Environmental Health Criteria 154 Acetonitrile Please note that the layout and pagination of this web version are not identical with the printed version. Acetonitrile (EHC 154, 1993) INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 154 ACETONITRILE 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 K. Hashimoto (Kanazawa University, Japan), Dr. K. Morimoto (National Institute of Hygienic Sciences, Japan) and Dr. S. Dobson (Institute of Terrestrial Ecology, Monks Wood Experimental Station, United Kingdom) 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 Acetonitrile. (Environmental health criteria ; 154) Page 1 of 68 Acetonitrile (EHC 154, 1993) 1.Acetonitriles - adverse effects 2.Acetonitriles - toxicity 3.Environmental exposure I.Series ISBN 92 4 157154 3 (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 ACETONITRILE 1. SUMMARY 1.1. Properties, uses and analytical methods 1.2. Environmental levels and sources of human exposure 1.3. Environmental distribution and transformation 1.4. Environmental effects 1.5. Absorption, distribution, biotransformation and elimination 1.6. Effects on laboratory mammals 1.7. Effects on humans 2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL METHODS 2.1. Identity 2.2. Physical and chemical properties 2.2.1. Physical properties 2.2.2. Chemical properties 2.3. Conversion factors 2.4. Analytical methods 2.4.1. Determination of acetonitrile in ambient air 2.4.1.1 Sampling methods Page 2 of 68 Acetonitrile (EHC 154, 1993) 2.4.1.2 Measurement of acetonitrile in collected air samples 2.4.2. Monitoring methods for the determination of acetonitrile and its metabolites in biological materials 2.4.2.1 Acetonitrile in urine 2.4.2.2 Acetonitrile in serum 2.4.2.3 Acetonitrile metabolites in tissues and biological fluids 3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE 3.1. Natural occurrence 3.2. Anthropogenic sources 3.2.1. Production levels and processes 3.2.2. Uses 4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION 4.1. Transport and distribution between media 4.1.1. Water 4.2. Transformation 4.2.1. Biodegradation 4.2.1.1 Water and sewage sludge 4.2.1.2 Soil 4.2.2. Abiotic degradation 4.2.2.1 Water 4.2.2.2 Air 5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 5.1. Environmental levels 5.1.1. Air 5.1.2. Water and bottom sediment 5.1.3. Food 5.1.4. Tobacco smoke 5.1.5. Other sources of exposure 5.2. Occupational exposure 5.3. Acetonitrile in various solvent products 6. KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS 6.1. Absorption 6.1.1. Human studies 6.1.2. Experimental animal studies 6.1.2.1 Intake through inhalation 6.1.2.2 Dermal absorption 6.1.2.3 Intake via the gastrointestinal tract 6.2. Distribution 6.2.1. Human studies 6.2.2. Experimental animal studies 6.3. Biotransformation and elimination 6.3.1. Human studies 6.3.2. Experimental animal studies and in vitro studies 6.3.2.1 Cyanide liberation from acetonitrile 6.3.2.2 The oxidative pathway of acetonitrile metabolism 6.4. Biological monitoring of acetonitrile uptake 7. EFFECTS ON LABORATORY MAMMALS; IN VITRO TEST SYSTEMS 7.1. Acute toxicity 7.1.1. Single exposure Page 3 of 68 Acetonitrile (EHC 154, 1993) 7.1.2. Clinical observations 7.1.2.1 Effect on skin 7.1.2.2 Effect on the eyes 7.1.2.3 Effect on respiration 7.1.2.4 Effect on adrenals 7.1.2.5 Effect on the gastrointestinal tract 7.1.3. Biochemical changes and mechanisms of acetonitrile toxicity 7.1.3.1 Effect on cytochrome oxidase 7.1.3.2 Effect on glutathione 7.1.4. Antidotes to acetonitrile 7.2. Subchronic toxicity 7.2.1. Inhalation exposure 7.2.2. Subcutaneous administration 7.3. Teratogenicity and embryotoxicity 7.4. Mutagenicity 7.4.1. Bacterial systems 7.4.2. Yeast assays 7.4.3. Drosophila melanogaster 7.4.4. Mammalian in vivo assays 7.4.5. Chromosome aberrations and sister chromatid exchange 7.5. Carcinogenicity 7.6. Cytotoxicity testing 8. EFFECTS ON HUMANS 8.1. Acute toxicity 8.1.1. Inhalation exposure 8.1.2. Dermal exposure 8.1.3. Oral exposure 8.2. Chronic toxicity 8.3. Mutagenicity and carcinogenicity 8.4. Occupational exposure to cyanide 8.5. Chronic poisoning by cyanides 8.5.1. Ingestion 9. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD 9.1. Microorganisms 9.2. Aquatic organisms 10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT 10.1. Evaluation of human health risks 10.2. Evaluation of effects on the environment 11. RECOMMENDATIONS FOR THE PROTECTION OF HUMAN HEALTH 12. FURTHER RESEARCH 13. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES REFERENCES RESUME RESUMEN WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ACETONITRILE Members Page 4 of 68 Acetonitrile (EHC 154, 1993) Dr R. Bruce, System Toxicants Assessment Branch, Office of Research and Development, Environmental Criteria and Assessment Office, US Environmental Protection Agency, Cincinnati, Ohio, USA (Joint Rapporteur) Dr R.J. Bull, College of Pharmacy, Washington State University, Pullman, Washington, USA Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood Experimental Station, Huntingdon, United Kingdom (Vice-Chairman) Dr K. Hashimoto, Department of Hygiene, School of Medicine, Kanazawa University, Kanazawa, Japan Dr P. Lauriola, Local Hygiene Unit, Office of Public Hygiene, Modena, Italy Dr M. Lotti, Institute of Occupational Medicine, University of Padua, Padua, Italy (Chairman) Dr K. Morimoto, Division of Biological Chemistry and Biologicals, National Institute of Hygienic Sciences, Tokyo, Japan (Joint Rapporteur) Dr Y.F. Panga, Department of Standard Setting, Chinese Academy of Preventive Medicine, Beijing, China Dr S.A. Soliman, Department of Pesticide Chemistry, College of Agriculture and Veterinary Medicine, King Saud University, Al-Qasseem, Bureidah, Saudi Arabia Secretariat Dr B.H. Chen, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland (Secretary) Dr E. Smith, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland a Invited but unable to attend. 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, Case postale 356, 1219 Châtelaine, Geneva, Switzerland (Telephone No. 9799111). * * * Page 5 of 68 Acetonitrile (EHC 154, 1993) This publication was made possible by grant number 5 U01 ES02617-14 from the National Institute of Environmental Health Sciences, National Institutes of Health, USA. WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ACETONITRILE A WHO Task Group on Environmental Health Criteria for Acetonitrile met in Modena, Italy, from 24 to 28 November 1992. Mr Giorgio Baldini, the President of the Province of Modena, opened the meeting and greeted the participants on behalf of the Province of Modena. Dr B.H. Chen of the International Programme on Chemical Safety (IPCS) welcomed the participants on behalf of the Director, IPCS, and the three IPCS cooperating organizations (UNEP/ILO/WHO). The Task Group reviewed and revised the draft criteria monograph and made an evaluation of the risks for human health and the environment from exposure to acetonitrile.