Environmental Health Criteria 149 Carbendazim Please note that the layout and pagination of this web version are not identical with the printed version. Carbendazim (EHC 149, 1993) INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 149 CARBENDAZIM 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 IPCS staff, using texts made available by Dr L.W. Hershberger and Dr G.T. Arce, Wilmington, Delaware, USA 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 Carbendazim. (Environmental health criteria ; 149) Page 1 of 87 Carbendazim (EHC 149, 1993) 1.Benzimidazoles - adverse effects 2.Benzimidazoles - toxicity 3.Fungicides, Industrial - adverse effects 4.Fungicides, Industrial -toxicity I.Series ISBN 92 4 157149 7 (NLM Classification: WA 240) ISSN 0250-8634 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 CARBENDAZIM 1. SUMMARY AND CONCLUSIONS 1.1. Summary 1.1.1. Identity, physical and chemical properties, and analytical methods 1.1.2. Sources of human and environmental exposure 1.1.3. Environmental transport, distribution and transformation 1.1.4. Environmental levels and human exposure 1.1.5. Kinetics and metabolism 1.1.6. Effects on laboratory mammals and in vitro test systems 1.1.7. Effects on humans 1.1.8. Effects on other organisms in the laboratory and field 1.2. Conclusions 2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL METHODS Page 2 of 87 Carbendazim (EHC 149, 1993) 2.1. Identity 2.1.1. Primary constituent 2.1.2. Technical product 2.2. Physical and chemical properties 2.3. Analytical methods 3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE 3.1. Natural occurrence 3.2. Anthropogenic sources 3.2.1. 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. Leaching 4.1.5. Crop uptake 4.2. Transformation 4.2.1. Soil biodegradation 4.2.2. Abiotic degradation 4.2.3. Bioaccumulation 5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 5.1. Environmental levels 5.1.1. Air, water and soil 5.1.2. Food and feed 5.1.3. Terrestrial and aquatic organisms 5.2. General population exposure 5.2.1. Sweden 5.2.2. The Netherlands 5.2.3. National maximum residue limits 5.3. Occupational exposure during manufacture, formulation, or use 5.3.1. Exposure during manufacture 5.3.2. Exposure during use 6. KINETICS AND METABOLISM 6.1. Absorption 6.2. Distribution and accumulation 6.3. Metabolic transformation 6.4. Elimination and excretion 6.5. Reaction with body components 7. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS 7.1. Single exposure 7.2. Short-term exposure 7.2.1. Gavage 7.2.2. Feeding 7.2.2.1 Rat 7.2.2.2 Dog 7.2.3. Dermal 7.3. Skin and eye irritation; sensitization 7.3.1. Dermal 7.3.2. Eye 7.3.3. Sensitization 7.4. Long-term exposure 7.4.1. Rat 7.4.2. Dog Page 3 of 87 Carbendazim (EHC 149, 1993) 7.4.3. Mouse 7.5. Reproduction, embryotoxicity and teratogenicity 7.5.1. Reproduction 7.5.2. Embryotoxicity and teratogenicity 7.6. Mutagenicity and related end-points 7.7. Carcinogenicity 7.8. Neurotoxicity 7.9. Toxicity of contaminants 7.10. Mechanisms of toxicity - mode of action 8. EFFECTS ON HUMANS 8.1. General population exposure 8.2. Occupational exposure 9. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD 9.1. Microorganisms 9.2. Aquatic organisms 9.3. Terrestrial organisms 9.4. Population and ecosystem effects 10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON ENVIRONMENT 95 10.1. Evaluation of human health risks 10.2. Evaluation of effects on the environment 10.3. Conclusions 11. FURTHER RESEARCH 12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES REFERENCES RESUME ET CONCLUSIONS RESUMEN Y CONCLUSIONES WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR BENOMYL AND CARBENDAZIM Members Dr G. Burin, Office of Pesticide Programmes, US Environmental Protection Agency, Washington, D.C., USA Dr R. Cooper, Reproductive Toxicology Branch, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA Dr I. Desi, Department of Public Health, Albert Szent-Györgyi University Medical School, Szeged, Hungary Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood, Abbots Ripton, Huntingdon, United Kingdom Dr A. Helweg, Department for Pesticide Analysis and Ecotoxicology, Danish Research Service for Plant and Soil Science, Flakkebjerg, Slagelse, Denmark Dr M. Lotti, Institute of Occupational Medicine, University of Padua, Padua, Italy (Chairman) Dr K. Maita, Toxicology Division, Institute of Environmental Page 4 of 87 Carbendazim (EHC 149, 1993) Toxicology, Kodaira-Shi, Tokyo, Japan Dr F. Matsumura, Department of Environmental Toxicology, Institute of Toxicology and Environmental Health, University of California, Davis, California, USA Dr T.K. Pandita, Microbiology and Cell Biology Laboratory, Indian Institute of Science, Bangalore, Indiaa Dr C. Sonich-Mullin, Environmental Criteria and Assessment Office, US Environmental Protection Agency, Cincinnati, Ohio, USA Dr P.P. Yao, Institute of Occupational Medicine, Chinese Academy of Preventive Medicine, Beijing, China Secretariat Dr B.H. Chen, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland ( Secretary) Dr L.W. Hershberger, Dupont Agricultural Products, Walker's Mill, Barley Mill Plaza, Wilmington, Delaware, USA Mr P. Howe, Institute of Terrestrial Ecology, Monks Wood, Abbots Ripton, Huntington, United Kingdom a Invited but unable to attend the meeting 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 CARBENDAZIM A WHO Task Group on Environmental Health Criteria for Benomyl and Carbendazim, sponsored by the US Environmental Protection Agency, met in Cincinnati, USA, from 14 to 19 September 1992. On behalf of the host agency, Dr T. Harvey opened the meeting and welcomed the participants. 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 carbendazim. The first draft of this monograph was prepared by the staff of IPCS, using texts made available by Dr L.W. Hershberger and Dr G.T. Arce, Wilmington,