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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    CONCISE INTERNATIONAL CHEMICAL ASSESSMENT DOCUMENT NO. 8


    TRIGLYCIDYL ISOCYANURATE


    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.

    INTER-ORGANIZATION PROGRAMME FOR THE SOUND MANAGEMENT OF CHEMICALS
    A cooperative agreement among UNEP, ILO, FAO, WHO, UNIDO, UNITAR and
    OECD

    First draft prepared by Ms D. Willcocks, Ms L. Onyon, Ms C. Jenkins,
    and Dr B. Diver, Chemical Assessment Division, National Occupational
    Health and Safety Commission, Australia

    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization, and produced within the framework of the
    Inter-Organization Programme for the Sound Management of Chemicals.


    World Health Organization     Geneva, 1998

         The International Programme on Chemical Safety (IPCS),
    established in 1980, is a joint venture of the United Nations
    Environment Programme (UNEP), the International Labour Organisation
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    Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and
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    sound management of chemicals in relation to human health and the
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    WHO Library Cataloguing in Publication Data

    Triglycidyl isocyanurate.

         (Concise international chemical assessment document ; 8)

         First draft prepared by D. Willcocks, L. Onyon, C. Jenkins and
         B. Diver

         1.Triazines - adverse effects   2.Triazines -
         toxicity   3.Environmental exposure   I.Willcocks, D.   II.Series

         ISBN 92 4 153008 1                  (NLM Classification: QD 401)
         ISSN 1020-6167

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    (c) World Health Organization 1998

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         The Federal Ministry for the Environment, Nature Conservation and
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    TABLE OF CONTENTS

         FOREWORD

    1. EXECUTIVE SUMMARY

    2. IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES

    3. ANALYTICAL METHODS

    4. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    5. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

    6. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

         6.1. Environmental levels
         6.2. Human exposure

    7. COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS

    8. EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

         8.1. Single exposure
         8.2. Irritation and sensitization
         8.3. Short-term exposure
         8.4. Long-term exposure
         8.5. Genotoxicity and related end-points
         8.6. Reproductive and developmental toxicity

    9. EFFECTS ON HUMANS

    10. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

    11. EFFECTS EVALUATION

        11.1. Evaluation of health effects
              11.1.1. Hazard identification and dose-response assessment
              11.1.2. Criteria for setting guidance values for triglycidyl isocyanurate
              11.1.3. Sample risk characterization
        11.2. Evaluation of environmental effects

    12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    13. HUMAN HEALTH PROTECTION AND EMERGENCY ACTION

        13.1. Human health hazards
        13.2. Advice to physicians

    14. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

        INTERNATIONAL CHEMICAL SAFETY CARD

        REFERENCES

        APPENDIX 1 - SOURCE DOCUMENT

        APPENDIX 2 - CICAD PEER REVIEW

        APPENDIX 3 - CICAD FINAL REVIEW BOARD

        RÉSUMÉ D'ORIENTATION

        RESUMEN DE ORIENTACION
    

    FOREWORD

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    1 International Programme on Chemical Safety (1994)  Assessing 
     human health risks of chemicals: derivation of guidance values for
     health-based exposure limits. Geneva, World Health Organization
    (Environmental Health Criteria 170).

    Procedures

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    FIGURE 1

    1.  EXECUTIVE SUMMARY

        This CICAD was based principally on the assessment of triglycidyl
    isocyanurate completed under the Australian National Industrial
    Chemicals Notification and Assessment Scheme (NICNAS) and published in
    April 1994 (NICNAS, 1994).  Information that has become available
    since completion of the NICNAS report, identified up to November 1997,
    has also been assessed and included in this CICAD.  Some additional
    information from the United Kingdom Health and Safety Executive's
    toxicity review of triglycidyl isocyanurate (HSE, 1992) has also been
    included.  Information on the nature of peer review and availability
    of the NICNAS report is presented in Appendix 1.  Information on the
    peer review of this CICAD is presented in Appendix 2.  This CICAD was
    approved as an international assessment at a meeting of the Final
    Review Board, held in Berlin, Germany, on 26-28 November 1997. 
    Participants at the Final Review Board meeting are listed in Appendix
    3.  The International Chemical Safety Card (ICSC 1274) for triglycidyl
    isocyanurate, produced by the International Programme on Chemical
    Safety (IPCS, 1997), has also been reproduced in this document.

        Triglycidyl isocyanurate (CAS no. 2451-62-9), a synthetic white
    powder or granule with no discernible odour at room temperature, is
    used mainly as a three-dimensional cross-linking or curing agent in
    polyester powder coatings (paints).  These powder coatings usually
    contain between 4 and 10% triglycidyl isocyanurate.  Triglycidyl 2
    isocyanurate is also used in solder "mask" inks in the printed circuit
    board industry.  The two-part inks contain approximately 60%
    triglycidyl isocyanurate in the hardener component.  Much of the
    triglycidyl isocyanurate in powder coatings and solder inks is
    immobilized through cross-linking in an insoluble matrix.

        Exposure of the general population to triglycidyl isocyanurate is
    expected to be minimal; however, there is potential for occupational
    exposure during the manufacture of triglycidyl isocyanurate and the
    manufacture and use of products containing the chemical.

        Little information is available on the effects of triglycidyl
    isocyanurate on humans.  Several cases of allergic contact dermatitis
    and one case of respiratory sensitization caused by occupational
    exposure to triglycidyl isocyanurate have been reported.

        In laboratory animals, triglycidyl isocyanurate is acutely toxic
    by ingestion and inhalation and can cause serious eye damage.  It is a
    skin sensitizer but not a skin irritant.  The data for
    repeated-exposure toxicity are limited.  In short-term (5-7 days)
    repeated-exposure studies in rats and mice, effects on the kidneys,
    liver, lungs, gastrointestinal tract, and spermatogonial cells were
    observed.  In a 13-week toxicity/fertility study in male rats, a
    dose-related reduction in the number of spermatozoa was observed.

         In vitro and  in vivo genotoxicity studies indicate that
    triglycidyl isocyanurate is a direct-acting mutagen capable of
    affecting the reproductive organs.  In view of its potential
    genotoxicity, all appropriate measures should be taken to minimize
    human exposure to triglycidyl isocyanurate.

        Owing to its low persistence and probable low ecotoxicity,
    triglycidyl isocyanurate is unlikely to pose a significant hazard to
    the environment, except in the case of an accident or inappropriate
    disposal.

    2.  IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES

        Triglycidyl isocyanurate (CAS no. 2451-62-9; C12H15N3O6;
    1,3,5-triglycidyl isocyanurate, tris(2,3-epoxypropyl) isocyanurate) is
    a synthetic chemical, manufactured and supplied as the technical
    grades TEPIC and Araldite PT 810.  Technical-grade triglycidyl
    isocyanurate is a mixture of two diastereomers, alpha and beta.  Some
    physical and chemical properties of triglycidyl isocyanurate
    (technical grades) are presented in Table 1.  Additional properties
    are presented in the International Chemical Safety Card reproduced in
    this document.

        Triglycidyl isocyanurate is a white powder or granule with no
    discernible odour at room temperature. The solubility of Araldite PT
    810 in various solvents at 25°C is as follows: epichlorohydrin, <22%;
    methanol, 7.3%; toluene, 3%; isopropanol, 1%.  Triglycidyl
    isocyanurate reacts rapidly with primary and secondary amines,
    carboxylic acids and anhydrides, thiols, phenols, and alcohols.  It
    can be polymerized by catalysts and may undergo violent
    autopolymerization.  Combustion products include carbon dioxide,
    carbon monoxide, and oxides of nitrogen.

    Table 1: Physical and chemical properties of triglycidyl isocyanurate
             (technical grades).

                                                                       

                                                    Araldite PT
    Property                        TEPICa          810b
                                                                       

    Degree of purity (%
      triglycidyl isocyanurate)     90 (approx.)    >97

    Melting point (°C)              90-125          95

    Vapour pressure 
      (kPa at 20°C)                 n.a.c           7.2 × 10-9

    Solubility in water 
      (g/litre at 25°C)d            9               8.7

    Partition coefficient 
      (log Kow)                     -0.8            n.a.

                                                                       

    a  Information provided by Nissan Chemical Industries (Nissan, 
       no date).
    b  Information provided by Ciba-Geigy (1991).
    c  n.a. = not available.
    d  The alpha and beta isomers have different water solubilities: 
       10.1 and 0.53 g/litre, respectively (Atassi et al., 1980).

    3.  ANALYTICAL METHODS

         Methods of detection and analysis include infrared spectroscopy,
    mass spectroscopy, epoxy equivalent weight, gas chromatography, and
    high-performance liquid chromatography.  Methodology for the sampling
    and analysis of triglycidyl isocyanurate in air has been developed by
    its manufacturers and involves the collection of the dust on a glass
    fibre filter, followed by high-performance liquid chromatography with
    ultraviolet detection (detection limit 0.8 µg/m3) (NICNAS, 1994). 
    Methodology for the analysis of triglycidyl isocyanurate in other
    environmental media is not available.

    4.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

         Triglycidyl isocyanurate does not occur naturally.  It is
    produced industrially by reacting cyanuric acid with excess
    epichlorohydrin.  The worldwide production of triglycidyl isocyanurate
    is approximately 7000-8000 tonnes per year.  Australia imports
    100-1000 tonnes per year as technical-grade triglycidyl isocyanurate
    for the manufacture of polyester powder coatings or as an ingredient
    in powder coatings.  The United Kingdom imports approximately 400
    tonnes of triglycidyl isocyanurate per year for use in powder
    coatings.  In the United Kingdom, approximately 30 tonnes of solder
    "mask" inks containing triglycidyl isocyanurate are manufactured per
    year by four or five companies (NICNAS, 1994).

         The main use of triglycidyl isocyanurate is as a
    three-dimensional cross-linking or curing agent in polyester powder
    coatings (paints).  In the manufacture of powder coatings, triglycidyl
    isocyanurate granules are mixed with other ingredients; the mix is
    then melted and extruded as a brittle sheet, chipped, and packaged. 
    Generally, the particle size of 90-95% of the powder coating is
    >10 µm.

         Powder coatings usually contain 4-10% triglycidyl isocyanurate
    and are sprayed onto metal objects by an electrostatic process.  The
    coated metal objects are then treated in an oven to a temperature of
    about 200°C.  This heating causes the powder coatings to melt, flow,
    and chemically cross-link.  The coatings are durable and resist
    ultraviolet damage; as a result, they are typically used in outdoor
    applications.  Triglycidyl isocyanurate is also used in solder "mask"
    inks in the printed circuit board industry.  The two-part inks contain
    approximately 60% triglycidyl isocyanurate in the hardener component. 
    The inks are applied by curtain coating, electrostatic spraying, or
    screen printing.  The coated circuit board is finally passed through
    an oven at 150°C to complete the curing.

         Release of the chemical to air is expected to be minimal.  During
    the manufacture of triglycidyl isocyanurate and the formulation of
    products containing triglycidyl isocyanurate, dust extractors and
    other pollution control devices remove particulate waste for disposal. 
    Triglycidyl isocyanurate contained in such waste is effectively
    immobilized after consignment to landfill, particularly if waste
    powder is heat-cured beforehand.  Release to the environment during
    normal use of powder coatings in spray painting workplaces is expected
    to be low, as electrostatic application is an efficient application
    method.  Triglycidyl isocyanurate may be released into water by
    facilities that manufacture, process, or use this chemical.

    5.  ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

         Much of the triglycidyl isocyanurate in powder coatings and
    solder inks is immobilized through cross-linking in an insoluble
    matrix.  As triglycidyl isocyanurate is an epoxide, any residues not
    captured in this way are expected to be rapidly degraded through
    microbial action or abiotic hydrolysis.

         Triglycidyl isocyanurate did not satisfy criteria for ready
    biodegradability in the modified Sturm test.  When exposed for 28 days
    to bacteria from a sewage treatment plant, 9% and 48% of theoretical
    amounts of carbon dioxide were evolved from solutions of 10 and 20 mg
    triglycidyl isocyanurate/litre, respectively (Ciba-Geigy, 1988d). 
    Although these results indicate incomplete mineralization, they are
    likely to reflect complete primary degradation, with slow opening of
    the triazine ring restricting the rate of mineralization, as has been
    noted for triazine herbicides (Scheunert, 1992).

         In a modified Zahn-Wellers test measuring carbon dioxide
    evolution rather than loss of dissolved organic carbon, triglycidyl
    isocyanurate was inherently biodegradable at 11.3 mg/litre, but not at
    21.1 mg/litre (44% and 1%, respectively, after 28 days) (Ciba-Geigy,
    1993b).  As the solubility of triglycidyl isocyanurate in this test
    was said to be poor, necessitating the use of an emulsifier to achieve
    the stated test concentration, the results of this study should be
    treated with caution.  Triglycidyl isocyanurate is not expected to
    accumulate in soil or sediment because of high mobility and limited
    persistence.  High mobility may be predicted by analogy with the
    triazine herbicide hexazinone, a chemical known to leach into
    groundwater.  The oxirane substituents are not expected to retard the
    mobility significantly, as methyloxirane has a low soil organic matter
    adsorption coefficient, generally between 3 and 30 (Howard, 1989).

         Persistence in the aquatic environment is expected to be limited,
    predicted by analogy with methyloxirane, which has a half-life in
    fresh surface waters of 6.6 days at pH 5 and 11.6 days at pH 7-9
    (Howard, 1989).  Hydrolysis proceeds more rapidly in the marine
    environment because of more rapid ring opening by chloride ions.  The
    reactivity of triglycidyl isocyanurate precludes any possibility of
    bioaccumulation.

    6.  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    6.1  Environmental levels

         Information on levels of triglycidyl isocyanurate in the general
    environment was not available.

    6.2  Human exposure

         Exposure of the general population to triglycidyl isocyanurate is
    expected to be minimal.  There is potential for occupational exposure,
    most likely via inhalation, during the manufacture of triglycidyl
    isocyanurate and the manufacture and use of products containing
    triglycidyl isocyanurate.  In powder coatings, triglycidyl
    isocyanurate is partially cross-linked to the polyester resin before
    application, and it is only the unbound triglycidyl isocyanurate that
    is bioavailable.  The amount of unbound triglycidyl isocyanurate
    varies between different powder coatings.  The triglycidyl
    isocyanurate in powder coatings after application to metal particles
    is fully cross-linked and is bound in a solid matrix, from which it
    would not be bioavailable.

          No monitoring data are available for the manufacture of
    triglycidyl isocyanurate; however, monitoring data are available for
    exposure to triglycidyl isocyanurate during the manufacture of powder
    coatings containing the chemical.  In an Australian plant, triglycidyl
    isocyanurate levels in air ranged from 0.02 to 1.34 mg/m3
    (time-weighted average) during July/August 1991 (NICNAS, 1994).  Two
    months later, levels of triglycidyl isocyanurate in air were <0.03
    mg/m3 (time-weighted average) after changes, primarily improved work
    practices, were implemented in the plant.  In a plant in Japan,
    triglycidyl isocyanurate levels up to 0.035 mg/m3 (time-weighted
    average) were measured in 1991 (NICNAS, 1994).  In a survey of five
    plants by the United Kingdom Health and Safety Executive in 1994,
    triglycidyl isocyanurate levels ranged from 0.01 to 0.44 mg/m3
    (time-weighted average; mean 0.1 mg/m3), with corresponding total
    inhalable particulate levels of 1.1-64 mg/m3 (mean 9.4 mg/m3) (HSE,
    1994).

         There are limited air monitoring data available for the
    application of powder coatings containing triglycidyl isocyanurate. 
    In a survey of eight spray painting workplaces in Australia in 1991,
    triglycidyl isocyanurate levels up to 6.5 mg/m3 (time-weighted
    average) were measured (NICNAS, 1994).  In a survey of 16 similar
    workplaces by the Health and Safety Executive in the United Kingdom in
    1994, triglycidyl isocyanurate levels ranged from 0.001 to 1.5 mg/m3
    (time-weighted average; mean 0.24 mg/m3), with corresponding total
    inhalable particulate levels between 0.2 and 131 mg/m3 (mean 13
    mg/m3) (HSE, 1994).  Air monitoring data for the printed circuit
    board industry were not available.

    7.  COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS
        AND HUMANS

         The only available human data are from clinical trials with
    alpha-triglycidyl isocyanurate (intravenous administration), which
    indicate that alpha-triglycidyl isocyanurate has a mean half-life in
    the blood of approximately 1 min and a mean total body clearance of
    5.7 litres/min (Ames et al., 1984; Neidhart, 1984; Rubin et al.,
    1987).  Less than 1% of the administered dose was recovered unchanged
    in urine within 24 h (Ames et al., 1984).

         In an oral (gavage) study in mice, at least 17% of the
    administered dose was absorbed within 24 h, with blood analysis
    indicating that the absorption of triglycidyl isocyanurate
    administered in aqueous solution was twice that of triglycidyl
    isocyanurate in sesame oil.  Triglycidyl isocyanurate was distributed
    to the liver, stomach, and testes (the only tissues studied).  Blood
    plasma analysis indicated that triglycidyl isocyanurate was
    metabolized by hydrolysis to the diol diepoxide, the bis-diol epoxide,
    and the fully hydrolysed tris-diol, with no free triglycidyl
    isocyanurate detected 8 h after treatment (Ciba-Geigy, 1990c).

         In oral (gavage) and intravenous studies with
    [14C]alpha-triglycidyl isocyanurate in rabbits, the radioactivity
    recovered in urine within 24 h was approximately 30% and 60-70%,
    respectively.  In the intravenous study, the half-life of triglycidyl
    isocyanurate in the blood was <5 min (Ames et al., 1984).

         In  in vitro studies, rapid hydrolysis of triglycidyl
    isocyanurate involving the enzyme epoxide hydrolase was observed in
    mouse liver preparations (Ciba-Geigy, 1990c).  Hydrolysis was also
    observed in rat liver preparations but not in rat lung preparations
    (Ames et al., 1984).  Microsomal epoxide hydrolase activity with
    triglycidyl isocyanurate as substrate measured in two human livers
    obtained from kidney donors was found to be greater than the activity
    in rat liver (Ciba-Geigy, 1993a).

    8.  EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

    8.1  Single exposure

         Triglycidyl isocyanurate is toxic to laboratory animals following
    acute oral administration and inhalation exposure.  The oral LD50 for
    triglycidyl isocyanurate ranges from 188 to 715 mg/kg body weight in
    rats (Ciba-Geigy, 1975a, 1982a, 1990a; Safepharm, 1988a).  Clinical
    signs of toxicity observed prior to death included sedation, dyspnoea,
    and emaciation.  Pathological findings included oedematous and
    haemorrhagic lungs, haemorrhagic thymus, intestines, and testes,
    involuted testes, and enlarged kidney.

         In rat inhalation (nose-only) studies, an LC50 of 650 mg/m3 was
    obtained with triglycidyl isocyanurate in dust form (Ciba-Geigy,
    1979a), and an LC50 of >300 mg/m3 was found with triglycidyl
    isocyanurate in liquid aerosol form (Ciba-Geigy, 1979b).  Slight
    inflammation of the nasal mucosa in the upper dose groups was
    observed.  There were no substance-related gross organ changes in
    sacrificed animals, and partial haemorrhage only was observed in the
    lungs of animals who died during the study.  An LC50 of 2000 mg/m3
    was obtained for the mouse (whole-body exposure to dust, particle size
    range 3.2-3.9 µm) (Bushy Run, 1991).  Clinical signs included
    hypoactivity and ocular and respiratory irritation.  Pathological
    observations included perinasal/periocular/perioral encrustation and
    lung discoloration.

         The dermal LD50 for rats was >2000 mg/kg body weight
    (Ciba-Geigy, 1975b, 1990b; Safepharm, 1988b).  There were no deaths or
    exposure-related adverse clinical signs; at necropsy, no gross organ
    changes were observed.

    8.2  Irritation and sensitization

         In several rabbit studies, triglycidyl isocyanurate caused slight
    skin irritation, with both very slight erythema and very slight oedema
    observed in the intact skin of some animals up to 72 h
    post-application (Ciba-Geigy, 1979c,d, 1982b; Safepharm, 1988c,d). 
    Triglycidyl isocyanurate caused serious eye damage in rabbits,
    including severe corneal opacity and chemosis (Ciba-Geigy, 1979e,
    1982c).

         Triglycidyl isocyanurate (commercial grade) was positive for skin
    sensitization in guinea-pigs in two modified Magnusson and Kligman
    studies (Ciba-Geigy, 1988b; Safepharm, 1988e).  In both studies,
    groups of 10 male and 10 female guinea-pigs were initially exposed to
    triglycidyl isocyanurate and challenged 2 weeks after induction. 
    Positive responses were observed in 25% of the test animals in one
    study (Ciba-Geigy, 1988b) and in 60% of the test animals in the other
    study (Safepharm, 1988e).  No skin reactions were noted in the control
    group at induction or when challenged with triglycidyl isocyanurate.

    8.3  Short-term exposure

         In a 7-day oral rat study, gross pathology was recorded for the
    lungs, kidney, liver, stomach, and intestines.  Renal tubular damage
    and haemorrhagic and degenerative changes involving the gastric and
    duodenal mucosa were observed at the high triglycidyl isocyanurate
    dose (216 mg/kg body weight per day for males and 172 mg/kg body
    weight per day for females).  Less marked changes to the renal tubules
    were noted at the low dose (54 mg/kg body weight per day for males and
    43 mg/kg body weight per day for females) (Shell, 1971).

         In a study in which male CD-1 mice were exposed (nose-only) to
    triglycidyl isocyanurate at 0, 10, 40, or 140 mg/m3, 6 h/day for 5
    days, mortality, body weight loss, and lung damage occurred at the
    highest concentrations (40 and 140 mg/m3).  No exposure-related
    effects were observed at 10 mg/m3.  Clinical signs of toxicity
    observed in the intermediate- and high-concentration groups included
    lethargy, ptosis, decreased respiratory rate, and noisy or gasping
    respiration.  Gross pathology and organ weights were recorded for the
    lungs, liver, kidney, and testes.  Pathological findings included dark
    or reddened lungs, pale liver, pale kidneys, and congestion of the
    small intestine (Safepharm, 1991).

    8.4  Long-term exposure

         Information from general subchronic or chronic toxicity studies
    was not available.1

    8.5  Genotoxicity and related end-points

         The genotoxicity of triglycidyl isocyanurate has been
    investigated in a wide range of  in vitro and  in vivo assays
    (Tables 2 and 3).  Triglycidyl isocyanurate was mutagenic in
     Salmonella typhimurium and mouse lymphoma cells and clastogenic in
    Chinese hamster ovary cells  in vitro. It induced chromosomal
    aberrations in bone marrow cells in hamsters and in germ cells in mice
    following oral administration.  Available data also indicate that
    triglycidyl isocyanurate has the potential to alkylate DNA.

         In two reverse mutation assays, commercial-grade triglycidyl
    isocyanurate induced mutations in the presence and absence of
    metabolic activation in  S. typhimurium strains TA1535, TA1538, TA98,
    and TA100, with the effect more pronounced in the latter two strains
    (Ciba-Geigy, 1982d; Hazleton, 1987).  Triglycidyl isocyanurate was not
    mutagenic in TA1537.  In one of these studies, triglycidyl 
    isocyanurate did not induce back mutation in  Escherichia coli 


              

    1 The final results of a chronic toxicity/carcinogenicity bioassay
    in rats conducted by the Centre Internationale de Toxicologie (CIT) in
    France were not available at the time this CICAD was prepared.

    WP2uvrA, with or without metabolic activation (Ciba-Geigy, 1982d). 
    All studies were well conducted, using appropriate negative and
    positive controls, with the results indicating that triglycidyl
    isocyanurate is a direct-acting mutagen.

         In a mouse lymphoma cell assay, triglycidyl isocyanurate induced
    forward mutations in the presence of metabolic activation at 6.0 µg/ml
    and in the absence of metabolic activation at 2.8 µg/ml (Ciba-Geigy,
    1983a).  Triglycidyl isocyanurate with and without metabolic
    activation induced sister chromatid exchanges and chromosomal
    aberrations in Chinese hamster ovary cells (Loveday et al., 1990;
    Sofuni et al., 1990).  Triglycidyl isocyanurate also tested positive
    for the induction of chromosomal aberrations without metabolic
    activation in Chinese hamster lung cells but was negative with
    metabolic activation (Sofuni et al., 1990).  In an unscheduled DNA
    synthesis assay in rat hepatocytes, a clear dose-response relationship
    was noted for triglycidyl isocyanurate over the range 5-20 µg/ml
    (Ciba-Geigy, 1988c).  However, in a similar study conducted with human
    fibroblasts, triglycidyl isocyanurate did not induce unscheduled DNA
    synthesis at concentrations up to 400 µg/ml (Ciba-Geigy, 1988a).  In
    two cell transformation studies in mouse embryo fibroblasts,
    triglycidyl isocyanurate did not induce any significant increase in
    either transformed colony number or size in the concentration range
    8.8-5000 ng/ml (Ciba-Geigy, 1983b, 1986a).

         Triglycidyl isocyanurate did not induce chromosomal aberrations
    in human lymphocytes at concentrations up to 2500 ng/ml.  Only one
    aberration was reported at each of the two higher concentrations of
    5000 and 10 000 ng/ml.  Significant numbers of aberrations were
    observed with the positive controls.  As only a very late sampling
    time was used, the results are considered questionable (Ciba-Geigy,
    1985).

         In a gavage study, male and female Chinese hamsters were
    administered 0, 140, 280, or 560 mg triglycidyl isocyanurate/kg body
    weight per day for 2 days.  Triglycidyl isocyanurate induced small but
    significant increases in nuclear anomalies in bone marrow cells at the
    two highest doses, indicative of clastogenicity (Ciba-Geigy, 1983c).

         Two gavage studies were conducted to determine the ability of
    triglycidyl isocyanurate to induce sister chromatid exchanges in bone
    marrow cells in male and female Chinese hamsters.  In one study, no
    increase in the number of sister chromatid exchanges was observed in
    animals administered a single dose of 0, 35, 70, or 140 mg triglycidyl
    isocyanurate/kg body weight (Ciba-Geigy, 1984).  In the study in which
    triglycidyl isocyanurate was administered at a single dose of 0, 140,
    280, or 560 mg/kg body weight, a dose-related increase in sister
    chromatid exchange in bone marrow cells (with statistically
    significant increases) was observed at all exposures (Ciba-Geigy,
    1983d).  The results of the mouse spot test were negative when
    triglycidyl isocyanurate was administered at doses of 13.5, 27, or 54
    mg/kg body weight in a single intraperitoneal injection to pregnant
    mice on the 10th day after conception (Ciba-Geigy, 1986d).


        Table 2:  Genotoxicity of triglycidyl isocyanurate  in vitro.

                                                                                                                           
                                                                                     Resultsa
                                                                                                     
                                                                              With         Without
    Species (test system)            End-point         Test concentration     activation   activation   Reference
                                                                                                                           

    Procaryotic systems

    Salmonella typhimurium           Gene mutation     1-10 000 µg/plate      +            +            Hazleton, 1987
    (TA1535, TA1538, TA98, TA100)                      5-5000 µg/plate        +            +            Ciba-Geigy, 1982d

    Escherichia coli WP2uvrA         Gene mutation     5-5000 µg/plate        -            -            Ciba-Geigy, 1982d

    Animal systems

    Mouse lymphoma                   Gene mutation     0.375-6.0 µg/ml        +            NT           Ciba-Geigy, 1983a
                                                       0.175-2.8 µg/ml        NT           +

    Rat hepatocytes                  Unscheduled       0.20-20 µg/ml          NT           +            Ciba-Geigy, 1988c
                                     DNA synthesis

    Chinese hamster ovary cells      Sister chromatid  1.98-19.8 µg/ml        +            NT           Loveday et al.,
                                     exchanges         0.066-0.66 µg/ml       NT           +            1990

    Chinese hamster ovary cells      Chromosomal       10-100 µg/ml           +            NT           Loveday et al., 
                                     aberrations       3-30 µg/ml             NT           +            1990

    Chinese hamster ovary cells      Chromosomal       10-100 µg/ml           +            NT           Sofuni et al., 1990
                                     aberrations       3-50 µg/ml             NT           +

    Chinese hamster lung cells       Chromosomal       1.25-5 µg/ml           -            +            Sofuni et al., 1990
                                     aberrations

    Mouse embryo fibroblasts         Cell              8.75-140 ng/ml         NT           -            Ciba-Geigy, 1983b
                                     transformation    0.3125-5 µg/ml         -            NT           Ciba-Geigy, 1986a
                                                                                                                           

    Table 2:  (continued)

                                                                                                                           
                                                                                     Resultsa
                                                                                                     
                                                                              With         Without
    Species (test system)            End-point         Test concentration     activation   activation   Reference
                                                                                                                           

    Human cells

    Human lymphocytes                Chromosomal       62.5-10 000 ng/ml      NT           Equivocal    Ciba-Geigy, 1985
                                     aberrations

    Human fibroblasts                Unscheduled       2.7-400 µg/ml          NT           -            Ciba-Geigy, 1988a
                                     DNA synthesis
                                                                                                                           

    a  NT = not tested; - = negative result; + = positive result.

    Table 3: Genotoxicity of triglycidyl isocyanurate  in vivo.

                                                                                                                                  

    Species (test                      Route of
    system)            End-point       exposure         Dose                                    Resultsa      Reference
                                                                                                                                  

    Chinese hamster    Nuclear         Oral             0, 140, 280, 560 mg/kg body weight      +             Ciba-Geigy, 1983c
      bone marrow      anomalies

    Chinese hamster    Sister          Oral             0, 35, 70, 140 mg/kg body weight        -             Ciba-Geigy, 1984
      bone marrow      chromatid       Oral             0, 140, 280, 560 mg/kg body weight      +             Ciba-Geigy, 1983d
                       exchange

    Mouse              Chromosomal     Oral             0, 43, 128 mg/kg body weight            +             Ciba-Geigy, 1986b
    spermatogonial     aberrations     Oral             0, 30, 125, 350 mg/kg body weight       +             Hazleton, 1989a
    cells                              Oral             0, 29, 58, 115 mg/kg body weight        +             Hazleton, 1991
                                       Oral             115 mg/kg body weight                   +             Safepharm, 1992
                                       Inhalation       0, 2.5, 10, 50 mg/m3                    Equivocal     Bushy Run, 1992a
                                       Inhalation       0, 7.8 mg/m3                            -             Safepharm, 1992

    Mouse              Chromosomal     Oral             0, 32, 96 mg/kg body weight             -             Ciba-Geigy, 1986e
    spermatocytes      aberrations

    Mouse spot test    Gene mutation   Intraperitoneal  13.5, 27, 54 mg/kg body weight          -             Ciba-Geigy, 1986d

    Mouse              Dominant        Oral             0, 160, 480 mg/kg body weight           Equivocalb    Ciba-Geigy, 1986c
                       lethal          Oral             0, 138, 275, 550 mg/kg body weight      -b            Hazleton, 1989b
                       mutations       Inhalation       0.25, 10, 50 mg/m3                      -             Bushy Run, 1992b

    Mouse stomach,     DNA binding     Oral             5, 17, 200 mg/kg body weight            +             Ciba-Geigy, 1990c
      liver, and 
      testis

    Rat liver          DNA binding     Oral,            20 mg/kg body weight                    +             Ciba-Geigy, 1993a
                                       intraperitoneal
                                                                                                                                  

    a  NT = not tested; - = negative result; + = positive result.
    b  Mating period included only first 3 weeks post-treatment.
    

         A number of oral studies have been conducted to investigate the
    potential of triglycidyl isocyanurate to induce chromosomal
    aberrations in mouse germ cells.  In male ICR mice administered 0, 30,
    125, or 350 mg triglycidyl isocyanurate/kg body weight for 5 days,
    chromosomal aberrations were induced in spermatogonial cells at the
    two highest doses (Hazleton, 1989a).  In another study in which male
    B6D2F1 mice were administered 0, 29, 58, or 115 mg triglycidyl
    isocyanurate/kg body weight for 5 days, chromosomal aberrations in
    spermatogonial cells were significantly increased at all doses
    (Hazleton, 1991).  When male TifMAGf mice were administered 0, 43, or
    128 mg triglycidyl isocyanurate/kg body weight for 5 days, a
    dose-related increase in chromosomal aberrations was observed in
    spermatogonial cells; however, a statistical analysis was not
    conducted (Ciba-Geigy, 1986b).  Chromosomal aberrations were not
    induced in the spermatocytes of male mice administered (by gavage)
    0, 32, or 96 mg triglycidyl isocyanurate/kg body weight for 4 days
    (Ciba-Geigy, 1986e).  In a single-dose oral study, chromosomal
    aberrations were induced in mouse spermatogonia at 115 mg triglycidyl
    isocyanurate/kg body weight (Safepharm, 1992).

         In a (whole-body) inhalation study, mice were exposed to 0, 2.5,
    10, or 50 mg triglycidyl isocyanurate/m3 (particle size range 2.5-3.5
    µm) for 6 h/day for 5 days.  Effects on mouse spermatogonial cells
    were measured by the induction of chromosomal aberrations. The results
    of this study were inconclusive (Bushy Run, 1992a).  The number of
    chromosomal aberrations in the control group was high, there was a
    very low number of scorable cells at the highest concentrations (10
    and 50 mg/m3), and cytotoxicity was not clearly established, as the
    cytotoxic ratio was not measured.  At 2.5 mg/m3, the number of
    chromosomal aberrations was only slightly higher than in the controls,
    which was unusually high.  In an (nose-only) inhalation study, male
    CD-1 mice were exposed to 0 or 7.8 mg triglycidyl isocyanurate/m3
    (mean particle size 1.6 µm) for 6 h/day for 5 days.  Chromosomal
    aberrations were not induced in spermatogonial cells at the single
    concentration tested (Safepharm, 1992).  In both these studies, body
    weight gain was unaffected, no deaths occurred, and no adverse
    clinical signs were observed.

         In a dominant lethal test, male TifMAGf(SPF) mice were
    administered (by gavage) 0, 160, or 480 mg triglycidyl isocyanurate/kg
    body weight.  In females mated to the high-dose males, there was a
    significant increase in the number of embryonic deaths when mating
    occurred during the 1st week after exposure, but not when mating took
    place 2-3 weeks after the males were exposed (Ciba-Geigy, 1986c).  No
    increase in embryonic deaths was noted in females mated to the
    low-dose males 1-3 weeks after exposure. The results of this study are
    considered equivocal.  In a study in which male ICR mice were
    administered (by gavage) 0, 138, 275, or 550 mg triglycidyl
    isocyanurate/kg body weight, no significant increase in the number of
    embryonic deaths was observed in the mated females (Hazleton, 1989b). 
    These studies are of limited value, as the mating periods covered only
    the first 3 weeks after the males had been exposed.  In another study,
    male CD-1 mice were exposed (by inhalation) to 0.25, 10, or 50 mg

    triglycidyl isocyanurate/m3.  A reduction in male fertility (i.e.
    number of sperm-positive and pregnant females) was observed in
    high-dose males in the first 3 weeks and 6th week post-exposure, as
    well as in mid-dose males in the 3rd week post-exposure only.  No
    dominant lethal effects were observed; however, the results are
    suggestive of an effect on mature sperm, maturing spermatids, and Type
    B spermatogonia.  This is the only dominant lethal study in which the
    mating period covered all stages of the spermatogenic cycle (Bushy
    Run, 1992b).

         The molecular structure of triglycidyl isocyanurate indicates a
    potential for alkylating DNA.  A dose-dependent increase in
    triglycidyl isocyanurate-DNA adduct formation was observed in a study
    in which male TifMAGf(SPF) mice were orally administered 5, 17, or 200
    mg triglycidyl isocyanurate/kg body weight.  DNA alkylation was
    measured as the covalent binding index.  For the highest dose, the
    ratio of covalent binding indices for the stomach, liver, and testes
    at 3 h after exposure was approximately 30 : 7 : 1.  The highest
    covalent binding index, for the stomach, was 8.9, compared with
    covalent binding indices of 20 000 for the potent liver carcinogen
    aflatoxin B1 and 200 for the moderate carcinogen 2-acetylaminofluorene
    (Ciba-Geigy, 1990c).  In a second DNA alkylation study, male
    TifRAIf(SPF) rats were pretreated with  trans-stilbene oxide at 0,
    100, or 400 mg/kg body weight to induce epoxide hydrolase activity,
    followed by triglycidyl isocyanurate administered orally or
    intraperitoneally (20 mg/kg body weight).  The dose-dependent increase
    in liver microsomal epoxide hydrolase activity was associated with a
    dose-dependent decrease in DNA binding by triglycidyl isocyanurate,
    calculated as the covalent binding index.  However, the relatively low
    covalent binding indices suggested that only a small proportion of
    triglycidyl isocyanurate binds to DNA.  As mentioned in section 7,
    microsomal epoxide hydrolase activity with triglycidyl isocyanurate as
    substrate measured in two human livers was greater than the activity
    in non-induced rat liver (Ciba-Geigy, 1993a).

    8.6  Reproductive and developmental toxicity

         In a 13-week toxicity/fertility study, groups of 10 male rats
    were given diets containing 0, 10, 30, or 100 ppm (mg/kg) triglycidyl
    isocyanurate (CIT, 1995).  This study followed a preliminary 19-day
    range-finding investigation in which signs of toxicity (large
    mesenteric lymph nodes, small prostate and seminal vesicles) were
    observed in animals administered diets containing 160 or 640 ppm
    (mg/kg) triglycidyl isocyanurate.  In the full study after 64 days of
    treatment, each male was placed with two females until mating
    occurred.  The females were then allocated to two subgroups (caesarean
    or normal delivery) on day 19 of pregnancy.  Females from the
    caesarean group were killed on day 20 of pregnancy and the ovaries and
    uterus examined to determine number of corpora lutea, live and dead
    fetuses, resorptions, and implantation sites.  The other group was
    allowed to deliver normally; litter size was noted, pups were examined
    for presence of clinical signs, and their development was recorded. 
    Between 22 and 25 days postpartum, the females in the normal delivery

    group were sacrificed, the main thoracic and abdominal organs were
    examined, and the number of implantation sites was noted.  In males at
    autopsy, all organ weights and macroscopic and microscopic changes
    were recorded in the control and highest-dose groups, with selected
    organs examined in the other test groups.

         No exposure-related clinical effects or deaths were observed. 
    Body weight gain was slightly lower over the first 6 weeks in animals
    from the 100 ppm (mg/kg) test group.  A dose-related reduction in the
    number of spermatozoa was noted; compared with the unexposed controls,
    there was a 5%, 13%, and 23% reduction in spermatozoa in males
    administered diets containing 10, 30, and 100 ppm (mg/kg) triglycidyl
    isocyanurate, respectively.  Spermatozoa viability was similar in the
    triglycidyl isocyanurate-exposed and control groups.  No
    exposure-related infertility was noted in males, and no effects on
    embryonic and pup development were observed in the offspring of
    females mated with triglycidyl isocyanurate-exposed males (CIT, 1995). 
    However, it should be noted that the highest concentration used in
    this study (100 ppm; mg/kg) was not a maximum tolerated dose.

         There were no other data available on the developmental toxicity
    of triglycidyl isocyanurate.

    9.  EFFECTS ON HUMANS

         Allergic contact dermatitis has been reported in several
    case-studies of exposure to triglycidyl isocyanurate and powder
    coatings containing triglycidyl isocyanurate.  Exposure occurred
    during the manufacture of triglycidyl isocyanurate (Nishioka et al.,
    1988) and powdered paint coatings (Foulds & Koh, 1992; Munro &
    Lawrence, 1992), during the application of products containing
    triglycidyl isocyanurate, including powder coatings (Matthias, 1988;
    McFadden & Rycroft, 1993) and hardener for epoxy acrylate ink (Jolanki
    et al., 1994), and while cleaning equipment contaminated with
    triglycidyl isocyanurate (Dooms-Goossens et al., 1989).  Symptoms
    included dermatitis, itchy rashes, and swelling on the face, hands,
    arms, neck, and thighs.  All subjects tested positive to patch testing
    with triglycidyl isocyanurate.

         A case-study reported asthma-like symptoms in a spray painter who
    had been using powder coatings containing triglycidyl isocyanurate for
    4 years (Piirila et al., 1997).  Symptoms included elevated blood
    eosinophils and serum immunoglobulin E (IgE), moderate bronchial
    hyper-reactivity, and a reduction in forced expiratory volume in 1
    second (FEV1) of 23% and 19% when challenged with 4% triglycidyl
    isocyanurate and 4% triglycidyl isocyanurate mixed with lactose,
    respectively.  The worker also had eczema on his hands, face, and
    body; the skin prick test was negative.

         Human trials were performed during clinical development of
    alpha-triglycidyl isocyanurate as an antitumour agent.  In these
    studies, alpha-triglycidyl isocyanurate was administered intravenously
    to cancer patients at doses up to 900 mg/kg body weight using a
    variety of dosing regimes.  Toxic signs included myelosuppression,
    nausea and vomiting, and, rarely, alopecia and leucopenia at high
    doses (>600 mg/kg body weight).  Owing to its severe local toxicity
    (thrombophlebitis) at the site of injection, the use of
    alpha-triglycidyl isocyanurate as an antitumour agent was not pursued
    (HSE, 1992).

         There were no epidemiological studies on triglycidyl isocyanurate
    available.

    10.  EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

         Only limited ecotoxicological data for triglycidyl isocyanurate
    are available.  No deaths were observed at the only concentration
    tested in a 96-h static test with zebra fish  (Brachydanio rerio);
    the no-observed-effect concentration (NOEC) was >77 mg/litre
    (Ciba-Geigy, 1988e).  The 24-h EC50 in a static immobilization test
    with  Daphnia magna was >100 mg/litre, with a NOEC of 58 mg/litre
    (Ciba-Geigy, 1988f).  These results indicate that triglycidyl
    isocyanurate is, at most, slightly toxic to aquatic fauna under
    conditions of acute exposure.  Chronic effects would not be expected
    because of limited aquatic persistence.

    11.  EFFECTS EVALUATION

    11.1  Evaluation of health effects

    11.1.1  Hazard identification and dose-response assessment

         The only reported health effects in humans are contact dermatitis
    and one case of respiratory sensitization.

         Acute animal toxicity studies reveal that triglycidyl
    isocyanurate is toxic by oral and inhalation routes of exposure but
    has low acute dermal toxicity.  Triglycidyl isocyanurate produces
    serious eye irritation.  It is a skin sensitizer but not a skin
    irritant.  Short-term repeated-dose studies revealed renal, lung,
    gastric/duodenal, and sperm cell damage.  In a subchronic
    toxicity/fertility study conducted in rats, a dose-dependent reduction
    in the number of spermatozoa was the only effect observed at
    concentrations of up to 100 ppm (mg/kg) triglycidyl isocyanurate in
    the diet.

         Triglycidyl isocyanurate has structural alerts suggesting
    direct-acting mutagenicity.  DNA binding of triglycidyl isocyanurate
    has been measured in mouse liver, testes, and stomach following oral
    administration.  The chemical has produced positive results in a range
    of  in vitro genotoxicity studies (gene mutation in bacterial and
    mammalian cells, unscheduled DNA synthesis, sister chromatid
    exchanges, and chromosomal aberration assays).  Genotoxic effects have
    also been observed  in vivo in somatic (bone marrow) cells and germ
    cells in the testes.  Triglycidyl isocyanurate therefore causes
    heritable mutations, and the demonstrated ability for triglycidyl
    isocyanurate to cause genetic damage also raises concern over
    potential carcinogenic effects.

         Genotoxicity studies have revealed that the inhalation of
    triglycidyl isocyanurate produces cytotoxicity and chromosomal
    aberrations in mouse spermatogonia, and therefore there may be a risk
    of reproductive effects.  A 13-week dietary study in rats has
    indicated no effects on male fertility, but no firm conclusions can be
    drawn in view of the low doses tested.  Overall, the reproductive
    toxicity of triglycidyl isocyanurate has not been adequately
    investigated.  As triglycidyl isocyanurate is a direct-acting
     in vivo mutagen, identification of a no-observed-effect level for
    the non-critical end-points of systemic toxicity may not be
    appropriate.

    11.1.2   Criteria for setting guidance values for triglycidyl 
             isocyanurate

         Exposure of the general public to triglycidyl isocyanurate is
    likely to be minimal.  The main risk to human health is through
    occupational exposure via inhalation.  Data from human and animal
    studies upon which to base a guidance value for occupational exposure
    to triglycidyl isocyanurate are very limited.  Based on the
    information available from animal studies, the critical effect for

    chronic exposure is the potential genotoxicity of triglycidyl
    isocyanurate.  Triglycidyl isocyanurate is a direct-acting  in vivo 
    mutagen, and it is not possible to identify a level of exposure below
    which there would be no risk to human health.

    11.1.3  Sample risk characterization

         Because triglycidyl isocyanurate is genotoxic, a
    no-observed-effect level cannot be determined, and a quantitative risk
    characterization is not considered appropriate.  Public exposure to
    the chemical is likely to be very low.  Owing to its genotoxic and
    sensitization effects, workplace exposures should be maintained at the
    lowest practicable level.

    11.2  Evaluation of environmental effects

         Triglycidyl isocyanurate is not expected to produce adverse
    effects, as environmental exposure is low.  Much of the triglycidyl
    isocyanurate contained in waste will be effectively immobile, as it is
    bound in the coating matrix of triglycidyl isocyanurate-containing
    materials.  Amounts released into the environment will have limited
    persistence because of rapid biodegradation.

         Some triglycidyl isocyanurate and triglycidyl
    isocyanurate-containing powder coatings may also be released to the
    atmosphere and the sewage system.  The limited ecotoxicological data
    indicate that the acute toxicity of triglycidyl isocyanurate in
    aquatic fauna is low (NOEC >58 mg/litre).  Chronic effects are not
    expected because of limited aquatic persistence.

    12.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

         Previous evaluations of triglycidyl isocyanurate by international
    bodies were not identified.  Information on international hazard
    classification and labelling is included in the International Chemical
    Safety Card reproduced in this document.

    13.  HUMAN HEALTH PROTECTION AND EMERGENCY ACTION

         Human health hazards, together with preventative and protective
    measures and first aid recommendations, are presented in the
    International Chemical Safety Card (ICSC 1274) reproduced in this
    document.

    13.1  Human health hazards

         Triglycidyl isocyanurate is a skin sensitizer and has the
    potential to cause heritable mutations in humans.  It may also cause
    serious eye damage.

    13.2  Advice to physicians

         In case of intoxication, the treatment is supportive.

    14.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

         Information on national regulations, guidelines, and standards
    can be found in the International Register of Potentially Toxic
    Chemicals (IRPTC), available from UNEP Chemicals (IRPTC), Geneva.

         The reader should be aware that regulatory decisions about
    chemicals taken in a certain country can be fully understood only in
    the framework of the legislation of that country.  The regulations and
    guidelines of all countries are subject to change and should always be
    verified with appropriate regulatory authorities before application.



        INTERNATIONAL CHEMICAL SAFETY CARD
                                                                                                                                              
    TRIGLYCIDYL ISOCYANURATE                                                                                                       ICSC: 1274
                                                                                                                                   08.10.1997
                                                                                                                                              
    CAS #      2451-62-9
    RTECS #    XZ1994900
                                                          1,3,5-Triglycidyl isocyanurate
                                                         s-Triazine-2,4,6(1H,3H,5H)-trione
                                                           Tris(epoxypropyl)isocyanurate
                                                                     C12H15N3O6
                                                               Molecular mass: 297.3
                                                                                                                                              
    TYPES OF HAZARD/   ACUTE HAZARDS/                         PREVENTION                              FIRST AID/FIRE FIGHTING
    EXPOSURE           SYMPTOMS
                                                                                                                                              

    FIRE               Combustible. Gives off irritating or   NO open flames.                         Foam, powder, carbon dioxide.
                       toxic fumes (or gases) in a fire.

    EXPLOSION          Finely dispersed particles form        Prevent deposition of dust; closed
                       explosive mixtures in air.             system, dust explosion-proof
                                                              electrical equipment and lighting.

    EXPOSURE                                                  PREVENT DISPERSION OF DUST!
                                                              AVOID ALL CONTACT!

    Inhalation                                                Local exhaust or breathing protection   Fresh air, rest.

    Skin                                                      Protective gloves.  Protective          Remove contaminated clothes.  Rinse skin 
                                                              clothing.                               with plenty of water or shower.

    Eyes               Redness. Pain.                         Safety goggles, or eye protection in    First rinse with plenty of water for
                                                              combination with breathing              several minutes (remove contact lenses if
                                                              protection.                             easily possible), then take to a doctor.

    Ingestion                                                 Do not eat, drink, or smoke during      Rinse mouth.  Induce vomiting (ONLY IN)
                                                              work.                                   CONSCIOUS PERSONS!). Refer for medical
                                                                                                      attention.
                                                                                                                                              

    (continued)

                                                                                                                                              
    SPILLAGE DISPOSAL                                                        PACKAGING & LABELLING
                                                                                                                                              

    Sweep spilled substance into sealable containers.  Carefully collect     Symbol
    remainder, then remove to safe place.  Do NOT let this chemical enter    R: 23/25-41-43-46
    the environment (extra personal protection: P2 filter respirator for     S:
    harmful particles).                                                      UN Hazard Class:
                                                                             UN Subsidiary Risks:
                                                                             UN Pack Group:

    EMERGENCY RESPONSE                                                       STORAGE
                                                                             Well closed.
                                                                                                                                              

                                                                  IMPORTANT DATA
                                                                                                                                              

    PHYSICAL STATE: APPEARANCE                                               ROUTES OF EXPOSURE:
    WHITE POWDER OR GRANULE                                                  The substance can be absorbed into the body by inhalation of its 
                                                                             aerosol and by ingestion.

    PHYSICAL DANGERS:                                                        INHALATION RISK:
    Dust explosion possible if in powder or granular form,                   No indication can be given about the rate in which a harmful 
    mixed with air.                                                          concentration in the air is reached on evaporation of this
                                                                             substance at 20°C.

    CHEMICAL DANGERS:                                                        EFFECTS OF SHORT-TERM EXPOSURE:
    The substance may polymerize due to heating to more than 120°C           The substance irritates severely the eyes.  The substance may
    for more than 12 hours, or under the influence of catalysts.             cause effects on the central nervous system, kidneys, liver,
    The substance decomposes on burning producing toxic fumes                lungs and gastrointestinal tract, resulting in tissue lesions.
    including nitrogen oxides.  Molten triglycidyl isocyanurate
    reacts rapidly with primary and secondary amines, carboxylic
    acids and anhydrides, thiols, phenols and alcohols.

    OCCUPATIONAL EXPOSURE LIMITS:                                            EFFECTS OF LONG-TERM OR REPEATED EXPOSURE:
    TLV not established.                                                     Repeated or prolonged contact may cause skin sensitization. May
                                                                             cause heritable genetic damage in humans.
                                                                                                                                              

    (continued)
                                                                                                                                              
                                                                   PHYSICAL PROPERTIES
                                                                                                                                              

    Melting point:              95°C
    Density:                    1.5 g/cm3

    Solubility in water, 
      g/100 ml at 25°C:         0.9 (technical grade)
    Flash point:                >170°C (technical grade)
    Auto-ignition temperature:  >200°C (technical grade)
    Octanol/water partition 
      coefficient as log Pow:   -0.8 (technical grade)
                                                                                                                                              

                                                                   ENVIRONMENTAL DATA

                                                                          NOTES
                                                                                                                                              

    Technical grade of this substance is a mixture of alpha and beta isomers.

                                                                                                                                              
    
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    Ciba-Geigy (1983a)  L5178Y/TK+/œ mouse lymphoma mutagenicity test 
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    Ciba-Geigy (1983c)  Nucleus anomaly test in somatic interphase nuclei
     of Chinese hamster with TK 10622 (No. 820931). Basel, Ciba-Geigy
    Ltd.

    Ciba-Geigy (1983d)  Sister chromatid exchange studies on somatic 
     cells of the Chinese hamster (No. 820932). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1984)  Sister chromatid exchange studies on somatic cells
     of Chinese hamster (No. 830989). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1985)  Chromosome studies on human lymphocytes in vitro
     with TK 10622 (No. 850071). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1986a)  Transformation/liver microsome test with TK 10622
     (No. 850072). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1986b)  Chromosome studies on male germinal epithelium of
     mouse spermatogonia (No. 850067). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1986c)  Dominant lethal test, mouse, three weeks (No.
     850069). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1986d)  Mammalian spot test, mouse, 8 weeks (No. 850070)
     with TK 10622. Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1986e)  Chromosome studies on male epithelium mouse
     spermatocytes (No. 850068) with TK 10622. Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1988a)  Autoradiographic DNA repair test on human
     fibroblasts with TK 10622 (No. 874267). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1988b)  Skin sensitization test in the guinea pig,
     modified maximization test (No. 884210). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1988c)  Autoradiographic DNA repair test on rat
     hepatocytes with TK 10622 (No. 874266). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1988d)  Report on the test for ready biodegradability of
     TK 10622 in the modified Sturm test (Report No. 884053). Basel,
    Ciba-Geigy Ltd.

    Ciba-Geigy (1988e)  Report on the test for acute toxicity of TK 10622
     to zebra fish (Brachydanio rerio). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1988f)  Report on the test for acute toxicity of TK 10622
     to Daphnia magna. Basel, Ciba-Geigy Ltd, March.

    Ciba-Geigy (1990a)  Acute oral toxicity in the rat (No. 894516) of TK
     10622 (Araldite PT 810). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1990b)  Acute dermal toxicity in the rat (No. 894517) 
     with TK 10622 (Araldite PT 810). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1990c)  Potential for DNA binding of Araldite PT 810 (No.
     PS32-01903). Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1991)  Analytical method, Araldite PT 810 pure in powder
     coatings. Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1993a)  Hazard assessment with Araldite PT 810:
     Inactivation by subcellular liver fractions and binding to liver 
     DNA, Project No. 924004. Basel, Ciba-Geigy Ltd.

    Ciba-Geigy (1993b)  Report on the test for inherent biodegradability 
     in a combined Zahn-Wellers/carbon dioxide evolution test of Araldite
     PT 810. Basel, Ciba-Geigy Ltd.

    CIT (1995)  13-week toxicity study and fertility study by oral route
     (dietary admixture) in male rats with PT 810(R)  (TGIC). Miserey,
    Centre Internationale de Toxicologie.

    Dooms-Goossens A, Bedert R, Vandaele M, Degreef H (1989) Airborne
    contact dermatitis due to triglycidyl isocyanurate.  Contact
     dermatitis, 21(3):202-203.

    Foulds IS, Koh D (1992) Allergic contact dermatitis from resin
    hardeners during the manufacture of thermosetting coating paints.
     Contact dermatitis, 26:87-90.

    Hazleton (1987)  Mutagenicity test on Araldite PT 810 in the Ames
    Salmonella/microsome reverse mutation assay (No. E-9782-0-401). 
    Veenendaal, Hazleton Biotechnologies.

    Hazleton (1989a)  Mutagenicity test on PL88-810 in the mouse
     spermatogonial cell cytogenetic assay (No. 10386-0-474). Kensington,
    MD, Hazleton Laboratories America Inc.

    Hazleton (1989b)  Mutagenicity test on PL88-810 in the dominant 
     lethal assay (No. 10386-0-471). Kensington, MD, Hazleton
    Laboratories America Inc.

    Hazleton (1991)  Study to evaluate the chromosome damaging potential
     of TK 10622 (PT810 [TGIC, 97%]) by its effects on the spermatogonial
     cells of treated mice. Heslington, York, Hazleton Microtest.

    Howard P (1989)  Handbook of environmental fate and exposure data for
     organic chemicals. Vol.1. Large production and priority pollutants. 
    Chelsea, MI, Lewis Publishers, p. 485.

    HSE (1992)  Toxicity review 27 - Part 1: Triglycidyl isocyanurate.
    United Kingdom, Health and Safety Executive, HMSO Publication (ISBN 0
    11 886343 6).

    HSE (1994)  Triglycidyl isocyanurate, a review of use and exposure. 
    United Kingdom, Health and Safety Executive, Hygiene Technology and
    Chemical Agents Unit.

    IPCS (1997)  International Chemical Safety Card - Triglycidyl
     isocyanurate. Geneva, World Health Organization, International
    Programme on Chemical Safety (No. 1274).

    Jolanki R, Kanerva L, Estlander T, Tarvainen K (1994) Concomitant
    sensitization to triglycidyl isocyanurate, diaminodiphenylmethane and
    2-hydroxyethyl methacrylate from silk-screen printing coatings in the
    manufacture of circuit boards.  Contact dermatitis, 30:12-15.

    Loveday KS, Anderson BE, Resnick MA, Zeiger E (1990) Chromosome
    aberration and sister chromatid exchange tests in Chinese hamster
    ovary cells  in vitro. V: Results with 46 chemicals.  Environmental 
     and molecular mutagenesis, 16:272-303.

    Matthias CG (1988) Allergic contact dermatitis from triglycidyl
    isocyanurate in polyester paint pigments.  Contact dermatitis, 
    19(1):67-68.

    McFadden JP, Rycroft RJG (1993) Occupational contact dermatitis from
    triglycidyl isocyanurate in a powder paint sprayer.  Contact 
     dermatitis, 28:251.

    Munro CS, Lawrence CM (1992) Occupational contact dermatitis from
    triglycidyl isocyanurate in a powder paint factory.  Contact 
     dermatitis, 26:59.

    Neidhart JA (1984) Phase I trial of Teroxirone.  Cancer treatment 
     reports, 68:1115-1119.

    NICNAS (1994)  Priority Existing Chemical No.1 - Triglycidyl 
     isocyanurate, full public report, National Industrial Chemicals 
     Notification and Assessment Scheme. Canberra, Australian Government
    Publishing Service, April.

    Nishioka K, Ogasawara M, Asagami C (1988) Occupational contact allergy
    to triglycidyl isocyanurate (TGIC, TEPIC).  Contact dermatitis, 
    19(5):379-380.

    Nissan (no date)  TEPIC, information on basic properties. Tokyo,
    Nissan Chemical Industries Ltd.

    Piirila P, Estlander T, Keskinen H, Jolanki R, Laakkonen A, Pfaffli P,
    Tupasela O, Tuppurainen M, Nordman H (1997) Occupational asthma caused
    by triglycidyl isocyanurate (TGIC).  Clinical and experimental 
     allergy, 27:510-514.

    Rubin J, Kovach JS, Ames MM, Moertel CG, Creagan ET, O'Connell MJ
    (1987) Phase I study of two schedules of Teroxirone.  Cancer 
     treatment reports, 71:489-492.

    Safepharm (1988a)  TEPIC-G: Acute oral toxicity test in the rat 
     (No. 14/10). Derby, Safepharm Laboratories Ltd.

    Safepharm (1988b)  TEPIC-G: Acute dermal toxicity (limit test) in 
     the rat (No. 14/11). Derby, Safepharm Laboratories Ltd.

    Safepharm (1988c)  TEPIC-G: Acute dermal irritation test in the 
     rabbit (No. 14/12). Derby, Safepharm Laboratories Ltd.

    Safepharm (1988d)  TEPIC-G: Acute dermal irritation test in the 
     rabbit (24-hour exposure) (No. 14/13). Derby, Safepharm Laboratories
    Ltd.

    Safepharm (1988e)  TEPIC-G: Magnusson and Kligman maximisation study
     in the guinea pig (No. 14/14). Derby, Safepharm Laboratories Ltd.

    Safepharm (1991)  TEPIC SP: Five-day repeat exposure inhalation
     toxicity study in the male mouse (No. 14/68). Derby, Safepharm
    Laboratories Ltd.

    Safepharm (1992)  TGIC technical and TGIC ten per cent powder:
     Chromosome analysis in mouse spermatogonial cells, comparative
     inhalation study (No. 14/75) [draft]. Derby, Safepharm Laboratories
    Ltd.

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    Springer-Verlag, p. 64.

    Shell (1971)  Toxicity studies on the diglycidyl esters of
     tetrahydrophthalic and hexahydrophthalic acids and of
     triglycidylisocyanurate: Repeated dosing experiments with rats
     (TLGR.0019.71). London, Shell Research Ltd.

    Sofuni T, Matsuoka A, Sawada M, Ishidate M Jr, Zeiger E, Shelby MD
    (1990) A comparison of chromosome aberration induction by 25 compounds
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     Mutation research, 241:175-213.

    APPENDIX 1 - SOURCE DOCUMENT

     National Industrial Chemicals Notification and Assessment Scheme -
     Triglycidyl Isocyanurate, Priority Existing Chemical No. 1, Full
     Public Report (1994)

         Copies of the NICNAS (1994) report on triglycidyl isocyanurate
    (prepared by D. Willcocks, L. Onyon, C. Jenkins, and B. Diver) may be
    obtained from:

         Australian Government Publishing Service
         Mail Order Service
         GPO Box 84
         Canberra 2601, Australia

         NICNAS reports are prepared to meet the requirements of the
     Industrial Chemicals Notification and Assessment Act, 1989, as
     amended.  In the preparation of the assessment report, both internal
    and external peer review are undertaken.  Under the NICNAS
    legislation, applicants for the assessment of a chemical (i.e.
    importers and manufacturers of the chemical) may apply for variations
    to the draft report.  The following companies participated in the
    review of the assessment at this stage: Ciba-Geigy Australia Ltd,
    Dulux Powder Coatings, Evode Powder Coatings Pty Ltd, Itochu Australia
    Ltd, Jotun Powder Coatings Pty Ltd, Sumitomo Australia Ltd, Taubmans
    Pty Ltd, and Western Coatings Ltd.

         In the assessment of triglycidyl isocyanurate, Ciba-Geigy
    Australia Ltd made several requests to vary the assessment report -
    notably in the areas of acute toxicity and mutagenicity - which the
    Director of NICNAS refused.  Consequently, Ciba-Geigy lodged an
    application for review of the Director's decision with the independent
    Administrative Appeals Tribunal (members included Justice D.F.
    O'Connor and Professor G. Johnston, Sydney University).  The
    Administrative Appeals Tribunal looked at all the material relevant to
    the assessment decisions in question and upheld the Director's
    decisions.1  During the Administrative Appeals Tribunal review
    process, the following expert witnesses were called upon: Dr D.J.
    Birkett, Flinders University School of Medicine, Australia; Dr M.E.
    McManus, University of Queensland, Australia; Dr H.J. Weideli,
    Ciba-Geigy Ltd, Basel, Switzerland; Dr C. Winder, University of New
    South Wales, Australia; and Dr E. Zeiger, National Institute of
    Environmental Health Sciences, Research Triangle Park, NC, USA.

              

    1 Administrative Appeals Tribunal, No. P93/339, Re Ciba-Geigy
    Australia Ltd (Applicant) and Worksafe Australia (Respondent), March
    1994.

    APPENDIX 2 - CICAD PEER REVIEW

         The draft CICAD on triglycidyl isocyanurate was sent for review
    to institutions and organizations identified by IPCS after contact
    with IPCS national Contact Points and Participating Institutions, as
    well as to identified experts.  Comments were received from:

         Ciba Speciality Chemicals Inc., Basel, Switzerland

         Department of Health, London, United Kingdom

         Department of Public Health Promotion, Prague, Czech Republic

         Environment Canada, Ottawa, Canada

         Health and Safety Executive, Bootle, United Kingdom

         Health Canada, Ottawa, Canada

         National Chemicals Inspectorate (KEMI), Solna, Sweden

         National Institute of Occupational Health, Budapest, Hungary

         National Institute of Public Health, Oslo, Norway

         United States Department of Health and Human Services (National
         Institute for Occupational Safety and Health, Cincinnati, USA;
         National Institute of Environmental Health Sciences, Research
         Triangle Park, USA)

         United States Environmental Protection Agency (National Center
         for Environmental Assessment, Office of Research and Development,
         Research Triangle Park, USA)

    APPENDIX 3 - CICAD FINAL REVIEW BOARD

    Berlin, Germany, 26-28 November 1997

    Members

    Dr H. Ahlers, Education and Information Division, National Institute
    for Occupational Safety and Health, Cincinnati, OH, USA

    Mr R. Cary, Health Directorate, Health and Safety Executive, Bootle,
    United Kingdom

    Dr S. Dobson, Institute of Terrestrial Ecology, Huntingdon, United
    Kingdom

    Dr R.F. Hertel, Federal Institute for Health Protection of Consumers &
    Veterinary Medicine, Berlin, Germany  (Chairperson)

    Mr J.R. Hickman, Health Protection Branch, Health Canada, Ottawa,
    Ontario, Canada

    Dr  I. Mangelsdorf, Documentation and Assessment of Chemicals,
    Fraunhofer Institute for Toxicology and Aerosol Research, Hanover,
    Germany

    Ms M.E. Meek, Environmental Health Directorate, Health Canada, Ottawa,
    Ontario, Canada  (Rapporteur)

    Dr K. Paksy, Department of Reproductive Toxicology, National Institute
    of Occupational Health, Budapest, Hungary

    Mr V. Quarg,  Ministry for the Environment, Nature Conservation &
    Nuclear Safety, Bonn, Germany

    Mr D. Renshaw, Department of Health, London, United Kingdom

    Dr J. Sekizawa, Division of Chemo-Bio Informatics, National Institute
    of Health Sciences, Tokyo, Japan

    Prof S. Soliman, Department of Pesticide Chemistry, Alexandria
    University, Alexandria, Egypt  (Vice-Chairperson)

    Dr M. Wallen, National Chemicals Inspectorate (KEMI), Solna, Sweden

    Ms D. Willcocks, Chemical Assessment Division, Worksafe Australia,
    Camperdown, Australia

    Dr M. Williams-Johnson, Division of Toxicology, Agency for Toxic
    Substances and Disease Registry, Atlanta, GA, USA

    Dr K. Ziegler-Skylakakis, Senatskommission der Deutschen
    Forschungsgemeinschaft zuer Pruefung gesundheitsschaedlicher
    Arbeitsstoffe, GSF-Institut fuer Toxikologie, Neuherberg,
    Oberschleissheim, Germany

    Observers

    Mrs B. Dinham,1 The Pesticide Trust, London, United Kingdom

    Dr R. Ebert, KSU Ps-Toxicology, Huels AG, Marl, Germany (representing
    ECETOC, the European Centre for Ecotoxicology and Toxicology of
    Chemicals)

    Mr R. Green,1 International Federation of Chemical, Energy, Mine and
    General Workers' Unions, Brussels, Belgium

    Dr B. Hansen,1 European Chemicals Bureau, European Commission, Ispra,
    Italy

    Dr J. Heuer, Federal Institute for Health Protection of Consumers &
    Veterinary Medicine, Berlin, Germany

    Mr T. Jacob,1 DuPont, Washington, DC, USA

    Ms L. Onyon, Environment Directorate, Organisation for Economic
    Co-operation and Development, Paris, France

    Dr H.J. Weideli, Ciba Speciality Chemicals Inc., Basel, Switzerland
    (representing CEFIC, the European Chemical Industry Council)

    Secretariat

    Dr M. Baril, International Programme on Chemical Safety, World Health
    Organization, Geneva, Switzerland

    Dr R.G. Liteplo, Health Canada, Ottawa, Ontario, Canada

    Ms L. Regis, International Programme on Chemical Safety, World Health
    Organization, Geneva, Switzerland

    Mr A. Strawson, Health and Safety Executive, London, United Kingdom

    Dr P. Toft, Associate Director, International Programme on Chemical
    Safety, World Health Organization, Geneva, Switzerland


              

    1 Invited but unable to attend.

    RÉSUMÉ D'ORIENTATION

         Ce CICAD est fondé principalement sur l'évaluation de
    l'isocyanurate de triglycidyle réalisée dans le cadre du NICNAS
    (Australian National Industrial Chemicals Notification and Assessment
    Scheme) et publiée en avril 1994 (NICNAS, 1994).  De nouvelles
    informations parues entre l'achèvement du rapport NICNAS et
    novembre 1997 ont également été évaluées et incorporées dans ce CICAD,
    de même que des informations complémentaires extraites de l'étude du
    United Kingdom Health and Safety Executive (HSE, 1992) portant sur la
    toxicité de cette substance.  Des informations relatives à l'examen du
    rapport NICNAS par les pairs et à sa disponibilité figurent à
    l'appendice 1.  Les renseignements concernant l'examen du CICAD par
    les pairs font l'objet de l'appendice 2.  Ce CICAD a été approuvé en
    tant qu'évaluation internationale lors d'une une réunion du Comité
    d'évaluation finale qui s'est tenue à Berlin (Allemagne) du 26 au
    28 novembre 1997.  La liste des participants à cette réunion figure à
    l'appendice 3.  La fiche d'information sur la sécurité chimique de
    l'isocyanurate de triglycidyle (ICSC 1274), établie par le Programme
    international sur la Sécurité chimique (IPCS, 1997), est également
    reproduite dans le présent document.

         L'isocyanurate de triglycidyle (CAS N° 2451-62-9) est une
    substance chimique de synthèse qui se présente sous la forme d'une
    poudre blanche ou d'un granulé pratiquement inodore à la température
    ambiante.  Il est employé principalement comme agent de polymérisation
    ou de réticulation tridimensionnelle dans les revêtements de polyester
    en poudre (peinture).  Ces revêtements en poudre contiennent
    généralement de 4 à 10 % d'isocyanurate de triglycidyle.  Il est
    également utilisé dans les encres servant à la fabrication de masques
    dans l'industrie des circuits imprimés.  L'encre est constituée de
    deux parties dont l'élément durcisseur contient approximativement 60 %
    d'isocyanurate de triglycidyle.  La plus grande partie de
    l'isocyanurate de triglycidyle présent dans ces revêtements en poudre
    et ces encres est immobilisée par réticulation dans une matrice
    insoluble.

         En principe, l'exposition de la population générale à
    l'isocyanurate de triglycidyle devrait être minime.  Par contre, il
    existe un risque d'exposition professionnelle lors de la fabrication
    et de l'utilisation de cette substance et des produits qui en
    contiennent.

         On dispose de peu d'informations sur les effets de l'isocyanurate
    de triglycidyle chez l'homme.  On a signalé plusieurs cas de dermatite
    allergique de contact et un cas de sensibilisation respiratoire à la
    suite d'une exposition professionnelle.

         L'isocyanurate de triglycidyle est très toxique par ingestion et
    inhalation chez les animaux de laboratoire et il peut provoquer de
    graves lésions oculaires.  Sur la peau, il agit comme sensibilisant,
    mais non comme irritant.  Les données sur sa toxicité à la suite d'une
    exposition répétée sont limitées.  Chez des rats et des souris soumis
    à des expositions répétées pendant une courte période (5-7 jours), on
    a constaté des effets sur les reins, le foie, les poumons, le tube
    digestif et les spermatogonies.  Une étude de 13 semaines menée sur
    des rats mâles pour évaluer la toxicité de l'isocyanurate de
    triglycidyle et ses effets sur la fécondité a révélé une réduction de
    nombre de spermatozoïdes liée à la dose.

         Des études de génotoxicité  in vitro et  in vivo ont montré que
    l'isocyanurate de triglycidyle est un mutagène à action directe
    capable d'agir sur les organes de la reproduction.  Compte tenu de sa
    génotoxicité potentielle, toutes les mesures appropriées doivent être
    prises pour réduire au minimum l'exposition humaine à cette substance.

         Compte tenu de sa faible persistance et d'une écotoxicité
    probablement faible, l'isocyanurate de triglycidyle ne devrait pas
    présenter de risque significatif pour l'environnement, sauf en cas de
    rejet accidentel ou d'élimination dans des conditions inadaptées.

    RESUMEN DE ORIENTACION

         Este CICAD se basa principalmente en la evaluación del
    isocianurato de triglicidilo realizada en el marco del Plan Nacional
    Australiano de Notificación y Evaluación de Sustancias Químicas
    Industriales (NICNAS) y publicada en abril de 1994 (NICNAS, 1994). 
    También se ha evaluado e incorporado a este CICAD la información
    aparecida desde la terminación del informe del NICNAS hasta noviembre
    de 1997.  Se ha incluido asimismo alguna información adicional
    procedente del examen de la toxicidad del isocianurato de triglicidilo
    de la Dirección de Salud y Seguridad del Reino Unido (HSE, 1992).  La
    información relativa al examen colegiado del informe del NICNAS y a su
    disponibilidad figura en el Apéndice 1.  La información sobre el
    examen colegiado de este CICAD se presenta en el Apéndice 2.  Este
    CICAD se aprobó como evaluación internacional en una reunión de la
    Junta de Evaluación Final celebrada en Berlín (Alemania) los días
    26-28 de noviembre de 1997.  La lista de participantes en la Junta de
    Evaluación Final figura en el Apéndice 3.  La Ficha internacional de
    seguridad química (ICSC 1274) para el isocianurato de triglicidilo,
    preparada por el Programa Internacional de Seguridad de las Sustancias
    Químicas (IPCS, 1997), también se reproduce en este documento.

         El isocianurato de triglicidilo (CAS Nº 2451-62-9), sustancia
    química sintética en forma de polvo blanco o granulada prácticamente
    inodora a temperatura ambiente, se utiliza sobre todo como agente de
    polimerización o de reticulación tridimensional en los revestimientos
    de poliéster en polvo (pintura).  Estos revestimientos en polvo suelen
    contener entre un 4% y un 10% de isocianurato de triglicidilo. 
    También se utiliza éste en las tintas que sirven para la fabricación
    de "máscaras" de soldadura en la industria de los circuitos impresos. 
    Las tintas constan de dos partes, cuyo elemento endurecedor contiene
    alrededor de un 60% de isocianurato de triglicidilo.  La mayor parte
    de esta sustancia presente en los revestimientos en polvo y las tintas
    mencionados se inmoviliza mediante la reticulación en una matriz
    insoluble.

         La exposición de la población general al isocianurato de
    triglicidilo se supone que es mínima; sin embargo, hay riesgo de
    exposición profesional durante la fabricación y la utilización de esta
    sustancia y de los productos que la contienen.

         Se dispone de escasa información sobre los efectos del
    isocianurato de triglicidilo en el ser humano.  Se han notificado
    varios casos de dermatitis alérgica por contacto y un caso de
    sensibilización respiratoria debidos a exposición profesional.

         El isocianurato de triglicidilo es muy tóxico en animales de
    laboratorio por ingestión e inhalación y puede provocar lesiones
    oculares graves.  Es sensibilizador cutáneo, pero no irritante de la
    piel.  Los datos sobre toxicidad por exposición repetida son
    limitados. En estudios de exposición repetida de corta duración (5-7
    días) en ratas y ratones, se observaron efectos en los riñones, el
    hígado, los pulmones, el aparato digestivo y los espermatogonios.  En

    un estudio de toxicidad/fecundidad de 13 semanas en ratas machos se
    observó una reducción del número de espermatozoides relacionada con la
    dosis.

         Los estudios de genotoxicidad  in vitro e  in vivo indican que
    el isocianurato de triglicidilo es un mutágeno de acción directa capaz
    de afectar los órganos de la reproducción.  A la vista de su
    genotoxicidad potencial, deben tomarse todas las medidas apropiadas
    para reducir al mínimo la exposición humana a esta sustancia.

         Debido a su escasa persistencia y su ecotoxicidad probablemente
    baja, no es probable que el isocianurato de triglicidilo represente un
    riesgo significativo para el medio ambiente, excepto en el caso de un
    accidente o de una eliminación inapropiada.

    




    See Also:
       Toxicological Abbreviations
       Triglycidyl isocyanurate (ICSC)