IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS WORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY FOR RESEARCH ON CANCER 1999 IARC LYON FRANCE VOLUME 71 RE-EVALUATION OF SOME ORGANIC CHEMICALS, HYDRAZINE AND HYDROGEN PEROXIDE WORLD HEALTH ORGANIZATION INTERNATIONALAGENCY FOR RESEARCH ON CANCER IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide VOLUME 71 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, 17–24 February 1998 1999 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 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/. This project has been 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, 1999 IARC Library Cataloguing in Publication Data Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide / IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1999 : Lyon, France). (IARC monographs on the evaluation of carcinogenic risks to humans ; 71 part 1, part 2 and part 3) 1. Carcinogens – congresses 2. Occupational Exposure – congresses I. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans II. Series ISBN 92 832 1271 1 (NLM Classification: W1) ISSN 1017-1606 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. Distributed by IARCPress (Fax: +33 4 72 73 83 02; E-mail: press@iarc.fr) and by the World Health Organization Distribution and Sales, CH-1211 Geneva 27 (Fax: +41 22 791 4857) PRINTED IN FRANCE NOTE TO THE READER 1 LIST OF PARTICIPANTS 3 PREAMBLE 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 SUMMARY OF FINAL EVALUATIONS 37 THE MONOGRAPHS Part One—Compounds reviewed in plenary sessions (comprehensive monographs) Acrylonitrile 43 1,3-Butadiene 109 Chloroprene 227 Dichloromethane 251 Part Two—Other compounds reviewed in plenary sessions Acetaldehyde 319 Aziridine 337 Benzoyl peroxide 345 –iii– CONTENTS IARC MONOGRAPHS VOLUME 71iv n-Butyl acrylate 359 γ-Butyrolactone 367 Caprolactam 383 Carbon tetrachloride 401 Catechol 433 α-Chlorinated toluenes and benzoyl chloride 453 1,2-Dibromo-3-chloropropane 479 1,2-Dichloroethane 501 Dimethylcarbamoyl chloride 531 Dimethylformamide 545 Dimethyl sulfate 575 1,4-Dioxane 589 Epichlorohydrin 603 1,2-Epoxybutane 629 Ethylene dibromide (1,2-dibromoethane) 641 Hydrogen peroxide 671 Hydroquinone 691 Methyl bromide 721 Methyl chloride 737 Phenol 749 Polychlorophenols and their sodium salts 769 1,1,2,2-Tetrachloroethane 817 Toluene 829 Toluene diisocyanates 865 1,1,1-Trichloroethane 881 Tris(2,3-dibromopropyl) phosphate 905 Vinyl bromide 923 Part Three—Compounds not reviewed in plenary sessions Part Three A—Extensive new data requiring new summaries 1,3-Dichloropropene 933 1,2-Dimethylhydrazine 947 Hydrazine 991 Isoprene 1015 Isopropanol 1027 Malonaldehyde (malondialdehyde) 1037 4,4′-Methylenediphenyl diisocyanate and polymeric 4,4′-methylenediphenyl diisocyanate 1049 Methyl methanesulfonate 1059 2-Nitropropane 1079 1,3-Propane sultone 1095 β-Propiolactone 1103 Resorcinol 1119 1,1,1,2-Tetrachloroethane 1133 Tetrafluoroethylene 1143 1,1,2-Trichloroethane 1153 Vinylidene chloride 1163 N-Vinyl-2-pyrrolidone and polyvinylpyrrolidone 1181 Xylenes 1189 Part Three B—Few new data Acetamide 1211 Acrylic acid 1223 Allyl chloride 1231 Allyl isovalerate 1241 1,4-Benzoquinone (para-quinone) 1245 1,4-Benzoquinone dioxime 1251 Benzyl acetate 1255 Bis(2-chloroethyl)ether 1265 1,2-Bis(chloromethoxy)ethane 1271 1,4-Bis(chloromethoxymethyl)benzene 1273 Bis(2-chloro-1-methylethyl)ether 1275 Bis(2,3-epoxycyclopentyl)ether 1281 Bisphenol A diglycidyl ether 1285 Bromochloroacetonitrile 1291 Bromodichloromethane 1295 Bromoethane 1305 Bromoform 1309 β-Butyrolactone 1317 Carbazole 1319 Chloroacetonitrile 1325 Chlorodibromomethane 1331 Chlorodifluoromethane 1339 Chloroethane 1345 Chlorofluoromethane 1351 2-Chloro-1,1,1-trifluoroethane 1355 Cyclohexanone 1359 Decabromodiphenyl oxide 1365 Dibromoacetonitrile 1369 Dichloroacetonitrile 1375 Dichloroacetylene 1381 trans-1,4-Dichlorobutene 1389 1,2-Dichloropropane 1393 1,2-Diethylhydrazine 1401 CONTENTS v Diethyl sulfate 1405 Diglycidyl resorcinol ether 1417 Diisopropyl sulfate 1421 1,1-Dimethylhydrazine 1425 Dimethyl hydrogen phosphite 1437 3,4-Epoxy-6-methylcyclohexylmethyl 3,4-epoxy-6-methyl- cyclohexane carboxylate 1441 cis-9,10-Epoxystearic acid 1443 Ethyl acrylate 1447 Glycidaldehyde 1459 Hexamethylphosphoramide 1465 Isopropyl oils 1483 Lauroyl peroxide 1485 Methyl acrylate 1489 2-Methylaziridine (propyleneimine) 1497 Methyl iodide 1503 Morpholine 1511 1,5-Naphthalene diisocyanate 1515 Pentachloroethane 1519 Phenyl glycidyl ether 1525 Tetrakis(hydroxymethyl)phosphonium salts 1529 Trichloroacetonitrile 1533 Triethylene glycol diglycidyl ether 1539 Tris(2-chloroethyl) phosphate 1543 1,2,3-Tris(chloromethoxy)propane 1549 Vinylidene fluoride 1551 CUMULATIVE INDEX TO THE MONOGRAPHS SERIES 1555 IARC MONOGRAPHS VOLUME 71vi 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– NOTE TO THE READER [...]... relevant biological and epidemiological data are collected by the Carcinogen Identification and Evaluation Unit of IARC from recognized sources of information on carcinogenesis, including data storage and retrieval systems such as MEDLINE and TOXLINE For chemicals and some complex mixtures, the major collection of data and the preparation of first drafts of the sections on chemical and physical properties,... a number of aspects of design and analysis as described in the report of the study Most of these considerations apply equally to case–control, cohort and correlation studies Lack of clarity of any of these aspects in the reporting of a study can decrease its credibility and the weight given to it in the final evaluation of the exposure Firstly, the study population, disease (or diseases) and exposure... Officer) A Meneghel, Unit of Chemoprevention D Mietton, Unit of Carcinogen Identification and Evaluation A Miller, Unit of Chemoprevention C Partensky, Unit of Carcinogen Identification and Evaluation E Rapiti1, Unit of Environmental Cancer Epidemiology J Rice, Unit of Carcinogen Identification and Evaluation (Head of Programme) J Wilbourn, Unit of Carcinogen Identification and Evaluation Secretarial... of the carcinogen and the route and length of exposure Evidence of an increased incidence of neoplasms with increased level of exposure strengthens the inference of a causal association between the exposure and the development of neoplasms The form of the dose–response relationship can vary widely, depending on the particular agent under study and the target organ Both DNA damage and increased cell... taxonomy and structure are described, and the degree of variability is given, when applicable Information on chemical and physical properties and, in particular, data relevant to identification, occurrence and biological activity are included For biological agents, mode of replication, life cycle, target cells, persistence and latency and host response are given A description of technical products of chemicals... does not imply acceptance of the adequacy of the study design or of the analysis and interpretation of the results, and limitations are clearly outlined in square brackets at the end of the study description It is necessary to take into account the possible roles of bias, confounding and chance in the interpretation of epidemiological studies By ‘bias’ is meant the operation of factors in study design... immunotoxicity and endocrine effects The presence and toxicological significance of cellular receptors is described Effects on reproduction, teratogenicity, fetotoxicity and embryotoxicity are also summarized briefly Tests of genetic and related effects are described in view of the relevance of gene mutation and chromosomal damage to carcinogenesis (Vainio et al., 1992) The adequacy of the reporting of sample... descriptions of the pathology of infection, molecular biology (integration and expression of viruses, and any genetic alterations seen in human tumours) and other observations, which might include cellular and tissue responses to infection, immune response and the presence of tumour markers 22 IARC MONOGRAPHS VOLUME 71 11 SUMMARY OF DATA REPORTED In this section, the relevant epidemiological and experimental... exposure circumstance and any studied cancer at any observed level of exposure A conclusion of ‘evidence suggesting lack of carcinogenicity’ is inevitably limited to the cancer sites, conditions and levels of exposure and length of observation covered by the available studies In addition, the possibility of a very small risk at the levels of exposure studied can never be excluded In some instances, the... Brennan, Unit of Environmental Cancer Epidemiology J Cheney (Editor) C Genevois-Charmeau, Unit of Carcinogen Identification and Evaluation Y Grosse, Unit of Carcinogen Identification and Evaluation V Krutovskikh, Unit of Multistage Carcinogenesis C Malaveille, Unit of Endogenous Cancer Risk Factors 6 IARC MONOGRAPHS VOLUME 71 D McGregor, Unit of Carcinogen Identification and Evaluation (Responsible Officer) . WORKING GROUP ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS: RE-EVALUATION OF SOME ORGANIC CHEMICALS, HYDRAZINE AND HYDROGEN PEROXIDE Lyon, 17–24 February 1998 LIST OF PARTICIPANTS 1 Present address:. Library Cataloguing in Publication Data Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide / IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1999 :. EVALUATION OF CARCINOGENIC RISKS TO HUMANS WORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY FOR RESEARCH ON CANCER 1999 IARC LYON FRANCE VOLUME 71 RE-EVALUATION OF SOME ORGANIC CHEMICALS, HYDRAZINE AND HYDROGEN