy, clear liquid.

Hexachlorobutadiene has a moderate-to-high acute oral toxicity. The LD(50)s reported for mice, rats, and guinea pigs are 87, 350, and 90 mg/kg, respectively (Murzakev 1963, as cited in ACGIH 1986/Ex. 1-3, p. 298). Gul'ko and co-workers (1964/Ex. 1-1082) reported LD(50) values of 116 mg/kg for mice and 270 mg/kg for rats (Gul'ko, Zimina, and Shroit 1964/Ex. 1-1082). The dermal LD(50) in rabbits is 1211 kg/mg (Dangerous Properties of Industrial Materials, 6th ed., p. 2145, Sax 1984). A single exposure of 133 to 150 ppm via inhalation has been fatal in rats when the exposure lasts for four to seven hours. All rats survived exposures at 161 ppm for 0.88 hour or 34 ppm for 3.3 hours; similar exposure of guinea pigs and cats to the same concentrations resulted in the death of most animals (Kociba, Schwetz, Keyes et al. 1977/Ex. 1-494). Another inhalation study in rats showed eye and nose irritation, respiratory difficulty, and damage to kidney tissue and the adrenal cortex after two 4-hour exposures at 250 ppm; twelve 6-hour exposures to 100 ppm caused eye and nose irritation, respiratory difficulty, weight loss, anemia in the female animals, and kidney and adrenal damage; fifteen 6-hour exposures at 25 ppm caused retarded weight gain in females, respiratory difficulty, and kidney damage; fifteen 6-hour exposures at 10 ppm caused retarded weight gain in females but no systemic injury; and fifteen 6-hour exposures at 5 ppm resulted in no adverse effects (Gage 1970/Ex. 1-318).

Reproductive studies in male and female rats demonstrated multiple toxicological effects, including kidney damage in both sexes and increased liver weight in males, at the high-dose level of 20 mg/kg/day. Dietary administration of 20, 2, or 0.2 mg/kg daily had no effect on conception percentages, gestational survival, neonatal survival, neonatal sex ratios, neonatal morphology, or neonatal body weights (except for the high-dose neonates) (Schwetz, Smith, Humiston et al. 1977/ Ex. 1-368). Results of lifetime dietary studies suggest that the no-effect level for hexachlorobutadiene in rats is 0.2 mg/kg/day, that a clear dose-response relationship exists for HCBD-induced toxicity affecting primarily the kidney, and that carcinogenic effects (i.e., renal neoplasms) result from ingestion of 20 mg/kg/day (Kociba, Schwetz, Keyes et al. 1977/Ex. 1-494). These authors also reported that HCBD-induced neoplasms occur only at HCBD doses higher than those causing discernible renal injury. The ACGIH states that "HCBD would seem to qualify as a carcinogen of intermediate potency" (ACGIH 1986/Ex. 1-3, p. 299). NIOSH (Ex. 8-47, Table N6A) concurs with the limit being established by OSHA and notes that this substance could be classified as a potential occupational carcinogen.

OSHA is not including a skin notation in the final rule. This decision is based on the Agency's policy in the matter of skin notations (see Section VI.C.18 of the preamble for a discussion of this issue). OSHA is establishing an 8-hour TWA limit of 0.02 ppm for this hazardous substance. Assuming a 10-m 3 per day breathing volume per 8-hour workshift and a 70-kg body weight for humans, this limit corresponds to a daily hexachlorobutadiene intake of approximately 0.03 mg/kg, which is about 10 times below the observed no-effect level in rats fed hexachlorobutadiene. The Agency concludes that this 0.02-ppm limit will protect workers exposed to HCBD from the significant risks of kidney damage; eye, skin, and pulmonary irritation; and renal neoplasms, all of which constitute material health impairments that are associated with exposure to HCBD at levels above the new limit.

HEXONE (METHYL ISOBUTYL KETONE) CAS: 108-10-1; CHEMICAL FORMULA: CH(3)COCH(2)CH(CH(3))(2) H.S. No. 1203

OSHA's former 8-hour TWA limit for hexone (methyl isobutyl ketone), or MIBK, was 100 ppm. The ACGIH has established a TLV-TWA of 50 ppm and a 15-minute STEL of 75 ppm for this substance. NIOSH recommends a TWA of 50 ppm for MIBK, which is a clear liquid with a characteristic ketone odor. OSHA proposed a 50-ppm 8-hour TWA and a 75-ppm STEL, and the final rule establishes these limits. NIOSH (Ex. 8-47, Table N1) concurred with the Agency's selection of these limits.

A four-hour exposure to 4000 ppm MIBK killed all exposed rats, but a similar exposure to 2000 ppm was not fatal to these animals (Smyth, Carpenter, and Weil 1951/Ex. 1-439). Guinea pigs exposed to a MIBK concentration of 10,000 ppm immediately showed signs of irritation (Specht, Miller, Valaer, and Sayers 1940/Ex. 1-1179).

MacEwen, Vernot, and Haun (1971/Ex. 1-194) exposed rats, mice, dogs, and monkeys to 100 or 200 ppm MIBK for two weeks and noted no signs of intoxication; however, rats exposed to 100 ppm had heavier kidneys and higher kidney-to-body-weight ratios, and, at 200 ppm, livers were heavier as well. Postmortem examination revealed nephrosis of the proximal tubules.

The same authors (MacEwen, Vernot, and Haun 1971/ Ex. 1-194), exposed rhesus monkeys, dogs, and rats continuously for 90 days to MIBK concentrations of 100 ppm. These authors observed no significant changes in clinical chemistry or blood test results, although the rats had heavier kidneys and livers, reversible hyaline droplet degeneration of the proximal tubules of the kidneys, and some necrosis of the tubules.

Silverman, Schulte, and First (1946/Ex. 1-142) determined that the maximum dose of MIBK tolerable to human volunteers for eight hours was 100 ppm; at 200 ppm, these subjects found the odor of MIBK objectionable and the vapor irritating. Linari and co-workers (1964/Ex. 1-1159) reported that more than half of all workers exposed to 500 ppm of MIBK for 20 to 30 minutes daily, and perhaps to 80 ppm for the remainder of the shift, experienced weakness, loss of appetite, headache, burning eyes, nausea, vomiting, and sore throat; several of these workers also reported insomnia, somnolence, heartburn, and intestinal pain. Some workers had enlarged livers and others had colitis. Clinical test results on these workers were normal (Linari, Perrelli, and Varese 1964/Ex. 1-1159).

In a follow-up study on this same group of centrifuge operation workers, Armeli and co-workers (1968/Ex. 1-1028) determined that reduction of MIBK levels (during the 15 to 30 minutes of centrifuge operation) to 100 to 105 ppm, and (for the remainder of the shift) to 50 ppm had also significantly reduced the symptomatology reported earlier by these workers. However, liver enlargement persisted in two workers, and a few workers continued to report gastrointestinal and nervous system effects (Armeli, Linari, and Martorano 1968/Ex. 1-1028).

Elkins (1959f/Ex. 1-734) noted that exposure to 100 ppm during boot-waterproofing operations caused workers to develop headache and nausea; another similarly exposed group experienced only irritation at 100 ppm.

The AFL-CIO (Ex. 194) commented on MIBK. The AFL-CIO supports the limits OSHA has established for this substance in the final rule.

In the final rule, OSHA is establishing an 8-hour TWA of 50 ppm and a 15-minute STEL of 75 ppm for hexone. The Agency concludes that these limits will work together to protect workers from the significant risks of headache, nausea, and irritation, as well as the potential kidney and liver effects that constitute material health impairments that are associated with exposures to hexone above the revised PELs.

Conclusion for Both Liver and Kidney Toxins
The health effects associated with occupational exposures to the hepato-
and nephrotoxins shown in Tables C4-1 and C4-2 can be acute or chronic, reversible or irreversible, temporarily disabling or threatening to life. Workers experiencing chemically induced hepatotoxic or nephrotoxic effects may have enlarged livers, high blood pressure, hormonal imbalances, and/or organ necrosis, all of which constitute material impairments of health or functional capacity within the meaning of the Act. In addition, exposure to the substances in this grouping is associated with a host of other adverse health effects, ranging from pulmonary irritation to cancer, and OSHA concludes that the new or revised limits will substantially reduce the risk of these effects as well.

5. Substances for Which Limits Are Based on Avoidance of Ocular Effects

Introduction

Five of the chemicals for which OSHA is establishing limits have the potential to cause serious ocular effects in the workplace setting. Certain chemicals in this group are also sensory irritants and have been classified separately from the other irritants only because of their ability to cause permanent damage to the corneas, lenses, or optic nerves of exposed individuals.

Table C5-1 lists these five chemicals, along with OSHA's former, proposed, and final rule PELs, and each chemical's CAS number and HS number. For N-ethyl morpholine, the former 8-hour TWA of 20 ppm has been reduced to 5 ppm; the skin notation has been retained. For methyl alcohol and naphthalene, OSHA has retained its former 8-hour TWA and added a STEL (in the case of methyl alcohol, a skin notation has been added as well). For methyl silicate, the Agency has promulgated a new 8-hour PEL, while for hydrogen sulfide, the former STEL of 20 ppm and ceiling of 50 ppm have been replaced with a 10-ppm 8-hour TWA, supplemented by a 15-ppm short-term exposure limit.

Table C5-1.  Substances for Which Limits Are Based on Avoidance
             of Ocular Effects
__________________________________________________________________________
H.S. Number/                      Former OSHA    Proposed    Final Rule
Chemical Name           CAS No.       PEL           PEL         PEL(1)
__________________________________________________________________________
1172 N-Ethylmorpholine 100-74-3  20 ppm TWA,    5 ppm TWA,   5 ppm TWA,
                                 Skin           Skin         Skin
1209 Hydrogen sulfide 7783-06-4  20 ppm STEL    10 ppm TWA   10 ppm TWA
                                 50 ppm Ceiling 15 ppm STEL  15 ppm STEL
1252 Methyl alcohol     67-56-1  200 ppm TWA    200 ppm TWA  200 ppm TWA
                                                250 ppm STEL 250 ppm STEL
                                                Skin         Skin
1266 Methyl silicate   681-84-5   --            1 ppm TWA    1 ppm TWA
1282 Naphthalene        91-20-3  10 ppm TWA     10 ppm TWA   10 ppm TWA
                                                15 ppm STEL  15 ppm STEL
_________________________________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures, its STELs are
for 15 minutes unless otherwise specified, and its ceilings are peaks not
to be exceeded for any period of time.

Description of the Health Effects

Damage to the eye caused by exposure to the chemicals in this group can occur in the form of corneal, lens, retinal, ganglion cell layer, or optic nerve effects. Depending on the severity of the exposure, individual susceptibility, and the particular chemical and circumstances involved, this damage may be transient, temporarily disabling, or permanently blinding.

Corneal effects. The cornea and conjunctiva are the outer surfaces of the eye and are thus directly exposed to external insults. Since the cornea must maintain transparency to remain functional, scar formation after injury to the cornea can destroy visual function completely. Recent evidence suggests that the transparency of the cornea is maintained by thin inner and outer boundary layers and that the death of these layers leads to loss of transparency (Potts 1986/Ex. 1-174). The corneal epithelium (outer layer) sometimes regenerates, depending on the depth of the burn or insult and the nature of the toxicant.

Some chemicals, including methyl silicate, produce painful corneal epithelial injuries that have a delayed symptom onset. These substances can continue to cause pain and loss of corneal epithelial cells for several hours after exposure. Typically, there is no discomfort during the actual exposure, but several hours later, the eyes begin to burn, vision blurs, and conjunctival hyperemia, tearing, photophobia, and squinting occur (Grant 1986/Ex. 1-975). Possible mechanisms of action are enzyme inhibition, denaturing of other proteins, alteration of the DNA, and interference with the mitotic process; after a period of exposure, the affected cells die. Although the damaged epithelium sometimes regenerates after this type of injury, the damage can also involve the corneal stroma and endothelium, leading to scarring, vascularization, opacity, and loss of vision. The poor warning properties characteristic of these substances (i.e., their failure to cause an immediate response) make the establishment of protective exposure limits particularly important.

Exposure to the vapors of some of the substances in this group produces painless edema of the corneal epithelium, which can be accompanied by the delayed onset of visual haloes. A chemical that produces these effects is N-ethylmorpholine, a catalyst used to manufacture urethane foam. Painless edema generally occurs in workers who have been exposed for several hours to levels that do not produce discomfort during the exposure itself. The visual effect produced by such exposures consists of the appearance of colored haloes around lights, an effect that is caused by the diffraction of light through the swollen epithelial cells of the eye. Visual haloes are severely distracting and restrict activity substantially, and the mechanism underlying this effect is not well understood (Grant 1986/Ex. 1-975).

Lens effects. The lens is a transparent, avascular tissue surrounded by a thin, collagenous capsule. The major portion of the lens is composed of long, thin fibers that form closely packed, onion-like layers. Transparency is dependent on several factors: a highly ordered cellular arrangement; fiber size, shape, and uniformity; molecular structure; and regularity of fiber packing (Potts 1986/Ex. 1-174). Interference with lens metabolism, with transport across cell boundaries, or with the integrity of the lens capsule itself can cause a loss of lens transparency and lead to decreased visual acuity (Potts 1986/Ex. 1-174). All such changes in lens transparency are referred to as cataracts.

Retinal effects. The retina is a compact neural structure that is responsible for converting the ocular light image to neural impulses. Because the retina is an internal structure, it is not generally affected by exposure to dust, splashes of liquids, or vapors. However, exposure to certain internally absorbed substances, such as methyl alcohol, may cause changes or lesions in the retina, including retinal edema or hemorrhage. Exposure to a few of these substances can cause acute narrowing of the retinal arteries themselves, which can lead, in turn, to damage of the optic nerve and loss of vision.

Effects on ganglion cell layer and optic nerve. Below the retinal surface layer lies the ganglion cell layer, which is composed of the cell bodies of neurons that extend to the midbrain via the optic nerve. Ganglion cells may be damaged directly when the chemical acts on the cell bodies themselves or secondarily when the toxin destroys the optic nerve. Depending on the severity of the exposure, loss of visual acuity or vision may ensue.

Dose-Response Relationships and Ocular Effects

For most of the chemicals on this list, limits have been established on the basis of health surveys and case reports of occupationally exposed populations. These studies indicate that exposures to concentrations of these substances at levels above the NOE level cause damage or pain to the eyes of exposed workers. In some cases only limited human data are available, and evidence from animal studies or knowledge of a chemical's structural analogy to another chemical known to have ocular effects provides the basis for the exposure limit. Animal models are generally good predictors of ocular effects in humans because the eyes of rodents, especially those of guinea pigs and rabbits, closely resemble human eyes. Thus, animal studies of the effects of exposure on the eye can be relied on to predict accurately how the chemicals that produce these effects in animals will behave in workers exposed in industrial situations. For the five chemicals in this group, the available toxicologic data, the record evidence, and OSHA's final determinations as to their limits are described below.

N-ETHYLMORPHOLINE CAS: 100-74-3; Chemical Formula: C(6)H(13)NO H.S. No. 1172

OSHA's former 8-hour TWA PEL for N-ethylmorpholine was 20 ppm, with a skin notation. The proposed permissible exposure limit was 5 ppm as an 8-hour TWA, also with a skin notation, and the final rule establishes this limit and retains the skin notation, which is consistent with the limits of the ACGIH. NIOSH (Ex. 8-47, Table N1) agrees with the selection of this limit. N-Ethylmorpholine is a colorless, flammable liquid with an ammonia-like odor; this substance is a severe eye irritant.

Prolonged exposure to fairly low concentrations of this substance causes corneal edema, blue-gray vision, and colored haloes. Typically, vision becomes misty and haloes appear a few hours after workers have been exposed to the vapors for a period of hours. Distortion of vision can occur even at levels considerably lower than those that cause irritation (Mastromatteo 1965/Ex. 1-146).

Reversible corneal edema has been observed in workers exposed to 40 ppm or more of N-ethylmorpholine for several hours (Dernehl 1966a/Ex. 1-62). Workers routinely exposed to 3- to 4-ppm concentrations but never to concentrations above 11 ppm complained of haloes and foggy vision as well as drowsiness (ACGIH 1986/Ex. 1-3, p. 263). The irritant effects of N-ethylmorpholine were also seen in a controlled-exposure experiment on volunteer subjects. Ten subjects exposed for 2.5 minutes to a concentration of 100 ppm experienced irritation of the eyes, nose, and throat; those exposed for 2.5 minutes to 50 ppm experienced slight irritation; and no irritation was reported after exposure for 2.5 minutes to 25 ppm (ACGIH 1986/Ex. 1-3, p. 263). N-ethylmorpholine is also readily absorbed through the skin (Smyth, Carpenter, Weil, and Pozzani 1954/Ex. 1-440).

OSHA's former 20-ppm PEL for N-ethylmorpholine did not protect exposed workers against the occurrence of corneal edema. Because corneal edema is painless as it is developing and symptoms have a delayed onset, workers are especially likely not to be aware of the danger of exposure. This is particularly hazardous because the effects on visual function of repeatedly exposing the eyes to substances that cause corneal edema are not known. The Agency received no comments on the health effects or revised exposure limits for N-ethylmorpholine, with the exception of NIOSH's submission.

OSHA concludes that reducing the PEL to 5 ppm as an 8-hour TWA (and retaining the skin notation) is necessary to protect occupationally exposed workers from ethylmorpholine's injurious ocular effects. The new, lower PEL will reduce the significant risk of material health impairment, which is manifested as corneal edema, visual distortion, and impaired vision, that is associated with exposure to this substance at concentrations above the revised PEL.

HYDROGEN SULFIDE CAS: 7783-06-4; Chemical Formula: H(2)S H.S. No. 1209

OSHA's former limits for hydrogen sulfide were a 20-ppm STEL (10-minute maximum duration) and a 50-ppm ceiling limit. The proposed and final rule for this substance are 10 ppm as an 8-hour TWA and 15 ppm as a STEL. These limits are consistent with those of the ACGIH. NIOSH has a REL for hydrogen sulfide of 10 ppm as a 10-minute ceiling. Hydrogen sulfide is a colorless, flammable gas with the odor of rotten eggs. It is widely used as an agricultural disinfectant, chemical intermediate, analytical reagent, and in the manufacture of heavy water in the utilities sector. However, occupational exposure to hydrogen sulfide occurs most frequently when it is encountered in natural oil or gas deposits or as a by-product in chemical reactions.

The 1986 ACGIH Documentation (Ex. 1-3, p. 318) cites several reports (Brieger 1964; Kranenburg and Kessener 1935; Masure 1950; Elkins 1950a/Ex. 1-953) of the occurrence of adverse ocular effects, including conjunctivitis, associated with exposure to 20 ppm or less of hydrogen sulfide. A study by Poda and Aiken (1966/Ex. 1-115) reports that the adoption of a voluntary limit of 10 ppm in two heavy-water plants eliminated exposure problems. An early study by Flury and Zernik (1931f, as cited in ACGIH 1986/Ex. 1-3, p. 318) reports that the conjunctivitis caused by exposure to 10 to 15 ppm of hydrogen sulfide for six hours endured for several days; however, OSHA is unaware of cases in which this substance caused irreversible eye damage. The National Institute for Occupational Safety and Health (NIOSH) relied essentially on the studies discussed above (Poda and Aiken 1966/Ex. 1-115; Flury and Zernik 1931f, as cited in ACGIH 1986/Ex. 1-3, p. 318) when recommending its limit for hydrogen sulfide of 10 ppm for 10 minutes; NIOSH (Ex. 8-47, Table N7) continues to recommend this ceiling for hydrogen sulfide (this issue is discussed further below).

OSHA received several comments related to the health effects and proposed limits for hydrogen sulfide (Exs. 3-1163, 3-216, 8-37, 8-47, 129; Tr. XI, pp. 114, 225). The Atlantic Electric Company (Ex. 3-1163) pointed out an error in the proposal, which listed the short-term exposure limit for hydrogen sulfide as 5 ppm rather than 15 ppm. The Edison Electric Institute (EEI) (Tr. XI, p. 225) explained that utility workers are exposed to hydrogen sulfide when they enter utility manholes and vaults that are located near coastal areas, where this gas seeps into underground spaces. The EEI reports that utility workers use respirators and ventilate these spaces before entering. The Montana Sulphur and Chemical Corporation (Ex. 3-216), a small-business manufacturer, handler, and shipper of hydrogen sulfide, commented that, in its opinion, "the evidence presented for significantly tightening the existing standards is not at all compelling." According to Montana Sulphur, the studies cited by OSHA in the proposal to support the revised limits of 10 ppm (TWA) and 15 ppm (STEL) for hydrogen sulfide involved concurrent exposures "to other pollutants or stressors peculiar to the incident involved" (Ex. 3-216, p. 2). In addition, Montana Sulphur objects to OSHA's reliance on a study by Poda and Aiken (1966/Ex. 1-115) showing that voluntary compliance with an internal standard of 10 ppm at a facility in the heavy-water industry eliminated complaints of eye irritation among hydrogen-sulfide-exposed workers at this facility (Ex. 3-216). Montana Sulphur and Chemical reports that, in its long experience of manufacturing and handling this "notoriously toxic" substance, it has never had a case of eye irritation that required medical treatment; it urges OSHA to promulgate a STEL for hydrogen sulfide in the range of 25 to 30 ppm rather than the proposed 15 ppm (Ex. 3-216).

OSHA appreciates this commenter's thoughtful and thorough discussion of his company's experience in dealing with hydrogen sulfide in the workplace. However, OSHA's revised 8-hour TWA for this substance is based on the best available evidence (i.e., data on a level of occupational exposure that has been shown not to produce the health effect of concern). The eye irritation potential of hydrogen sulfide at levels below 20 ppm is widely recognized; the comment from Montana Sulphur (Ex. 3-216) acknowledges that reduction of the 8-hour TWA to 10 to 12 ppm is warranted. OSHA finds that a STEL of 15 ppm is justified by reports of eye irritation caused by short-term exposures to levels below 15 ppm (ACGIH 1986/Ex. 1-3, p. 318). OSHA is also aware that conditions in industry often involve simultaneous exposures to more than one hazardous substance and that such mixed exposures may increase the severity of the effects experienced by workers. However, the Agency must establish exposure limits based on the best available evidence for each individual substance to be regulated; it cannot attempt to set different limits for substances on the basis of the enormous number of other substances with which they could potentially be associated in actual use.

OSHA also received a comment on hydrogen sulfide from NIOSH (Ex. 8-47, Table N7). NIOSH recommends a single 10-ppm 10-minute ceiling for this substance. The United Paperworkers International Union (Ex. 8-37) also recommends adoption of the NIOSH 10-minute ceiling of 10 ppm. The Agency believes that the protection provided by NIOSH's 10-ppm short-term limit is essentially equivalent to that provided by OSHA's combined TWA-STEL limits, and that the combination of a 10-ppm 8-hour TWA and a 15-ppm STEL established in the final rule will provide broader protection in workplaces characterized either by short-term or by steady-state exposures.

The New Jersey Department of Health (Ex. 144) urged OSHA to base its limits for hydrogen sulfide on EPA's IRIS data. OSHA discusses this approach and New Jersey's comment in Section VI.A of this preamble.

OSHA concludes that the former 20-ppm (10-minute) short-term limit and 50-ppm ceiling limit did not adequately protect workers against the adverse ocular effects associated with exposure to concentrations of hydrogen sulfide below 20 ppm, as reported in several studies. OSHA finds that the eye irritation and conjunctivitis associated with such exposures represent a significant risk of material health impairment to workers, who may be forced to seek medical treatment after such exposure and who may also be unable to work during the period of recovery. OSHA has accordingly established an 8-hour TWA limit for hydrogen sulfide of 10 ppm and a short-term limit of 15 ppm. These levels have been demonstrated to be effective in preventing irritation and conjunctivitis in the workplace (Poda and Aiken 1966/ Ex. 1-115). The Agency finds that this dual limit will provide protection both in continuous steady-state exposure situations and in those characterized by sharp peaks and will do so more effectively than a single, short-term limit such as that recommended by NIOSH.

METHYL ALCOHOL CAS: 67-56-1; Chemical Formula: CH(3)OH H.S. No. 1252

OSHA's former 8-hour TWA limit for methyl alcohol was 200 ppm. The proposed limits were an 8-hour TWA of 200 ppm, a STEL of 250 ppm, and a skin notation. The final rule establishes these limits, which are consistent with those of the ACGIH. NIOSH previously recommended exposure limits for this substance of 200 ppm as a TWA and 800 ppm as a STEL; however, after reviewing the health evidence for methyl alcohol, NIOSH concurs with OSHA's final rule PELs for this substance (Ex. 8-47, Table N1). Methyl alcohol is a mobile, highly polar, flammable liquid that is widely used as an industrial solvent.

As stated in the proposal (53 FR 21061), workers exposed to concentrations of methyl alcohol between 200 and 375 ppm experience severe recurrent headaches, and at levels between 1200 and 8300 ppm, studies by Kingsley and Hirsch (1954/ Ex. 1-212) report that the visual capacities of exposed individuals are diminished. OSHA finds that a 250-ppm STEL is necessary because an 8-hour PEL of 200 ppm alone does not protect workers from exposure to short-term peaks at levels that cause eye irritation and severe, recurrent headaches in exposed workers. Although the skin LD(50) in rabbits is 20 g/kg, OSHA is adding a skin notation for methyl alcohol in the final rule (see Section VI.C.18 for a discussion of the Agency's policy on skin notations). The Agency's reason for establishing a skin notation for methyl alcohol despite this high dermal LD(50) in rabbits is that a dermal LD(Lo) of 500 mg/kg has been reported for this substance in monkeys (Dangerous Properties of Industrial Materials, 7th ed., Sax and Lewis 1989, p. 1377).

Several commenters submitted information to the record on methyl alcohol (Exs. 150 (Comments on Methyl Alcohol), 194, 3-661, 3-902, and 3-896). The Motor Vehicle Manufacturers Association (MVMA)(Ex. 3-902) presented no substantive comment with regard to methyl alcohol; instead, the MVMA listed 41 chemicals, including methyl alcohol, that, in the opinion of the MVMA, require "more review...to allow OSHA and industry additional time to properly assess...[the technological and economic] consequences" of revising the limit. Both the Eastman Kodak Company (Ex. 3-661) and the Chevron Corporation (Ex. 3-896) submitted specific comments on OSHA's proposal to add a STEL of 250 ppm to the existing 8-hour TWA of 200 ppm. Representing Chevron, Stanley Dryden stated:

We do not believe that the proposed 250-ppm STEL is justified by the discussion in [OSHA's] preamble (Ex. 3-896, p. 10).

According to Kodak, the study by Kingsley and Hirsch (1954/ Ex. 1-212) that was cited by OSHA in support of the STEL involved exposures to a duplicating machine fluid that contained between 5 and 98 percent methyl alcohol and 2 to 9 percent of an unidentified fluid(s). Kodak is of the opinion that the severe headaches experienced by exposed employees may have been related to the unidentified components of the fluid rather than to methyl alcohol, and further that these exposures may not have been the result of short-term exposures (Ex. 3-661).

OSHA finds Chevron's and Eastman Kodak's comments unpersuasive, for several reasons. First, the measured airborne levels of methyl alcohol reported in the Kingsley and Hirsch study (1954/Ex. 1-212) ranged from 200 to 375 ppm when employees were using direct process duplicating fluids; other studies also report that exposure to methyl alcohol at these levels causes headaches (Henson 1960, as cited in ACGIH 1986/Ex. 1-3, p. 372). Thus, the effects cited in the Kingsley and Hirsch study (1954/Ex. 1-212) are biologically plausible and consistent with those reported in other studies of the effects of this substance. Second, OSHA believes that a 250-ppm STEL is needed to ensure that workers are not exposed, even for short periods, to the elevated levels that have been shown to cause these effects. NIOSH has reevaluated the toxicological evidence for a STEL for methyl alcohol and concurs with the 250-ppm limit OSHA is establishing in the final rule. According to NIOSH (Ex. 150, Comments on Methyl Alcohol):

[T]here appears to be no justification for a ceiling of 800 ppm [the ceiling level formerly recommended by NIOSH]. It appears that data are more supportive of the OSHA and ACGIH STEL of 250 ppm...it seems reasonable to update the NIOSH recommended ceiling (Ex. 150).

Thus, OSHA has determined that the addition of a STEL is necessary to reduce the significant risk of disturbed vision and headaches to which workers could be and have been exposed in the absence of a limit on short-term exposures. As discussed above, NIOSH concurs with OSHA that a short-term limit of 250 ppm is appropriate for methyl alcohol; NIOSH described a recent study (Frederic et al. 1984, as cited in Ex. 150, Comments on Methyl Alcohol) that found that teachers' aides exposed to 80 to 3080 ppm of methyl alcohol while using duplicating machines experienced blurred vision, headaches, dizziness, and skin problems. The AFL-CIO (Ex. 194, p. A-12) supports the addition of a STEL and a skin notation for methyl alcohol.

The final rule promulgates an 8-hour TWA of 200 ppm, a STEL of 250 ppm, and a skin notation for methyl alcohol. OSHA concludes that the 8-hour TWA and 15-minute STEL will work together to reduce substantially the significant risk of headaches and blurred vision presented by short-term occupational exposures to methyl alcohol at concentrations above 250 ppm. The Agency finds that the headache, blurred vision, and other ocular effects associated with exposure to methyl alcohol constitute material impairments of health.

METHYL SILICATE CAS: 681-84-5; Chemical Formula: (CH(3)O)(4)Si H.S. No. 1266

OSHA did not formerly have a limit for methyl silicate; the Agency proposed the adoption of a 1-ppm 8-hour TWA for this substance, and NIOSH (Ex. 8-47, Table N1) concurred with this selection. The final rule establishes this limit, which is consistent with that of the ACGIH. Methyl silicate exists in the form of colorless needles.

Methyl silicate damages the cornea and is associated with a delayed onset of symptoms. In many cases of methyl silicate exposure, the eyes recover completely, but there are reports of damage to the deep layers of the cornea that caused permanent opacification and, in one worker, loss of vision in one eye (Grant 1986/Ex. 1-975). It is estimated that exposing humans to methyl silicate at concentrations of 200 to 300 ppm for 15 minutes will produce lesions, and that exposure to 1000 ppm for this period will produce injury requiring hospitalization (ACGIH 1986/Ex. 1-3, p. 409).

Rabbits exposed to 1000 ppm of methyl silicate in dry air experienced delayed eye burns (ACGIH 1986/Ex. 1-3, p. 409). Exposure of these animals to approximately 15,000 ppm for five minutes caused eye burns, but exposure to this level for four minutes caused no appreciable effect. Guinea pigs showed maximum no-effect levels of 135 ppm for 15 minutes, 90 ppm for one hour, and 20 ppm for 8 one-hour periods. The latency period for ocular changes was 16 hours for serious effects and up to three days for mild involvement (ACGIH 1986/Ex. 1-3, p. 409). Only NIOSH commented on this substance.

Because the onset of response to this toxin is delayed, because exposure in the workplace could have a duration substantially greater than that in the animal bioassays, and because of interspecies variability, it is necessary to establish a PEL considerably below the NOE level in animals to reduce the significant risk of ocular damage to employees. The Agency is therefore establishing a 1-ppm 8-hour TWA limit for methyl silicate to reduce the significant risk of severe ocular effects associated with the uncontrolled exposures formerly possible in the absence of a PEL. The Agency concludes that this limit will substantially reduce this significant risk by protecting workers from the ocular effects of methyl silicate exposure, which constitute material impairments of health.

NAPHTHALENE CAS: 91-20-3; Chemical Formula: C(10)H(8) H.S. No. 1282

OSHA's former exposure limit for naphthalene was 10 ppm as an 8-hour TWA. The final rule retains this TWA and adds a short-term limit of 15 ppm for this substance, which occurs as a colorless to brown solid and has the odor of mothballs. The ACGIH also has a 10-ppm 8-hour TWA and a 15-ppm STEL for naphthalene. NIOSH (Ex. 8-47, Table N1) concurs with the PELs selected for this substance.

The oral LD(50) for naphthalene in rats is 1760 mg/kg (Flury and Zernik 1931g/Ex. 1-995). In humans, the inhalation of naphthalene vapor causes headache, loss of appetite, and nausea (Flury and Zernik 1931g/Ex. 1-995; Patty 1949b, as cited in ACGIH 1986/Ex. 1-3, p. 420). These authors also report that exposure causes optical neuritis, corneal damage, and kidney injury. Eight of 21 workers exposed for five years to unspecified levels of naphthalene developed opacities of the lens of the eye (Ghetti and Mariani 1956/Ex. 1-739). Ingestion of large amounts of naphthalene causes severe hemolytic anemia and hemoglobinuria (Stokinger and Mountain 1963/Ex. 1-765). The lethal dose in humans has been reported as 50 mg/kg (NIOSH 1977i/Ex. 1-1182). Concentrations somewhat above 15 ppm are reported to cause marked eye irritation (Robbins 1951/ Ex. 1-799).

Only the American Iron and Steel Institute (AISI) and NIOSH commented on naphthalene. The AISI (Exs. 129 and 188) believes that a STEL for naphthalene is not warranted by the evidence. However, the Robbins (1951/Ex. 1-799) study discussed above clearly shows that excursions to 15 ppm cause severe eye irritation, and OSHA thus finds the STEL both necessary and appropriate.

In the final rule, the Agency is retaining the 8-hour TWA of 10 ppm and adding a 15-minute STEL of 15 ppm for naphthalene. This STEL is designed to protect against the eye irritation observed in workers at elevated levels (Robbins 1951/Ex. 1-799). The Agency concludes that these limits will protect workers from the significant risks of eye irritation and serious ocular effects, which constitute material health impairments that are potentially associated with exposure to levels above the 8-hour limit.

Conclusions for This Group of Ocular Toxins

OSHA finds that promulgation of the final rule's limits for this group of chemicals, which have the potential to cause adverse ocular effects ranging from transient discomfort to permanent blindness, will substantially reduce the significant risk of visual impairment associated with occupational exposure to these substances. The toxicological basis for the final rule's limits include evidence derived from occupationally exposed workers and results obtained in animals that have been shown to be excellent predictors of human responses. The risks being protected against have serious consequences, both in terms of material impairment of health and interference with the functional capacity of those workers who are themselves exposed and the safety and well-being of these workers and their co-workers. Thus, OSHA finds that the limits established by the final rule are necessary to reduce these significant occupational risks, which constitute material health impairments of health within the meaning of the Act.

6. Substances for Which Limits Are Based on Avoidance of Respiratory Effects Introduction

Limits are being established for a total of 36 substances or materials for which exposure has been shown to cause adverse respiratory effects. The chemicals in this group cause acute pulmonary edema, alveolar damage, or chronic respiratory damage through the general mechanisms of cellular damage or fibrosis. At sufficient doses, these effects can be permanent, disabling, and life-threatening.

Some of the materials in this group are composites of naturally occurring minerals, and, for these, the Agency is establishing limits based on the most hazardous component. For several materials (coal dust, crystalline tripoli, silica, and graphite), OSHA is requiring the TWA to be measured as the respirable quartz fraction of the dust, because it is exposure to this fraction that presents the greatest risk to exposed workers.

Table C6-1 lists the 36 substances in this group, along with the former, proposed, and final rule PELs, and CAS and HS numbers. There was no former OSHA PEL for 13 of these substances. For one substance, OSHA is establishing a ceiling limit to replace an existing 8-hour TWA, and for ten substances, a lower TWA and/or STEL are being established. In three instances, OSHA is establishing a STEL to augment its former TWA-PELs. For nine substances, OSHA is changing only the form in which the limit is being expressed.

C6-1.  Substances for Which Limits Are Based on Avoidance of Respiratory
       Effects
         (Because of its width, this table has been divided; see
          continuation for additional columns)
___________________________________________________________________
H.S. Number/
Chemical Name                   CAS No.       Former PEL
___________________________________________________________________
1017 Aluminum                 7429-90-5       --
      (pyro powders)
1034 Bismuth telluride        1304-82-1       --
       (Se-doped)
1080 Chlorine dioxide        10049-04-4       0.1 ppm TWA
1093 Chromium metal           7440-47-3       1 mg/m(3) TWA
1096 Coal dust,                    None       2.4 mg/m(3) TWA(a)
       @  5% quartz
1097 Coal dust, # 5% quartz        None       10 mg/m(3)
                                              __________
                                              % SiO(2)+2
1161 Ethyl acrylate            140-88-5       25 ppm TWA, Skin
1177 Ferrovanadium dust      12604-58-9       1 mg/m(3) TWA
1178 Fibrous glass                 None       15 mg/m(3) TWA
1190 Grain dust (oat,              None       --
       wheat, barley)
1191 Graphite, natural,       7782-42-5       15 mppcf TWA
       respirable @ 1%
       quartz
1213 Indium & compounds       7440-74-6       --
1215 Iron oxide (dust         1309-37-1       10 mg/m(3) TWA
       and fume)
1272 Methylene bis            5124-30-1       --
       (4-Cyclohexyliso-
       cyanate)
1276 Mica, respirable dust   12001-26-2       20 mppcf TWA
       containing <  1%
       quartz
1277 Mineral wool fiber            None       15 mg/m(3) TWA
1283 Nickel                   7440-02-0       1 mg/m(3) TWA
     (soluble compounds)
1289 Nitrogen dioxide        10102-44-0       5 ppm Ceiling
1300 Oxygen difluoride        7783-41-7       0.05 ppm TWA
1301 Ozone                   10028-15-6       0.1 ppm TWA
1303 Paraquat,                4685-14-7       0.5 mg/m(3) TWA,
       respirable dust                        Skin
1354 Silica, crystalline     14464-46-1       1/2 value calculated
       cristobalite (as                       for quartz
       respirable quartz
       dust)
1355 Silica, crystalline     14808-60-7       10 mg/m(3)
       quartz, respirable                     __________
                                              % SiO(2)+2
1356 Silica, crystalline     15468-32-3       1/2 value calculated
       tridymite (as                           for quartz
       respirable quartz
       dust)
1357 Silica, crystalline      1317-95-9       10 mg/m(3)
       tripoli (as                            __________
       respirable quartz                      % Si0(2)+2
       dust)
1358 Silica, fused           60676-86-0       10 mg/m(3)
                                              __________
                                              % SiO(2)+2
1363 Soapstone, total dust         None       20 mppcf TWA
1363A Soapstone,                   None       --
       respirable dust
1375 Sulfur dioxide           7446-09-5       5 ppm TWA
1378 Sulfur tetrafluoride     7783-60-0       --
1381 Talc (containing no)    14807-96-6       20 mppcf TWA
       asbestos)
1395 Tin oxide                7440-31-5       --
1409 Trimellitic anhydride     552-30-7       --
1430A Wood dust, hard              None       --
1403B Wood dust, soft              None       --
1430C Wood dust, allergenic        None       --
        (Western Red Cedar)
___________________________________________________________________


C6-1.  Substances for Which Limits Are Based on Avoidance of
       Respiratory Effects (Continuation)
_____________________________________________________________________
H.S. Number/
Chemical Name                Proposed PEL        Final Rule PEL(1)
_____________________________________________________________________
1017 Aluminum                5 mg/m(3) TWA        5 mg/m(3) TWA
       (pyro powders)
1034 Bismuth telluride       5 mg/m(3) TWA        5 mg/m(3) TWA
       (Se-doped)
1080 Chlorine dioxide        0.1 ppm TWA          0.1 ppm TWA
                             0.3 ppm STEL         0.3 ppm STEL

1093 Chromium metal          0.5 mg/m(3) TWA      1 mg/m(3) TWA
1096 Coal dust,              2 mg/m(3) TWA(a)     2 mg/m(3) TWA(a)
       @ 5% quartz
1097 Coal dust,              0.1 mg/m(3) TWA(b)   0.1 mg/m(3) TWA(b)
       # 5% quartz
1161 Ethyl acrylate          5 ppm TWA            5 ppm TWA
                             25 ppm STEL,Skin     25 ppm STEL, Skin
1177 Ferrovanadium dust      1 mg/m(3) TWA        1 mg/m(3) TWA
                             3 mg/m(3) STEL       3 mg/m(3) STEL
1178 Fibrous glass           5 mg/m(3) TWA        See text
1190 Grain dust (oat,        4 mg/m(3) TWA        10 mg/m(3) TWA
       wheat, barley)
1191 Graphite, natural,      2.5 mg/m(3) TWA      2.5 mg/m(3) TWA
       respirable @ 1%
       quartz
1213 Indium & compounds      0.1 mg/m(3) TWA      0.1 mg/m(3) TWA
1215 Iron oxide (dust        10 mg/m(3) TWA       5 mg/m(3) TWA
       and fume)
1272 Methylene bis           0.01 ppm Ceiling     0.01 ppm Ceiling
       (4-Cyclohexyliso-
       cyanate)
1276 Mica, respirable dust   3 mg/m(3) TWA        3 mg/m(3) TWA
       containing <  1%
       quartz
1277 Mineral wool fiber      10 mg/m(3) TWA       See text
1283 Nickel                  0.1 mg/m(3) TWA      0.1 mg/m(3) TWA
     (soluble compounds)
1289 Nitrogen dioxide        1 ppm STEL           1 ppm STEL
1300 Oxygen difluoride       0.05 ppm Ceiling     0.05 ppm Ceiling
1301 Ozone                   0.1 ppm TWA          0.1 ppm TWA
                             0.3 ppm STEL         0.3 ppm STEL
1303 Paraquat,               0.1 mg/m(3) TWA,     0.1 mg/m(3) TWA,
       respirable dust       Skin                 Skin
1354 Silica, crystalline     0.05 mg/m(3) TWA     0.05 mg/m(3) TWA
       cristobalite (as
       respirable quartz
       dust)
1355 Silica, crystalline     0.1 mg/m(3) TWA      0.1 mg/m(3) TWA
       quartz, respirable
1356 Silica, crystalline     0.05 mg/m(3) TWA     0.05 mg/m(3) TWA
       tridymite (as
       respirable quartz
       dust)
1357 Silica, crystalline     0.1 mg/m(3) TWA      0.1 mg/m(3) TWA
       tripoli (as
       respirable quartz
       dust)
1358 Silica, fused           0.1 mg/m(3) TWA      0.1 mg/m(3) TWA
1363 Soapstone, total dust   6 mg/m(3) TWA        6 mg/m(3) TWA
1363A Soapstone,             3 mg/m(3) TWA        3 mg/m(3) TWA
        respirable dust
1375 Sulfur dioxide          2 ppm TWA            2 ppm TWA
                             5 ppm STEL           5 ppm STEL
1378 Sulfur tetrafluoride    0.1 ppm Ceiling      0.1 ppm Ceiling
1381 Talc (containing no)    2 mg/m(3) TWA        2 mg/m(3) TWA
       asbestos)
1395 Tin oxide               2 mg/m(3) TWA        2 mg/m(3) TWA
1409 Trimellitic anhydride   0.005 ppm TWA        0.005 ppm TWA
1430A Wood dust, hard        1 mg/m(3) TWA        5 mg/m(3) TWA
                                                  10 mg/m(3) TWA
1403B Wood dust, soft        5 mg/m(3) TWA        5 mg/m(3) TWA
                                                  10 mg/m(3) TWA
1430C Wood dust, allergenic  --                   2.5 mg/m(3) TWA
        (Western Red Cedar)
______________________________________________________________________
  Footnote(a) For coal dust, respirable fraction less than 5 percent SiO(2).
  Footnote(b) For coal dust, respirable fraction more than 5 percent SiO(2).
  Footnote(1) OSHA's TWA limits are for 8-hour exposures; its STELs are
for 15 minutes unless otherwise specified; and its ceilings are peaks not
to be exceeded for any period of time.

Description of the Health Effects

The respiratory system is a major route of occupational exposure for toxic substances. Because of the vital nature of pulmonary function, respiratory toxicants present a serious health hazard both from acute and chronic exposures. Acute respiratory disease can be life threatening.

Chronic pulmonary disease can result from long-term exposure to respiratory toxicants and is potentially crippling because it greatly reduces the quality of life and the productivity of its victims. In addition, the onset of respiratory disease can be insidious, because it may be indicated only by the gradual development of a few nonspecific signs (Petersdorf et al., Harrison's Principles of Internal Medicine, 10th ed., 1983).

The difficulties of detecting irreversible respiratory effects complicate the prevention of pulmonary disease. Pulmonary function can be evaluated with a variety of tests, including measurements of the vital capacity and of the resting and forced expiratory volumes. However, certain conditions, including emphysema and fibrosis, are difficult to diagnose even with such tests. In addition, these same diseases often continue to progress even after the affected individual has recognized the problem and obtained medical assistance. Furthermore, these diseases may continue to progress even after exposure has ceased, which makes prevention even more vital.

In addition to the threat posed to the general occupational population by respiratory toxins, certain subpopulations, such as persons with impaired lung function caused by asthma, bronchitis, emphysema, and pulmonary fibrosis, are at special risk from the adverse effects of respiratory toxins. Tobacco smoking can cause or aggravate all of the respiratory conditions discussed above and can interact additively or synergistically with respiratory toxins to increase their adverse effects on the pulmonary system. For example, tobacco smoking acts additively with coal dust to diminish pulmonary function. Because tobacco smoke contains nitrogen oxides, cadmium, and ammonia, occupationally exposed workers who smoke have an additional source of exposure to these respiratory toxins.

Two general categories of lung injuries are relevant to the group of substances under consideration:

* Damage to cells lining the airways, which results in necrosis (localized areas of dead cells), increased permeability, and edema.

* Production of fibrosis, which may become massive and greatly reduce lung capacity.

Cellular damage resulting in edema and emphysema. A number of substances cause damage to cells lining the airways. This can result in increased permeability of cell membranes and subsequent edema, hemorrhage, and localized necrosis (areas of dead cells). Chronic inhalation of certain chemicals causes destruction of the alveolar septa and results in emphysema. Cellular damage may be either localized or diffuse, depending on the distribution of the toxicant in the lung.

Edema is the release of fluid into the lumen (open spaces of the airways) or alveoli. Serious edema can take several hours to develop so that, in some cases, life-threatening or even fatal exposures can take place without the individual's being aware at the time of exposure of the extent of the damage. Ozone, nitrogen dioxide, and paraquat all cause localized cellular damage leading to edema (Klaassen, Amdur, Doull et al. 1986/Ex. 1-99). Fatalities from pulmonary edema have resulted from exposures to concentrations of nitrogen dioxide of about 200 ppm (Dangerous Properties of Industrial Materials, 6th ed., Sax 1984). Paraquat is unusual in that it can cause delayed pulmonary damage following exposure, even when exposure occurs via routes other than inhalation (Klaassen, Amdur, Doull et al. 1986/Ex. 1-99).

Necrotic changes can reduce the functional surface area of the lung. One type of lesion often noted in persons exposed to respiratory toxins is benign granulomas, which are localized masses formed when the immune system attempts to sequester a foreign object. Depending on the extent of the damage, these masses may reduce the functional capacity of the lung. Exposure to selenium-doped bismuth telluride has been associated with the production of benign granulomas without fibrosis (Wagner, Madden, Zimber, and Stokinger 1974, as cited in ACGIH 1986/Ex. 1-3, p. 59).

Emphysema is caused by a gradual destruction of the cells of the alveolar septa, which causes a loss of elasticity in the lung. A slight degree of emphysema is present in much of the adult population and does not cause any functional impairment. As the disease progresses, however, serious and lifethreatening reductions in functional capacity can occur. Once the disease has advanced to the point of serious functional impairment, it is, for the most part, irreversible (Petersdorf et al. 1983). There is evidence that a number of the substances in this group cause emphysema, including sulfur tetrafluoride (ACGIH 1986/Ex. 1-3), ozone, and nitrogen dioxide (Klaassen, Amdur, Doull et al. 1986/Ex. 1-99).

Fibrotic changes. Pulmonary fibrosis was one of the earliest recognized forms of occupational disease. Fibrosis should be distinguished from pneumoconiosis, although these terms are often used interchangeably. Pneumoconiosis is a more general term indicating the presence of a foreign substance in the lungs, as determined by radiographic (X-ray) analysis. This definition encompasses a variety of conditions and does not by itself necessarily indicate functional damage (Petersdorf et al. 1983). In contrast, fibrosis is a seriously debilitating disease. One type of fibrosis is interstitial fibrosis, which is a kind of pneumoconiosis characterized by deposition of fibrous tissue in the interstitial spaces between the alveolar membrane and the pulmonary capillary membrane. Interstitial fibrosis greatly reduces the diffusing capacity of the lung and thus causes oxygen deprivation in the body (Guyton 1981/Ex. 1-1002). Like emphysema, fibrosis is largely irreversible; it sometimes progresses even in the absence of further exposure (Petersdorf et al. 1983).

Silicosis is a form of interstitial fibrosis that is caused by exposure to respirable silica particles (Klaassen, Amdur, Doull et al. 1986/Ex. 1-99). Exposure to coal dust causes a pneumoconiosis with fibrosis that can be severely debilitating (Petersdorf et al. 1983). In addition, exposure to graphite, mica, and grain dust have all been associated with fibrosis in workers (ACGIH 1986/Ex. 1-3).

Dose-Response Relationships and Respiratory Effects

For most of the substances in this group, permissible exposure limits have been based on health surveys and case reports of occupationally exposed populations. In some cases, animal studies provide the evidence of a substance's toxicity. As is the case for most of the substances for which OSHA is establishing new, reduced, or revised limits, the dose-response curve for respiratory irritants tends to be S-shaped.

Table C6-2 presents dose-response data on the adverse pulmonary effects of representative chemicals in this group, the populations exposed, and the endpoints observed. The following discussions describe the record evidence, present OSHA's findings for all the substances on Table C6-1, and describe the nature of the risks faced by workers exposed to them.

TABLE C6-2.  Summary of Dose-Response Evidence for Adverse Respiratory
             Effects
             (NOTE: Because of its width, this table has been divided; see
             continuation for additional columns)
_______________________________________________________________________
                                                      FINAL
H.S. Number/                        FORMER            RULE
Chemical Name            CAS No.    PEL               PEL(1)
_______________________________________________________________________
1034 Bismuth           1304-82-1    --                5 mg/m(3)
       telluride
       (Se Doped)
1096 Coal Dust,        None         2.4 mg/m(3) TWA   2 mg/m(3) TWA
     5% quartz
1097 Coal Dust,        None         10 mg/m(3)        0.1 mg/m(3) TWA
      | 5% quartz                   % SiO(2)+2
1190 Grain Dust        None         --                10 mg/m(3) TWA
       (oat, wheat,
       barley)
1191 Graphite,         7782-42-5    15 mppcf TWA      2.5mg/m(3) TWA
     natural,
     respirable
1213 Indium &          7440-74-6    --                0.1 mg/m(3) TWA
      compounds
1276 Mica             12001-26-2    20 mppcf TWA      3 mg/m(3) TWA
1289 Nitrogen         10102-44-0    5 ppm Ceiling     1 ppm STEL
      dioxide
1300 Oxygen            7783-41-7    0.05 ppm TWA      0.05 ppm
      difluoride                                      Ceiling
1283 Nickel (soluble   7440-02-0    1 mg/m(3) TWA     0.1 mg/m(3) TWA
      compounds)
1301 Ozone            10028-15-6    0.1 ppm TWA       0.1 ppm TWA
1303 Paraquat,         4685-14-7    0.5 mg/m(3) TWA,  0.1 mg/m(3) TWA
      respirable                    Skin              Skin
      dust
1354 Silica,          14464-46-1    1/2 value         0.05 mg/m(3)
      crystalline                   for quartz        TWA
      cristobalite
1355 Silica,          14808-60-7    10 mg/m(3)         0.1 mg/m(3)
      crystalline                   % SiO(2)+2         TWA
      quartz,
      respirable
1356 Silica,          15468-32-3     1/2 value         0.05 mg/m(3)
      crystalline                    for quartz        TWA
      tridymite
1357 Silica,           1317-95-9     10 mg/m(3)        0.1 mg/m(3)
      crystalline                    % SiO(2)+2        TWA
      tripoli
1375 Sulfur dioxide    7446-09-5     5 ppm TWA         2 ppm TWA
                                                       5 ppm STEL
1378 Sulfur            7783-60-0     --                0.1 ppm
      tetrafluoride                                    Ceiling
1409 Trimellitic        552-30-7     --                0.005 ppm TWA
      anhydride
_________________________________________________________________________


TABLE C6-2.  Summary of Dose-Response Evidence for Adverse Respiratory
             Effects (Continuation)
-------------------------------------------------------------------------
                                     Dose Response Data
                    _____________________________________________________
                     Dose/Duration
                     Associated
                     With
H.S. Number/         Observed
Chemical Name        Effects       Species       Comments
_________________________________________________________________________
1034 Bismuth         15 mg/m(3)     Dogs     Granulomatous lesions in
       telluride     1 year        Rats     lungs seen after 6 months of
       (Se-Doped)                  Rabbits  exposure

1096 Coal Dust,      4 mg/m(3)      Humans   Calculated estimate of 10 %
     5% quartz       35 years               probability of developing
                                            pneumoconiosis with fibrosis
1097 Coal Dust                              after 35 years of exposure
       | 5% quartz                          to coal dust. (Quartz content
                                            not identified.)

1190 Grain Dust      # 10 mg/m(3)  Humans   Chronic bronchitis, shortness
      (oat, wheat,                          of breath, reduced function,
                                            increased incidence of
      barley)                               respiratory symptoms.

                     @ 10 mg/m(3)  Humans   Increased incidence of
                                            respiratory symptoms.

                                   Humans   Fibrosis and mottling,
                                            pneumoconiosis.

1191 Graphite,         N/A         Humans   Anthracosilicosis, similar
       natural,                             to that seen in coal miners.
       respirable

1213 Indium &        24-97 mg/m(3) Rats     Widespread alveolar edema
     compound                               following exposure to In2O(2).

1276 Mica              N/A         Humans   Signs and symptoms resembling
                                            silicosis and pneumoconiosis
                                            in 8 of 57 workers.

1289 Nitrogen          N/A         Humans   Fatal pulmonary edema.
      dioxide
                     0.4-2.7 ppm   Humans   Change in pulmonary vital
                     chronic                capacity.

1300 Oxygen          0.5 ppm       Lab.     Lethal to a wide variety of
      difluoride     two 7-hr      Animals  laboratory species, causing
                     exposures              pulmonary edema and
                                            hemorrhage after several
                                            hours of exposure.

1283 Nickel (soluble 1 mg/m(3)     Rats     Signs of interstitial fibrotic
     compounds)      6 months               lesions and increased lung
                                            weight.
                     0.1  mg/m(3)   Rats     Pulmonary irritation and
                     2 weeks                damage in form of marked
                                            mucus secretion, hyperplasia
                                            and accumulation of alveolar
                                            macrophages.

1301 Ozone           1.5 ppm        Humans  Significant reduction in
                     3 hrs/day              pulmonary vital capacity.

                     1 ppm          Mice    Damage to alveolar tissue.
                     1 day

1303 Paraquat,         N/A          Humans  69 accidental deaths from
      respirable                            pulmonary injury reported
      dust                                  through 1972.

1354 Silica,         0.5 mg/m(3)    Dogs    Cellular infiltration of lung
      crystalline    (as total dust)        and fibrotic nodules in
      cristobalite   2.5 years              pulmonary lymph node.

1355 Silica,         0.1 mg/m(3)    Humans  Accelerated loss of pulmonary
      crystalline    chronic                function over effects of aging
      quartz,                               alone.
      respirable

1356 Silica,           N/A          Rats    Most active form of free
      crystalline                           silica when administered by
      tridymite                             intratracheal injections.

1357 Silica,           N/A          Lab.    Progressive nodular fibrosis.
      crystalline                   Animals
      tripoli

1375 Sulfur dioxide  1 ppm          Humans  Accelerated loss of pulmonary
                                            function.

1378 Sulfur          4 ppm          Rats    Emphysema, marked clinical
      tetrafluoride  4 hrs/day/             signs of respiratory
                      10 days

1409 Trimellitic                    Rats    Intra-alveolar hemorrhage. (No
      anhydride                             exposure duration indicated.)
__________________________________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures; its STELs are
for 15 minutes unless otherwise specified; and its ceilings are peaks not
to be exceeded for any period of time.

N/A = Not available.


ALUMINUM (PYRO POWDERS)
CAS: 7429-90-5; Chemical Formula: Al
H.S. No. 1017


OSHA previously had no permissible exposure limit for aluminum pyro powders. The ACGIH has an 8-hour TLV-TWA of 5 mg/m(3). The proposed and final rules have a PEL of 5 mg/m(3) for the aluminum pyro powders; NIOSH (Ex. 8-47, Table N1) concurs with this limit. Powders and flake aluminum are flammable and can form explosive mixtures in air.

Aluminum pyro powders have a higher reported toxicity than aluminum metal dusts (Stokinger 1981a/Ex. 1-1133). Several British studies have examined the effects of exposure to this finely flaked aluminum on workers in paints and pyrotechnics plants. Their findings revealed that pulmonary fibrosis may result from exposure to pyro powders, although epidemiologic evidence indicates that additives used to prevent oxidation and agglomeration may have contributed to the incidence and nature of the disease (Edling 1961/Ex. 1-733; Jordan 1961/Ex. 1-559; Mitchell, Manning, Molyneux, and Lane 1961/Ex. 1-564). Exposures that have previously caused lung changes in workers are presumed to have been extremely high (ACGIH 1986/Ex. 1-3, p. 22). No comments, other than NIOSH's, were received on these powders.

OSHA concludes that the permissible exposure limit of 5 mg/m(3) TWA for aluminum pyro powders will prevent the significant risk of lung changes in workers exposed at the concentrations formerly permitted by the absence of an OSHA limit. The Agency has determined that these lung changes constitute material impairment of health.


BISMUTH TELLURIDE (DOPED)
CAS: 1304-82-1; Chemical Formula: Bi(2)Te(3)
H.S. No. 1034


OSHA had no former limit for doped bismuth telluride (Bi(2)Te(3)). The ACGIH has a TLV-TWA of 5 mg/m(3) for Bi(2)Te(3) that has been doped with selenium sulfide. The proposed PEL was 5 mg/m(3) as an 8-hour TWA; NIOSH (Ex. 8-47, Table N1) concurs with this limit, and the final rule establishes it. Bismuth telluride appears as gray, hexagonal platelets; it is also available as ingots or single crystals.

Wagner, Madden, Zimber, and Stokinger (1974, as cited in ACGIH 1986/Ex. 1-3, p. 59) conducted a one-year study in which rabbits, dogs, and rats were exposed for six hours/day, five days/week to doped bismuth telluride dust (containing 80.04 mol % Bi2Te3 and 0.20 mol % SnTe, plus a small stoichiometric excess of Te) of 1.04 um particle diameter at a mean concentration of 15 mg/m(3). Small, granulomatous lesions without fibrosis appeared in the lungs of dogs at six months. In dogs that were sacrificed four months after an eight-month exposure, the lesions had regressed, and the affected lymph nodes were without cellular reaction. Rabbits exhibited similar histologic effects, but with decreased numbers of pulmonary macrophages, no fibrous tissue proliferation, and no cellular or fibrous tissue reaction around the dust deposits in the lymph nodes. The rats showed fewer granulomas but some areas of epithelialization of the alveolar walls. As was true for the other species, the rats showed neither fibrosis nor cellular reaction in the lymph nodes, despite accumulation of the intermetallic dust (Wagner, Madden, Zimber, and Stokinger 1974, as cited in ACGIH 1986/Ex. 1-3, p. 59). Only NIOSH commented on this substance.

In the final rule, an 8-hour PEL of 5 mg/m(3) TWA is established for Se-doped bismuth telluride to prevent the occurrence of the pulmonary lesions seen in experimental animals. OSHA concludes that this limit will substantially reduce the significant risk of these pulmonary effects.


CHLORINE DIOXIDE
CAS: 10049-04-4; Chemical Formula: ClO(2)
H.S. No. 1080


Previously, OSHA had an 8-hour TWA limit of 0.1 ppm for chlorine dioxide. The ACGIH recommends the same time-weighted average and a 15-minute STEL of 0.3 ppm. The proposal retained the same TWA and added a 15-minute STEL of 0.3 ppm, and NIOSH (Ex. 8-47, Table N1) concurred with these limits, which are established in the final rule. Chlorine dioxide is a red-yellow gas at ordinary temperatures.

Rats exposed to 0.1-ppm concentrations of chlorine dioxide for 10 weeks at five hours daily showed no adverse effects from exposures. Other data in animals are not available (Dalhamn 1957/Ex. 1-307).

Data on human exposures indicate that marked irritation occurs on inhalation of 5 ppm (no time specified), and that one death occurred at 19 ppm (Elkins 1959b, as cited in ACGIH 1986/Ex. 1-3, p. 118). Repeated exposures in humans have been linked to bronchitis and pronounced emphysema (Petry 1954/Ex. 1-1163). Clinical studies conducted by Gloemme and Lundgren (1957/Ex. 1-323) revealed that the majority of workers who had been exposed for five years to average concentrations of chlorine dioxide below 0.1 ppm, in combination with about 1.0 ppm chlorine, experienced eye and respiratory irritation and slight bronchitis. Some gastrointestinal irritation was also observed in these workers. Gloemme and Lundgren (1957/Ex. 1-323) attributed all of these effects to elevated short-term exposures involving excursions above the 0.1 ppm level. Ferris, Burgess, and Worcester (1967/Ex. 1-316) have shown that concentrations occasionally ranging as high as 0.25 ppm were associated with respiratory effects in workers concomitantly exposed to chlorine. The United Paperworkers International Union (UPIU) supported the development of comprehensive standards for irritant gases such as chlorine dioxide.

In the final rule, OSHA is retaining the 0.1-ppm 8-hour TWA and adding a 15-minute STEL of 0.3 ppm for chlorine dioxide. The Agency concludes that both of these limits are necessary to protect workers against the significant risk of respiratory, skin, and eye irritation known to occur as a result of short-term exposures above the TWA of 0.1 ppm. OSHA has determined that these adverse effects constitute material impairments of health.


CHROMIUM, METAL
CAS: 7440-47-3; Chemical Formula: Cr
H.S. No. 1093


OSHA formerly had an 8-hour TWA of 1 mg/m(3) for chromium metal. The proposed PEL was 0.5 mg/m(3); NIOSH (Ex. 8-47, Table N1) concurred with the proposed limit. The ACGIH has established an 8-hour TWA of 0.5 mg/m(3) for chromium, which is a steel-grey metal. In the final rule, OSHA is retaining the former 8-hour TWA PEL of 1 mg/m(3) for chromium metal.

According to the ACGIH, a 0.5 mg/m(3) TLV-TWA for chromium "should be adequate to prevent pulmonary disease or other toxic effects" (ACGIH 1986/Ex. 1-3, p. 139). Many commenters objected to the proposed 0.5 mg/m(3) PEL for chromium metal (Exs. 3-236, 3-829, 3-902, 3-1095, 3-1123, 129, 145, and 188; Tr. pp. 11-136 to 11-137). These commenters argued that there was no health basis for lowering the PEL for chromium metal and questioned the studies described in the health effects discussion for this substance. For example, Peter Hernandez, Vice President for Employee Relations at the American Iron and Steel Institute (AISI), commented in several submissions that one of the studies (Mancuso and Hueper 1951/Ex. 1-215) relied on by OSHA, which was performed for the Indian government in 1951, found "exaggerated pulmonary markings" on the X-rays of exposed workers but failed to demonstrate that these markings constituted a health risk to these workers (Ex. 188, p. 18). The AISI also criticized the results of another study relied on by OSHA, the work of Princi et al. (1962, as cited in ACGIH 1986/Ex. 1-3, p. 139), which detected pulmonary disease in workers exposed to chromium at levels of 0.27 mg/m(3) (Princi, Miller, Davis, and Cholak 1962, as cited in ACGIH 1986/Ex. 1-3, p. 139). According to the AISI, "the results of this study are highly questionable...because other dust and fumes besides chromium were present, including 36.7 percent silica" (Ex. 188, p. 19).

In response to these comments, OSHA has further reviewed the toxicological literature on chromium metal. The Agency finds that the metallic form of chromium, in its pure state, does not present a significant risk to exposed workers at levels below 1 mg/m(3), OSHA's former 8-hour TWA PEL for this substance. This view of chromium metal's toxicity is shared by several toxicologists. For example, Proctor, Hughes, and Fischman (Chemical Hazards of the Workplace, 2nd ed., 1988, p. 155) state, "Chromium metal is relatively nontoxic...." OSHA finds that the markings associated with exposure to chromium metal (which were not suggestive of alteration of the architecture of the lung) and reported in the Mancuso and Hueper (1951/Ex. 1-215) study do not present a risk of material impairment of health because they do not presage any decrement in pulmonary function or interfere with the functional capacity of exposed workers.

OSHA also agrees with the AISI that [A] major problem [in] defining the health effects which may be associated with exposure to metallic chromium is the frequent co-existence of the metallic form with both trivalent and hexavalent salts (Tr. p. 11-136).

The Princi et al. study (1962, as cited in ACGIH 1986/Ex. 1-3, p. 139) reflects the problem of confounding exposures to which the AISI alludes. In this study, ferrochrome alloy workers were exposed to several toxic contaminants simultaneously, including chromium salts, silica, iron oxide, and chromium metal. OSHA believes it likely that exposure to the other contaminants present, which included a high percentage of silica, accounts for the development of pulmonary disease in these workers. The ACGIH (1986/Ex. 1-3, p. 139) stated, after reviewing the Mancuso and Hueper (1951/Ex. 1-215) and the Princi et al. (1962, as cited in ACGIH 1986/Ex. 1-3, p. 139) studies, that "[e]xposure to chromium metal does not give rise to pulmonary fibrosis or pneumoconiosis."

Thus, after a reanalysis of the toxicological data and the record evidence, OSHA concludes that there is no health basis for reducing the Agency's former limit of 1 mg/m(3) for chromium metal. OSHA finds that the 1 mg/m(3) PEL provides appropriate worker protection from the toxic effects of exposure to chromium metal.

Accordingly, in the final rule, OSHA is retaining the former 8-hour TWA limit of 1.0 mg/m(3) for chromium metal. The Agency concludes that this limit protects workers against the significant risk of pulmonary effects potentially associated with exposure to the metallic form of chromium.

COAL DUST, < 5% QUARTZ COAL DUST, > 5% QUARTZ CAS: None; Chemical Formula: None H.S. Nos. 1096 and 1097

OSHA's former limits for coal dust included a formula limit of 10 mg/m(3)/% SiO(2)+2 for coal dust containing a respirable quartz fraction greater than 5 percent and a 2.4 mg/m(3) limit for coal dust containing a respirable quartz fraction of less than 5 percent. The ACGIH has a TLV-TWA of 0.1 mg/m(3) for the respirable quartz fraction of coal dust containing more than 5 percent quartz, and 2 mg/m(3) for the respirable dust fraction of coal dust containing less than 5 percent quartz. OSHA proposed 8-hour TWA limits of 0.1 mg/m(3) for the respirable quartz fraction of coal dust containing more than 5 percent quartz and 2 mg/m(3) for the respirable dust fraction containing less than 5 percent quartz; the final rule establishes these limits. OSHA's proposed and final rule limits do not represent an actual change in the value of the limits for coal dust containing more than 5 percent respirable quartz; instead, they do away with the Agency's previous and cumbersome formula limit. Coal is a dark brown to black solid formed from fossilized plants.

Because OSHA is not lowering the limits for coal dust or considering the health effects evidence for these limits but is merely changing the form in which the limits are expressed, no discussion of the health evidence is included in the final rule. The Gulf Power Company (Exs. 3-938 and 3-1144) believed that OSHA was proposing to change the value of the coal dust limits rather than the form in which those limits were being expressed. In the final rule, OSHA has clarified this fact by emphasizing it in the beginning and end of this discussion. Lawrence Hecker, Corporate Director of Industrial Hygiene and Toxicology for Abbott Laboratories, requested that both Z-table entries for coal dust in the final rule specifically indicate that it is the "respirable quartz fraction" that is to be measured (Ex. 367f, p.9). In response to this comment, OSHA intended to identify the "respirable fraction" in the final rule Z-1-A table since OSHA's intent was only to simplify the units and not make any substantive changes (see last paragraph of discussion on coal dust). The suggested change by Mr. Hecker (respirable quartz fraction) would result in up to an order of magnitude increase in the PEL for a highly toxic substance.

NIOSH (Ex. 8-47, Table N2; Tr. p. 3-86) believes that the limit for quartz-bearing coal dust should be reduced to 0.05 mg/m(3) as an 8-hour TWA on the basis of the potential carcinogenicity of respirable crystalline silica. OSHA is aware of some recent studies (NIOSH 1986b; Hurley and Maclaren 1987; IARC 1987) on the health effects of exposure to coal dust, and the Agency is monitoring this literature to assess the need for a reevaluation of this limit.

In the final rule, OSHA is establishing an 8-hour TWA PEL of 0.1 mg/m(3), measured as the respirable dust fraction, for coal dust having a respirable quartz fraction of more than 5 percent quartz, and an 8-hour TWA PEL of 2 mg/m(3) TWA, measured as the respirable dust fraction, for coal dust having a respirable quartz fraction of less than 5 percent quartz. The Agency's previous formula limit for silica containing more than 5 percent quartz (respirable fraction) is equivalent to the 0.1 mg/m(3) limit in terms of airborne concentration. Thus, the final rule's limit is intended to simplify the units used to measure and express the limit; it does not represent an actual change in the value of the limit (see discussion for crystalline silica-quartz later in this section). OSHA believes that this revision will simplify employee exposure monitoring.

ETHYL ACRYLATE CAS: 140-88-5; Chemical Formula: CH(2) = CHCOOC(2)H(5) H.S. No. 1161

OSHA formerly had an 8-hour TWA limit of 25 ppm for ethyl acrylate, with a skin notation. The ACGIH has a TLV-TWA of 5 ppm, a TLV-STEL of 25 ppm, and a skin notation for ethyl acrylate, which is a colorless liquid. The proposed PEL was an 8-hour TWA of 5 ppm and a 15-minute STEL of 25 ppm, with a skin notation; the final rule establishes these limits.

Ethyl acrylate produces irritation of the skin, eyes, mucous membranes, gastrointestinal tract, and respiratory system (Dreisbach 1974/Ex. 1-896).

The oral LD(50) in rats fed this substance is 1020 mg/kg, and the 4-hour inhalation LC(50) for these animals ranges between 1000 ppm and 2000 ppm. In rabbits, the dermal LD(50) is 1790 mg/kg (Pozzani, Weil, and Carpenter 1949/Ex. 1-925), and the minimum oral LD(50) is 280 to 420 mg/kg (Treon, Sigmon, Wright, and Kitzmiller 1949/Ex. 1-769). Animal studies also indicate that severe chronic effects may result from exposure to this substance. Rats exposed to levels of 70, 300, or 540 ppm of ethyl acrylate for up to 30 days showed accelerated mortality and pathologic changes in the lungs, liver, and kidneys. In those animals that developed pneumonia, renal and hepatic lesions were also seen. In a parallel study, rats, rabbits and guinea pigs who were subjected to ethyl acrylate concentrations in excess of 75 ppm for 50 seven-hour inhalation periods exhibited pulmonary edema; degenerative changes in the heart, liver, and kidneys; and death (Treon, Sigmon, Wright, and Kitzmiller 1949/ Ex. 1-769). Miller et al. (1980, as cited in ACGIH 1986/Ex. 1-3, p. 240) reported that rats and mice exposed to 75 or 225 ppm, six hours per day for 30 days, developed nasal lesions and other degenerative inflammatory changes in the nasal structure. In other studies, rats and mice administered 100 or 200 mg/kg ethyl acrylate by gavage five times per week for 103 weeks developed inflammation and hyperplasia of the forestomach in addition to squamous cell carcinomas and papillomas in the same area (NTP 1983b, as cited in ACGIH 1986/Ex. 1-3, p. 240). Based on a study by Miller et al. (1980, as cited in ACGIH 1986/Ex. 1-3, p. 240), in which rats and mice exposed to 25 or 75 ppm ethyl acrylate for six hours per day, five days per week for 27 months developed lesions in the nasal cavity even at the lowest dose, the ACGIH (1986/Ex. 1-3, p. 240) concurs with the American Industrial Hygiene Association (1966/Ex. 1-1195) that a 25-ppm limit for ethyl acrylate is too high to prevent irritating effects in exposed humans.

In a study by Nemec and Bauer (1978, as cited in ACGIH 1986/Ex. 1-3, p. 240), human volunteers experienced drowsiness, headache, and nausea after prolonged inhalation exposures at 50 to 75 ppm. Opdyke (1975/Ex. 1-922) reported that the application of a 4-percent concentration of ethyl acrylate produced skin-sensitization reactions in 10 out of 24 volunteers.

NIOSH (Ex. 8-47, Table N6B; Tr. pp. 3-97 to 3-98) believes that a full Section 6(b) rulemaking is needed for this potential occupational carcinogen. A comment from Basic Acrylic Monomer Manufacturers (Ex. 184) urges OSHA not to adopt values still on the ACGIH Notice of Intended Changes. As discussed in Section IV, OSHA is not adopting these limits.

In the final rule, OSHA is establishing an 8-hour TWA of 5 ppm and a 15-minute STEL of 25 ppm for ethyl acrylate; the skin notation is being retained. The Agency concludes that these limits will protect workers from the significant risk of severe eye, nose, and skin irritation associated with exposure to this substance at the levels permitted by OSHA's former limit. The Agency considers these adverse effects material impairments to health.

FERROVANADIUM DUST CAS: 12604-58-9; Chemical Formula: FeV H.Z. No. 1177

OSHA formerly had a limit of 1 mg/m(3) for ferrovanadium dust. The ACGIH has a TLV-TWA limit of 1 mg/m(3) with a TLV-STEL of 3 mg/m(3); the NIOSH-recommended exposure limit for metallic vanadium is 1 mg/m(3) as a 10-hour TWA. The proposed PEL was 1 mg/m(3), with a STEL of 3 mg/m(3). NIOSH (Ex. 8-47, Table N1) concurred with these limits, which are established by the final rule. Ferrovanadium dust exists as dark, odorless, solid particles.

Soviet studies in animals showed ferrovanadium dust to be less toxic than vanadium pentoxide. Roshchin (1952/Ex. 1-1166) reported that no acute intoxication occurred in animals exposed to ferrovanadium dust at concentrations as high as 10,000 mg/m(3); however, serious chronic pulmonary changes were observed after short-term exposures (one hour) on alternate days for two months to concentrations in the 1000- to 2000 mg/m(3) range. These pulmonary changes consisted of chronic bronchitis and chronic lung inflammation. Only NIOSH commented on this substance.

OSHA is establishing a PEL of 1 mg/m(3) TWA and a STEL of 3 mg/m(3) for ferrovanadium dust to reduce the significant risk of chronic pulmonary damage shown to be associated with exposures to this substance at the elevated short-term levels formerly permitted by the TWA limit alone. OSHA considers the pulmonary damage caused by exposure to ferrovanadium dust to be material impairments of health. The Agency concludes that the combined TWA limit and STEL will substantially reduce this risk.

FIBROUS GLASS CAS: None. Chemical Formula: None H.S. No. 1178

The Agency proposed a PEL of 5 mg/m(3) (the TLV established by the ACGIH) for total fibrous glass. NIOSH (1977d/Ex. 1-261) has recommended that employee exposures to fibrous glass dust not exceed 5 mg/m(3) as an 8-hour TWA (as total dust) or 3 fiber/cc for fibers greater than 10 um long.

Extensive evidence was submitted to the record regarding the proposed PEL for fibrous glass. Because of the conflicting nature of some of the evidence and the complexity of the issues raised, OSHA has not yet been able to reach a final conclusion. Therefore, OSHA is temporarily delaying a final decision regarding the establishment of a separate PEL for fibrous glass; however, OSHA will make this final decision within a reasonable period of time.

GRAIN DUST (OAT, WHEAT, AND BARLEY) CAS: None; Chemical Formula: None H.S. No.: 1190

A decision by the Occupational Safety and Health Review Commission (Secretary of Labor v. Krause Milling Company, OSAHRC Docket No. 78-2307, April 22, 1986) has held that there was no former OSHA PEL for grain dust. Based on the ACGIH recommendation, OSHA proposed to establish a 4 mg/m(3) 8-hour TWA PEL for dust generated from wheat, oats, and barley, and NIOSH (Ex. 8-47, Table N1) supported the proposal. However, in the final rule the Agency is establishing an 8-hour TWA limit of 10 mg/m(3) for these dusts. Grain dust is a complex mixture of husk particles, cellulose hairs and spikes, starch granules, spores of fungi, insect debris, pollens, rat hair, and approximately 5 percent mineral particles. The mean particle size of the airborne dusts may be less than 5 um. A substantial amount of information was submitted to the record addressing the health evidence and feasibility of attaining a 4 mg/m(3) TWA limit in the feed industry (Exs. 3-751, 3-752, 3-755, 8-55, 104, 109, 118, 180, 185, and 198; Tr. pp. 6-247 to 6-319). OSHA has carefully reviewed this evidence and has determined that an exposure limit for grain dust is necessary to reduce the significant risk of adverse respiratory effects associated with exposure to this material. OSHA's review of the health evidence, described below, shows that grain workers will experience adverse respiratory symptoms upon exposure to grain dust levels exceeding the current nuisance dust limit of 15 mg/m(3) TWA; this observation was not disputed in the record. Respiratory symptoms are also prevalent among grain dust workers exposed to levels below 10 mg/m(3) TWA, as total dust, although these symptoms are diminished compared with those associated with exposure to higher dust levels. Because of uncertainties in establishing a clear threshold exposure level for respiratory effects and in determining the feasibility of the proposed 4 mg/m(3) limit (see Section VII, Summary Economic Impact and Regulatory Flexibility Analysis), OSHA is establishing a 10 mg/m(3) limit as an 8-hour TWA for wheat, oat, and barley dust to reduce the risk of respiratory disease.

The adverse effects of inhaling grain dust have been known for at least two-and-one-half centuries, dating back to Rammazini who, in 1713, described the respiratory hazards associated with exposure to cereal grain dust. More recently, several epidemiological studies conducted over the past few decades (cited by ACGIH 1986/Ex. 1-3 and Rankin et al. 1986) have demonstrated that exposure to grain dust causes "grain fever," wheezing, chest tightness, productive cough, eye and nasal irritation, and symptoms of chronic respiratory disease. Grain dust may also induce asthmatic reactions via an allergic mechanism, particularly in individuals who are predisposed to developing allergies (i.e., atopic individuals). Thus, OSHA believes that the need for an occupational limit on exposure to grain dust is clear.

The basis for OSHA's proposed 4 mg/m(3) limit was a NIOSH-sponsored study of grain workers by Rankin et al. (Study of the Prevalence of Chronic, Non-Specific Lung Disease and Related Health Problems in the Grain Handling Industry, DHHS (NIOSH) Pub. No. 86-117, 1986). A 1980 draft of this study by Rankin and do Pico (Ex. 1-1193) formed the basis for the ACGIH-recommended limit of 4 mg/m(3) TWA. This study evaluated the health status of 310 grain handlers in Wisconsin and Minnesota. The grain handlers were selected from eight elevator companies, from state grain inspection agencies, and from longshoring companies. Health status was determined by questionnaire and by physical examination, which included an assessment of pulmonary function, immunologic evaluation, blood and urine chemistries, and chest roentgenograms. The comparison group that served as controls consisted of 239 city workers who spent the majority of their workdays outside.

From the questionnaires, Rankin et al. (1986) found that the grain handlers had a higher prevalence of respiratory symptoms than did the city workers. The prevalence of respiratory symptoms was highly significant (Rankin et al. 1986, Table 13), and was independent of smoking status. The symptoms reported by grain handlers represented both acute and chronic airways reactions (occupational asthma and chronic bronchitis). Wheezing and/or chest tightness generally started within two hours of beginning the work shift. Episodes of grain fever occurred infrequently; this was attributed by the workers to improved working conditions over the previous three years. Acute recurrent conjunctivitis and rhinitis were reported to occur among most grain workers.

Lung function tests showed that exposure to grain dust had a highly significant adverse effect on pulmonary function (Rankin et al. 1986, Table 30). There was, however, no correlation between reduced pulmonary function and job category, length of employment, or place of work. The lung function decrement observed among grain handlers was not related to smoking history alone; grain handlers who were smokers or ex-smokers showed significant declines in pulmonary function when compared to city workers who were smokers or ex-smokers.

Grain workers who reported symptoms had lower values of ventilatory function than did workers without symptoms. The prevalence of chronic bronchitis symptoms with measured airways obstruction was higher in grain workers than in controls, regardless of smoking history. Chronic bronchitis with airways obstruction was also related to length of employment. Rankin et al. (1986) concluded that these findings "suggest that chronic grain dust exposure may result in chronic obstructive pulmonary disease" (p. 26).

Rankin et al.'s (1986) study also included a work-shift study in which 248 grain workers and 192 city workers were sampled for grain dust exposure during a work shift. Symptoms occurring during the shift were recorded and pulmonary function readings were taken before and after the shift. Only 14 percent of grain workers were exposed to an 8-hour TWA level exceeding 5 mg/m(3) total grain dust; 7 percent were exposed above 10 mg/m(3). Rankin et al. (1986) reported that grain workers showed a significant excess of cough and expectoration during a work shift in which dust concentrations were below 5 mg/m(3). At dust levels between 10 and 15 mg/m(3), there was a significantly increased prevalence of wheezing and dyspnea during the shift among grain workers as compared with controls (Rankin et al. 1986, Table II-156). Workers with pre-existing airways obstruction experienced significant pre- to post-shift declines in ventilatory function at dust levels below 10 mg/m(3). However, the changes observed in pre- to post-shift pulmonary function did not correlate with the presence of symptoms during the shift.

Rankin et al. (1986) also conducted a short-term (three-year) follow-up study of lung function among grain workers. Their results showed no greater declines in FEV or FVC over the three-year period than could be accounted for by age alone. However, there was a significant decline in other measures of lung function (MMF, Vmax50, Vmax75) among both smoking and nonsmoking grain workers. The authors concluded that, although a grain-dust-related decline in these measures was observed, the long-term effects of smoking on lung function were probably greater than those caused by grain dust.

The ACGIH (1986/Ex. 1-3) recommended the 4 mg/m(3) TLV based largely on the following conclusion by Rankin et al. (1986):

The incidence of respiratory symptoms was higher among grain workers exposed to mean total airborne dust (time-weighted average concentration) of 13.9 mg/m(3) when compared to grain workers exposed to 4 mg/m(3) or less. In the latter group of grain workers the incidence of symptoms was similar to that found among controls (Rankin et al. 1986, p. 51).

This conclusion by Rankin et al. (1986) was derived by correlating the incidence of respiratory symptoms with workers' subjective estimations of dust levels encountered during the work-shift study; workers who judged their dust exposures during the shift to be "more than average" were exposed to mean dust levels of 13.9 + 12 mg/m(3) TWA and had significantly higher incidences of respiratory symptoms than did workers who judged their exposures to be "average" (mean TWA dust exposures of 4 + 8.6 mg/m(3)). From this observation, the ACGIH (1986/Ex. 1-3) interpreted 4 mg/m(3) to be a no-observed-effect level.

This interpretation of Rankin et al.'s (1986) results was heavily criticized by rulemaking participants. For example, the National Grain and Feed Association (NGFA) (Ex. 8-55) argued:

OSHA states that the study found that acute bronchial symptoms did not appear among workers exposed at or below 4 mg/m(3). This figure is in fact an average estimated exposure of 4.21 + 8.62 mg/m(3) and...was based on workers' arbitrary interpretation[s] of 'average' exposure. The researchers grossly overstated their results by implying that a specific level of 4 mg/m(3) was an absolute limit below which the incidence of symptoms among workers was similar to [that among] controls (Ex. 8-55, p. 28).

Although it is true that reliance on employees' subjective impressions of the magnitude of dust exposure during a shift is not as precise as taking quantitative samples of dust exposure, it must be emphasized that Rankin et al. (1986) did find a significant excess of respiratory symptoms among grain workers whose TWA exposures were objectively determined, by air sampling, to be less than or equal to 10 mg/m(3) TWA; an excess incidence of wheezing and dyspnea were also reported among grain workers exposed to levels of between 10 and 15 mg/m(3) TWA.

The NGFA also criticized the Rankin et al. (1986) study for failing to address potential biases in the design and administration of the health questionnaire (Ex. 8-55, p. 25). In Appendix C of its submission, the NGFA cites a discussion of questionnaire biases by Gamble and Battigelli (in Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., vol. 1, pp. 129-32, Clayton and Clayton 1981) and states that questionnaires provide a large source of error that must be guarded against," particularly when the questionnaire is self-administered (Ex. 8-55, Appendix C, pp. 3-4). OSHA believes that, although such biases are possible, Rankin et al. (1986) took measures to reduce such biases. First, their study population derives from many workplaces, including eight grain elevators, state grain inspection agencies, and longshoring companies; it thus appears unlikely that the overall results obtained from the questionnaires would be substantially biased as a result of employee dissatisfaction with the working conditions of a particular worksite. Second, Rankin et al. (1986) did rely on trained interviewers to review all questionnaires for completeness and to assist in the completion of a questionnaire when necessary. The use of trained interviewers, according to Gamble and Battigelli (Ex. 8-55, Appendix C, p. 3), may correct such biases. In addition, Rankin et al. (1986) found a correlation between symptoms reported on questionnaires and exposure levels, which suggests that the questionnaire results were not heavily biased.

Despite some of the criticisms of the Rankin et al. (1986) study, these authors' results are consistent with some other published studies of grain workers. Dr. Roy Buchan, Chief of the Occupational Health and Safety Section, College of Veterinary Medicine and Biomedical Sciences at Colorado State University, performed a study of the general health of 31 grain handlers (submitted as part of Ex. 3-751). A total of 204 personal TWA dust samples were taken, of which only six exceeded 10 mg/m(3). Dr. Buchan found that neither age of facility, smoking history, nor past exposure to grain dust had any significant effect on symptom responses. There was a statistically significant association between grain dust exposure levels and symptom responses. The reported symptoms included nasal and throat irritation, chest discomfort, and phlegm production. Dr. Buchan concluded that, "although the association was mathematically weak but statistically significant, it would rationally be expected that symptom severity would become more pronounced as dust concentrations increase, since dust exposures in this investigation were surprisingly low (mean = 0.7 mg/m(3) TWA)." In a larger study of 390 Canadian grain workers, Cotton , Graham, Li et al. (1983, submitted as part of Ex. 3-751) also reported a significant excess incidence of respiratory symptoms among grain workers despite total dust concentrations generally below 10 mg/m(3).

Although these studies show a consistent pattern of increased prevalence of respiratory symptoms among grain handlers exposed below 10 mg/m(3), the association between low-level exposure to grain dust and the development of chronic pulmonary disease remains open to interpretation. Several studies, including Rankin et al. (1986), Chan-Yeung, Giclas, and Henson (1980/Ex. 1-474), and Broder, Corey, Davies et al. (1985, as cited in Ex. 3-751) have generally not found decrements in pulmonary function associated with long-term exposure to grain dust. In addition, chest roentgenograms have found no evidence of lung scarring or fibrosis (Rankin et al. 1986) among grain handlers. However, symptoms of chronic bronchitis have been frequently noted among grain handlers, including those who have never smoked (Rankin et al. 1986; Cotton, Graham, Li et al. 1983). According to Cotton et al. (1983, as cited in Ex. 3-751, p. 139), "The significance of the increase in chronic bronchitis and cough in workers and wheezing in nonsmoking workers in terms of eventual respiratory disability remains uncertain but the nuisance and discomfort of these symptoms for workers must also be considered."

Because of the conflicting evidence for an association between exposure to grain dust and the development of chronic lung damage, the NGFA (Exs. 8-55 and 180) and the American Feed Industry Association (AFIA) (Ex. 185) take the position that grain dust has been shown to be a nuisance dust. For example, in its posthearing brief, the AFIA stated:

[F]eed industry workers are generally healthy, and experience no unique adverse health effects resulting from current levels of grain dust exposure. Therefore, setting a PEL for grain dust is unwarranted and unnecessary.

The studies relied on by OSHA...fail to show that grain dust, at current levels, is a "harmful physical agent"....Granted, grain dust may have some effect on some individuals' health; however, nothing in the record demonstrates that these effects, at typical current levels, are anything more than reversible and non-serious (Ex. 180, p. 14).

OSHA does not concur with this view. In the studies described above, as well as in others in the record, grain workers have consistently reported an excess prevalence of respiratory symptoms, including chronic bronchitis, at low levels of exposure to grain dust. OSHA believes that these symptoms, even in the absence of definitive evidence of irreversible lung damage, constitute material impairment of health and interfere with the well-being of workers. This was attested to at the informal hearing by Deborah Berkowitz, Director of Safety and Health for the Food and Allied Trades Department, AFL-CIO:

I want to make it clear that study after study documents a very real acute hazard to grain workers. Living with chronic bronchitis is not a hazard that should go unchecked. In fact, study after study point to the possibility of very real long-term damage from chronic cumulative effects of exposure to grain dust. But even without the possibility of long-term disability, acute hazards clearly pose significant risk[s] to workers (Tr. pp. 6-306 to 6-307)

OSHA concludes that employees are placed at significant risk of respiratory symptoms, including chronic bronchitis, as a result of exposure to grain dust. It is clear that such symptoms occur at grain dust levels exceeding OSHA's former limit for dusts and particulates (15 mg/m(3) TWA); in addition, workers have reported symptoms of wheezing and dyspnea upon exposure to dust levels between 10 and 15 mg/m(3) TWA. Increases in respiratory symptoms have also been reported to occur among grain workers exposed generally to less than 10 mg/m(3), although symptoms are diminished at these lower levels. At this time, it is difficult to identify the threshold at which adverse respiratory effects are likely to occur. This uncertainty is reflected in a posthearing submission by the NGFA (Ex. 118) in which Dr. George Bardwell of the University of Denver performed a statistical analysis of the FEV measurements reported by Chan-Yeung, Giclas, and Henson (1980/Ex. 1-474) in grain workers. Dr. Bardwell estimated that the threshold for reduced FEV is 6.41 mg/m(3), with a 95-percent confidence interval of between 0 and 24.4 mg/m(3).

In addition, considerable information was entered into the record addressing the technological feasibility of achieving the proposed 4 mg/m(3) grain dust PEL (Exs. 3-751, 3-752, 3-755, 8-55, 109, 118, 180, 185, and 198). These data are conflicting, particularly with regard to smaller grain elevators. In light of these uncertainties, OSHA is establishing a 10 mg/m(3) 8-hour TWA limit for grain dust, measured as total dust. OSHA finds that establishing this limit will substantially reduce the risk of adverse respiratory effects that occur at higher levels of exposure. OSHA has also concluded that a 10 mg/m(3) TWA limit is technologically feasible (see Section VII).

The American Feed Industry Association (Ex. 185) objected to OSHA's inclusion of oat and barley dust in the definition of grain dust, stating that the studies relied on by OSHA in the NPRM pertaining to oat and barley dust (Darke, Knowelden, Lacey, and Ward 1976; Cockcroft et al. 1983) were not relevant to addressing the effects of exposure to oat and barley dust at levels below 15 mg/m(3). However, Rankin et al. (1986) reported in their study, which involved exposure to much lower levels of grain dust, that the types of dust most likely to bring on or aggravate symptoms of cough and/or expectoration were durum wheat and barley, followed by spring wheat, rye, and oat. Least likely were corn, soybean, sunflower, and others. In addition, Mr. George Talley and Mr. Michael Garcia, industrial hygienists at Los Alamos National Laboratory, commented that, according to their personal experience, barley beards are more irritating than wheat dust (Ex. 3-1095). Therefore, OSHA finds that there is sufficient evidence to include oat and barley in the definition of grain dust.

At the informal hearing, Ms. Berkowitz raised the question as to whether OSHA intended to apply the grain dust limit to flour mills and bakeries (Tr. 6-310). To support this position, she submitted several reports describing asthma occurring among bakers; bakers' asthma has been attributed to flour dust exposure (Ex. 3-751). As with all other substances included in this rulemaking, OSHA intends the new limit for grain dust to apply to all workplaces, including flour mills and bakeries where there is the potential for exposure to grain dust.

In the final rule, OSHA is establishing an 8-hour TWA limit of 10 mg/m(3) for grain dust, measured as total dust. Grain dusts other than oat, wheat, and barley are regulated under OSHA's generic "particulates not otherwise regulated" PEL of 15 mg/m(3) (total particulate) and 5 mg/m(3) (respirable fraction). The Agency concludes that this limit will substantially reduce the significant risk of acute and chronic respiratory symptoms and disease associated with exposure to grain dust at the levels formerly permitted by the absence of an OSHA limit. The Agency has determined that the respiratory effects caused by exposure to grain dust represent material impairments of health.

GRAPHITE, NATURAL CAS: 7782-42-5; Chemical Formula: None H.S. No. 1191

The former OSHA limit for natural graphite (total dust) was 15 million particles per cubic foot (mppcf), which is equivalent to 2.5 mg/m(3) as respirable dust (assuming that respirable mass is one-half total particle mass). The proposed PEL was 2.5 mg/m(3) for respirable natural graphite dust containing less than 1 percent quartz; NIOSH (Ex. 8-47, Table N1) concurred with this limit, and the final rule promulgates it. The ACGIH has a graphite TLV of 2.5 mg/m(3) for respirable dust containing less than 1 percent quartz. Graphite is a mineral substance that is best known for its use as the "lead" in pencils.

Early reports established that graphite deposited in the lungs of occupationally exposed workers caused pneumoconiosis (Koopman 1924/Ex. 1-131). Subsequent research described the condition produced by exposure to graphite as anthracosilicosis, a pulmonary condition similar to that seen in coal miners, based on radiographic and histologic examinations in exposed individuals (Harding and Oliver 1949/Ex. 1-71). The fibrotic changes seen in graphite workers appear to be related to the silica content of the graphite; experimental animals that were administered graphite that did not contain silica did not develop fibrotic changes (Ray, King, and Harrison 1951/Ex. 1-46), while another study found that graphite containing only a small amount of silica produced fibrotic changes in exposed animals (Ottowicz and Paradowski 1961/Ex. 1-190). Radiologic changes were also observed among graphite mine and production workers exposed to graphite containing from 3.6 to 10 percent silica (Pendergrass, Vorwald, Mishkin et al. 1967/Ex. 1-77). OSHA received no comments on this substance except for those from NIOSH.

In the final rule, OSHA is revising its former limit of 15 mppcf to a limit of 2.5 mg/m(3) for the respirable fraction of graphite containing less than 1 percent quartz; this change represents a change only in the units used to express or measure the limit, not a change in the value of the limit. OSHA is revising its limit to simplify the monitoring of employee exposures, because the use of impingers and microscopic analyses are not required to measure exposures that are expressed in mg/m(3) rather than in mppcf.

INDIUM AND COMPOUNDS CAS: 7440-74-6; Chemical Formula: In H.S. No. 1213

There was no former OSHA limit for indium and compounds; however, the proposed and final rule PEL is 0.1 mg/m(3) as an 8-hour TWA. NIOSH (Ex. 8-47, Table N1) concurred with this limit. The ACGIH recommends that exposures to indium not exceed 0.1 mg/m(3) over an 8-hour shift. Indium metal is silver-white, shiny, and ductile.

Although there is no direct human evidence of the effect of indium compounds, severe effects have been produced by indium exposures in experimental animals. Rats that inhaled the sesquioxide form of indium at airborne concentrations ranging from 24 to 97 mg/m(3) daily for a total of 224 hours developed widespread alveolar edema; these histologic lesions did not change over a 12-week post-exposure period (Leach, Scott, Armstrong et al. 1961, as cited in ACGIH 1986/Ex. 1-3, p. 322). Exposure of animals to indium reduces alveolar clearance and may be associated with chronic respiratory insufficiency, recurrent acute pneumonitis, and death (Jones 1960, as cited in ACGIH 1986/Ex. 1-3, p. 322). NIOSH was the only commenter on this substance.

Because of the severity of indium-induced injury and the persistence of such injuries, OSHA concludes that, in the absence of any exposure limit, exposed employees are at significant risk of developing chronic lung function impairment. The Agency is establishing an 8-hour TWA limit of 0.1 mg/m(3) for indium and compounds to substantially reduce this risk.

IRON OXIDE (DUST AND FUME) CAS: 1309-37-1; CHEMICAL FORMULA: Fe(2)O(3) H.S. No. 1215

OSHA formerly had an 8-hour TWA limit of 10 mg/m(3) for iron oxide fume. The ACGIH has established a limit of 5 mg/m(3), measured as iron, total particulate. The proposed PEL was 5 mg/m(3), and NIOSH (Ex. 8-47, Table N1) supported the proposed limit. However, the final rule retains OSHA's former limit of 10 mg/m(3) for this substance. The fume of iron oxide is red-brown in color.

Animals exposed to iron oxide or to iron oxide mixed with less than 5 percent silica by inhalation or by intratracheal injection did not develop pulmonary fibrosis (Naeslund 1940/Ex. 1-650; Harding, Grout, Durkan et al. 1950, as cited in ACGIH 1986/Ex. 1-3, p. 325). Inhalation of iron oxide dust also did not produce lung cancer in mice (Muller and Erhardt 1956/Ex. 1-648).

The evidence of iron oxide's toxicity in humans is conflicting. Drinker, Warren, and Page (1935/Ex. 1-315) concluded that exposures to iron oxide fume should be maintained below 10 mg/m(3), and a U.S. Department of Labor study (1941, as cited in ACGIH 1986/Ex. 1-3, p. 325) found that exposures below 30 mg/m(3) were without adverse effect. There are several studies, on the other hand, that report chest X-ray abnormalities in miners, welders, silver polishers, electrolytic iron oxide workers, foundry workers, and boiler scalers (Doig and McLaughlin 1936/Ex. 1-626; Stewart and Faulds 1934/Ex. 1-764; Doig and McLaughlin 1948/Ex. 1-627; McLaughlin, Grout, Barrie, and Harding 1945/Ex. 1-642; Davidson 1951, as cited in McLaughlin 1951/Ex. 1-727; Pendergrass and Leopold 1945/Ex. 1-653; Dunner and Hermon 1944/Ex. 1-731) exposed to iron oxide dust or fume. Some of these workers developed disabling pneumoconiosis; however, the exposures of many of these workers were mixed and in some cases included exposure to varying amounts of silica.

McLaughlin (1951/Ex. 1-727), whose opinion on the subject is widely accepted, believes that the presence of iron oxide dust or fume in the lung causes a pigmentation (termed siderosis) that is responsible for the changes seen in exposed individuals' chest X-rays. Siderosis is believed not to progress to fibrosis, and 6 to 10 years of exposure to about 15 mg/m(3) iron oxide dust is required before this condition develops (Fawcett 1943/Ex. 1-736; Fleischer, Nelson, and Drinker 1945/Ex. 1-1051; Hamlin and Weber 1950/Ex. 1-698). However, no studies are available that correlate exposure levels with X-ray changes.

Dr. Stuart M. Brooks (NIOSH 1986b, p. 425) notes that "[m]ore sophisticated physiologic testing, including measurement of the lung's mechanical properties, is required to better document lung function changes that may occur following inhalation of iron-containing dusts. In vitro studies or animal experimentation might be helpful in determining dose-response relationships, understanding lung clearance mechanisms for iron, and elucidating any fibrogenic properties of various ferrous compounds."

Some studies have shown that workers with exposures to iron oxide and such other substances as silica, radon gas, diesel exhaust, corn oils, and the thermal decomposition products of synthetic resins (Faulds 1957/Ex. 1-635; Dreyfus 1936/ Ex. 1-897; Bidstrup 1959/Ex. 1-1030; Boyd, Doll, Faulds, and Leiper 1970/Ex. 1-716; Braun, Guillerm, Pierson, and Sadoul 1960/Ex. 1-1141; Monlibert and Roubille 1960/Ex. 1-647; Jorgensen 1973/Ex. 1-1023; Muller and Erhardt 1956/Ex. 1-648; Koskela, Hernberg, Karava et al. 1976/Ex. 1-744; Gibson, Martin, and Lockington 1977/Ex. 1-1053) have a greater risk of developing lung cancer. However, OSHA agrees with the ACGIH that, "at this time, it is not generally accepted that exposure to iron oxide dust or fume causes cancer in man" (ACGIH 1986/ Ex. 1-3, p. 325). Stokinger (1984/Ex. 1-672) concluded that exposure to iron oxide dust and fume per se was not carcinogenic.

Several industry commenters (Exs. 8-22, 3-349, 3-829, 129, and 188; Tr. XI, pp. 137-138) objected to the proposed reduction in the PEL for iron oxide on the grounds that exposure to this substance does not cause fibrosis or pulmonary impairment, but rather siderosis, which is a benign pneumoconiosis. The American Iron and Steel Institute (Ex. 129, pp. 12-13) described siderosis as "simply a description of a condition that appears on radiographs." OSHA disagrees with Mr. Hernandez' assessment of the health effects potentially associated with exposure to iron oxide because the Agency believes that any occupational exposure that causes foreign substance to lodge in body tissues is undesirable. However, the Agency concurs with NIOSH's Dr. Brooks (NIOSH 1986b, p. 425) that additional research is necessary to determine why the lung is unable to clear iron-containing dusts after inhalation.

Accordingly, OSHA finds it appropriate to retain the Agency's former PEL for iron oxide dust and fume of 10 mg/m(3), measured as total particulate.

The Agency concludes, based on the evidence currently available, that this limit will protect workers from developing of siderosis, a benign pneumoconiosis that occurs after many years of exposure to levels of iron oxide dust or fume in excess of 15 mg/m(3), and accumulation of iron dust in the lungs associated with ferric oxide exposure.

METHYLENE BIS-(4-CYCLOHEXYLISOCYANATE) CAS: 5124-30-1; Chemical Formula: C(15)H(22)N(2)O(2) H.S. No. 1272

OSHA had no former limit for methylene bis-(4-cyclohexylisocyanate). Prior to 1988, the ACGIH had a TLV ceiling of 0.01 ppm for this alicyclic diisocyanate compound. OSHA proposed a ceiling of 0.01 ppm, and NIOSH (Ex. 8-47, Table N1) supported the proposal. The final rule establishes that limit. OSHA notes that ACGIH adopted a new limit for this substance in 1988 of 0.005 ppm TWA. The NIOSH RELs for methylene bis-(4-cyclohexylisocyanate) are a 0.005-ppm 10-hour TWA and a 0.02-ppm 10-minute ceiling.

Methylene bis-(4-cyclohexylisocyanate) is a pulmonary, skin, and eye irritant. The oral LD(50) in rats is 9.9 g/kg. A 5-percent solution applied to the skin of guinea pigs produced strong erythema and edema, and rabbits treated with 0.1 mg showed severe skin reactions (Younger Laboratories 1965, as cited in ACGIH 1986/Ex. 1-3, p. 392).

Rats inhaling a lethal concentration of 20 ppm for five hours exhibited marked respiratory irritation, tremors, and convulsions during exposure, and their lungs revealed severe congestion and edema after death (E.I. du Pont de Nemours and Co. Inc. 1976, as cited in ACGIH 1986/Ex. 1-3, p. 392). Repeated inhalation exposure at 0.4 ppm produced initial weight loss in rats; exposure at 1.2 ppm caused respiratory irritation and decreased growth (E.I. du Pont de Nemours and Co. Inc. 1978, as cited in ACGIH 1986/Ex. 1-3, p. 392). Guinea pigs exposed to 0.12 ppm and mice exposed to 0.65 ppm did not exhibit dermal sensitivity (Stadler and Karol 1984/Ex. 1-612). Unlike toluene diisocyanate, which is a sensory irritant, methylene bis(4-cyclohexylisocyanate) depresses respiration by producing pulmonary irritation; for example, an exposed mouse showed a 50-percent decrease in respiration rate, along with lung irritation, when exposed to 3.7 ppm of this substance (Weyel and Schaffer 1985/Ex. 1-581).

Human exposures to this compound have resulted in skin sensitization but only infrequently in pulmonary sensitization (Emmett 1976/Ex. 1-552; Israeli, Smirnov, and Sculsky et al. 1981/Ex. 1-701).

NIOSH (Ex. 150, Comments on Methylene Bis-(4-Cyclohexyliso-cyanate)) notes that both the REL and TLV for this substance have been based on the toxicological properties of toluene diisocyanate (TDI) and that "a recent study by NTP (1986a) of chronic effects in animals has produced evidence that cancer is associated with exposure to commercial grade TDI...and to a TDI hydrolysis product, 2,4-TDA...treatment of rats and mice of both sexes by gavage to commercial grade TDI resulted in tumor induction, primarily in the pancreas and liver in male and female rats, and in female mice. The tumorigenic responses observed in both rats and mice treated with TDI meet the criteria of the OSHA cancer policy (29 CFR 1990) for classifying a substance as a potential occupational carcinogen." NIOSH suggests that the recommended RELs (0.005 ppm TWA and 0.02 ppm 10-minute ceiling) be considered as an interim level to be applied to methylene bis-(4-cyclohexylisocyanate) until adequate testing information is available. The AFL-CIO (Ex. 194) supported OSHA's proposed ceiling limit for this substance.

OSHA believes that a ceiling limit of 0.01 ppm is as protective as a 0.005-ppm TWA; the Agency therefore is establishing a ceiling limit of 0.01 ppm for methylene bis-(4-cyclohexylisocyanate). The Agency concludes that this limit will protect workers against the significant risk of eye, skin, and pulmonary irritation potentially associated with occupational exposures to this substance at the levels formerly permitted by the absence of an OSHA limit. The Agency considers these irritant effects caused by exposure to methylene bis-(4-cyclohexylisocyanate) to be material impairments of health.

MICA CAS: 12001-26-2; Chemical Formula: K(2)Al(4)(Al(2)Si(6)O(20))(OH)(4) H.S. No. 1276

OSHA formerly had a PEL of 20 mppcf TWA for mica containing less than 1 percent crystalline silica; this limit is equivalent to a 3 mg/m(3) limit.

The ACGIH recommends a limit of 3 mg/m(3) TWA for the respirable dust of mica containing less than 1 percent quartz. OSHA proposed, and the final rule establishes, an 8-hour TWA limit of 3 mg/m(3) for the respirable dust of mica containing less than 1 percent quartz. NIOSH (Ex. 8-47, Table N1) agreed with this decision.

Mica is a colorless, odorless, nonflammable, nonfibrous, water-insoluble silicate occurring in plate form and containing less than 1 percent quartz; it includes nine different species.

The final rule establishes an 8-hour TWA limit of 3 mg/m(3) for respirable mica dust containing less than 1 percent quartz; this limit corresponds to the existing 20-mppcf PEL and is in keeping with the Agency's decision to delete mppcf values in favor of respirable dust values expressed in mg/m(3). The Agency has decided to express this and other similar limits as mg/m(3) to facilitate employee exposure monitoring.

MINERAL WOOL FIBER CAS: None. Chemical Formula: None H.S. No. 1277

OSHA proposed a limit of 10 mg/m(3) TWA for mineral wool fiber, measured as total particulate containing less than 1 percent quartz; this was the same limit recommended by the ACGIH (1986/Ex. 1-3). NIOSH recommends a 5 mg/m(3) (8-hour TWA) limit, measured as total dust, as well as a 3-fiber/cc limit for fibers greater than 10 um long.

Extensive evidence was submitted to the record regarding the proposed PEL for mineral wool. Because of the conflicting nature of some of the evidence and the complexity of the issues raised, OSHA has not yet been able to reach a final conclusion. Therefore, OSHA is temporarily delaying a final decision regarding the establishment of a separate PEL for mineral wool fiber; however, OSHA will make this final decision within a reasonable period of time.

NICKEL (SOLUBLE COMPOUNDS) CAS: 7440-02-0; Chemical Formula: Varies H.S. No. 1283

The former OSHA PEL for all forms of inorganic nickel (as Ni) was 1 mg/m(3) TWA. Based on the ACGIH recommendation, OSHA proposed revising this limit to 0.1 mg/m(3) TWA; this limit is established in the final rule. NIOSH recommends that exposure to any form of inorganic nickel be maintained at or below 0.015 mg/m(3).

A variety of toxic effects results from exposure to nickel compounds. Soluble nickel salts cause contact dermatitis in sensitized individuals and eye irritation (ACGIH 1986/Ex. 1-3, p. 422). Cases of asthmatic lung disease have been reported among nickel-plating workers (EPA 1986a/Ex. 1-1132).

OSHA's proposal to lower the PEL for soluble nickel compounds to 0.1 mg/m(3) was based primarily on evidence that exposure to soluble nickel at low levels and for relatively short durations causes pathological changes in the lungs of experimental animals. In addition, OSHA reviewed several animal and human studies designed to investigate the carcinogenic potential of soluble nickel compounds. Three soluble nickel compounds have been tested for their carcinogenic potential: nickel chloride, nickel sulfate, and nickel acetate. Some sparingly soluble compounds, nickel carbonate and nickel hydroxide, have also been studied.

The results of animal studies suggest that some soluble nickel compounds are potentially carcinogenic; however the data are derived predominately from injection studies and results are conflicting. Results from occupational studies on soluble nickel compounds are also conflicting and are confounded by the presence of several types of nickel compounds in the facilities studied.

In the proposal, OSHA made a preliminary finding that exposure to soluble nickel compounds presented a potential cancer mortality risk to workers. Since publication of the proposal, however, OSHA has reviewed all of the record evidence, including an additional epidemiologic study, and has determined that further analysis is necessary before any definitive findings can be made with regard to the carcinogenic potential of the soluble nickel compounds. OSHA wishes to emphasize, however, that this determination does not negate the evidence that exposure of experimental animals to low levels of soluble nickel causes pathological changes in the lung. Accordingly, OSHA is establishing the 0.1 mg/m(3) TWA PEL in the final rule, as proposed, but is basing this limit on the respiratory toxicity of these compounds. OSHA's findings on the evidence on soluble nickel compounds is presented below.

Bingham, Barkley, Zerwas et al. (1972/Ex. 1-204) exposed rats by inhalation to 0.1 mg/m(3) nickel chloride for 12 hours per day for two weeks. Animals showed evidence of pulmonary irritation and damage in the form of marked mucous secretion, hyperplasia, and accumulations of alveolar macrophages. Fluid obtained by lung lavage appeared very cloudy and viscous due to the presence of free alveolar cells. Rats and guinea pigs exposed daily to 1.0 mg/m(3) (as Ni) nickel chloride for six months showed increased lung weight, which is an indication of pulmonary damage and hyperplasia (Clary 1977, as cited in ACGIH 1986/Ex. 1-3, p. 422); exposed rats also developed signs of interstitial fibrotic lesions. Rabbits inhaling 0.3 mg/m(3) (as Ni) nickel chloride aerosol for 30 days showed a doubling in alveolar cell number and volume of alveolar epithelial cells, as well as nodular accumulation of macrophages and laminated structures (Johansson, Curstedt, Robertson, and Camner 1983/Ex. 1-273). These studies clearly show that exposure at or below the former OSHA PEL of 1.0 mg/m(3) for soluble nickel, even for durations considerably less than a working lifetime, is associated with increased cell turnover and pathological changes in the lung. These pathological changes, in particular the appearance of fibrotic lesions, observed in animals exposed to low levels of soluble nickel salts indicate that lung damage has occurred and suggests that significant decrements in lung function may result from prolonged exposure to these low levels. Furthermore, the appearance of hyperplasia is indicative of abnormal cell growth and suggests the presence of pre-cancerous lesions.

Nickel chloride has been reported to be mutagenic in Salmonella typhimurium and Cornebacterium, but negative in E. coli (EPA 1986a/Ex. 1-1132). The positive studies are not considered conclusive, however, because the S. typhimurium report is an abstract lacking detailed data and Cornebacterium is not the usual species used in these tests. Amacher and Paillet (1980/Ex. 1-286) reported that nickel chloride was mutagenic in mouse lymphoma cells and demonstrated a dose-response relationship for this endpoint.

Some in vitro studies using soluble nickel compounds report finding chromosomal aberrations (EPA 1986a/Ex. 1-1132). These studies do not demonstrate a dose-response relationship or statistical significance, which weakens their findings. Several in vivo studies have failed to detect chromosomal aberrations (EPA 1986a/Ex. 1-1132). However, several in vitro studies on nickel sulfate and nickel chloride have reported findings of sister chromatid exchanges (EPA 1986a/Ex. 1-1132).

Some animal studies on soluble nickel compounds suggest that these compounds are carcinogenic in animals. Strain A mice receiving intraperitoneal injections of nickel acetate had an increased rate of lung adenomas and adenocarcinomas that was statistically significant in the high-dose group (Stoner, Shimkin, Troxell et al. 1976/Ex. 1-203). The animals were injected three times per week for eight weeks at 72, 180, or 360 mg/kg.

EPA (1986a/Ex. 1-1132) reported a study in which rats were given monthly intramuscular injections of 35 mg/kg nickel acetate for four to six months (Haro, Furst, and Falk 1968/Ex. 1-1022). Twenty-two percent of the treated rats developed sarcomas. Payne (1964/Ex. 1-200) observed tumor responses in rats after intramuscular implantation of 7 mg nickel acetate, nickel sulfate, nickel chloride, or nickel carbonate. Implant-site sarcomas developed in one of 35 rats exposed to nickel acetate, one of 35 rats exposed to nickel sulfate, none of 35 rats exposed to nickel chloride, and four of 35 rats exposed to nickel carbonate.

Results of other studies on nickel sulfate have been negative. Three studies used intramuscular injection in rats and reported that no tumors developed in the treated group (Gilman 1962/Ex. 1-205; Gilman 1966, as cited in EPA 1986/Ex. 1-1132; Kasprzak, Gabryel, and Jaraczewska 1983/Ex. 1-201). An ingestion study also reported no tumors among treated rats or dogs (Ambrose, Larson, Borzelleca et al. 1976/Ex. 1-211).

Gilman (1966, as cited in EPA 1986a/Ex. 1-1132) administered 5 mg nickel hydroxide to rats by intramuscular injection in each thigh. Nineteen out of 40 injection sites developed sarcomas. Kasprzak, Gabryel, and Jaraczewska (1983/Ex. 1-201) gave rats intramuscular injections of nickel hydroxide in gel, crystalline, or colloidal form. Five out of 19 animals receiving the gel developed sarcomas (two with metastasis to the lung), three out of 20 receiving the crystalline form developed sarcomas (one with metastasis to the lung), and none of 13 rats receiving the colloid developed tumors.

Inco United States, Inc. (with its subsidiary, Inco Ltd.) (Exs. 3-915 and 167) and the Nickel Producers Environmental Research Association (NiPERA), Inc. (Ex. 3-668) discussed the limitations of the animal data. For example, both of these commenters noted that soluble nickel compounds have produced tumors in animals only by injection and that the results among studies were conflicting. In the NPRM and in the discussion above, OSHA recognized many of these limitations of the data. Although it is true, as Inco pointed out (Exs. 3-915 and 167), that EPA (1986a/Ex. 1-1132) concluded that the animal data are "too limited to support any definitive judgment regarding... [the] carcinogenic potential [of soluble nickel compounds]" (EPA 1986a/Ex. 1-1132, p. 8-229), EPA also concluded that:

The observation of pulmonary tumors in strain A mice from the administration of nickel acetate by intraperitoneal injections and the ability of nickel acetate to transform mammalian cells in culture and to inhibit RNA and DNA synthesis provides limited evidence for the carcinogenicity of nickel acetate and supports a concern for the carcinogenic potential of other soluble nickel compounds (EPA 1986a/Ex. 1-1132, p. 8-229).

OSHA agrees with EPA's assessment that, although some studies are suggestive of a carcinogenic effect and an ability of soluble nickel to transform cells, overall the animal data are too equivocal at this time to support any firm conclusions that soluble nickel compounds do or do not cause cancer in experimental animals.

In addition to the animal evidence described above, OSHA reviewed studies conducted on workers exposed to soluble nickel compounds. Electrolysis workers at a refinery in Kristiansand, Norway, experienced a higher lung cancer risk than employees from the same facility who worked in three other job categories, including roasting and smelting workers (Magnus, Andersen, and Hogetveit 1982/Ex. 1-241). Electrolysis workers were exposed to an aerosol composed predominantly of nickel sulfate, which was estimated to contain soluble nickel at a concentration of 0.2 mg/m(3) (EPA 1986a/Ex. 1-1132); these workers also had higher plasma and urine levels of nickel than did roasting and smelting workers, who were predominately exposed to insoluble nickel subsulfides and oxides. However, exposure to nickel subsulfide and oxides may have occurred in the electrolysis building, and the electrolysis workers may also have worked in other process departments (Grandjean, Andersen, and Nielsen 1988/Ex. 1-207). Roasting and smelting workers were exposed to an estimated average of 0.5 mg/m(3) (as Ni) of roasting dust.

The standardized mortality ratios (SMRs) for lung cancer were 550 for electrolysis workers, 390 for other process workers, and 360 for roasting and smelting workers. The pattern of SMRs for nasal cancer, which is a rare form of cancer in humans, was different among these groups: 2600 for electrolysis workers, 2000 for other process workers, and 4000 for roasting and smelting workers. The results seem consistent with studies that show that roasting and smelting workers have the highest concentrations of nickel in the nasal mucosa, presumably because of the relatively larger particles resulting from roasting. Conversely, electrolysis workers, who showed a larger lung cancer risk than roasting and smelting workers, have higher plasma and urine levels of nickel, suggesting that nickel aerosolized by this process penetrates to the deep lung (EPA 1986a/Ex. 1-1132).

In the NPRM, OSHA presented quantitative estimates of the cancer risk believed to be associated with exposure to soluble nickel; these estimates were based on the Magnus et al. (1982/Ex. 1-241) study of electrolysis workers. During the rulemaking proceeding, OSHA re-evaluated the underlying exposure data and now believes that, because the electrolysis workers may have been concurrently exposed to some insoluble forms of nickel, the data from the Magnus et al. (1982/ Ex. 1-241) study may not be appropriate to use to develop a quantitative estimate of the cancer risk associated with exposure to the soluble forms of nickel.

In contrast to the study of Norwegian nickel refinery workers, a study of 4,288 refinery workers at Port Colborne, Ontario, failed to find an increased lung or nasal cancer mortality rate among electrolysis workers (Roberts et al. 1982; Roberts et al. 1984). Excess incidences of larynx and kidney cancer deaths were reported to be elevated among electrolysis workers, but the numbers of observed deaths were small (two deaths observed for each cause of death). The Roberts et al. studies did report substantially increased incidences of lung and nasal cancer deaths among sinter plant workers exposed to insoluble forms of nickel, a finding consistent with that of Magnus et al. (1982/Ex./1-241) for the Norwegian workers and with many other studies (EPA 1986a/Ex./1-1132).

The stark contrast between these two studies is difficult to explain. According to Inco (Ex./3-915, p. 5), exposures to soluble nickel at the Ontario facility, where no excess risk was found among electrolysis workers, were probably similar to those at the Norwegian facility, where cancer mortality was increased. Exposure data taken during the late 1970s at the Ontario facility (Ex./3-915, Table 1c) indicate that, in most job categories, electrolysis workers were exposed to both soluble and insoluble forms of nickel; this is evidenced by the higher reported employee sampling results for total nickel than for soluble nickel. Thus, concurrent exposure to both soluble and insoluble forms of nickel existed at both the Ontario and Norwegian facilities. The size of the cohort at the Ontario facility was approximately twice that of the Norwegian study; thus, the Ontario study has sufficient power to detect the sizable increases in the incidences of nasal and lung cancer that were reported in the Norwegian study. It is possible, as EPA (1986a/Ex./1-1132) has suggested, that quantitative or qualitative differences in the conditions of exposure between the two cohorts accounts for the discrepant results; however, no information contained in the Ontario or Norwegian reports suggests that there were substantial differences in exposure to soluble nickel. Given the magnitude of the difference in the reported cancer mortality for these two groups of electrolysis workers, it is clear that additional investigation is required to identify the risk factors that account for the different mortality patterns observed in Ontario and Norway. Therefore, OSHA concludes that, at this time, the available human data do not permit any definitive conclusion to be made linking occupational exposure to the soluble forms of nickel with an elevated cancer mortality risk in humans.

The primary impetus to revise the PEL for soluble nickel was the finding that exposure of animals for relatively short periods of time to soluble nickel aerosols at levels equal to or below the former PEL of 1 mg/m(3) produced increased cellular growth and pathological changes that reflect the lung's defense against chemical insult; this finding is consistent across three animal studies conducted in several species (Bingham, Barkley, Zerwas et al. 1972/Ex./1-204; Clary 1977, as cited in ACGIH 1986/Ex./1-3, p. 422; Johansson, Curstedt, Robertson, and Camner 1983/Ex./1-273). Furthermore, these observations were made in animals that were exposed for as short a duration as two weeks and for no more than six months; thus, the consequences of continued, low-level exposure for a full lifetime are unknown. Both Inco (Exs. 3-915 and 167) and NiPERA, Inc. (Ex./3-668) agree that these studies provide an appropriate basis for establishing a 0.1 mg/m(3) PEL for soluble nickel. NIOSH (Ex. 8-47, Table N6B) does not concur with the selection of this limit and believes that a full 6(b) rulemaking is appropriate for the soluble (or inorganic) compounds of nickel.

OSHA concludes that these studies, one of which demonstrated pathological and perhaps precancerous changes following exposure to 0.1 mg/m(3), clearly demonstrate that exposure to the former PEL of 1.0 mg/m(3) presents a significant risk to workers of lung irritation accompanied by pathological changes that may presage cancer. OSHA has determined that these effects constitute material impairments of health and functional capacity. OSHA also concludes that the final rule's reduction in the PEL will substantially reduce these significant risks. Accordingly, OSHA is establishing a revised 8-hour TWA PEL of 0.1 mg/m(3) (as Ni) for the soluble nickel compounds in the final rule.

NITROGEN DIOXIDE CAS: 10102-44-0; Chemical Formula: NO(2) H.S. No. 1289

Both the ACGIH and NIOSH have recommended occupational limits for nitrogen dioxide. The current ACGIH recommendation is for a 3 ppm TWA and a 5 ppm STEL. The NIOSH REL is 1 ppm as a 15-minute short-term limit. OSHA's former PEL was 5 ppm as a ceiling value. The Agency proposed, and the final rule establishes, a permissible exposure limit for nitrogen dioxide of 1 ppm as a 15-minute STEL. NIOSH (Ex. 8-47, Table N1) agreed with the selection of this PEL. Nitrogen dioxide is a reddish-brown gas.

The previous ACGIH TLV of 5 ppm as a ceiling concentration (the basis for the former OSHA limit) was based primarily on the animal studies of Gray, MacNamee, and Goldberg (1952/ Ex. 1-154), Gray, Goldberg, and Patton (1954/Ex. 1-165), and Wagner, Duncan, Wright, and Stokinger (1965/Ex. 1-102). Gray, MacNamee, and Goldberg (1952/Ex. 1-154), and Gray, Goldberg and Patton (1954/Ex. 1-165) demonstrated lung injury among rats exposed for eight or more weeks to an 8-ppm concentration of a mixture of NO(2) and nitric acid, but these authors did not see such lesions in rats exposed for six months to 4-ppm concentrations of this mixture. Wagner, Duncan, Wright, and Stokinger (1965/Ex. 1-102) reported transient, mild, acute effects but no adverse chronic effects in rats exposed to 1 ppm, 5 ppm, or 25 ppm pure NO(2) for 18 months. The ACGIH's recommendation that the 5-ppm TLV be defined as a ceiling rather than as an 8-hour TWA was based on reports that NO(2) accelerated lung tumor development among lung-tumor-susceptible mice; in the late 1960s, the ACGIH believed that a TLV-ceiling value would minimize the risk of accelerating lung tumor development.

The current ACGIH TLVs for NO(2) are a 3-ppm 8-hour TWA and a 5-ppm STEL, and they are based on human studies that indicate that normal respiratory function may be compromised at exposures below the current OSHA ceiling limit of 5 ppm NO(2). In particular, Kosmider, Ludyga, Misiewicz et al. (1972/ Ex. 1-224) reported a slight reduction in vital capacity and maximum respiratory volume in 70 men exposed to 0.4- to 2.7-ppm concentrations of the oxides of nitrogen six to eight hours daily for four to six years. These authors also reported an unspecified number of cases of chronic bronchitis among men in this group. Another study by Vigdortschik, Ancheeva, Matussevistch et al. (1937/Ex. 1-49) reported possible cases of chronic bronchitis and emphysema among 127 workers generally exposed below 2.8 ppm NO(2); these workers were also believed to be exposed to sulfuric acid mist at levels sufficient to cause dental erosion.

The NIOSH REL for NO(2) of 1 ppm as a 15-minute STEL is based on the two human studies discussed above, as well as some human studies involving short-term exposure. Abe (1967/Ex. 1-98) found a 40-percent decrease in effective lung capacity among healthy adult males 30 minutes after a 10-minute exposure to 4-to 5-ppm NO(2). Expiratory and inspiratory maximum viscous resistance also increased by 92 percent after exposure. NIOSH (1976j/Ex. 1-265) concluded that Abe's results "document a definite and undesirable effect" at exposures approaching the former OSHA limit. A significant decrease in carbon monoxide diffusing capacity was observed by Von Nieding, Krekeler, Fuchs et al. (1973/Ex. 1-770) in healthy adults exposed to 5 ppm for 15 minutes. NIOSH also cites the work of Von Nieding, Wagner, Krekeler et al. (1971/Ex. 1-1204) and by Von Nieding and Krekeler (1971/Ex. 1-1175), who reported significant increases in airway resistance among 88 chronic bronchitis patients after a 15-minute exposure to a concentration of NO(2) as low as 1.5 ppm. NIOSH (1976j/ Ex. 1-265) concluded that the specific concentration of NO(2) required to produce pulmonary changes in normal, healthy adults is unknown, but "is likely to be about the same or perhaps a slightly higher concentration than the one inducing pulmonary changes in humans with existing chronic bronchitis" (1.5 ppm). Therefore, NIOSH recommended a 1-ppm 15-minute short-term limit for nitrogen dioxide. To provide additional support for a short-term rather than a TWA limit, NIOSH cites several animal studies that indicate that the toxic effects associated with exposure to NO(2) are primarily determined by peak, and not average, concentrations of exposure.

In its posthearing submission, NIOSH (Ex. 150, Comments on Nitrogen Dioxide) reported on a recent study by Mohsenin (1988, as cited in Ex. 150) in which no significant pulmonary function changes were noted among 18 healthy subjects exposed to NO(2) for one-hour periods. NIOSH (Ex. 150) noted that, in 1984, the World Health Organization, after an independent review of cross-sectional occupational health surveys, recommended a short-term occupational exposure limit of 1.8 mg/m(3) (0.9 ppm) for NO(2) and 8-hour TWA limit of 0.9 mg/m(3) (0.45 ppm). NIOSH also reviewed studies that suggest that NO(2) is mutagenic and is embryotoxic and teratogenic in rats.

The AFL-CIO (Ex. 194) supported OSHA's proposed limit for NO 2. However, several commenters (Exs. 3-349, 3-670, 3-739, 3-666, 3-1144, 133, and 133A) objected to OSHA's proposal to establish the NIOSH REL for NO(2) in the final rule, believing that the ACGIH TLVs of 3 ppm TWA and 5 ppm STEL were sufficiently protective. For example, David L. Van Lewen, Manager of Industrial Hygiene for BASF, referred to the Von Nieding et al. (1971/Ex. 1-1204) study as evidence that a 1-ppm short-term limit was not necessary:

The Von Nieding study (1971/Ex. 1-1204) of chronic bronchitis patients...showed increased airway resistance when exposed to concentrations of nitrogen dioxide between 1.5 and 5.0 ppm. Lower concentrations had no significant effect. When this sensitive population does not show significant effects at concentrations below 1.5 ppm, it is not reasonable to set a workplace limit at a STEL of 1.0 ppm (Ex. 3-666).

Mr. Lawrence J. Ogden, representing the Intestate Natural Gas Association of America (INGAA) (Ex. 3-739), and Mr. Vincent D. Lajiness of the American Natural Resources Company (ANR) (Ex. 3-670) criticized the studies described in the NPRM, and in particular the Von Nieding et al. (1971/Ex. 1-1204) study; both rulemaking participants indicated that the data base developed by EPA to establish EPA's ambient air quality limit for NO(2) is superior. Mr. Ogden stated that

[a] far more extensive body of studies about NO(2) health effects is available than is cited by OSHA in the proposed rulemaking. Much of this literature has been pulled together by the Environmental Protection Agency (EPA). The EPA review and assessment of scientific studies on the health effects of NO(2) exists in the EPA NO(2) Criteria Document and the Staff Memorandum, which have been provided to the record....

EPA's action should be addressed in the OSHA proposal because it represents a more recent evaluation than NIOSH, a far more concentrated Agency evaluation by research and regulatory personnel, and an extensive scientific peer review process. As a result of its evaluation, EPA decided in 1982 that evidence was insufficient that a short-term air standard for NO(2) was needed. This conclusion has been re-examined annually by EPA and checked against the latest health studies related to NO(2) effects (Ex. 3-739, pp. 7, 10).

Mr. Ogden also referred OSHA to the 1979 National Academy of Science's Committee on Toxicology report on the health evidence for NO(2).

The EPA staff memorandum referred to by Mr. Ogden is the 1982 Office of Air Quality Planning and Standards (OAQPS) Staff Paper on the assessment of scientific information on NO(2) (EPA/450/5-82/002, Ex. 3-2e). This document summarizes the findings expressed in EPA's Air Quality Criteria for Oxides of Nitrogen (EPA/600/8-82/026, Ex. 3-2f). Based on these reports, EPA issued a final rule retaining its 1971 ambient air quality standard for NO(2), which is 0.053 ppm (100 mg/m(3)) as averaged over a one-year period.

The EPA Staff Paper concludes that the 1971 Von Nieding et al. (Ex. 1-1204) study "provides convincing evidence that chronic bronchitics exposed to NO(2) concentrations of 1.6 ppm or greater for approximately 3 minutes experience increases in airway resistance" (Ex. 3-2e, p. 18). A number of other studies were cited by EPA in which healthy adults were exposed to NO(2) concentrations in the range of 0.5 to 2.5 ppm. Folinsbee, Horvath, Bedi, and Delehunt (1978, as cited in Ex. 3-2e) reported no significant physiological changes in healthy adults exercising for up to one hour during a two-hour exposure to 0.6 ppm NO(2). Suzuki and Ishikawa (1965, as cited in Ex. 3-2e) reported a 50-percent increase in inspiratory flow resistance in healthy adults 10 minutes after a 10-minute exposure to an NO(2) concentration between 0.7 and 2 ppm.

Small changes in pulmonary function and a slight increase in the prevalence of respiratory symptoms occurred among healthy adults exposed to 1 ppm NO(2) for two hours (Hackney, Thiede, Linn et al. 1978, as cited in Ex. 3-2e). Beil and Ulmer (1976, as cited in Ex. 3-2e) reported a statistically significant increase in airway resistance among healthy adults following exposure to 2.5 ppm NO(2) for two hours, but not following exposure to 1 ppm. Based on their review of these data, the EPA staff paper concluded:

[T]he lowest level of NO(2) exposure that credible studies have associated with measurable impairment of pulmonary function appears to be in the range of 1.0 -1.6 ppm....Several CASAC members have expressed concern that a standard designed to prevent relatively small changes in pulmonary function (such as those observed in the Suzuki and Ishikawa (1965) and Von Nieding et al. (1971) studies) from occurring more than once per year would be unnecessarily stringent. The CASAC members indicated that they were more concerned about the health implications of repeated exposures to the peak concentrations observed in the two studies than the effects associated with a single exposure (Ex. 3-2e, p. 18).

EPA also reviewed research reports that have become available since publication of the EPA Criteria Document and Staff Paper, in particular the reports by Linn and Hackney (1983 and 1984) that reported finding no pulmonary effects among exercising healthy adults and asthmatics exposed to 4 ppm NO(2). EPA concluded that these studies present "mixed and conflicting results," and that a more complete assessment of these studies was not possible because "many...have yet to be published in the peer-reviewed scientific literature" (50 FR 25535/Ex. 3-2d).

Regarding EPA's decision not to issue a short-term ambient-air-quality limit for NO(2), a review of the preamble to EPA's final rule shows that EPA addressed this issue only with regard to existing ambient short-term levels of NO(2). EPA reported that, under its current 0.053-ppm annual average limit, the vast majority of metropolitan areas would be expected to have fewer than two days with a daily maximum hourly value of 0.2 ppm or greater (50 FR 25536/Ex. 3-2d). Because of the uncertainties regarding the evidence for adverse effects at NO(2) concentrations below 1 ppm, EPA concluded that the current annual average limit would "provide some measure of protection against possible short-term health and welfare effects" (50 FR 25537/Ex. 3-2d). It is also worth noting that, since 1971, EPA has designated a 2-ppm (one-hour average) level for NO(2) as representing a "significant harm level" requiring an emergency response. Thus, OSHA finds that EPA's recent actions and reasoning regarding a short-term ambient limit for NO(2) supports the establishment of 1 ppm as a STEL.

OSHA has also reviewed the most recent analysis of NO(2) toxicity conducted by the National Academy of Science's (NAS) Committee on Toxicology for the Department of Defense (Emergency and Continuous Exposure Guidance Levels for Selected Airborne Contaminants, Vol. 4, pp. 83-96, National Academy Press 1985); the earlier 1979 review was cited by Mr. Ogden of the INGAA. In its more recent review, the NAS concluded that exposures to NO(2) at levels between 0.5 and 1.5 ppm have demonstrated "little or no persistent change in pulmonary function" (NAS 1985, p. 89). The NAS Committee on Toxicology recommended short-term public emergency guidance levels (SPEGLs) for NO(2) of 1 ppm, averaged over a 60-minute period, and 0.12 ppm as an 8-hour average.

OSHA concludes that the evidence reviewed by the EPA and the NAS and the several studies referenced by EPA and NAS reaffirm the conclusion expressed by NIOSH in its 1976 criteria document (NIOSH 1976j/Ex. 1-265) that "humans with normal respiratory function may be acutely affected by exposure [to NO(2)] at or below...[5 ppm]. Furthermore, the conditions of workers with chronic respiratory diseases, such as chronic bronchitis, may be aggravated by exposure to nitrogen dioxide at a concentration of approximately one-third of the current Federal standard" (NIOSH 1976j/Ex. 1-265, p. 117). In addition to the studies by Von Nieding et al. (1971/Ex. 1-1204) and Abe (1967/Ex. 1-98) described in the NPRM, both EPA (Ex. 3-2e) and the NAS (1985) cite a number of other published reports that show that exposure to NO(2) at concentrations below 5 ppm causes increased airway resistance in both healthy adults and chronic bronchitics; these reports include the studies of Suzuki and Ishikawa (1965), Rokaw et al. (1968), Stresemann and Von Nieding (1970), and Beil and Ulmer (1976). Furthermore, these and other studies cited by EPA (Ex. 3-2e) and the NAS (1985) generally indicate that exposure to 1 ppm NO(2) is not normally associated with significant airway resistance, even among workers with already-compromised respiratory function.

Thus, OSHA concludes that the former 5-ppm ceiling limit for NO(2) is not sufficient to protect employees from experiencing increased airway resistance, and that establishing the ACGIH TLVs of 3 ppm TWA and 5 ppm STEL, as suggested by rulemaking participants (Exs. 3-349, 3-670, 3-739, 3-666, and 3-1144), would not provide sufficient protection. OSHA also concludes that the risk of increased airway resistance would be substantially reduced by promulgation of a 1-ppm short-term limit for NO(2); a short-term limit is clearly indicated for NO(2) since all of the studies cited above demonstrate that increased airway resistance is associated with exposure to NO(2) for durations of between three minutes and two hours. OSHA considers the increased airways resistance caused by exposure to NO(2) to be a material impairment of health. Therefore, to reduce the significant risk associated with short-term exposure to NO(2), the Agency is establishing a 1-ppm limit, averaged over a 15-minute period, for nitrogen dioxide in the final rule.

OXYGEN DIFLUORIDE CAS: 7783-41-7; Chemical Formula: OF(2) H.S. No. 1300

The former PEL for oxygen difluoride was 0.05 ppm as an 8-hour TWA. The ACGIH has established a limit of 0.05 ppm as a ceiling value. The revision of the TLV for oxygen difluoride from an 8-hour TWA to a ceiling value reflects the general position of the ACGIH that ceiling TLVs are more appropriate for chemicals that cause acute but not chronic health effects. OSHA proposed a permissible exposure limit of 0.05 ppm ceiling for oxygen difluoride. NIOSH (Ex. 8-47, Table N1) concurred with the selection of this limit, and it is established in the final rule. Oxygen difluoride is an unstable, colorless gas with a foul odor.
Oxygen difluoride is a substance having extremely high acute toxicity;
it is an acute irritant and causes fatal pulmonary edema and hemorrhage in animals exposed to 0.5 ppm for a few hours (ACGIH 1986/Ex. 1-3). A single exposure to 0.1 ppm also had an effect on the lungs, as evidenced by development in animals of a tolerance to the acute effects of this substance after an isolated exposure. Animals acutely exposed to oxygen difluoride have also exhibited gross changes in the kidneys and internal genitalia (LaBelle, Metcalf, Suter, and Smith 1945, as cited in ACGIH 1986/Ex. 1-3, p. 452; Lester and Adams 1965/Ex. 1-963). Only NIOSH commented on this substance.

Because of the extreme acute toxicity of this compound and the effects noted at 0.1 ppm, the former TWA-PEL of 0.05 ppm was not sufficiently protective of workers; this former limit would still permit the brief periods of high exposure that have been associated with severe lung damage, which the Agency has determined represents a material impairment of health. Therefore, to reduce the significant risk of acute lung damage associated with brief excursion exposures to oxygen difluoride, OSHA is establishing a ceiling limit of 0.05 ppm for this substance.

OZONE CAS: 10028-15-6; Chemical Formula: O(3) H.S. No. 1301

The former OSHA PEL for ozone was 0.1 ppm TWA. In the interval since this limit was adopted in 1971, the ACGIH has recommended that 15-minute short-term exposures to ozone not exceed 0.3 ppm. NIOSH has no REL for ozone. OSHA proposed, and the final rule establishes, permissible exposure limits of 0.1 ppm TWA and 0.3 ppm STEL for ozone. The Agency notes that the ACGIH has placed ozone on its 1988-89 Notice of Intended Changes and is proposing a new TLV of 0.1 ppm as a ceiling value. Ozone is a liquid or an explosive gas.

Ozone is highly injurious and lethal in experimental animals at concentrations as low as a few parts per million (Stokinger 1957/Ex. 1-97). A study in which young mice were exposed to 1 ppm ozone for one or two days reported damage to alveolar tissue (Bils 1970/Ex. 1-58). Human populations chronically exposed to lower concentrations of ozone have been observed to have changes in lung function. In one study, human volunteers exposed to 0.5 ppm ozone for three hours per day, six days per week, for 12 weeks showed significant changes in lung function (Jaffe 1967/Ex. 1-101). Other authors reported a 20-percent reduction in timed vital capacity in persons exposed to average concentrations of ozone of 1.5 ppm (range not indicated) for two hours (Griswold, Chambers, and Motley 1957/Ex. 1-128). Welders exposed to maximal ozone concentrations of 9 ppm were observed to have pulmonary congestion (Kleinfeld and Giel 1956/Ex. 1-120).

OSHA received a number of comments on the proposed PEL for ozone. The Edison Electric Institute (EEI) (Ex. 133A, pp. 22-23) stated that the studies by Bils (1970/Ex. 1-58), Jaffe (1967/Ex. 1-101), and Griswold et al. (1957/Ex. 1-128), cited above, do not provide substantial evidence for the proposed PEL. With regard to Bils' (1970/Ex. 1-58) finding of damaged alveolar tissue in mice exposed to a 1-ppm concentration of ozone for one or two days, EEI notes that "OSHA does not explain how these data can be translated to humans in the workplace" (Ex. 133A, p. 22). In addition, EEI is concerned that "OSHA neither critically evaluates...nor explains why the changes in lung function reported by [the Jaffe (1967/ Ex. 1-101)] study represent a significant risk...," and OSHA has not presented a substitute for a STEL of 0.3 ppm. Finally, EEI questions the relevance of the study by Griswold et al. (1957/Ex. 1-128) to the formulation of the proposed PEL (Ex. 133A, p. 23). The Agency believes that these three studies point to the short-term effect (i.e., less than eight hours) of ozone exposure; the Bils (1970/Ex. 1-58) data demonstrate that the lung is the target organ; the Jaffe (1967/Ex. 1-101) data point to an effect level of 0.5 ppm and show that a STEL of 0.3 ppm will afford protection; and the Griswold et al. (1957/Ex. 1-128) data provide further evidence of reduced lung function as a result of short-term, acute exposure, rather than chronic exposure.

In addition, EEI commented that "OSHA's health assessment and feasibility analysis with respect to the facilities of the electric utility industry are deficient. Thus, EEI recommends that OSHA consider explaining that its ozone proposal does not apply to that industry" (Ex. 133A, p. 22). This same concern was reflected in the submission of the second commenter, Gulf Power Company (Ex. 3-938, p. 3). In response to these comments, OSHA emphasizes that the standards established in this rulemaking are based on the evidence of adverse health effects associated with exposure to toxic substances in the workplace. These effects would be the same, regardless of industry sector, if the exposure levels were the same. If, as EEI and Gulf Power Company contend, ozone exposures in power plants pose no significant risk to workers' health because they are controlled at or below the permissible exposure limits being promulgated in this rulemaking, then the electric utility industry is already in compliance and will not be impacted by the new PELs. The Agency has determined that the scientific evidence establishes the need for a short-term limit to substantially reduce the significant risk of pulmonary dysfunction that exists as a result of acute or chronic intermittent exposure to ozone.

The Gulf Power Company also expressed its belief that the 0.3-ppm short-term limit proposed by OSHA is unsubstantiated:

Exposing someone to 1 ppm of ozone for 15 minutes may be just as valid a ceiling limit as 0.3 ppm.... We think that it is arbitrary to select a value of 0.3 ppm without further study (Ex. 3-938, pp. 3-4; see also Ex. 3-1144).

The Agency notes, again, that an effect level of 0.5 ppm is demonstrated by the Jaffe (1967/Ex. 1-101) data. Further justification for a STEL of 0.3 ppm is found in Proctor, Hughes, and Fischman (Chemical Hazards of the Workplace, 2nd ed., 1988), who report that, "except for one report, the threshold for effects in humans appears to be between 0.2 and 0.4 ppm" (Menzel 1984, as cited in Proctor, Hughes, and Fischman 1988, p. 388). The selection of 0.3 ppm as a short-term limit was neither invalid nor arbitrary, but rather, was based on the best available scientific evidence.

NIOSH (Ex. 8-47, Table N2) believes that ozone's toxicity requires an even more stringent limit. According to NIOSH, "Ozone is a chemical capable of inducing serious adverse health effects at low exposure concentrations, tenths of a part per million...." The AFL-CIO (Ex. 194) agrees with NIOSH's assessment. OSHA agrees that ozone's health effects require a protective limit, and it is for this reason that the final rule promulgates TWA and STEL limits for ozone.

In the final rule, OSHA is retaining the 8-hour TWA limit of 0.1 ppm and establishing a 15-minute STEL of 0.3 ppm for ozone based on observations that significant declines in pulmonary function can result from repeated intermittent exposures or even from a single short-term exposure (Bils 1970/Ex. 1-58; Jaffe 1967/Ex. 1-101; Griswold, Chambers, and Motley 1957/Ex. 1-128). OSHA believes that, in the absence of a STEL, employees will continue to be at significant risk of material impairment in pulmonary functional capacity associated with short-term exposures that could occur if exposures are controlled only by an 8-hour TWA. Thus the Agency concludes that it is necessary to supplement the former PEL with a STEL of 0.3 ppm to substantially reduce this risk.

PARAQUAT CAS: 4685-14-7; Chemical Formula: H.S. No. 1303

OSHA's former limit for paraquat was 0.5 mg/m(3) as an 8-hour TWA, with a skin notation. The ACGIH has established a limit of 0.1 mg/m(3) as an 8-hour TWA. The Agency proposed, and the final rule establishes, a permissible exposure limit of 0.1 mg/m(3) TWA for this substance; the skin notation is retained. NIOSH (Ex. 8-47, Table N1) concurs. Paraquat refers to a group of compounds that are odorless, yellow solids. The principal compounds are: 1,1'-dimethyl-4,4'-bipyridinium; 1,1'-dimethyl-4,4'-bipyridinium bis (methyl sulfate); and 1,1'-dimethyl-4,4'-bipyridinium dichloride.

The toxicity of these compounds depends on the compound's cationic moiety. Acute oral toxicity is reported as 30 mg/kg ion as cation for guinea pigs and 127 mg/kg ion for female rats, while the dermal LD(50) in rabbits is 240 mg/kg ion (Clark 1964, as cited in ACGIH 1986/Ex. 1-3, p. 456; Clark, McElligott, and Hurst 1966/Ex. 1-503; McElligott 1965, as cited in ACGIH 1986/Ex. 1-3, p. 456). Paraquat can penetrate broken skin after it has broken down the skin's usual barriers (Swan 1969/Ex. 1-576; Clark, McElligott, and Hurst 1966/Ex. 1-503). By inhalation or intratracheal injection, paraquat is very toxic because of its irritant properties (Gage 1968/ Ex. 1-508). Rats exposed once for six hours to a concentration of 1 mg/m(3) died if the aerosol contained particles with diameters of 3 to 5 microns (Gage 1968/Ex. 1-508). Rats exposed six hours/day for three weeks to the same aerosol at 0.4 mg/m(3) exhibited signs of pulmonary irritation; no effects were observed for the same exposure regimen at 0.1 mg/m(3) (Gage 1968/Ex. 1-508).

When the diameter of the particles in the aerosol are not of respirable size, toxicity is greatly reduced. The 4-hour LC(50) for rats is 6400 mg/kg, and dogs, rats, and guinea pigs tolerated three weeks of daily exposures to 100 mg/m(3) without apparent pulmonary effect (although nosebleeds were observed) (Palazzolo 1965, as cited in ACGIH 1986/Ex. 1-3, p. 456).

Dietary administration, for 90 days, of doses ranging from 300 to 700 ppm showed dose-related effects ranging from pulmonary edema to intraalveolar hemorrhage and death (Kimbrough and Gaines 1970/Ex. 1-560).

Paraquat's teratogenic potency in mice is low (Bus and Gibson 1975/Ex. 1-539), although 100 ppm administered in the drinking water of pregnant rats increased postnatal mortality significantly (Bus and Gibson 1975/Ex. 1-539).

In humans, 69 accidental deaths and 81 suicides were attributed to the effects of paraquat exposure up to 1972 (Chipman Chemicals 1972, as cited in ACGIH 1986/Ex. 1-3, p. 456). Bouletreau, Ducluzeau, Bui-Xuan et al. (1977/ Ex. 1-538) reported 31 cases of renal insufficiency, and a spray applicator was killed when he absorbed a lethal dose of inadequately diluted paraquat through the skin (Jaros 1978/Ex. 1-513). Workers using a 0.05- to 1-percent solution of paraquat developed skin and mucous membrane irritation but experienced no symptoms of systemic poisoning (Howard 1978/Ex. 1-512). Fugita, Suzuki, and Ochiai (1976, as cited in ACGIH 1986/Ex. 1-3, p. 456) reported five cases of reversible kerato-conjunctivitis, with corneal injury, after one month of exposure to paraquat. Only NIOSH commented on paraquat.

OSHA is establishing an 8-hour TWA limit of 0.1 mg/m(3) for paraquat, with a skin notation. The Agency concludes that this limit will protect workers from the significant risk of skin, eye, and pulmonary irritation observed in animals exposed to aerosols of respirable size at levels below OSHA's former PEL for paraquat. The Agency considers the irritant effects of paraquat to be material impairments of health. OSHA is retaining the skin notation for this substance because of its capacity to penetrate the skin.

SILICA, CRYSTALLINE - CRISTOBALITE CAS: 14464-46-1; Chemical Formula: SiO(2) H.S. No. 1354

The former OSHA PEL for respirable cristobalite was one-half the value calculated from the mass formula for quartz, measured as respirable dust. This limit corresponds to a range of 0.04 to 0.05 mg/m(3), measured as silica, for dusts containing 10 to 100 percent quartz. The ACGIH recommends an 8-hour TWA limit of 0.05 mg/m(3), measured as respirable silica dust. Although expressed differently, the current ACGIH and former OSHA limit for cristobalite are comparable. The ACGIH's mg/m(3) limit, adopted in 1985, does not reflect a re-evaluation of cristobalite's toxicity but was adopted merely to simplify the monitoring of cristobalite dust concentrations. The ACGIH limit is based on a study by Gardner (1938, as cited in ACGIH 1986/Ex. 1-3, p. 522) that was confirmed by King, Mohanty, Harrison, and Nagelschmidt (1953/Ex. 1-85). Experimental animals injected with cristobalite showed a more severe response than that produced by quartz, and the fibrosis that followed was diffuse rather than nodular. OSHA proposed, and the final rule establishes, a permissible exposure limit of 0.05 mg/m(3) TWA for cristobalite, measured as respirable silica dust. Cristobalite, one of the three major forms of silicon dioxide, is transparent, tasteless, and stable at high temperatures.

The final rule replaces OSHA's former limit for cristobalite, which is expressed, as described above, with a numerically equivalent limit of 0.05 mg/m(3); the Agency is establishing this time-weighted average limit to simplify employee exposure monitoring. NIOSH (Ex. 8-47, Table N6A; Tr. pp. 3-96 to 3-97) concurred with the selection of this limit but recommended that cristobalite be designated as a potential human carcinogen. OSHA's discussion of this and other rulemaking issues appears in the following entry describing the record evidence on quartz dust.

SILICA, CRYSTALLINE - QUARTZ CAS: 14808-60-7; Chemical Formula: None H.S. No. 1355

The former OSHA limit for silica-containing dusts is a respirable dust limit expressed as the following formula:
(10 mg/m(3))/(% respirable quartz + 2).
At one time, the ACGIH also expressed its silica limit in terms of this formula. However, the current ACGIH TLV is 0.1 mg/m(3), measured as respirable quartz dust. OSHA proposed, and the final rule establishes, a permissible exposure limit of 0.1 mg/m(3) TWA, as respirable quartz. Quartz is a colorless, odorless, noncombustible solid.

The ACGIH does not see this change in the value of its limit for occupational exposure to silica as significant; instead, the ACGIH made this change to conform its limit for this dust to its TLVs for other dusts. If the former OSHA formula is used to calculate a limit for a dust containing 100 percent quartz, the limit would be 0.098 mg/m(3), a value that is not appreciably different from the ACGIH's revised limit of 0.1 mg/m(3) for respirable quartz dust. For quartz dusts containing less than 100 percent free silica, the former OSHA formula would yield a limit of, for example, 0.83 mg/m(3) for respirable dust containing 10 percent quartz. This result is somewhat more stringent than the ACGIH's TLV of 0.1 mg/m(3). For cristobalite and tridymite, the former OSHA formula and the ACGIH limits yield approximately the same results: both are approximately one-half the limit established by these two entities for quartz dust (see the discussions below).

Occupational exposure to free silica has been known for many years to produce silicosis, a chronic, disabling lung disease characterized by the formation of silica-containing nodules of scar tissue in the lungs. Simple silicosis, in which the nodules are less than 1 cm in diameter (as measured on chest X-ray films) is generally asymptomatic but can be slowly progressive, even in the absence of continued exposure. Complicated silicosis (i.e., with nodules greater than 1 cm in diameter) is more often associated with disability and can also progress in the absence of continuing exposure.

The health basis underlying the ACGIH's limit for crystalline silica is the work of Russell et al. (1929/Ex. 1-156), which suggested that a limit of 10 mppcf would protect workers from the effects of exposure to granite dust; a study by Ayer (1969/Ex. 1-129) demonstrated that 10 mppcf of granite dust is approximately equal to 0.1 mg/m(3) of respirable quartz dust (ACGIH 1986/Ex. 1-3).

NIOSH has recommended an exposure limit of 0.05 mg/m(3) as respirable free silica for all crystalline forms of silica. As applied to cristobalite and tridymite, the NIOSH REL is 0.05 mg/m(3), the same as the ACGIH TLV, but NIOSH's 0.05 mg/m(3) REL for quartz dust is one-half the value of the ACGIH TLV for quartz dust. To support its more stringent REL for quartz dust, NIOSH cites the work of Hosey, Ashe, and Trasko (1957, as cited in ACGIH 1986/Ex. 1-3, p. 524), which reported that no new cases of silicosis occurred in workers in Vermont granite sheds who were generally exposed to 0.05 mg/m(3) or less of granite dust. The recommendation was also partly based on studies by Theriault, Burgess, DiBerardinis et al. (1974/Ex. 1-94a); Theriault, Peters, and Fine (1974/Ex. 1-110); and Theriault, Peters, and Johnson (1974/Ex. 1-94b), which found that annual declines in pulmonary function and abnormal chest X-rays occurred among 192 granite shed workers exposed to an average quartz concentration of 0.05 mg/m(3). NIOSH noted that the exposure estimates reported in the Theriault et al. (1974/Exs. 1-94a, 1-94b, and 1-110) studies failed to account for the higher exposures that probably occurred in the years before exposure sampling was initiated and, therefore, that the Theriault et al. (1974) exposure data may have understated average exposures to quartz. Thus, NIOSH believes that the exposures responsible for the declines in pulmonary function were actually above 0.05 mg/m(3). The ACGIH (1986/Ex. 1-3) found NIOSH's reasoning unpersuasive, citing a report by Graham, O'Grady, and Dubuc (1981/Ex. 1-172), who measured the pulmonary function of the same group of workers studied by Theriault et al. (1974/Exs. 1-94a, 1-94b, and 1-110), and found, in contrast to Theriault, that these workers experienced "an overall increase in FVC and FEV" (ACGIH 1986/Ex. 1-3).

Although OSHA did not propose a significant change in the exposure limit, there were several comments that focused on two issues: (1) the adequacy of the proposed 0.1 mg/m(3) respirable quartz limit in reducing the risk of silicosis; and (2) recent evidence describing the potential carcinogenicity of silica dust.

With regard to the first issue, Dr. Philip Landrigan of the Mount Sinai School of Medicine, representing the American Public Health Association, testified as follows at the informal hearing:

Numerous epidemiologic studies have been undertaken in this century, which have established a dose-response relationship between occupational exposure to silica dust and the development of silicosis. These studies have shown clearly that there is a positive dose-response relationship between chronic silica exposure and the development of silicosis.

The most recent of these reviews which have examined that relationship is presented in the 1986 NIOSH text on occupational respiratory diseases, a most authoritative book in the field, widely read by medical scientists in this country and abroad. The data which was summarized in that chapter indicate quite clearly that the dose-response relationship between silica exposure and silicosis is present in people with lifetime exposure to silica below the current...standard of 100 micrograms per cubic meter. Indeed, the data suggests that the dose-response relationship extends downward even to levels of exposure below the current NIOSH recommended standard of 50 micrograms per cubic meter.

And against the authoritative NIOSH review...OSHA has cited one short three-page article...[Graham et al. 1981/Ex. 1-172] to indicate that the dose-response relationship between silica and silicosis does not extend downward to below 100 micrograms per cubic meter (Tr. pp. 3-277 to 3-278).

Several commenters (Exs. 3-678, 3-733, 130, 138, 139, 147, 161, and 126) disagreed with Dr. Landrigan's assessment. For example, Frederick A. Renninger of the National Stone Association (Ex. 139) cited Dr. John Peters, the author of the chapter in the NIOSH reference referred to by Dr. Landrigan. In his chapter, Dr. Peters concluded as follows:

All of the studies described in this section provide evidence for adverse pulmonary effects at levels of exposure above 10 mppcf or 0.1 mg/m(3). Some showed that foundry workers exposed to the equivalent of 0.05 mg/m(3) of quartz developed silicosis while those with less exposure did not....All the Vermont findings were seen with an average exposure of around 0.05 mg/m(3) of quartz. It is possible, however, that since this was the average exposure, individuals whose exposure exceeded this level accounted for the noted effects. (The "no effect" level was probably below 0.05 mg/m(3), but the available data did not allow accurate determinations.) (Peters, J.M., "Silicosis." In: Occupational Respiratory Diseases, p. 229, J.S. Merchant, ed. DHHS (NIOSH) Pub. No. 86-102, NIOSH 1986b).

Mr. Renninger also points to the difficulty in equating impinger sampling results, which were used in the Vermont granite shed studies, to gravimetric (mg/m(3)) measures of respirable dust. He cited Dr. Peters as reporting that "gravimetric and impinger sampling are known to be poorly correlated" (Ex. 139, p. 5). Mr. Renninger also pointed out that the conversion between mppcf and mg/m(3) measurements for silica will vary with the industry, thus adding another level of uncertainty in interpreting the health data.

OSHA's decision to propose a 0.1 mg/m(3) PEL for respirable silica dust, rather than the NIOSH REL of 0.05 mg/m(3), was partly based on the report by Dr. William Graham et al. (Graham, O'Grady, and Dubuc 1981/Ex. 1-172) discussed above. In a posthearing submission, Dr. Graham discussed the findings of Theriault and co-workers (1974/Exs. 1-94a, 1-94b, and 1-110), which heavily influenced the decision by NIOSH to issue a REL of 0.05 mg/m(3) (Ex. 147). Dr. Graham discussed three limitations of the Theriault et al. (1974) studies. First, the X-ray films were interpreted by a single reader who was neither certified nor a chest physician; Dr. Peters points out that it is generally accepted that X-ray films must be read by three experienced readers. Second, there was no attempt to study workers hired after 1938 and exposed to low dust levels separately from workers exposed to higher dust levels prior to 1938. Third, there was a group of workers who were judged to have abnormal X-ray findings despite a reported lack of exposure to dust, which raises the question about the accuracy of interpretations.

Dr. Graham also interpreted his own findings of granite shed workers as showing that the loss in pulmonary function predicted to occur among these workers by Theriault et al. (1974/Exs. 1-94a, 1-94b, and 1-110) had, in fact, not occurred. One explanation offered by Dr. Graham is the possibility that technical difficulties arose during the Theriault et al. (1974) studies in the administration of spirometric tests, and may have resulted in spuriously low values for pulmonary function. Dr. Graham discussed a continuation of his own work in which he has found neither pulmonary function losses nor high prevalences of abnormal chest X-rays among granite shed workers who were employed after 1938-1940, when lower dust levels prevailed (Ex. 147, pp. 8-9). However, the analysis of quartz content in the dust samples collected has not yet been completed (Ex. 147, p. 8).

In addition to the evidence on the dose-response relationship for silicosis, rulemaking participants discussed at length recent data suggesting that silica may be carcinogenic (Exs. 147, 161, 194, 138, 3-1159, 3-1060, and 139; Tr. p. 3-94, Tr. p. 7-80, Tr. p. 11-104). NIOSH (Ex. 8-47, Table N6B) believes that the data on silica are such that the Agency should consider a separate 6(b) rulemaking for this substance. Dr. Frank Mirer, Director of the Health and Safety Department of the United Auto Workers, summarized the evidence on silica's potential carcinogenicity at the hearing:

The most prominent study [on the health effects of silica exposure is] by Holland and coworkers...[it] provided really clear evidence that silica was carcinogenic in rats by inhalation. Non-malignant pulmonary effects were also observed. There is a considerable line of other work in rats and hamsters, in the development of both lung tumors and lymphatic tumors from exposure to silica.

In epidemiology, there's ample evidence that crystalline silica is carcinogenic and that it is hazardous at levels below the proposed PEL. The IARC monograph reviewed the data available in 1986 and described a considerable body of evidence. Despite the methodological limitations pointed out by IARC, the sheer number and consistency of the findings is most persuasive (Tr. pp. 7-80 to 7-81).

Studies [exist] of workers in a variety of industries where high exposure of silica-containing dusts have revealed high lung cancer risks. These results include ten positive studies among mine workers, four in ceramics and glass industries, [and] four in the foundry industry. We also bring to your attention at least four additional studies published since the IARC criteria document was completed. These, in particular, we think create an iron-clad case for the problems presented by this material (Tr. pp. 7-80 to 7-81).

In a posthearing submission by the Refractories Institute, Dr. John Craighead of the University of Vermont reviewed the human and animal data and concluded as follows:

I find the experimental evidence in animals, suggesting a possible role of silica in the pathogenesis of bronchogenic carcinomas, to be faulty and incomplete. I also conclude that the epidemiological studies in humans provide inadequate evidence to conclude that man is at increased risk of developing carcinoma of the lung as a result of silica dust exposure. My comments in no way exclude from consideration silica as a cause of bronchogenic carcinoma, but only point out the inadequacies of the scientific information and emphasize the need for additional, carefully designed systematic studies (Ex. 161A, p. 5)

In similar attachments to the Refractories Institute's submission, Dr. Marvin Kushner, Professor of Pathology at the State University of New York at Stony Brook, pointed to the lack of similarity between the pulmonary lesions found in exposed rats and silicosis lesions in humans; he suggested that the carcinomas seen in rats may be due to a "non-specific" effect that is not a direct result of silica inducing malignant transformation (Ex. 161C). Dr. Carl Shy, Professor of Epidemiology at the University of North Carolina, reviewed the epidemiological evidence and concluded that "the role of occupational silica exposure in causing lung cancer remains undetermined" (Ex. 161D, p. 8).

OSHA believes that the issues raised above deserve a careful and thorough scientific evaluation of the literature. The evidence that silica may present a carcinogenic hazard has been developing over the past few years and is continuing to receive considerable attention by investigators. OSHA will continue to monitor with great interest emerging developments in this area. At this time, however, OSHA believes that the record evidence leaves many questions unanswered regarding the need to reduce the PEL for silica. Therefore, in the final rule, OSHA is establishing an 8-hour TWA PEL of 0.1 mg/m(3) for quartz, measured as the respirable silica fraction. This limit represents no substantial change from OSHA's former formula limit, but will simplify sampling procedures, as indicated in the NPRM.

SILICA, CRYSTALLINE - TRIDYMITE CAS: 15468-32-3; Chemical Formula: SiO(2) H.S. No. 1356

The former OSHA PEL for respirable tridymite was expressed as one-half the value of the mass formula for quartz dust. This formula corresponds to a range of 0.04 to 0.05 mg/m(3), measured as silica, for dusts containing 10 to 100 percent tridymite. The Agency proposed, and the final rule establishes, a PEL of 0.05 mg/m(3) TWA for tridymite. The ACGIH recommends an 8-hour TWA limit of 0.05 mg/m(3), measured as silica dust. The ACGIH limit is based on a study conducted by King, Mohanty, Harrison, and Nagelschmidt (1953/Ex. 1-85) that found tridymite to be the most active of the free silica forms when injected intratracheally into rats. Tridymite is a transparent, tasteless form of free silica.

Although expressed in different units, the current ACGIH and former OSHA limits for tridymite are comparable. The ACGIH's mg/m(3) limit, adopted in 1985, does not reflect a re-evaluation of tridymite's toxicity but was adopted merely to simplify the monitoring of tridymite dust concentrations. NIOSH (Ex. 8-47, Table N6A) concurs with the selection of this limit but recommends that tridymite be designated as a potential occupational carcinogen. No other comments were received on tridymite.

OSHA is replacing its former limit for tridymite, which is described above, with a numerically equivalent limit of 0.05 mg/m(3), measured as respirable silica dust; the final rule establishes this change to simplify employee exposure monitoring.

SILICA, CRYSTALLINE - TRIPOLI CAS: 1317-95-9; Chemical Formula: SiO(2) H.S. No. 1357

Tripoli is a colorless microcrystalline form of quartz. Although OSHA's Table Z-2 did not specifically indicate a limit for tripoli, OSHA formerly specified a limit for crystalline quartz based on the formula measured as total respirable dust: 10 mg/m(3)/ % SiO(2)+2. Expressed as mg/m(3), this limit corresponds to a limit in the range of 0.08 to 0.1 mg/m(3) for respirable dust containing from 10 to 100 percent silica. The 8-hour TWA ACGIH limit for tripoli is 0.1 mg/m(3), measured as respirable silica dust. This limit was adopted by the ACGIH in 1985 to simplify the monitoring of quartz dust concentrations. Thus, this revision does not represent a re-evaluation of toxicity data for tripoli. NIOSH (Ex. 8-47, Table N6B) does not concur with the final rule's limit and recommends a separate 6(b) rulemaking for tripoli, which NIOSH considers a potential occupational carcinogen. (see section above on Crystalline Quartz for OSHA's discussion of the record evidence on the carcinogenicity of silica). No other comments were received on tripoli.

OSHA is replacing its limit for quartz, which is expressed as the formula presented above, with a numerically equivalent limit of 0.1 mg/m(3) TWA as respirable silica dust; the final rule establishes this limit for tripoli.

SILICA, FUSED CAS: 60676-86-0; Chemical Formula: SiO(2) H.S. No. 1358

Fused silica is a colorless, odorless solid that is a form of quartz. As such, it was formerly covered by OSHA's limit for quartz (Table Z-3). Exposure to fused silica has long been known to cause the fibrogenic lung disease, silicosis. OSHA's former limit for quartz dust was the formula 10 mg/m(3)/ % SiO(2) + 2, measured as total respirable dust. This limit corresponds to a respirable quartz concentration ranging from 0.08 to 0.1 mg/m(3), measured as free silica. The ACGIH recommends an 8-hour TWA limit of 0.1 mg/m(3), measured as free silica; the ACGIH adopted this limit in 1985 to simplify the monitoring of quartz dust concentrations. Thus, this revision does not represent a re-evaluation of the toxicity data for fused silica. NIOSH (Ex. 8-47, Table N6B) does not concur with the final rule's limit and recommends a separate 6(b) rulemaking for fused silica, which NIOSH considers a potential occupational carcinogen.

OSHA is replacing its limit for fused silica, which is expressed as the formula presented above, with a numerically equivalent limit of 0.1 mg/m(3) as total respirable silica dust; the Agency is establishing this limit to simplify employee exposure monitoring.

SOAPSTONE, TOTAL DUST SOAPSTONE, RESPIRABLE DUST CAS: None; Chemical Formula: 3 MgO-4 SiO(2)-H(2)O H.S. No. 1363 (total dust) H.S. No. 1363A (respirable dust)

OSHA's former exposure limit for soapstone, total dust, was 20 mppcf (6 mg/m(3)), and the Agency had no separate limit for the respirable fraction. The ACGIH has established individual TLV-TWAs for these two forms of soapstone: 6 mg/m(3) for total dust, and 3 mg/m(3) for the respirable fraction, both measured as total dust or respirable dust containing less then 1 percent quartz. Because the ratio of total dust mass to the mass of the respirable fraction is 2:1 (ACGIH 1984, p. 480), the 6 mg/m(3) total dust limit automatically implies a 3 mg/m(3) limit for the respirable fraction. OSHA proposed, and the final rule establishes, permissible exposure limits of 6 mg/m(3) TWA (total dust) and 3 mg/m(3) TWA (respirable dust) for soapstone. NIOSH (Ex. 8-47, Table N1) concurred with this determination.

A study by Dreessen and DallaValle (1935/Ex. 1-588) of mill workers exposed to soapstone showed lung changes in these workers, but it is believed that the dusts involved in these exposures were actually steatite talc, which had a tremolite content of 10 percent. Experiments by Miller and Sayers (1941/Ex. 1-595) showed no measurable toxic effects in guinea pigs injected intraperitoneally with various samples of soapstone. No comments were received on soapstone other than those submitted by NIOSH.

The final rule expresses the limit for soapstone as total dust in mg/m(3), rather than mppcf, to simplify employee sampling and analysis. The total dust limit being established, 6 mg/m(3), is equivalent to the previous limit of 20 mppcf, and the new limit of 3 mg/m(3) for respirable dust is actually implicit in the total dust limit.

SULFUR DIOXIDE CAS: 7446-09-5; Chemical formula: SO(2) H.S. No. 1375

OSHA's former limit for sulfur dioxide (SO(2)) was 5 ppm as an 8-hour TWA. The Agency proposed to revise this limit to 2 ppm as an 8-hour TWA and to supplement this limit with a 15-minute STEL of 5 ppm. Although NIOSH recommends a limit of 0.5 ppm for sulfur dioxide, NIOSH did concur (Ex. 8-47, Table N1) with the proposed limits. The ACGIH has a TLV-TWA of 2 ppm and a TLV-STEL of 5 ppm. In the final rule, OSHA is establishing a 2-ppm 8-hour TWA and a 5-ppm 15-minute STEL for SO(2). Sulfur dioxide is a colorless, nonflammable gas or liquid with a suffocating odor.

OSHA has studied the effects of occupational exposure to SO(2) for several years. The Agency's 5-ppm limit for this substance was established in 1971 on the basis of the 1968 ACGIH TLV-TWA. In 1975, OSHA proposed to revise this limit downward to 2 ppm and held public hearings to gather information on industrial exposures to SO(2). In response to shifting priorities within the Agency, OSHA did not promulgate a final standard at that time. The following discussion summarizes the record evidence relevant to SO(2) both from the earlier (1975-1976) record and from the record of the present rulemaking.

Workplace exposure to sulfur dioxide causes both acute and chronic effects. The chronic effects of exposure include permanent pulmonary impairment, which is caused by repeated episodes of broncho constriction. A number of human and animal studies demonstrate this effect (Skalpe 1964/Ex. 1-438; Smith, Peters, Reading, and Castle 1977/Ex. 1-805; Archer and Gillam 1978/Ex. 1-711; Ministry of Health (Canada) 1976/Ex. 1-1208; Lewis, Campbell, and Vaughan 1969, as cited in ACGIH 1986/Ex. 1-3, p. 542).

Kehoe, Machle, Kitzmiller, and LeBlanc (1932/Ex. 1-339) studied two groups of male refrigeration workers with long-term (average of four years) exposures to average SO(2) concentrations of 20 to 30 ppm, with a range of exposures from 10 to 70 ppm. These workers were believed to have been exposed prior to 1927 to SO(2) levels considerably higher and averaging from 80 to 100 ppm. This study showed that SO(2) exposure caused an increased incidence of nasopharyngitis, shortness of breath on exertion (dyspnea), and chronic fatigue (Kehoe, Machle, Kitzmiller, and LeBlanc 1932/Ex. 1-339).

In a study of Norwegian paperpulp mill workers, Skalpe (1964/Ex. 1-438) reported that average SO(2) concentrations were believed to range from 2 to 36 ppm. Results showed a significantly higher frequency of respiratory disease symptoms, including coughing, expectoration, and dyspnea, among workers less than 50 years of age (i.e., those with the shortest exposure). Workers older than 50, however, did not display symptomatology different from that of controls.

More recently, Smith, Peters, Reading, and Castle (1977/Ex. 1-805) studied a group of smelter workers exposed, on average, to less than 2 ppm SO(2) but concurrently exposed to respirable particulate at levels generally less than 2 mg/m(3). These workers showed a decrement in forced vital capacity (FVC) and forced expiratory volume (FEV1) of 4.8 percent when compared with controls. These authors concluded that workers exposed to SO(2) levels above 1 ppm had an accelerated loss of pulmonary function. This study has been criticized on the grounds that the control population itself may have been exposed to respiratory toxins and that other contaminants, such as iron sulfites, may have contributed to the pulmonary decrement seen in these smelter workers. On average, 60 percent more of the workers exposed to greater than 1 ppm SO(2) reported symptoms of chronic cough than did workers who were exposed to SO(2) at a concentration below 1 ppm. The prevalence of chronic sputum production was elevated for workers who had never smoked and who were exposed above 1 ppm.

Archer and Gillam (1978/Ex. 1-711) studied workers at the same smelter facility and obtained results similar to those of Smith, Peters, Reading, and Castle (1977/Ex. 1-805). Significant reductions in FVC and FEV1 were found to be associated with chronic exposures to 0.4 to 3 ppm SO(2) (TWA) with concomitant exposure to particulate. These authors also found a corresponding increase in some symptoms of respiratory disease (chronic bronchitis) that was not attributable to smoking. Tomono and coworkers (1961, as cited in ACGIH 1986/Ex. 1-3, p. 542) found that 1.6 ppm was the lowest concentration that produced bronchoconstriction in 46 healthy male subjects.

OSHA's June 7, 1988 proposal also discussed the basis for NIOSH's recommendation of a 0.5 ppm 8-hour TWA limit for SO(2). In addition to the studies by Archer and Gillam (1977/Ex. 1-711) and Smith, Peters, Reading, and Castle (1977/Ex. 1-805) described above, NIOSH relied on a third study (Ministry of Health (Canada) 1976/Ex. 1-1208) of smelter workers exposed to SO(2) levels of 2.5 ppm for 10 or more years, which showed an increased incidence of respiratory disease in these workers. A fourth study cited by NIOSH (NIOSH 1977m, as cited in ACGIH 1986/Ex. 1-3, p. 542) reported that 10,000 workers exposed to SO 2 at levels of 0.35 ppm showed no adverse exposure-related effects.

Alarie and co-workers (1970 and 1972, as cited in ACGIH 1986/Ex. 1-3, p. 542) found that guinea pigs exposed to SO(2) by inhalation showed no decrement in pulmonary function at SO(2) levels of 5 ppm; monkeys exposed to 1.3 ppm for 78 weeks also showed no deficit (Alarie, Ulrich, Busey et al. 1970 and 1972, both as cited in ACGIH 1986/Ex. 1-3, p. 542). However, in another study, dogs exposed continuously to 5 ppm for 225 days showed increased pulmonary flow resistance and a decrease in lung compliance (Lewis, Campbell, and Vaughan 1969, as cited in ACGIH 1986/Ex. 1-3, p. 542). In addition, rats exposed to 10 ppm SO(2) daily for six weeks developed a thickening of the mucous layer that interfered with effective particle clearance (Dalhamn 1956, as cited in ACGIH 1986/Ex. 1-3, p. 542).

The acute effects of SO(2) exposure have been recognized for years in industrial settings; symptoms of acute overexposure include upper respiratory tract irritation, rhinorrhea, choking, and coughing. These symptoms are so disagreeable that most persons will not tolerate exposure for longer than 15 minutes. Within 5 to 15 minutes of the onset of exposure, workers develop temporary reflex bronchoconstriction and increased airway resistance. Short-term exposure causes measurable bronchoconstriction (Frank, Amdur, Worcester, and Whittenburger 1962, as cited in ACGIH 1986/Ex. 1-3, p. 542; Weir, Stevens, and Bromberg 1972/Ex. 1-401); the ACGIH (1986/Ex. 1-3, p. 542) reports that this bronchoconstriction is dose-related and is manifested as an increase in pulmonary flow resistance.

Efforts have been made to quantify the acute no-adverse-effect level for SO(2)-induced increased airway resistance. Frank, Amdur, Worcester, and Whittenberger (1962, as cited in ACGIH 1986/Ex. 1-3, p. 542) reported that, at SO(2) concentrations of 1 ppm, one in 11 healthy subjects developed pulmonary flow resistance; at concentrations of 5 or 13 ppm, there was a 39-and 72-percent increase, respectively, in such resistance. Weir, Stevens, and Bromberg (1972/Ex. 1-401) noted a statistically significant but reversible increase in small-airway resistance and a decrease in lung compliance at a concentration of 3 ppm; however, Burton et al. (1969) reported no effects, even among smokers, at a level of 2.1 ppm.

N.R. Frank, Professor of Medicine at the University of Washington State, commented during the 1977 hearing (NIOSH 1977m) that sulfur dioxide may not by itself be hazardous to the lungs but that an aerosol of sulfur dioxide and water or SO(2) oxidized to sulfate particulate may increase the toxic potential of SO(2) (Ex. 40, Docket H-039). Dr. Frank also presented evidence showing that a single short-term exposure to very high SO(2) levels (200 to 1000 ppm) can produce lung damage (Ex. 40, Docket H-039).

In the current generic rulemaking, participants such as the American Iron and Steel Institute (AISI) (Exs. 3-1123 and 188) and the Corn Refiners Association (Exs. 8-65 and 177) raised issues similar to those raised during OSHA's 1977 rulemaking on SO(2). These included:

* Lack of evidence that long-term exposure to SO(2) causes chronic respiratory disease; and

* The potentiation of SO(2)'s adverse effects by the formation of sulfates or higher sulfur oxides from interactions between SO(2) and water or SO(2) and particulate matter.

Regarding the first point, the Corn Refiners Association (CRA) referred OSHA to studies and testimony on the effects of SO(2) exposure on employees in corn wet-milling from the earlier rulemaking (Ex. 66, Docket H-039). The CRA reported that the chronic respiratory disease and pulmonary impairment seen in SO(2)-exposed smelter workers did not occur in corn milling plant employees (Ex. 66-1, Docket H-039). The CRA sponsored a study performed by Drs. Ferris and Essex from the Harvard School of Public Health (Ex. 66-3, Docket H-039). Fifty corn wet-milling workers involved in the early, SO(2)-using stage of the wet-milling process were studied. Exposures (8-hour TWAs) in this group ranged from 0.5 to more than 5 ppm SO(2), particulates ranged from 0.0 to 0.17 mg/m(3), and water-soluble sulfates ranged from 0.0 to 40.0 mg/m(3). Results of this study showed that, at levels of about 3 ppm SO(2), acute symptoms such as coughing developed, but chronic, irreversible symptoms were not seen at exposure levels below 5 ppm (Ex. 66-1, Docket H-039). These authors concluded:

Taken as a whole, the results suggest that no significant chronic respiratory impairments occurred at exposure levels under 5 ppm. The lack of association between the most serious symptoms of respiratory disease and exposure levels below 5 ppm also suggests that the atmosphere in question is quite distinct from that found in the copper smelter studies (Ex. 66-3, Docket H-039).

In addition, the studies by Smith, Peters, Reading, and Castle (1977/Ex. 1-373) and Archer and Gillam (1978/Ex. 1-711) were criticized in OSHA's earlier rulemaking for not taking into consideration the impact on the studied workers' health of the higher SO(2) levels to which these employees had been exposed in prior years. Arthur D. Little, Inc. (Ex. 95, Docket H-044) also criticized these studies, noting that their observation periods were too short to derive reliable data on chronic effects.

These criticisms and the lack of chronic effects observed in animals at levels below 5 ppm (Alarie, Ulrich, Busey et al. 1970 and 1972, as cited in ACGIH 1986/Ex. 1-3, p. 542) caused commenters to question whether chronic lung disease results from long-term exposure to SO(2) below the current 5-ppm PEL. Dr. Alarie appeared at the 1977 hearing and testified on animal studies conducted by him and others on sulfur dioxide (NIOSH 1977m, as cited in ACGIH 1986/Ex. 1-3, p. 542). He testified that, in his opinion, the long-term studies in animals support the establishment of a ceiling value for SO(2) but do not indicate that benefits would be gained by reducing the time-weighted average from 5 to 2 ppm. OSHA agrees with Dr. Alarie that a STEL is necessary to minimize high short-term exposures to SO(2); however, OSHA does not agree that no effects have been seen in animals at levels at or below 5 ppm. For example, Lewis, Campbell, and Vaughan (1969, as cited in ACGIH 1986/Ex. 1-3, p. 542) showed that beagles exposed to 5 ppm SO(2) exhibited decreased dynamic compliance and increased flow resistance. In addition, NIOSH (1974b/Ex. 1-235) has reported:

[M]an is considered to be more sensitive than other mammals to the effects of sulfur dioxide in ranges commonly employed experimentally...(Ex. 1-235).

It is therefore not surprising that humans have also been shown to develop respiratory effects, including bronchoconstriction, coughing, and sputum production, at levels below 5 ppm (Smith, Peters, Reading, and Castle 1977/Ex. 1-805; Archer and Gillam 1978/Ex. 1-711; Frank, Amdur, Worcester, and Whittenburger 1962, as cited in ACGIH 1986/Ex. 1-3, p. 542; Weir, Stevens, and Bromburg 1972/Ex. 1-401).

Many rulemaking participants (Exs. 3-1123, 8-57, 86, 86A, 117, 177, and 188) were of the opinion that the lack of chronic effects demonstrated that exposure to SO(2) did not cause material impairment of health at levels below 5 ppm. For example, the Edison Electric Institute (EEI) (Ex. 133) criticized the Ferris et al. (1967/Ex. 1-316) study as being too old to be relevant. According to the EEI, the finding that the control group in the Ferris et al. (1967/Ex. 1-316) study also had an elevated incidence of disease and that there was no statistically significant difference in the extent of the respiratory disease incidence between the controls and the SO(2)-exposed group invalidates this study's finding of a serious pulmonary effect in the SO(2)-exposed workers. OSHA does not agree with this interpretation of the Ferris et al. (1967/Ex. 1-316) study. OSHA believes that a more accurate interpretation of the results of this study would be that both groups of workers were occupationally exposed to respiratory toxins; this is a very likely occupational scenario because the SO(2)-exposed workers in this study were pulpmill workers, while those in the control group worked in a papermill, an occupational environment also recognized as hazardous.

Taken together, the evidence from all of the studies described in this subsection clearly shows that exposure to SO(2) below 5 ppm does cause respiratory symptoms, including repeated episodes of bronchoconstriction. The studies by Smith, Peters, Reading, and Castle (1977/Ex. 1-373), Archer and Gillam (1978/Ex. 1-711), and Frank, Amdur, Worcester, and Whittenberger (1962, as cited in ACGIH 1986/Ex. 1-3, p. 542) consistently demonstrate that persons exposed to concentrations of SO(2) below 5 ppm have an accelerated loss of pulmonary function and exhibit adverse pulmonary symptoms.

OSHA believes that these effects constitute material impairments of health and are significant. In addition, OSHA does not agree that these studies demonstrate the absence of chronic effects at low SO(2) exposure levels; long-term exposure to SO(2) has produced pulmonary function changes in dogs, and daily exposures of rats to 10 ppm (only twice the former PEL) for six weeks produced a thickened mucous layer and reduced the effectiveness of particle clearance from the trachea (Dalhamn 1956, as cited in ACGIH 1986/Ex. 1-3, p. 542).

The second point raised by commenters concerned the formation of other toxic and irritating products from the interaction between SO(2) and water or between SO(2) and particles. Some of the participants in the earlier rulemaking, such as Dr. Colucci of the Corn Refiners Association, testified that it would be more protective to identify and limit exposure to each of these by-products, rather than to regulate SO(2) alone. OSHA disagrees with this approach; since these products are all formed from sulfur dioxide, limiting exposure to SO(2) will concurrently limit exposure to these SO(2) by-products. This approach is more straightforward and easier to implement than attempting to identify the myriad decay products that may be formed in different industrial settings. Furthermore, the studies discussed above clearly establish a relationship between airborne SO(2) levels and adverse effects; no quantitative relationship on which to base a PEL has been established for the decay products of SO(2) reactions. Therefore, to reduce the significant risk of respiratory symptoms among exposed workers, OSHA finds that limiting exposure to SO(2) will be effective.

After considering all of the relevant evidence from both the 1977 and the present dockets, OSHA concludes that a TWA of 2 ppm and a STEL of 5 ppm are necessary to reduce the significant risk of adverse respiratory effects that have been demonstrated to occur in workers exposed to SO(2) above these levels. Accordingly, OSHA is establishing these limits in the final rule. The Agency finds that the coughing, increase in sputum production, and bronchoconstriction observed in workers exposed to SO(2) at the levels permitted by the former limit constitute material impairments of health and functional capacity, and must be protected against. This discussion is also a final statement of reasons for the 1977 rulemaking.

Some evidence has been submitted by the steel and nonferrous metal industries that the STEL cannot be regularly achieved with engineering and work-practice controls in specific operations in SIC 33. These involve furnace areas in nonferrous metal smelters, blast furnace operations, and the sulfur plant. There is no evidence to the contrary in the record. See the further discussion in the Feasibility section.

OSHA will, therefore, permit more flexibility in the use of respirators for these operations. The burden of proof will not be on employers to demonstrate that compliance with engineering and work-practice controls are infeasible in a compliance action for these operations in SIC 33 as related to meeting the requirements of the STEL.

There may be a few other operations in this category, and for the TWA, where the record is unclear for SIC 33. Based on an appropriate showing pursuant to the OSH Act, OSHA would favorably consider requests for variances for specific operations in Sector 33 on methods of compliance for the STEL and for the TWA. Of course, all requests for variances or any matters will be considered based on their merits.

SULFUR TETRAFLUORIDE CAS: 7783-60-0; Chemical Formula: SF(4) H.S. No. 1378

OSHA's former Z tables had no exposure limits for sulfur tetrafluoride. The proposed PEL was 0.1 ppm as a ceiling; NIOSH (Ex. 8-47, Table N1) concurs with this limit, and the final rule establishes it. This limit is consistent with that of the ACGIH. Sulfur tetrafluoride is a colorless, noncombustible gas.

On contact with moisture, sulfur tetrafluoride produces sulfur dioxide and hydrogen fluoride (HF) (Lester 1971, as cited in ACGIH 1986/Ex. 1-3, p. 546), and it is the release of HF that is primarily responsible for sulfur tetrafluoride's toxic effects (Zapp 1971, as cited in ACGIH 1986/Ex. 1-3, p. 546). A du Pont (1961, as cited in ACGIH 1986/Ex. 1-3, p. 546) study of rats exposed for four hours to 4 ppm sulfur tetrafluoride over a period of 10 days reported that the animals demonstrated nasal discharge, difficulty in breathing, and weakness. Autopsies of these animals revealed evidence of emphysema, but those rats surviving exposure and given a two-week rest period after exposure showed no significant pathological changes. In the same study by du Pont (1961, as cited in ACGIH 1986/Ex. 1-3, p. 546), a four-hour exposure to 20 ppm sulfur tetrafluoride proved lethal to one of two rats. In a study by Clayton (1962/Ex. 1-409), irregular breathing and signs of irritation were observed following exposures to concentrations of 20 ppm and lower; animals receiving lethal amounts of sulfur tetrafluoride showed pulmonary edema on autopsy, and those with sublethal exposures demonstrated no pathologic changes 14 days later.

In the final rule, OSHA is establishing a 0.1-ppm ceiling limit for this highly toxic gas. The Agency concludes that establishing this limit for this previously unregulated chemical will reduce the significant risk of chronic respiratory effects potentially associated with exposure to sulfur tetrafluoride at the levels permitted by the absence of any OSHA limit. OSHA considers the chronic respiratory effects caused by exposure to sulfur tetrafluoride to be material impairments of health. NIOSH was the only commenter to the rulemaking record on this substance.

TALC (CONTAINING NO ASBESTOS) CAS: 14807-96-6; Chemical Formula: H(2)O(3)Si 3/4Mg H.S. No. 1381

The former OSHA PEL for nonasbestiform talc was 20 million particles per cubic foot of air (mppcf) as an 8-hour TWA; when expressed as mg/m(3), this is comparable to 3 mg/m(3). The ACGIH has a TLV-TWA of 2 mg/m(3) (15 mppcf) for talc, measured as respirable dust, and this is the limit proposed by OSHA and included in the final rule. NIOSH (Ex. 8-47, Table N1) concurred that this limit is appropriate. Talc is a fine powder that is white to gray-white in color; it is found as a mineral, and the main component is a crystalline hydrated silicate of magnesium that is usually in the form of plates but occasionally may be in the form of fibers.

The health-effects evidence for talc is complicated by the fact that talcs contain amphiboles and other minerals, in addition to platiform talc crystals; adverse health effects appear to be related to the nonplatiform content (that is, to the fiber content) of the talc in question (ACGIH 1986/Ex. 1-3, p. 550). There are conflicting views regarding the extent to which the fibrous constituents are asbestos; however, no health effects information is available that is specifically related to fibrous talc (ACGIH 1986/Ex. 1-3, p. 550).

Numerous epidemiological studies have documented the effects on workers of long-term exposures to talc. In 1942, Porro et al. (1942, as cited in Stokinger 1981b/Ex. 1-1127) published a report in which 15 cases of talc pneumoconiosis, including five postmortem examinations, showed that asbestotic bodies were almost always present in fibrotic areas of the lungs of those workers with talcosis. Siegal and colleagues (1943, as cited in Stokinger 1981b/Ex. 1-1127) noted that the incidence of advanced fibrosis in a group of 221 talc miners and millers was 14.5 percent. These workers were primarily exposed to fibrous talc, which was believed to be responsible for the pathology of the asbestos-like lung lesions. A study by McLaughlin et al. (1949, as cited in Stokinger 1981b/Ex. 1-1127) revealed that talc-induced pneumoconiosis was caused by the fibrous varieties of talc; in animal studies by Schepers and Durkan (1955, as cited in Stokinger 1981b/Ex. 1-1127), the degree of fibrosis in the lung tissue was found to be a function of the length of the talc fibers, rather than of the composition of the talc itself. A paper by Kleinfeld, Giel, Majeranowski, and Messite (1963, as cited in Stokinger 1981b/Ex. 1-1127) reported that postmortem examinations on six talc industry workers showed that the asbestotic bodies found in the lung bronchioles or embedded in fibrous tissue were indistinguishable from the asbestos bodies seen in cases of asbestosis.

Kleinfeld, Messite, Kooyman, and Zaki (1967/Ex. 1-704) later conducted a cohort study of 220 workers who had been employed in a mine that produced talc that had a tremolite and anthophyllite content. Of the 91 deaths in this group, 10 resulted from respiratory cancer and 28 were attributed to pneumoconiosis. The proportional mortality rate from respiratory cancer was four times the expected rate. In 1974, when Kleinfeld, Messite, and Zaki (Ex. 1-705) performed a follow-up study of this group (which at that time consisted of 260 workers [108 deaths]), they found significant differences between the expected and observed mortality in the period 1950 to 1954, but not during 1960 to 1969. These investigators attributed this finding to the reduction in talc dust counts (from averages of 25 to 73 mppcf (approximately 4 to 12 mg/m(3)) in the years 1948 to 1965 to averages of 9 to 43 mppcf (approximately 1.5 to 6.5 mg/m(3)) in the period 1966 to 1969). This study also showed a decrease of greater than 50 percent in deaths due to pneumoconiosis in the 1965-to-1969 time period.

Studies by NIOSH (Dement and Zumwald 1978, as cited in ACGIH 1986/Ex. 1-3, p. 552) of 398 white male workers employed between 1947 and 1959 in the talc industries found that 74 of these men had died, and that bronchogenic cancer was the cause of death in nine men; only 3.3 deaths from this cause would have been expected. Nonmalignant respiratory disease (NMRD) exclusive of influenza, pneumonia, and tuberculosis accounted for three deaths; 1.5 would have been expected. From these data, NIOSH concluded that a significant increase in mortality due to bronchogenic cancer and NMRD had occurred as a result of occupational exposure to talc dust. NIOSH's report also included a morbidity study of 12 talc industry workers, currently employed, in which chest X-rays, lung function tests, and questionnaires were used. This study concluded that a higher prevalence of cough, phlegm, dyspnea, and irregular opacities in chest X-rays existed in these workers than in potash miners; instances of pleural thickening and calcification were greater than in coal and potash miners; and the pulmonary function of talc workers overall was reduced in comparison with that of coal and potash miners employed for the same length of time. The reductions in pulmonary function among the talc workers were dose- and duration-related.

The ACGIH (1986/Ex. 1-3, p. 552) concludes that serious health effects have been associated in the past (i.e., prior to 1945) with exposures to amphibole-containing talc. However, the ACGIH believes that the introduction of mining improvements has all but eliminated "the excess of death rates from pneumoconiosis and lung cancer" (ACGIH 1986/Ex. 1-3, p. 552).

Two recent studies of the health effects associated with talc exposures (Rubino, Scansetti, Piolatto, and Romano 1976/Ex. 1-801; Selevan, Dement, Wagoner, and Froines 1979/Ex. 1-989) are available. The Rubino, Scansetti, Piolatto, and Romano (1976/Ex. 1-801) study found that miners and millers exposed to an average of 849 to 8470 mppcf-years (miners) or 76 to 651 mppcf-years (millers) showed no increase in the number of observed (compared to expected) deaths from causes other than silicosis. These authors concluded that the disease-causing factor in these workers was silica rather than talc (Rubino, Scansetti, Piolatto, and Romano 1976/Ex. 1-801).

The Selevan, Dement, Wagoner, and Froines (1979/Ex. 1-989) study of 392 workers exposed to talc in five mines found nonmalignant respiratory deaths for millers to be almost eight times the expected rate, while miners experienced more than three times the expected mortality rate for NMRD. The ACGIH (1986/Ex. 1-3, p. 552) believes that the Selevan et al. (1979/Ex. 1-989) study is incomplete because confounding factors were not adequately identified and controlled for.

With regard to NIOSH's findings (Dement and Zumwald 1978, as cited in ACGIH 1986/Ex. 1-3, p. 552) of excess cancer deaths among talc workers, OSHA is currently reviewing the scientific and toxicological data describing the effects of exposure to the nonasbestiform varieties of mineral fibers that are found in talc deposits. OSHA is considering a separate rulemaking to address this issue.

OSHA received few comments regarding its proposed revision to the PEL for respirable talc. John W. Kelse, Corporate Industrial Hygienist for R.T. Vanderbilt, Inc. (Ex. 3-108), supported the proposed 2 mg/m(3) respirable talc PEL. Mr. Kelse also recommended that OSHA revise its Table Z-3 entry for "Talc (nonasbestiform)" to "Talc (not containing asbestos)" and the entry for "Talc (fibrous)" to "Talc (containing asbestos)." These changes were suggested because of the potentially ambiguous meanings of the term "fibrous" and "asbestiform." OSHA concurs with this suggestion and has accordingly revised the respective entries in Tables Z-1-A and Z-3 in this rulemaking. In response to a suggestion by Richard Bidstrup, representing the Rubber Manufacturers Association (Ex. 173, p. 9), OSHA has also revised the entry for talc to clarify that the PEL is measured as respirable dust.

On a related issue, Mr. F.A. Renninger, Senior Vice President of the National Stone Association (Ex. 3-528), suggested that OSHA delete or clarify its current Table Z-3 entry for "Tremolite (see talc fibrous)" since it suggests that all forms of tremolite are considered to be asbestos. As Mr. Renninger points out, the applicability of OSHA's asbestos standard to the nonasbestiform varieties of tremolite, actinolite, and anthophyllite is currently under administrative stay, and OSHA is presently examining the health evidence for these mineral varieties. However, during this period of administrative stay, exposure to the nonasbestiform varieties of these minerals is covered by OSHA's comprehensive standard, which appears at 29 CFR 1910.1101. OSHA has therefore revised the entry for tremolite in Table Z-3 to refer to the standard at 29 CFR 1910.1101.

OSHA is establishing an 8-hour TWA limit of 2 mg/m(3) for the respirable dust of talc containing no asbestos fibers and less than 1 percent silica.

The Agency concludes that this limit will protect workers from the significant risk of nonmalignant respiratory effects associated with exposure to talc dust; OSHA considers these effects material impairments of health. According to the ACGIH (1986/Ex. 1-3), talc may, at times, occur in a fibrous form. At this time, OSHA has not made any determinations with regard to the possible health consequences resulting from exposure to talc fibers.

TIN OXIDE CAS: 7440-31-5; Chemical Formula: SnO H.S. No. 1395

OSHA formerly had no exposure limit for tin oxide. The ACGIH has an exposure limit of 2 mg/m(3) as an 8-hour TWA. The proposed PEL was 2 mg/m(3) as an 8-hour TWA PEL; NIOSH (Ex. 8-47, Table N1) concurs, and this limit is established by the final rule. Tin oxide may be a white or yellow-brown powder.

Injection of tin dust intraperitoneally into guinea pigs resulted in a nonspecific, well-vascularized chronic granulomatous reaction (Oyanguren, Haddad, and Maass 1958/Ex. 1-652). Chronic exposure to tin oxide fume and dust results in stannosis, a form of pneumoconiosis. The fume of tin oxide is considered to be a more important source of stannosis than the dust (Dundon and Hughes 1950/Ex. 1-732), but other authorities consider the quality of the dust and the duration of exposure equally important (Robertson and Whittaker 1955/Ex. 1-987). The onset of the symptoms of stannosis may be delayed for years; the appearance of the condition is signaled by difficulty in breathing. One worker who had been exposed to unspecified tin oxide levels for 22 years was tested for stannosis and registered a vital breathing capacity 70 percent of normal and a maximal breathing capacity 61 percent of the predicted value (Spencer and Wycoff 1954/Ex. 1-611).

More than 150 cases of stannosis have been reported in the world literature (Robertson and Whittaker 1955/Ex. 1-987), and five cases were reported in the United States before 1954. No cases of massive fibrosis caused by exposure to tin oxide dust or fume have been reported (ACGIH 1986/Ex. 1-3, p. 574). Only NIOSH commented on tin oxide.

In the final rule, OSHA is establishing an 8-hour TWA of 2 mg/m(3) for tin oxide dust and fume. The Agency concludes that this limit will protect workers from the significant risks of reduced pulmonary capacity and stannosis, which are considered material impairments of health, associated with exposure to this substance at the levels permitted by the absence of an OSHA limit.

TRIMELLITIC ANHYDRIDE (TMAN) CAS: 552-30-7; Chemical Formula: C(9)H(4)O(5) H.S. No. 1409

OSHA previously had no exposure limit for trimellitic anhydride. In 1981, the ACGIH set 0.005 ppm (0.04 mg/m(3)) as the 8-hour TWA limit for this substance. The proposed PEL was 0.005 ppm as an 8-hour TWA, and the final rule promulgates this limit. NIOSH (Ex. 8-47, Table N1) concurs with this limit. Trimellitic anhydride is a colorless solid.

Exposure to trimellitic anhydride (TMAN) causes irritation of the eyes, nose, skin, and pulmonary tract. NIOSH (1978n, as cited in ACGIH 1986/Ex. 1-3, p. 606) reported in a current intelligence bulletin that trimellitic anhydride should be considered an extremely toxic workplace hazard, because exposure to it can cause noncardiac pulmonary edema and immunological sensitization, as well as upper respiratory tract irritation.

Pulmonary edema has occurred in workers exposed to TMAN at unreported air concentrations; the development of pulmonary edema in these workers without upper respiratory tract irritation suggests that TMAN is a sensitizer (Rice, Jenkins, Gray, and Greenburg 1977/Ex. 1-358). Zeiss, Patterson, Pruzansky, and colleagues (1977/Ex. 1-501) described TMAN-related illnesses among a group of workers synthesizing TMAN. These authors believe there are three separate syndromes associated with TMAN exposure: rhinitis/asthma; a flu-like condition; and irritation of the upper respiratory tract. Another case of TMAN-related occupational sensitization occurred in a worker exposed during the application of an epoxy resin coating (Fawcett, Taylor, and Pepys 1977/Ex. 1-636).

At levels averaging 1.5 and 2.8 mg/m(3) in two processes, NIOSH reported that employees reported eye and nose irritation, shortness of breath, coughing, nausea, headache, skin irritation, and throat irritation (NIOSH 1974c/Ex. 1-1181). Pulmonary hemorrhage and hemolytic anemia have been reported in workers exposed to TMAN at unspecified levels (Ahmad, Morgan, Patterson et al. 1979/Ex. 1-460).

Rats have shown intraalveolar hemorrhage after TMAN exposures to concentrations of 0.01 ppm (Amoco Chemical Corporation 1978, as cited in ACGIH 1986/Ex. 1-3, p. 606).

Based on this study, in the final rule OSHA is revising the PEL for trimellitic anhydride to an 8-hour TWA level of 0.005 ppm. The Agency concludes that this limit will protect workers from the severe pulmonary effects, sensitization, and skin and upper respiratory tract irritation observed in workers exposed to this extremely toxic substance. The Agency has determined that these effects constitute material impairments of health. OSHA finds that this limit will substantially reduce these significant risks, which were formerly not controlled because of the absence of any OSHA PEL.

WOOD DUST CAS: None; Chemical Formula: None H.S. No. 1430A (Hard Wood) H.S. No. 1430B (Soft Wood) H.S. No. 1430C (Western Red Cedar)

Before 1985, OSHA regulated wood dust under its nuisance dust standard of 15 mg/m(3) (29 CFR 1910.1000, Table Z-3). However, in a 1985 enforcement proceeding before the Occupational Safety and Health Review Commission, wood dust was held not to be covered by the nuisance dust standard. It held that the standard only covered inorganic dusts. (12 OSHC 1785). The Agency did not regulate this substance after this decision. Consequently, OSHA had no PEL for wood dust when this generic rulemaking was undertaken. The ACGIH has a TLV-TWA of 1 mg/m(3) for hard wood dust, and a TLV-TWA of 5 mg/m(3) and STEL of 10 mg/m(3) for soft wood dust. OSHA proposed a 1 mg/m(3) 8-hour TWA for hard wood dust and a 5 mg/m(3) 8-hour TWA for soft wood dust. In the final rule, OSHA is establishing a single 8-hour TWA of 5 mg/m(3) and a STEL of 10 mg/m(3) for all hard wood and soft wood dusts except Western red cedar. For Western red cedar, a highly allergenic species of soft wood, the Agency is establishing an 8-hour TWA limit of 2.5 mg/m(3). Wood dust is defined as any wood particles arising from the processing or handling of woods. Hard woods derive from the deciduous broad-leaved flowering species of trees, and soft woods include the coniferous species that do not shed their leaves in the winter.

Exposure to wood dust has long been associated with a variety of adverse health effects, including dermatitis, allergic respiratory effects, mucosal and nonallergic respiratory effects, and cancer. The toxicity data in animals are limited, particularly with regard to exposure to wood dust alone; there are, however, a large number of studies in humans. The discussion below first describes some of the relevant toxicological studies and then presents the record evidence on wood dust.

Animal Studies

Groups of male guinea pigs were injected intratracheally with suspensions containing 75 mg of sheesham or mango wood dust or of hemp or bagasse fibers, or 20 mg of jute fiber (Bhattacharjee, Dogra, Lal, and Zaidi 1979/Ex. 1-463; Bhattacharjee and Zaidi 1982/Ex. 1-464). Animals were sacrificed serially at intervals up to 90 days after injection. Lung examination revealed that, at 90 days, Grade I fibrosis of the lungs had occurred in the guinea pigs injected with mango or jute, while those treated with sheesham or hemp had developed Grade II pulmonary fibrosis.

In another experiment involving guinea pigs, animals were exposed by inhalation to average respirable dust concentrations of 1143 mg/m(3) for 30 minutes/day, 5 days/week for 24 weeks (McMichael, DiPalma, Blumenstein et al. 1983, Ex. 1-644). Histopathological examination showed lung changes, described by the authors as moderate to severe, in all exposed guinea pigs. The changes seen included an increase in septal connective tissue components and aggregation of lymphocytes; however, no pulmonary fibrosis or extensive destruction of the parenchymal tissue occurred. The authors of this study concluded that exposure to fir bark dust may cause inflammatory changes in the lung.

Two studies examined the effect of exposing Syrian golden hamsters to beech wood dust by inhalation, with or without concurrent administration of the known carcinogen diethylnitrosamine (DEN) (Wilhelmsson, Hellquist, Olofsson, and Klintenberg 1985/Ex. 1-402; Wilhelmsson, Jernudd, Ripe, and Holmberg 1985/Ex. 1-1042; Drettner, Wilhelmsson and Lundh 1985/Ex. 1-312). In each study, the animals were divided into four separate groups. In Study I, there were 12 animals per group. Two groups were exposed to fresh beech wood dust (a hard wood dust) at a mean total dust concentration of 15 mg/m(3) for six hours/day, five days/week for 36 weeks, and one of these groups was also given 1.5 mg of DEN once a week for the first 12 weeks. The third group in Study I was given the DEN doses only (positive control), and the fourth group was given no exposure at all (negative control).

In Study II, there were 24 animals in each of four groups. Two groups of animals were exposed to fresh beech wood dust at a mean total dust concentration of 30 mg/m(3) for six hours/day, five days/week for 40 weeks. The positive and negative control groups were treated as in Study I.

In Study I, none of the hamsters had lung or nasal tumors or metaplasia. Four hamsters exposed to wood dust and DEN exhibited squamous cell papillomas of the trachea, as did three animals in the positive control group and one in the negative control group. No differences in organs other than the respiratory organs were seen between the treated and control groups in Study I.

In Study II, all DEN-exposed hamsters had nasal lesions ranging from hyperplasias and dysplasias to papillomas. In addition, half of all DEN-exposed hamsters developed nasal adenocarcinomas, whether or not they had also been exposed to wood dust. Half of the DEN-exposed animals also had papillomas of the larynx and trachea. In the wood-dust-exposure-only group, two of the animals had nasal lesions, one of which was an unclassifiable malignant nasal tumor and the other of which consisted of focal metaplasia with mild dysplasia. The authors concluded that exposure to wood dust did not increase the tumor incidence in DEN-exposed animals but did affect the respiratory tract of all exposed animals.

Human Studies

Dermatitis. There are a large number of case reports, epidemiological studies, and other data on the health effects of wood dust exposure in humans. Dermatitis caused by exposure to wood dusts is common, and can be caused either by chemical irritation, sensitization (allergic reaction), or both of these together. As many as 300 species of trees have been implicated in wood-caused dermatitis.

The chemicals associated with allergic reactions are generally found in the inner parts of a tree, e.g., the heartwood, and the workers most prone to these reactions are those involved in secondary wood processing (e.g., carpenters, joiners, and finishers).

The symptoms of sensitization are redness, scaling, and itching, which may progress to vesicular dermatitis and, after repeated exposures, to chronic dermatitis. The parts of the body most often affected are the hands, forearms, eyelids, face, neck, and genitals. This form of dermatitis generally appears after a few days or weeks of contact.

Allergic respiratory effects. Allergic respiratory responses are mediated by the immune system, as is also the case with allergic dermatitis. Many authors have reported cases of allergic reactions in workers exposed to wood dust (Sosman, Schlueter, Fink, and Barboriak 1969/Ex. 1-444; Greenberg 1972/Ex. 1-482; Pickering, Batten, and Pepys 1972/Ex. 1-655; Eaton 1973/Ex. 1-478; Booth, LeFoldt, and Moffitt 1976/Ex. 1-466; Chan-Yeung, Ashley, Corey et al. 1978/Ex. 1-622; Edwards, Brooks, Henderson, and Apol 1978/ Ex. 1-950; Innocenti and Angotzi 1980/ Ex. 1-1036; Bush and Clayton 1983/Ex. 1-469; Cartier, Chan, Malo et al. 1986/Ex. 1-472). Asthma is the most common response to wood dust exposure, and the allergic nature of such reactions has been demonstrated by the presence of IgE antibodies and positive skin reactions on patch testing. The best-studied of the allergic reactions to wood dust is Western red cedar (WRC) asthma; it is estimated that 5 percent of the workers handling this species are allergic to it. However, only one study is available that relates exposure level to ventilatory function. In that study, exposure to concentrations of 2 mg/m(3) of WRC dust caused significant decreases in forced vital capacity and forced expiratory volume (Vedal, Chan-Yeung, Enarson et al. 1986/Ex. 1-397). These authors also found that exposures to concentrations above 3 mg/m(3) produced eye irritation.

Mucosal and nonallergic respiratory effects. This section discusses changes in the structure and function of the nasal mucosa and respiratory tract that are caused by exposure to wood dust. These changes include nasal dryness, irritation, bleeding, and obstruction; coughing, wheezing, and sneezing; sinusitis; and prolonged colds. These symptoms have been observed even at wood dust concentrations below 4 mg/m(3).

Bellion, Mattei, and Treves (1964, as cited in NIOSH 1987a/Ex. 1-1005) found that 97 of 225 workers (carpenters, sawmill workers, woodworkers) exposed from 3 to 24 years to the dust of several different hard woods showed radiologic evidence of pulmonary abnormalities. Black, Evans, Hadfield et al. (1974/Ex. 1-299) studied nine woodworkers from a woodworking factory in England. In all of these workers, mucociliary movement was markedly depressed, leading these authors to conclude that exposure to wood dust in the furniture industry for 10 years or more can impair mucociliary clearance. These findings were confirmed in a Danish study involving furniture makers (Solgaard and Andersen 1975/Ex. 1-443; Andersen, Solgaard, and Andersen 1976/Ex. 1-297; Andersen, Andersen, and Solgaard 1977/Ex. 1-296); compared with controls, the mucociliary transport rate was also significantly impaired in these woodworkers, and dose-response effects were noted.

A respiratory survey conducted by Chan-Yeung, Giclas, and Henson (1980/Ex. 1-474) in pulp and paper mill workers in British Columbia showed that workers exposed to wood dust at a mean total dust concentration of 0.5 mg/m(3) had a slight but statistically significant decrease in pulmonary function values compared with controls. The authors concluded that the chemical preservatives used to treat the wood could also have been responsible for these adverse effects.

In a cross-sectional survey of 1,157 American woodworkers (both hard and soft wood), Whitehead, Ashikaga, and Vacek (1981/Ex. 1-454) found that exposure to higher (10+ mg-years/m(3)), as compared with lower (0 to 2 mg-years/m(3)), dust concentrations was associated with a statistically significant and higher incidence of decreased pulmonary function. However, dose-response effects were observed only for soft wood (i.e., pine) dusts.

A later study by Beckman, Ashikaga, and Whitehead (1980, as cited in NIOSH 1987a/Ex. 1-1005) examined subgroups of the workers studied by Whitehead and found no correlation between years of exposure to pine wood dust and pulmonary function.

In a pilot study of 55 workers in a North Carolina hardwood furniture plant, Goldsmith (1983, as cited in NIOSH 1987a/ Ex. 1-1005) found that, at mean area wood dust concentrations of 2 mg/m(3) or below, peak ventilatory flow correlated significantly with cumulative person-years of exposure. Goldsmith interpreted this finding to mean that inhalation of wood dust may impair large-airway function.

A study of Italian woodworkers showed that the number of wood-dust-exposed workers who had developed anosmia (loss of smell) was significantly higher than in a control group of nonexposed workers (Innocenti, Valiani, Vessio et al. 1985/ Ex. 1-1037). Amoore (1986/Ex. 1-1029) confirmed this finding in other workers exposed to hardwood dusts.

Summary of mucosal and nonallergic respiratory effects. A large number of studies have demonstrated that occupational exposure to wood dust causes both statistically significant and nonsignificant increases in respiratory symptoms at exposure levels as low as 2 mg/m(3). These symptoms range from irritation to bleeding, wheezing, sinusitis, and prolonged colds. In addition, chronic wood dust exposure causes mucociliary stasis (i.e., the absence of effective clearance) in the nose and, in some workers, also causes changes in the nasal mucosa. Several studies have demonstrated decreased pulmonary function among wood-dust-exposed workers, although other studies have not confirmed these findings.

Carcinogenicity

The association between occupational exposure to wood dust and various forms of cancer has been explored in many studies and in many countries. In 1987, the International Agency for Research on Cancer (IARC) classified furniture manufacturing in Category I (confirmed human carcinogen) and carpentry in Category 2B (suspected human carcinogen). NIOSH (Ex. 8-47) considers both hard and soft wood dust to be potentially carcinogenic in humans; for soft wood dust, NIOSH recommends a separate 6(b) rulemaking (Ex. 8-47, Table N6B). NIOSH concurred, however, with the proposed PEL of 1 mg/m(3) TWA for hard wood dust (Ex. 8-47, Table N6A).
The discussion below focuses on selected U.S. studies. Nasal and sinus cavity cancer. The earliest U.S. study of wood dust exposure and nasal cancer was conducted by Brinton, Stone, Blot, and Fraumeni (Ex. 1-468) in 1976. These authors analyzed cancer death rates between 1950 and 1969 in 132 U.S. counties having at least 1 percent of their population employed in furniture and wood-fixture manufacturing. This study revealed that the age-adjusted mortality rate for cancer of the nasal cavity and sinuses among white males in the "furniture" counties was significantly higher than in nonfurniture counties.
In a later case-control study, these authors (Brinton, Blot, Becker et al. 1984/Ex. 1-467) analyzed cases of nasal and sinus cancers occurring in North Carolina and Virginia between 1970 and 1980. This study identified a significantly elevated risk of adenocarcinomas in males working in the furniture manufacturing industry, but no increased risk among lumber, carpentry, or construction workers. There was no significant increase in the risk of squamous cell carcinoma in workers from any other wood-related industry.

In a study sponsored by the Inter-Industry Wood Dust Task Force, Viren, Vogt, and Dixon (1982, as cited in NIOSH 1987a/ Ex. 1-1005) described a death certificate case-control study of nasal cancer deaths for 1963 to 1977 in North Carolina, Mississippi, Washington, and Oregon. Findings of this study included a relative nasal cancer risk of 1.95 for industries involving lumber and wood products; however, no significant relative risk of nasal cancer was seen for workers in the furniture-manufacturing industry.

Imbus and Dyson conducted a study of nasal cancer and North Carolina furniture workers (1985, as cited in NIOSH 1987a/ Ex. 1-1005). This study found: (1) that there was a statistically significant increase of nasal cancer among furniture workers; (2) that the nasal cancer rates among North Carolina furniture workers were much lower than those reported for English furniture workers; (3) that the number of nasal cancer deaths among North Carolina furniture workers decreased between 1956 and 1977; and (4) that a slight excess in nasal cancer may have existed among North Carolina furniture workers but is currently either declining or nonexistent.

At present, the National Cancer Institute is conducting a cohort mortality study of 36,622 workers employed in the wood, metal, and plastic furniture manufacturing industries (Miller et al. 1988, as cited in NIOSH 1987a/Ex. 1-1005). Results are too preliminary to be described at this time.

Summary of evidence for nasal and sinus cavity cancers. NIOSH (1987a/Ex. 1-1005) concluded that the literature clearly demonstrates an association between occupational wood dust exposure and nasal cancer. English studies first identified this link by showing a 10- to 20-times-greater incidence of nasal adenocarcinoma among woodworkers in the furniture industry than among other woodworkers and 100 times greater than in the general population. In the United States, three studies have reported a fourfold risk of nasal cancer or adenocarcinoma in furniture workers, and another study noted a similar relationship between nasal cancer and wood dust exposure. One other study failed to find such an association for furniture workers, but did find an increase among logging and timber industry workers.

Pulmonary cancer. A number of studies investigating the association between wood dust exposure and the development of lung cancer have been conducted. Milham (1974/Ex. 1-943) found a significant excess of malignant tumors of the bronchus and lung in workers who had belonged to the AFL-CIO United Brotherhood of Carpenters and Joiners of America. Only construction workers showed a statistically significant increase in lung cancer rate.

In a study of lung cancer in Florida residents, Blot, Davies, Brown et al. (1982/Ex. 1-465) found that an elevated risk of lung cancer that was statistically significant existed among workers in the lumber and wood industry and in construction; however, smoking may have been a confounding factor in these results.

Summary of evidence for pulmonary cancer. The association between lung cancer and occupational wood dust exposure is inconclusive, although several epidemiological studies have reported increases in lung cancer among wood-dust-exposed workers.

Hodgkin's disease. The data on the relationship between exposure to wood dust and the development of Hodgkin's disease are conflicting. Milham (1967/Ex. 1-750) and Milham and Hesser (1967/Ex. 1-645) concluded, on the basis of a case-cohort study of 1,549 white males dying of this disease between 1940-1953 and 1957-1964, that there was an association between Hodgkin's disease and exposure to wood dust.

Another study (Spiers 1969/Ex. 1-445) concluded that men working in the wood industries in the eastern United States were at special risk for Hodgkin's disease, and suggested that pine pollen exposure might be responsible for the increase.

A Washington State epidemiological study (Petersen and Milham 1974/Ex. 1-654) also found that woodworkers had an increased risk of Hodgkin's disease, and the work of these authors was supported by the results of another study (Grufferman, Duong, and Cole 1976/Ex. 1-484), which showed a nonsignificant increase in the relative risk for Hodgkin's disease among woodworkers.

Summary of evidence for Hodgkin's disease. Although the data are conflicting, several epidemiological studies of U.S. workers do report increases in the incidence of Hodgkin's disease among woodworkers. This excess is particularly apparent among carpenters.

Other cancers. NIOSH (1987a/Ex. 1-1005) concluded that the data on the relationship between occupational exposure to wood dust and the development of cancers other than nasal, Hodgkin's disease, or lung cancers are insufficient and inconclusive.

Record Evidence

Many participants submitted comments to the record pertaining to wood dust (see, for example, Exs. 8-34, 3-748, 3-233, 3-349, 3-362, 3-626, 3-682, 3-824, 3-836, 3-859, 3-899, 3-955, 3-1160, 3-917, 115, 127, 131, 141, 155, 168, 183, 191, 194, 3-1453, 195, 196, 189, 82, 80, and 3-911; Tr. 12, pp. 144 to 455). These commenters described their facilities and woodworking processes, employee safety and health programs, and concerns about the impact of the proposed rule's limits for wood dust on their industries. The issues raised by these participants concerned the following topics:
(1) The technological and economic feasibility of the proposed limits;

(2) The justification for a separate standard for soft wood and hard wood;

(3) The health effects evidence;

(4) The appropriate levels for the final rule's PELs; and

(5) The evidence for a separate limit for allergenic wood dusts.

The discussions below deal with each of these points in turn. Representatives from many affected segments of the wood industry stated that achieving the proposed limits of 1 mg/m(3) for hard wood and 5 mg/m(3) for soft wood would be technologically or economically infeasible or extremely difficult (Exs. 8-34, 3-917, 168, 183, 191, 80, and 3-911). OSHA has determined that, at the present time, the health evidence suggests that a single PEL of 5 mg/m(3) is appropriate for both hard and soft wood dust, with the exception of Western red cedar, for which a PEL of 2.5 mg/m(3) is being set. These revised PELs have been determined to be feasible (see the detailed discussion of these issues in the Technological Feasibility and Economic Impact sections of this preamble).
OSHA proposed separate permissible exposure limits for soft wood (5 mg/m(3)) and hard wood (1 mg/m(3)). The Agency received comments on this topic from many participants; these commenters were unanimously opposed to the setting of separate limits for these two types of wood dust (Exs. 8-34, 3-748, 3-682, 3-859, 3-899, 3-917, 191, 196, 80G, 80L, 80N, and 3-911; Tr. XII, pp. 12-290, 12-326, and 12-331). These participants stated that there was no health basis for making a distinction between hard wood and soft wood dusts (Exs. 33-899, 3-955, 3-917, and 191; Tr. 12, pp. 326-331; Tr. 12, p. 290). According to Dr. Harold Imbus, speaking for the Inter-Industry Wood Dust Coordinating Committee (Tr. pp. 12-58, 12-60), the distinction between the two woods derived from the fact that the early studies showing an increased cancer incidence in woodworking employees involved British furniture makers, who predominantly used hard wood; this association caused investigators to attribute greater toxicity to hard wood dust.

Commenters were of the opinion that this distinction was no longer warranted by the evidence; in fact, Dr. Lawrence Whitehead, certified industrial hygienist and a professor at the University of Texas School of Public Health (Tr. p. 12-331), stated that his own work suggested that some soft wood dust exposures might actually produce stronger adverse effects than equivalent exposures to some hard wood dusts.

Other commenters reported that it is not possible to distinguish soft wood from hard wood dust except by chemical analysis (Ex. 8-34, p. 28), that most facilities in the wood industries use both hard and soft woods (Exs. 3-682, 3-859, and 3-899), and that the distinction between the two types of woods is inappropriate (Ex. 3-917). For example, Joseph Gerard, Vice President of the American Furniture Manufacturers Association (Ex. 3-917) stated:

The distinction between hard woods and soft woods is purely botanical. Many so-called "softwoods" are actually hard (i.e., Douglas fir as a softwood is harder than the hardwood birch) and one of the softest woods in existence (balsa) is botanically a hardwood (Ex. 3-917, p. 2).

Jamie Cohen, speaking for the United Petitioners, a coalition of labor unions (Tr. 12, p. 294), believes that a bifurcated standard for the two types of dusts would place an undue burden on employers and could lead to compliance problems. The posthearing brief submitted by the United Brotherhood of Carpenters and Joiners of America (Ex. 196) reiterated these points by stating: "Given the frequent intermixture of wood types in the workplace, this [setting two separate standards] would render OSHA's compliance efforts virtually worthless" (Ex. 196, p. 7).

After a review of this record evidence, OSHA has determined that the health evidence for the toxicity of wood dust cannot be separately distinguished for soft wood and hard wood. In addition, the Agency is convinced by the many comments from wood industry employers that most operations involve both kinds of wood and are performed on the same machines and equipment and in the same facility. Thus, any controls installed to reduce exposures would of necessity need to be sufficient to reduce airborne dust levels to the lower of the two limits (i.e., to the proposed wood dust limit of 1 mg/m(3)). According to the Inter-Industry Wood Dust Coordinating Committee:

[I]mposition of a limit of 1 mg/m(3) for hardwood dust and 5 mg/m(3) for softwood dust effectively imposes a limit of 1 mg/m(3) on a large number of plants, including those where only small amounts of hardwood are used (Ex. 3-748, p. 3).

Many commenters took exception to the review of the health effects evidence for wood dust presented by OSHA in the preamble to the proposed rule. Objections were raised by the Inter-Industry Wood Dust Coordinating Committee (Exs. 8-34, 3-748, and 168), the Appalachian Hardwood Manufacturers (Ex. 3-626), the American Furniture Manufacturers Association (Exs. 3-917 and 191), the Georgia-Pacific Corporation (Exs. 3-955 and 183), the Hardwood Plywood Manufacturing Association (Ex. 3-911), and others.

These participants criticized many of the individual studies described by OSHA; some commenters found fault with several of these studies on the grounds that they involved British or other non-U.S. woodworkers (see, for example, Exs. 8-34, 191, 3-626, and 3-917), involved only a small number of subjects (see, for example, Exs. 8-34, 168, and 191), had inconsistent results (see, for example, Ex. 8-34), or failed to demonstrate a dose-response relationship between wood dust exposure and the health effect of concern (see, for example, Exs. 8-34, 3-626, 3-917, and 191). The Inter-Industry Wood Dust Coordinating Committee (IWDCC) stated:

[T]he observations in the European studies are not representative of conditions in U.S. workplaces, especially under modern conditions....

The English and other European experience does not provide an accurate predictive model for the incidence of nasal cancer....The excesses of nasal cancer observed in the European studies simply have not been observed in the United States at any time...(Ex. 3-748, pp. 2, 52).

OSHA agrees with the IWDCC that the incidence of nasal cancer seen in the United States is substantially lower than that seen in other countries, particularly in Great Britain. However, the Agency does not agree that excesses in nasal cancers, and particularly of nasal adenocarcinomas, have not been observed in American woodworkers. Several U.S. studies have reported excesses in nasal cancer risks among employees in the wood industries (Brinton, Stone, Blot, and Fraumeni 1976/Ex. 1-468; Brinton, Blot, Becker et al. 1984/Ex. 1-467; Viren, Vogt, and Dixon 1982, and Imbus and Dyson 1985, both as cited in NIOSH 1987a/Ex. 1-1005).

In response to those commenters who argued that none of the studies described by OSHA presented sufficient dose-response data to be used as a basis for establishing a limit, the Agency emphasizes that it is not relying on any single study to determine that wood dust presents a significant risk of material health impairment. Instead, OSHA is making this determination on the basis of the findings in the dozens of studies reporting on the respiratory, irritant, allergic, and carcinogenic properties of wood dust. The Agency finds the results of these studies biologically plausible and their findings reproducible and consistent. It is true that some of these studies, like all human studies, have limitations of sample size, involve confounding exposures, have exposure measurement problems, and often do not produce the kind of dose-response data that can be obtained when experimental animals are subjected to controlled laboratory conditions. What the large group of studies being relied upon by OSHA to establish the significance of the risk associated with exposure to wood dust do show is that the overall weight of evidence that such exposures are harmful and cause loss of functional capacity and material impairment of health is convincing beyond a reasonable doubt.

The industry strongly supported a single 5 mg/m(3) standard for both hard wood and soft wood dusts (Exs. 8-34, 3-626, 3-682, 3-824, 3-899, 3-1160, 3-917, 168J, 183, 191, 80 and attachments, and 3-911); some commenters (Exs. 3-859, 194, and 196) argued for a 1 mg/m(3) limit for all wood dust, while others (Exs. 3-955, 155, and 183) were of the opinion that the nuisance dust limit of 10 mg/m(3) was appropriate for wood dust. Four unions (Carpenters, Paperworkers, Furniture Workers and Woodworkers)(Tr. p. 12-294) strongly endorsed a 1 mg/m(3) standard for wood dust of all types on the grounds that the available health evidence clearly supports this limit.

OSHA finds that the health evidence in the record as a whole does not support a PEL of 1 mg/m(3) for all wood dusts. In addition, the Agency believes that a 1 mg/m(3) limit would present serious problems of feasibility for affected parties (see Section VII, Summary Economic Impact and Regulatory Flexibility Analysis). The Agency also finds that the health evidence clearly indicates that occupational exposure to wood dust poses a significant risk of material health impairment at the 10 mg/m(3) (or particulate) level. OSHA concludes that establishing an 8-hour PEL of 5 mg/m(3) and a 15-minute STEL of 10 mg/m(3) for all wood dusts (except Western red cedar) will substantially reduce this significant risk.

The final rule establishes an 8-hour TWA PEL of 2.5 mg/m(3) for Western red cedar wood dust, based on its widely recognized ability to cause immune-system-mediated allergic sensitization. Evidence in the record demonstrates the seriousness of this effect. A study by Brooks, Edwards, Apol, and Edwards (1980) that was submitted by the United Petitioners (Ex. 82D) reports that:

a high prevalence of occupational asthma was observed among workers exposed to WRC wood dust (Ex. 82D, p. 315).

At the hearing, Dr. Brooks described occupational asthma as follows:

[T]here are spasms of the bronchial tubes, there is reduced air flow on expiration...[the extent of which depends] on the extent of the exposure, and also...on the duration of the exposure....as a consequence of this sensitization and airway injury from the sensitization and the asthmatic reaction and the various biochemical and cellular changes that occur, there develops an associated process....the airways develop an increased sensitivity and an increased bronchospastic responsiveness to many different non-specific stimuli. So such things as cold air, dust, fumes, gases that are non-specific and wouldn't normally...[affect] most individuals [will affect] the individual with occupational asthma. And it's [such] hyper-reactive airways that cause individuals to continue to have disability and to continue to have symptoms once they leave the work place....They develop this non-specific bronchial hyper-reactivity which may last the rest of their life (Tr. pp. 12-339 to 12-343).

Some commenters (Exs. 8-34, 183, and 191) opposed the establishment of a separate PEL for Western red cedar. These participants argued that a lower PEL "for wood dust generally would be necessary or appropriate to address allergic symptoms" (Ex. 8-34, Health Effects Comments, p. 8, footnote 6). According to the Inter-Industry Wood Dust Coordinating Committee (IIWDCC):

[P]revention of allergic reactions is best achieved by good housekeeping measures directed specifically at the allergenic species (Ex. 8-34, p. 8).

Among the work practices recommended by these commenters were maintaining clean work spaces, wearing protective clothing, and avoiding skin contact with the allergenic species (Ex. 8-34, Health Effects Comments, p. 17).

Although OSHA endorses training, good work practices, and the use of appropriate protective clothing, the Agency does not agree that a reduced PEL for Western red cedar (WRC) is unnecessary. The health effects associated with occupational exposure to WRC are too severe not to be cause for concern. In addition, there is good evidence in the record of the dose-response relationship between occupational exposure to WRC dust and woodworkers' asthma. A study by Vedal, Chan-Yeung, Enarson et al. (1986/Ex. 1-397) shows such a relationship, with asthma beginning at a WRC level of 3.4 mg/m(3) and a statistically significant reduction in forced respiratory capacity noted in workers exposed to 2 mg/m(3) WRC dust or more. Harold Imbus, a physician representing the IIWDCC, stated:

This study, small though it may be, tends to support dose response, and a threshold level between 2 and 3.4 mg/m(3) for the protection of effects of WRC (Ex. 8-34, p. 7).

The 1980 study by Brooks, Edwards, Apol, and Edwards found a dose-related relationship between total WRC dust level and prevalence of asthma in employees in jobs with the greatest dust exposures. The Brooks et al. study found asthma in zero percent of WRC workers exposed at 0.5 mg/m(3); however, at 3.56 mg/m(3), this percentage rose to 5 percent.

The United Petitioners submitted a 1988 paper by Goldsmith and Shy that found that there is a clearly defined asthma syndrome produced by WRC (Ex. 3-362). OSHA finds these studies convincing evidence of WRC's allergenic potential; in addition, the Agency believes that a threshold for occupational asthma exists and lies between 2 and 3.4 mg/m(3). Based on this evidence, OSHA concludes that an 8-hour PEL of 2.5 mg/m(3) is necessary to protect workers from the significant and often permanent effects of immune-mediated occupational asthma associated with exposure to WRC dust at levels above this limit. Several record comments agree that a separate PEL for WRC dust is warranted and that the threshold level is as described above (see, for example, Exs. 8-34 (Imbus review, p. 6), 168, and 191; Tr. p. 12-292; Tr. pp. 12-317, 12-318, and 12-320).

Some commenters (Tr. p. 12-316) were of the opinion that many other woods, such as Douglas fir, pine, red and white oak, redwood, walnut, spruce, boxwood, cocobolo, teak, mahogany, and others, should also be designated by OSHA as allergenic in this rulemaking. However, OSHA finds that, as Dr. Imbus of the IIWDCC notes, "it is unlikely that species other than WRC are responsible for large numbers of cases of respiratory allergies" (Ex. 8-34, Imbus review, p. 6). The authors of the Goldsmith and Shy (1988) paper concur:

Other commonly used woods such as oak, birch, redwood, pine, teak, alder, and hemlock, produce pulmonary effects that are less well described than the asthma responses to Western red cedar (Ex. 3-362, p. 13).

The IIWDCC contends that, at the present time, there is "no consensus even as to which species should be considered allergenic" (Ex. 168). OSHA concludes that other species are somewhat allergenic. The evidence in the literature does not indicate that any other species is nearly as allergenic as WRC or would cause nearly as high a proportion of allergic reactions among exposed workers. However, the Agency will monitor the literature on these other potentially allergenic species so that other woods with demonstrably allergenic properties can be identified in the future.

Based on the evidence presented above, OSHA is establishing a PEL of 5 mg/m(3) as an 8-hour TWA and 10 mg/m(3) as a 15-minute STEL for hard and soft wood dust, with the exception of Western red cedar, for which a PEL of 2.5 mg/m(3) (8-hour TWA) is being established. OSHA concludes that promulgation of these exposure limits will substantially reduce the significant risk of material impairment in the form of pulmonary dysfunction (including changes in peak flow, interference with mucociliary clearance, respiratory symptoms, and chronic effects) that is associated with exposure to wood dust at the higher levels that would be permitted in the absence of any limit.

Conclusions For All Respiratory Toxicants

As Table C6-2 and the discussions above show, limits for the respiratory toxins have been established to control employee exposures to or below the airborne concentrations of these substances that have been associated with the development of acute or chronic respiratory effects. For most of these substances, the evidence is sufficient to identify the NOE or low-effect levels that are related to these effects in humans or animals. Accordingly, OSHA concludes that maintaining employee exposures at or below these limits will greatly decrease the likelihood that employees will be at significant risk of respiratory effects when they are exposed to these substances in the workplace. Because the chronic pulmonary disease caused by exposure to toxic dusts is often incapacitating, such exposures can effectively end the working life of severely affected individuals. Less-serious pulmonary disease can result in lost workdays, both as a result of the associated symptoms themselves and as a consequence of increased susceptibility to respiratory infections. The effects of exposure to acute pulmonary toxins, such as ozone or trimellitic anhydride, range from reduced lung function to life-threatening pulmonary edema. OSHA has determined that these adverse pulmonary effects constitute material impairments of health. Lowering the Agency's former limits or establishing limits where none previously existed will substantially reduce these significant occupational risks.

7. Substances for Which Limits Are Based on Avoidance of Cardiovascular Effects

Introduction

For seven chemicals, OSHA is revising or establishing limits based on their adverse effects on the cardiovascular system. Table C7-1 lists the former, proposed, and final Z-table limits for these substances, along with their CAS numbers and HS numbers. OSHA is revising its current ceiling limits for two substances (ethylene glycol dinitrate and nitroglycerin) by replacing them with lower short-term limits. OSHA is reducing the TWA-PEL for carbon disulfide to 4 ppm and adding a STEL of 12 ppm. For one other substance (fluorotrichloromethane), OSHA is replacing its current TWA-PEL with a ceiling value; for 1,1,2-trichloro-1,2,2-trifluoroethane, OSHA is adding a STEL to its existing 8-hour TWA. The Agency is establishing new limits for two cardiovascular toxins, chloropentafluoroethane and sodium azide.

TABLE C7-1.  List of Substances for Which Limits Are Based on
             Avoidance of Cardiovascular Effects
             (NOTE: Because of its width, this table has been divided;
             see continuation for additional columns)
___________________________________________________________________
H.S. Number/
Chemical Name                   CAS No.       Former PEL
___________________________________________________________________
1070 Carbon disulfide           75-15-0       20 ppm TWA
30 ppm STEL
                                              (30 min)
                                              100 ppm Ceiling

1087 Chloropenta-                76-15-3      --
       fluoroethane

1170 Ethylene glycol            628-96-6      1 mg/m(3) Ceiling,
       dinitrate                              Skin

1180 Fluorotrichloro-            75-69-4      1000 ppm TWA
       methane

1290 Nitroglycerin               55-63-0      1 mg/m(3) Ceiling,
                                              Skin

1364 Sodium azide             26628-22-8      --

1403 1,1,-Trichloro-             76-13-1      1000 ppm TWA
1,2,2-trifluoro-
       ethane
_________________________________________________________________________


TABLE C7-1.  List of Substances for Which Limits Are Based on
             Avoidance of Cardiovascular Effects (Continuation)
_____________________________________________________________________
H.S. Number/
Chemical Name                Proposed PEL        Final Rule PEL(1)
_____________________________________________________________________
1070 Carbon disulfide        1 ppm TWA           4 ppm TWA
                             10 ppm STEL         12 ppm STEL, Skin

1087 Chloropenta-            1000 ppm TWA        1000 ppm TWA
       fluoroethane

1170 Ethylene glycol         0.1 mg/m(3) STEL    0.1 mg/m(3) STEL,
       dinitrate             (20 min)            Skin

1180 Fluorotrichloro-        1000 ppm Ceiling    1000 ppm Ceiling
       methane

1290 Nitroglycerin           0.1 mg/m(3) STEL    0.1 mg/m(3) STEL,
                             (20 min)            Skin

1364 Sodium azide            0.1 ppm Ceiling     0.1 ppm Ceiling,
                                                 Skin

1403 1,1,2-Trichloro-        1000 ppm TWA        1000 ppm TWA
       1,2,2-trifluoro-      1250 ppm STEL       1250 ppm STEL
       ethane
_____________________________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures; its STELs are for
15 minutes unless otherwise specified; and its ceilings are peaks not to
be exceeded for any period of time.

Description of the Health Effects

Although the cardiovascular system can be adversely affected in many different ways by exposure to toxic substances, the adverse effects caused by exposure to the seven chemicals in Table C7-1 are limited to three categories: (1) cardiac sensitization; (2) vasodilation; and (3) atherosclerosis. Because these effects can have potentially disabling or life-threatening outcomes, OSHA has determined that these effects clearly constitute material impairments of health and functional capacity.

Cardiac sensitization is not mediated by the immune system and does not cause an allergic reaction. Instead, this form of sensitization occurs when a chemical "sensitizes" the heart to the effects of a class of biological compounds called sympathomimetic amines. The physiological action of sympathomimetic amines is to stimulate the heart to beat faster. The hormone adrenaline, also called epinephrine, is an example of a sympathomimetic amine. Adrenaline is normally secreted into the bloodstream when the body anticipates an increase in physical exertion, such as occurs when someone is frightened. A concentration of epinephrine equal to or higher than the no-effect level for this substance is necessary to increase the heartbeat rate in exposed individuals. The effect of a cardiac sensitizer is to lower the no-effect level so that the heartbeat rate is stimulated by a lower concentration of adrenaline. The region of the heart that becomes sensitized is the pacemaking and conduction system, which determines the rhythm and rate of the heartbeat. Unregulated or unnecessary interference with this region of the heart can result in arrhythmia, an abnormality in the rhythm or rate of the heartbeat (Levy 1985/ Ex. 1-210). The clinical consequences of an arrhythmia vary among individuals, e.g., a young person with a healthy heart may not be adversely or seriously affected by an arrhythmia. However, fatal arrhythmias have occurred in healthy young people and, in older people or in individuals whose cardiovascular systems have already been compromised, arrhythmias can cause symptoms of cerebral or myocardial ischemia, shock, or congestive heart failure.

Vasodilators are compounds that cause blood vessels to expand, resulting in a decrease in blood pressure (hypotension) and a decrease in the amount of blood reaching the organs. Acute hypotension is a common cause of shock (Harrison's Principles of Internal Medicine, 10th ed., Petersdorf et al. 1983). Chronic hypotension may result in a number of symptoms, including lethargy, weakness, easy fatigability, and dizziness or faintness.

Atherosclerosis is a serious disease produced by a degenerative process in the arteries. Plaques containing lipids, complex carbohydrates, blood products, and calcium form on the inside walls of arteries, usually on major blood vessels. These plaques are also called atheromas; their presence makes arteries narrower. Depending on which arteries in the body contain atheromas, different clinical consequences may result; these include renal hypertension, stroke, and myocardial ischemia (inadequate circulation of blood to the myocardium) (Balazs, Hanig, and Herman 1986/Ex. 1-176). Some chemicals can enhance or accelerate the formation of atheromas and thereby encourage the development of atherosclerosis, a major cause of coronary heart disease.

Dose-Response Relationships and Cardiac Effects

For four of the chemicals in Table C7-1 (carbon disulfide, ethylene glycol dinitrate, nitroglycerin, and sodium azide), the final rule's limits are based primarily on health surveys and case reports indicating that occupationally exposed workers subjected to concentrations above a no-adverse-effect level experience these cardiovascular effects. However, human data for the other three chemicals (chloropentafluoroethane, fluorotrichloromethane, and 1,1,2-trichloro-,1,2-trifluoro-ethane) are scarce. For these chemicals, limits are based on the results of studies in laboratory animals.

Chemically induced cardiovascular disease occurs in a pattern that corresponds to a typical effect-level dose-response relationship; that is, an exposure level and exposure duration exist below which the substance appears unlikely to exert an adverse effect. Thus, the limits for substances in this group are designed to maintain exposures below this apparent no-adverse-effect level.

The following discussions describe the record evidence and OSHA's findings for some substances in this group and point to the seriousness of the cardiovascular effects associated with exposure to these substances. associated with fibrosis in workers (ACGIH 1986/Ex. 1-3).

CARBON DISULFIDE CAS: 75-15-0; Chemical Formula: CS(2) H.S. No. 1070

OSHA's former limits for carbon disulfide were 20 ppm as an 8-hour TWA, a 30-minute STEL of 30 ppm, and a ceiling limit of 100 ppm that was never to be exceeded. OSHA proposed revising these limits to 1 ppm as an 8-hour TWA and 10 ppm as a 15-minute STEL, and NIOSH (Ex. 8-47, Table N1) supported these proposed limits. OSHA has evaluated all of the evidence and testimony presented in the record and has determined that a 4-ppm 8-hour TWA limit, a 12-ppm STEL, and a skin notation are necessary to reduce the risk of cardiovascular disease and reproductive effects among carbon-disulfide-exposed workers, and the Agency is establishing these limits for carbon disulfide in the final rule. The need for a lower limit is based on evidence that exposure to carbon disulfide presents risks of cardiovascular, fetotoxic, and neurological material impairment of health.

OSHA's decision to promulgate a 4-ppm limit rather than the proposed 1-ppm limit is principally based on the feasibility evidence available to OSHA (see Section VII, Technological Feasibility and Economic Impact Assessment). A skin notation has been added because there is evidence that carbon disulfide can cause systemic toxicity via the dermal route. Carbon disulfide is a clear, colorless, or faintly yellow liquid with a strong, disagreeable odor.

OSHA's proposal to reduce the limits for carbon disulfide was based on a number of human studies reviewed by the ACGIH (1986/Ex. 1-3) and NIOSH (1977b/ Ex. 1-260) that suggested that exposure to carbon disulfide levels between 10 and 40 ppm was associated with an excess risk of coronary heart disease and of adverse neurological effects. These reports comprise a series of studies carried out on carbon-disulfide-exposed workers in Great Britain (Tiller, Schilling, and Morris l968/Ex. 1-92) and Finland (Seppalainen and Tolonen 1974/Ex. 1-100; Tolonen et al. 1975/Ex. 1-392; Tolonen, Nurminen, and Hernberg 1979/ Ex. 1-158). The British cohort was recently followed up by Sweetnam et al. (1987), and the Finnish workers have been followed up by Nurminen and Hernberg (1985).

The study by Tiller et al. (1968/Ex. 1-92) of British rayon workers was the first to relate exposure to carbon disulfide to the development of coronary heart disease. These authors found that, among men employed for more than 10 years in the rayon industry and followed from 1950 to 1964, those exposed to carbon disulfide had death rates from coronary heart disease more than twice the rate in other rayon workers. Thus, the Tiller et al. (1968/Ex. 1-92) study demonstrated that 10 years or more of exposure to carbon disulfide was associated with a significantly elevated risk of coronary disease.

The United Kingdom's threshold limit value for carbon disulfide, which had been 20 ppm in the 1960s, was subsequently reduced to 10 ppm in the 1970s. To examine the effect of this reduced limit on occupational risk, Sweetnam et al. (1987) conducted a follow-up study on the cohort first described by Tiller et al. (1968/Ex. 1-92). The health status and cause of death for 2,848 members of this cohort were ascertained up to the end of 1982. Exposure scores representing cumulative exposure to carbon disulfide were developed for each cohort member, based on an analysis of personal and area sampling results, job category, and time spent in each job category. Sweetnam et al. (1987) found the pattern of mortality similar to that found by Tiller, Schilling, and Morris (1968/Ex. 1-92): among spinner operators, who had the highest CS(2) exposures of any job category, 73 deaths from ischemic heart disease (IHD) were identified, compared with 42.5 expected deaths (SMR = 172), a finding that was statistically significant. A statistically significant trend was found between cumulative exposure since first exposure and incidence of IHD mortality, which indicates a dose-related effect. A second (and perhaps most important) finding of this study was that recent (or current) exposure to carbon disulfide, as well as total cumulative exposure, were both risk factors for IHD. The authors established this association by examining the relationship between IHD mortality risk and each worker's total CS(2) exposure in the two years preceding death or the end of the study. The third result of this study was that workers with current CS(2) exposure also had significantly higher risk than workers who had ceased exposure. The dose-related relationship between increased IHD mortality risk and recent exposure to carbon disulfide suggested to the authors of this study that the effect of carbon disulfide on the cardiovascular system was direct and reversible.

Thus, the Sweetnam et al. (1987) follow-up determined that there is a relationship between the risk of IHD mortality and increased cumulative exposure to CS(2). Among workers who terminated exposure, this risk declined to non-statistically-significant levels after one year of no exposure. However, risk continued to be elevated among workers who continued to be exposed or who had not been exposure-free for a full year. OSHA interprets the findings of this important study to indicate that cumulative CS(2) dose from time of first exposure is a risk factor for IHD, and that this elevated risk continues unless exposure is terminated. That is, OSHA finds that workers who have been exposed to CS(2) in the past continue to be at increased risk as long as they are exposed to CS(2), even when their recent exposure is to lower levels (approximately 10 ppm, the current U.K. TLV).

This finding was confirmed by Nurminen and Hernberg (1985) in their follow-up study of 343 Finnish rayon workers who had been exposed to carbon disulfide for at least five years. Health status data were obtained for these workers for the period 1967 to 1982. In 1972, a preventive program had been instituted that included establishing a 10-ppm exposure limit and removing workers at high risk of coronary disease from continued exposure to carbon disulfide. Median exposure levels (largely from area samples) for the period 1975 to 1980 did not exceed 5 to 6 ppm, and third-quartile exposure levels did not exceed 10 ppm. These levels were about half those reported for the period 1967 to 1975.

Nurminen and Hernberg (1985) reported a 4.7-fold increase in IHD mortality incidence for the period 1967 to 1972, prior to the establishment of the protective measures described above. Five years after these measures were instituted, only 19 percent of the cohort continued to be exposed to carbon disulfide (compared to 53 percent of the cohort exposed in 1972). The relative risk for the first seven years of follow-up (1967 to 1974) was 3.2, compared to a relative risk of 1.0 for the last eight years (1974 to 1982). The excess risk of IHD mortality thus declined steadily throughout the follow-up period; this trend was statistically significant. The authors concluded that "...the cardiotoxic effects of CS(2) are reversible in the sense that the cessation of, or a radical decrease in, exposure reduces the risk of cardiovascular mortality to background levels" (Nurminen and Hernberg 1985, p. 34). Thus, the Nurminen and Hernberg (1985) study shows that reducing exposure levels below 10 ppm (combined, in their case, with a rigorous medical removal program to terminate exposure for employees who had developed signs or symptoms of coronary heart disease) can reduce the significant risk of IHD mortality to baseline levels.

In addition to NIOSH (Exs. 8-47 and 193), the AFL-CIO (Ex. 194) and Dr. James Melius, Director of the Division of Occupational Health and Environmental Epidemiology of the New York Department of Health (Ex. 152), supported OSHA's proposed 1-ppm PEL for carbon disulfide. However, several rulemaking participants criticized the studies relied on by OSHA, primarily on the grounds that the cohorts in which excess deaths from cardiovascular disease had been seen included workers who, these participants argued, were exposed for many years to levels of carbon disulfide much higher than the 10- to 40-ppm levels generally reported in these studies (Exs. 3-747, 3-1158, 8-19, 8-45, 31, 125, and 174; Tr. pp. 4-74 to 4-107). For example, Dr. Ernest Dixon, a toxicology consultant for the Inter-Industry Committee on Carbon Disulfide, testified as follows on these studies, which were also relied on by NIOSH to determine NIOSH's recommended standard:

The NIOSH document presents a recitation of the toxic reviews, neurotoxic effects, and the various cardiovascular studies from chiefly Scandinavia, largely epidemiologic studies which attempted to determine whether or not ischemic or other cardiovascular abnormalities caused an excess of deaths among workers exposed to elevated levels of CS(2). Essentially, all of these were from the viscose manufacturing industry.

Air sampling for carbon disulfide in the period prior to a decade ago was cumbersome, costly, and took a long time for chemical analysis. As cited in numerous other reports, the practices of that period were to obtain area rather than personal samples. Work practices examined in the studies were such that the area sample results relied upon are believed to have significantly underestimated [both] the actual exposures and [the fact] that there were substantially higher exposures than have existed in more recent years.

Accordingly, many of the workers in such studies had encountered many years of greatly higher exposure, especially for the earliest period of their exposure (Tr. p. 4-77).

In discussing the Tiller, Schilling, and Morris (1968/Ex. 1-92) study, Dr. Dixon emphasized that the coronary mortality risk of viscose production workers was not reported in this study to have been elevated, despite the fact that 17 percent of samples taken in production areas exceeded 20 ppm. However, there was a substantial excess in mortality from cardiovascular disease among spinners, where 50 percent of area samples exceeded 20 ppm (Tr. p. 4-80). In addition, Dr. Dixon pointed out that the populations studied by Vigliani (1954/Ex. 1-103) and by Seppalainen and Tolonen (1974/Ex. 1-100) were likely to have been exposed during high-viscose-production periods at the time of World War II, when exposures were higher than in later periods.

As discussed above, OSHA believes that both cumulative exposure and current exposure are risk factors for IHD among CS(2)-exposed workers; the Agency has also determined that excess risk continues for exposed workers as long as exposure continues. As to Dr. Dixon's point about area samples, OSHA does not agree that it is possible to infer that earlier area samples underestimate exposures. It is common industrial hygiene practice to measure problem areas in a facility to determine where additional control is needed. In addition, there is no way of determining, without actually taking both personal and area samples, whether the results of personal sampling would in fact be higher or lower than area samples taken in the same facility; whether breathing zone samples are higher or lower than area samples depends on a host of factors, including the positioning of the area sample in relation to the source of emissions, the location of the worker in relation to the same source, and the amount of time the worker spends in the vicinity of the emission source.

The Inter-Industry Committee on Carbon Disulfide submitted to the record a recent epidemiologic study by MacMahon and Monson (1988/Ex. 125). The study cohort consisted of 10,418 men employed between 1957 and 1979 in the four principal U.S. viscose rayon plants. The mortality status of the cohort was ascertained up to mid-1983. Cohort members were placed into general exposure categories according to job title; these categories were highest, intermediate, variable, least, and none. The authors found no significant increase in overall mortality in the 4,448 employees with the highest potential for CS(2) exposure compared with the mortality among 3,311 employees with no CS(2) exposure. However, there was a statistically significant excess of arteriosclerotic heart disease (ASHD) among the most heavily exposed workers (242 deaths versus 195.6 expected). No clear relationship was observed between exposure duration or latency and excess ASHD mortality; however, the data suggested that the risk was higher among employees exposed to CS(2) for 15 or more years and among employees hired prior to 1960.

In addition, MacMahon and Monson (1988/Ex. 125) found a statistically significant increase in the SMR (SMR = 150) for ASHD among members of the cohort who had been exposed to CS(2) the year immediately preceding the date of death or the termination date of the study (Ex. 125, Attachment B, Table 7, p. 702); however, there was no general pattern of increased SMRs among cohort members whose time since last exposure exceeded one year. This finding is consistent with the results of the British studies, which also found an increased risk of heart disease among recently exposed employees but not among employees who had left their jobs.

The Inter-Industry Committee on Carbon Disulfide interpreted the MacMahon and Monson (1988/Ex. 125) study to mean that U.S. workers employed since 1960 were not at risk of ASHD (Tr. 4-96), and NIOSH (Ex. 193, Comments on Carbon Disulfide) noted that the study lacked exposure data. However, OSHA finds the results of the MacMahon and Monson (1988/Ex. 125) study supportive and consistent with those of the British and Finnish studies discussed above. First, all of the studies clearly demonstrate a positive association between exposure to carbon disulfide and increased risk of mortality from heart disease. Second, studies from all three countries link the excess risk to cumulative CS(2) exposure. Third, the studies from all three countries demonstrate that significant risk can be substantially reduced or eliminated by reducing or stopping exposure, even after a considerable CS(2) dose has accumulated; both the U.S. and British studies report a significantly increased risk of death from heart disease among workers who were recently exposed. However, no increased risk was seen among workers whose exposures had ended one year or longer prior to death or the end of the study. Moreover, the Finnish study reported steady declines in heart disease mortality among workers after exposure levels were reduced to below 10 ppm and a rigorous medical screening and removal program was instituted. These findings clearly demonstrate that current or continued exposure to carbon disulfide at the levels presently encountered in these facilities is as important a risk factor for heart disease mortality as cumulative exposure.

In addition to evidence that carbon disulfide is a cardiovascular toxin, there is a substantial body of evidence that exposure to carbon disulfide presents a fetotoxic hazard and that this substance may also be a teratogen. Some of the early (pre-1977) animal data on reproductive effects were reviewed in the NIOSH (1977b/Ex. 1-260) criteria document on carbon disulfide. In its posthearing submission, NIOSH (Ex. 193) mentions two relevant reports. One by Cai and Bao (1981, as cited in Ex. 193) reported increased incidences of menstrual disturbances and of pregnancy toxemia, a potentially lethal condition, in rayon workers. These authors also presented evidence that CS(2) can cross the placental barrier and be secreted into mothers' milk. The second report cited by NIOSH (Hemminki and Niemi 1982, as cited in Ex. 193) found a significantly elevated incidence of spontaneous abortions among women employed in viscose rayon facilities in Finland; however, data on the specific CS(2) exposure levels were generally lacking.

The Rohm and Haas Company submitted a summary (Ex. 10-5) of the evidence on the reproductive toxicity of carbon disulfide to the OSHA docket; this information shows that carbon disulfide has caused fetal deaths and malformations in CS(2)-exposed laboratory animals. Rohm and Haas cite a series of abstracts by Tabacova and others in which oral administration of CS(2) to female rats during gestation produced both teratogenic and fetotoxic effects. These effects were magnified in the F(2) offspring of the prenatally exposed F(1) generation, which suggests that CS(2) has a multigenerational effect that continues to cause malformations in successive generations.

Jones-Price et al. (1984, NTIS/PB84-192343) found both maternal and fetal toxicity in CD rats exposed orally to 200, 400, or 600 mg/kg/d CS(2) during days 6 through 15 of gestation. No dose-related increases in the incidence of teratogenicity were observed. In another report, Jones-Price et al. (1984, NTIS/PB84-192350) found significant dose-related increases in percent resorptions/litter, percent non-live (dead or resorbed)/litter, and percent of fetuses affected (non-live and malformed)/litter among New Zealand White rabbits exposed orally to 25, 75, or 150 mg/kg/d during days 6 through 19 of gestation. The percentage of malformed fetuses per litter increased with dose and was statistically significant at the highest dose tested.

In an inhalation study, Hardin, Bond, Sikov et al. (1981/Ex. 1-699) exposed rats and rabbits to 20 or 40 ppm CS(2) for 6.5 hours per day during days 1 through 19 (rats) or 1 through 24 (rabbits) of gestation. No embryotoxic or fetotoxic effects were noted, indicating that 40 ppm is a no-effect level for these effects in rats and rabbits. According to the analysis by Rohm and Haas, the lowest-reported-effect level (25 mg/kg/d) documented by Jones-Price et al. (1984) for rabbits corresponds to an equivalent airborne exposure of 58 ppm; this lowest-reported-effect level is in close agreement with the no-effect level reported by Hardin et al. (1981/Ex. 1-699) for the same species.

OSHA believes that this evidence, which shows that consistent fetotoxic and teratogenic effects are associated with exposure to carbon disulfide, warrants considerable concern. OSHA is particularly alarmed at the multigenerational effect of CS(2) exposure that has been demonstrated to occur in rats. This risk of reproductive effects, combined with the previously recognized risk of cardiovascular disease, have convinced OSHA that a substantial reduction in the PEL for carbon disulfide is clearly justified.

Several foreign governments and standards-setting organizations have already established 8-hour TWA exposure limits for carbon disulfide that range from 1 to 10 ppm. For example, NIOSH has recommended a 1-ppm TWA limit for this substance, and Rohm and Haas established an internal limit of 4 ppm as an 8-hour TWA (Ex. 10-5). Several foreign countries, including West Germany, Italy, Japan, Sweden, and Switzerland, currently have 10-ppm limits. The ACGIH has established a 10-ppm TLV for CS(2); however, the ACGIH limit does not consider any of the evidence of CS(2)'s fetotoxic or teratogenic effects.

Based on the evidence in the record and the toxicological literature, OSHA concludes that 4 ppm is a reasonable and prudent level at which to establish a revised 8-hour TWA PEL for carbon disulfide. This limit should provide for a substantial reduction in the significant risk both of cardiovascular disease and adverse reproductive effects associated with CS(2) exposures; clearly, these effects constitute material impairments of health and functional capacity. In addition, because of the seriousness of the effects associated with exposure to carbon disulfide, and in accordance with the policy described in Section VI.C.17 on short-term exposure limits, OSHA finds that a STEL is necessary to ensure that the 8-hour TWA limit is not exceeded during operations characterized by intermittent exposures to elevated levels of CS(2). Rohm and Haas (Ex. 10-5) has established an internal guideline of 12 ppm as a short-term limit to ensure that the 8-hour TWA limit is not exceeded, and NIOSH also recommends a short-term limit to ensure that full-shift exposures are maintained under good control. In the final rule, OSHA is accordingly establishing a 12-ppm STEL to supplement the 4-ppm TWA PEL.

OSHA's assessment of the feasibility of this limit indicates that, under normal operating conditions, a 4 ppm TWA PEL and a 12 ppm STEL are generally achievable by using engineering and work-practice controls. Evidence in the record demonstrates that engineering controls and work practices are not feasible to achieve compliance and respiratory protection may be required during certain operations in industries that regenerate cellulose from viscose to form commercial products such as rayon staple, rayon yarn, cellophane, sponges and casings. Accordingly, respirators may be worn to achieve compliance with the Air Contaminants Standard when employees are performing the following tasks:

- Maintenance-type tasks (regardless of whether such tasks are performed by "maintenance personnel" or by others), such as tank washing, opening and redressing filters, cleaning process liquor screens, and handling unwashed, unpurified viscose and viscose products;

- Opening of production lines, e.g., to troubleshoot production quality, take tank samples, set thickness of cellophane, change spinerettes, clear jams, spin, thread and align film and fiber strands during extrusion, regeneration, and cutting, and manually puncture casings;

- Handling of fibers and filament bundles that have been removed from process equipment;
- Effecting product-line changes; and
- Loading alkali cellulose, and unloading, washing and dissolving xanthate, viscose and viscose products.

CHLOROPENTAFLUOROETHANE CAS: 76-15-3; Chemical Formula: ClCF(2)CF(3) H.S. NO. 1087

OSHA previously had no limit for chloropentafluoroethane (FC-115). The proposed PEL for this substance was 1000 ppm as an 8-hour TWA, and NIOSH (Ex. 8-47, Table N1) supported the proposal. The final rule establishes this limit. The ACGIH has a TLV-TWA of 1000 ppm for this colorless, odorless gas.

Chloropentafluoroethane is an asphyxiant at high concentrations. In dogs and rats, gastrointestinal absorption following intragastric intubation has been shown to be minimal (Terrill 1974/Ex. 1-1070; Clayton, Hood, Nick, and Waritz 1966/Ex. 1-952). Rats exposed to 800,000 ppm FC-115 with 20 percent oxygen for four hours showed no clinical or histopathologic effects (Clayton, Hood, Nick, and Waritz 1966/Ex. 1-952). Rats and guinea pigs showed no adverse clinical effects at inhalation levels of 600,000 ppm FC-115 in oxygen for two hours (Weigand 1971/Ex. 1-1102), and guinea pigs exposed to 200,000 ppm FC-115 in air for varying intervals up to two hours also exhibited no adverse signs (Breen and Wallis 1963, as cited in ACGIH 1986/Ex. 1-3, p. 133). Rats, mice, rabbits, and dogs have tolerated six-hour daily exposures of 100,000 ppm FC-115 for 90 days without adverse effects (Clayton, Hood, Nick, and Waritz 1966/Ex. 1-952), and laboratory animals have tolerated doses of 200,000 ppm for 3.5 hours daily, five days per week, for four weeks (Weigand 1971/Ex. 1-1102). FC-115's potential for cardiac sensitization caused one of 13 unanesthetized dogs to develop cardiac sensitization after exposure to 150,000 ppm intravenously (Trochimowicz, Azar, Terrill, and Mullin 1974/Ex. 1-448). Several other studies indicate that unanesthetized dogs, rats, and monkeys receiving dosages of between 100,000 ppm and 200,000 ppm may show increased blood pressure, accelerated heart rate, myocardial depression, or altered pulmonary effects under certain conditions (Belej and Aviado 1975/Ex. 1-462; Friedman, Cammarato, and Aviado 1973/Ex. 1-416; Aviado and Belej 1975/Ex. 1-616). There were no reports of mutagenic, teratogenic, or carcinogenic toxicities in these studies. The Agency received no comments addressing chloropentafluoroethane, other than those submitted by NIOSH.

OSHA is establishing an 8-hour TWA permissible exposure limit of 1000 ppm for chloropentafluoroethane. The Agency concludes that this limit will protect workers from the significant risk of cardiac effects, which constitutes material impairment of health and functional capacity, at the high levels formerly permitted by the absence of an OSHA limit.

ETHYLENE GLYCOL DINITRATE CAS: 628-96-6; Chemical Formula: CH(2)NO(3)CH(2)NO(3) H.S. No. 1170

NITROGLYCERIN CAS: 55-63-0; Chemical Formula: CH(2)NO(3)CHNO(3)CH(2)NO(3) H.S. No. 1290

The former OSHA PELs for ethylene glycol dinitrate (EGDN) and nitroglycerin (NG) were ceilings of 0.2 ppm which were equivalent to 1 mg/m(3) and 2 mg/m(3), respectively, both with skin notations. The proposed PELs for these substances were 20 minute STELs of 0.1 mg/m(3), (0.02 and 0.01 ppm, respectively) and NIOSH (Ex. 8-47, Table N1) supported the proposal (which was based on NIOSH's recommended limits). The ACGIH (1986/Ex. 1-3) has established a TLV-TWA of 0.05 ppm (0.3 mg/m(3)) for EGDN and a TLV-TWA of 0.05 ppm (0.5 mg/m(3)) for NG, both with skin notations. In the final rule, OSHA is establishing 15-minute STELs of 0.1 mg/m(3) for EGDN and NG and retaining the skin notations for these substances. EGDN is a yellowish, oily, explosive liquid, and NG is a pale yellow, viscous liquid.

Most occupational exposures to EGDN actually involve mixtures of EGDN and NG. Because EGDN is 160 times more volatile than nitroglycerin and most of the mixtures of these two substances used in industry consist of 60 to 80 percent EGDN, the adverse effects associated with the inhalation of the vapors from such mixtures can be attributed primarily to EGDN.

Trainor and Jones (1966/Ex. 1-107) reported that exposure to EGDN:NG at a level of 0.7 mg/m(3) for 25 minutes was sufficient to produce decreased blood pressure and a slight headache in humans. These authors also reported that workers at a munitions plant developed headaches when exposed to EGDN:NG concentrations between 0.1 and 0.53 mg/m(3) (0.36 mg/m(3) average). Morikawa, Muraki, Ikoma et al. (1967/Ex. 1-55) found that workers in an explosives plant exposed to low concentrations of EGDN:NG (0.066 ppm (approximately 0.5 mg/m(3)) was the highest average level) had a much higher incidence of abnormal pulse waves than did controls (143 out of 1,271 versus 0 out of 175). Abnormal pulse waves often indicate a clinically significant defect in the functioning of the heart and/or circulatory system (Braunwald 1978/Ex. 1-1001).

In its criteria document for NG and EGDN, NIOSH (1978h/Ex. 1-234) refers to a report of a dynamite worker who died when exposed to EGDN:NG concentrations between 0.3 and 1.4 mg/m(3), as well as to another report of two workers who died suddenly following exposure to EGDN:NG at concentrations ranging from 1.7 to 2.7 mg/m(3). NIOSH (1978h/Ex. 1-234) observed that skin absorption may have contributed significantly to the exposures causing these deaths.

OSHA received several comments on EGDN and NG (Exs. 3-661, 8-66, 121, 190, and 154). These commenters raised two issues: the technological and economic feasibility of the proposed limits, and the strength of the evidence and significance of the adverse effects associated with exposure to EGDN and NG.

In regard to the issue of technological and economic feasibility, which was raised by ICI Americas, Inc. (Ex. 154) and the Institute of Makers of Explosives (IME) (Ex. 121), OSHA has reviewed the record and has concluded that explosive manufacturers will be able to meet these limits through a combination of equipment improvements and respiratory protection. OSHA believes that, if compliance cannot be achieved via engineering controls and/or process improvements, air-supplied respirators with quick-release couplings could be used to achieve the final rule's limits. The Agency's reasoning is discussed in detail in the Technological Feasibility section of the preamble (Section VII).

On the second point addressed by commenters, the meaning of the health effects observed to occur in connection with exposure to EGDN:NG, the IME states that:

[T]he NIOSH Criteria Document relied upon in the... [proposal] was based on outdated and irrelevant information. Its findings are based on exposure conditions and data that, because of industry-initiated improvements, was not reflective of the improved conditions in NG/EGDN-manufacturing plants...in 1978, and is not reflective of the greatly improved conditions prevailing in plants at the present time....industry hygiene programs...[have] eliminated the bulk of...workplace exposure[s] (Ex. 190, p. 4).

According to the IME, OSHA's proposal did not "identify any significant health risk" of EGDN:NG exposure at the former PEL; the IME asserts that "headaches are transitory phenomena which pose no significant health risk" (Ex. 190, p. 5).

OSHA does not share the IME's view of the significance of chemically induced headaches. The Agency believes that such headaches impair performance, cause pain and suffering, affect the safety of the victim and his or her co-workers, and contribute to absenteeism. In the case of EGDN:NG-induced headaches, however, headaches have a greater meaning: they are an early warning of vasodilation, an indicator of systemic toxicity. OSHA also finds the report of an EGDN:NG-induced death in an explosives manufacturing facility both convincing and troubling. The Agency continues to be persuaded by the evidence in the Trainor and Jones (1966/Ex. 1-107) study, the NIOSH criteria document (1978h/Ex. 1-234), and the Morikawa, Muraki, Ikoma et al. (1967/Ex. 1-55) study that the health effects associated with exposure to very low levels of EGDN:NG (i.e., in the range of 0.1 to 1.4 mg/m(3)) are acute, may occur after brief exposures, and have been shown to be lethal.

According to NIOSH (Ex. 150, Comments on EGDN:NG), the 15-minute 0.1 mg/m(3) limits being established in the final rule will protect against "angina pectoris, other signs and symptoms of cardiac ischemia or heart damage, and against sudden death...since all of these...seem to be related to compensatory vasoconstriction induced by repeated exposure to NG or EGDN" (Ex. 150). NIOSH also reports that a preliminary study of mortality resulting from heart disease and other causes among NG workers by Reeve, Bloom, Rinsky, and Smith (1983a and 1983b, as cited in Ex. 150) suggests an association between NG exposure and cardiovascular disease mortality; at the facilities where this increase in cardiovascular disease occurred, exposures were being maintained near or below 0.02 ppm (0.2 mg/m(3)) (Ex. 150).

Hypotension and headache have been observed in populations exposed to EGDN:NG at levels below 0.5 mg/m(3) for brief periods (25 minutes), and fatalities have occurred after EGDN:NG exposures at concentrations between 0.3 and 1.4 mg/m(3), in one instance, and between 1.7 and 2.7 mg/m(3), in another. OSHA's former standard was 1.0 mg/m(3); since worker deaths have occurred at or near this level, OSHA is establishing short-term limits for EGDN and NG of 0.1 mg/m(3) and retaining the skin notations for these substances in the final rule. OSHA concludes that these limits are necessary to prevent fatalities and to protect against the significant risks of vasodilation and cardiac effects associated with exposures to EGDN:NG in the workplace. The Agency has determined that the cardiovascular effects caused by EGDN:NG represent material impairments of health. Because EGDN:NG is readily absorbed through the skin and can produce systemic effects by this exposure route (Tr. pp. 9-149 to 9-150), OSHA is retaining the skin notations for both substances.

FLUOROTRICHLOROMETHANE (TRICHLOROFLUOROMETHANE) CAS: 75-69-4; Chemical Formula: CCl(3)F H.S. No. 1180

Fluorotrichloromethane (trichlorofluoromethane), also known as FC-11, is a member of a large family of chemicals, the chlorofluorocarbons. The former OSHA PEL was an 8-hour TWA of 1000 ppm. The proposed PEL was a ceiling of 1000 ppm and NIOSH (Ex. 8-47, Table N1) supported the proposal. The final rule establishes this limit. At ordinary temperatures, FC-11 is a noncombustible, colorless liquid or gas.

Inhalation of large doses of FC-11 has caused cardiac sensitization and death in humans. Experimental mice that inhaled aerosol containing 10 percent FC-11 exhibited cardiac arrhythmias. In the same study, dogs that inhaled aerosol containing 2.5 percent FC-11 had decreased myocardial function; monkeys that inhaled an aerosol containing 5 percent FC-11 developed tachycardia and hypotension (Drinking Water and Health, National Research Council 1977).

Exposure to 5000 ppm FC-11 has induced cardiac sensitization and arrhythmia in dogs that were intravenously injected with epinephrine (Reinhardt, Azar, Maxfield, Smith, and Mullin 1971/Ex. 1-78). Jenkins, Jones, Coon, and Siegel (1970/Ex. 1-95) found that four species of animals (monkeys, dogs, rats, and guinea pigs) suffered no ill effects after 90 days of continuous exposure to 1000 ppm of FC-11. Other than those submitted by NIOSH, OSHA received no comments on FC-11.

The cardiac sensitization exhibited by FC-11-exposed animals is an acute effect. OSHA's former 1000-ppm TWA PEL would permit workers to be exposed to short-term concentrations of FC-11 that are sufficiently high to sensitize the heart to sympathomimetic amines; OSHA considers this effect to be a material impairment of health. Accordingly, OSHA concludes that, at the former limit, workers are at significant risk of experiencing arrhythmia. Revising this limit to a 1000-ppm ceiling limit will substantially reduce this significant risk of cardiac sensitization.

SODIUM AZIDE CAS: 26628-22-8; Chemical Formula: NaN(3) H.S. No. 1364

There was no former OSHA PEL for sodium azide. The proposed PELs were a ceiling of 0.1 ppm as hydrazoic acid vapor (HN(3)) and a ceiling of 0.3 mg/m(3) as sodium azide (NaN(3)); NIOSH (Ex. 8-47, Table N1) concurred with the Agency's selection. The final rule establishes this limit. In addition, a skin notation is being added to the limit in the final rule. The ACGIH (1986/Ex. 1-3) has ceiling limits for sodium azide of 0.1 ppm (as hydrazoic acid vapor) and 0.3 mg/m(3) (as NaN3). Sodium azide is a colorless, crystalline solid.

Sodium azide is known to produce hypotension in laboratory animals and humans. An intravenous dose of 1 mg/kg was reported to lower blood pressure in cats (Graham 1949/Ex. 1-109). In the 1950s, the medicinal usefulness of sodium azide as a hypotensive agent was tested in 30 hypertensive patients. Their hypertension was reduced, but observed side effects included headaches; in addition, 20 of 30 patients developed increased sensitivity to sodium azide, necessitating a reduction in the dose (Black, Zweifach, and Speer 1954/Ex. 1-163). Hicks (1950, cited in ACGIH 1986/Ex. 1-3, p. 533) reported that repeated intraperitoneal injections of 5 to 10 mg/kg in rats caused demyelination of nerve fibers of the CNS. Alben and Fager (1972, cited in ACGIH 1986/Ex. 1-3, p. 533) showed that sodium azide formed strong complexes with hemoglobin and blocked oxygen transport in the blood.

Acute inhalation by humans of hydrazoic acid vapor (which forms when sodium azide contacts water) results in lowered blood pressure, eye irritation, bronchitis, headache, weakness, and collapse (Fairhall et al. 1943/Ex. 1-130; Graham 1949/Ex. 1-109). The exposure levels that produce these effects were not reported by these authors. Haas and Marsh (1970/Ex. 1-121) reported that exposure to concentrations of hydrazoic acid vapor as low as 0.5 ppm "cause[d] some discomfort to laboratory personnel." Dr. Hecker of Abbott Laboratories (Ex. 3-678) commented that the limit for sodium azide should include a skin notation, and Sax and Lewis (Dangerous Properties of Industrial Materials, 7th ed., 1989) report the dermal LD(50) in rabbits to be 20 mg/kg, demonstrating that sodium azide readily penetrates the skin and causes systemic poisoning. Grace Ziem, an independent occupational physician, also supported a skin notation for sodium azide (Ex. 46). In the final rule, OSHA is therefore adding a skin notation for sodium azide.

Because of its hypotensive effect in humans, OSHA concludes that ceiling limits of 0.1 ppm (as HN(3)) and 0.3 mg/m(3) (as NaN(3)) should be established for sodium azide to reduce the significant risk of cardiovascular and irritation effects posed to workers at the levels formerly permitted by the absence of an OSHA limit. The Agency considers the effects associated with exposure to sodium azide as material impairments of health. To reduce this significant risk substantially, OSHA is establishing these ceiling limits for sodium azide in the final rule. In addition, OSHA is adding a skin notation to the PEL to alert employers to the fact that sodium azide readily penetrates intact skin and that dermal exposure can contribute significantly to overall worker exposure.

1,1,2-TRICHLORO-1,2,2-TRIFLUOROETHANE CAS: 76-13-1; Chemical Formula: CCl(2)FCClF(2) H.S. No. 1403

1,1,2-Trichloro-1,2,2-trifluoroethane (FC-113) is a member of the chlorofluorocarbon family. The former OSHA PEL was an 8-hour TWA of 1000 ppm. The Agency proposed to retain this limit and to add a STEL, and NIOSH (Ex. 8-47, Table N1) concurred that these limits are appropriate. The final rule retains the 8-hour TWA of 1000 ppm and supplements it with a 1250-ppm STEL. The ACGIH has an 8-hour TLV-TWA of 1000 ppm and a 15-minute STEL of 1250 ppm for FC-113. FC-113 is a colorless, noncombustible liquid.

Cardiac sensitization following the administration of epinephrine is the most significant effect observed after exposure to FC-113. Reinhardt, Mullin, and Maxfield (1973/Ex. 1-114) observed that 10 out of 29 dogs exposed to 5000 ppm FC-113 for 5 minutes and simultaneously injected with epinephrine developed serious arrhythmias. Similar experiments, in which the dogs were exposed to 2000 to 2500 ppm of this substance for longer periods of time (from 30 minutes to 6 hours) and simultaneously administered epinephrine, resulted occasionally in arrhythmia (Aviado 1975, as cited in ACGIH 1986/Ex. 1-3, p. 603). However, when the experiment was repeated using four 6-hour exposures to 1000 ppm in conjunction with an injection of epinephrine, no arrhythmias were observed.

A study by Stopps and McLaughlin (1967/Ex. 1-122) of human volunteers revealed that exposure to 2500 ppm FC-113 for 1.5 hours resulted in impairment of psychomotor performance (described as lethargy and inability to concentrate). This effect was not observed at concentrations below 2500 ppm. Within the first one-half to one hour of exposure to 2500 ppm or more, subjects reported subjective sensations including loss of concentration, a tendency to somnolence, and a feeling of "heaviness" in the head. Dr. Lawrence Hecker of Abbott Laboratories (Ex. 3-678) commented that there was no basis for a STEL for FC-113. OSHA does not agree with Dr. Hecker's assessment because the results of the Stopps and McLaughlin (1967/Ex. 1-122) study described above demonstrate that FC-113 can induce subjective effects in humans on short-term exposure. Thus, OSHA finds that a STEL is necessary to prevent these effects. The UAW (Tr. pp. 7-67 to 7-69) and the AFL-CIO (Ex. 194) supported short-term or ceiling limits for FC-113 lower than the proposed STEL.

The evidence described above demonstrates that FC-113 can exert toxic effects at levels of exposure comparable to the levels that were formerly permitted by excursions above the former OSHA TWA limit of 1000 ppm; such levels thus pose a significant risk of cardiac sensitization to exposed workers. The Agency considers cardiac sensitization induced by FC-113 as material impairment of health and functional capacity. OSHA concludes that a STEL of 1250 ppm will provide a wider margin of safety against cardiac sensitization and will reduce the risk of impaired psychomotor performance by limiting the potentially high, short-term exposures formerly permitted by the 8-hour TWA limit alone. The final rule establishes limits of 1000 ppm TWA and 1250 ppm STEL for 1,1,2-trichloro-1,2,2-trifluoroethane to substantially reduce the significant risks associated with exposure to this substance.

Conclusions

Of all the physiological systems, the cardiovascular system is especially vulnerable to occupational hazards because cardiovascular diseases are already so prevalent in our society. According to Levy (1985/Ex. 1-210), "an estimated 40 million Americans have some form of cardiovascular disease." The major risk factors, as revealed by epidemiology, are age, male sex, hypertension, cigarette smoking, the existence of low-density and high-density plasma lipoproteins, cholesterol, and diabetes (Levy 1985/Ex. 1-210). Many American workers exposed to the chemicals grouped on the basis of their cardiovascular effects have one or more of these risk factors and are therefore particularly susceptible to exposure to cardiovascular toxicants. Although the precise interactions among these risk factors and exposures to cardiovascular toxins are difficult to demonstrate with accuracy, few would argue that they do not occur.

OSHA concludes that the potential for cardiovascular system damage associated with exposure to these cardiac sensitizers, vasodilators, and atherosclerosis-causing substances poses a significant risk to employees in a broad range of workplaces. The effects experienced by exposed workers include arrhythmia, low blood pressure, stroke, and blockage of the flow of blood to the myocardium. OSHA has demonstrated that these effects clearly constitute material impairment of health and functional capacity. Revising or establishing exposure limits for these cardiovascular toxins will substantially reduce these significant risks.

8. Substances for Which Limits Are Based on Avoidance of Systemic Toxicity

Introduction

For a number of substances, OSHA's revised limits are based primarily on evidence that exposure is associated with general systemic toxicity. This group of substances is unique among the groupings discussed in this preamble in that no single organ system can be identified as the target of low-dose exposure to these chemicals. Instead, these substances have been shown either to affect several organ systems simultaneously or to cause a variety of nonspecific adverse signs and symptoms that are indicative of general toxicity.

The 34 substances belonging to this group and their CAS numbers, HS numbers, and former, proposed, and final rule PELs are shown in Table C8-1. OSHA is establishing exposure limits for 17 substances in this group that were not formerly regulated and retaining the former PELs for eight substances to which STELs are being added. For six substances, OSHA is lowering its former 8-hour TWA PELs. For two substances that formerly had 8-hour TWA PELs, OSHA is deleting the full-shift limit and replacing it with a short-term limit or a ceiling. For one substance, OSHA is establishing an 8-hour TWA in place of a former ceiling limit.

TABLE C8-1.  Substances for Which Limits Are Based on Avoidance of
             Systemic Toxicity
    (NOTE: Because of its width, this table has been divided; see
             continuation for additional columns).
___________________________________________________________________
H.S. Number/
Chemical Name                   CAS No.       Former PEL
___________________________________________________________________
1005 Acetonitrile                5-05-8       40 ppm TWA
1006 Acetylsalicylic            50-78-2       --
       acid (Aspirin)
1019 Aluminum                 7429-90-5       --
       (Welding fumes)
1046 2-Butoxyethanol           111-76-2       50 ppm TWA,
                                              Skin
1052 n-Butyl glycidyl ether   2426-08-6       50 ppm TWA
1067 Captan                    133-06-2       --
1088 beta-Chloroprene          126-99-8       25 ppm TWA,
                                              Skin
1109 Cyclohexylamine           108-91-8       --
1112 Cyhexatin               13121-70-5       --
1113 Dichlorodiphenyl-          50-29-3       1 mg/m(3) TWA,
        trichloroethane                        Skin
        (DDT)
1120 2-N-Dibutylamino-         102-81-8       --
       ethanol
1139 Diglycidyl ether         2238-07-5       0.5 ppm Ceiling
1159 Ethanolamine              141-43-5       3 ppm TWA
1167 Ethylene chlorohydrin     107-07-3       5 ppm TWA,
                                                Skin
1189 Glycidol                  556-52-5       50 ppm TWA
1198 Hexafluoroacetone         684-16-2       --
1207 Hydrogen cyanide           74-90-8       10 ppm TWA,
                                                Skin
1210 Hydrogenated            61788-32-7       --
       terphenyls
1223 2-Isopropoxyethanol       109-59-1       --
1227 Isopropyl glycidyl       4016-14-2       50 ppm TWA
       ether
1273 4,4'-Methylene bis        101-14-4       --
       (2-chloroaniline)
1317 Phenylhydrazine           100-63-0       5 ppm TWA,
                                                Skin
1318 Phenylphosphine           638-21-1       --
1321 Phosphine                7803-51-2       0.3 ppm TWA
1330 Piperazine dihydro-       142-64-3       --
       chloride
1340 n-Propyl nitrate          627-13-4       25 ppm TWA
1366 Sodium fluoroacetate       62-74-8       0.05 mg/m(3)
                                              TWA, Skin
1412 Trimethyl benzene       25551-13-7       --
1416 Tungsten Compounds       7440-33-7       --
       (insoluble)
1417 Tungsten Compounds       7440-33-7       --
       (soluble)
1428 Vinylidene chloride        75-35-4       --
1430 Welding fumes               --           --
     (Total particulate)
1437 Zinc oxide (Fume)        1314-13-2       5 mg/m(3) TWA
1439 Zirconium compounds      7440-67-7       5 mg/m(3) TWA
____________________________________________________________________


TABLE C8-1.  Substances for Which Limits Are Based on Avoidance of
             Systemic Toxicity (Continuation)
_____________________________________________________________________
H.S. Number/
Chemical Name                Proposed PEL         Final Rule PEL(1)
_____________________________________________________________________
1005 Acetonitrile            20 ppm TWA, Skin     40 ppm TWA,
1006 Acetylsalicylic         5 mg/m(3) TWA        5 mg/m(3) TWA
       acid (Aspirin)
1019 Aluminum                5 mg/m(3) TWA        5 mg/m(3) TWA
       (Welding fumes)
1046 2-Butoxyethanol         25 ppm TWA,          25 ppm TWA,
                             Skin                 Skin
1052 n-Butyl glycidyl ether  25 ppm TWA           25 ppm TWA
1067 Captan                  5 mg/m(3) TWA        5 mg/m(3) TWA
1088 beta-Chloroprene        10 ppm TWA,          10 ppm TWA,
                             Skin                 Skin
1109 Cyclohexylamine         10 ppm TWA           10 ppm TWA
1112 Cyhexatin               5 mg/m(3) TWA        5 mg/m(3) TWA
1113 Dichlorodiphenyl-       1 mg/m(3) TWA,       1 mg/m(3) TWA,
       trichloroethane       Skin                 Skin
       (DDT)
1120 2-N-Dibutylamino-       2 ppm TWA,           2 ppm TWA
       ethanol               Skin
1139 Diglycidyl ether        0.1 ppm TWA          0.1 ppm TWA
1159 Ethanolamine            3 ppm TWA            3 ppm TWA,
                             6 ppm STEL           6 ppm STEL
1167 Ethylene chlorohydrin   1 ppm Ceiling,       1 ppm Ceiling,
                             Skin                 Skin
1189 Glycidol                25 ppm TWA           25 ppm TWA
1198 Hexafluoroacetone       0.1 ppm TWA,         0.1 ppm TWA,
                             Skin                 Skin
1207 Hydrogen cyanide        4.7 ppm Ceiling      4.7 ppm STEL,
                             (10 min)             Skin
1210 Hydrogenated            0.5 ppm TWA          0.5 ppm TWA
       terphenyls
1223 2-Isopropoxyethanol     25 ppm TWA           25 ppm TWA
1227 Isopropyl glycidyl      50 ppm TWA           50 ppm TWA,
       ether                 75 ppm STEL          75 ppm STEL
1273 4,4'-Methylene bis      0.02 ppm TWA         0.02 ppm TWA,
       (2-chloroaniline)     Skin                 Skin
1317 Phenylhydrazine         5 ppm TWA            5 ppm TWA
                             10 ppm STEL          10 ppm STEL,
                             Skin                 Skin
1318 Phenylphosphine         0.05 ppm Ceiling     0.05 ppm Ceiling
1321 Phosphine               0.3 ppm TWA          0.3 ppm TWA,
                             1 ppm STEL           1 ppm STEL
1330 Piperazine dihydro-     5 mg/m(3) TWA        5 mg/m(3) TWA
       chloride
1340 n-Propyl nitrate        25 ppm TWA           25 ppm TWA
                             40 ppm STEL          40 ppm STEL
1366 Sodium fluoroacetate    0.05 mg/m(3) TWA     0.05 mg/m(3) TWA
                             0.15 mg/m(3) STEL    0.15 mg/m(3) STEL,
                             Skin                 Skin
1412 Trimethyl benzene       25 ppm TWA           25 ppm TWA
1416 Tungsten Compounds      5 mg/m(3) TWA        5 mg/m(3) TWA
       (insoluble)           10 mg/m(3) STEL      10 mg/m(3) STEL
1417 Tungsten Compounds      1 mg/m(3) TWA        1 mg/m(3) TWA
       (soluble)             3 mg/m(3) STEL       3 mg/m(3) STEL
1428 Vinylidene chloride     5 ppm TWA            1 ppm TWA
                             20 ppm STEL
1430 Welding fumes           5 mg/m(3) TWA        5 mg/m(3) TWA
     (Total particulate)
1437 Zinc oxide (Fume)       5 mg/m(3) TWA        5 mg/m(3) TWA
                             10 mg/m(3) STEL      10 mg/m(3) STEL
1439 Zirconium compounds     5 mg/m(3) TWA        5 mg/m(3) TWA
                             10 mg/m(3) STEL      10 mg/m(3) STEL
_____________________________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures; its STELs are
for 15 minutes unless otherwise specified; and its ceilings are peaks not
to be exceeded for any period of time.

Description of the Health Effects

For each substance included in this grouping, limits have been established to protect against a variety of adverse exposure-related effects that are manifested at multiple target organ sites. In some instances, the nature of the toxic effects associated with exposure is well-defined and clearly understood (for example, CNS depression, histological organ changes, embryo-toxicity, methemoglobinemia, conjunctivitis, liver and kidney damage, testicular damage). The effects of exposure to other substances in this group, however, have been demonstrated only by such nonspecific indicators as dizziness, respiratory irritation, hematuria, chest tightness, weight loss or decreased rate of weight gain, lethargy, loss of appetite, nervousness, or gastrointestinal disturbances. Although the specificity of the systemic effect caused by exposure to the substances in this group may vary, all of these substances have been shown to be biologically active in mammalian species, to interfere significantly with biological processes, and to impair normal organ function.

Table C8-2 summarizes the toxic effects reported in humans and experimental animals that support the establishment of limits for these substances. This table shows the variety of adverse health effects that adoption of the final rule's limits will minimize or prevent. The table also shows that, for the vast majority of substances in this group, the risks of exposure have been defined in studies of humans or animals and are known to include respiratory effects, neurological effects, adverse effects on the reproductive system, organ damage, hematopoietic effects, sensitization, and mucosal irritation. All of these effects are indicative of generalized systemic effects rather than localized effects occurring at the site of chemical contact.

TABLE C8-2.  Summary of Adverse Health Effects Reported for
             Substances Producing General Systemic Toxicity
________________________________________________________________________
H.S. Number/            Effects Reported            Effects Reported
Chemical Name           in Humans                   in Animals
________________________________________________________________________
1005 Acetonitrile       Tightness in chest;         Embryotoxicity;
                        flushing of face            teratogenicity at
                                                    maternally
                                                    toxic doses;
                                                    liver, blood count
                                                    changes

1006 Acetylsalicylic    Mucosal irritation;         Teratogenicity at
       acid             respiratory sensitization;  high doses
                                                    internal bleeding

1019 Aluminum welding   No data                     Respiratory effects
      fumes

1046 2-Butoxyethanol    Mild sensory irritation     Severe hemoglobinuria;
                                                    lung, kidney, liver
                                                    changes; hemolytic
                                                    anemia; increased
                                                    osmotic fragility in
                                                    erythrocytes

1052 n-Butyl glycidyl   Dermatitis; skin            Delirium; depression
       ether             sensitization

1067 Captan             Recurrent urticaria         Decreased fertility
                                                    index in males;
                                                    polyploid carcinoma
                                                    of duodenum

1088 Chloroprene        CNS depression;             Minimal systemic
                        lung, liver, kidney injury;    effects
                        conjunctivitis; necrosis of
                        cornea;
                        lowering of blood pressure

1109 Cyclohexylamine    Acute toxicity;             Mutagenic and
                        sensitization               reproductive effects

1112 Cyhexatin          No data                     Microscopic changes
                                                    in liver, kidneys,
                                                    adrenal glands

1113 Dichlorodiphenyl-  Mild poisoning              Cancer of liver,
      trichloroethane                               lungs, lymph system
       (DDT)

1120 2-N-Dibutylamino-  No data                     Weight loss; elevated
     ethanol                                        liver- and kidney-to-
                                                    body-weight ratios

1139 Diglycidyl ether   Mucosal irritation          CNS depression,
                                                    clouding of cornea;
                                                    respiratory
                                                    irritation;
                                                    hematopoietic effects

1159 Ethanolamine       No data                     Pulmonary, hepatic,
                                                    and renal lesions;
                                                    decreased alertness;
                                                    temporary weight loss

1167 Ethylene           Liver and brain damage;     Respiratory
      chlorohydrin      mucosal irritation;         depression; liver and
                        gastrointestinal            kidney damage
                        disturbance

1189 Glycidol           No data                     Pneumonitis;
                                                    emphysema

1198 Hexafluoroacetone  No data                     Renal dysfunction;
                                                    increased lung
                                                    weight; testicular
                                                    damage; hematopoietic
                                                    effects; fetotoxicity

1210 Hydrogenated       No data                     Decreased weight
       terphenyls                                   gain; liver, kidney
                                                    damage; lung changes,
                                                    bronchopneumonia

1207 Hydrogen cyanide  Cyanide poisoning;           None reported
                       weakness; mucosal irritation;
                       colic; nervousness;
                       enlargement of thyroid

1223 2-Isopropoxyethanol No data                    Anemia;
                                                    hemoglobinuria;
                                                    lung congestion

1227 Isopropyl         Mucosal irritation           Reduced weight gain;
     glycidyl ether                                 hemoglobin increase;
                                                    emphysematous changes
                                                    in lungs; CNS
                                                    depression

1273 4,4'-methylene-bis Bladder cancer;             Cyanosis;
      (2-chloroaniline)    hematuria                methemoglobinemia;
                                                    liver, lung tumors

1317 Phenylhydrazine    Skin sensitization          Anemia; irregular
                                                    growth; general
                                                    weakness; blood
                                                    vessel tumors

1318 Phenylphosphine    No data                     Mild hemolytic
                                                    anemia; testicular
                                                    degeneration; hind
                                                    leg tremor; nausea;
                                                    loss of appetite;
                                                    hypersensitivity to
                                                    sound and touch

1321 Phosphine          Pulmonary edema;            Respiratory
                        gastrointestinal            irritation
                        disturbances; dizziness

1330 Piperazine         Skin burns; sensitization;  No data
     dihydro-chloride   asthma

1340 n-Propyl nitrate   No data                     Cyanosis;
                                                    methemoglobinemia;
                                                    hypotension;
                                                    respiratory
                                                    depression

1366 Sodium             No data                     Fluctuation in growth
     fluoroacetate                                  rate; tissue changes

1412 Trimethylbenzene   Nervousness, tension,       CNS depression
                        anxiety; asthmatic          Lymphopenia;
                        bronchitis; hypochromic     neutrophilia
                        anemia

1416 Tungsten compounds  No data                    Gross changes in
       (insoluble)                                  liver and spleen;
                                                    lung tissue changes

1417 Tungsten compounds  No data                    Generalized cellular
       (soluble)                                    asphyxiation; colic;
                                                    incoordination;
                                                    dyspnea

1428 Vinylidene         No data                      Nasal irritation;
       chloride                                      liver cell
                                                     degeneration;
                                                     retarded weight gain;
                                                     embryotoxicity;
                                                     kidney adenocarcinoma

1430 Welding fumes      Pulmonary irritation         Pulmonary irritation
     (total particulate)

1437 Zinc oxide (fume)  Metal fume fever; gastritis  No data

1439 Zirconium          No data                      Toxic effects from
      compounds                                      zirconium
                                                     tetrachloride due to
                                                     liberation of
                                                     hydrochloric acid
_________________________________________________________________________

Dose-Response Relationships and Systemic Effects

As Table C8-2 shows, adverse toxic reactions have been reported to occur in humans for 19 of the 34 substances in this group; thus, for more than half of these substances, it has been established conclusively that exposure is associated with adverse health effects in humans. Experimental animal data comprise the principal evidence for the toxicologic action of the remaining substances. As is the case for many substances for which limits are being established, apparent no-observed-effect levels, supplemented by the use of appropriate margins of protection, provide the basis for setting limits. The systemic effects caused by exposure to substances in this group appear to follow an NOE dose-response pattern. That is, as intensity and/or duration of exposure decreases, the severity of the effect on organ systems also decreases until a point is reached (the NOE level) where there is no detectable effect, at least at observable levels, on organ systems. No-effect exposure levels have been identified in humans and animals for several of the substances in this group; where no-effect levels have been identified (i.e., for diglycidyl ether and phenylphosphine), they have provided the primary basis for the new limits.

In instances where no-effect levels have not been reported (e.g., for n-butyl glycidyl ether, trimethylbenzene, and acetylsalicylic acid), OSHA has used safety factors and expert judgment to derive an NOE value.

The following discussions describe the record evidence and OSHA's findings for these systemic toxicants and present a summary of the material impairments of health associated with exposure to these substances.

ACETONITRILE CAS: 75-05-8; Chemical Formula: CH(3)CN H.S. No. 1005

Acetonitrile is most widely used in industry as a specialty solvent and chemical intermediate. OSHA's former occupational exposure limit for acetonitrile was a 40-ppm 8-hour TWA. The ACGIH has a 40-ppm TLV-TWA with a 60-ppm TLV-STEL, in addition to a skin notation. OSHA proposed to reduce the former 8-hour TWA PEL to 20 ppm with a skin notation; this was the NIOSH REL, and NIOSH concurred with the proposed limit (Ex. 8-47, Table N1). However, after a thorough evaluation of the record evidence, OSHA has concluded that the ACGIH limits for this substance will provide appropriate protection against acetonitrile's systemic toxicity. Accordingly, the final rule establishes an 8-hour TWA of 40 ppm and a STEL of 60 ppm, without a skin notation, for acetonitrile.

In animal studies, acetonitrile has been found to be embryotoxic and teratogenic in rodents exposed to levels sufficiently high to cause maternal toxicity (Berteau, Levinskas, and Rodwell 1982/Ex. 1-179; Willhite 1983/ Ex. 1-43). A 13-week inhalation study conducted by the National Toxicology Program (Hazleton Laboratories, Inc. 1983, as cited in ACGIH 1986/Ex. 1-3, p. 8) found pathological changes in the liver and some blood changes in mice and rats exposed to concentrations of 400 ppm acetonitrile.

The human evidence describing the toxic effects associated with exposure to acetonitrile consists of a report by Pozzani, Carpenter, Palm et al. (1959/Ex. 1-106), who exposed human subjects to acetonitrile vapor, and a case report by Amdur (1959/Ex. 1-143), who described a poisoning incident involving acetonitrile. None of three subjects exposed to 40 ppm for four hours reported any adverse responses during the exposure period, but one subject experienced tightness of the chest a few hours after termination of exposure, as well as a cooling sensation in the lungs the following day. None of the subjects had elevated blood cyanide levels; one subject showed a slightly elevated urinary thiocyanate level. Pozzani et al. (1959/Ex. 1-106) also exposed two subjects to 80 ppm and 160 ppm of acetonitrile for four hours. When exposed to 80 ppm, subjects reported no adverse response; however, at 160 ppm, one subject experienced slight flushing of the face and chest tightness a few hours after exposure (Pozzani, Carpenter, Palm et al. 1959/Ex. 1-106).

In addition to the Pozzani et al. (1959/Ex. 1-106) study, NIOSH (1978g/Ex. 1-262) cites a report by Amdur (1959/Ex. 1-143), who investigated an incident in which 16 painters became ill (with one death) after using an acetonitrile-containing material in a confined space. Amdur (1959/Ex. 1-143) reported no further incidents after adequate ventilation was installed and acetonitrile levels were maintained at about 17 ppm. NIOSH concluded that exposure to 40 ppm may have produced minimal effects and that no observable effects were produced at 17 ppm (NIOSH 1978g/Ex. 1-262, p. 97). Therefore, NIOSH recommended that exposure not exceed 20 ppm as a 10-hour TWA. Other than the comment by NIOSH (Ex. 8-47), no comments were received on this substance.

OSHA has carefully re-evaluated the evidence of acetonitrile's toxicity to determine the appropriate permissible exposure limits to establish in the final rule. The Agency concludes that the evidence in humans suggests that no adverse effects are experienced at long-term exposures of 40 ppm and that a short-term limit of 60 ppm will provide protection against the facial flushing and chest tightness experienced by workers exposed for several hours to levels above these concentrations. In addition, in accordance with the policy on skin notations enunciated in Section VI.C.18, OSHA is not including a skin notation for acetonitrile in the final rule (the dermal LD(50) in rabbits is 1250 mg/kg).

In the final rule, OSHA is therefore retaining its existing 8-hour TWA for acetonitrile and adding a STEL of 60 ppm to protect against this substance's systemic effects. The Agency concludes that these limits will prevent the significant risk of acute illness (and, in one case, death) observed in workers exposed to excessive short-term exposures of acetonitrile; the Agency finds that these health effects clearly constitute material impairments of health. In the proposal, OSHA specifically requested information on the feasibility of achieving the proposed limit; no comments were received, and OSHA accordingly assumes that the final rule's limits, which are higher than the limit proposed, are feasible.

ACETYLSALICYLIC ACID (ASPIRIN) CAS: 50-78-2; Chemical Formula: CH(3)COOC(6)H(4)COOH H.S. No. 1006

There was no former OSHA exposure limit for acetylsalicylic acid. The ACGIH has a TLV of 5 mg/m(3) as an 8-hour TWA. The proposed PEL was 5 mg/m(3) as an 8-hour TWA. NIOSH (Ex. 8-47, Table N1) concurs with this limit, and this is the limit established by the final rule. Acetylsalicylic acid is a white crystal or powder that is essentially odorless and has a slightly bitter taste.

The work of O'Brien (1968/Ex. 1-47) reports that a normal therapeutic dose of 600 mg aspirin will interfere with platelet aggregation in subjects exposed for a period of five days or more. Hart (1947/Ex. 1-137) also reported that 150 mg is the smallest oral dose of acetylsalicylic acid that will produce this effect. Unpublished data from the Dow Chemical Company (cited in ACGIH 1986/Ex. 1-3, p. 10) indicate that aspirin concentrations exceeding 100 mg/m(3) are tolerated except for occasional skin irritation. However, no data are available on the long-term effects on organ systems of inhalation exposure to aspirin. Secondary sources report that aspirin is an acute irritant to the gastric mucosa and respiratory tract. No comments other than that by NIOSH (Ex. 8-47) were received on this substance.

In the final rule, OSHA is establishing an 8-hour TWA of 5 mg/m(3) for acetylsalicylic acid. The Agency concludes that this reduced limit will protect workers from experiencing the adverse blood effects and gastric and respiratory irritation, which constitute material impairments of health that are potentially associated with exposure to this substance at the previously uncontrolled levels.

ALUMINUM (WELDING FUMES) CAS: 7429-90-5; Chemical Formula: Al H.S. No. 1019

OSHA formerly had no permissible exposure limit for aluminum welding fumes. The proposed PEL was 5 mg/m(3), which is consistent with the ACGIH limit. The final rule promulgates an 8-hour TWA for aluminum welding fumes of 5 mg/m(3), measured as aluminum. NIOSH (Ex. 8-47, Table N1) concurs with this limit.

OSHA received two comments pertaining to aluminum welding fumes. The first commenter (Ex. L3-1330) sought clarification as to whether the term "aluminum welding fumes" refers to aluminum fumes or to the gases and fumes usually associated with aluminum welding, such as ozone, nitrous gases, carbon monoxide, and carbon dioxide. The second commenter, the Specialty Steel Industry of the United States (Ex. 3-829), objected to the establishment of a permissible exposure limit for aluminum welding fumes because, in this commenter's opinion, no scientific evidence was cited in the proposal to indicate that exposure resulted in deleterious effects (Ex. 3-829, p. 6).

The PEL addresses the aluminum fume that is released in the welding process; this limit is being established to keep the total aluminum particulate concentrations low enough to prevent aluminum particle accumulation in the lungs. However, to the extent either that other toxic substances or materials are released in the welding process or that conditions are conducive to the formation of toxic gases, employers must pay attention to the permissible exposure limits for these substances as well. For example, in Appendix B of the 1987-88 Threshold Limit Values and Biological Exposure Indices (ACGIH 1987/Ex. 1-16), the ACGIH states that "reactive metals and alloys such as aluminum and titanium are arc-welded in a protective, inert atmosphere such as argon. These arcs create relatively little fume, but an intense radiation which can produce ozone" (ACGIH 1987/Ex. 1-16, Appendix B, p. 42). In such an instance, employers would be required to meet the ozone limits established in this rulemaking (0.1 ppm TWA and 0.3 ppm STEL) as well as the PEL for aluminum welding fumes.

The ACGIH states that "most welding, even with primitive ventilation, does not produce exposures inside the welding helmet above 5 mg/m(3). That which does...should be controlled" (ACGIH 1987/Ex. 1-16, Appendix B, p. 43). In those rare instances where internal helmet exposures do exceed 5 mg/m(3), employees are at risk from the irritant effects of hot metal fumes, which enter the lung deeply and accumulate.

Because workers exposed to arc welding fumes have previously not been protected by a permissible exposure limit, OSHA is establishing a PEL of 5 mg/m(3) TWA for these fumes, (measured in the breathing zone of the welder; the details of the appropriate positioning of the sampler should be determined on the basis of guidance in the Field Operations Manual (OSHA 1984). This is consistent with a past OSH Review Commission decision (8 OSHRC 1049). The Agency concludes that this limit will protect welders and other workers in the vicinity of the welding from experiencing the significant irritation potentially associated with inhalation of these fumes; OSHA finds the respiratory irritation caused by exposure to these fumes constitutes a material health impairment.

2-BUTOXYETHANOL CAS: 111-76-2; Chemical Formula: C(4)H(9)OCH(2)CH(2)OH H.S. No. 1046

OSHA's former permissible exposure limit for 2-butoxyethanol, one of the family of substances known as the glycol ethers, was 50 ppm as an 8-hour TWA, with a skin notation. The ACGIH has a limit of 25 ppm TWA, also with a skin notation, for this colorless liquid with a mild ether odor. The proposed PEL was 25 ppm as an 8-hour TWA, and this limit is established by the final rule. The skin notation is retained. NIOSH (Ex. 8-47, Table N1) concurs with the 25-ppm limit for 2-butoxyethanol.

2-Butoxyethanol has long been known to be toxic, with early studies indicating that a single seven-hour exposure to 700 ppm was lethal to laboratory animals (Werner, Mitchell, Miller, and von Oettingen 1943a, as cited in ACGIH 1986/Ex. 1-3, p. 71). Exposures near the lethal level caused systemic toxicity in the form of hemoglobinuria and lung, kidney, and liver changes. Carpenter, Pozzani, Weil, and associates (1956/Ex. 1-303) reported hemolytic anemia and increased fragility of the red blood cells in rats repeatedly exposed to 2-butoxyethanol at 320 ppm for five weeks. However, repeated exposure for 12 weeks at 400 ppm was only slightly injurious to dogs (Werner, Mitchell, Miller, and von Oettingen 1943b, as cited in ACGIH 1986/Ex. 1-3, p. 71).

Humans appear to be less susceptible to butoxyethanol poisoning than experimental animals. In humans, several single 8-hour exposures at levels of 200 ppm and 100 ppm caused urinary excretion of butoxyacetic acid; these subjects experienced irritation and discomfort after these exposures (Carpenter, Pozzani, Weil et al. 1956/Ex. 1-303). A recent study has confirmed that the increased erythrocyte osmotic fragility observed in rats exposed to many of the glycol ethers is a very sensitive indicator of toxicity and correlates with the development of hemoglobinuria at higher exposure levels (Moffett, Linnett, and Blair 1976, as cited in ACGIH 1986/Ex. 1-3, p. 71). These findings indicate that the no-effect level in animals is approximately 25 ppm. The ACGIH suggests that 2-butoxyethanol's toxicity may be more likely to occur as a result of skin absorption than as a consequence of inhalation (ACGIH 1986/Ex. 1-3, p. 71).

The Independent Lubricant Manufacturers (Ex. 3-830) objected to the establishment of a PEL for 2-butoxyethanol on the basis of a 25-ppm no-effect level in animals, particularly when the evidence suggests that humans may be less susceptible than animals to the effects of this substance (Ex. 3-830, p. 5). In response to this comment, OSHA notes that Patty's Industrial Hygiene and Toxicology (3rd rev. ed., Clayton and Clayton 1982) states that "the lowest concentration of ethylene glycol butyl ether vapor considered to be unpleasant and therefore disagreeable was 40 ppm" (Vol. 2C, p. 3939). This level is below OSHA's former PEL of 50 ppm, and the Agency thus believes that its former standard for 2-butoxyethanol was too high.

OSHA concludes that the former PEL of 50 ppm was insufficiently protective against the risk of 2-butoxyethanol's irritant, hematological, and other potential systemic effects, which constitute material health impairments. The limit of 25 ppm included in the final rule will reduce this significant risk to a level below that at which these toxic effects have been observed in animals and humans. This lower limit will also prevent the discomfort experienced by workers at exposure levels of 40 ppm. The skin notation is retained because of 2-butoxyethanol's ability to be absorbed dermally in toxic quantities (2-butoxyethanol's dermal LD(50) in rabbits is 490 mg/kg [RTECS 1988]).

n-BUTYL GLYCIDYL ETHER CAS: 2426-08-6; Chemical Formula: C(4)H(9)OCH(2)CH(2)OH H.S. No. 1052

The former OSHA limit for n-butyl glycidyl ether was 50 ppm as an 8-hour TWA. The ACGIH-recommended TLV is 25 ppm; NIOSH has recommended that occupational exposure to n-butyl glycidyl ether not exceed 5.6 ppm as a 15-minute short-term level. The proposed PEL was 25 ppm as an 8-hour TWA, and the final rule promulgates this limit. n-Butyl glycidyl ether is a clear, colorless liquid.

OSHA's former PEL of 50 ppm, which was adopted from the ACGIH's 1968 TLV list, was based on a Dow Chemical Company report (cited in ACGIH 1986/Ex. 1-3) that showed that repeated applications of n-butyl glycidyl ether to the skin of humans caused irritation and sensitization; at the time, the ACGIH concluded that a limit of 50 ppm would prevent these irritant responses. Subsequently, the ACGIH reduced the TLV to 25 ppm, noting that the 50-ppm limit was only 13 times lower than the 8-hour LC(50) (670 ppm) reported for this chemical in rats, and that a wider margin of protection was desirable.

The NIOSH limit of 5.6 ppm was recommended in the Institute's June 1978 criteria document on glycidyl ethers (NIOSH 1978d/Ex. 1-232). This limit was based, in large part, on mutagenic studies conducted in microbial and mammalian test systems, as well as on some evidence for other members of the glycidyl ether family showing that exposure is associated with testicular atrophy and hematopoietic abnormalities in laboratory animals. After publication of its Criteria Document, NIOSH received a confidential report prepared for the Shell Development Company by Anderson et al. (1957, as cited in ACGIH 1986/Ex. 1-3, p. 81), who had conducted a rat inhalation study. In this research, rats were exposed to 38 ppm, 75 ppm, 150 ppm, or 300 ppm n-butyl glycidyl ether for seven hours daily, five days per week for 10 weeks. Atrophic testes were found in 5 of 10 rats exposed to 300 ppm, very small testes were found in 1 of 10 rats exposed to 150 ppm, and patchy atrophy was found in the testes of 1 of 10 rats exposed to 75 ppm. No effects were observed in rats exposed at 38 ppm. Based on this additional evidence, NIOSH reaffirmed its REL for n-butyl glycidyl ether in a current intelligence bulletin (NIOSH 1978p, as cited in ACGIH 1986/Ex. 1-3, p. 81).

The Workers Institute for Safety and Health (WISH) and the AFL-CIO submitted posthearing comments on butyl glycidyl ether (Exs. 116, 194). These commenters opposed OSHA's proposal to adopt the ACGIH TLV for this substance on the basis of the reproductive study published in a NIOSH CIB (discussed above) which shows testicular atrophy in exposed laboratory animals. According to WISH:

OSHA's review of this substance in the proposal attempts to state that the 25 ppm ACGIH level is protective against these reproductive effects because a no-effect level of 38 ppm was observed (Ex. 116).

WISH found this conclusion unjustifiable because of the short exposure period (10 weeks) used in the study establishing the NOEL for reproductive effects and because considerable uncertainty always surrounds no-effect-level studies. In addition, WISH pointed out that "fertility in rats is less sensitive to certain testicular effects than human fertility" and, therefore, that this animal is not the best predictor of human reproductive effects (Ex. 116). In response to these comments, OSHA wishes to clarify that the Agency did not intend to imply in the proposal that the 25-ppm limit would protect against all risk of possible reproductive effects. In fact, the proposal merely noted that 25 ppm was below the no-effect level for reproductive effects in rats. The Agency agrees with WISH that the use of a longer exposure period in the Anderson et al. (1957, as cited in ACGIH 1986/Ex. 1-3, p. 81) reproductive study might have established a lower NOEL.

However, based on the existing evidence for reproductive effects linked to n-butyl glycidyl ether exposure, OSHA concludes that reducing the PEL from 50 ppm to 25 ppm will substantially reduce the significant risk of these reproductive effects and will also protect workers against the irritation and sensitization effects, all of which constitute material health impairment caused by exposure to this chemical. The Agency notes that NIOSH's REL of 5.6 ppm (15-minute STEL) is based on the result of in vitro testing in both microbial and mammalian systems; extensive extrapolation is required to predict effects in humans on these bases. The final rule establishes a permissible exposure limit of 25 ppm TWA for n-butyl glycidyl ether.

CAPTAN CAS: 133-06-2; Chemical Formula: C(9)H(8)Cl(3)NO(2)S H.S. No. 1067

OSHA did not formerly regulate captan. The ACGIH has a TLV-TWA of 5 mg/m(3) for this substance, which is a white, crystalline, odorless solid. The proposed PEL was an 8-hour TWA of 5 mg/m(3), and the final rule promulgates this limit.

Skin applications of 900 mg/kg captan produce skin irritation in experimental animals. Long-term feeding studies did not reveal adverse effects in dogs fed captan in the diet at levels of 100 mg/kg/day for 66 weeks or in rats fed 1000 mg/kg/day for two years (Martin 1971/Ex. 1-1161; Spencer 1968, as cited in ACGIH 1986/Ex. 1-3, p. 98). Male mice showed decreased fertility at levels of 50 or 100 mg/kg/day for five days (Collins 1972/Ex. 1-893).

Studies on the mutagenicity of captan indicate that the substance acts as an alkylating agent and induces chromosome rearrangements in rats and point mutations in Neurospora crassa (Epstein and Legator, as cited in ACGIH 1986/Ex. 1-3, p. 98). Legator and colleagues (1969, as cited in ACGIH 1986/Ex. 1-3, p. 98) reported that captan concentrations of 10 ug/ml inhibited DNA in human embryo cells, and concentrations of 1.5 ug/ml produced chromosomal aberrations in the somatic and germ cells of kangaroo rats. Animal evidence concerning the carcinogenicity of captan is contradictory, although high doses caused significant incidences of polyploid carcinoma of the duodenum and adenomatous polyps in mice (NCI 1977a, as cited in ACGIH 1986/Ex. 1-3, p. 98).

Some captan-exposed individuals experience skin irritation (Spencer 1968, as cited in ACGIH 1986/Ex. 1-3, p. 98). A case of recurrent urticaria caused by captan exposure has been reported and confirmed (Croy 1973/Ex. 1-894), and captan caused high reactivity when administered in a battery of patch tests (Rudner 1977/Ex. 1-967).

NIOSH (Ex. 8-47, Table N6A) concurs with the limit being established, but notes that captan could be classified as a potential occupational carcinogen. No other comments were received on this substance.

In the final rule, OSHA is establishing a PEL of 5 mg/m(3) TWA to protect workers exposed to captan from the significant risk of exposure-related skin irritation, reproductive effects, mutagenicity, and, perhaps, carcinogenicity, all of which constitute material health impairments. The Agency concludes that this limit will substantially reduce these significant risks.

CHLOROPRENE CAS: 126-99-8; Chemical Formula: CH(2):CClCH:CH(2) H.S. No. 1088

The former OSHA limit for beta-chloroprene was an 8-hour TWA of 25 ppm, with a skin notation. The ACGIH has a 10-ppm TLV-TWA, with a skin notation, and NIOSH (1977c/Ex. 1-277) recommended a limit of 1 ppm, measured over a 15-minute period. The proposed PEL was an 8-hour TWA of 10 ppm, and the final rule establishes this limit and retains the skin notation. NIOSH (Ex. 8-47, Table N1) concurs that this limit is appropriate. Chloroprene is a colorless, highly flammable liquid.

The ACGIH recommended a reduction in the TLV for chloroprene from 25 ppm to 10 ppm in 1981, based on a review of the world literature by Trochimowicz, who prepared the 1980 ACGIH documentation, and by Reinhardt (1980, as cited in ACGIH 1986/Ex. 1-3, p. 135). Reinhardt concluded that there was no evidence indicating that the former 25-ppm PEL was not protective, but OSHA believes the systemic effects (i.e., growth retardation) seen in rats and hamsters exposed to 39 ppm chloroprene for four weeks or to 50 ppm for a lifetime suggest that the 25-ppm PEL is not sufficiently protective.

In recommending a 1-ppm 15-minute exposure limit for chloroprene, NIOSH (1977c/Ex. 1-277) cited three reports on facilities in the Soviet Union. Katsova (1973, as cited in ACGIH 1986/Ex. 1-3, p. 135) reported finding a significant excess of chromosomal abnormalities in the blood of workers exposed to approximately 5 ppm chloroprene. Volkova, Fomenko, Bagdinov et al. (1976/Ex. 1-1025) reported similar findings in a plant where chloroprene levels ranged from 0.8 to 1.95 ppm. In the third study, Sanotskii (1976/Ex. 1-662) reported abnormal sperm morphology among workers exposed at levels of from 0.28 to 1.94 ppm; a threefold increase in the rate of spontaneous abortion among wives of these workers was also found. In addition, NIOSH (1977c/Ex. 1-277) cited a study by Davtian, Fomenko, and Andreyeva (1973/Ex. 1-1032) that reported a significant excess of embryonic mortality in female rats that were mated to male rats exposed to 1 ppm chloroprene. These investigators also found chromosomal aberrations in the bone marrow cells of exposed male rats. NIOSH (1977c/Ex. 1-277) also cited a number of reports showing chloroprene to be mutagenic in a variety of test systems. NIOSH concluded that it was prudent to reduce exposure to 1 ppm over a 15-minute period, to reduce the risk of genetic abnormalities being transmitted to subsequent generations. This exposure represents the lowest concentration that can be measured reliably over a 15-minute period.

The Workers Institute for Safety and Health (WISH) and the AFL-CIO commented on OSHA's proposed limit for chloroprene (Ex. 116; Tr. VII, pp. 130-131; Ex. 194). WISH raised questions about the adequacy of the ACGIH documentation for this substance, which is critical of the Soviet literature that served as the basis for the issuance of the first NIOSH Current Intelligence Bulletin on Chloroprene (l975c). OSHA notes that sizeable discrepancies exist between the findings from the Russian studies and results from other studies that were undertaken to confirm the Soviet claims. Torkelson and Rowe (1981c, in Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2B, Clayton and Clayton 1981) offer two possible explanations for these discrepancies:

beta-Chloroprene is a very unstable compound, which, unless handled with extreme care,...[epoxidizes] and polymerizes to toxic compounds. This might explain the alleged effects in animals. Alleged effects in humans may be due to this same cause or to the use of different chemical processes which produce different types of impurities. Many other causes can be postulated, but in our opinion more credence must be given to animal studies in which the sample is known to have been handled with extreme care and to the results of experience in U.S. industry where the method of handling has been reported (Torkelson and Rowe 1981c, p. 3578).

These authors report that when the purity of the sample was carefully controlled, repeated exposures to 25 ppm or less of the vapor have caused no reproductive, teratological, or embryotoxic effects in rats: "Despite frank clinical toxicity in exposed pregnant rats, fetuses showed no teratogenic effects at beta-chloroprene levels as high as 175 ppm" (Trokelson and Rowe 1981c, pp. 3579-80) WISH also expressed concern about the "unscientific" use by the ACGIH of uncertainty factors with regard to this substance. WISH notes that the ATSDR protocol for uncertainty factors would require a TLV of 0.05 ppm based on lowest effect level data on growth retardation (Ex. ll6). (See OSHA's discussion of the use of safety factors in establishing occupational exposure limits in Section VI.A. of this preamble.) The 1-ppm (15-minute STEL) value recommended by NIOSH is based on studies reported in the Soviet literature; in addition, this limit is set at the analytical limit of detection. OSHA's 10-ppm PEL is based on a 1981 critical review of the world literature (Trochimowicz 1980, as cited in ACGIH 1986/Ex. 1-3, p. 135) and on the observation that only mild systemic effects are observed at 38 ppm. In the final rule, OSHA is establishing an 8-hour TWA PEL of 10 ppm, with a skin notation, to substantially reduce the significant risk of reproductive and systemic effects, which constitute material health impairments that are potentially associated with exposure to chloroprene. The Agency concludes that this limit will substantially reduce this significant risk.

CYCLOHEXYLAMINE CAS: 108-91-8; Chemical Formula: C(6)H(13)N H.S. No. 1109

OSHA had no former limit for cyclohexylamine. The ACGIH has a TLV-TWA of 10 ppm. OSHA proposed an 8-hour TWA PEL of 10 ppm; NIOSH (Ex. 8-47, Table N1) concurred with the proposed limit, and the final rule promulgates this limit. Cyclohexylamine is a liquid with a strong, fishy, amine odor.

Data concerning the acute toxicity of cyclohexylamine were reported by Eastman Kodak in 1958 (ACGIH 1986/Ex. 1-3, p. 161). In rats, the oral LD(50) of a 5-percent solution in water was between 400 and 800 mg/kg; mice fed a diet of the 1-percent aqueous solution or the undiluted amine had LD(50)s of between 200 and 400 mg/kg. Injection of the 5-percent aqueous solution in rats produced LD(50)s of between 5 and 25 mg/kg, while mice injected intraperitoneally with the 1-percent solution had LD(50)s of between 5 and 10 mg/kg. In guinea pigs, the dermal LD(50) of undiluted cyclohexylamine is reported to be between 1 and 5 ml/kg. Edema, necrosis, and eschars were reported as a consequence of these dermal exposures. In rabbits, one drop of a 50-percent solution caused complete destruction of the eye. Six-hour inhalation exposures at a vapor concentration of 12,000 ppm caused deaths in rats, but exposure to 1000 ppm caused neither toxic effects nor deaths.

Legator, Palmer, Green, and Petersen (1969/Ex. 1-496) considered cyclohexylamine to be a potential carcinogen, mutagen, or teratogen on the basis of dose-dependent chromosomal abnormalities observed in rats injected intraperitoneally with cyclohexylamine. Khera, Stolz, Gunner et al. (1971/Ex. 1-343) noted adverse effects on rat fertility, and Becker and Gibson (1970/Ex. 1-298) reported embryotoxic effects in mice intraperitoneally injected with cyclohexylamine. In contrast, Kennedy, Sanders, Weinberg et al. (1969, as cited in ACGIH 1986/Ex. 1-3, p. 161) reported no effects of exposure to cyclohexylamine on rabbit and rat fertility, reproduction, embryogenesis, or perinatal and postnatal development.

In general, there is agreement concerning the moderate to severe toxicity of cyclohexylamine and its potential for intense skin irritation and moderate skin sensitization (Sax 1968b, as cited in ACGIH 1986/Ex. 1-3, p. 161). The chemical is well known to be pharmacologically active, having sympathomimetic activity (Barger and Dale 1910/Ex. 1-1104). However, Litchfield and Swan (1971/Ex. 1-346) report that human dietary levels of 5 g/day for seven to eight days produced no pharmacologically active levels in the tissues; furthermore, no changes were detected in blood pressure, heart rate, or electrocardiograms of exposed subjects. Chronic experimental toxicity data are lacking, but Watrous and Schulz (1950/Ex. 1-940) have reported that exposure to 4 to 10 ppm of cyclohexylamine caused no symptoms of any kind in acutely exposed workmen. No comments other than those of NIOSH (Ex. 8-47) were received on this substance.

In the final rule, OSHA is establishing an 8-hour TWA PEL of 10 ppm for cyclohexylamine. The Agency concludes that limiting workplace exposures to this previously unregulated substance to the 10-ppm level will protect workers from the significant risk of severe skin and eye irritation and sensitization, all material health impairments that are associated with exposure to cyclohexylamine. OSHA has determined that this limit will substantially reduce these significant occupational risks.

CYHEXATIN CAS: 13121-70-5; Chemical Formula: (C(6)H(11))(3)SnOH H.S. No. 1112

Previously, OSHA had no limit for cyhexatin. The ACGIH has a TLV-TWA of 5 mg/m(3). The proposed PEL was an 8-hour TWA of 5 mg/m(3). NIOSH (Ex. 8-47) concurred with the proposed limit and this is the limit established by the final rule. At room temperature, cyhexatin exists in the form of white crystals.

Cyhexatin has oral LD(50)s of 500, 700, and 654 mg/kg for rabbits, guinea pigs, and chickens, respectively. The intraperitoneal LD(50) for the rat is 13 mg/kg (NIOSH 1977i/ Ex. 1-1182), and the oral LD(50) for rats has been reported to be 190 mg/kg (ACGIH 1974, as cited in ACGIH 1986/Ex. 1-3, p. 165). Skin exposure to a 1- to 2-percent solution of cyhexatin in goats and cattle caused mild effects; sheep showed mild effects after application of a 0.5-percent solution. One of five sheep died from multiple skin applications of a 1-percent suspension (Johnson, Younger, Witzel, and Radeleff 1975/Ex. 1-336).

The toxicity of cyhexatin is considered to be moderate, although it is greater than the toxicity of most other organic tin compounds. Long-term feeding in rats produced no behavioral changes, mortality, tissue changes, or hematologic or biochemical changes in response to two years of dosing at 12 mg/kg per day; however, dosed animals were smaller than controls. After daily doses by gavage of 24 mg/kg per day for two weeks, rats showed microscopic changes in the liver, kidneys, and adrenal glands at autopsy. Six mg/kg is considered to be the no-effect level in rats, and in dogs, the no-effect feeding level is reported to be 3 mg/kg. Rats fed 4 to 6 mg/kg, and rabbits fed 3 mg/kg, showed no ill effects on indices for fertility, gestation, viability, or lactation (Dow Chemical Company 1973d, as cited in ACGIH 1986/Ex. 1-3, p. 165). No inhalation data on animals are available, and there are no human data. Other than the comment by NIOSH (Ex. 8-47), no comments were received on this substance.

In the final rule, OSHA is establishing an 8-hour TWA limit of 5 mg/m(3) for cyhexatin. OSHA concludes that a PEL of 5 mg/m(3) will protect workers against the significant risk of skin and respiratory irritation, as well as other possible adverse effects associated with exposure to this tin compound in the absence of a current limit. The Agency considers eye and respiratory irritation to be material health impairments within the meaning of the Act.

DICHLORODIPHENYLTRICHLOROETHANE (DDT) CAS: 50-29-3; Chemical Formula: C(14)H(9)Cl(5) H.S. No. 1113

OSHA's existing limit for dichlorodiphenyltrichloroethane (DDT) is 1 mg/m(3) TWA as an 8-hour TWA, with a skin notation. The ACGIH has the same 8-hour TWA limit for DDT, without a skin notation. NIOSH has a REL of 0.5 mg/m(3) for DDT. The Agency proposed to retain both the skin notation for DDT and the existing 8-hour TWA limit. The final rule retains the skin notation and the Agency's 8-hour TWA PEL. DDT is a noncombustible, colorless to white powder with a slightly aromatic odor.

The U.S. Public Health Service (Neal, von Oettingen, Smith et al. 1944, as cited in ACGIH 1986, p. 168) reports that six daily exposures of one hour each to 423 mg/m(3) DDT was without effect in human volunteers. Barnes (1953, as cited in ACGIH 1986, p. 168/Ex. 1-3) reported that a review of the world literature revealed no illness among workers from many countries who applied DDT as an insecticide. At chronic exposure levels of 35 mg/person/day, no adverse health effects are observed in humans, but DDT does accumulate in the fatty tissues of the body and it is possible that delayed effects might occur after many years (ACGIH 1986, p. 168/Ex. 1-3). OSHA received no comments on DDT except those from NIOSH (Ex. 8-47, Table N6B), which urged regulation of DDT as a potential occupational carcinogen. The dermal LD(50) in rabbits is 400 mg/kg (Dangerous Properties of Industrial Materials, 7th ed., Sax and Lewis 1989), indicating a significant degree of percutaneous absorption that justifies the skin notation.

Based on a review of the evidence of the health effects of exposure to DDT, OSHA concludes that the existing PEL of 1.0 mg/m(3) is adequate to protect workers from the significant risk of bioaccumulation of DDT in adipose tissue, which may have the potential to produce delayed ill effects in later years. The Agency finds that the existing limit, with its skin notation, provides appropriate protection against DDT's systemic effects.

2-N-DIBUTYLAMINOETHANOL CAS: 102-81-8; Chemical Formula: (C(4)H(9))(2)NCH(2)CH(2)OH H.S. No. 1120

OSHA formerly had no limit for 2-N-dibutylaminoethanol (DBAE). The ACGIH has a TLV-TWA of 2 ppm, with a skin notation, for this colorless, combustible liquid, which has a faint, amine-like odor. The proposed PEL was 2 ppm as an 8-hour TWA. NIOSH (Ex. 8-47) concurred with this limit, and this is the limit established by the final rule. The proposed skin notation is not retained in the final rule.

In rats, 2-N-dibutylaminoethanol has a single-dose oral LD(50) of 1.7 g/kg and a corresponding intraperitoneal LD(50) of 0.14 g/kg; these values are approximately analogous to the oral and intraperitoneal LD(50)s for diethanolamine (Hartung and Cornish 1968/Ex. 1-328). The LD(50) for skin absorption in rabbits is 1.68 g/kg (Smyth, Carpenter, Weil, and Pozzani 1954/Ex. 1-440). In male rats, the lowest five-week drinking water dose tolerated without weight loss was 0.13 g/kg/day. Rats that ingested a dose of 0.43 g/kg/day showed elevated kidney-to-body-weight ratios but no histologic changes at autopsy (Cornish, Dambrauskas, and Beatty 1969/Ex. 1-411). In inhalation studies of rats, 6-hour exposures at 70 ppm for five days killed one rat; the surviving rats showed a 57-percent average body weight loss, as well as a doubling of kidney-to-body-weight ratios, a tenfold increase in serum bilirubin, a slight increase in clotting time,and an elevated hematocrit. Inhalation of 33 ppm for one week caused a 3-percent body weight loss and a slight increase in clotting time, but significant changes in the other variables observed. Twenty-seven weeks of exposure to 22 ppm resulted in no differences between exposed rats and controls in the variables measured (Cornish, Dambrauskas, and Beatty 1969/Ex. 1-411). 2-N-dibutylaminoethanol is a more potent inhibitor of acetylcholinesterase in vitro than is diethylamine (DEA) (Hartung and Cornish 1968/Ex. 1-328). NIOSH was the only commenter to the rulemaking record for DBAE.

In the final rule, OSHA is establishing an 8-hour TWA PEL of 2 ppm for 2-N-dibutylaminoethanol. The Agency concludes that this limit will protect workers from the significant risk of metabolic effects associated with inhalation exposure at the levels permitted in the absence of any OSHA limit. OSHA has determined that this substance does not present a significant risk of systemic toxicity via percutaneous absorption (2-N-dibutylaminoethanol's dermal LD(50) in rabbits is 1.68 g/kg) and therefore, that no skin notation is required. Accordingly, the skin notation proposed for DBAE is not retained in the final rule.

DIGLYCIDYL ETHER CAS: 2238-07-5; Chemical Formula: C(6)H(10)O(3) H.S. No. 1139

The former OSHA limit for diglycidyl ether (DGE) was 0.5 ppm as a ceiling concentration, and the ACGIH-recommended TLV is 0.1 ppm as an 8-hour TWA. NIOSH recommends a limit of 0.2 ppm for DGE as a 15-minute ceiling. OSHA proposed an 8-hour TWA of 0.1 ppm, and this limit is established in the final rule.

Both the previous ACGIH 0.5-ppm TLV and that organization's current TLV are based on the results of an animal study reported by Hine and Rowe (1963b, as cited in ACGIH 1986/Ex. 1-3, p. 202) in which rats were administered repeated 4-hour exposures of 20, 3, or 0.3 ppm DGE. Rats exposed to 20 ppm of DGE showed respiratory irritation, loss of body weight, decreased leukocyte count, involution of the spleen and thymus, and hemorrhagic bone marrow. Residual hematopoietic effects were observed among rats exposed to 3 ppm, and no observed effects were noted among rats exposed to 0.3 ppm, even after as many as 60 exposures. The ACGIH's previous TLV of 0.5 ppm as a ceiling value was based on the no-observed-effect level of 0.3 ppm reported in the Hine and Rowe (1963b, as cited in ACGIH 1986/Ex. 1-3, p. 202) study and on industrial experience. In 1979, the ACGIH reconsidered its limit for DGE, noting that, "in view of the seriousness of some of the effects produced [in the rat study], a TLV below the no-ill-effect level [of 0.3 ppm] would normally be adopted" (ACGIH 1986/Ex. 1-3). The ACGIH consequently revised the TLV to 0.1 ppm as an 8-hour TWA.

NIOSH concurs with this limit but notes that DGE may be a potential occupational carcinogen (Ex. 8-47), and the Workers Institute for Safety and Health (Ex. 116) objected to the establishment of a ceiling limit. No other comments were received on this substance.

In the final rule, OSHA concludes that the revised 8-hour TWA limit of 0.1 ppm will protect workers against the significant risk of hematopoietic and irritant effects, which constitute material health impairments and to which they were potentially exposed at OSHA's former PEL. The risks of DGE exposure range from respiratory irritation to bone marrow effects. The final rule's limit for DGE will reduce this risk substantially.

ETHANOLAMINE CAS: 141-43-5; Chemical Formula: NH(2)CH(2)CH(2)OH H.S. No. 1159

OSHA formerly had an 8-hour TWA limit of 3 ppm for ethanolamine. The ACGIH has the same TWA limit, along with a 15-minute STEL of 6 ppm. OSHA proposed to retain the 8-hour TWA PEL of 3 ppm and to supplement this limit with a 6-ppm STEL; NIOSH (Ex. 8-47, Table N1) concurred with the proposed limits, and the final rule establishes them. Ethanolamine is a colorless liquid with a mild smell like that of ammonia.

The health hazards associated with exposures to ethanolamine include irritation and necrosis of the skin and central nervous system depression. The oral LD(50) in rats is reported as 3.32 g/kg, and the intraperitoneal LD(50) in rats is 981 mg/kg (Hartung and Cornish 1968/Ex. 1-328). The dermal toxicity of ethanolamine is considerably higher, with an LD(50) of 1 mg/kg reported in the rabbit. Dermal application of the undiluted liquid also caused redness, swelling, and burns comparable to mild first-degree burns (Union Carbide Corporation, as cited in ACGIH 1986/Ex. 1-3, p. 235). The eye injury potential of ethanolamine is just slightly less than that of undiluted ammonia (Carpenter and Smyth 1946/Ex. 1-859). Rats fed 0.5 percent (320 mg/kg/day) ethanolamine in their food for 90 days (Smyth, Carpenter, and Weil 1951/Ex. 1-439) showed no adverse effects, but at 1.28 g/kg/day, fatalities occurred. Treon, Cleveland, Stemmer, and associates (1957/Ex. 1-1172) reported lung, liver, and kidney damage in various species exposed to high concentrations of the vapor and mist. In tests of various species, Weeks and co-workers (1960/Ex. 1-941) reported marked dermal effects from continuous exposures (24 hours/day, seven days/week, for from 24 to 90 days) at various concentrations of the vapor; at 12 to 26 ppm, dermal effects were less severe, but at 5 ppm, skin irritation was still evident. After 90 days of exposure to 5 ppm, dogs also experienced a slight and temporary weight loss as well as decreased activity and alertness (Weeks, Downing, Musselman et al. 1960/Ex. 1-941). Luck and Wilcox (1953/Ex. 1-917) demonstrated that a portion of low doses of ethanolamine is not excreted and is presumably retained in the body of cats, rats, and rabbits.

In studies of anesthetized dogs, Priddle (1954, as cited in ACGIH 1986/Ex. 1-3, p. 235) reported that sublethal doses of ethanolamine cause central nervous system stimulation, while lethal doses cause CNS depression. Ethanolamine's irritant and necrotic effects on the skin are not related to its alkalinity (Hinglais 1947/Ex. 1-909). OSHA received no comments, other than the one by NIOSH (Ex. 8-47), on this substance.

In the final rule, OSHA is establishing a PEL of 3 ppm as an 8-hour TWA and a 15-minute STEL of 6 ppm for ethanolamine. The Agency concludes that both of these limits are required to protect workers against the significant risk of irritation and neuropathic effects, which constitute material health impairments that are potentially associated with exposure to ethanolamine at levels permitted above the 8-hour TWA limit. The Agency has determined that these limits will substantially reduce this significant risk.

ETHYLENE CHLOROHYDRIN CAS: 107-07-3; Chemical Formula: ClCH(2)CH(2)OH H.S. No. 1167

OSHA formerly had an 8-hour TWA limit of 5 ppm, with a skin notation, for ethylene chlorohydrin. The ACGIH has a ceiling limit of 1 ppm, also with a skin notation. The proposed PEL was a ceiling of 1 ppm, with a skin notation. NIOSH (Ex. 8-47) concurred with the proposed limit, and the final rule establishes this limit and retains the skin notation. Ethylene chlorohydrin is a colorless liquid with a faint, ethereal odor.

A broad range of serious health hazards are associated with exposure to this substance; these include central nervous system effects, cardiovascular effects, liver damage, kidney damage, gastrointestinal effects, skin irritation, eye irritation, and mutagenic effects. OSHA considers that all of these effects constitute material health impairments. The oral LD(50) for rats is 72 mg/kg, and the intraperitoneal LD(50) in the same species is 56 mg/kg (Goldblatt and Chiesman 1944/Ex. 1-980). In guinea pigs, the intraperitoneal LD(50) is 98 mg/kg, and the percutaneous LD(50) is 205 mg/kg (Wahlberg and Boman 1978/Ex. 1-938).

The skin absorption rate for ethylene chlorohydrin is high; Semenova and associates (1978/Ex. 1-932) determined that the LD(50) must be reduced to one-fifth of its original value if ethylene chlorohydrin is administered daily for 20 days (Semenova, Kazanina, Fedyanina et al. 1978/Ex. 1-932).

The inhalation toxicity of ethylene chlorohydrin is also high. Ambrose (1950/Ex. 1-888) reported that a single one-hour exposure at 7.5 ppm and repeated one-hour exposures at 2 ppm can be fatal to rats. Exposures of 15 minutes daily at concentrations of from 900 to 1000 ppm were fatal to rats within a few days (Goldblatt and Chiesman 1944/Ex. 1-980).

In subacute and chronic studies, rats have died from a daily dietary dose of 67.5 mg/kg (Oser, Morgareidge, Cox, and Carson 1975/Ex. 1-923). Semenova and associates (1980, as cited in ACGIH 1986/Ex. 1-3, p. 248) reported a four-month no-effect inhalation level of 0.0033 ppm; at 0.017 ppm, slight CNS changes and alterations in the urinary secretion of nitrogen were observed after four months. These investigators also observed increased chromosomal aberrations in bone marrow in rats exposed at the 0.22-ppm level for four months (Semenova, Kazanina, Fedyanina et al. 1980, as cited in ACGIH 1986/Ex. 1-3, p. 248).

Voogt and Vet (1969/Ex. 1-1205) tested ethylene chlorohydrin in Klebsiella pneumoniae and found it strongly mutagenic. This finding was confirmed by the Ames test in Salmonella typhimurium ; ethylene chlorohydrin reacts with DNA, since it inhibits the growth of DNA-deficient bacteria (Rosenkranz and Wlodkowski 1974/Ex. 1-1201). A dose-related increase of liver protein and depletion in glutathion was observed in rats after a single dose of ethylene chlorohydrin of from 10 to 50 mg/kg (Friedman, Scalera, Balazs et al. 1977/Ex. 1-1198).

One fatal and several nonfatal cases of poisoning in industrial workers have been reported from exposure (for unspecified periods of time) to ethylene chlorohydrin at levels of between 300 and 500 ppm. An autopsy of the worker who died revealed severe damage to the liver and brain, as well as effects in other organs. The survivors experienced nausea, vomiting, and irritation of the eyes, nose, and lungs (Bush, Abrams, and Brown 1949/Ex. 1-1196). Dierker and Brown (1944/Ex. 1-1197) reported that a two-hour inhalation exposure to 300 ppm was fatal in one accidental exposure. OSHA received no comments, other than that of NIOSH (Ex. 8-47), on this substance.

In the final rule, OSHA is establishing a ceiling limit of 1 ppm for ethylene chlorohydrin and is retaining the skin notation. The Agency concludes that this limit will substantially reduce the significant risk of central nervous system and other systemic effects associated with workplace exposures at the levels permitted by the TWA limit alone. The skin notation is retained because ethylene chlorohydrin is readily absorbed through the skin.

GLYCIDOL (2,3-EPOXY-1-PROPANOL) CAS: 556-52-5; Chemical Formula: C(3)H(6)O(2) H.S. No. 1189

Previously, OSHA had an 8-hour TWA limit of 50 ppm TWA for glycidol. The ACGIH has a limit of 25 ppm TWA for this colorless liquid. The proposed PEL was an 8-hour TWA of 25 ppm. NIOSH (Ex. 8-47) concurred with this limit, and the final rule promulgates this PEL.

Glycidol causes eye, respiratory, and pulmonary irritation. Hine and associates (1956/Ex. 1-331) conducted a study of animal toxicity caused by glycidol exposure and reported that glycidol is irritating to the lungs, with mice and rats exhibiting pneumonitis and emphysema resulting from vapor inhalation. The LC(50) reported for mice is 450 ppm for a four-hour exposure; the 8-hour LC(50) for rats is 580 ppm (Hine, Kodama, Wellington et al. 1956/Ex. 1-331). A single dermal application was only mildly irritating (Draize score 4.5); however, repeated daily skin applications were severely irritating after four days. One drop of pure glycidol in the rabbit eye caused severe but reversible corneal injury (Hine, Kodama, Wellington et al. 1956/Ex. 1-331). In rats, chronic exposures to 400 ppm (seven hours/day for 50 days) did not cause systemic toxicity, but eye irritation and respiratory distress were observed after the first few exposures (Hine, Kodama, Wellington et al. 1956/Ex. 1-331). A study to determine glycidol's tumorigenic potential on the skin of mice showed negative results (Van Duuren, Langseth, Goldschmidt, and Orris 1967/Ex. 1-1203). OSHA received no comments, other than that of NIOSH (Ex. 8-47), on this substance.

In the final rule, OSHA is establishing an 8-hour TWA limit of 25 ppm TWA for glycidol. The Agency concludes that this limit will protect workers against the significant risk of eye, respiratory, and pulmonary irritation potentially associated with exposures to this substance. The Agency has determined that this limit will substantially reduce these significant risks.

HEXAFLUOROACETONE CAS: 684-16-2; Chemical Formula: C(3)F(6)O H.S. No. 1198

Previously, OSHA had no limit for hexafluoroacetone. The ACGIH has a TLV-TWA of 0.1 ppm, with a skin notation, for this colorless, nonflammable, highly reactive gas. The proposed PEL was an 8-hour TWA of 0.1 ppm, with a skin notation. NIOSH (Ex. 8-47) concurred with these limits, which are established by the final rule.

Inhalation studies of hexafluoroacetone in animals have shown varied systemic toxicities, including injury to the liver, kidney, testes, thymus, and bone marrow. In rats and dogs exposed six hours/day, five days/week for 13 weeks at concentrations of about 0.1, 1.0, or 12 ppm, no effects (other than increased lung weights in dogs) were observed in either species at 0.1 ppm. However, the 12-ppm exposures produced severe effects in both species, including marked but reversible testicular damage and slight hypoplasia of the spleen, thymus, and lymph nodes (E.I. du Pont de Nemours & Company, Inc. 1971, as cited in ACGIH 1986/Ex. 1-3,p. 303). Reversible kidney damage in rats and increased lung weights in dogs occurred during the 1.0-ppm exposures. An earlier four-hour acute exposure of rats demonstrated that 300 ppm was a lethal concentration (E.I. du Pont de Nemours and Co., Inc. 1971, as cited in ACGIH 1986/Ex. 1-3, p. 303).

In rats, two-week dermal exposures of 65, 130, or 250 mg/kg resulted in numerous adverse effects, including testicular damage and corresponding changes in lipid metabolism (Kennedy, Henry, Chen, and Dashiell 1982/Ex. 1-1038). A dermal dose of 13 mg/kg produced no adverse effects in rats (Lee and Gillies 1984/Ex. 1-561). An injected dose of radiolabeled hexafluoroacetone was, for the most part, rapidly excreted in the urine in unmetabolized form; this material also did not accumulate in rat testes (Gillies and Rickard 1984/Ex. 1-322). Brittelli and co-workers (1979/Ex. 1-300) reported that hexafluoroacetone was fetotoxic in rats. Dermal application of 90 mg/kg/day to pregnant rats resulted in maternal toxicity. Fetal toxicity occurred at maternal doses of 25 mg/kg, and fetal size was reduced at maternal doses of 5 and 25 mg/kg; however, 1 mg/kg produced no fetal effect. Although soft-tissue damage and external abnormalities were observed, teratogenicity could not be demonstrated definitively (Brittelli, Culik, Dashiell, and Fayerweather 1979/Ex. 1-300). Other than the comment by NIOSH (Ex. 8-47), OSHA received no comments on this substance.

The final rule establishes an 8-hour TWA PEL of 0.1 ppm TWA and a skin notation for hexafluoroacetone. The Agency concludes that these limits, taken together, will protect workers from the significant risk of systemic injuries at multiple organ sites, reproductive effects, kidney damage, and fetotoxic effects, all of which constitute material health impairments that are associated with exposure to hexafluoro-acetone at levels above the new PEL.

HYDROGEN CYANIDE CAS: 74-90-8; Chemical Formula: HCN H.S. No. 1207

The former OSHA limit for hydrogen cyanide was a 10-ppm 8-hour TWA, with a skin notation. The ACGIH has a 10-ppm ceiling limit, also with a skin notation. NIOSH (1976e/ Ex. 1-240) has recommended that workplace exposures to hydrogen cyanide not exceed 4.7 ppm (5 mg/m(3)) as a 10-minute ceiling. OSHA proposed a 10-minute ceiling of 4.7 ppm for hydrogen cyanide, and the final rule establishes this limit as a 15-minute STEL. The skin notation is retained. NIOSH (Ex. 8-47, Table N1) concurs with the selection of this PEL. Hydrogen cyanide is a colorless gas at room temperature.

The ACGIH (1986/Ex. 1-3) has summarized the extensive body of human evidence on the adverse effects resulting from exposure to hydrogen cyanide. The Documentation notes that exposure to levels of 45 to 54 ppm hydrogen cyanide can be tolerated for one hour with no immediate or delayed effects, but that 18 to 36 ppm produces "slight" symptoms after several hours of exposure. The ACGIH also cites Grabois (1954/ Ex. 1-1150), who reported that workers in apricot kernel processing plants experienced no ill effects when exposed to hydrogen cyanide at a concentration of approximately 10 ppm.

The NIOSH recommendation of 4.7 ppm as a 10-minute ceiling limit is based largely on an epidemiologic study by El Ghawabi et al. (1975/Ex. 1-632) that showed an increase in symptoms of headache, weakness, throat irritation, vomiting, dyspnea, lacrimation, colic, and nervousness among workers exposed to cyanide for an average of 7.5 years. The 36 male workers that were studied were employed in three electroplating factories. Breathing zone samples (15 minutes in duration) were collected and ranged from 4.2 to 12.4 ppm. Cyanide levels at two of the three plants did not exceed 9.6 ppm. El Ghawabi et al. (1975/Ex. 1-632) also reported that two workers in one plant suffered from psychotic episodes; these conditions were reported to be similar to cases that occurred during the therapeutic use of thiocyanate. Mean values of urinary thiocyanate in the 36 workers correlated well with air concentrations of cyanide (El Ghawabi, Gaafar, El-Saharti et al. 1975/Ex. 1-632).

Symptoms resulting from chronic exposure to cyanide were also reported by Radojicic (1973, as cited in NIOSH 1976e/Ex. 1-240) among workers exposed to HCN levels between 5.4 and 12.3 ppm, and by Saia, DeRosa, and Galzigna (1970, as cited in NIOSH 1976e/Ex. 1-240). NIOSH (1976e/Ex. 1-240) interpreted the significance of these studies as follows:

Colle (1972)...advanced the belief that these symptoms of headache, dyspnea, epigastric burning, vertigo, tinnitus, nausea, vomiting, tremor, and precordial pain represent a true clinical entity and that they are sufficiently documented and characteristic of chronic cyanide exposure to be grouped into a true syndrome....

Chaumont (1960)...also stated that there is no clinical evidence to deny that cyanides can cause this type of occupational intoxication. He apparently found the debate on whether this intoxication is truly chronic or whether it involves repeated subacute symptoms to be semantic in nature and opted for the admission that chronic intoxication caused by HCN and the cyanide salts is a true occupational disease....

Thus, one might describe chronic cyanide poisoning as a slow deterioration of resistance, and, therefore, an intensified sensitivity, due to inadequate time between exposures for replacement of damaged tissues, enzyme systems and metabolic stores, the elimination of detoxication products, and the regeneration of homeostatic mechanisms (NIOSH 1976e/Ex. 1-240, pp. 90-91).

OSHA received a few comments, in addition to that made by NIOSH (Ex. 8-47), on its proposal to revise the PEL for HCN to 4.7 ppm (5 mg/m(3)) as a short-term limit. Dr. Lawrence Hecker, representing Abbott Laboratories (Ex. 3-678), recommended that OSHA retain its former skin notation for HCN; OSHA's intention to do so was inadvertently omitted from the discussion of hydrogen cyanide in the NPRM. There is ample evidence that cyanide penetrates the skin in sufficient quantities to cause systemic effects (NIOSH 1976e/Ex. 1-240).

Accordingly, OSHA is retaining its skin notation for HCN in the final rule. BP America (Ex. 8-57; Tr. 9-127) urged OSHA to establish the ACGIH TLV rather than the NIOSH REL for HCN, and the New Jersey Department of Health urged use of EPA's IRIS data to set a PEL for this substance (Ex. 144). In response to these commenters, OSHA notes that the ACGIH is not, in the Agency's opinion, sufficiently protective. Use of the IRIS data is discussed in Section VI.A.

OSHA concludes that a variety of symptoms are associated with exposure to hydrogen cyanide at levels less than 10 ppm. This shows that neither the former PEL nor the ACGIH TLV is sufficiently protective. In the final rule, OSHA is therefore establishing a 4.7-ppm 15-minute STEL as the PEL. The Agency finds that the final rule's short-term limit will protect workers from the significant risk of headache, weakness, colic, and nervousness, which together constitute material impairment of health; these effects have been observed in individuals exposed at the 10-ppm level over a full working shift. OSHA concludes that this limit will substantially reduce these significant risks.

HYDROGENATED TERPHENYLS CAS No.: 61788-32-7; Chemical Formula: None H.S. No. 1210

Previously, OSHA did not regulate the hydrogenated terphenyls. The ACGIH has a TLV-TWA of 0.5 ppm (approximately 5 mg/m(3)) TWA for these complex mixtures of ortho-, meta-, and para-terphenyls in various stages of hydrogenation. The proposed PEL was 0.5 ppm as an 8-hour TWA; NIOSH (Ex. 8-47) concurred with the proposed limit, and the final rule establishes that limit.

Acute exposure to the hydrogenated terphenyls poses a risk of potential lung, eye, and skin damage. Chronic exposure presents a risk of systemic toxicity involving injury to the liver, kidneys, and blood-forming organs, as well as possible metabolic disturbances and cancer (ACGIH 1986/Ex. 1-3, p. 311).

Early studies of unhydrogenated terphenyl isomers determined that the LD(50) in rats is low, i.e., 1900 mg/kg for the ortho isomer, 2400 mg/kg for the meta isomer, and 10,000 mg/kg for the para isomer (Cornish, Bahor, and Ryan 1962/Ex. 1-410). Thirty-day oral administration of 500 mg/kg/day in the diet of rats indicated possible liver and kidney damage, which was suggested by increases in the liver and kidney-to-body-weight ratios and decreases in the rate of weight gain (Cornish, Bahor, and Ryan 1962/Ex. 1-410). Other studies have demonstrated nephrotoxicity and liver damage in rats fed 33 mg/kg or more of unirradiated terphenyl isomers (Petkau and Hoogstraaten 1965/Ex. 1-432; Young, Petkau, and Hoogstraaten 1969/Ex. 1-459). Inhalation studies showed that bronchopneumonia is associated with exposure at 88 to 356 ppm to the ortho and meta isomers, but not to the para isomer at 103 ppm (Haley, Detrick, Komesu et al. 1959/Ex. 1-326). The work of Cornish, Bahor, and Ryan (1962/Ex. 1-410) showed that none of the isomers caused skin irritation in rabbits following a 24-hour dermal application. For terphenyls that are approximately 40-percent hydrogenated, the acute oral LD(50) in rats is reported as 17,500 mg/kg; in mice, it is 12,500 mg/kg (Adamson and Weeks 1973/Ex. 1-295). This study also demonstrated that an irradiated hydrogenated terphenyl mixture is three times more acutely toxic by ingestion than is a nonirradiated mixture. This finding was confirmed in 16-week chronic ingestion studies (Adamson, Bowden, and Wyatt 1969/Ex. 1-293); these authors found that 1200 mg/kg of an irradiated mixture was lethal to mice, while the same dose in nonirradiated form produced only an irreversible interstitial nephritis. In the same study, no effects were observed for either mixture at a dose level of 250 mg/kg.

Eight-day inhalation studies in mice showed some pathologic changes in lung tissue after 500 mg/m(3) (50 ppm) exposures to nonirradiated hydrogenated terphenyls; eight-week exposures at 2000 mg/m(3) (200 ppm) resulted in the same lung damage, as well as in some proliferation of the smooth endoplastic reticulum in the liver (Adamson, Bowden, and Wyatt 1969/Ex. 1-293; Adamson and Weeks 1973/Ex. 1-295). Carcinogenesis in mice has been reported from 8-week skin exposures to the irradiated mixture (Henderson and Weeks 1973/Ex. 1-784). The significance of the changes observed by Adamson and Furlong (1974/Ex. 1-294) in the mouse lung after eight weeks of inhalation exposure to the irradiated mixture is difficult to interpret in terms of the potential of the hydrogenated terphenyls to cause pulmonary cancer; particles were found to clear the lungs rapidly but to accumulate and clear more slowly in the intestine, kidney, and liver. No comments other than those of NIOSH (Ex. 8-47) were received on this substance.

In the final rule, OSHA is establishing a 0.5-ppm 8-hour TWA for the complex mixtures of ortho-, meta-, and paraterphenyls (either irradiated or nonirradiated) in various stages of hydrogenation. The Agency concludes that this limit will protect workers from the significant risks of eye, skin, and lung damage and of systemic toxicity to the liver, kidneys, and blood-forming organs, all material health impairments that are potentially associated with exposure to these substances at levels above the new PEL.

2-ISOPROPOXYETHANOL CAS: 109-59-1; Chemical Formula: (CH(3))(2)CHOCH(2)CH(2)OH H.S. No. 1223

OSHA had no former limit for 2-isopropoxyethanol. The ACGIH has a TLV-TWA of 25 ppm for this mobile liquid. The proposed PEL was 25 ppm as an 8-hour TWA, and the final rule establishes this limit.

2-Isopropoxyethanol has been demonstrated to produce systemic toxicity in laboratory animals. In studies of rats, 15 six-hour exposures at 1000 ppm caused hemoglobinuria, anemia, and lung congestion, but no fatalities (Gage 1970/Ex. 1-318). At 300 ppm, Gage reported transient hemoglobin and MCHC decreases and lung congestion after 15 exposures. Exposure at the 100-ppm level produced no effect (Gage 1970/Ex. 1-318). Another study reported a significant increase in the osmotic fragility of erythrocytes in female rats after a four-hour inhalation exposure to 62 ppm, but no effect was observed at 32 ppm (Carpenter, Pozzani, Weil et al. 1956/Ex. 1-303). Studies of four species exposed at concentrations of 200, 50, or 25 ppm for six hours/day for 26 weeks resulted in hematologic changes only in rats; increased osmotic fragility of erythrocytes was marked at 200 ppm, slight at 50 ppm, and minimal at 25 ppm (Moffett, Linnett, and Blair 1976, as cited in ACGIH 1986/Ex. 1-3, p. 235).

NIOSH (Ex. 8-47) did not concur with OSHA's proposed limit of 25 ppm, noting that 25 ppm represented an effect level. Although "slight" increases in osmotic fragility were reported in animals subchronically exposed (Moffett, Linnett, and Blair 1976, as cited in ACGIH 1986/Ex. 1-3, p. 235), OSHA notes that a marked reaction did not occur until exposure was increased eightfold. Therefore, at this time, OSHA judges the 25-ppm PEL to be sufficiently protective.

OSHA is establishing an 8-hour TWA PEL of 25 ppm for 2-isopropoxyethanol in the final rule. The Agency concludes that this limit will substantially reduce the significant risk of hemolytic effects, which are material health impairments that are associated with exposure to this substance at levels above the new PEL.

ISOPROPYL GLYCIDYL ETHER CAS: 4016-14-2; Chemical Formula: C(6)H(12)O(2) H.S. No. 1227

OSHA's former limit for isopropyl glycidyl ether (IGE) was 50 ppm as an 8-hour TWA. The ACGIH has an 8-hour TWA of 50 ppm and a 15-minute STEL of 75 ppm for IGE. NIOSH (Ex. 8-47, Table N7) recommends a limit of 50 ppm as a 15-minute ceiling. OSHA proposed an 8-hour TWA of 50 ppm and a 15-minute STEL of 75 ppm for IGE, and these limits are established in the final rule. IGE is a colorless, volatile liquid.

The 4-hour LC(50) for IGE in mice was 1500 ppm and the 8-hour LC(50) in rats was 1100 ppm (Hine, Kodama, Wellington et al. 1956/Ex. 1-331). The intragastric LD(50)s in mice and rats were 1.30 and 4.2 g/kg, respectively; in rabbits, the dermal LD(50) was 9.65 g/kg (Hine, Kodama, Wellington et al. 1956/Ex. 1-331). Fifty daily seven-hour exposures of rats to 400 ppm caused a reduced rate of weight gain, an increase in hemoglobin, a decrease in peritoneal fat, and, in some animals, emphysematous lungs and mottling of the liver (Hine, Kodama, Wellington et al. 1956/Ex. 1-331). Animals in this study also exhibited signs of ocular irritation and respiratory distress.

In humans, eye, nose, and upper respiratory irritation occurred in the technicians handling the animals in the Hine and co-workers (1956/Ex. 1-331) study; exposure levels were not specified. Dermatitis has also been reported in workers exposed to other glycidyl ethers during manufacture, and one such case involved IGE exposure (ACGIH 1986/Ex. 1-3, p. 340).

In the final rule, OSHA is retaining the 8-hour TWA of 50 ppm and adding a 15-minute STEL of 75 ppm for IGE. The Agency concludes that both the TWA and STEL are necessary to reduce the risk to workers of chronic organ effects, such as those demonstrated to occur in animals (Hine, Kodama, Wellington et al. 1956/Ex. 1-331), and the significant risk of eye, skin, and upper respiratory tract irritation associated with short-term IGE exposures at the levels permitted in the absence of a short-term limit. OSHA considers sensory irritation, dermatitis, and chronic organ effects to be material impairments of health.

4,4-METHYLENE BIS (2-CHLOROANILINE) CAS: 101-14-4; Chemical Formula: CH(2)(C(6)H(4)ClNH(2))(2) H.S. No. 1273

Previously, OSHA had no limit for 4,4-methylene bis (2-chloroaniline), or MBOCA, although in 1974, OSHA did issue a standard for MBOCA as part of the Agency's "14 Carcinogens" rulemaking; however, the reviewing court set the MBOCA standard aside on procedural grounds. The ACGIH has a limit of 0.02 ppm (0.22 mg/m(3)) TWA, with a skin notation, and classifies MBOCA as a suspected human carcinogen (A2). NIOSH recommends a TWA limit of 3 ug/m(3) for MBOCA, which NIOSH considers a potential occupational carcinogen. OSHA proposed an 8-hour TWA of 0.02 ppm TWA for MBOCA, with a skin notation; the final rule establishes these limits. MBOCA is a tan-colored solid.

MBOCA is highly toxic, causing cyanosis, kidney irritation, methemoglobinemia, and cancer. It is similar in effect to the other aromatic amines (Hosein and van Roosmalen 1978/ Ex. 1-1054; Mastromatteo 1965/Ex. 1-146).

Steinhoff and Grundmann (1969/Ex. 1-762) demonstrated that feeding MBOCA at unspecified levels to rats on a protein-deficient diet caused a high incidence of liver cancer. Russfield, Homburger, Boger and associates (1975/Ex. 1-929) reported liver and lung tumors in rats fed MBOCA while on a standard diet. Dogs fed MBOCA at a dose of 100 mg/day, five days/week showed no hepatic cancer, but malignant nodules in the bladder occurred in a dog fed MBOCA for nine years (Stula et al. 1977, as cited in ACGIH 1986/Ex. 1-3, p. 392.4).

In industry, reversible hematuria has been reported among MBOCA-exposed workers, but precise concentration data are lacking (Mastromatteo 1965/Ex. 1-146). An early study of workers exposed for as long as 18 years to MBOCA showed no adverse effects, although the substance and its metabolites were detected in the urine of these subjects (Linch, O'Connor, Barnes et al. 1971/Ex. 1-791). Hosein and van Roosmalen (1978/Ex. 1-1054) reported an industrial accident in which molten MBOCA was splashed in a worker's face; urinary levels of 3.6 mg/L MBOCA, as well as protein, were detected in the urine, and the subject experienced nausea. However, this worker recovered quickly.

A recent NIOSH retrospective study involving 370 workers employed in a MBOCA-manufacturing plant evaluated the carcinogenicity of this substance, which is structurally similar to benzidine. This study found two cases of bladder cancers in very young workers (less than 30 years of age), both of whom were nonsmokers.

The Polyurethane Manufacturers Association (PMA) expressed its support for establishing a 0.02-ppm TWA for MBOCA, stating that the proposal "will significantly assist in assuring that any exposure to the chemical is appropriately controlled while imposing a regulation which can be feasibly complied with by employers" (Ex. 3-683, p. 4). In addition, the PMA indicated that, with currently applied engineering and work practice controls, MBOCA "can be used with no or very limited employee exposure" (Ex. 3-683, p. 5). The PMA also supported establishment of a PEL for MBOCA "to provide OSHA with a chemical-specific enforcement capability to deal with any isolated instances where a user of the chemical also disregards recognized industry practices and fails to reasonably control employee exposure to the chemical" (Ex. 3-683, p. 7). The PMA supported the addition of a skin notation for MBOCA, identifying dermal contact as a "principal potential route for employee exposure" (Ex. 3-683, p. 7).

NIOSH (Ex. 8-47, Table N6B) did not concur with OSHA's proposed PEL and recommended instead that the Agency undertake a separate 6(b) rulemaking for MBOCA. OSHA is aware of the two bladder cancer cases reported by NIOSH, and will continue to monitor the toxicologic evidence on MBOCA in the future to determine whether the evidence warrants a further reduction in the exposure limit. The AFL-CIO (Ex. 194) urged OSHA to promulgate ancillary limits for MBOCA; however, as discussed in Section IV.D., the Agency is not at this time promulgating such provisions because of the size and scope of this rulemaking.

In the final rule, OSHA is establishing an 8-hour TWA limit of 0.02 ppm for MBOCA, with a skin notation. The Agency concludes that this limit will protect workers against the significant risks of cyanosis, methemoglobinemia, kidney irritation, and bladder cancer, all material health impairments potentially associated with exposure to this substance. A skin notation is established to protect against the percutaneous absorption and systemic toxicity demonstrated by this substance in industrial accidents.

PHENYLHYDRAZINE CAS: 100-63-0; Chemical Formula: C(6)H(5)NHNH(2) H.S. No. 1317

OSHA's former limit for phenylhydrazine was 5 ppm TWA as an 8-hour, with a skin notation. The ACGIH has a TLV-TWA of 5 ppm with a STEL of 10 ppm, and a skin notation. NIOSH (1978e/Ex. 1-263) recommends that workplace exposures not exceed 0.14 ppm as measured over a two-hour period. OSHA proposed to retain the PEL of 5 ppm as an 8-hour TWA and to add a STEL of 10 ppm, with a skin notation, and these limits are established in the final rule. Phenylhydrazine may be either yellow crystals or an oily liquid that darkens on exposure to air and light.

No data are available on the effects of phenylhydrazine resulting from inhalation. The ACGIH limits are based on the high acute toxicity of the compound when administered orally or subcutaneously to animals; single doses on the order of 20 mg/kg have resulted in the death of dogs within 22 days (Hesse, Franke, and Hering 1935/Ex. 1-785) and produced a marked decrease in erythrocyte count in rodents (von Oettingen and Deichmann-Greubler 1936/Ex. 1-771). Anemia and hemolysis are the characteristic responses seen in animals fed or injected with phenylhydrazine.

In its criteria document on the hydrazines, NIOSH (1978e/Ex. 1-263) reviewed four studies on the carcinogenicity of phenylhydrazine in mice. One study (Toth and Shimizu 1976/Ex. 1-675) found significant increases in blood vessel tumors. Another study (Clayson, Biancifiori, Milia, and Santilli 1966, as cited in ACGIH 1986/Ex. 1-3, p. 477) reported increased incidences of lung adenomas and adenocarcinomas. Two other studies (Roe, Grant, and Millican 1967/Ex. 1-659; Kelly, O'Gara, Yancy et al. 1969/Ex. 1-703) were negative. NIOSH concluded that phenylhydrazine should be considered a potential human carcinogen and recommended that exposures not exceed 0.14 ppm over a two-hour sampling period, which represents the lowest level that can be detected reliably. The ACGIH (1986/Ex. 1-3) has placed phenylhydrazine on its A2 (suspected human carcinogens) list.

NIOSH (Ex. 8-47, Table N6B; Tr. 3-97 to 3-98), the Workers Institute for Safety and Health (WISH) (Ex. 116), the AFL-CIO (Ex. 194), the Oil Chemical and Atomic Workers (Tr. 9-218), and the American Industrial Hygiene Association (Ex. 8-16) were of the opinion that OSHA's proposed revision of the PEL for phenylhydrazine was not sufficiently protective. NIOSH (Ex. 8-47) indicated that phenylhydrazine may be a suitable candidate for an individual 6(b) rulemaking. Typical of the views of these commenters was the statement of WISH (Ex. 116), which commented that the ACGIH had, at one time, considered reducing its 5-ppm TLV-TWA, and cited a 1974 study in which rabbits given intravenous injections of phenylhydrazine showed blood and liver effects. The evidence of phenylhydrazine's possible carcinogenicity was also cited by WISH as additional support for a more stringent limit. In response, OSHA notes that the Agency is also concerned about the evidence for these adverse effects of phenylhydrazine exposure and will continue to monitor and evaluate the toxicologic literature on phenylhydrazine to determine whether there is a need in the future for a further reduction in the occupational exposure limit.

However, at the present time, OSHA is retaining the 5-ppm 8-hour TWA and adding a 10-ppm STEL for phenylhydrazine; the skin notation is also retained. The Agency concludes that these two limits will work together to keep workplace exposures well controlled and will reduce the significant health risks associated with exposure to this substance. These risks include acute blood-related toxicity and may also include cancer; these effects clearly constitute material impairments of health. OSHA finds that the TWA and STEL limits established in the final rule will substantially reduce these significant risks.

PHENYLPHOSPHINE CAS: 638-21-1; Chemical Formula: C(6)H(5)PH(2) H.S. No. 1318

OSHA had no former requirement for limiting worker exposure to phenylphosphine; NIOSH also has no REL for this substance. The ACGIH has recommended a ceiling limit of 0.05 ppm for this solid. The proposed PEL was a ceiling of 0.05 ppm; NIOSH (Ex. 8-47, Table N1) concurred with the proposed limit, and this limit is established in the final rule.

A 90-day inhalation study conducted by the du Pont Company, in which rats and beagle dogs were exposed to average concentrations of 0.6 ppm or 2.2 ppm phenylphosphine for six hours per day, five days per week, showed that rats exposed to 2.2 ppm had significant hematologic changes and testicular degeneration (E.I. du Pont de Nemours & Co., Inc. 1970, as cited in ACGIH 1986/Ex. 1-3, p. 479). These effects were not noted among rats exposed to 0.6 ppm, but rats exposed at the lower level did show hypersensitivity to sound and touch and mild hyperemia. The dogs tolerated the higher exposure level better than the rats in that some regeneration of testicular damage occurred in dogs during a one-month recovery period. Dogs exposed to 0.6 ppm exhibited intermittent nausea, diarrhea, lacrimation, and hind leg tremor (ACGIH 1986/Ex. 1-3). The ACGIH considered 0.6 ppm to be an NOE level for severe effects in animals and recommended a 0.05-ppm ceiling TLV to provide a tenfold safety margin to protect workers against the changes exhibited by the test animals at the 0.6-ppm level. No comments other than that from NIOSH (Ex. 8-47) were received by OSHA.

OSHA concludes that workers formerly exposed to uncontrolled levels of phenylphosphine were at significant risk of experiencing the nausea, irritation, and CNS effects found to be associated with such exposures in animals. OSHA finds that these effects constitute material health impairments. The Agency concludes that the final rule's ceiling of 0.05 ppm will reduce these significant risks substantially.

PHOSPHINE CAS: 7803-51-2; Chemical Formula: PH(3) H.S. No. 1321

OSHA formerly had a PEL of 0.3 ppm TWA for phosphine. The ACGIH recommends a TLV-TWA of 0.3 ppm and a TLV-STEL of 1.0 ppm. The proposal retained the 8-hour TWA of 0.3 ppm and added a STEL of 1 ppm. NIOSH (Ex. 8-47) concurred with this proposal. These limits are established in the final rule. Phosphine is a colorless gas with a disagreeable, garlic-like odor.

Early studies reported that laboratory animals could tolerate phosphine in four-hour-daily exposures of 5 ppm for two months, but fatalities were observed from seven similar exposures at 10 ppm (Muller 1940/Ex. 1-919). In 1975, Waritz and Brown (Ex. 1-451) reported a 4-hour LC(50) of 11 ppm in rats; these lethal exposures caused effects typical of respiratory irritation.

Prior to 1958, numerous cases of phosphine-related occupational poisonings and deaths were reported, including a fatality caused by pulmonary edema that was attributed to an exposure of 8 ppm for two hours daily (Harger and Spolyar 1958/Ex. 1-327). Sublethal symptoms (without chronic effects) occurred at phosphine exposures averaging 10 ppm or less, with excursions of up to 35 ppm; recorded symptoms included diarrhea, nausea, vomiting, respiratory distress, and dizziness (Jones, Jones, and Longley 1964/Ex. 1-420). The literature contains no documented reports of chronic poisoning caused by prolonged exposure to phosphine, although several authorities have asserted that this is a possibility (Henderson and Haggard 1943e/Ex. 1-1086; Fairhall 1957h, as cited in ACGIH 1986/Ex. 1-3, p. 883; Johnstone and Miller 1960/Ex. 1-1114; Patty 1963f, as cited in ACGIH 1986/Ex. 1-3, p. 883; American Industrial Hygiene Association (AIHA) 1964/Ex. 1-407).

Joel Carr, Health and Safety Research Director for the American Federation of Grain Millers Union, testified on the toxicology of and employee exposures to phosphine in grain elevators and flour mills (Ex. 8-1; Tr. pp. 7-240 to 7-259). Mr. Carr described a report of a group of industrial hygiene studies published by NIOSH (Zaebst 1986; Zaebst, Blade, Morelli-Schroth et al. 1987; Zaebst, Blade, Burroughs et al. 1988), in which applicators of phosphine were found to be exposed above the proposed TWA PEL and STEL; nonapplicator workers also become exposed while working near fumigated grain, while loading or transferring fumigated grain, or while working in elevators and mills.

Mr. Carr also cited additional health studies, including a report of chronic neurological problems following an acute episode of phosphine poisoning (Kurzbauer and Keise 1987), animal data indicating that phosphine inhibits catalase activity (Price and Walter 1987), and studies showing phosphine to be mutagenic both in vitro and in vivo (Occupational/ Environmental Pathology Review 1988)(Tr. p. 7-246; Ex. 45A). He cited another NIOSH report (Studies of the Prevalence of Chronic, Non-Specific Lung Disease and Related Health Problems in the Grain Handling Industry, Rankin et al. 1986) that identified several symptoms associated with phosphine exposure, including headaches, dizziness, diarrhea, nausea, and dyspnea, as well as palpable abdomen (Tr. p. 7-247). Mr. Carr also mentioned the preliminary results of an NCI mortality study of grain workers in which elevated relative risks were found for non-Hodgkin's lymphoma (Tr. p. 7-254). Mr. Carr urged OSHA to adopt a short-term limit of 0.3 ppm, which is consistent with EPA's Maximum Concentration Limit for phosphine applicators (Tr. p. 7-250); in addition, he recommended that OSHA establish provisions for exposure and medical monitoring, training, and respiratory protection for phosphine.

OSHA appreciates the information supplied by Mr. Carr on phosphine toxicity and awaits completion of the ongoing studies discussed by him at the hearing. In response to Mr. Carr's request that OSHA establish other requirements in addition to the PEL, OSHA notes that the Agency is currently conducting rulemaking activities to develop generic standards for respiratory protection, medical surveillance, and exposure monitoring, but that the sole purpose of this rulemaking is to revise OSHA's outdated exposure limits.

In the final rule, OSHA is retaining the 8-hour TWA PEL for phosphine of 0.3 ppm and adding a 15-minute STEL of 1 ppm. The Agency concludes that both of these limits are required to substantially reduce the significant risk of lung damage, diarrhea, and nausea, all material health impairments associated with elevated short-term and long-term exposure to this gas.

PIPERAZINE DIHYDROCHLORIDE CAS: 142-64-3; Chemical Formula: C(4)H(10)N(2) 2 HCl H.S. No. 1330

Previously, OSHA had no limit for piperazine dihydrochloride. The ACGIH recommends a TLV-TWA limit of 5 mg/m(3). The proposed PEL was an 8-hour TWA of 5 mg/m(3); NIOSH (Ex. 8-47) concurred with the proposed PEL, and this limit is established in the final rule. Piperazine dihydrochloride is a solid.

Piperazine dihydrochloride is a water-soluble solid with low systemic toxicity and mild irritant properties; the compound is biologically active. The oral LD(50) for rats has been reported as 4.9 g/kg (NIOSH 1984, as cited in ACGIH 1986/Ex. 1-3, p. 491).

Eye and skin irritation have been reported as a result of human exposures to high (not further specified) levels of piperazine dihydrochloride; subjects experienced mild to moderate skin burns and sensitization. Inhalation of the dust has been associated with asthmatic reactions (Dow Chemical Company 1977h, as cited in ACGIH 1986/Ex. 1-3, p. 491). OSHA received no comments other than that from NIOSH (Ex. 8-47) on this substance.

In the final rule, OSHA is establishing a limit of 5 mg/m(3) as an 8-hour TWA for piperazine dihydrochloride. The Agency concludes that this limit will reduce the significant risks of sensitization and eye and skin irritation, which constitute material health impairments and are potentially associated with exposures to this substance at levels above the new limit.

n-PROPYL NITRATE CAS: 627-13-4; Chemical Formula: CH(3)CH(2)CH(2)ONO(2) H.S. No. 1340

OSHA formerly had an 8-hour TWA limit of 25 ppm for n-propyl nitrate. The ACGIH has a 25-ppm TWA and a 15-minute STEL of 40 ppm; these limits were proposed by OSHA. NIOSH (Ex. 8-47) concurred with these proposed limits, and these limits are established in the final rule. n-Propyl nitrate is a pale yellow liquid with a sickly sweet odor.

Rats inhaling propyl nitrate vapor for four hours at a concentration of 10,000 ppm exhibited cyanosis and methemoglobinemia before they died (Hood 1953, as cited in ACGIH 1986/Ex. 1-3, p. 505). The intravenous LD(50) in unanesthetized rabbits has been reported to be between 200 and 250 mg/kg; in anesthetized dogs and cats, intravenous doses of between 100 and 200 mg/kg were usually fatal (Murtha, Stabile, and Wills 1956/Ex. 1-649). Murtha and associates (1956/Ex. 1-649), who conducted these studies, concluded that n-propyl nitrate exerts a direct action on the vascular smooth muscle and that the ensuing cardiac effects and respiratory depression contribute to the compound's hypotensive action (Murtha, Stabile, and Wills 1956/Ex. 1-649). Inhalation trials in mice, rats, hamsters, guinea pigs, and dogs have established 4-hour LC(50) values ranging from 9000 to 10,000 ppm for rats, 6000 to 7000 ppm for mice, and 2000 to 2500 ppm for dogs. Dogs survived repeated exposures (six hours/day, five days/week) at 260 ppm for six months, although slight clinical signs were observed during the first two weeks of exposure (Rinehart, Garbers, Greene, and Stoufer 1958/Ex. 1-524). The percutaneous toxicity of n-propyl nitrate is low but may cause inflammation and thickening of the skin after repeated exposures; these effects are sometimes transient (ACGIH 1986/Ex. 1-3, p. 505). To protect against cardiovascular and respiratory depressant effects requires both TWA and STEL limits. NIOSH (Ex. 8-47) was the only commenter to the rulemaking record for this substance.

In the final rule, OSHA is retaining the PEL of 25 ppm TWA and adding a STEL of 40 ppm for n-propyl nitrate. The Agency concludes that this combined PEL-STEL limit will protect workers against the significant risk of cyanosis, methemoglobinemia, and hypotension, all material health impairments are potentially associated with exposure to n-propyl nitrate at levels above the 8-hour TWA PEL.

SODIUM FLUOROACETATE CAS: 62-74-8; Chemical Formula: CH(2)FCOONa H.S. No. 1366

The former OSHA standard for sodium fluoroacetate was 0.05 mg/m(3) as an 8-hour TWA, with a skin notation. The ACGIH has established exposure limits of 0.05 mg/m(3) TLV-TWA and 0.15 mg/m(3) TLV-STEL, with a skin notation. The proposal retained the former 8-hour TWA PEL and added a STEL of 0.15 mg/m(3) with a skin notation; NIOSH (Ex. 8-47) concurred with this proposal, and these limits are established in the final rule. The skin notation is retained. Sodium fluoroacetate is a fine white powder, which is sometimes dyed black for commercial use.

Sodium fluoroacetate causes vomiting, convulsions, and ventricular fibrillation. It is highly toxic by inhalation, ingestion, or via absorption through the skin (Occupational Health Guidelines for Chemical Hazards, NIOSH/OSHA 1981). The ACGIH calculated and set the threshold limit of 0.05 mg/m(3) based on studies of rats indicating an oral LD(50) of 1.7 mg/kg (Lehman 1951/Ex. 1-790). Tissue changes in rats were noted in a later study by the same author in which the animals were fed 0.25 mg sodium fluoroacetate/kg/day (Lehman 1952, as cited in ACGIH 1986/Ex. 1-3, p. 534); the equivalent level in humans would be 17 mg/person/day. A further study by Miller and Phillips (1955, as cited in ACGIH 1986/Ex. 1-3, p. 534) examined growth rates in rats fed various dosages of sodium fluoroacetate. Rats who received 10 ppm in their diet experienced a transient fluctuation in growth rate. At 20 ppm (approximately 2 mg/kg in young rats), the growth rate declined markedly the first week; the rats survived and resumed growth at the normal rate in three to four weeks. Tolerance for the chemical lasted less than two weeks, and those rats who had adjusted to sodium fluoroacetate showed a second retardation of growth when returned to a dietary level of 20 ppm after a two-week interval of eating a normal diet. Miller and Phillips (1955, as cited in ACGIH 1986/Ex. 1-3, p. 534) noted that rats conditioned to a dietary level of 20 ppm were then able to adjust to a level of 40 ppm (a dose that is greater than the single LD(50) dose per day). The comment from NIOSH (Ex. 8-47) was the only one made to the record on sodium fluoroacetate.

In the final rule, OSHA is retaining the 8-hour TWA of 0.05 mg/m(3) and adding a STEL of 0.15 mg/m(3) for sodium fluoroacetate; the skin notation is also retained. The Agency concludes that the 8-hour TWA and short-term exposure limits, with a skin notation, will reduce the risk of systemic effects possible as a result of short-term exposures above the 8-hour TWA of 0.05 mg/m(3).

TRIMETHYLBENZENE CAS: 25551-13-7; Chemical Formula: (CH(3))(3)C(6)H(3) H.S. No. 1412

OSHA formerly had no exposure limit for trimethylbenzene. The ACGIH TLV for all isomers of trimethylbenzene is 25 ppm as an 8-hour TWA. The proposed PEL was 25 ppm as an 8-hour TWA; NIOSH (Ex. 8-47, Table N1) concurred with the 25-ppm TWA limit, and the final rule establishes this limit for this liquid.

A study by Battig, Grandjean, and Turrian (1957/Ex. 1-104) provides the basis for the final rule's limit; this work reports symptoms among 27 workers exposed to a solvent containing 30 percent 1,3,5-trimethylbenzene and 50 percent 1,2,3-trimethylbenzene. A "significant number" of these workers were reported to have experienced symptoms of nervousness, tension and anxiety, and asthmatic bronchitis. The peripheral blood of these workers "showed a tendency to hypochromic anemia" and a somewhat abnormal clotting ability. This group of workers had been occupationally exposed to total hydrocarbon concentrations ranging from 10 to 60 ppm for several years. The authors of the study recommended maintaining employee exposures below 35 ppm (Battig, Grandjean, and Turrian 1957/Ex. 1-104). No comments other than that from NIOSH (Ex. 8-47) were received on this substance.

In the final rule, OSHA is establishing a 25-ppm 8-hour PEL to reduce the significant risks of bronchitis and blood effects reported to occur in exposed workers.

TUNGSTEN AND COMPOUNDS (INSOLUBLE) CAS: 7440-33-7; Chemical Formula: W H.S. No. 1416

Previously, OSHA had no exposure limits for insoluble tungsten and its compounds. The ACGIH has established 5 mg/m(3) as an 8-hour TWA and 10 mg/m(3) as a short-term exposure limit for these substances. NIOSH recommends a limit of 5 mg/m(3) as a 10-hour TWA. The proposed PEL for this group of substances was 5 mg/m(3) as an 8-hour TWA and 10 mg/m(3) as a 15-minute STEL. NIOSH (Ex. 8-47) concurred with OSHA's proposed limits. The final rule promulgates a 5 mg/m(3) 8-hour TWA and a 10 mg/m(3) 5-minute STEL, measured as tungsten. Tungsten is a gray, hard metal.

Rats fed a diet containing 0.5 percent insoluble tungsten compounds died, and another group of rats fed 0.1 percent of these compounds suffered noticeable weight loss (Kinard and Van de Erve 1941/Ex. 1-492). Studies in rats fed tungsten at 2, 5, or 10 percent of their diet showed that females in all dose groups had a 15-percent reduction in weight gain (Kinard and Van de Erve 1943/Ex. 1-493). The intraperitoneal LD(50) for tungsten metal powder in rats was 5 g/kg body weight; survivors showed minor liver and spleen changes at necropsy (Fredrick and Bradley 1946, as cited in ACGIH 1986/Ex. 1-3, p. 614). Studies of the tissues of guinea pigs intratracheally injected with tungsten metal and tungsten carbide revealed moderate interstitial cellular proliferation and no changes, respectively. However, Soviet studies involving similar intratracheal injections showed proliferation of the intra-alveolar septa (Kaplun and Mezentseva 1960, as cited in ACGIH 1986/Ex. 1-3, p. 614). The NIOSH criteria document for tungsten (1977h, as cited in ACGIH 1986/Ex. 1-3, p. 614) reports that Russian investigators found a 9- to 11-percent incidence of pulmonary fibrosis in workers exposed to tungsten (Kaplun and Mezentseva 1959/Ex. 1-961; and Mezentseva 1967, as cited in ACGIH 1986/Ex. 1-3, p. 614). NIOSH (1977h) recommended that the standard for tungsten and its insoluble compounds be set at 5 mg/m(3) to protect against pulmonary effects.

Stokinger (in Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2A, Clayton and Clayton 1981) reported on several epidemiological studies of workers in the "hard metal industry," in which tungsten carbide is machined. These studies describe a condition known as hard metal disease, which may be accompanied by pulmonary fibrosis. The disease is characterized by a moderate incidence of cough, dyspnea, and wheezing, a high incidence of minor radiological abnormalities with a few instances of marked abnormalities, and development of hypersensitivity asthma in some workers (which may be due to exposure to the cobalt that is used as a binding agent). The disease is progressive and potentially lethal. Stokinger (in Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2A, Clayton and Clayton 1981, p. 1992) reported that, unlike other lung diseases produced by inorganic dust, there is no correlation between onset of symptoms, length of exposure, and the development of interstitial fibrosis. Analysis of the lung of one worker who had clinical signs and radiological changes showed the presence of large amounts of tungsten with much smaller amounts of other metals.

Mr. H.K. Thompson, Corporate Industrial Hygiene Manager for Caterpillar, Inc. (Ex. 3-349), questioned the need for a STEL for tungsten. OSHA believes that, given the potential seriousness of hard metal disease and the uncertainties regarding the relationship between exposure and response, a short-term limit for tungsten will provide additional assurance that the 8-hour TWA PEL is not exceeded. Therefore, in accordance with OSHA's policy for establishing STELs in this rulemaking (see Section IV.C.17), OSHA finds that a STEL for tungsten is necessary.

In the final rule, OSHA is establishing an 8-hour TWA of 5 mg/m(3) and a STEL of 10 mg/m(3) for tungsten and its insoluble compounds, measured as tungsten. The Agency concludes that these limits will substantially reduce the significant risk of pulmonary fibrosis and other lung effects, which constitute material impairments of health that are associated with exposure to this metal and its insoluble compounds at levels above the new PELs.

TUNGSTEN AND COMPOUNDS (SOLUBLE) CAS: 7440-33-7; Chemical Formula: W H.S. No. 1417

OSHA had no former limit for exposure to tungsten and its soluble compounds. The ACGIH limit is 1 mg/m(3) TWA, with a 3 mg/m(3) STEL, measured as tungsten. NIOSH recommends a 1 mg/m(3) 10-hour TWA for tungsten and its soluble compounds. OSHA proposed an 8-hour TWA PEL of 1 mg/m(3) and a 15-minute STEL of 3 mg/m(3); NIOSH (Ex. 8-47, Table N1) concurred with the addition of a STEL to the 1 mg/m(3) TWA limit. The final rule establishes limits of 1 mg/m(3) as an 8-hour TWA and 3 mg/m(3) as a 15-minute STEL, measured as tungsten. Tungsten is a grey, hard metal.

Animal studies have shown that the LD(50) for soluble sodium tungstate when injected subcutaneously in rats ranges from 140 to 160 mg/kg (Kinard and Van de Erve 1940/Ex. 1-788). Soluble tungsten's lethal effects are the result of systemic poisoning that occurs as the compound is absorbed by multiple organs; this is followed by cellular asphyxiation (International Labour Office [ILO] 1934c, as cited in ACGIH 1986/Ex. 1-3, p. 614). Karantassis (1924, as cited in ACGIH 1986/Ex. 1-3, p. 614) also observed a systemic response in guinea pigs given soluble sodium tungstate or pure soluble tungsten either orally or intravenously; the animals developed anorexia, colic, trembling, and difficulty in breathing prior to death. Rats fed a diet containing 0.5 percent tungsten as soluble sodium tungstate or tungsten oxide died from this dose. Dietary doses of 0.1 percent tungsten oxide and the sodium salt caused weight loss in rats, but no deaths (Kinard and Van de Erve 1941/Ex. 1-492). Tungsten is believed to act by antagonizing the action of molybdenum (Higgins, Richert, and Westerfield 1956/Ex. 1-487). In its criteria document for tungsten (1977h, as cited in ACGIH 1986/Ex. 1-3, p. 614), NIOSH states that information on the effects of exposure to soluble tungsten compounds in the working population is not available. The ACGIH (1986/Ex. 1-3, p. 614) recommends a lower TLV for the soluble, as compared to the insoluble, compounds of tungsten because of the former's greater systemic toxicity. No comments other than those of NIOSH (Ex. 8-47) were received on this substance.

In the final rule, OSHA is establishing an 8-hour TWA of 1 mg/m(3) and a STEL of 3 mg/m(3) for tungsten and its soluble compounds, measured as tungsten. The Agency concludes that these limits will protect workers against the significant risks of systemic toxicity, anorexia, colic, incoordination, trembling, and dyspnea, all of which constitute material health impairments that are associated with exposure to these compounds at levels above the new PELs.

VINYLIDENE CHLORIDE (1.1-DICHLOROETHYLENE) CAS: 75-35-4; Chemical Formula: CH(2) = CCl(2) H.S. No. 1428

Previously, OSHA's Z tables did not include a limit for vinylidene chloride (VDC). The ACGIH has established 5 ppm as an 8-hour TWA and 20 ppm as a 15-minute STEL. NIOSH and OSHA, in 1978, jointly recommended that employee exposure to VDC be reduced to the lowest feasible level on the basis of VDC's carcinogenicity (NIOSH/OSHA 1978/Ex. 1-1119). OSHA proposed a PEL of 5 ppm (8-hour TWA) and a STEL of 20 ppm. However, in response to record comments, the final rule promulgates a 1-ppm limit as an 8-hour TWA. Vinylidene chloride is a colorless liquid that polymerizes readily.

The acute oral LD(50) for male rats is 2500 mg/kg (Jenkins, Trabulus, and Murphy 1972/Ex. 1-960). The LC(50) for rats exposed to a single four-hour exposure of VDC vapor was reported as 6350 ppm in one study (Siegel, Jones, Coon, and Lyon 1971/Ex. 1-371) and 32,000 ppm in an earlier study (Carpenter, Smyth, and Pozzani 1949/Ex. 1-722). Liquid VDC causes transient irritation to the eyes of rats but has little effect on exposed skin if the VDC is allowed to evaporate (Torkelson and Rowe 1981b, as cited in ACGIH 1986/Ex. 1-3, p. 628).

Prendergast and co-workers (1967/Ex. 1-926) exposed rats, rabbits, guinea pigs, and monkeys eight hours/day, five days/week for six weeks to 395 mg/m(3) (100 ppm); these authors saw no visible signs of toxicity while the exposure was in process, but rabbits and monkeys lost weight. These same species were exposed continuously to VDC concentrations of 5, 15, 25, or 47 ppm for 90 days; only the animals exposed to 5 ppm showed no increases in mortality (Prendergast, Jones, Jenkins, and Siegel 1967/Ex. 1-926).

Nasal irritation, liver cell degeneration, and retarded weight gain were reported in rats following 20 six-hour exposures to 500 ppm VDC (Gage 1970/Ex. 1-318); at 200 ppm, only nasal irritation occurred. Studies by Torkelson and Rowe (1981b, as cited in ACGIH 1986/Ex. 1-3, p. 628) in which rats, rabbits, guinea pigs, and dogs were exposed to 25, 50, or 100 ppm VDC for eight hours per day, five days per week for six months revealed injury of the kidneys and liver in all animals at all levels of exposure. Maltoni (1977/Ex. 1-985) and Maltoni, Cotti, Mercy, and Chieco (1977/Ex. 1-1090) conducted an evaluation of VCD's carcinogenicity in which mice, rats and hamsters were exposed to levels from 10 to 150 ppm for four hours per day, five days per week for 52 weeks, with results reported through week 98 of the study. In those mice exposed to 25 ppm VCD, 21 percent of the males and 1.5 percent of the females developed kidney adenocarcinomas; these tumors were not seen in rats exposed to amounts of VDC up to 150 ppm. Exposures of 100 or 150 ppm in rats did produce a significant increase in mammary adenocarcinomas, and this response was dose-related (Maltoni 1977/Ex. 1-985; Maltoni, Cotti, Morisi, and Chieco 1977/Ex. 1-1090). Overt toxicity and mortality occurred early in the studies after four-hour exposures at levels of 50 ppm in mice and 200 ppm in rats; hamsters exposed to 20 ppm VDC showed no increase in tumor incidence (Maltoni 1977/Ex. 1-985; Maltoni, Cotti, Morisi, and Chieco 1977/Ex. 1-1090).

A study by Murray, Nitschke, Rampy, and Schwetz (1979/Ex. 1-920) investigated the embryotoxic, fetotoxic, and teratogenic effects of inhaled and ingested VDC (in rats) and inhaled VDC (in rabbits). In the inhalation studies, rats were exposed to 20, 80, or 160 ppm VDC for seven hours per day. VDC was toxic to both the adults and their embryos at levels of 80 and 160 ppm among the rats, and at 160 ppm in rabbits. At exposure levels of 20 ppm in rats and 80 ppm in rabbits, neither maternal toxicity nor effects on embryonic or fetal development were noted. In the ingestion study with rats, drinking water containing 200 ppm VDC caused no toxic effects in either the rats or their offspring.

Two strains of rats exposed to 75 or 100 ppm VDC for five days/week, six hours/day for 12 months did not show a significant increase in tumors (Viola and Caputo 1977/Ex. 1-937). Other investigators exposed rats to 25 or 75 ppm by inhalation for six hours/day, five days/week for 18 months, or to 60, 100, or 200 ppm VDC in their drinking water for two years, and found no increase in tumor incidence in these animals (Rampy, Quast, Humiston et al. 1977, as cited in ACGIH 1986/Ex. 1-3, p. 628). In mice, VDC was not active either as a whole mouse skin carcinogen or by subcutaneous injection.

In other studies, VDC proved mutagenic in both E. coli and S . typhimurium strains (Greim, Bonse, Radwan et al. 1975/Ex. 1-904; Bartsch, Malaveille, Montesano, and Tomatis 1975/Ex. 1-889). VDC has been implicated as a tumor initiator in a carcinogenesis bioassay by Van Duuren, Goldschmidt, Loewengart et al. (1979/Ex. 1-936). Studies by Reitz, Watanabe, McKenna et al. (1980/Ex. 1-927) suggest that VCD's tumorigenicity is a result of its ability to initiate cell injury, rather than of its ability to alter the genetic material of an injured cell. However, VDC has been shown to alkylate DNA in situ and increase the rate of DNA repair to a small extent in mice (Norris and Reitz 1984/Ex. 134B). The actual cell injury is caused by VDC metabolites, which are highly reactive and cytotoxic (Maltoni 1977/Ex. 1-985; Hathway 1977/Ex. 1-906; Henschler and Bonse 1977/Ex. 1-908).

A cohort study of 138 VCD-exposed workers did not identify any VCD-related health effects in these workers (Ott, Fishbeck, Townsend, and Schneider 1976/Ex. 1-924). The cohort was too small to provide any evidence that VDC is not likely to be carcinogenic.

The Chemical Manufacturers Association submitted the results of an NTP gavage study of VDC in mice and rats (NTP 1982/Ex. 134B). The only observed significant increase in tumor incidence occurred in low-dose female mice; this increase was not considered to be related to VDC administration because similar effects were not observed in high-dose female mice, male mice, or rats. The NTP (1982/Ex. 134B) concluded that VDC was not carcinogenic in mice or rats exposed by gavage, but cautioned that a maximum tolerated dose had not been demonstrated and that previously reported studies had shown that carcinogenicity is associated with VDC inhalation by animals.

Based on the carcinogenicity evidence described above, NIOSH (Ex. 8-47, Table N6B) indicated that VDC is a suitable candidate for an individual 6(b) rulemaking. However, the CMA (Ex. 165) was of the opposite opinion, stating that the demonstrated lack of tumor response in most studies, coupled with evidence that VDC metabolism is species-specific, "demonstrates that VDC is unlikely to pose an oncogenic risk to humans" (Ex. 165, p. 42). CMA also objected to the statement by NIOSH and OSHA in the joint Current Intelligence Bulletin on VDC (NIOSH/OSHA 1978/Ex. 1-1119) that VDC be considered a potential carcinogen because of its structural similarity to vinyl chloride; the CMA considered this statement inappropriate, given the toxicity data available.

Matthew Gillen and Scott Schneider of the Workers Institute for Safety and Health (WISH) commented that the proposed 5-ppm PEL and 20-ppm STEL for VDC would not provide sufficient protection from systemic effects (Ex. 116). They pointed out that the study by Prendergast et al. (1967/Ex. 1-926) found 15 ppm to be the lowest effect level for increased mortality in animals, and that the Torkelson and Rowe (1981b, as cited in ACGIH 1986/Ex. 1-3, p. 628) study found liver and kidney injury in animals. These commenters stated that the "ACGIH TLV cannot be considered to provide adequate protection for this substance. Given this fact, OSHA should consider the NIOSH REL of 1 ppm as an interim value until further risk assessment studies can be carried out" (Ex. 116).

OSHA has re-examined the health evidence in light of the comment by WISH, and has determined that the proposed 5-ppm TWA PEL for VDC does not afford workers sufficient protection from systemic effects. Although it is questionable, in the Prendergast et al. (1967/Ex. 1-926) study, that the observed deaths at lower exposure levels were compound-related, histopathologic examination of animals exposed to 47 ppm showed treatment-related liver and kidney damage. Using an exposure regimen similar to occupational exposure (i.e., eight hours/day, five days/week), Torkelson and Rowe (1981b, as cited in ACGIH 1986/Ex. 1-3, p. 628) demonstrated kidney and liver toxicity in four species of animals after exposure to VDC levels as low as 25 ppm were administered for only six months.

OSHA believes that these studies clearly demonstrate that VDC can cause adverse liver and kidney damage at airborne concentrations as low as 25 to 50 ppm and suggest that VDC is a potential occupational carcinogen. Liver and kidney damage and cancer clearly constitute material health impairments within the meaning of the Act. Therefore, OSHA concludes that the proposed limits of 5 ppm as an 8-hour TWA and 20 ppm as a STEL will not sufficiently protect workers from the significant risk of organ damage, and that a further reduction in the PEL is warranted. Accordingly, OSHA is establishing a 1-ppm 8-hour TWA limit for vinylidene chloride in the final rule.

WELDING FUMES CAS: None; Chemical Formula: Not available H.S. No. 1430

OSHA formerly had no limit for exposure to welding fumes, which are defined as fumes that are generated by the manual metal arc or oxy-acetylene welding of iron, mild steel, or aluminum. The ACGIH has set an 8-hour TWA of 5 mg/m(3) for these welding fumes, measured as total particulate in the welder's breathing zone. OSHA proposed an 8-hour TWA of 5 mg/m(3) for these fumes; this limit is established in the final rule. This limit applies to the total fume concentration generated during the welding of iron, mild steel, or aluminum; the fumes generated by the welding of stainless steel, cadmium, or lead-coated steel, or other metals such as copper, nickel, or chrome are considerably more toxic and shall be kept at or below the levels required by their respective PELs. Welding fumes consist of metallic oxides generated by the heating of metal being welded, the welding rod, or its coatings.

Although these types of welding generally produce fumes consisting of aluminum, iron, or zinc oxides, other toxic gases may also be produced in large amounts (Ferry and Ginther 1952/Ex. 1-900; Ferry 1954/Ex. 1-782; Silverman 1956/Ex. 1-1169; Homer and Mohr 1957/Ex. 1-787). The welding of iron metals may give off fumes of manganese, silicate, and various organic binders. Aluminum welding may generate fumes consisting of fluorine, arsenic, copper, silicon, and beryllium (NIOSH 1975h and American Welding Society 1974, both as cited in ACGIH 1986/Ex. 1-3, p. 634). Eighteen different substances, including fluoride, manganese, silicon, titanium, and sodium and potassium silicates, have been measured in the fumes resulting from the welding of mild steel (ACGIH 1986/Ex. 1-3, p. 634).

Excessive exposure to welding fume can cause a variety of disorders, most notably metal fume fever. It has been estimated that 30 to 40 percent of all welders have experienced metal fume fever at some time (Abraham 1983, in Environmental and Occupational Medicine, W.N. Rom, ed., p. 146). This disorder, which results from exposure to freshly formed metal fume, results in the appearance of delayed, flu-like symptoms, including dyspnea, coughing, pains in muscles and joints, fever, and chills. Recovery usually requires one or two days of time away from work. In addition to fume fever, exposure to welding fume may damage the small airways, causing interstitial pneumonia (Abraham 1983).

Several commenters, the American Iron and Steel Institute (Exs. 129, 188), the Abbott Laboratories (Tr. 9-155 to 9-156), and the American Welding Society (Ex. 3-860), were of the opinion that OSHA's discussion of welding fumes in the NPRM was not clear with regard to whether the limit applied to exposure samples taken inside or outside of the welding helmet. OSHA wishes to clarify that welding fume is to be measured in the breathing zone of the welder; the specific details of the appropriate positioning of the sampler should be determined on the basis of guidance in the Field Operations Manual (OSHA 1984). This is consistent with a past OSH Review Commission decision Secretary of Labor v. Caterpillar Tractor (8 OSHRC 1043 (1979)).

NIOSH (Ex. 8-47) stated at the hearing that welding fumes should be designated as a carcinogen. This view was also endorsed by Dr. James Melium, of the New York State Department of Health (Tr. p. 11-104). In response to these commenters, OSHA notes that there are few data sufficient to establish a dose-response for the fumes. Accordingly, OSHA believes it would be premature to identify these fumes as potential occupational carcinogens.

OSHA concludes that a PEL for welding fumes is needed to protect workers involved in the welding of aluminum, iron, or mild steel from the significant risk of metal fume fever and respiratory irritation associated with the generation of welding fumes. In the final rule, OSHA is establishing a TWA of 5 mg/m(3) for these particular types of welding fumes, measured as total particulate inside the welder's breathing zone. The Agency finds that this limit will substantially reduce the significant risk of material health impairment to which manual metal arc or oxy-acetylene welders of iron, mild steel, or aluminum were previously exposed in the absence of any OSHA limit.

ZINC OXIDE (FUME) CAS: 1314-13-2; Chemical Formula: ZnO H.S. No. 1437

OSHA's former exposure limit for zinc oxide fume was 5 mg/m(3) as an 8-hour TWA. The ACGIH recommends a 5 mg/m(3) TWA and also has a STEL of 10 mg/m(3). NIOSH recommends a 5 mg/m(3) 10-hour TWA limit with a 15-minute ceiling of 15 mg/m(3). OSHA proposed to retain the 5 mg/m(3) 8-hour TWA and to add a STEL of 10 mg/m(3), and NIOSH (Ex. 8-47, Table N1) concurs with this proposal. The final rule establishes these limits. When heated, zinc oxide produces a white fume.

The most prevalent toxic effect of zinc oxide fume is a condition known as "metal fume fever," whose symptoms include chills, fever, muscular pain, nausea, and vomiting (Turner and Thompson 1926/Ex. 1-1124). Studies in the workplace have shown that welders exposed to zinc oxide fume at concentrations of 320 to 580 mg/m(3) reported nausea, with the development of chills, shortness of breath, and severe chest pains 2 to 12 hours later. Most workers took approximately 4 days to recover, and some eventually developed pneumonia (Hammond 1944/Ex. 1-981). Other studies have reported the frequent occurrence of chills in workers exposed to zinc oxide at levels as low as 5 mg/m(3) (Hickish 1963 and Wall 1970, both as cited in ACGIH 1986/Ex. 1-3, p. 645). Hammond (1944/Ex. 1-981) reported that workers exposed to 8 to 12 mg/m(3) of zinc oxide fume did not suffer from metal fume fever.

Zinc oxide exposures of guinea pigs that lasted only an hour caused a drop in body temperature, followed 6 to 18 hours later by an increase above normal levels (Turner and Thompson 1926/Ex. 1-1124). The animals in the high-exposure group (2500 mg/m(3) for three to four hours) died after exposure.

Early studies (Drinker, Thomson, and Finn 1927/Ex. 1-356) suggested that metal fume fever was unlikely to occur at concentrations below 15 mg/m(3), but subsequent experience shows that exposures even at 5 mg/m(3) can cause this syndrome (Hickish 1963 and Wall 1970, both as cited in ACGIH 1986/Ex. 1-3, p. 646).

NIOSH's criteria document (1975d, as cited in ACGIH 1986/Ex. 1-3, p. 645) reported that the development of metal fume fever was unlikely at levels as low as 5 mg/m(3), but the Institute stated that exposures to the fume at this level could cause chronic respiratory effects. Dr. Lawrence Hecker, representing Abbott Laboratories (Ex. 3-678), objected to a STEL for zinc oxide fume. However, in both its criteria document (1975d) and post-hearing testimony (Ex. 150, Comments on Zinc Oxide Fume), NIOSH indicated that a short-term limit is necessary to "prevent pathological tissue changes in the lung from acute exposure." Therefore, OSHA finds that a STEL for zinc oxide fume is necessary to prevent or minimize these effects.

In the final rule, OSHA is retaining the 5 mg/m(3) 8-hour TWA and adding a STEL of 10 mg/m(3). The Agency concludes that both of these limits will protect workers from the significant risk of metal fume fever, which constitutes a material health impairment that is associated with acute and chronic exposure to zinc oxide fumes.

ZIRCONIUM COMPOUNDS CAS: 7440-67-7; Chemical Formula: Zr H.S. No. 1439

The former OSHA limit for zirconium compounds was an 8-hour TWA of 5 mg/m(3), measured as zirconium. The ACGIH has established a TLV-TWA of 5 mg/m(3), supplemented by a 10 mg/m(3) STEL, (as Zr). The proposal retained the 8-hour TWA but added a STEL of 10 mg/m(3); these limits are promulgated by the final rule. Zirconium compounds may be either bluish-black powders or grayish-white lustrous metals.

The toxic effects of inhalation exposures to zirconium compounds include the formation of granulomas, both in the lungs and on the skin. Sax (Dangerous Properties of Industrial Materials, 6th ed., 1984) reports cases of pulmonary granulomas in workers exposed to zirconium aerosols. In laboratory animals, oral toxicity is low (NIOSH 1972b, as cited in ACGIH 1986/Ex. 1-3, p. 647), and inhalation studies conducted for one year at levels of 3.5 mg zirconium/m(3) dust and mist resulted in limited toxicity (Stokinger 1981c/Ex. 1-1134).

NIOSH (Ex. 8-47) recommended that zirconium tetrachloride should not be included among the compounds for which the proposed zirconium PEL is applied. NIOSH cites an animal study by Spiegl et al. (1956, as cited in ACGIH 1986/Ex. 1-3, p. 647), in which a 60-day exposure to zirconium tetrachloride at a concentration of 6 mg/m(3) (six hours/day, five days/week) resulted in increased mortality in rats and guinea pigs and a decrease "of borderline significance" in blood hemoglobin and red blood cell levels in dogs. Given that the observed effect level for mortality of 6 mg/m(3) is close to the proposed 5 mg/m(3) limit, NIOSH (Ex. 8-47) stated that a separate PEL should be considered for zirconium tetrachloride.

At this time, OSHA is establishing the PELs as proposed for all zirconium compounds, including zirconium tetrachloride. There are no reports, other than the one cited by NIOSH, that indicate that exposure to zirconium compounds causes severe toxicity at levels near the proposed 5 mg/m(3) TWA PEL; in addition, the toxic reaction of dogs exposed to 6 mg/m(3) was of borderline significance.

OSHA concludes that the 5 mg/m(3) TWA and 10 mg/m(3) STEL limits for the zirconium compounds, measured as zirconium, will protect workers from the significant risk of pulmonary effects potentially associated with the short-term exposures permitted by the 8-hour TWA alone. The Agency has determined that these effects constitute material health impairments.

Conclusions for This Group of Systemic Toxicants

For the group of systemic toxicants shown on Table C8-1, OSHA concludes that the risks associated with occupational exposures are significant. As Table C8-2 shows, the systemic effects caused by such exposures include cancer, liver and kidney damage, testicular damage, fetal poisoning, central nervous system depression, and asthma, each of which constitutes material impairment of health within the meaning of the Act. Affected employees may experience dizziness, nausea, generalized weakness, respiratory irritation, blood in the urine, chest tightness, hives, and necrosis of the cornea. These effects represent significant impairments of health and functional capacity, and reducing the limits for these systemic toxins will substantially reduce these significant risks.

9. Substances for Which Limits Are Based on No-Observed-Adverse-Effect Levels

Introduction

For a group of 23 toxic substances, OSHA is establishing limits based on evidence that these substances cause toxic responses at higher levels but have been shown not to produce adverse effects in animals or exposed populations at the permissible exposure limits being established. These substances are shown in Table C9 - 1, along with their CAS numbers, H.S. numbers, and former, proposed, and final rule limits. OSHA is establishing limits for 17 chemicals in this group that have not formerly been regulated by the Agency. The Agency is retaining its 8-hour TWA PEL and adding a STEL for two substances, reducing the 8-hour TWA and adding a STEL in the case of uranium (insoluble compounds), reducing the 8-hour TWA for one substance (petroleum distillates), and retaining the existing 8-hour TWA for two chemicals.

 Table C9 - 1 Substances for Which Limits Are Based On a No-Observed -
              Adverse-Effect Level
             (NOTE: Because of its width, this table has been divided;
              see continuation for additional columns).
_______________________________________________________________
H.S. Number/                 CAS No.          Former
Chemical Name                                  PEL
_______________________________________________________________

1029 Atrazine                 1912-24-9         --
1041 Bromacil                 314-40-9          --
1056 p-tert-Butyltoluene      98-51-1         10 ppm TWA
1085 Chlorodiflouromethane    75-45-6           --
1090 o-Chlorotoluene          95-49-8           --
1110 Cyclonite                121-82-4          --
1117 2,6-Di-tert-butyl-       128-37-0          --
       p-cresol
1134 Diethanolamine           111-42-2          --
1136 Diethyl phthalate        84-66-2           --
1144 Dinitolmide              148-01-6          --
1147 Diphenylamine            122-39-4          --
1153 Diuron                   330-54-1          --
1249 Methyl acetate           79-20-9        200 ppm TWA
1275 Metribuzin               21087-64-9        --
1297 Oil mist (mineral)       8012-95-1      5 mg/m(3) TWA
1312 Petroleum distillates    8002-05-9      500 ppm TWA
      (naphtha)
1327 m-Phthalodinitrile       626-17-5          --
1332 Platinum, metal          7440-06-4         --
1346 Resorcinol               108-46-3          --
1382 Tantalum, metal dust     7440-25-7      5 mg/m(3) TWA
      and oxide
1410 Trimethyl phosphite      121-45-9          --
1415 Triphenyl amine          603-34-9          --
1418 Uranium (insoluble       7440-61-1     0.25 mg/m(3) TWA
       compounds)
_______________________________________________________________


 Table C9 - 1 Substances for Which Limits Are Based On a
            No-Observed-Adverse-Effect Level (continuation)
_______________________________________________________________
H.S. Number/                   Proposed        Final Rule
Chemical Name                    PEL              PEL(1)
_______________________________________________________________
1029 Atrazine                5 mg/m(3) TWA      5 mg/m(3) TWA
1041 Bromacil                1 ppm TWA          1 ppm TWA
1056 p-tert-Butyltoluene     10 ppm TWA         10 ppm TWA
                             20 ppm TWA         20 ppm TWA
1085 Chlorodiflouromethane   1000 ppm TWA       1000 ppm TWA
                             1250 ppm STEL
1090 o-Chlorotoluene         50 ppm TWA         50 ppm TWA
                             75 ppm STEL
1110 Cyclonite               1.5 mg/m(3) TWA    1.5 mg/m(3) TWA
                             3 mg/m(3) STEL     Skin
                             Skin
1117 2,6-Di-tert-butyl-      10 mg/m(3) TWA     10 mg/m(3) TWA
       p-cresol
1134 Diethanolamine          3 ppm TWA          3 ppm TWA
1136 Diethyl phthalate       5 mg/m(3) TWA      5 mg/m(3) TWA
1144 Dinitolmide             5 mg/m(3) TWA      5 mg/m(3) TWA
1147 Diphenylamine           10 mg/m(3) TWA     10 mg/m(3) TWA
1153 Diuron                  10 mg/m(3) TWA     10 mg/m(3) TWA
1249 Methyl acetate          200 ppm TWA        200 ppm TWA
                             250 ppm STEL
1275 Metribuzin              5 mg/m(3) TWA      5 mg/m(3) TWA
1297 Oil mist (mineral)      5 mg/m(3) TWA      5 mg/m(3) TWA
                             10 mg/m(3) STEL
1312 Petroleum distillates   400 ppm TWA        400 ppm TWA
      (naphtha)
1327 m-Phthalodinitrile      5 mg/m(3) TWA      5 mg/m(3) TWA
1332 Platinum, metal         1 mg/m(3) TWA      1 mg/m(3) TWA
1346 Resorcinol              10 ppm TWA         10 ppm TWA
                             20 ppm STEL        20 ppm STEL
1382 Tantalum, metal dust    5 mg/m(3) TWA      5 mg/m(3) TWA
      and oxide              10 mg/m(3) STEL
1410 Trimethyl phosphite     2 ppm TWA          2 ppm TWA
1415 Triphenyl amine         5 mg/m(3) TWA      5 mg/m(3) TWA
1418 Uranium (insoluble      0.2 mg/m(3) TWA    0.2 mg/m(3) TWA
       compounds)            0.6 mg/m(3) STEL   0.6 mg/m(3) STEL
_________________________________________________________________
  Footnote(1) OSHA's TWA limits are for 8-hour exposures; its STELs are
for 15 minutes unless otherwise specified; and its ceilings are peaks not
to be exceeded for any period of time.

Description of the Health Effects

The substances included in this group cause a wide range of adverse health effects in both animals and humans. Unlike most of the other groupings described in this preamble, these toxicants do not affect the same target organ or system: some are central nervous system depressants, several are upper respiratory tract irritants, and still others have their primary effect on the heart, liver, and/or kidney.

The commonality among these otherwise diverse substances is that apparent no-observed-adverse-effect levels (NOAELs) have been defined for all of them; that is, there are data demonstrating that overt toxic effects caused by exposure to these substances at higher levels do not occur below a certain "no-observed-adverse-effect" level. Permissible exposure limits have been developed for these chemicals on the basis of these no-observed-adverse-effect levels. Table C9 - 2 shows the health effects observed in animals and observed or likely to occur in humans exposed to these substances.

TABLE C9 - 2.  Health Effects Associated With Substances for Which
               Limits are Based on No-Observed-Adverse-Effect Levels
               (NOTE: Because of its width, this table has been divided;
               see continuation for additional columns).
_______________________________________________________________________
H.S. Number/                                Health Effects
Chemical Name                 CAS No.      Observed in Animals
_______________________________________________________________________
1029 Atrazine               1912-24-9      Ataxia, dyspnea,
                                           convulsions
1041 Bromacil                314-40-9      Irritation,
                                           thyroid damage
1056 p-tert-Butyl-toluene     98-51-1      CNS depression,
                                           respiratory tract
                                           irritation,
                                           liver and kidney
                                           changes
1085 Chlorodifluoromethane    75-45-6      Cardiac sensitization
1090 o-Chlorotoluene          95-49-8      Weakness, vasodilation,
                                           incoordination,
                                           convulsions, irritation
1110 Cyclonite               121-82-4      Death
1117 2,6-Di-tert-            128-37-0      Growth rate decrease,
         butyl-p-cresol                    increase in liver
                                           weight
1134 Diethanolamine          111-42-2      Impaired vision,
                                           skin irritation
1136 Diethyl phthalate        84-66-2      Polyneuritis,
                                           disturbance of
                                           balance
1144 Dinitolmide             148-01-6      Liver changes
1147 Diphenylamine           122-39-4      Liver, kidney, spleen
                                           changes
1153 Diuron                  330-54-1      Anemia, methe-
                                           moglobinemia
1249 Methyl acetate           79-20-9         --
1275 Metribuzin            21087-64-9      CNS depression,
                                           thyroid and liver
                                           changes
1297 Oil mist (mineral)     8012-95-1      Lung irritation
1312 Petroleum distillates  8030-30-6      Motor incoordination,
       (naphtha)                           convulsions
1327 m-Phthalodinitrile      626-17-5      Skin irritation
1332 Platinum, metal        7440-06-4      Tumorigen by
                                           implantation
1346 Resorcinol              108-46-3      Eye, skin irritation;
                                           mutagenicity;
                                           hemolytic effects
1382 Tantalum, metal dust   7440-25-7      Bronchitis, pneumonitis,
       and oxide                           hyperemia
1410 Trimethyl phosphite     121-45-9      Teratogenicity,
                                           ocular irritation
1415 Triphenyl amine         603-34-9      Skin irritation
1418 Uranium (insoluble     7440-61-1      Kidney damage,
       compounds)                          blood disorders
_____________________________________________________________________



TABLE C9 - 2.  Health Effects Associated With Substances for Which
             Limits are Based on No-Observed-Adverse-Effect Levels
             (Continued)
______