835. Introduction (Pesticide residues in food: 1992 evaluations Part II Toxicology)

PESTICIDE RESIDUES IN FOOD - 1992 JOINT FAO/WHO MEETING ON PESTICIDE RESIDUES EVALUATIONS 1992 PART II - TOXICOLOGY Sponsored jointly by FAO and WHO with the support of the International Programme on Chemical Safety (IPCS) Joint meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues Rome, 21-30 September 1992 This report contains the collective views of two international groups of experts and does not necessarily represent the decisions nor the stated policy of the Food and Agriculture Organization of the United Nations or the World Health Organization. INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY The preparatory work for the toxicological evaluations of pesticide residues carried out by the WHO Expert Group on Pesticide Residues for consideration by the FAO/WHO Joint Meeting on pesticide Residues in Food and the Environment is actively supported by the International Programme on Chemical Safety (IPCS). 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. One of the main objectives of the IPCS is to carry out and disseminate evaluations of the effects of chemicals on human health and the quality of the environment. IPCS gratefully acknowledges the assistance of Mr. D. Clegg, Carp. Ontario, Canada, for editing these monographs. ISBN 92 4 166508 4 (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. For rights of reproduction or translation of WHO publications, in part or in toto, application should be made to the Office of Publications, World Health Organization, Geneva, Switzerland. The World Health Organization welcomes such applications. The designations employed and the presentation of the material in this publication do not imply the impression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of every 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. TABLE OF CONTENTS List of those attending the Meeting Abbreviations Introduction The Monographs * Abamectin Aldicarb * Bifenthrin Chlorothalonil Chlorpyrifos-methyl * Cycloxydim Dicofol * Dithianon Fenbutatin oxide Iprodione Methidathion * Myclobutanil * Penconazole Piperonyl butoxide Pirimiphos-methyl * Propham Pyrazophos Thiram ANNEX I. Reports and other documents resulting from previous Joint Meetings of the FAO panel of experts on pesticide residues in food and the environment and WHO expert groups on pesticide residues * First full evaluation 1992 JOINT MEETING OF THE FAO PANEL OF EXPERTS ON PESTICIDE RESIDUES IN FOOD AND THE ENVIRONMENT AND THE WHO EXPERT GROUP ON PESTICIDE RESIDUES Rome, 21-30 September 1992 PARTICIPANTS WHO Expert Group on Pesticide Residues Prof. U.G. Ahlborg, Head, Unit of Toxicology, Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden Dr Vaclav Benes, Head, National Reference Centre for Pesticides, National Institute of Public Health, Prague, Czechoslovakia Dr A.L. Black, Medical Services Adviser in Toxicology, Department of Health, Housing and Community Services, Canberra, Australia ( Rapporteur) Prof. J.F. Borzelleca, Professor, Pharmacology, Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, USA ( Vice-Chairman) Dr P. Fenner-Crisp, Director, Health Effects Division, Office of Pesticide Programs, US Environmental Protection Agency, Washington, DC, USA Prof. A. Rico, Head, Chemical and Metabolic Toxicology Laboratory, Ecole Nationale Vétérinaire, Toulouse, France Dr P. Yao, Professor of Toxicology, Institute of Occupational Medicine, CAPM, Ministry of Public Health, Beijing, China FAO Panel of Experts on Pesticide Residues in Food and the Environment Dr A. Ambrus, Budapest Plant Health and Soil Conservation Station, Budapest, Hungary ( Rapporteur) Dr R. Greenhalgh, Ottawa, Ontario, Canada Dr D. Hamilton, Senior Principal Scientist, Agricultural Chemistry, Department of Primary Industries, Queensland Government, Brisbane, Queensland, Australia ( Chairman) Mr N.F. Ives, Health Effects Division, US Environmental Protection Agency, Washington, DC, USA Dr J.-R. Lundehn, Federal Biological Research Centre for Agriculture and Forestry, Braunschweig, Germany Dr K. Voldum-Clausen, National Food Agency, Ministry of Health, Soborg, Denmark Mr Wu Ji Zhuang, Associate Professor, Head of the Department of Research Chemicals, China Import and Export Commodity Inspection Institute, Beijing, China Secretariat Dr E. Bosshard, Federal Office of Public Health, Division of Food Science, c/o Institute of Toxicology, Schwerzenbach, Switzerland ( WHO Temporary Adviser) Dr J.R.P. Cabral, Scientist, International Agency for Research on Cancer, Lyon, France Mrs M. Caris, Toxicological Evaluation Division, Bureau of Chemical Safety, Health and Welfare Canada, Ottawa, Ontario, Canada ( WHO Temporary Adviser) Dr S. Caroldi, Università di Padova, Istituto di Medicina del Lavoro, Padova, Italy ( WHO Temporary Adviser) Dr E. Casadei, Joint FAO/WHO Food Standards Programme, Food and Agriculture Organization, Rome, Italy Mr D.J. Clegg, Carp, Ontario, Canada ( WHO Temporary Adviser) Dr M.A. Clevenger, Senior Toxicologist, Toxicology Branch I, Health Effects Division, Office of Pesticide Programs, US Environmental Protection Agency, Washington, DC, USA ( WHO Temporary Adviser) Mr W.H. van Eck, Food and Product Safety Division, Ministry of Welfare, Health and Cultural Affairs, Rijswijk, The Netherlands ( Chairman CCPR) Dr J.L. Herrman, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland ( WHO Joint Secretary) Dr Jens-Jorgen Larsen, Head, Department of General Toxicology, Institute of Toxicology, National Food Agency, Ministry of Health, Soborg, Denmark ( WHO Temporary Adviser) Mr A.F. Machin, London, UK ( FAO Consultant) Dr T.C. Marrs, Medical Toxicology and Environmental Health, Department of Health, London, UK ( WHO Temporary Adviser) Mr W.J. Murray, Pesticide Residues Specialist Plant Protection Service, Food and Agriculture Organization of the United Nations, Rome, Italy ( FAO Joint Secretary) Dr A. Takanaka, Head, Division of Pharmacology, Biological Safety Research Center, National Institute of Hygienic Sciences, Tokyo, Japan ( WHO Temporary Adviser) Dr E.M. den Tonkelaar, Toxicologist, Toxicology Advisory Centre, National Institute of Public Health and Environmental Protection, Bilthoven, Netherlands ( WHO Temporary Adviser) Dr G. Vettorazzi, International Toxicology Information Centre, San Sebastian, Spain ( WHO Temporary Adviser) Mr M. Watson, Head, Risk Evaluation Branch, Pesticide Safety Division, Ministry of Agriculture, Fisheries and Food, Harpenden, Herts, UK ( WHO Temporary Adviser) ABBREVIATIONS USED IN THESE MONOGRAPHS ACH acetylcholine AChE acetylcholinesterase ACTH adenocorticotropic hormone ADI acceptable daily intake ADP adenosine diphosphate A/G albumin/globulin ratio a.i. active ingredient ALAT alanine aminotransferase ALP alkaline phosphatase ALT alanine transaminase ASAT aspartate aminotransferase AST aspartate transaminase ATP adenosine triphosphate AUC area under the curve BUN blood urea nitrogen bw body weight cf confer, compare to ChE cholinesterase Ci curie CHO Chinese hamster ovary CMC carboxymethylcellulose CNS central nervous system DMSO dimethylsulfoxide DNA deoxyribonucleic acid ECG electrocardiogram EEG electroencephalogram ELP exploratory locomotion pattern ESR erythrocyte sedimentation rate F female F₀ parental generation F₁ filial generation, first F₂ filial generation, second dGC gas chromatography GGT gamma-glutamyltransferase G.I. gastrointestinal GIT gastrointestinal tract GM Geiger meter GOT glutamate-oxoloacetate transaminase GPT glutamate-pyruvate transaminase GSH reduced glutathione GSSG oxidized glutathione GST glutathione-S-transferase GTP alpha-glutamyltranspeptidase H hour Ha hectare Hb haemoglobin HCT haematocrit HGRPT hypoxanthine-guanine phosphoribosyl transferase HPLC high pressure liquid chromatography Ht haematocrit I₅₀ inhibitory dose, 50% IBT Industrial Bio-Test Laboratories, Inc. i.m. intramuscular inh inhalation i.p. intraperitoneal IPCS International Programme on Chemical Safety i.v. intravenous JMPR Joint FAO/WHO Meeting on Pesticide Residues l litre LC₅₀ lethal concentration, median LD₅₀ lethal dose, median LDH lactate dehydrogenase LOAEL lowest-observed-adverse-effect-level m metre M male MCH mean corpuscular haemoglobin MCHC mean corpuscular haemoglobin concentration MCV mean corpuscular volume MFO mixed function oxidase(s) MHEC methylhydroxyethylcellulose ml milliliter mTD minimum toxic dose MTD maximum tolerated dose NADPH nicotinamide adenine dinucleotide phosphate (reduced) NMR nuclear magnetic resonance NOAEL no-observed-adverse-effect level NOEL no-observed-effect level NSE non-specific esterase NTE neurotoxic target esterase OCT ornithylcarbamyl transferase 2-PAM 2-pralidoxime PCV haematocrit (packed corpuscular volume) PEG polyethylene glycol p.o. by mouth PI primary irritation ppm parts per million PSP phenolsulfophthalein PrT prothrombin time PT thromboplastin time PTT partial thromboplastin time RBC red blood cell RNA ribonucleic acid SAP serum alkaline phosphatase s.c. subcutaneous(ly) SCE sister chromatide exchange SD standard deviation SDH sorbitol dehydrogenase SER smooth endoplasmic reticulum SGOT serum GOT SGPT serum GPT SPF specific pathogen free T₃ tri-iodothyronine T₄ thyroxine TLC thin layer chromatography TOCP tri-ortho-cresyl phosphate TSH thyrotropine TWA time weighted average UDS unscheduled DNA synthesis v/v volume/volume WBC white blood cell W/W weight to weight INTRODUCTION The toxicological monographs and monograph addenda contained in this volume were prepared by a WHO Expert Group on Pesticide Residues that met with the FAO Panel of Experts on Pesticide Residues in Food and the Environment in a Joint Meeting on Pesticide Residues (JMPR) in Rome, Italy, 21 September to 30 September 1992. These monographs summarize the safety data on those pesticide residues for which sufficient information was provided to the WHO Expert Group for it to make decisions regarding acceptable daily intakes. Most of the compounds considered by the WHO Expert Group at this Meeting had been evaluated at previous meetings. For some compounds, only new information is summarized in the relevant "monograph addenda". In the case of aldicarb, dicofol, fenbutatin oxide, iprodione, methidathion and pirimiphos-methyl, toxicological monographs, summarizing the data that were received recently and incorporating the previous monographs and monograph addenda on these compounds, were prepared. Reference is made to reports and other documents resulting from previous Joint Meetings of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and WHO Expert Groups on Pesticide Residues which are listed in Annex 1. For monograph addenda, the appropriate documents should be consulted to obtain a full toxicological profile of the chemicals under consideration. The report of the Joint Meeting has been published by the Food and Agriculture Organization (FAO) of the United Nations as FAO Plant Production and Protection Paper No. 116. The report contains brief comments on the compounds under consideration, acceptable daily intakes established by the WHO Expert Group, and maximum residue limits or guideline levels established by the FAO Panel of Experts. Residues monographs prepared by the FAO Panel of Experts have been published as a companion volume to this one: Evaluations 1992, Part I- Residues, in the FAO Plant Production and Protection Paper series. The toxicological monographs and monograph addenda contained in this volume are based upon working papers that were prepared by Temporary Advisers in advance of the 1992 Joint Meeting. A special acknowledgement is given to those who prepared these working papers. The monographs were edited by Mr D.J. Clegg, Carp, Ontario, Canada. The preparation and editing of the monographs included in this volume have been made possible through the technical and financial contributions of the lead institutions of the International Programme on Chemical Safety (IPCS), which support the activities of JMPR. 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 Central Unit of the IPCS concerning the legal status of any country, territory, city, or area or 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 IPCS in preference to others of a similar nature that are not mentioned. Any comments or new information on the biological or toxicological data on the compounds reported in this document should be addressed to: Joint WHO Secretary of the Joint FAO/WHO Meeting on Pesticide Residues, International Programme on Chemical Safety, World Health Organization, Avenue Appia, 1211 Geneva 27, Switzerland.








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       Toxicological Abbreviations