~.-.VJ WORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY FOR RESEARCH ON CANCER IARC MONOGRAPHS ON THE EVALUATION OF THE CARCINOGENIC RISK OF CHEMICALS TO HUMANS Sorne Aromatic Amines, Anthraauinones and Nitroso Compounds, and Inorganic Fluorides U sed in Drinking-water and Dental Preparations VOLUME 27 This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans which met in Lyon, 10-17 February 1981 April 1982 INTERNATIONAL AGENCY FOR RESEARCH ON CANCER lARe MONOGRAPHS ln 1971, 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. ln 1980, the programme was expanded to include the evaluation of the carcinogenic risk associated with employment 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 chemicals and complex mixtures to which humans are known to be exposed, and on specific occupational exposures, to evaluate those 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. International Agency for Research on Cancer 1982 ISBN 92 8 321227 4 PRINTED lN SWITZERLAND eONTENTS LIST OF PARTICIPANTS .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. " .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 5 NOTE TO THE READER .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 9 PREAMBLE .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 11 Background . 11 Objective and Scope . 11 Selection of Chemicals for Monographs 12 Working Procedures 13 Data for Evaluations 13 The Working Group 13 General Principles for Evaluating the Carcinogenic Risk of Chemicals 14 Explanatory Notes on the Monograph Contents . 19 GENERAL REMARKS ON THE SUBSTANCES CONSIDERED 31 THE MONOGRAPHS .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 35 Aromatic amines Aniline and aniline hydrochloride ........... 39 ortho- and para-Anisidine and their hydrochlorides . 63 4-Chloro-ortho- and 4-chloro-meta-phenylenediamine 81 meta- and para-Cresidine . 91 2,4-Diaminoanisole and 2,4-diaminoanisole sulphate 103 4,4'-Methylenebis(N;N-dimethyl)benzenamine 119 5-Nitro-ortho-anisidine1,5-Naphthalenediamine .. .. 133127 4,4'-Thiodianiline2,2',5,5'-Tetrachlorobenzidine . 147 141 ortho- T oluidine and ortho-toluidine hydrochloride 155 2,4,5- and 2,4,6-Trimethylaniline and their hydrochlorides 177 Anthraquinones2-Aminoanthraquinone . 191 1-Amino-2-methylanthraquinone 199 2-Methyl-1-nitroanthraquinone 205 N-NitrosodiphenylamineNitroso compounds 213 para-Nitrosodiphenylamine 227 Inorganic fluorides used in drinking-water and dental preparations 237 4 IARC MONOGRAPHS VOLUME 27 APPENDIX 1 : EPIDEMIOLOGICAL EVIDENCE RELA TING TO THE POSSIBLE CARCINOG- ENIC EFFECTS OF HAIR OYES lN HAIRDRESSERS AND USERS OF HAIR OYES .. 307 SUPPLEMENT ARY CORRIGENDA TO VOLUMES 1-26 ................... 321 CUMULATIVE INDEX TO MONOGRAPHS .......................... 323 lARe WORKING GROUP ON THE EVALUATION OF THE CARCINOGENle RISK OF eHEMleALS TO HUMANS: SOME AROMATle AMINES, ANTHRAQUINONES AND NITROSO eOMPOUNDS, AND INORGANle FLUOR IDES USED lN DRINKING- WATER AND DENTAL PREPARATIONS Lyon, 10-17 February 1981 Members 1 B.K. Armstrong, NHRMRC Research Unit in Epidemiology and Preventive Medicine, Department of Medicine, Medical School Building, The Queen Elizabeth Il Medical Centre, Nedlands, Western Australia 6009, Australia (Chairman; co-rapporteur section 3.3) R. Bass, Institute of Pharmaceutics of the Federal Ministry of Health, Postal Box 330013, 1000 Berlin 33, Federal Republic of Germany N. Breslow, Department of Biostatistics, SC-32, University of Washington, Seattle, WA 98195, USA I.N. Chernozemsky, Head, Laboratory of Chemical Carcinogenesis and Testing, Institute of Oncology, Medical Academy, Sofia 1156, Bulgaria (Vice-chairman; co-rapporteur section 3.1) G. Della Porta, Director, Division of Experimental Oncology, Nationallnstitute for the Study and Treatment of Tumours, Via Venezian 1, 20133 Milan, Italy H.K. Kang, Health Scientist, Office of Carcinogen Identification and Classification, Health Standards Programs, Occupational Safety & Health Administration, US Department of Labor, Washington DC 20210, USA B.J. Kilbey, University of Edinburgh, Department of Genetics and ARC Unit of Animal Genetics, Institute of Animal Genetics, West Mains Road, Edinburgh EH9 3JN, UK C.M. King, Chairman, Department of Chemical Carcinogenesis, Michigan Cancer Foundation, 110 East Warren Avenue, Detroit, MI 48201, USA (Co-rapporteur section 3.2) E. Kriek, Chief, Chemical Carcinogenesis Division, The Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands N.P. Napalkov, Director, N.N. Petrov Research Institute of Oncology, Leningradskaya Street 68, Pesochny-2, Leningrad 188646, USSR H.S. Rosenkranz2, Department of Microbiology, New York Medical College, Basic Science Building, Valhalla, NY 10595, USA (Co-rapporteur section 3.2) 1 Unable to attend: E. Arrhenius, Vindkallsvaeden 3, 18261 Djunsholm, Sweden; S.M. Brown, PO Box 3254, Berkeley, CA 94703, USA; P. Cole, University of Alabama, Department of Epidemiology, Tidwell Hall 203, Birmingham, AL 35295, USA; M.R. Parkhie, Visiting Scientist, MRC Toxicology Unit, Medical Research Council Laboratories, Woodmansterne Road, Carshalton, Surrey SM5 4EF, UK 2 Present address: Director, Center for the Environmental Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA 6 IARC MONOGRAPHS VOLUME 27 S.S. Thorgeirsson, Laboratory of Chemical Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, Building 37, Room 5A 13, Bethesda, MD 20205, USA J.M. Ward, Veterinary Pathologist. National Cancer Institute, National Toxicology Program, Bethesda, MD 20205, USA M. Webb, Medical Research Council, Toxicology Unit. MRC Laboratories, Woodmansterne Road, Carshalton, Surrey SM5 4EF, UK F. Zad je la, Director, U22 INSERM, Curie Institute, Bldg 110, 91405 Orsay, France Representative From the National Cancer Institute H. Kraybill, Scientific Coordinator for Environmental Cancer, Division of Cancer Cause and Prevention, Landow Building, Room 3C37, National Cancer Institute, Bethesda, MD 20205, USA Representative From SRI International M. McCaleb, Director, Chemical-Environmental Program, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA (Rapporteur sections 2.1 & 2.2) Representative from the ChemIcal Manufacturas' Association A.M. Kaplan, E.1. du Pont de Nemours Co., Haskell Laboratory, Elkton Road, Newark, DE 19711, USA Representative From the Commission of the European Communities M.-T. van der Venne, Directorate General for Employment and Social Affairs, Health & Safety Directorate, Commission of the European Communities, Jean Monnet Building, Plateau du Kirchberg, BP 1907, Luxembourg, Grand Duchy of Luxembourg Representative From the European Chemical Industry Ecology and Toxicology Centre J.lshmael, ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK 1 0 4T J, UK PARTICIPANTS 7 Observers M. Gilbert, Scientific Affairs Officer, International Register of Potentially Toxic Chemicals, United Nations Environment Programme, 16 Avenue Jean Tremblay, Petit Saconnex, 1209 Geneva, Switzerland J. Matthews, Association of Scientific, Technical and Managerial Staffs, Health & Safety Research Officer, Whitehall Office, Dane O'Coys Road, Bishops Stortford, Herts, UK Secretariat3 C. Agthe, Division of Epidemiology and Biostatistics A. Aitio, Division of Environmental Carcinogenesis H. Bartsch, Division of Environmental Carcinogenesis (Co-rapporteur section 3.2) J.R.P. Cabral, Division of Environmental Carcinogenesis W.Davis, Programme of Research Training and Liaison (TechnIcal edItor IARC) M. Friesen, Division of Environmental Carcinogenesis L. Haroun, Division of Environmental Carcinogenesis (Co-secretary) E. Heseltine, Charost, France (Editor) A. Likhachev, Division of Environmental Carcinogenesis D. Mietton, Division of Environmental Carcinogenesis (Libraryassistant) R. Montesano, Division of Environmental Carcinogenesis (Co-rapporteur section 3.1) 1. O'Neill, Division of Environmental Carcinogenesis (Rapporteur sections 1 & 2.3) C. Partensky, Division of Environmental Carcinogenesis (TechnicaJ of1cer) 1. Peterschmitt, Division of Environmental Carcinogenesis, Geneva (Bibliographic researcher) R. Saracci, Division of Epidemiology and Biostatistics (Co-rapporteur section 3.3) L. Simonato, Division of Epidemiology and Biostatistics J. Wilbourn, Division of Environmental Carcinogenesis (Co-secretary) SecretariaJ assistance M.-J. Ghess K. Masters S. Reynaud J. Smith 3 Unable to attend: L. Tomatis, Director, Division of Environmental Carcinogenesis (Head of the Programme) NOTE TO THE READER The term 'carcinogenic risk' in the lARC Monograph series is taken to mean the probability that exposure to a chemical or complex mixture or employment in a particular occupation willlead to cancer in humans. The fact that a monograph