IARC Monographs on the Evaluation of

569 Pages·2012·38.22 MB·English

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WORLD HEALTH ORGANIZATION
INTERNATIONAL AGENCY FOR RESEARCH ON CANCER
IAC MONOGRAHS
ON THE
EVALUATION OF CARCINOGENIC
RISKS TO HUMAS
Sorne Industrial Chemicals
VOLUME 60
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 1994
1994
IARC MONOGRAHS
ln 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. ln 1980 and 1986, the programme
was expanded to include evaluations of carcinogenic risks associated with exposures to
complex mixtures and other agents.
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.
This project is supported by PHS Grant No. 5-U01 CA33193-12 awarded by the US
National Cancer Institute, Department of Realth and Ruman Servces. Additional support
has been provided since 1986 by the European Commission.
(êlnternational Agency for Research on Cancer 1994
ISBN 92 832 1260 6
ISSN 0250-9555
Publications of the World Health Organization enjoy copyright protection in accordance
col 2 of the Universal Copyright Convention.
with the provisions of Proto
AIl rights reserved. Application for rights of reproduction or translation, in part or in tata,
should be made to the International Agency for Research on Cancer.
Distributed for the International Agency for Research on Cancer
by the Secretariat of the World Health Organization, Geneva
PRINTED lN THE UNITED KlNGDOM
CONTENTS
ADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
NOTE TO THE RE
LIST OF PARTICIPANTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
PREAMBLE .......................................................... 13
Background ........................................................ 13
Objective and Scope ................................................. 13
Selection of Topics for Monographs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Data for Monographs ................................................ 15
The Working Group ................................................. 15
Working Procedures ................................................. 15
Exposure Data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Studies of Cancer in Humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Studies of Cancer in Experimental Animais .............................. 21
Other Relevant Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Summary of Data Reported ........................................... 24
Evaluation ......................................................... 26
References ......................................................... 30
GENERA REMARKS ON THE AGENTS CONSIDERED
35
THE MONOGRAHS
Ethylene ............................................................ 45
Ethylene oxide ..................................................... .. 73
Propylene .......................................................... 161
Propylene oxide ..................................................... 181
Isoprene ........................................................... 215
Styene ............................................................ 233
Styene-7,8-oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 321
4-Vinylcyclohexene .................................................. 347
4- Vinylcyclohexene diepoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 361
Vinyl toluene ....................................................... 373
Acrylamide ......................................... . . . . . . . . . . . . . . .. 389
N-Methylolacrylamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 435
CONTENTS
Methyl methacrylate ................................................. 445
2-Ethylhexyl acrylate ................................................. 475
SUMMARY OF FINAL EVALUATIONS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 487
APPENDIX 1. SUMMARY TABLES OF GENETIC AND RELATED EFFECTS . 489
APPENDIX 2. ACTIVITY PROFILES FOR GENETIC AND RELATED
EFFECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 509
CUMULATIVE INDEX TO THE MONOGRAPHS SERIES. . . . . . . . . . . . . . . . . .. 533
NOTE TO THE READER
The term 'carcinogenic risk' in the lARC Monographs series is taken to me an the proba-
ad to cancer in humans.
bility that exposure to an agent will le
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
an that it is not carcinogenic.
evaluated in a monograph does not me
The evaluations of carcinogenic risk are made by international working groups of in-
dependent scientists and are qualitative in nature. No recommendation is given for regu-
lation or legislation.
Anyone who is aware of published data that may alter the evaluation of the carcinogenic
ans is encouraged to make this information available w the Unit of
risk of an agent to hum
Carcinogen Identification and Evaluation, International Agency for Research on Cancer,
150 cours AIbert Thomas, 69372 Lyon Cedex 08, France, in order that the agent may be
considered for re-evaluatIon by a future Working Group.
AIthough 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.
-5-

IARC WORKING GROUP ON THE EVALUATION OF
CARCINOGENIC RISKS TO HUMANS:
SOME INDUSTRIAL CHEMICALS
Lyon, 15-22 February 1994
LIST OF PARTICIPANTS
Members
P.A. Bertazzi, Institute of Occupational Health, Clinica deI Lavoro 'Luigi Devoto',
University of Milan, via S. Barnaba 8, 20122 Milan, Italy
Cl. Calleman, School of Public Health and Community Medicine, Department of
Environmental Health, SC-34, University of Washington, Seattle, WA 98195, USA
D. Coggon, MRC Environmental Epidemiology Unit, Southampton General Hospital,
Southampton, S09 4XY, United Kingdom
T.A. Dragani, Division of Experimental Oncology A, National Institute for the Study and
Treatment of Tumours, via Venezian 1, 20133 Milan, Italy
M.R. Elwell, Toxicology Research and Testing Program, National Institute of Environmental
Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA
H.l. Evans, MRC Human Genetic Unit, Western General Hospital, Crewe Road, Edinburgh
EH4 2XU, United Kingdom (Chairperson)
l.G. Filser, GSF Institute of Toxicology, Neuherberg, PO Box 1129, 85758 Oberschleiss-
heim, Germany
M. Gérin, University of Montréal, Department of Occupational and Environmental Health,
Faculty of Medicine, CP 6128, Station A, Montréal, Québec, Canada H3C 317
K. Hemminki, Centre for Nutrition and Toxicology, Karolinska Institute, Novum, 141 57
Huddinge, Sweden
C Hogstedt, National Institute of Occupational Health, 171 84 Solna, Sweden
M. Kirsch- Volders, Laboratorium Antropogenetica, Free University of Brussels, Pleinlaan 2,
1050 Brussels, Belgium
W. Lutz, Institute of Toxicology, Swiss Federal Institute of Technology, Schorenstrasse 16,
8603 Schwerzenbach, Switzerland1
lPresent address: Department of Würzburg, Versbacher Strasse 9,97089 Würzburg,
Toxicology, University of
Germany
-7-
8 IARC MONOGRAPHS VOLUME 60
s.s. Olin, International Life SCiences Institute, Risk Science Institute, 1126 Sixteenth Street
NW, Washington DC 20036, USA
Hygiene, Gyáli ut. 2-6, 1966 Budapest, Hungary
A. Pintér, 'lohan Béla' National Institute of
P. Schulte, Screening and Notification Section, National Institute for Occupational Safety
and Health, Robert A. Taft Laboratories, 4676 Columbia Parkway, R-42, Cincinnati,
OH 45226-1998, USA
T. Sofuni, Division of Genetics and Mutagenesis, Biological Safety Research Centre,
National Institute of Hygienic Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158,
1 apan
M. Sorsa, Institute of Occupational Health, Topeliuksenkatu 41 a A, 00250 Helsinki, Finland
(Vice-Chairperson)
F.M. Sullivan, Division of Pharmacology and Toxicology, UMDS, St Thomas's Hospital,
Lambeth Palace Road, London SEI 7ER, United Kingdom
YS. Turusov, Cancer Research Centre, Russian Academy of Medical Sciences, Kashirskoye
Shosse 24, 115478 Moscow, Russian Federation
M.A. Waters, National Institute for Occupational Safety and Health, 4676 Columbia
Parkway, R-14, Cincinnati, OH 45226-1998, USA
M.D. Waters, International Programs, MD-51A, Health Effects Research Laboratory, US
Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Rep resen tati ves/ observers
Natžonal Cancer Institute
D. Longfellow, Division of Cancer Etiology, National Cancer Institute, Building 31, Room
i 1A03, Bethesda, MD 20892, USA
American Industry Health Council
l.A. Swenberg, Departments of Environmental Sciences and Engineering, and Pathology,
The University of North Carolina at Chapel Hill, CB 7400, Room 357, Rosenau Hall,
Chapel Hill, NC 27599-7525, USA
European Commission
M. laroszewski, Health and Safety Directorate, European Commission, Bâtiment lean
Monnet, 2920 Luxembourg, Grand Duchy of Luxembourg
European Centre for Ecotoxicology and Toxicology of Chemicals
H.-P. Gelbke, Department of Toxicology, BASF AG, 67056 Ludwigshaven, Germany
E. Leibold, Department of Toxicology, BASF AG, 67056 Ludwigshaven, Germany
Japan Styrene Industry Association
l. Miyamoto, Sumitomo Chemical Co., 4-5-33 Kitahama, Chuo-ku, Osaka, lapan
PARTICIPANS
9
Secretariat
International Programme on Chemical Safety
RH. Chen, International Programme on Chemical Safety, World Health Organization, 1211
Geneva 27, Switzerland
IARC
P. Boffetta, Unit of Analytical Epidemiology
E. Cardis, Unit of Analytical Epidemiology
M. Friesen, Unit of Environmental Carcinogenesis
M.-l. Ghess, Unit of Carcinogen Identification and Evaluation
E. Heseltine, 24290 St Léon-sur- Vézère, France
P. Kleihues, Director
M. Kogevinas, Unit of Analytical Epidemiology2
V Krutovskikh, Unit of Multistage Carcinogenesis
l. Little, Unit of Analytical Epidemiology
D. McGregor, Unit of Carcinogen Identification and Evaluation
D. Mietton, Unit of Carcinogen Identification and Evaluation
H. Møller, Unit of Carcinogen Identification and Evaluation
V Moreno, Unit of Field and Intervention Studies3
C. Partensky, Unit of Carcinogen Identification and Evaluation
1. Peterschmitt, Unit of Carcinogen Identification and Evaluation, Geneva, Switzerland
H. Vainio, Unit of Carcinogen Identification and Evaluation
l. Wilbourn, Unit of Carcinogen Identification and Evaluation
H. Yamasaki, Unit of Multistage Carcinogenesis
Secretarial assistance
M. Lézère
l. Mitchell
S. Reynaud
2Present address: Department of Epidemiology and Public Health, Municipal Institute of Medical Investiga-
tion, calle Doctor Aiguades 80, 08003 Barcelona, Spain
3Present address: Autonornous University, Faculty of Medicine, Bellaterra, 08193 Barcelona, Spain