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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 71



    TRIMELLITIC ANHYDRIDE
    HEALTH AND SAFETY GUIDE








    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION





    WORLD HEALTH ORGANIZATION, GENEVA 1992

    Published by the World Health Organization for the International
    Programme on Chemical Safety (a collaborative programme of the
    United Nations Environment Programme, the International Labour
    Organisation, and the World Health Organization)

    This report contains the collective views of an international group
    of experts and does not necessarily represent the decisions or the
    stated policy of the United Nations Environment Programme, the
    International Labour Organisation, or the World Health Organization

    WHO Library Cataloguing in Publication Data

    Trimellitic anhydride : health and safety guide.

    (Health and safety guide ; no. 71)

    1. Phthalic anhydrides - adverse effects
    2. Phthalic anhydrides - standards
    3. Phthalic anhydrides - toxicity
    4. Accidents, Occupational - prevention & control
    5. Environmental exposure
    6. Occupational diseases - chemically induced
    I.Series

    ISBN 92 4 151071 4          (NLM Classification: QD 341.A2)
    ISSN 0259-7268

    The World Health Organization welcomes requests for permission to
    reproduce or translate its publications, in part or in full. 
    Applications and enquiries should be addressed to the Office of
    Publications, World Health Organization, Geneva, Switzerland, which
    will be glad to provide the latest information on any changes made
    to the text, plans for new editions, and reprints and translations
    already available.

    (c) World Health Organization 1992

    Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention.  All rights reserved.

    The designations employed and the presentation of the material in
    this publication do not imply the expression of any opinion
    whatsoever on the part of the Secretariat of the World Health
    Organization concerning the legal status of any country, territory,
    city or area or of its authorities, or concerning the delimitation
    of its frontiers or boundaries.

    The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar
    nature that are not mentioned.  Errors and omissions excepted, the
    names of proprietary products are distinguished by initial capital
    letters.

    CONTENTS

    INTRODUCTION

    1. PRODUCT IDENTITY AND USES
         1.1. Identity
         1.2. Physical and chemical properties
         1.3. Composition
         1.4. Analytical methods
         1.4. Production and uses

    2. SUMMARY AND EVALUATION
         2.1. Exposure to trimellitic anhydride
         2.2. Absorption, metabolism, and excretion
         2.3. Fate in the environment and effects on organisms
         2.4. Effects on animals
              2.4.1. Acute toxicity
              2.4.2. Short-term toxicity
              2.4.3. Long-term toxicity
         2.5. Effects on human beings

    3. CONCLUSIONS AND RECOMMENDATIONS
         3.1. Conclusions
         3.2. Recommendations

    4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY
         ACTION

         4.1. Main human health hazards, prevention and protection,
              first aid
              4.1.1. Surveillance
              4.1.2. First aid
         4.2. Advice to physicians
         4.3. Explosion and fire hazards
         4.4. Storage and transport
         4.5. Spillage
         4.6. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. SUMMARY OF CHEMICAL SAFETY INFORMATION

    7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
         7.1. Previous evaluations by international bodies
         7.2. Exposure limit values
         7.3. Specific restrictions
         7.4. Transport and labelling

    BIBLIOGRAPHY
    

    INTRODUCTION

    This Health and Safety Guide is not based on an existing
    Environmental Health Criteria document, but on critical national
    reviews.  The hazard evaluation in the Health and Safety Guide was
    made on the basis of carefully selected studies, after scrutiny of
    the original publications.

    In order to assist the peer-review process of the present Health and
    Safety Guide, a background companion document was prepared by the
    IPCS and can be obtained from the Director on request;  the IPCS
    does not intend that the background document should be published.

    The first three sections of this Health and Safety Guide present
    essential technical information and the hazard evaluation.  Section
    4 includes advice on preventive and protective measures and
    emergency action; health workers should be thoroughly  familiar with
    the medical information to ensure that they can act efficiently in
    an emergency.  The section on regulatory information has been
    extracted from the legal file of the International Register of
    Potentially Toxic Chemicals (IRPTC) and from other United Nations
    sources.

    The target readership includes occupational health services, those
    in ministries, governmental agencies, industry, and trade unions who
    are involved in the safe use of chemicals and the avoidance of
    environmental health hazards, and those wanting more information on
    this topic.  An attempt has been made to use only terms that will be
    familiar to the intended user.  However, sections 1 and 2 inevitably
    contain some technical terms.

    Revision of the information in this Guide will take place in due
    course, and the eventual aim is to use standardized terminology. 
    Comments on any difficulties encountered in using the Guide would be
    very helpful and should be addressed to:

    The Director
    International Programme on Chemical Safety
    World Health Organization
    1211 Geneva 27
    Switzerland

    THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING
    POINT TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME

    1.  PRODUCT IDENTITY AND USES

    1.1  Identity

    Chemical formula:        C9H4O5

    Chemical structure:

    CHEMICAL STRUCTURE 1

    Common name:             trimellitic anhydride

    Common synonyms:         anhydro trimellitic acid; 
                             1,2,4-benzenetricarboxylic acid
                             1,2-anhydride; 1,2,4-benzenetricarboxylic
                             anhydride; 4-carboxyphthalic anhydride;
                             1,3-dioxo-5-phthalancarboxylic acid;
                             5-phthalancarboxylic acid, 1,3-dioxo-TMAN;
                             trimellitic acid 1,2-anhydride; TMA;a
                             TMAN

    IUPAC systematic name:   1,3-dihydro-1,3-dioxo-5-isobenzofuran-
                             carboxylic acid

    CAS registry number:     552-30-7

    RTECS registry number:   DC2050000

    Conversion factor:       1 mg/m3 aprox. 0.13 ppm

    Relative molecular mass: 192.12


            

    a TMA is also an acronym for i.a. trimethylamine.


    1.2  Physical and chemical properties

    Trimellitic anhydride is a white solid in the form of flakes. It is
    readily hydrolysed in water to trimellitic acid, which is moderately
    soluble in water. Trimellitic anhydride is readily soluble in
    acetone, cyclohexanone, 2-butane, ethyl acetate, and dimethyl
    formamide (from 49.6 to 15.5% w/w at 25 C).

    Trimellitic anhydride reacts with alcohols forming the corresponding
    esters.  Reactions with ammonia yield amides, imides, and
    amide-imides.

    Flaked or molten trimellitic anhydride will burn if ignited,
    producing an explosive dust.  Similarly, the vapour from molten
    trimellitic anhydride forms dangerously explosive mixtures with air. 

    Some additional physical and chemical properties are given in the
    Summary of Chemical Safety Information (see section 6).

    1.3  Composition

    The purity of commercial trimellitic anhydride is greater than 99%.

    1.4  Analytical methods

    Airborne trimellitic anhydride can be sampled on various adsorbents,
    such as cellulose ester membrane filter, glass fibre filter, or PVC
    membrane.  It can be determined by high performance liquid
    chromatography (HPLC), gas chromatography, or polarography.  HPLC
    allows the accurate measurement of as little as 0.1 g trimellitic
    anhydride.

    1.5  Production and uses

    Trimellitic anhydride has been produced since the 1960s.  Production
    was estimated to be 50 000 tonnes per annum in 1990.

    The preparation of trimellitic anhydride is based on the
    liquid-phase air-oxidation of pseudocumene to form trimellitic acid,
    this being subsequently dehydrated.  An alternative process consists
    of heating crude trimellitic acid with vanadium pentoxide.

    Trimellitic anhydride is a very reactive chemical of low relative
    molecular mass.  Many of its industrial uses depend on the
    reactivity of the anhydride group.  It is mainly used in the
    synthesis of trimellitate esters.  These esters are used as
    plasticizers for polyvinyl chloride, especially when temperature
    stability is required, e.g., in wire and cable coatings. 
    Trimellitic anhydride esters are less volatile and less water

    soluble than corresponding phthalates, and have begun to replace
    them in some applications, e.g., car interior linings.  An important
    use for trimellitic anhydride polymers is in the production of the
    wire enamels used to coat magnetic wire or for other applications
    where high thermal resistance is required.

    Trimellitic anhydride is also used in the production of polyester
    resins for water-based and conventional solvent-based coatings and
    paints, to make resins for electrodeposition and powder coatings,
    and as a binder for glass fibres, sand, and other aggregates.

    In addition, trimellitic anhydride is used as an embossing agent for
    foam-backed vinyl flooring and as a curing agent for epoxy and other
    resins. It is also used as a plasticizer in materials used to store
    and cover food and in the synthesis of various anticorrosive surface
    coatings, agricultural chemicals, and pharmaceutical products.

    2.  SUMMARY AND EVALUATION

    2.1  Exposure to trimellitic anhydride

    Exposure to trimellitic anhydride occurs in many different
    occupational settings; 20 000 workers are known to be exposed
    through manufacturing and use in the USA and the worldwide total is
    considerably greater. Exposure occurs mainly by inhalation of dust
    or fumes. Since trimellitic anhydride has a very low vapour pressure
    at room temperature, extensive exposure occurs mainly when dust is
    generated from the powder, by mixing or spraying, or by inhalation
    of the fumes generated during processes requiring high temperature,
    e.g., oven curing. Exposure to very high levels of trimellitic
    anhydride fumes occurs when heated metal surfaces are sprayed with
    anticorrosive materials containing trimellitic anhydride-based
    compounds. High levels of trimellitic anhydride dust are found in
    bagging areas.

    Exposure of the general population to trimellitic anhydride is
    possible, for example, around industrial plants, through its use in
    food storage and protection materials, from car interior linings,
    and during transportation of the compound. However, the likelihood
    of exposure from these sources is very low. When trimellitate
    plasticizers are used, trimellitic anhydride itself is not present,
    but rather its ester derivatives; these are stable and do not
    migrate. There are no reports of populations being affected in the
    vicinity of industrial sites.

    2.2  Absorption, metabolism, and excretion

    In a distribution study, rats were exposed through inhalation to
    950 g 14C-labelled trimellitic anhydride/m3 for 45 minutes.
    Treated rats were sacrificed at intervals ranging from 3 hours to 32
    days. Maximum concentrations of 14C in all tissues occurred 3 hours
    after exposure; these levels then declined in all tissues, except
    for the lymph nodes associated with the lung, where there was an
    initial decline followed by a second increase, peaking at the eighth
    day and then declining.

    There is no information on metabolism. Trimellitic anhydride reacts
    with the free amino groups on proteins to form conjugates.

    2.3  Fate in the environment and effects on organisms

    There is very limited information on the fate and effects of
    trimellitic anhydride in the environment. However, exposure is
    expected to be very low, except from spills and accidents.

    In a laboratory degradation study, more than 60% of the theoretical
    quantity of carbon dioxide was generated in 10 days.  Hydrolysis of
    the anhydride was not checked during the study.  Trimellitic
    anhydride can thus be considered as readily degradable by by
    bacteria.  Data on aquatic toxicity, e.g., on fish species, are not
    yet available

    2.4  Effects on animals

    2.4.1  Acute toxicity

    The acute toxicity of trimellitic anhydride for experimental animals
    is low. For the mouse, the most susceptible species, the oral LD50
    was 1300 mg/kg body weight. Treated mice showed gastrointestinal
    mucosal irritation, with hyperaemia and haemorrhage; in some cases,
    perforations were noted.  For the rat, the oral LD50 was 2730 mg/kg
    body weight, and the dermal LD50 was estimated to be greater than
    2000 mg/kg body weight.

    A single application of trimellitic anhydride (TMA) to rabbit skin
    resulted in mild dermatitis. TMA caused severe irritation to the
    eyes of rabbits, leading to corrosive lesions and chemical burns in
    the cornea.

    2.4.2  Short-term toxicity

    Animal inhalation studies, for 2-13 weeks, have shown a clear
    correlation between TMA exposure and the occurrence of lung damage.
    The development of lung injury is concurrent with a rise in antibody
    levels in the products of broncho-alveolar lavage and in serum.
    There are marked species differences in susceptibility to
    trimellitic anhydride-induced respiratory sensitization. In one
    recent study, the rat appeared to be the most sensitive experimental
    animal. No sensitization response was observed on challenge 3 weeks
    after a 6-hour exposure at 1.6 g TMA/m3, but sensitization was
    seen after exposure at 7.7 g/m3.  Repeated respiratory exposure to
    TMA resulted in dose-related focal haemorrhagic areas in the lungs,
    with oedema and lobular bronchopneumonia.

    An unusual finding in a 13-week rat inhalation study was the
    apparent development of tolerance to TMA during the study, as
    indicated by reductions in antibody titres and the prevalence of
    lung lesions. The results suggest adaptation in rats to TMA after
    short-term continuous exposure (Leach et al. 1989).

    Repeated skin applications of TMA in guinea-pigs induce significant
    dermal sensitization reactions. 

    Conjugates formed between protein groups and trimellitic anhydride
    are able to trigger an allergic response.

    Data on genotoxicity and reproductive toxicity are limited; the only
    results available on genetic toxicity are those from Ames tests,
    which were negative. No developmental toxicity was recorded in a
    teratology screeningstudy on pregnant mice. However, trimellitic
    anhydride-specific antibody can be transferred from mother to fetus
    in rats and guinea-pigs.

    2.4.3  Long-term toxicity

    There are no data on which the long-term toxicity or carcinogenicity
    of TMA can be assessed.

    2.5  Effects on human beings

    Trimellitic anhydride dust or fumes are highly irritating to the
    eyes and respiratory system. The dust may cause corrosive eye
    damage, and frequent exposure can lead to respiratory sensitization,
    with, in rare cases, quite severe symptoms. Trimellitic anhydride
    can produce skin irritation following prolonged or repeated
    exposure.

    TMA is a potent respiratory sensitizer; it has caused
    immunologically-mediated respiratory illness in 29% of workers,
    exposed prior to 1979 to levels considerably above the present
    threshold limit value. The period from 1979 to 1985 was
    characterized by implementation of control measures to reduce
    exposure to TMA in the workplace. These measures clearly resulted in
    a marked decrease in both clinical symptoms and levels of TMA
    antibody formation.

    Four clinical syndromes have been identified.  Three of these
    syndromes are associated with immunological reactions.  The first is
    an  immediate type airway response characterized by asthma or
    rhinitis, or both.  These symptoms only occur when individuals are
    sensitized following a latent period of exposure, which may be weeks
    or years.  Once sensitization is acquired, symptoms occur within
    seconds or minutes of exposure.  The syndrome is associated with an
    increase in antibody levels.

    The second form, the  late respiratory systemic syndrome, often
    termed "TMA-flu", also requires a latent period of exposure for
    sensitization.  It is characterized by a delayed onset of symptoms
    after exposure, such as coughing and wheezing that  occur 4-12 hours
    after exposure to trimellitic anhydride;  however, the syndrome also
    includes muscle and joint pains, and fever.  High levels of
    antibodies are also associated with this syndrome.

    The most severe and rare reaction is the  pulmonary-disease-anaemia
     syndrome, which may lead to respiratory failure.  No fatal cases
    have been reported.  This illness has appeared only after exposures
    to high concentrations of trimellitic anhydride fumes, from the
    heating of materials containing trimellitic anhydride, for
    relatively short periods.  The symptoms vary in severity and may
    include cough, with blood-stained sputum, and breathlessness,
    resulting in severe pathological changes in the lung.  The disease
    also requires a latent period of exposure before the onset of
    symptoms and it is characterized by high serum antibody levels. 
    These symptoms are, however, reversible after trimellitic anhydride
    exposure has ceased.

    The fourth respiratory syndrome is a  non-immunological irritant
     reaction to trimellitic anhydride characterized by a transient
    irritation in the upper airways, with lacrimation and rhinorrhoea. 
    The irritant symptoms are related to exposure level and can occur in
    any worker after a single high-level exposure to trimellitic
    anhydride powder or fumes.

    Descriptions of the human syndromes are summarized in Table 1.


        Table 1. Characteristics of syndromes in humans related to the inhalation of trimellitic anhydridea

                                                                                                                              

                                                                    Syndrome
                                                                                                                              

    Characteristic            Rhinitis and immediate-   Late respiratory systemic    Pulmonary disease-   Irritant syndrome
                              type asthma               syndrome                     anaemia              
                                                                                                                              

    Latent period (duration   Months to years of        Months to years of           Weeks to months      Occurs on first high-
    of work exposure prior    work exposure             work exposure                of work exposure     level exposure
    to onset of symptoms

    Onset of symptoms         Immediate (minutes)       4-12 hours                   Progressive with     Variable, depending
    after work exposure                                                              further work         on exposure
                                                                                     exposure

    Type/degree of exposure   TMA dust or fumes/        TMA dust or fumes/           TMA fumes/high       Fumes or dust/high
                              mild                      moderate
                                                                                                                              

    a  From Zeiss et al. (1982).
    

    3.  CONCLUSIONS AND RECOMMENDATIONS

    3.1  Conclusions

    Trimellitic anhydride is extensively used in industry throughout the
    world. It is hazardous to human health in the workplace. Exposure
    may result in irritant and/or sensitization respiratory effects,
    ranging from mild to severe. It is a mild irritant and sensitizer to
    the skin, and corrosive to the eye. Eye damage is frequently
    irreversible.

    Trimellitic anhydride-related immune response and illness can be
    reduced with proper workplace control.

    Flaked or molten trimellitic anhydride will burn if ignited,
    producing an explosive dust. The vapour from molten trimellitic
    anhydride forms dangerously explosive mixtures with air.

    3.2  Recommendations

    (a) This compound should be handled strictly in accordance with safe
    work and good-housekeeping practices. If these are not feasible, the
    use of less hazardous alternatives to TMA should be considered.

    (b) Since trimellitic anhydride is a respiratory sensitizer, some
    response in previously sensitized workers may occur even at the
    recommended threshold limit value (TLV); exposure to TMA in the
    workplace should, therefore, be kept as low as possible.

    (c) Workers with a previous history of asthma or allergies should
    not be exposed to trimellitic anhydride. It is advisable to have a
    pre-employment chest X-ray.

    (d) Pre-employment and subsequent periodic medical surveillance
    should be carried out, including the determination of antibody
    levels and careful examination of eyes, respiratory tract, and skin.

    4.  HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY
        ACTION

    4.1  Main human health hazards, prevention and protection, first aid

    Since the packaging and handling of trimellitic anhydride can result
    in exposure, procedures for diminishing worker exposures to
    trimellitic anhydride are essential.  In the work area, closed
    systems with continuous ventilation should be used, or, if not
    feasible, mechanical ventilation and local exhaust should be
    installed.  If ventilation is insufficient to maintain exposures
    below the recommended limit, a full face-piece, cartridge respirator
    is required as the minimum protection.  A combination type cartridge
    may be used for dust or fume concentrations up to 50 times the
    recommended exposure limit.  For higher concentrations, an
    air-supplied, full face-piece respirator is required.  Overalls or
    other appropriate clothing, chemical goggles, and gloves must be
    worn by persons engaged in work that  results in direct contact with
    trimellitic anhydride.  Contaminated clothing should be removed and
    thoroughly cleaned and dried before reuse.  High dust concentration
    may form a flammable or explosive mixture with air and should be
    avoided.  Dry dust can be charged electrostatically by turbulence,
    pneumatic transport, pouring, and in exhaust ducts and during
    transportation. Build-up of electrostatic charges should be
    prevented by grounding.

    Users of TMA should consult the manufacturers with regard to
    appropriate and effective exhaust ventilation, and precautions to be
    followed when using the compound.

    4.1.1  Surveillance

    Antibody titres should be determined in workers exposed to
    trimellitic anhydride every 6 months.

    4.1.2  First aid

    In the case of exposure to TMA, medical attention should be sought
    immediately; in the meantime, render first aid. Move the patient to
    fresh air, remove contaminated clothing. Wash contaminated skin with
    soap and water and provide artificial respiration if necessary. In
    the case of splashes in the eyes, irrigate the eyes with plenty of
    water for 15 minutes. If large amounts are ingested, vomiting should
    not be in induced, to avoid the potential complication of aspiration
    pneumonitis.

    4.2  Advice to physicians

    No specific antidote is known. General symptomatic and supportive
    therapy is indicated, depending on the system affected: respiratory
    system, eyes, or skin.

    4.3  Explosion and fire hazards

    Trimellitic anhydride is not readily combustible.  However, high
    dust concentrations have a potential for combustion or explosion. 
    Trimellitic anhydride forms an explosive mixture with air; the lower
    and upper explosive limits are 1% and 7%, respectively.  Care should
    be taken to keep dust concentrations low and to prevent ignition. 
    High-voltage static electricity build-up is possible when
    significant quantities of dust are present.

    In the event of a fire, use water fog, foam, or dry chemical. 
    Personnel should wear full protective clothing and breathing
    apparatus.

    4.4  Storage and transport

    Containers of trimellitic anhydride should be protected from
    physical damage to prevent any leakage of the contents.  The
    substance should be stored in well-ventilated areas.

    During transport, containers should be sound and well sealed to
    prevent loss of contents.

    4.5  Spillage

    Spills should be carefully swept or gathered up to avoid producing
    dust and transferred to a sealable container. Alternatively, an
    approved high-efficiency vacuum may be used, fitted with
    high-efficiency (HEPA) filters, so that very fine dust will not be
    blown through the filters and become airborne.  Subsequently, flush
    the area with water. Liquid spills should be absorbed with earth or
    sand and collected for disposal.  Persons involved in cleaning up
    spills should be adequately protected against eye contact and
    inhalation of the powder.  The fire brigade should be called to deal
    with a large spill.

    4.6  Disposal

    Waste should be disposed of in an approved landfill site or in a
    suitable incinerator, unless directed otherwise by local
    authorities.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    Exposure of organisms in the environment to trimellitic anhydride is
    expected to be very low, except in the case of accidents or spills.
    A laboratory study suggests that trimellitic anhydride is readily
    degraded by bacteria.  Data on aquatic toxicity, e.g., on fish
    species, are not yet available.

    6.  SUMMARY OF CHEMICAL SAFETY INFORMATION

          This summary should be easily available to all health workers
          concerned with, and users of, trimellitic anhydride. It should
          be displayed at, or near, entrances to areas where there is
          potential exposure to trimellitic anhydride, and on processing
          equipment and containers.  The summary should be translated
          into the appropriate language(s).  All persons potentially
          exposed to the chemical should also have the instructions in
          the summary clearly explained.

          Space is available for insertion of the National Occupational
          Exposure Limit, the address and telephone number of the
          National Poison Control Centre, and local trade names.


        SUMMARY OF CHEMICAL SAFETY INFORMATION

    TRIMELLITIC ANHYDRIDE
    (1,2,4-benzenetricarboxylic acid 1,2-anhydride;
    4-carboxyphthalic anhydride; 1,3-dioxo-5-phthalancarboxylic acid;  TMA)
    C9H4O5
    IUPAC systematic name:  1,3-dihydro-1,3-dioxo-5-isobenzofurancarboxylic acid
    CAS registry number:  552-30-7
    RTECS registry number:  DC2050000

                                                                                                                                   

    PHYSICAL PROPERTIES                                        OTHER CHARACTERISTICS
    Relative molecular mass        192.12                      White flakes, musty acid odour;  fine dust can be released
    Boiling point (C)             390                         during handling;  flaked or molten trimellitic anhydride
    Melting point (C)             165                         will burn if ignited, producing an explosive dust; the vapour
    Solubility (g/100 g)(25 C)                                from molten trimellitic anhydride forms dangerously 
      acetone                      49.6                        explosive mixtures with air
      cyclohexanone                38.4
      2-butane                     36.5
      ethyl acetate                21.6
      dimethylformamide            15.5
      mixed xylenes                0.4
      ligroin                      0.06
      carbon tetrachloride         0.002
    Water solubility               moderate after hydrolysis 
                                   to trimellitic acid
    Specific density (20 C)       1.54
    Relative vapour density        6.6
      (air=1)
    Vapour pressure                below 1.1  10-7
      (mmHg) (25 C)
    Flash point (C) (open cup)    227
                                                                                                                                   

                                                                                                                              

    HAZARDS/SYMPTOMS                         PREVENTION AND PROTECTION             FIRST AID
                                                                                                                              

    SKIN: Mildly irritating to skin; can     Avoid skin contact; wear suitable     Wash exposed skin with soap and water;
    cause skin sensitization                 protective clothing and gloves        remove contaminated clothing and thoroughly
                                                                                   clean and dry all garments before reuse

    EYES: Causes eye burns                   Avoid exposure;  wear chemical        Immediately flush eyes with plenty of water
                                             goggles                               for at least 15 minutes; seek immediate
                                                                                   medical advice

    INHALATION: Causes irritation of         Avoid exposure; use exhaust venti-    Remove patient to uncontaminated area;
    respiratory tract; may cause sensi-      lation and breathing protectiona        seek medical advice
    tization by inhalation, with effects
    such as pulmonary oedema, cough
    with blood-stained sputum, anaemia,
    and fever

    INGESTION: May cause oral and            Unlikely occupational hazard          Give plenty of water to drink; do not induce
    gastrointestinal irritation                                                    vomiting; seek medical attention

    Other effects: Children of women         Avoid exposure
    sensitized to trimellitic anhydride
    may also be sensitized

                                                                                                                              
    a  If ventilation is inadequate, use respirator that will protect against organic vapour/particulates.
       If dust concentration exceeds assigned protection limit for air-purifying respirator, use supplied-air respirator.

                                                                                                                              

    SPILLAGE                                   STORAGE                            FIRE AND EXPLOSION
                                                                                                                              

    Spills must be carefully swept or          Protect container from physical    High dust concentration may form a
    gathered up; alternatively vacuum          damage; provide adequate           flammable or explosive mixture; its explosive
    promptly, with high efficiency filters,    ventilation (8-10 air changes      limits are 1-7%; in case of fire, use dry
    into a dust-tight container; creation of   per hour)                          chemical, carbon dioxide, water fog, or foam
    dust is to be avoided; subsequently,
    flush the area with water; for personal 
    protection use protective clothing and 
    equipment to prevent inhalation, and 
    eye or skin contact 

                                                                                                                              

    WASTE DISPOSAL                                              NATIONAL INFORMATION
                                                                                                                              

    Deposit in an approved landfill site or                     National occupational exposure limit:
    incinerate in an approved facility, 
    unless directed otherwise by local 
    authorities
                                                                National poison control centre:

                                                                Local trade names:
                                                                                                                              
    

    7.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    7.1  Previous evaluations by international bodies

    There have not been any previous evaluations by international
    bodies. 

    7.2  Exposure limit values

    Some exposure limit values are given in the table on the page
    opposite. Some of these values are incorporated in regulations and
    some are recommendations. These have been taken from entries in the
    International Register of Potentially Toxic Chemicals (IRPTC) Legal
    File.

    7.3  Specific restrictions

    The United States of America permits trimellitic anhydride to be
    used as a cross-linking agent for epoxy resins intended for use with
    food (effective 1983) with limits of 15% by weight of the resin. The
    European Economic Community (EEC) has included TMA in Section B of
    Directive 90/128/EEC (List of substances that may still be used at
    national level, pending a decision on inclusion in Section A
    (Community list)).  The Scientific Committee for Food has not yet
    evaluated TMA, because of the lack of technical and toxicological
    data.

    Restrictions on the handling of trimellitic anhydride by pre-adults,
    pregnant women, and nursing mothers (effective 1980) are operative
    in Germany.

    7.4  Transport and labelling

    The European Community legislation requires labelling as a dangerous
    substance using the symbol:

    FIGURE 1



        CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    Tolerances and exposure limits for air in the workplace a

                                                                                                                             

    Country             Exposure limit description                         Value                             Effective date

                                                                                                                             

    Australia           Threshold limit value (TLV)
                         - Time-weighted average (TWA)                     0.04 mg/m3 (0.005 ppm)
    Belgium             Threshold limit value TLV 
                         - Time-weighted average (TWA)                     0.04 mg/m3 (0.005 ppm)
    Canada              Threshold limit value TLV 
                         - Time-weighted average (TWA)                     0.04 mg/m3 (0.005 ppm)              1980
    Czechoslovakia      Maximum workplace concentration (MAK)              0.005 mg/m3 (fumes)
                                                                           0.04 mg/m3 (fine dust)
    Germany             Maximum workplace concentration (MAK)
                         - Time-weighted average (8-h) (TWA)               0.04 mg/m3 (0.005 ppm)
                         - Short-term exposure limit (5 min) (STEL)        0.08 mg/m3 (0.01 ppm)
    Netherlands         Maximum workplace concentration (MAK)              0.04 mg/m3 (0.005 ppm)
    Sweden              Threshold limit value (TLV)                        0.04 mg/m3 (0.005 ppm)              1988
    United Kingdom      Occupational exposure standard (OES)               0.04 mg/m3 (0.005 ppm)              1987
    USA                 Threshold limit value (TLV)
                         - Time-weighted average (TWA)                     0.04 mg/m3 (0.005 ppm)

                                                                                                                             
    a  Where no effective date is given, the limits are recommendations, not regulations.
    

    The label must read:

          Irritating to eyes, respiratory system and skin; may cause
          sensitization by inhalation; do not breathe gas/fumes/
          vapour/spray (appropriate wording to be specified by the
          manufacturer); after contact with skin, wash immediately with
          plenty of ..... (to be specified by the manufacturer).

    The WHO Task Group that reviewed this publication did not consider
    that the above risk and safety expressions fully indicated the
    potential risk of severe and irreversible eye damage that has been
    reported for trimellitic anhydride. 

    BIBLIOGRAPHY

    AMOCO CHEMICAL COMPANY (1990)  Biodegradation of TMA. Chicago,
    Illinois (personal communication).

    AMOCO   Trimellitic anhydride.  TMA health and safety information.
    Amoco Chemical Company, Chicago, Illinois, 11 pp. (Bulletin TM-131
    c).

    AMOCO (1990)   Material safety data sheet. Amoco Chemical Company,
    Chicago, Illinois, 6 pp. (MSDS. No. 08001260).

    BEMIS, A.G., DINDORF, J.A., HARWOOD, B. & SAMANS, C. (1982) Phthalic
    acids.  In:  Grayson, M. & Eckroth, D. ed.  Kirk-Othmer encyclopedia
     of chemical technology, 3rd edition. New York, John Wiley and
    Sons, Inc., pp. 736-767.

    GILLNER, M. (1989)  Trimellitic anhydride (TMA) - A hazard analysis.
    Solna, Sweden, The National Chemicals Inspectorate, 45 pp. (Kemi
    Report Series No. 1/89).

    LEACH, C.L., HATOUM, N.S., ZEISS, C.R. & GARVIN, P.J. (1989)
    Immunologic tolerance in rats during 13 weeks of inhalation exposure
    to trimellitic anhydride.  Fundamental and applied toxicology, 12:
    519-529.

    NIOSH (1978)   Trimellitic anhydride (TMA). Cincinnati, Ohio, US
    National Institute for Occupational Safety and Health (Current
    intelligence bulletin 21, Publication No. 78-121 DHHS (NIOSH)).

    NIOSH (1988)  Registry of toxic effects of chemical substances
     (1985-86). Washington, DC, US National Institute for Occupational
    Safety and Health (Publication No. 87-111 DHHS (NIOSH)).

    RYAN, B.M. (1988)   Teratological evaluation of trimellitic
     anhydride (TMA) in rats and guinea-pigs. Chicago, Illinois, 
    School of Advanced Studies of Illinois Institute of Technology.

    SANTODONATO, J. BOSCH, S. MEYLAN, W., BECKER, J. & NEAL, M. (1985)
     Monograph on human exposure to chemicals in the workplace: 
     Trimellitic anhydride. Springfield, VA, US Department of Commerce,
    National Technical Information Service (PB-14932).

    THRASHER, J.D., MADISON, R., BROUGHTON, A. & GARD, Z. (1989) 
    Building-related illness and antibodies to albumin conjugates of
    formaldehyde, toluene diisocyanate, and trimellitic anhydride.   Am.
     J. ind. Med, 15: 187-195.

    WINDHOLZ, M., ed. (1983)  The Merck index. Rahway, NJ, Merck and
    Co., Inc.

    ZEISS, C.R., PATTERSON, R., PRUZANSKY, J.J., MILLER, M.M.,
    ROSENBERG, M & LEVITZ, D. (1977)  Trimellitic anhydride-induced
    airway syndromes:  Clinical and immunologic studies.   J. Allergy
     clin. Immunol., 60: 96-103.

    ZEISS, C.R., GRAMMER, L. & PATTERSON, R. (1989)  Amoco Report-Joliet
     survey 1988-89. Chicago, Illinois, The Veterans Administration
    Medical Center, 42 pp.

    ZEISS,  C.R.,  WOLKONSKY,  P.,  PRUZANSKY,  J.J.,  & PATTERSON, R.
    (1982) Clinical and immunologic evaluation of trimellitic anhydride
    workers in multiple industrial settings.   J. Allergy clin.
     Immunol., 70(1): 15-18.


    See Also:
       Toxicological Abbreviations
       Trimellitic anhydride (ICSC)