Disclaimer: These guidelines were developed under contract using generally accepted secondary sources. The protocol used by the contractor for surveying these data sources was developed by the National Institute for Occupational Safety and Health (NIOSH), the Occupational Safety and Health Administration (OSHA), and the Department of Energy (DOE). The information contained in these guidelines is intended for reference purposes only. None of the agencies have conducted a comprehensive check of the information and data contained in these sources. It provides a summary of information about chemicals that workers may be exposed to in their workplaces. The secondary sources used for supplements 111 and 1V were published before 1992 and 1993, respectively, and for the remainder of the guidelines the secondary sources used were published before September 1996. This information may be superseded by new developments in the field of industrial hygiene. Therefore readers are advised to determine whether new information is available.

OCCUPATIONAL SAFETY AND HEALTH GUIDELINE FOR HALOTHANE

INTRODUCTION

This guideline summarizes pertinent information about halothane for workers and employers as well as for physicians, industrial hygienists, and other occupational safety and health professionals who may need such information to conduct effective occupational safety and health programs. Recommendations may be superseded by new developments in these fields; readers are therefore advised to regard these recommendations as general guidelines and to determine whether new information is available.

SUBSTANCE IDENTIFICATION

* Formula

CF(3)CHBrCl

* Structure

(For Structure, see paper copy)

* Synonyms

2-Bromo-2-chloro-1,1,1,-trifluoroethane; Bromochlorotrifluoroethane;

1,1,1-Trifluoro-2,2-chlorobromoethane; Fluothane

* Identifiers

1. CAS No.: 151-67-7

2. RTECS No.: KH6550000

3. Specific DOT number: None

4. Specific DOT label: None

* Appearance and odor

Halothane is a highly volatile, clear, nonflammable, colorless liquid with a pleasant odor. An odor threshold of 33 parts per million (ppm) parts of air has been reported.

CHEMICAL AND PHYSICAL PROPERTIES

* Physical data

1. Molecular weight: 197.39

2. Boiling point (at 760mm Hg): 50.2 degrees C (122.4 degrees F)

3. Specific gravity (water = 1): 1.871 at 20 degrees C (68 degrees F)

4. Vapor density: Data not available.

5. Melting/Freezing point/Decomposition temperature: Data not available.

6. Vapor pressure at 20 degrees C (68 degrees F): 243 mm Hg

7. Solubility: Slightly soluble in water; miscible in petroleum ether and other fat solvents.

8. Evaporation rate: Data not available.

* Reactivity

1. Conditions contributing to instability: Halothane is sensitive to light but can be stabilized with 0.01 percent thymol. Contact with light causes decomposition.

2. Incompatibilities: Contact of halothane with light should be avoided. Contact with acids, acid fumes, heat, or flame causes toxic fume emissions.

3. Hazardous decomposition products: Toxic gases (such as bromine, chlorine, and fluorine) may be released in a fire involving halothane.

4. Special precautions: Halothane attacks some coatings and some forms of plastic and rubber.

* Flammability

The National Fire Protection Association has not assigned a flammability rating to halothane.

1. Flash point: Not applicable.

2. Autoignition temperature: Not applicable.

3. Flammable limits in air: Not applicable.

4. Extinguishant: Use an extinguishant that is suitable for the materials involved in the surrounding fire.

Fires involving halothane should be fought upwind from the maximum distance possible. Isolate the hazard area and deny access to unnecessary personnel. Firefighters should wear a full set of protective clothing and self-contained breathing apparatus when fighting fires involving halothane.

EXPOSURE LIMITS

* OSHA PEL

The Occupational Safety and Health Administration (OSHA) does not currently regulate halothane.

* NIOSH REL

The National Institute for Occupational Safety and Health (NIOSH) has established a recommended exposure limit (REL) of 2 parts per million (ppm) parts of air (16.2 milligrams per cubic meter (mg/m(3))) for halothane (as a waste anesthetic gas) as a 60-minute ceiling limit that should not be exceeded during any part of the workday [NIOSH 1992].

* ACGIH TLV

The American Conference of Governmental Industrial Hygienists (ACGIH) has assigned halothane a threshold limit value (TLV) of 50 ppm (404 mg/m(3)) as a TWA for a normal 8-hour workday and a 40-hour workweek [ACGIH 1994, p. 22].

* Rationale for Limits

The NIOSH limit is based on the risk of reproductive effects and decreased audiovisual performance associated with exposure to halothane [NIOSH 1992].

The ACGIH limit was established by analogy with the health effects posed by previously used anesthetic agents (chloroform and trichloroethylene) [ACGIH 1991, p. 723].

HEALTH HAZARD INFORMATION

* Routes of Exposure

Exposure to halothane can occur through inhalation, ingestion, and eye or skin contact.

* Summary of Toxicology

1. Effects on animals: Halothane causes eye irritation and liver and kidney damage. This substance may also be a reproductive toxin in animals [ACGIH 1991; NIOSH 1993]. Instilled into the eyes of rabbits, halothane caused severe eye irritation [NIOSH 1993]. The LC(50) in rats is 29,000 ppm for an unspecified duration, and the oral LD50 in rats is 5,680 mg/kg [NIOSH 1993]. Guinea pigs repeatedly given anesthetic doses of halothane developed hepatic lesions and necrosis of the liver [ACGIH 1991]. Other studies in rabbits and rats exposed subchronically showed dose-dependent increases in liver-to-body weight ratios in these animals [ACGIH 1991]. The offspring of rats exposed daily during gestation to 10 ppm of halothane showed reduced learning ability and, at autopsy, liver damage [ACGIH 1991]. Daily exposure of pregnant mice to 500 ppm halothane caused only a small decrease in maternal and fetal weight gain [ACGIH 1991]. The offspring of mice anesthetized with halothane on 3 consecutive days during pregnancy showed an increased incidence of cleft palate and reduced ossification [ACGIH 1991]. Other studies have failed to show reproductive effects [ACGIH 199l]. The International Agency for Research on Cancer (IARC) has determined that the evidence for the carcinogenicity of halothane in animals is inadequate [ACGIH 1991; IARC 1987].

2. Effects on Humans: Halothane causes central nervous system depression, affects the cardiovascular system, may cause hepatitis, and has reproductive effects in humans. When used as a clinical anesthetic, halothane induces amnesia, analgesia, anesthesia, and respiratory depression [Hathaway et al. 1991]. Anesthetic doses range from 5000 to 30,000 ppm [ACGIH 1991]. During anesthesia, cardiac output may be reduced and arrhythmias may occur [Hathaway et al. 1991]. A syndrome called "halothane hepatitis" occurs in 1 in 10,000 halothane-induced anesthesia patients; this syndrome involves fever, anorexia, nausea, and vomiting and may progress to hepatic failure and death [Hathaway et al. 1991]. This syndrome usually occurs in patients who have been anesthetized with halothane more than once in a short period of time [ACGIH 1991; Hathaway et al. 1991]. Volunteers exposed to 4,000 ppm halothane exhibited amnesia for word pairs and impaired manual dexterity, while those exposed to 1,000 ppm showed no effects [ACGIH 1991]. A number of epidemiological studies of occupationally exposed populations, primarily operating room personnel, have shown increased risks of spontaneous abortion, premature delivery, involuntary infertility, cancer, diseases of the liver and kidney, and congenital abnormalities in their children [Hathaway et al. 1991]. Some authors point out that the populations in these studies were exposed to other potential reproductive toxins, such as cigarette smoke and other anesthetic gases [ACGIH 1991].

* Signs and symptoms of exposure

1. Acute symptoms: The signs and symptoms of acute exposure to halothane in humans may include redness and tearing of the eyes and central nervous system effects (dizziness, a sense of fatigue, headache, sleepiness, slurred speech, reduced respiratory rate).

2. Chronic symptoms: The signs and symptoms of chronic exposure to halothane may include jaundice, enlarged and tender liver, and reproductive effects (spontaneous abortion, infertility, premature delivery, and congenital abnormalities).

EMERGENCY MEDICAL PROCEDURES

* Emergency procedures:

[NIOSH to supply]

Rescue: Remove an incapacitated worker from further exposure and implement appropriate emergency procedures (e.g., those listed on the Material Safety Data Sheet required by OSHA's Hazard Communication Standard [29 CFR 1910.1200]). All workers should be familiar with emergency procedures, the location and proper use of emergency equipment, and methods of protecting themselves during rescue operations.

EXPOSURE SOURCES AND CONTROL METHODS

The following operations may involve halothane and lead to worker exposures to this substance:

* Use as an inhalation anesthetic

* Manufacture and transportation of halothane

Workers responding to a release or potential release of hazardous substances must be protected as required by paragraph (q) of OSHA's Hazardous Waste Operations and Emergency Response Standard [29 CFR 1910.120].

Methods that are effective in controlling worker exposures to halothane, depending on the feasibility of implementation, are as follows:

* Process enclosure
* Local exhaust ventilation
* General dilution ventilation
* Personal protective equipment

Good sources of information about control methods are as follows:

1. ACGIH [1992]. Industrial ventilation--a manual of recommended practice. 21st ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.

2. Burton DJ [1986]. Industrial ventilation--a self study companion. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.

3. Alden JL, Kane JM [1982]. Design of industrial ventilation systems. New York, NY: Industrial Press, Inc.

4. Wadden RA, Scheff PA [1987]. Engineering design for control of workplace hazards. New York, NY: McGraw-Hill.

5. Plog BA [1988]. Fundamentals of industrial hygiene. Chicago, IL: National Safety Council.

MEDICAL SURVEILLANCE

OSHA is currently developing requirements for medical surveillance. When these requirements are promulgated, readers should refer to them for additional information and to determine which substances require employers to implement medical surveillance procedures.

Medical Screening:

Workers who may be exposed to chemical hazards should be monitored in a systematic program of medical surveillance that is intended to prevent occupational injury and disease. The program should include education of employers and workers about work-related hazards, early detection of adverse health effects, and referral of workers for diagnosis and treatment. The occurrence of disease or other work-related adverse health effects should prompt immediate evaluation of primary preventive measures (e.g., industrial hygiene monitoring, engineering controls, and personal protective equipment). A medical surveillance program is intended to supplement, not replace, such measures. To detect and control work-related health effects, medical evaluations should be performed (1) before job placement, (2) periodically during the term of employment, and (3) at the time of job transfer or termination.

* Preplacement medical evaluation

Before a worker is placed in a job with a potential for exposure to halothane, a licensed health care professional should evaluate and document the worker's baseline health status with thorough medical, environmental, and occupational histories, a physical examination, and physiologic and laboratory tests appropriate for the anticipated occupational risks. These should concentrate on the function and integrity of the central nervous system, cardiovascular system, liver, and reproductive system.

A preplacement medical evaluation is recommended to assess medical conditions that may be aggravated or may result in increased risk when a worker is exposed to halothane at or below the prescribed exposure limit. The health care professional should consider the probable frequency, intensity, and duration of exposure as well as the nature and degree of any applicable medical condition. Such conditions (which should not be regarded as absolute contraindications to job placement) include a history and other findings consistent with diseases of the central nervous system, caradiovascular system, liver, or reproductive system.

* Periodic medical evaluations

Occupational health interviews and physical examinations should be performed at regular intervals during the employment period, as mandated by any applicable Federal, State, or local standard. Where no standard exists and the hazard is minimal, evaluations should be conducted every 3 to 5 years or as frequently as recommended by an experienced occupational health physician. Additional examinations may be necessary if a worker develops symptoms attributable to halothane exposure. The interviews, examinations, and medical screening tests should focus on identifying the adverse effects of halothane on the central nervous system, caradiovascular system, liver, or reproductive system. Current health status should be compared with the baseline health status of the individual worker or with expected values for a suitable reference population.

* Termination medical evaluations

The medical, environmental, and occupational history interviews, the physical examination, and selected physiologic or laboratory tests that were conducted at the time of placement should be repeated at the time of job transfer or termination to determine the worker's medical status at the end of his or her employment. Any changes in the worker's health status should be compared with those expected for a suitable reference population.

* Biological Monitoring

Biological monitoring involves sampling and analyzing body tissues or fluids to provide an index of exposure to a toxic substance or metabolite. No biological monitoring test acceptable for routine use has yet been developed for halothane.

WORKPLACE MONITORING AND MEASUREMENT

Determination of a worker's exposure to airborne halothane is made using an Anasorb 747 tube (140/70 mg sections). Samples are collected at a maximum flow rate of 0.5 liter/minute until a maximum collection volume of 12 liters is reached. The sample is then treated with carbon disulfide. Analysis is conducted by gas chromatography with a flame ionization detector. This method is described in the OSHA Computerized Information System (OSHA Method #103), [OSHA 1992].

PERSONAL HYGIENE PROCEDURES

If halothane contacts the skin, workers should flush the affected areas immediately with plenty of water, followed by washing with soap and water.

Clothing contaminated with halothane should be removed immediately, and provisions should be made for the safe removal of the chemical from the clothing.

A worker who handles halothane should thoroughly wash hands, forearms, and face with soap and water before eating, using tobacco products, using toilet facilities, applying cosmetics, or taking medications.

Workers should not eat, drink, use tobacco products, apply cosmetics, or take medications in areas where halothane or a solution containing halothane is handled, processed, or stored.

STORAGE

Halothane should be stored in a cool, dry, well-ventilated area in tightly sealed containers that are labeled in accordance with OSHA's Hazard Communication Standard [29 CFR 1910.1200]. Opaque, chemically resistant containers should be used for storage. Containers of halothane should be protected from physical damage and should be stored separately from acids, direct sunlight, heat, sparks, and open flame. Because containers that formerly contained halothane may still hold product residues, they should be handled appropriately.

SPILLS AND LEAKS

In the event of a spill or leak involving halothane, persons not wearing protective equipment and clothing should be restricted from contaminated areas until cleanup has been completed. The following steps should be undertaken following a spill or leak:

1. Notify safety personnel.

2. Ventilate the area of the spill or leak.

3. For small spills, take up with sand or other noncombustible absorbent material and place into closed containers for later disposal.

SPECIAL REQUIREMENTS

U.S. Environmental Protection Agency (EPA) requirements for emergency planning, reportable quantities of hazardous releases, community right-to- know, and hazardous waste management may change over time. Users are therefore advised to determine periodically whether new information is available.

* Emergency planning requirements

Halothane is not subject to EPA emergency planning requirements under the Superfund Amendments and Reauthorization Act (SARA) (Title III) [42 USC 11022].

* Reportable quantity requirements for hazardous releases

Although halothane is not specifically listed as a hazardous waste under the Resource Conservation and Recovery (RCRA) [40 USC 6901 et seq.], EPA requires employers to treat waste as hazardous if it exhibits any of the following characteristics: ignitability, corrosivity, reactivity, or toxicity as defined in 40 CFR 261.21- 261.24.

Providing detailed information about the removal and disposal of specific chemicals is beyond the scope of this guideline. The U.S. Department of Transportation, EPA, and State and local regulations should be followed to ensure that removal, transport, and disposal of this substance are conducted in accordance with existing regulations. To be certain that chemical waste disposal meets EPA regulatory requirements, employers should address any questions to the RCRA hotline at (202) 382-3000 (in Washington, D.C.) or toll-free at (800) 424-9346 (outside Washington, D.C.). In addition, relevant State and local authorities should be contacted for information on any requirements they may have for the waste removal and disposal of this substance.

RESPIRATORY PROTECTION

* Conditions for respirator use

Good industrial hygiene practice requires that engineering controls be used where feasible to reduce workplace concentrations of hazardous materials to the prescribed exposure limit. However, some situations may require the use of respirators to control exposure. Respirators must be worn if the ambient concentration of halothane exceeds prescribed exposure limits. Respirators may be used (1) before engineering controls have been installed, (2) during work operations such as maintenance or repair activities that involve unknown exposures, (3) during operations that require entry into tanks or closed vessels, and (4) during emergencies. Workers should only use respirators that have been approved by NIOSH and the Mine Safety and Health Administration (MSHA).

* Respiratory protection program

Employers should institute a complete respiratory protection program that, at a minimum, complies with the requirements of OSHA's Respiratory Protection Standard [29 CFR 1910.134]. Such a program must include respirator selection, an evaluation of the worker's ability to perform the work while wearing a respirator, the regular training of personnel, respirator fit testing, periodic workplace monitoring, and regular respirator maintenance, inspection, and cleaning. The implementation of an adequate respiratory protection program (including selection of the correct respirator) requires that a knowledgeable person be in charge of the program and that the program be evaluated regularly. For additional information on the selection and use of respirators and on the medical screening of respirator users, consult the latest edition of the NIOSH Respirator Decision Logic [NIOSH 1987b] and the NIOSH Guide to Industrial Respiratory Protection [NIOSH 1987a].

PERSONAL PROTECTIVE EQUIPMENT

Workers should use appropriate personal protective clothing and equipment that must be carefully selected, used, and maintained to be effective in preventing skin contact with halothane. The selection of the appropriate personal protective equipment (PPE) (e.g., gloves, sleeves, encapsulating suits) should be based on the extent of the worker's potential exposure to halothane. The resistance of a protective material to permeation by halothane is shown below:

(*) Materials with breakthrough times of <1 hr are not recommended for use against halothane.

To evaluate the use of this material with halothane, users should consult the best available performance data and manufacturers' recommendations. Significant differences have been demonstrated in the chemical resistance of generically similar PPE materials (e.g., butyl) produced by different manufacturers. In addition, the chemical resistance of a mixture may be significantly different from that of any of its neat components.

Any chemical-resistant clothing that is used should be periodically evaluated to determine its effectiveness in preventing dermal contact. Safety showers and eye wash stations should be located close to operations that involve halothane.

Splash-proof chemical safety goggles or face shields (20 to 30 cm long, minimum) should be worn during any operation in which a solvent, caustic, or other toxic substance may be splashed into the eyes.

In addition to the possible need for wearing protective outer apparel (e.g., aprons, encapsulating suits), workers should wear work uniforms, coveralls, or similar full-body coverings that are laundered each day. Employers should provide lockers or other closed areas to store work and street clothing separately. Employers should collect work clothing at the end of each work shift and provide for its laundering. Laundry personnel should be informed about the potential hazards of handling contaminated clothing and be instructed about measures to minimize their health risk.

Protective clothing should be kept free of oil and grease and should be inspected and maintained regularly to preserve its effectiveness.

Protective clothing may interfere with the body's heat dissipation, especially during hot weather or during work in hot or poorly ventilated work environments.

REFERENCES

ACGIH [1991]. Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.

ACGIH [1994-1995]. Threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.

CFR. Code of Federal regulations. Washington, DC: U.S. Government Printing Office, Office of the Federal Register.

Forsberg K, Mansdorf SZ [1993]. Quick selection guide to chemical protective clothing. New York, NY: Van Nostrand Reinhold.

Genium [1990]. Material safety data sheet No. 699. Schenectady, NY: Genium Publishing Corporation.

Hathaway GJ, Proctor NH, Hughes JP, and Fischman ML [1991]. Proctor and Hughes' chemical hazards of the workplace. 3rd ed. New York, NY: Van Nostrand Reinhold.

IARC [1987]. IARC monographs on the evaluation of carcinogenic risks to humans. Volumes 1 to 42, Supplement 7. Lyon, France: World Health Organization, International Agency for Research on Cancer.

Lewis RJ, ed. [1993] Hawley's condensed chemical dictionary. 12 ed. New York, NY: Van Nostrand Reinhold Company.

Mickelsen RL, Hall RC [1987]. A breakthrough time comparison of nitrile and neoprene glove materials produced by different glove manufacturers. Am Ind Hyg Assoc J 48(11): 941-947.

Mickelsen RL, Hall RC, Chern RT, Myers JR [1991]. Evaluation of a simple weight-loss method for determining the permeation of organic liquids through rubber films. Am Ind Hyg Assoc J 52(10): 445-447.

NFPA [1986]. Fire protection guide on hazardous materials. 9th ed. Quincy, MA: National Fire Protection Association.

NIOSH [1993]. Registry of toxic effects of chemical substances: Halothane. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Insititute for Occupational Safety and Health, Division of Standards Development and Technology Transfer, Technical Information Branch.

NIOSH [1992]. Recommendations for occupational safety and health: Compendium of policy documents and statements. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health. DHHS (NIOSH) Publication No. 92-100.

NIOSH [1987a]. NIOSH guide to industrial respiratory protection. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 87-116.

NIOSH [1987b]. Respirator decision logic. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 87-108.

OSHA [1992]. Computerized information system. Washington, DC: U.S. Department of Labor, Occupational Safety and Health Administration.

Patnaik, P [1992]. A comprehensive guide to the hazardous properties of chemical substances. New York, NY: Van Nostrand Reinhold.

Sax NI, Lewis RJ [1989]. Dangerous properties of industrial materials. 7th ed. New York, NY: Van Nostrand Reinhold Company.

Sittig M [1991]. Handbook of toxic and hazardous chemicals. 3rd ed. Park Ridge, NJ: Noyes Publications.

USC. United States code. Washington. DC: U.S. Government Printing Office.

Windholz M. ed. [1983]. Merck Index. 10th ed. Rahway, NJ: Merck & Company.