Environmental Health Criteria 143 Methyl Ethyl Ketone
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Environmental Health Criteria 143 Methyl ethyl ketone Please note that the layout and pagination of this web version are not identical with the printed version. Methyl ethyl ketone (EHC 143, 1992) INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 143 METHYL ETHYL KETONE 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 First draft prepared by Dr R.B. Williams, United States Environmental Protection Agency World Health Orgnization Geneva, 1993 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. WHO Library Cataloguing in Publication Data Methyl ethyl ketone. (Environmental health criteria ; 143) Page 1 of 101 Methyl ethyl ketone (EHC 143, 1992) 1.Butanones - adverse effects 2.Butanones - toxicity 3.Occupational exposure I.Series ISBN 92 4 157143 8 (NLM Classification: QV 633) ISSN 0250-863X 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 already available. (c) World Health Organization 1993 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 METHYL ETHYL KETONE 1. SUMMARY 1.1. Properties and analytical methods 1.2. Sources of exposure and uses 1.2.1. Production and other sources 1.2.2. Uses and loss to the environment 1.3. Environmental transport and distribution 1.4. Environmental levels and human exposure 1.5. Kinetics and metabolism 1.6. Effects on experimental species 1.7. Effects on humans 1.7.1. MEK alone 1.7.2. MEK in solvent mixtures 1.8. Enhancement of the toxicity of other solvents 2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES AND ANALYTICAL METHODS 2.1. Identity 2.2. Chemical and physical properties 2.3. Conversion factors 2.4. Sampling and analytical methods 2.4.1. General considerations 2.4.2. Air 2.4.3. Water Page 2 of 101 Methyl ethyl ketone (EHC 143, 1992) 2.4.4. Solids 2.4.5. Biological materials 3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE 3.1. Natural occurrence 3.2. Production levels, processes and uses 3.2.1. World production 3.2.2. Production processes 3.2.3. Other sources 3.2.4. Uses 3.3. Release into the environment 4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION 4.1. Transport in the environment 4.2. Bioaccumulation and biodegradation 5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 5.1. Environmental levels 5.1.1. Air 5.1.2. Water 5.1.3. Foodstuffs 5.2. General population exposure 5.3. Occupational exposure 5.4. Peri-occupational exposure 6. KINETICS AND METABOLISM 6.1. Absorption 6.1.1. Percutaneous absorption 6.1.2. Inhalation absorption 6.1.3. Ingestion absorption 6.1.4. Intraperitoneal absorption 6.2. Distribution 6.3. Metabolic transformation 6.3.1. Animal studies 6.3.2. Human studies 6.4. Elimination and excretion 6.5. Turnover 6.6. Metabolic interactions 6.7. Mechanisms of action 7. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS 7.1. Acute exposure 7.1.1. Lethal doses 7.1.2. Non-lethal doses 7.1.3. Skin and eye irritation 7.2. Repeated exposures 7.3. Neurotoxicity 7.3.1. Behavioural testing 7.3.2. Histopathology 7.4. Developmental toxicity 7.5. Mutagenicity and related end-points 7.6. Carcinogenicity 8. EFFECTS ON HUMANS 8.1. General population exposure 8.2. Effects of short-term exposure 8.3. Skin irritation and sensitization 8.4. Occupational exposure Page 3 of 101 Methyl ethyl ketone (EHC 143, 1992) 8.4.1. MEK alone 8.4.2. MEK in solvent mixtures 8.5. Carcinogenicity 9. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD 9.1. Microorganisms 9.2. Aquatic organisms 9.3. Terrestrial organisms 9.3.1. Animals 9.3.2. Plants 10. ENHANCEMENT OF THE TOXICITY OF OTHER SOLVENTS BY MEK 10.1. Hexacarbon neuropathy 10.1.1. Introduction 10.1.2. Animal studies 10.1.3. Human studies 10.1.3.1 Solvent abuse 10.1.3.2 Occupational exposure 10.2. Haloalkane solvents 10.2.1. Studies in animals 10.2.2. Potentiation of haloalkane toxicity in humans 11. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT 11.1. Human health risks 11.1.1. Non-occupational exposure 11.1.2. Occupational exposure 11.1.3. Relevant animals studies 11.2. Effects on the environment 12. RECOMMENDATIONS FOR THE PROTECTION OF HUMAN HEALTH AND THE ENVIRONMENT 12.1. Human heath protection 12.2. Environmental protection 13. FURTHER RESEARCH REFERENCES APPENDIX 1. Conversion factors for various solvents RESUME RESUMEN WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR METHYL ETHYL KETONE Members Professor E.A. Bababunmi, Postgraduate Institute for Medical Research and Training, College of Medicine, Ibadan, Nigeria Dr P.E.T. Douben, Department of Ecotoxicology, Institute for Forestry and Nature Research, Arnhem, The Netherlands Professor C.L. Galli, Toxicology Laboratory, Institute of Pharmacological Sciences, University of Milan, Milan, Italy (Chairman) Page 4 of 101 Methyl ethyl ketone (EHC 143, 1992) Dr R.F. Hertel, Fraunhofer Institute of Toxicology and Aerosol Research, Hanover, Germany Dr H.P.A. Illing, Head of Toxicology, Health and Safety Executive, Bootle, United Kingdom Professor A. Massoud, Department of Community, Environmental & Occupational Health, Faculty of Medicine, Ain Shams University, Abbassia, Egypt (Joint Rapporteur) Dr K. Morimoto, Division of Chem-Bio Informatics, National Institute of Hygienic Sciences, Setagaya-ku, Tokyo, Japan Dr V. Riihimäki, Institute of Occupational Health, Helsinki, Finland Dr E. de Souza Nascimento, University of Sao Paulo, Sao Paulo, Brazil Dr H. Tilson, Neurotoxicology Division, Health Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, USA Dr R.B. Williams, Office of Research and Development, US Environmental Protection Agency, Washington D.C., USA (Joint Rapporteur) Secretariat Dr P.G. Jenkins, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland Dr E. Smith, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland NOTE TO READERS OF THE CRITERIA MONOGRAPHS Every effort has been made to present information in the criteria monographs as accurately as possible without unduly delaying their publication. In the interest of all users of the Environmental Health Criteria monographs, readers are kindly requested to communicate any errors that may have occurred to the Director of the International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland, in order that they may be included in corrigenda. * * * A detailed data profile and a legal file can be obtained from the International Register of Potentially Toxic Chemicals, Palais des Nations, 1211 Geneva 10, Switzerland (Telephone No. 7988400 or 7985850). ENVIRONMENTAL HEALTH CRITERIA FOR METHYL ETHYL KETONE A WHO Task Group on Environmental Health Criteria for Methyl Ethyl Ketone (MEK) met at the World Health Organization, Geneva, from 9 to 13 September 1991. Dr E. Smith welcomed the participants on behalf of Dr M. Mercier, Director, IPCS, and on behalf of the heads of the three IPCS cooperating organizations (UNEP/ILO/WHO). The Task Group reviewed and revised the draft monograph and made an evaluation of the risks for human health and the environment from exposure to MEK. Page 5 of 101 Methyl ethyl ketone (EHC 143, 1992) The first draft of this monograph was prepared by Dr R.B. Williams, Office of Research and Development, US Environmental