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Environmental Health Criteria 52 TOLUENE Environmental Health Criteria 52 TOLUENE Please note that the layout and pagination of this web version are not identical with the printed version. Toluene (EHC 52, 1986) INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 52 TOLUENE This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organisation, or the World Health Organization. Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization World Health Orgnization Geneva, 1985 The International Programme on Chemical Safety (IPCS) is a joint venture of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization. The main objective of the IPCS is to carry out and disseminate evaluations of the effects of chemicals on human health and the quality of the environment. Supporting activities include the development of epidemiological, experimental laboratory, and risk-assessment methods that could produce internationally comparable results, and the development of manpower in the field of toxicology. Other activities carried out by the IPCS include the development of know-how for coping with chemical accidents, coordination of laboratory testing and epidemiological studies, and promotion of research on the mechanisms of the biological action of chemicals. ISBN 92 4 154192 X The World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. Applications and enquiries should be addressed to the Office of Publications, World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information on any changes made to the text, plans for new editions, and reprints and translations Page 1 of 104 Toluene (EHC 52, 1986) already available. (c) World Health Organization 1985 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. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. CONTENTS ENVIRONMENTAL HEALTH CRITERIA FOR TOLUENE 1. SUMMARY AND RECOMMENDATIONS 1.1. Summary 1.1.1. Identity and analytical methods 1.1.2. Production, uses, and sources of exposure 1.1.3. Kinetics, biotransformation, and biological monitoring 1.1.4. Effects on experimental animals 1.1.5. Effects on human beings 1.1.6. Effects on aquatic and terrestrial organisms in the environment 1.2. Conclusions and recommendations 1.2.1. Conclusions 1.2.2. Recommendations 2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS 2.1. Identity 2.2. Physical and chemical properties 2.3. Organoleptic properties 2.4. Conversion factors 2.5. Analytical methods 2.5.1. Sampling procedures 2.5.1.1 Air 2.5.l.2 Water 2.5.1.3 Soils and sediments 2.5.2. Biological monitoring of toluene exposure 2.5.2.1 Blood, expired air, body fluids, and tissues 2.5.2.2 Urine 2.5.2.3 Human breast milk 2.5.3. Food and food containers 2.5.4. Detection of marketed toluene purity 3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE Page 2 of 104 Toluene (EHC 52, 1986) 3.1. Natural occurrence 3.2. Man-made sources 3.2.1. Production levels, processes, and uses 3.2.1.1 Production 3.2.1.2 World production figures 3.2.1.3 Manufacturing processes 3.2.2. Uses 4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION 4.1. Transport and distribution between media 4.1.1. Air 4.1.2. Water 4.1.3. Soil 4.1.4. Entry into the food chain 4.2. Biotransformation 4.2.1. Biodegradation 4.2.2. Bioaccumulation 5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 5.1. Environmental levels 5.1.1. Air 5.1.2. Water 5.2. General population exposure 5.3. Occupational exposure during manufacture, formulation, or use 6. EFFECTS ON ORGANISMS IN THE ENVIRONMENT 6.1. Microorganisms 6.2. Aquatic organisms 6.3. Terrestrial organisms 6.4. Population and ecosystem effects 6.5. Effects on the abiotic environment 7. KINETICS AND METABOLISM 7.1. Absorption 7.1.1. Inhalation 7.1.1.1 Rat 7.1.1.2 Dog 7.1.1.3 Human volunteers 7.1.2. Dermal 7.1.2.1 Guinea-pig 7.1.2.2 Human volunteers 7.1.3. Oral 7.2. Distribution 7.2.1. Inhalation 7.2.1.1 Mouse 7.2.1.2 Rat 7.2.1.3 Human volunteers 7.2.2. Oral 7.2.2.1 Rat 7.2.3. Intraperitoneal 7.2.3.1 Rat 7.3. Metabolic transformation 7.3.1. Oral 7.3.2. Inhalation 7.3.2.1 Human beings 7.3.3. In vitro studies 7.4. Elimination and excretion in expired air, faeces, and urine Page 3 of 104 Toluene (EHC 52, 1986) 7.4.1. Toluene 7.4.1.1 Laboratory animals 7.4.1.2 Human beings 7.4.2. Excretion of metabolites 7.4.2.1 Human beings 8. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS 8.1. Single exposures 8.1.1. Inhalation 8.1.2. Oral 8.1.3. Intraperitoneal and intravenous injection 8.1.4. Subcutaneous injection 8.2. Short-term exposures 8.2.1. Inhalation 8.2.1.1 Mouse 8.2.1.2 Rat 8.2.1.3 Dog 8.2.2. Other animal species and routes 8.2.3. Oral 8.2.3.1 Rat 8.3. Skin and eye irritation; sensitization 8.3.1. Skin 8.3.2. Eye 8.4. Long-term exposures 8.4.1. Inhalation 8.4.1.1 Rat 8.5. Reproduction, embryotoxicity, and teratogenicity 8.5.1. Reproduction 8.5.2. Embryotoxicity and teratogenicity 8.5.2.1 Inhalation 8.5.2.2 Oral 8.6. Mutagenicity and related end-points 8.6.1. DNA damage 8.6.2. Mutation 8.6.3. Chromosomal effects 8.7. Carcinogenicity 8.7.1. Inhalation 8.7.2. Oral 8.7.3. Dermal 8.8. Special studies 8.8.1. Central nervous system (CNS) 8.8.2. Effects on electrical activity in the brain 8.8.3. Effects on neurotransmitters 8.8.4. Behaviour 8.8.5. Liver 8.9. Factors modifying toxicity; toxicity of metabolites 8.9.1. Effects of combined exposure to toluene and other chemicals 8.9.1.1 Benzene and toluene 8.9.1.2 Xylene and toluene 8.9.1.3 n-Hexane and toluene 8.9.1.4 Toluene and other chemicals 9. EFFECTS ON MAN 9.1. Acute toxicity 9.2. Effect of short- and long-term exposure including controlled human studies 9.2.1. Controlled human studies 9.2.2. Short- and long-term abuse in the general population 9.2.3. Epidemiological studies Page 4 of 104 Toluene (EHC 52, 1986) 9.3. Occupational exposure 9.3.1. Skin and mucous membranes 9.3.2. Central nervous system 9.3.3. Peripheral nervous system 9.3.4. Blood and haematopoietic system 9.3.5. Liver and kidney 9.3.6. Menstruation 9.3.7. Chromosome damage 10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT 10.1. Evaluation of human health risks 10.2. Acute and short-term effects on man 10.3. Evaluation of environmental hazards of toluene 11. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES REFERENCES WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR TOLUENE Members Dr K.S. Channer, Department of Medicine, Bristol Royal Infirmary, Bristol and Weston Health Authority, Bristol, United Kingdom (Rapporteur) Mr M. Greenberg, Office of Research and Development, Environmental Criteria Assistance Office, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA Dr I. Gut, Institute of Hygiene and Epidemiology, Prague, Czechoslovakia (Chairman) Dr J. Mäki-Paakkanen, Institute of Occupational Health, Department of Industrial Hygiene and Toxicology, Helsinki, Finland Dr C. Maltonia, Institute of Oncology and Centre for Tumours, Bologna, Italy Dr B.O. Osuntokun, Department of Medicine, University of Ibadan, Ibadan, Nigeria Dr S.S. Pawar, Department of Chemistry, Marathwada University, Aurangabad, Maharashtra, India (Vice-Chairman) Dr Y. Takeuchi, Department of Hygiene, Nagoya University School of Medicine, Showa-Ku, Nagoya, Japan Dr GY. Ungvary, Toxicology Section, National Institute of Occupational Health, Budapest, Hungary Dr G.D. Veith, Environmental Research Laboratory, US Environmental Protection Agency, Duluth, Minnesota, USA Representatives from Other Organizations Dr J. Wilbourn, International Agency for Research on Cancer, Lyons, France Secretariat Dr H.W. de Koning, Environmental Hazards and Food Protection, World Health Organization, Geneva, Switzerland Page 5 of 104 Toluene (EHC 52, 1986) Dr M. Mercier, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland Dr L.A. Moustafa, International Programme on Chemical Safety, Interregional Research Unit, Research Triangle Park, North Carolina, USA (Secretary) Ms F. Ouane, International Register of Potentially Toxic Chemicals, Geneva, Switzerland --------------------------------------------------------------------------- a Invited, but unable to attend. Secretariat (contd.) Dr C. Xintaras, Office of Occupational Health, World Health Organization, Geneva, Switzerland Observers Dr A. Berlin, Commission of the European Communities, Luxembourg, Luxembourg Dr M.-A. Boillat, Department de l'Intérieur et de la Santé publique, Institut Universitaire de Medecine du Travail et d'Hygiéne industrielle, Lausanne, Switzerland NOTE TO READERS OF THE CRITERIA DOCUMENTS Every effort has been made to present information in the criteria documents as accurately as possible without unduly delaying their publication.
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