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WORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY FOR RESEARCH ON CANCER IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS VOLUME 77 SOME INDUSTRIAL CHEMICALS 2000 IARC LYON FRANCE WORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY FOR RESEARCH ON CANCER IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS Some Industrial Chemicals VOLUME 77 This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, which met in Lyon, 15–22 February 2000 2000 IARC MONOGRAPHS In 1969, the International Agency for Research on Cancer (IARC) initiated a programme on the evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, life-style factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate and publish in the form of monographs critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations; to evaluate these data in terms of human risk with the help of international working groups of experts in chemical carcinogenesis and related fields; and to indicate where additional research efforts are needed. The lists of IARC evaluations are regularly updated and are available on Internet: http://www.iarc.fr/, under Publications. This project was supported by Cooperative Agreement 5 UO1 CA33193 awarded by the United States National Cancer Institute, Department of Health and Human Services. Addi- tional support has been provided since 1986 by the European Commission, since 1993 by the United States National Institute of Environmental Health Sciences and since 1995 by the United States Environmental Protection Agency through Cooperative Agreement Assistance CR 824264. ©International Agency for Research on Cancer, 2000 Distributed by IARCPress (Fax: +33 4 72 73 83 02; E-mail: [email protected]) and by the World Health Organization Distribution and Sales, CH-1211 Geneva 27 (Fax: +41 22 791 4857; E-mail: publications@)who.int) Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved. Application for rights of reproduction or translation, in part or in toto, should be made to the International Agency for Research on Cancer. IARC Library Cataloguing in Publication Data Some industrial chemicals / IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2000 : Lyon, France) (IARC monographs on the evaluation of carcinogenic risks to humans ; 77) 1. Carcinogens – congresses 2. Occupational Exposure – congresses I. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans II. Series ISBN 92 832 1277 0 (NLM Classification: W1) ISSN 1017-1606 PRINTED IN FRANCE CONTENTS NOTE TO THE READER............................................................................................1 LIST OF PARTICIPANTS............................................................................................3 PREAMBLE ................................................................................................................9 Background..............................................................................................................9 Objective and Scope ................................................................................................9 Selection of Topics for Monographs ....................................................................10 Data for Monographs ............................................................................................11 The Working Group ..............................................................................................11 Working Procedures ..............................................................................................11 Exposure Data........................................................................................................12 Studies of Cancer in Humans ................................................................................14 Studies of Cancer in Experimental Animals..........................................................17 Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms ..........................................................................................20 Summary of Data Reported ..................................................................................22 Evaluation ..............................................................................................................23 References..............................................................................................................27 GENERAL REMARKS..............................................................................................33 THE MONOGRAPHS................................................................................................39 Di(2-ethylhexyl) phthalate ....................................................................................41 Di(2-ethylhexyl) adipate......................................................................................149 Cinnamyl anthranilate..........................................................................................177 Coumarin ............................................................................................................193 Ethylbenzene........................................................................................................227 ortho-Toluidine ....................................................................................................267 4-Chloro-ortho-toluidine ....................................................................................323 5-Chloro-ortho-toluidine ....................................................................................341 Diethanolamine....................................................................................................349 Triethanolamine ..................................................................................................381 N-Nitrosodiethanolamine ....................................................................................403 2,3-Dibromopropan-1-ol......................................................................................439 2,2-Bis(bromomethyl)propane-1,3-diol ..............................................................455 –iii– iv IARC MONOGRAPHS VOLUME 77 Glycidol ..............................................................................................................469 Nitromethane ......................................................................................................487 Pyridine................................................................................................................503 SUMMARY OF FINAL EVALUATIONS ..............................................................529 CUMULATIVE INDEX TO THE MONOGRAPHS SERIES..................................531 NOTE TO THE READER The term ‘carcinogenic risk’ in the IARC Monographs series is taken to mean the probability that exposure to an agent will lead to cancer in humans. Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the published data have been examined. Equally, the fact that an agent has not yet been evaluated in a monograph does not mean that it is not carcinogenic. The evaluations of carcinogenic risk are made by international working groups of independent scientists and are qualitative in nature. No recommendation is given for regulation or legislation. Anyone who is aware of published data that may alter the evaluation of the carcino- genic risk of an agent to humans is encouraged to make this information available to the Unit of Carcinogen Identification and Evaluation, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France, in order that the agent may be considered for re-evaluation by a future Working Group. Although every effort is made to prepare the monographs as accurately as possible, mistakes may occur. Readers are requested to communicate any errors to the Unit of Carcinogen Identification and Evaluation, so that corrections can be reported in future volumes. –1– IARC WORKING GROUP ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS: SOME INDUSTRIAL CHEMICALS Lyon, 15–22 February 2000 LIST OF PARTICIPANTS Members S.J. Borghoff, CIIT, PO Box 12137, Research Triangle Park, NC 27709, United States J. Caldwell, Division of Biomedical Sciences, Imperial College School of Medicine, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, United Kingdom R.C. Cattley, Amgen, MS-15-2-B, One Amgen Center Drive, Thousand Oaks, CA 91320, United States S. Cordier, Unit of Epidemiological and Statistical Research on the Environment and Health, INSERM–U 170, 16 avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France N. Danford, Microptic Cytogenetic Services, 2 Langland Close, Mumbles, Swansea SA3 4LY, United Kingdom P.A. Demers, School of Occupational and Environmental Hygiene, University of British Columbia, 2206 East Mall, 3rd floor, Vancouver BC V6T 1Z3, Canada T.A. Dragani, Istituto Nazionale per lo Studio e la Cura dei Tumori, via G. Venezian 1, 20133 Milan, Italy J.K. Dunnick, National Institute
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