Disclaimer: The information contained in these guidelines is intended for reference purposes only. It provides a summary of information about chemicals that workers may be exposed to in their workplaces. The information contained in these guidelines is current as of date of publication (September, 1996); recommendations may be superseded by new developments in the field of industrial hygiene. Readers are therefore advised to regard these recomendations as general guidelines and to determine whether new information is available.

OCCUPATIONAL SAFETY AND HEALTH GUIDELINE FOR TRIMELLITIC ANHYDRIDE

INTRODUCTION

This guideline summarizes pertinent information about trimellitic anhydride 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 Recommendations may be superseded by new developments in these fields; readers are therefore advised to regard these recommendations as general guidelines and to determine whether new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

C(9)H(4)O(5)

* Structure

(For Structure, see paper copy)

* Synonyms

Anhydrotrimellitic acid; 1,3-dihydro-1,3-dioxo-5-isobenzofurancarboxylic acid; trimellitic acid anhydride; TMA; TMAN

* Identifiers

1. CAS No.: 552-30-7

2. RTECS No.: DC2050000

3. Specific DOT number: None.

4. Specific DOT label: None.

* Appearance and odor

Trimellitic anhydride is a white and thinly flaked crystalline solid.

CHEMICAL AND PHYSICAL PROPERTIES

* Physical data

1. Molecular weight: 192.13

2. Boiling point (at 14 mm Hg): 240 degrees C (464 degrees F)

3. Specific gravity: Data not available.

4. Vapor density: Data not available.

5. Melting point: 161 degrees to 163.5 degrees C (322 degrees to 326 degrees F)

6. Vapor pressure at 20 degrees C (68 degrees F): 4.0 X 10 (-6) mm Hg

7. Solubility: Slightly soluble in carbon tetrachloride, ligroin, mixed xylenes; soluble in dimethylformamide, acetone, and ethyl acetate.

8. Evaporation rate: Data not available.

* Reactivity

1. Conditions contributing to instability: None reported.

2. Incompatibilities: None reported.

3. Hazardous decomposition products: None reported.

4. Special precautions: None reported.

* Flammability

The National Fire Protection Association has not assigned a flammability rating to trimellitic anhydride. Other sources rate trimellitic anhydride as combustible when this substance is exposed to heat or open flame.

1. Flash point: Data not available.

2. Autoignition temperature: Data not available.

3. Flammable limits in air: Data not available.

4. Extinguishant: Use dry chemical, carbon dioxide, water spray, or foam to fight fires involving trimellitic anhydride.

Fires involving trimellitic anhydride 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 trimellitic anhydride.

EXPOSURE LIMITS

* OSHA PEL

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

* NIOSH REL

The National Institute for Occupational Safety and Health (NIOSH) has established a recommended exposure limit (REL) for trimellitic anhydride of 0.005 part per million (ppm) parts of air (0.04 milligrams per cubic meter (mg/m³)) as a TWA for up to a 10-hour workday and a 40-hour workweek [NIOSH 1992].

* ACGIH TLV

The American Conference of Governmental Industrial Hygienists (ACGIH) has assigned trimellitic anhydride a ceiling limit value of 0.04 mg/m³, which should not be exceeded during any part of the working exposure [ACGIH 1994, p. 35].

* Rationale for Limits

The NIOSH limit is based on the risk of pulmonary edema, immunologic sensitization, and pulmonary, eye, nose, and skin irritation [NIOSH 1992].

The ACGIH limit is based on the risk of sensitization [ACGIH 1991, p. 1643].

HEALTH HAZARD INFORMATION

* Routes of Exposure

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

* Summary of toxicology

1. Effects on Animals: Trimellitic anhydride is an irritant and sensitizing agent in experimental animals. Trimellitic anhydride is a severe ocular irritant that has produced ocular burns in the rabbit eye [ACGIH 1991]. The oral LD(50) in rats is 5,600 mg/kg [NIOSH 1991]. No deaths or adverse effects were observed in rats exposed to 950 ppm for four hours [ACGIH 1991]. Rats are the most sensitive species examined to the sensitizing effects of trimellitic anhydride [ACGIH 1991]. A single six hour inhalation exposure to 0.001 ppm trimellitic anhydride has caused sensitization in rats [ACGIH 1991]. In an inhalation study, rats were exposed to 0, 0.0003, 0.002, or 0.006 ppm for 6 hours/day, 5 days/week for 6.5 or 13 weeks [ACGIH 1991]. These repeated exposures resulted in a concentration-related increase in focal pulmonary hemorrhage, microscopic alveolar hemorrhage, pulmonary edema, and lobular bronchopneumonia [ACGIH 1991]. A feeding study exposing rats to 1,000, 5,000, and 10,000 ppm trimellitic anhydride in the diet for 90 days resulted in no deaths [Rom 1992]. The only adverse effect reported was leukocytosis beginning at a dose of 5,000 ppm [Rom 1992]. Trimellitic anhydride was not mutagenic in the Ames assay [Rom 1992].

2. Effects on Humans: Trimellitic anhydride is an irritant and a sensitizing agent which can affect the respiratory system and blood. Trimellitic anhydride is irritating to the respiratory tract, eyes, and skin [ACGIH 1991]. Repeated exposures can result in the development of an allergic reaction [ACGIH 1991]. Three different immune mediated syndromes have been described in workers exposed to trimellitic anhydride. The first condition is an asthma-rhinitis syndrome which consists of an immediate-onset asthma and allergic rhinitis that is mediated by immunoglobulin E [Rom 1992]. The second syndrome is late respiratory systemic syndrome which is a hypersensitivity pneumonitis-like reaction followed by a flu-like syndrome 4 to 12 hours after exposure; this syndrome is associated with moderate exposures [Rom 1992]. The third syndrome is pulmonary disease anemia characterized by dyspnea, hemoptysis, pulmonary infiltrates, restrictive lung function, and hemolytic anemia; this syndrome primarily develops in workers exposed to high levels of trimellitic anhydride [Rom 1992].

* Signs and symptoms of exposure

1. Acute exposure: Acute symptoms of exposure to trimellitic anhydride may include irritation of mucous membranes, cough, and rhinorrhea [Hathaway et al. 1991].

2. Chronic exposure: Following sensitization to trimellitic anhydride, symptoms may include rhinitis, wheezing, dyspnea, malaise, chills, fever, and aching muscles and joints. In addition, hemoptysis, compromised respiratory function, hypoxemia, and anemia may be observed [Hathaway et al. 1991].

EMERGENCY MEDICAL PROCEDURES

* Emergency medical procedures: [NIOSH to supply]

5. 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 trimellitic anhydride and lead to worker exposures to this substance:

* The manufacture and transportation of trimellitic anhydride
* Use in the preparation of resins, dyes, adhesives, polymers, and printing inks
* Use as a plasticizer and chemical intermediate
* Use in agricultural chemicals and pharmaceuticals

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

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

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

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 whether employers whose employees are exposed to trimellitic anhydride are required 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 trimellitic anhydride, 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 respiratory system. Medical surveillance for respiratory disease should be conducted using the principles and methods recommended by the American Thoracic Society.

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 trimellitic anhydride 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 respiratory 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 trimellitic anhydride exposure. The interviews, examinations, and medical screening tests should focus on identifying the adverse effects of trimellitic anhydride on the respiratory 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 trimellitic anhydride.

WORKPLACE MONITORING AND MEASUREMENT

Determination of a worker's exposure to airborne trimellitic anhydride is made using two coated glass fiber filters (37 mm). The filters are coated with 10 mg veratryaminne and 10 mg di-n-octylphthalate. Samples are collected at a maximum flow rate of 2 liters/minute until a maximum collection volume of 480 liters is reached. The sample is then treated with 0.02N ammonium hydroxide. Analysis is conducted by high performance liquid chromatography using an ultraviolet detector (HPLC/UV). This method (OSHA 98) is described in the OSHA Computerized Information System [OSHA 1994] and is fully validated. NIOSH also has a published method for the sampling of trimellitic anhydride. This method requires sample collection on a 0.8 micron PVC-copolymer filter. The analysis is performed by gas chromatography using a flame ionization detector (GC/FID). This method (Method No. 5036) is described in the NIOSH manual of analytical methods [NIOSH 1994].

PERSONAL HYGIENE PROCEDURES

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

Clothing contaminated with trimellitic anhydride should be removed immediately, and provisions should be made for the safe removal of the chemical from the clothing. Persons laundering the clothes should be informed of the hazardous properties of trimellitic anhydride, particularly its potential for causing sensitization.

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

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

STORAGE

Trimellitic anhydride 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]. Containers of trimellitic anhydride should be protected from physical damage and should be stored separately from incompatible chemicals.

SPILLS AND LEAKS

In the event of a spill or leak involving trimellitic anhydride, 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. Do not touch the spilled material; stop the leak if it is possible to do so without risk.

2. Notify safety personnel.

3. Remove all sources of heat and ignition.

4. For small dry spills, use a clean shovel and place the material into a clean, dry, acid-resistant or plastic recovery container; cover and remove the container from the spill area.

5. For small liquid spills or residual solids, soda ash or sodium bicarbonate and water can be used to neutralize the material.

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

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

* Reportable quantity requirements for hazardous releases

A hazardous substance release is defined by EPA as any spilling, leaking, pumping, pouring, emitting, emptying, discharging, injecting, escaping, leaching, dumping, or disposing into the environment (including the abandonment or discarding of contaminated containers) of hazardous substances. In the event of a release that is above the reportable quantity for that chemical, employers are required to notify the proper Federal, State, and local authorities [40 CFR 355.40].

Employers are not required by the emergency release notification provisions in 40 CFR Part 355.40 to notify the National Response Center of an accidental release of trimellitic anhydride; there is no reportable quantity for this substance.

* Community right-to-know requirements

Employers are not required by EPA in 40 CFR Part 372.30 to submit a Toxic Chemical Release Inventory form (Form R) to EPA reporting the amount of trimellitic anhydride emitted or released from their facility annually.

* Hazardous waste management requirements

EPA considers a waste to be hazardous if it exhibits any of the following characteristics: ignitability, corrosivity, reactivity, or toxicity as defined in 40 CFR 261.21-261.24. Under the Resource Conservation and Recovery Act (RCRA) [40 USC 6901 et seq.], EPA has specifically listed many chemical wastes as hazardous. Although trimellitic anhydride is not specifically listed as a hazardous waste under RCRA, EPA requires employers to treat waste as hazardous if it exhibits any of the characteristics discussed above.

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 (703) 412-9810 (in the Washington, D.C. area) 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 trimellitic anhydride 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 trimellitic anhydride. 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 trimellitic anhydride. There are no published reports on the resistance of various materials to permeation by trimellitic anhydride.

To evaluate the use of PPE materials with trimellitic anhydride, 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 trimellitic anhydride.

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

ATS [1987]. Standardization of spirometry -- 1987 update. American Thoracic Society. Am Rev Respir Dis 136:1285-1296.

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

Genium [1990]. Material safety data sheet No. 330. 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.

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.

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]. NIOSH 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.

NIOSH [1991]. Registry of toxic effects of chemical substances: Trimellitic anhydride. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute 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 [1994]. NIOSH manual of analytical methods. 4th ed. 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. 94-113.

NJDH [1986]. Hazardous substance fact sheet: Trimellitic anhydride. Trenton, NJ: New Jersey Department of Health.

NLM [1992]. Hazardous substances data bank: Trimellitic anhydride. Bethesda, MD: National Library of Medicine.

OSHA [1994]. Computerized information system. Washington, DC: U.S. Department of Labor, Occupational Safety and Health Administration.

Parmeggiani L [1983]. Encyclopedia of occupational health and safety. 3rd rev. ed. Geneva, Switzerland: International Labour Organisation.

Rom WN [1992]. Environmental and occupational medicine. 2nd ed. Boston, MA: Little, Brown and 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.

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