triglycidyl isocyanurate - world health … report contains the collective views of an international...

This report contains the collective views of an international group of experts and does notnecessarily represent the decisions or the stated policy of the United Nations EnvironmentProgramme, the International Labour Organisation, or the World Health Organization.

Concise International Chemical Assessment Document 8

TRIGLYCIDYL ISOCYANURATE

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

Please note that the layout and pagination of this pdf file are not identical to the printedCICAD

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

World Health OrganizationGeneva, 1998

The International Programme on Chemical Safety (IPCS), established in 1980, is a joint ventureof the United Nations Environment Programme (UNEP), the International Labour Organisation (ILO),and the World Health Organization (WHO). The overall objectives of the IPCS are to establish thescientific basis for assessment of the risk to human health and the environment from exposure tochemicals, through international peer review processes, as a prerequisite for the promotion of chemicalsafety, and to provide technical assistance in strengthening national capacities for the sound managementof chemicals.

The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) wasestablished in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO,the United Nations Industrial Development Organization, and the Organisation for Economic Co-operationand Development (Participating Organizations), following recommendations made by the 1992 UNConference on Environment and Development to strengthen cooperation and increase coordination in thefield of chemical safety. The purpose of the IOMC is to promote coordination of the policies andactivities pursued by the Participating Organizations, jointly or separately, to achieve the soundmanagement of chemicals in relation to human health and the environment.

WHO Library Cataloguing in Publication Data

Triglycidyl isocyanurate.

(Concise international chemical assessment document ; 8)

First draft prepared by D. Willcocks, L. Onyon, C. Jenkins andB. 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

The World Health Organization welcomes requests for permission to reproduce or translate itspublications, in part or in full. Applications and enquiries should be addressed to the Office ofPublications, World Health Organization, Geneva, Switzerland, which will be glad to provide the latestinformation on any changes made to the text, plans for new editions, and reprints and translations alreadyavailable.

©World Health Organization 1998

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

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

The Federal Ministry for the Environment, Nature Conservation and Nuclear Safety, Germany,provided financial support for the printing of this publication.

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TABLE OF CONTENTS

FOREWORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1. EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

2. IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

3. ANALYTICAL METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

4. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

5. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION . . . . . . . . . . . . . . . . . . . 5

6. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

6.1 Environmental levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66.2 Human exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

7. COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS ANDHUMANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

8. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS . . . . . . . . . . . . . . . . . . . . . . . 7

8.1 Single exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78.2 Irritation and sensitization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78.3 Short-term exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78.4 Long-term exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88.5 Genotoxicity and related end-points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88.6 Reproductive and developmental toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

9. EFFECTS ON HUMANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

10. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD . . . . . . . . . . . . . . . . . . . . . . . . . 11

11. EFFECTS EVALUATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

11.1 Evaluation of health effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 11.1.1 Hazard identification and dose–response assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

11.1.2 Criteria for setting guidance values for triglycidyl isocyanurate . . . . . . . . . . . . . . . . . . . . . . . 12 11.1.3 Sample risk characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1211.2 Evaluation of environmental effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

13. HUMAN HEALTH PROTECTION AND EMERGENCY ACTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

13.1 Human health hazards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1313.2 Advice to physicians . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

14. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

INTERNATIONAL CHEMICAL SAFETY CARD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16


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APPENDIX 1 — SOURCE DOCUMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

APPENDIX 2 — CICAD PEER REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

APPENDIX 3 — CICAD FINAL REVIEW BOARD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

RÉSUMÉ D’ORIENTATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

RESUMEN DE ORIENTACIÓN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Triglycidyl isocyanurate

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FOREWORD

Concise International Chemical AssessmentDocuments (CICADs) are the latest in a family ofpublications from the International Programme onChemical Safety (IPCS) — a cooperative programme ofthe World Health Organization (WHO), the InternationalLabour Organisation (ILO), and the United NationsEnvironment Programme (UNEP). CICADs join theEnvironmental Health Criteria documents (EHCs) asauthoritative documents on the risk assessment ofchemicals.

CICADs are concise documents that providesummaries of the relevant scientific informationconcerning the potential effects of chemicals uponhuman health and/or the environment. They are basedon selected national or regional evaluation documents oron existing EHCs. Before acceptance for publication asCICADs by IPCS, these documents undergo extensivepeer review by internationally selected experts to ensuretheir completeness, accuracy in the way in which theoriginal data are represented, and the validity of theconclusions drawn.

The primary objective of CICADs ischaracterization of hazard and dose–response fromexposure to a chemical. CICADs are not a summary of allavailable data on a particular chemical; rather, theyinclude only that information considered critical forcharacterization of the risk posed by the chemical. Thecritical studies are, however, presented in sufficientdetail to support the conclusions drawn. For additionalinformation, the reader should consult the identifiedsource documents upon which the CICAD has beenbased.

Risks to human health and the environment willvary considerably depending upon the type and extentof exposure. Responsible authorities are stronglyencouraged to characterize risk on the basis of locallymeasured or predicted exposure scenarios. To assist thereader, examples of exposure estimation and riskcharacterization are provided in CICADs, wheneverpossible. These examples cannot be considered asrepresenting all possible exposure situations, but areprovided as guidance only. The reader is referred toEHC 1701 for advice on the derivation of health-basedguidance values.

While every effort is made to ensure that CICADsrepresent the current status of knowledge, newinformation is being developed constantly. Unlessotherwise stated, CICADs are based on a search of thescientific literature to the date shown in the executivesummary. In the event that a reader becomes aware ofnew information that would change the conclusionsdrawn in a CICAD, the reader is requested to contact theIPCS to inform it of the new information.

Procedures

The flow chart shows the procedures followed toproduce a CICAD. These procedures are designed totake advantage of the expertise that exists around theworld — expertise that is required to produce the high-quality evaluations of toxicological, exposure, and otherdata that are necessary for assessing risks to humanhealth and/or the environment.

The first draft is based on an existing national,regional, or international review. Authors of the firstdraft are usually, but not necessarily, from the institutionthat developed the original review. A standard outlinehas been developed to encourage consistency in form. The first draft undergoes primary review by IPCS toensure that it meets the specified criteria for CICADs.

The second stage involves international peerreview by scientists known for their particular expertiseand by scientists selected from an international rostercompiled by IPCS through recommendations from IPCSnational Contact Points and from IPCS ParticipatingInstitutions. Adequate time is allowed for the selectedexperts to undertake a thorough review. Authors arerequired to take reviewers’ comments into account andrevise their draft, if necessary. The resulting seconddraft is submitted to a Final Review Board together withthe reviewers’ comments.

The CICAD Final Review Board has severalimportant functions:

– to ensure that each CICAD has been subjected toan appropriate and thorough peer review;

– to verify that the peer reviewers’ comments havebeen addressed appropriately;

– to provide guidance to those responsible for thepreparation of CICADs on how to resolve anyremaining issues if, in the opinion of the Board, theauthor has not adequately addressed all commentsof the reviewers; and

– to approve CICADs as international assessments.

Board members serve in their personal capacity, not asrepresentatives of any organization, government, orindustry. They are selected because of their expertise inhuman and environmental toxicology or because of their

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


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S E L E C T I O N O F H I G H Q U A L I T YNATIONAL/REGIONAL

ASSESSMENT DOCUMENT(S)

CICAD PREPARATION FLOW CHART

FIRST DRAFTPREPARED

REVIEW BY IPCS CONTACT POINTS/SPECIALIZED EXPERTS

FINAL REVIEW BOARD 2

FINAL DRAFT 3

EDITING

APPROVAL BY DIRECTOR, IPCS

PUBLICATION

SELECTION OF PRIORITY CHEMICAL

1 Taking into account the comments from reviewers.2 The second draft of documents is submitted to the Final Review Board together with the reviewers’ comments.3 Includes any revisions requested by the Final Review Board.

REVIEW OF COMMENTS (PRODUCER/RESPONSIBLE OFFICER),PREPARATION

OF SECOND DRAFT 1

PRIMARY REVIEW BY IPCS (REVISIONS AS NECESSARY)


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experience in the regulation of chemicals. Boards arechosen according to the range of expertise required for ameeting and the need for balanced geographicrepresentation.

Board members, authors, reviewers, consultants,and advisers who participate in the preparation of aCICAD are required to declare any real or potentialconflict of interest in relation to the subjects underdiscussion at any stage of the process. Representativesof nongovernmental organizations may be invited toobserve the proceedings of the Final Review Board. Observers may participate in Board discussions only atthe invitation of the Chairperson, and they may notparticipate in the final decision-making process.


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1. EXECUTIVE SUMMARY

This CICAD was based principally on the assess-ment of triglycidyl isocyanurate completed under theAustralian National Industrial Chemicals Notificationand Assessment Scheme (NICNAS) and published inApril 1994 (NICNAS, 1994). Information that has becomeavailable since completion of the NICNAS report,identified up to November 1997, has also been assessedand included in this CICAD. Some additionalinformation from the United Kingdom Health and SafetyExecutive’s toxicity review of triglycidyl isocyanurate(HSE, 1992) has also been included. Information on thenature of peer review and availability of the NICNASreport is presented in Appendix 1. Information on thepeer review of this CICAD is presented in Appendix 2. This CICAD was approved as an internationalassessment at a meeting of the Final Review Board, heldin Berlin, Germany, on 26–28 November 1997. Participants at the Final Review Board meeting are listedin Appendix 3. The International Chemical Safety Card(ICSC 1274) for triglycidyl isocyanurate, produced by theInternational Programme on Chemical Safety (IPCS,1997), has also been reproduced in this document.

Triglycidyl isocyanurate (CAS no. 2451-62-9), asynthetic white powder or granule with no discernibleodour at room temperature, is used mainly as a three-dimensional cross-linking or curing agent in polyesterpowder coatings (paints). These powder coatingsusually contain between 4 and 10% triglycidyl isocyan-urate. Triglycidyl isocyanurate is also used in solder“mask” inks in the printed circuit board industry. Thetwo-part inks contain approximately 60% triglycidylisocyanurate in the hardener component. Much of thetriglycidyl isocyanurate in powder coatings and solderinks is immobilized through cross-linking in an insolublematrix.

Exposure of the general population to triglycidylisocyanurate is expected to be minimal; however, there ispotential for occupational exposure during the manu-facture of triglycidyl isocyanurate and the manufactureand use of products containing the chemical.

Little information is available on the effects oftriglycidyl isocyanurate on humans. Several cases ofallergic contact dermatitis and one case of respiratorysensitization caused by occupational exposure to tri-glycidyl isocyanurate have been reported.

In laboratory animals, triglycidyl isocyanurate isacutely toxic by ingestion and inhalation and can causeserious eye damage. It is a skin sensitizer but not a skinirritant. The data for repeated-exposure toxicity arelimited. In short-term (5–7 days) repeated-exposure

studies in rats and mice, effects on the kidneys, liver,lungs, gastrointestinal tract, and spermatogonial cellswere observed. In a 13-week toxicity/fertility study inmale rats, a dose-related reduction in the number ofspermatozoa was observed.

In vitro and in vivo genotoxicity studies indicatethat triglycidyl isocyanurate is a direct-acting mutagencapable of affecting the reproductive organs. In view ofits potential genotoxicity, all appropriate measuresshould be taken to minimize human exposure to trigly-cidyl isocyanurate.

Owing to its low persistence and probable lowecotoxicity, triglycidyl isocyanurate is unlikely to pose asignificant hazard to the environment, except in the caseof an accident or inappropriate disposal.

2. IDENTITY AND PHYSICAL/CHEMICALPROPERTIES

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 gradesTEPIC and Araldite PT 810. Technical-grade triglycidylisocyanurate is a mixture of two diastereomers, alpha andbeta. Some physical and chemical properties oftriglycidyl isocyanurate (technical grades) are presentedin Table 1. Additional properties are presented in theInternational Chemical Safety Card reproduced in thisdocument.

Triglycidyl isocyanurate is a white powder orgranule with no discernible odour at room temperature.The solubility of Araldite PT 810 in various solvents at25 °C is as follows: epichlorohydrin, <22%; methanol,7.3%; toluene, 3%; isopropanol, 1%. Triglycidyl iso-cyanurate reacts rapidly with primary and secondaryamines, carboxylic acids and anhydrides, thiols, phenols,and alcohols. It can be polymerized by catalysts andmay undergo violent autopolymerization. Combustionproducts include carbon dioxide, carbon monoxide, andoxides of nitrogen.

3. ANALYTICAL METHODS

Methods of detection and analysis include infraredspectroscopy, mass spectroscopy, epoxy equivalentweight, gas chromatography, and high-performanceliquid chromatography. Methodology for the sampling


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

Property TEPICaAraldite PT

810b

Degree of purity (%triglycidyl isocyanurate)

90 (approx.) >97

Melting point (°C) 90–125 95

Vapour pressure (kPa at20 °C)

n.a.c 7.2 × 10–9

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

9 8.7

Partition coefficient (logKow)

!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).

and analysis of triglycidyl isocyanurate in air has beendeveloped by its manufacturers and involves the collec-tion of the dust on a glass fibre filter, followed by high-performance liquid chromatography with ultravioletdetection (detection limit 0.8 :g/m3) (NICNAS, 1994). Methodology for the analysis of triglycidyl isocyanuratein other environmental media is not available.

4. SOURCES OF HUMAN ANDENVIRONMENTAL EXPOSURE

Triglycidyl isocyanurate does not occur naturally. It is produced industrially by reacting cyanuric acid withexcess epichlorohydrin. The worldwide production oftriglycidyl isocyanurate is approximately 7000–8000tonnes per year. Australia imports 100–1000 tonnes peryear as technical-grade triglycidyl isocyanurate for themanufacture of polyester powder coatings or as aningredient in powder coatings. The United Kingdomimports approximately 400 tonnes of triglycidyl iso-cyanurate per year for use in powder coatings. In theUnited Kingdom, approximately 30 tonnes of solder“mask” inks containing triglycidyl isocyanurate aremanufactured per year by four or five companies(NICNAS, 1994).

The main use of triglycidyl isocyanurate is as athree-dimensional cross-linking or curing agent inpolyester powder coatings (paints). In the manufactureof powder coatings, triglycidyl isocyanurate granules aremixed 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 powdercoating is >10 :m.

Powder coatings usually contain 4–10% triglycidylisocyanurate and are sprayed onto metal objects by anelectrostatic process. The coated metal objects are thentreated in an oven to a temperature of about 200 °C. Thisheating causes the powder coatings to melt, flow, andchemically cross-link. The coatings are durable andresist ultraviolet damage; as a result, they are typicallyused in outdoor applications. Triglycidyl isocyanurateis also used in solder “mask” inks in the printed circuitboard industry. The two-part inks contain approximately60% triglycidyl isocyanurate in the hardener component. The inks are applied by curtain coating, electrostaticspraying, or screen printing. The coated circuit board isfinally passed through an oven at 150 °C to complete thecuring.

Release of the chemical to air is expected to beminimal. During the manufacture of triglycidyl isocyan-urate and the formulation of products containing trigly-cidyl isocyanurate, dust extractors and other pollutioncontrol devices remove particulate waste for disposal. Triglycidyl isocyanurate contained in such waste iseffectively immobilized after consignment to landfill,particularly if waste powder is heat-cured beforehand. Release to the environment during normal use of powdercoatings in spray painting workplaces is expected to below, as electrostatic application is an efficient applicationmethod. Triglycidyl isocyanurate may be released intowater by facilities that manufacture, process, or use thischemical.

5. ENVIRONMENTAL TRANSPORT,DISTRIBUTION, AND TRANSFORMATION

Much of the triglycidyl isocyanurate in powdercoatings and solder inks is immobilized through cross-linking in an insoluble matrix. As triglycidyl isocyan-urate is an epoxide, any residues not captured in thisway are expected to be rapidly degraded throughmicrobial action or abiotic hydrolysis.

Triglycidyl isocyanurate did not satisfy criteria forready biodegradability in the modified Sturm test. Whenexposed for 28 days to bacteria from a sewage treatmentplant, 9% and 48% of theoretical amounts of carbondioxide were evolved from solutions of 10 and 20 mgtriglycidyl isocyanurate/litre, respectively (Ciba-Geigy,1988d). Although these results indicate incompletemineralization, they are likely to reflect complete primarydegradation, with slow opening of the triazine ring


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restricting the rate of mineralization, as has been notedfor triazine herbicides (Scheunert, 1992).

In a modified Zahn-Wellers test measuring carbondioxide evolution rather than loss of dissolved organiccarbon, triglycidyl isocyanurate was inherently biode-gradable 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 testwas said to be poor, necessitating the use of anemulsifier to achieve the stated test concentration, theresults of this study should be treated with caution. Triglycidyl isocyanurate is not expected to accumulate insoil or sediment because of high mobility and limitedpersistence. High mobility may be predicted by analogywith the triazine herbicide hexazinone, a chemical knownto leach into groundwater. The oxirane substituents arenot expected to retard the mobility significantly, asmethyloxirane has a low soil organic matter adsorptioncoefficient, generally between 3 and 30 (Howard, 1989).

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

6. ENVIRONMENTAL LEVELS ANDHUMAN EXPOSURE

6.1 Environmental levels

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

6.2 Human exposure

Exposure of the general population to triglycidylisocyanurate is expected to be minimal. There ispotential for occupational exposure, most likely viainhalation, during the manufacture of triglycidylisocyanurate and the manufacture and use of productscontaining triglycidyl isocyanurate. In powder coatings,triglycidyl isocyanurate is partially cross-linked to thepolyester resin before application, and it is only theunbound triglycidyl isocyanurate that is bioavailable. The amount of unbound triglycidyl isocyanurate variesbetween different powder coatings. The triglycidylisocyanurate in powder coatings after application to

metal particles is fully cross-linked and is bound in asolid matrix, from which it would not be bioavailable.

No monitoring data are available for the manufac-ture of triglycidyl isocyanurate; however, monitoringdata are available for exposure to triglycidyl isocyan-urate during the manufacture of powder coatings con-taining the chemical. In an Australian plant, triglycidylisocyanurate 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 triglycidylisocyanurate in air were #0.03 mg/m3 (time-weightedaverage) after changes, primarily improved workpractices, were implemented in the plant. In a plant inJapan, 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 UnitedKingdom Health and Safety Executive in 1994, triglycidylisocyanurate levels ranged from 0.01 to 0.44 mg/m3 (time-weighted average; mean 0.1 mg/m3), with correspondingtotal inhalable particulate levels of 1.1–64 mg/m3 (mean9.4 mg/m3) (HSE, 1994).

There are limited air monitoring data available forthe application of powder coatings containing triglycidylisocyanurate. In a survey of eight spray painting work-places in Australia in 1991, triglycidyl isocyanuratelevels up to 6.5 mg/m3 (time-weighted average) weremeasured (NICNAS, 1994). In a survey of 16 similarworkplaces by the Health and Safety Executive in theUnited Kingdom in 1994, triglycidyl isocyanurate levelsranged from 0.001 to 1.5 mg/m3 (time-weighted average;mean 0.24 mg/m3), with corresponding total inhalableparticulate levels between 0.2 and 131 mg/m3 (mean 13mg/m3) (HSE, 1994). Air monitoring data for the printedcircuit board industry were not available.

7. COMPARATIVE KINETICS ANDMETABOLISM IN LABORATORY ANIMALS

AND HUMANS

The only available human data are from clinicaltrials with "-triglycidyl isocyanurate (intravenousadministration), which indicate that "-triglycidyl iso-cyanurate has a mean half-life in the blood of approxi-mately 1 min and a mean total body clearance of 5.7litres/min (Ames et al., 1984; Neidhart, 1984; Rubin et al.,1987). Less than 1% of the administered dose wasrecovered unchanged in urine within 24 h (Ames et al.,1984).

In an oral (gavage) study in mice, at least 17% ofthe administered dose was absorbed within 24 h, with


7

blood analysis indicating that the absorption of trigly-cidyl isocyanurate administered in aqueous solution wastwice that of triglycidyl isocyanurate in sesame oil. Triglycidyl isocyanurate was distributed to the liver,stomach, and testes (the only tissues studied). Bloodplasma analysis indicated that triglycidyl isocyanuratewas metabolized by hydrolysis to the diol diepoxide, thebis-diol epoxide, and the fully hydrolysed tris-diol, withno free triglycidyl isocyanurate detected 8 h after treat-ment (Ciba-Geigy, 1990c).

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

In in vitro studies, rapid hydrolysis of triglycidylisocyanurate involving the enzyme epoxide hydrolasewas observed in mouse liver preparations (Ciba-Geigy,1990c). Hydrolysis was also observed in rat liverpreparations but not in rat lung preparations (Ames etal., 1984). Microsomal epoxide hydrolase activity withtriglycidyl isocyanurate as substrate measured in twohuman livers obtained from kidney donors was found tobe greater than the activity in rat liver (Ciba-Geigy,1993a).

8. EFFECTS ON LABORATORYMAMMALS AND IN VITRO TEST SYSTEMS

8.1 Single exposure

Triglycidyl isocyanurate is toxic to laboratory

animals following acute oral administration and inhala-tion exposure. The oral LD50 for triglycidyl isocyanurateranges from 188 to 715 mg/kg body weight in rats (Ciba-Geigy, 1975a, 1982a, 1990a; Safepharm, 1988a). Clinicalsigns of toxicity observed prior to death includedsedation, dyspnoea, and emaciation. Pathologicalfindings included oedematous and haemorrhagic lungs,haemorrhagic thymus, intestines, and testes, involutedtestes, and enlarged kidney.

In rat inhalation (nose-only) studies, an LC50 of 650mg/m3 was obtained with triglycidyl isocyanurate in dustform (Ciba-Geigy, 1979a), and an LC50 of >300 mg/m3 wasfound with triglycidyl isocyanurate in liquid aerosol form(Ciba-Geigy, 1979b). Slight inflammation of the nasalmucosa in the upper dose groups was observed. Therewere no substance-related gross organ changes insacrificed animals, and partial haemorrhage only wasobserved in the lungs of animals who died during the

study. An LC50 of 2000 mg/m3 was obtained for themouse (whole-body exposure to dust, particle size range3.2–3.9 :m) (Bushy Run, 1991). Clinical signs includedhypoactivity and ocular and respiratory irritation. Pathological observations included perinasal/periocular/perioral encrustation and lung discoloration.

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

8.2 Irritation and sensitization

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

Triglycidyl isocyanurate (commercial grade) waspositive for skin sensitization in guinea-pigs in twomodified Magnusson and Kligman studies (Ciba-Geigy,1988b; Safepharm, 1988e). In both studies, groups of 10male and 10 female guinea-pigs were initially exposed totriglycidyl isocyanurate and challenged 2 weeks afterinduction. Positive responses were observed in 25% ofthe test animals in one study (Ciba-Geigy, 1988b) and in60% of the test animals in the other study (Safepharm,1988e). No skin reactions were noted in the controlgroup at induction or when challenged with triglycidylisocyanurate.

8.3 Short-term exposure

In a 7-day oral rat study, gross pathology wasrecorded for the lungs, kidney, liver, stomach, andintestines. Renal tubular damage and haemorrhagic anddegenerative changes involving the gastric andduodenal mucosa were observed at the high triglycidylisocyanurate dose (216 mg/kg body weight per day formales and 172 mg/kg body weight per day for females). Less marked changes to the renal tubules were noted atthe low dose (54 mg/kg body weight per day for malesand 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 140mg/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 wereobserved at 10 mg/m3. Clinical signs of toxicity observedin the intermediate- and high-concentration groups


8

included lethargy, ptosis, decreased respiratory rate, andnoisy or gasping respiration. Gross pathology andorgan weights were recorded for the lungs, liver, kidney,and testes. Pathological findings included dark orreddened lungs, pale liver, pale kidneys, and congestionof the small intestine (Safepharm, 1991).

8.4 Long-term exposure

Information from general subchronic or chronictoxicity studies was not available.1

8.5 Genotoxicity and related end-points

The genotoxicity of triglycidyl isocyanurate hasbeen investigated in a wide range of in vitro and in vivoassays (Tables 2 and 3). Triglycidyl isocyanurate wasmutagenic in Salmonella typhimurium and mouselymphoma cells and clastogenic in Chinese hamsterovary cells in vitro. It induced chromosomal aberrationsin bone marrow cells in hamsters and in germ cells inmice following oral administration. Available data alsoindicate that triglycidyl isocyanurate has the potential toalkylate DNA.

In two reverse mutation assays, commercial-gradetriglycidyl isocyanurate induced mutations in the pres-ence and absence of metabolic activation in S. typhimur-ium strains TA1535, TA1538, TA98, and TA100, with theeffect more pronounced in the latter two strains (Ciba-Geigy, 1982d; Hazleton, 1987). Triglycidyl isocyanuratewas not mutagenic in TA1537. In one of these studies,triglycidyl isocyanurate did not induce back mutation inEscherichia coli WP2uvrA, with or without metabolicactivation (Ciba-Geigy, 1982d). All studies were wellconducted, using appropriate negative and positivecontrols, with the results indicating that triglycidylisocyanurate is a direct-acting mutagen.

In a mouse lymphoma cell assay, triglycidyl iso-cyanurate induced forward mutations in the presence ofmetabolic activation at 6.0 :g/ml and in the absence ofmetabolic activation at 2.8 :g/ml (Ciba-Geigy, 1983a). Triglycidyl isocyanurate with and without metabolicactivation induced sister chromatid exchanges andchromosomal aberrations in Chinese hamster ovary cells(Loveday et al., 1990; Sofuni et al., 1990). Triglycidylisocyanurate also tested positive for the induction ofchromosomal aberrations without metabolic activation inChinese hamster lung cells but was negative withmetabolic activation (Sofuni et al., 1990). In anunscheduled DNA synthesis assay in rat hepatocytes, a

clear dose–response relationship was noted for trigly-cidyl isocyanurate over the range 5–20 :g/ml (Ciba-Geigy, 1988c). However, in a similar study conductedwith human fibroblasts, triglycidyl isocyanurate did notinduce unscheduled DNA synthesis at concentrationsup to 400 :g/ml (Ciba-Geigy, 1988a). In two cell transfor-mation studies in mouse embryo fibroblasts, triglycidylisocyanurate did not induce any significant increase ineither transformed colony number or size in the concen-tration range 8.8–5000 ng/ml (Ciba-Geigy, 1983b, 1986a).

Triglycidyl isocyanurate did not induce chromo-somal aberrations in human lymphocytes at concentra-tions up to 2500 ng/ml. Only one aberration wasreported at each of the two higher concentrations of 5000and 10 000 ng/ml. Significant numbers of aberrationswere observed with the positive controls. As only avery late sampling time was used, the results are con-sidered questionable (Ciba-Geigy, 1985).

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

Two gavage studies were conducted to determinethe ability of triglycidyl isocyanurate to induce sisterchromatid exchanges in bone marrow cells in male andfemale Chinese hamsters. In one study, no increase inthe number of sister chromatid exchanges was observedin animals administered a single dose of 0, 35, 70, or 140mg triglycidyl isocyanurate/kg body weight (Ciba-Geigy,1984). In the study in which triglycidyl isocyanurate wasadministered at a single dose of 0, 140, 280, or 560 mg/kgbody weight, a dose-related increase in sister chromatidexchange in bone marrow cells (with statisticallysignificant increases) was observed at all exposures(Ciba-Geigy, 1983d). The results of the mouse spot testwere negative when triglycidyl isocyanurate was admin-istered at doses of 13.5, 27, or 54 mg/kg body weight in asingle intraperitoneal injection to pregnant mice on the10th day after conception (Ciba-Geigy, 1986d).

A number of oral studies have been conducted toinvestigate the potential of triglycidyl isocyanurate toinduce chromosomal aberrations in mouse germ cells. Inmale ICR mice administered 0, 30, 125, or 350 mgtriglycidyl isocyanurate/kg body weight for 5 days,chromosomal aberrations were induced in spermato-gonial cells at the two highest doses (Hazleton, 1989a). In another study in which male B6D2F1 mice wereadministered 0, 29, 58, or 115 mg triglycidyl isocyanurate/kg body weight for 5 days, chromosomal aberrations inspermatogonial cells were significantly increased at alldoses (Hazleton, 1991). When male

1 The final results of a chronic toxicity/carcinogenicitybioassay in rats conducted by the Centre Internationalede Toxicologie (CIT) in France were not available at thetime this CICAD was prepared.


9

Table 2: Genotoxicity of triglycidyl isocyanurate in vitro.

Resultsa

Species (test system) End-point Test concentrationWith

activationWithout

activation Reference

Procaryotic systems

Salmonella typhimurium

(TA1535, TA1538, TA98,TA100)

Gene mutation 1–10 000 :g/plate5–5000 :g/plate

++

++

Hazleton, 1987Ciba-Geigy,1982d

Escherichia coli WP2uvrA Gene mutation 5–5000 :g/plate ! ! Ciba-Geigy,1982d

Animal systems

Mouse lymphoma Gene mutation 0.375–6.0 :g/ml0.175–2.8 :g/ml

+NT

NT+

Ciba-Geigy,1983a

Rat hepatocytes UnscheduledDNA synthesis

0.20–20 :g/ml NT + Ciba-Geigy,1988c

Chinese hamster ovary cells Sisterchromatidexchanges

1.98–19.8 :g/ml0.066–0.66 :g/ml

+NT

NT+

Loveday et al.,1990

Chinese hamster ovary cells Chromosomalaberrations

10–100 :g/ml3–30 :g/ml

+NT

NT+

Loveday et al.,1990

Chinese hamster ovary cells Chromosomalaberrations

10–100 :g/ml3–50 :g/ml

+NT

NT+

Sofuni et al.,1990

Chinese hamster lung cells Chromosomalaberrations

1.25–5 :g/ml ! + Sofuni et al.,1990

Mouse embryo fibroblasts Celltransformation

8.75–140 ng/ml0.3125–5 :g/ml

NT!

!NT

Ciba-Geigy,1983bCiba-Geigy,1986a

Human cells

Human lymphocytes Chromosomalaberrations

62.5–10 000 ng/ml NT Equivocal Ciba-Geigy, 1985

Human fibroblasts UnscheduledDNA synthesis

2.7–400 :g/ml NT ! Ciba-Geigy,1988a

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

TifMAGf mice were administered 0, 43, or 128 mg trigly-cidyl isocyanurate/kg body weight for 5 days, a dose-related increase in chromosomal aberrations wasobserved in spermatogonial cells; however, a statisticalanalysis was not conducted (Ciba-Geigy, 1986b). Chromosomal aberrations were not induced in thespermatocytes of male mice administered (by gavage)0, 32, or 96 mg triglycidyl isocyanurate/kg body weightfor 4 days (Ciba-Geigy, 1986e). In a single-dose oralstudy, chromosomal aberrations were induced in mousespermatogonia at 115 mg triglycidyl isocyanurate/kgbody weight (Safepharm, 1992).

In a (whole-body) inhalation study, mice wereexposed to 0, 2.5, 10, or 50 mg triglycidyl isocyanurate/m3 (particle size range 2.5–3.5 :m) for 6 h/day for 5 days. Effects on mouse spermatogonial cells were measuredby the induction of chromosomal aberrations. Theresults of this study were inconclusive (Bushy Run,

1992a). The number of chromosomal aberrations in thecontrol group was high, there was a very low number ofscorable cells at the highest concentrations (10 and 50mg/m3), and cytotoxicity was not clearly established, asthe cytotoxic ratio was not measured. At 2.5 mg/m3, thenumber of chromosomal aberrations was only slightlyhigher than in the controls, which was unusually high. In an (nose-only) inhalation study, male CD-1 mice wereexposed to 0 or 7.8 mg triglycidyl isocyanurate/m3 (meanparticle size 1.6 :m) for 6 h/day for 5 days. Chromo-somal aberrations were not induced in spermatogonialcells at the single concentration tested (Safepharm,1992). In both these studies, body weight gain wasunaffected, no deaths occurred, and no adverse clinicalsigns were observed.

In a dominant lethal test, male TifMAGf(SPF) micewere administered (by gavage) 0, 160, or 480 mgtriglycidyl isocyanurate/kg body weight. In females


10

Table 3: Genotoxicity of triglycidyl isocyanurate in vivo.

Species (testsystem) End-point

Route ofexposure Dose Resultsa Reference

Chinese hamsterbone marrow

Nuclearanomalies

Oral 0, 140, 280, 560 mg/kg bodyweight

+ Ciba-Geigy, 1983c

Chinese hamsterbone marrow

Sisterchromatidexchange

OralOral

0, 35, 70, 140 mg/kg body weight0, 140, 280, 560 mg/kg bodyweight

!+

Ciba-Geigy, 1984Ciba-Geigy, 1983d

Mousespermatogonialcells

Chromosomalaberrations

OralOralOralOralInhalationInhalation

0, 43, 128 mg/kg body weight0, 30, 125, 350 mg/kg body weight0, 29, 58, 115 mg/kg body weight115 mg/kg body weight0, 2.5, 10, 50 mg/m3

0, 7.8 mg/m3

++++

Equivocal!

Ciba-Geigy, 1986bHazleton, 1989aHazleton, 1991Safepharm, 1992Bushy Run, 1992aSafepharm, 1992

Mousespermatocytes

Chromosomalaberrations

Oral 0, 32, 96 mg/kg body weight ! Ciba-Geigy, 1986e

Mouse spot test Genemutation

Intraperitoneal

13.5, 27, 54 mg/kg body weight ! Ciba-Geigy, 1986d

Mouse Dominantlethalmutations

OralOralInhalation

0, 160, 480 mg/kg body weight0, 138, 275, 550 mg/kg bodyweight0.25, 10, 50 mg/m3

Equivocalb!b

!

Ciba-Geigy, 1986cHazleton, 1989bBushy Run, 1992b

Mouse stomach,liver, and testis

DNA binding Oral 5, 17, 200 mg/kg body weight + Ciba-Geigy, 1990c

Rat liver DNA binding Oral,intraperitoneal

20 mg/kg body weight + Ciba-Geigy, 1993a

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

mated to the high-dose males, there was a significantincrease in the number of embryonic deaths when matingoccurred during the 1st week after exposure, but notwhen mating took place 2–3 weeks after the males wereexposed (Ciba-Geigy, 1986c). No increase in embryonicdeaths was noted in females mated to the low-dosemales 1–3 weeks after exposure. The results of this studyare considered equivocal. In a study in which male ICRmice were administered (by gavage) 0, 138, 275, or 550mg triglycidyl isocyanurate/kg body weight, nosignificant increase in the number of embryonic deathswas observed in the mated females (Hazleton, 1989b). These studies are of limited value, as the mating periodscovered only the first 3 weeks after the males had beenexposed. In another study, male CD-1 mice wereexposed (by inhalation) to 0.25, 10, or 50 mg triglycidylisocyanurate/m3. A reduction in male fertility (i.e.number of sperm-positive and pregnant females) wasobserved in high-dose males in the first 3 weeks and 6thweek post-exposure, as well as in mid-dose males in the3rd week post-exposure only. No dominant lethal effectswere observed; however, the results are suggestive ofan effect on mature sperm, maturing spermatids, andType B spermatogonia. This is the only dominant lethal

study in which the mating period covered all stages ofthe spermatogenic cycle (Bushy Run, 1992b).

The molecular structure of triglycidyl isocyanurateindicates a potential for alkylating DNA. A dose-dependent increase in triglycidyl isocyanurate–DNAadduct formation was observed in a study in which maleTifMAGf(SPF) mice were orally administered 5, 17, or 200mg triglycidyl isocyanurate/kg body weight. DNAalkylation was measured as the covalent binding index. For the highest dose, the ratio of covalent bindingindices for the stomach, liver, and testes at 3 h afterexposure was approximately 30 : 7 : 1. The highestcovalent binding index, for the stomach, was 8.9,compared with covalent binding indices of 20 000 for thepotent liver carcinogen aflatoxin B1 and 200 for themoderate carcinogen 2-acetylaminofluorene (Ciba-Geigy,1990c). In a second DNA alkylation study, maleTifRAIf(SPF) rats were pretreated with trans-stilbeneoxide at 0, 100, or 400 mg/kg body weight to induceepoxide hydrolase activity, followed by triglycidylisocyanurate administered orally or intraperitoneally(20 mg/kg body weight). The dose-dependent increasein liver microsomal epoxide hydrolase activity wasassociated with a dose-dependent decrease in DNAbinding by triglycidyl isocyanurate, calculated as the


11

covalent binding index. However, the relatively lowcovalent binding indices suggested that only a smallproportion of triglycidyl isocyanurate binds to DNA. Asmentioned in section 7, microsomal epoxide hydrolaseactivity with triglycidyl isocyanurate as substratemeasured in two human livers was greater than theactivity in non-induced rat liver (Ciba-Geigy, 1993a).

8.6 Reproductive and developmentaltoxicity

In a 13-week toxicity/fertility study, groups of 10male rats were given diets containing 0, 10, 30, or 100ppm (mg/kg) triglycidyl isocyanurate (CIT, 1995). Thisstudy followed a preliminary 19-day range-findinginvestigation in which signs of toxicity (large mesentericlymph nodes, small prostate and seminal vesicles) wereobserved in animals administered diets containing 160 or640 ppm (mg/kg) triglycidyl isocyanurate. In the fullstudy after 64 days of treatment, each male was placedwith two females until mating occurred. The femaleswere then allocated to two subgroups (caesarean ornormal delivery) on day 19 of pregnancy. Females fromthe caesarean group were killed on day 20 of pregnancyand the ovaries and uterus examined to determine num-ber of corpora lutea, live and dead fetuses, resorptions,and implantation sites. The other group was allowed todeliver normally; litter size was noted, pups were exam-ined for presence of clinical signs, and their developmentwas recorded. Between 22 and 25 days postpartum, thefemales in the normal delivery group were sacrificed, themain thoracic and abdominal organs were examined, andthe number of implantation sites was noted. In males atautopsy, all organ weights and macroscopic andmicroscopic changes were recorded in the control andhighest-dose groups, with selected organs examined inthe other test groups.

No exposure-related clinical effects or deaths wereobserved. Body weight gain was slightly lower over thefirst 6 weeks in animals from the 100 ppm (mg/kg) testgroup. A dose-related reduction in the number ofspermatozoa was noted; compared with the unexposedcontrols, there was a 5%, 13%, and 23% reduction inspermatozoa in males administered diets containing 10,30, and 100 ppm (mg/kg) triglycidyl isocyanurate,respectively. Spermatozoa viability was similar in thetriglycidyl isocyanurate-exposed and control groups. No exposure-related infertility was noted in males, andno effects on embryonic and pup development wereobserved in the offspring of females mated with trigly-cidyl isocyanurate-exposed males (CIT, 1995). However,it should be noted that the highest concentration used inthis study (100 ppm; mg/kg) was not a maximumtolerated dose.

There were no other data available on the develop-mental toxicity of triglycidyl isocyanurate.

9. EFFECTS ON HUMANS

Allergic contact dermatitis has been reported inseveral case-studies of exposure to triglycidyl isocyan-urate and powder coatings containing triglycidyl iso-cyanurate. Exposure occurred during the manufactureof triglycidyl isocyanurate (Nishioka et al., 1988) andpowdered paint coatings (Foulds & Koh, 1992; Munro& Lawrence, 1992), during the application of productscontaining triglycidyl isocyanurate, including powdercoatings (Matthias, 1988; McFadden & Rycroft, 1993)and hardener for epoxy acrylate ink (Jolanki et al., 1994),and while cleaning equipment contaminated withtriglycidyl isocyanurate (Dooms-Goossens et al., 1989). Symptoms included dermatitis, itchy rashes, andswelling on the face, hands, arms, neck, and thighs. Allsubjects tested positive to patch testing with triglycidylisocyanurate.

A case-study reported asthma-like symptoms in aspray painter who had been using powder coatingscontaining triglycidyl isocyanurate for 4 years (Piirila etal., 1997). Symptoms included elevated blood eosino-phils and serum immunoglobulin E (IgE), moderatebronchial hyper-reactivity, and a reduction in forcedexpiratory volume in 1 second (FEV1) of 23% and 19%when challenged with 4% triglycidyl isocyanurate and4% 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 clinicaldevelopment of "-triglycidyl isocyanurate as an anti-tumour agent. In these studies, "-triglycidyl isocyan-urate was administered intravenously to cancer patientsat doses up to 900 mg/kg body weight using a variety ofdosing regimes. Toxic signs included myelosuppres-sion, nausea and vomiting, and, rarely, alopecia andleucopenia at high doses (>600 mg/kg body weight). Owing to its severe local toxicity (thrombophlebitis) atthe site of injection, the use of "-triglycidyl isocyan-urate as an antitumour agent was not pursued (HSE,1992).

There were no epidemiological studies ontriglycidyl isocyanurate available.

10. EFFECTS ON OTHER ORGANISMS INTHE LABORATORY AND FIELD

Only limited ecotoxicological data for triglycidylisocyanurate are available. No deaths were observed atthe only concentration tested in a 96-h static test withzebra fish (Brachydanio rerio); the no-observed-effect


12

concentration (NOEC) was >77 mg/litre (Ciba-Geigy,1988e). The 24-h EC50 in a static immobilization test withDaphnia magna was >100 mg/litre, with a NOEC of 58mg/litre (Ciba-Geigy, 1988f). These results indicate thattriglycidyl isocyanurate is, at most, slightly toxic toaquatic fauna under conditions of acute exposure. Chronic effects would not be expected because of limitedaquatic persistence.

11. EFFECTS EVALUATION

11.1 Evaluation of health effects

11.1.1 Hazard identification and dose–responseassessment

The only reported health effects in humans arecontact dermatitis and one case of respiratory sensiti-zation.

Acute animal toxicity studies reveal that triglycidylisocyanurate is toxic by oral and inhalation routes ofexposure but has low acute dermal toxicity. Triglycidylisocyanurate produces serious eye irritation. It is a skinsensitizer but not a skin irritant. Short-term repeated-dose studies revealed renal, lung, gastric/duodenal, andsperm cell damage. In a subchronic toxicity/fertilitystudy conducted in rats, a dose-dependent reduction inthe number of spermatozoa was the only effect observedat concentrations of up to 100 ppm (mg/kg) triglycidylisocyanurate in the diet.

Triglycidyl isocyanurate has structural alerts sug-gesting direct-acting mutagenicity. DNA binding oftriglycidyl isocyanurate has been measured in mouseliver, testes, and stomach following oral administration. The chemical has produced positive results in a range ofin vitro genotoxicity studies (gene mutation in bacterialand mammalian cells, unscheduled DNA synthesis,sister chromatid exchanges, and chromosomal aberrationassays). Genotoxic effects have also been observed invivo in somatic (bone marrow) cells and germ cells in thetestes. Triglycidyl isocyanurate therefore causesheritable mutations, and the demonstrated ability fortriglycidyl isocyanurate to cause genetic damage alsoraises concern over potential carcinogenic effects.

Genotoxicity studies have revealed that the inhala-tion of triglycidyl isocyanurate produces cytotoxicityand 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 inview of the low doses tested. Overall, the reproductivetoxicity of triglycidyl isocyanurate has not beenadequately investigated. As triglycidyl isocyanurate isa direct-acting in vivo mutagen, identification of a no-observed-effect level for the non-critical end-points ofsystemic toxicity may not be appropriate.

11.1.2 Criteria for setting guidance values fortriglycidyl isocyanurate

Exposure of the general public to triglycidyl

isocyanurate is likely to be minimal. The main risk tohuman health is through occupational exposure viainhalation. Data from human and animal studies uponwhich to base a guidance value for occupationalexposure to triglycidyl isocyanurate are very limited. Based on the information available from animal studies,the critical effect for chronic exposure is the potentialgenotoxicity of triglycidyl isocyanurate. Triglycidylisocyanurate is a direct-acting in vivo mutagen, and it isnot possible to identify a level of exposure below whichthere would be no risk to human health.

11.1.3 Sample risk characterization

Because triglycidyl isocyanurate is genotoxic, ano-observed-effect level cannot be determined, and aquantitative risk characterization is not consideredappropriate. Public exposure to the chemical is likely tobe very low. Owing to its genotoxic and sensitizationeffects, workplace exposures should be maintained atthe lowest practicable level.

11.2 Evaluation of environmental effects

Triglycidyl isocyanurate is not expected toproduce adverse effects, as environmental exposure islow. Much of the triglycidyl isocyanurate contained inwaste will be effectively immobile, as it is bound in thecoating matrix of triglycidyl isocyanurate-containingmaterials. Amounts released into the environment willhave limited persistence because of rapid biodegrada-tion.

Some triglycidyl isocyanurate and triglycidylisocyanurate-containing powder coatings may also bereleased to the atmosphere and the sewage system. Thelimited ecotoxicological data indicate that the acutetoxicity of triglycidyl isocyanurate in aquatic fauna islow (NOEC $58 mg/litre). Chronic effects are notexpected because of limited aquatic persistence.


13

12. PREVIOUS EVALUATIONS BYINTERNATIONAL BODIES

Previous evaluations of triglycidyl isocyanurate byinternational bodies were not identified. Information oninternational hazard classification and labelling isincluded in the International Chemical Safety Cardreproduced in this document.

13. HUMAN HEALTH PROTECTION ANDEMERGENCY ACTION

Human health hazards, together with preventativeand 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 andhas 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 Registerof Potentially Toxic Chemicals (IRPTC), available fromUNEP Chemicals (IRPTC), Geneva.

The reader should be aware that regulatory deci-sions about chemicals taken in a certain country can befully understood only in the framework of the legislationof that country. The regulations and guidelines of allcountries are subject to change and should always beverified with appropriate regulatory authorities beforeapplication.

Prepared in the context of cooperation between the InternationalProgramme on Chemical Safety and the European Commission

© IPCS 1999

SEE IMPORTANT INFORMATION ON THE BACK.

IPCSInternationalProgramme onChemical Safety

TRIGLYCIDYL ISOCYANURATE 1274October 1997

CAS No: 2451-62-9RTECS No: XZ1994900UN No: EC No: 615-021-00-6

1,3,5-Triglycidyl isocyanurates-Triazine-2,4,6(1H,3H,5H)-trioneTris(epoxypropyl)isocyanurateC12H15N3O6

Molecular mass: 297.3

TYPES OFHAZARD/EXPOSURE

ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING

FIRE Combustible. Gives off irritating ortoxic fumes (or gases) in a fire.

NO open flames. Foam, powder, carbon dioxide.

EXPLOSION Finely dispersed particles formexplosive mixtures in air.

Prevent deposition of dust; closedsystem, dust explosion-proofelectrical equipment and lighting.

EXPOSURE PREVENT DISPERSION OF DUST!AVOID ALL CONTACT!

Inhalation Local exhaust or breathingprotection.

Fresh air, rest.

Skin Protective gloves. Protectiveclothing.

Remove contaminated clothes.Rinse skin with plenty of water orshower.

Eyes Redness. Pain. Safety goggles, or eye protection incombination with breathingprotection.

First rinse with plenty of water forseveral minutes (remove contactlenses if easily possible), then taketo a doctor.

Ingestion Do not eat, drink, or smoke duringwork.

Rinse mouth. Induce vomiting(ONLY IN CONSCIOUSPERSONS!). Refer for medicalattention.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Sweep spilled substance into sealable containers.Carefully collect remainder, then remove to safeplace. Do NOT let this chemical enter theenvironment (extra personal protection: P2 filterrespirator for harmful particles).

Symbol TR: 46-23/25-41-43-48/22-52/53S: 53-45-61Note: E

EMERGENCY RESPONSE STORAGE

Well closed.

Melting point: 95�CDensity: 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 (technicalgrade)

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible for the use which might be made of this information

© IPCS 1999

1274 TRIGLYCIDYL ISOCYANURATE

IMPORTANT DATA

Physical State; AppearanceWHITE POWDER OR GRANULE.

Physical DangersDust explosion possible if in powder or granular form, mixedwith air.

Chemical DangersThe substance may polymerize due to heating to more than120�C for more than 12 hours, or under the influence ofcatalysts. The substance decomposes on burning producingtoxic fumes including nitrogen oxides. Molten triglycidylisocyanurate reacts rapidly with primary and secondaryamines, carboxylic acids and anhydrides, thiols, phenols andalcohols.

Occupational Exposure LimitsTLV (as TWA): 0.05 mg/m3 (ACGIH 1998).

Routes of ExposureThe substance can be absorbed into the body by inhalation ofits aerosol and by ingestion.

Inhalation RiskEvaporation at 20�C is negligible; a harmful concentration ofairborne particles can, however, be reached quickly whendispersed, especially if powered.

Effects of Short-term ExposureThe substance irritates severely the eyes. The substance maycause effects on the central nervous system, kidneys, liver,lungs and gastrointestinal tract, resulting in tissue lesions.

Effects of Long-term or Repeated ExposureRepeated or prolonged contact may cause skin sensitization.May cause heritable genetic damage in humans.

PHYSICAL PROPERTIES

ENVIRONMENTAL DATA

NOTES

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

ADDITIONAL INFORMATION


16

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application of TK 10622/3 (No. 790340). Basel, Ciba-Geigy Ltd.

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application of TK 10622 (No. 790337). Basel, Ciba-Geigy Ltd.

Ciba-Geigy (1979e) Eye irritation in the rabbit after single

application of TK 10622/3 (No. 790341). Basel, Ciba-Geigy Ltd.

Ciba-Geigy (1982a) Acute oral toxicity in the rat (No. 820694)

with TK 10622. Basel, Ciba-Geigy Ltd.

Ciba-Geigy (1982b) Acute skin irritation in the rabbit with TK

10622 (No. 820697). Basel, Ciba-Geigy Ltd.

Ciba-Geigy (1982c) Acute eye irritation study in the rabbit with

TK 10622 (No. 820696). Basel, Ciba-Geigy Ltd.

Ciba-Geigy (1982d) Salmonella and Escherichia/liver microsome

test with TK 10622. Basel, Ciba-Geigy Ltd.

Ciba-Geigy (1983a) L5178Y/TK+/! mouse lymphoma

mutagenicity test with TK 10622 (No. 830797). Basel, Ciba-Geigy Ltd.

Ciba-Geigy (1983b) BALB/3T3 cell transformation assay with TK


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

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Ciba-Geigy (1986a) Transformation/liver microsome test with TK


Ciba-Geigy (1986b) Chromosome studies on male germinal

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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

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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-GeigyLtd.

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.

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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

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evolution test of Araldite PT 810. Basel, Ciba-Geigy Ltd.


17

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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 resinhardeners during the manufacture of thermosetting coatingpaints. Contact dermatitis, 26:87–90.

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Ames Salmonella/microsome reverse mutation assay (No. E-

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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, HazletonMicrotest.

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, InternationalProgramme on Chemical Safety (No. 1274).

Jolanki R, Kanerva L, Estlander T, Tarvainen K (1994)Concomitant sensitization to triglycidyl isocyanurate,diaminodiphenylmethane and 2-hydroxyethyl methacrylate fromsilk-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 inChinese hamster ovary cells in vitro . V: Results with 46chemicals. Environmental and molecular mutagenesis,16:272–303.

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

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

Munro CS, Lawrence CM (1992) Occupational contact dermatitisfrom 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, AustralianGovernment Publishing Service, April.

Nishioka K, Ogasawara M, Asagami C (1988) Occupationalcontact 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 ofTeroxirone. Cancer treatment reports, 71:489–492.

Safepharm (1988a) TEPIC-G: Acute oral toxicity test in the rat

(No. 14/10). Derby, Safepharm Laboratories Ltd.

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the rat (No. 14/11). Derby, Safepharm Laboratories Ltd.

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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, SafepharmLaboratories 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.

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powder: Chromosome analysis in mouse spermatogonial cells,

comparative inhalation study (No. 14/75) [draft]. Derby,Safepharm Laboratories Ltd.

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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 aberrationinduction by 25 compounds tested by two Chinese hamster cell(CHL and CHO) systems in culture. Mutation research,241:175–213.


18

APPENDIX 1 — SOURCE DOCUMENT

National Industrial Chemicals Notification andAssessment Scheme — Triglycidyl Isocyanurate,Priority Existing Chemical No. 1, Full PublicReport (1994)

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

Australian Government Publishing ServiceMail Order ServiceGPO Box 84Canberra 2601, Australia

NICNAS reports are prepared to meet the requirements ofthe Industrial Chemicals Notification and Assessment Act, 1989,

as amended. In the preparation of the assessment report, bothinternal and external peer review are undertaken. Under theNICNAS legislation, applicants for the assessment of a chemical(i.e. importers and manufacturers of the chemical) may apply forvariations to the draft report. The following companiesparticipated in the review of the assessment at this stage: Ciba-Geigy Australia Ltd, Dulux Powder Coatings, Evode PowderCoatings Pty Ltd, Itochu Australia Ltd, Jotun Powder CoatingsPty Ltd, Sumitomo Australia Ltd, Taubmans Pty Ltd, andWestern Coatings Ltd.

In the assessment of triglycidyl isocyanurate, Ciba-GeigyAustralia Ltd made several requests to vary the assessmentreport — 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 decisionwith the independent Administrative Appeals Tribunal(members included Justice D.F. O’Connor and Professor G.Johnston, Sydney University). The Administrative AppealsTribunal looked at all the material relevant to the assessmentdecisions in question and upheld the Director’s decisions. 1 During the Administrative Appeals Tribunal review process, thefollowing 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 ofNew South Wales, Australia; and Dr E. Zeiger, National Instituteof Environmental Health Sciences, Research Triangle Park, NC,USA.

APPENDIX 2 — CICAD PEER REVIEW

The draft CICAD on triglycidyl isocyanurate was sent forreview to institutions and organizations identified by IPCS aftercontact with IPCS national Contact Points and ParticipatingInstitutions, as well as to identified experts. Comments werereceived from:

Ciba Speciality Chemicals Inc., Basel, Switzerland

Department of Health, London, United Kingdom

Department of Public Health Promotion, Prague, CzechRepublic

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 EnvironmentalHealth Sciences, Research Triangle Park, USA)

United States Environmental Protection Agency (NationalCenter for Environmental Assessment, Office of Researchand Development, Research Triangle Park, USA)

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


19

APPENDIX 3 — CICAD FINAL REVIEWBOARD

Berlin, Germany, 26–28 November 1997

Members

Dr H. Ahlers, Education and Information Division, NationalInstitute 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 ofConsumers & Veterinary Medicine, Berlin, Germany(Chairperson)

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

Dr I. Mangelsdorf, Documentation and Assessment ofChemicals, Fraunhofer Institute for Toxicology and AerosolResearch, Hanover, Germany

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

Dr K. Paksy, Department of Reproductive Toxicology, NationalInstitute 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, UnitedKingdom

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

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

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

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

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

Dr K. Ziegler-Skylakakis, Senatskommission der DeutschenForschungsgemeinschaft zuer Pruefung gesundheitsschaedlicherArbeitsstoffe, 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 Ecotoxicologyand 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, EuropeanCommission, 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 forEconomic Co-operation and Development, Paris, France

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

Secretariat

Dr M. Baril, International Programme on Chemical Safety, WorldHealth 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, UnitedKingdom

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

1 Invited but unable to attend.


20

RÉSUMÉ D’ORIENTATION

Ce CICAD est fondé principalement sur l’évalu-ation de l’isocyanurate de triglycidyle réalisée dans lecadre du NICNAS (Australian National IndustrialChemicals Notification and Assessment Scheme) etpubliée en avril 1994 (NICNAS, 1994). De nouvellesinformations parues entre l’achèvement du rapportNICNAS et novembre 1997 ont également été évaluéeset incorporées dans ce CICAD, de même que desinformations complémentaires extraites de l’étude duUnited Kingdom Health and Safety Executive (HSE,1992) portant sur la toxicité de cette substance. Desinformations relatives à l’examen du rapport NICNASpar les pairs et à sa disponibilité figurent à l’appendice 1. Les renseignements concernant l’examen du CICAD parles pairs font l’objet de l’appendice 2. Ce CICAD a étéapprouvé en tant qu’évaluation internationale lors d’uneune réunion du Comité d’évaluation finale qui s’esttenue à Berlin (Allemagne) du 26 au 28 novembre 1997. La liste des participants à cette réunion figure àl’appendice 3. La fiche d’information sur la sécuritéchimique de l’isocyanurate de triglycidyle (ICSC 1274),établie par le Programme international sur la Sécuritéchimique (IPCS, 1997), est également reproduite dans leprésent document.

L’isocyanurate de triglycidyle (CAS N° 2451-62-9)est une substance chimique de synthèse qui se présentesous la forme d’une poudre blanche ou d’un granulépratiquement inodore à la température ambiante. Il estemployé principalement comme agent de polymérisationou de réticulation tridimensionnelle dans lesrevêtements de polyester en poudre (peinture). Cesrevêtements en poudre contiennent généralement de 4 à10 % d’isocyanurate de triglycidyle. Il est égalementutilisé dans les encres servant à la fabrication demasques dans l’industrie des circuits imprimés. L’encreest constituée de deux parties dont l’élément durcisseurcontient approximativement 60 % d’isocyanurate detriglycidyle. La plus grande partie de l’isocyanurate detriglycidyle présent dans ces revêtements en poudre etces encres est immobilisée par réticulation dans unematrice insoluble.

En principe, l’exposition de la population généraleà l’isocyanurate de triglycidyle devrait être minime. Parcontre, il existe un risque d’exposition professionnellelors de la fabrication et de l’utilisation de cette sub-stance et des produits qui en contiennent.

On dispose de peu d’informations sur les effets del’isocyanurate de triglycidyle chez l’homme. On asignalé plusieurs cas de dermatite allergique de contact

et un cas de sensibilisation respiratoire à la suite d’uneexposition professionnelle.

L’isocyanurate de triglycidyle est très toxique paringestion et inhalation chez les animaux de laboratoire etil peut provoquer de graves lésions oculaires. Sur lapeau, il agit comme sensibilisant, mais non commeirritant. Les données sur sa toxicité à la suite d’uneexposition répétée sont limitées. Chez des rats et dessouris soumis à des expositions répétées pendant unecourte période (5-7 jours), on a constaté des effets surles reins, le foie, les poumons, le tube digestif et lesspermatogonies. Une étude de 13 semaines menée surdes rats mâles pour évaluer la toxicité de l’isocyanuratede triglycidyle et ses effets sur la fécondité a révélé uneréduction de nombre de spermatozoïdes liée à la dose.

Des études de génotoxicité in vitro et in vivo ontmontré que l’isocyanurate de triglycidyle est un muta-gène à action directe capable d’agir sur les organes de lareproduction. Compte tenu de sa génotoxicité poten-tielle, toutes les mesures appropriées doivent être prisespour réduire au minimum l’exposition humaine à cettesubstance.

Compte tenu de sa faible persistance et d’uneécotoxicité probablement faible, l’isocyanurate detriglycidyle ne devrait pas présenter de risque significatifpour l’environnement, sauf en cas de rejet accidentel oud’élimination dans des conditions inadaptées.


21

RESUMEN DE ORIENTACIÓN

Este CICAD se basa principalmente en laevaluacióón del isocianurato de triglicidilo realizada enel marco del Plan Nacional Australiano de Notificacióóny Evaluacióón de Sustancias Quíímicas Industriales(NICNAS) y publicada en abril de 1994 (NICNAS, 1994).Tambiéén se ha evaluado e incorporado a este CICAD lainformacióón aparecida desde la terminacióón delinforme del NICNAS hasta noviembre de 1997. Se haincluido asimismo alguna informacióón adicionalprocedente del examen de la toxicidad del isocianuratode triglicidilo de la Direccióón de Salud y Seguridad delReino Unido (HSE, 1992). La informacióón relativa alexamen colegiado del informe del NICNAS y a sudisponibilidad figura en el Apééndice 1. La informacióónsobre el examen colegiado de este CICAD se presenta enel Apééndice 2. Este CICAD se aprobóó comoevaluacióón internacional en una reunióón de la Juntade Evaluacióón Final celebrada en Berlíín (Alemania) losdíías 26-28 de noviembre de 1997. La lista departicipantes en la Junta de Evaluacióón Final figura enel Apééndice 3. La Ficha internacional de seguridadquíímica (ICSC 1274) para el isocianurato de triglicidilo,preparada por el Programa Internacional de Seguridad delas Sustancias Quíímicas (IPCS, 1997), tambiéén sereproduce en este documento.

El isocianurato de triglicidilo (CAS Nºº 2451-62-9),sustancia quíímica sintéética en forma de polvo blanco ogranulada práácticamente inodora a temperaturaambiente, se utiliza sobre todo como agente depolimerizacióón o de reticulacióón tridimensional en losrevestimientos de poliééster en polvo (pintura). Estosrevestimientos en polvo suelen contener entre un 4% yun 10% de isocianurato de triglicidilo. Tambiéén seutiliza ééste en las tintas que sirven para la fabricacióónde "mááscaras" de soldadura en la industria de loscircuitos impresos. Las tintas constan de dos partes,cuyo elemento endurecedor contiene alrededor de un60% de isocianurato de triglicidilo. La mayor parte deesta sustancia presente en los revestimientos en polvo ylas tintas mencionados se inmoviliza mediante lareticulacióón en una matriz insoluble.

La exposicióón de la poblacióón general alisocianurato de triglicidilo se supone que es míínima; sinembargo, hay riesgo de exposicióón profesional durantela fabricacióón y la utilizacióón de esta sustancia y delos productos que la contienen.

Se dispone de escasa informacióón sobre losefectos del isocianurato de triglicidilo en el ser humano.Se han notificado varios casos de dermatitis aléérgica

por contacto y un caso de sensibilizacióón respiratoriadebidos a exposicióón profesional.

El isocianurato de triglicidilo es muy tóóxico enanimales de laboratorio por ingestióón e inhalacióón ypuede provocar lesiones oculares graves. Essensibilizador cutááneo, pero no irritante de la piel. Losdatos sobre toxicidad por exposicióón repetida sonlimitados. En estudios de exposicióón repetida de cortaduracióón (5-7 díías) en ratas y ratones, se observaronefectos en los riññones, el híígado, los pulmones, elaparato digestivo y los espermatogonios. En un estudiode toxicidad/fecundidad de 13 semanas en ratas machosse observóó una reduccióón del núúmero deespermatozoides relacionada con la dosis.

Los estudios de genotoxicidad in vitro e in vivoindican que el isocianurato de triglicidilo es unmutáágeno de accióón directa capaz de afectar losóórganos de la reproduccióón. A la vista de sugenotoxicidad potencial, deben tomarse todas lasmedidas apropiadas para reducir al míínimo laexposicióón humana a esta sustancia.

Debido a su escasa persistencia y su ecotoxicidadprobablemente baja, no es probable que el isocianuratode triglicidilo represente un riesgo significativo para elmedio ambiente, excepto en el caso de un accidente o deuna eliminacióón inapropiada