855. Introduction (Pesticide residues in food: 1993 evaluations Part II Toxicology)

PESTICIDE RESIDUES IN FOOD - 1993 JOINT FAO/WHO MEETING ON PESTICIDE RESIDUES EVALUATIONS 1993 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 Geneva, 20-29 September 1993 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. ISBN 92 4 166509 2 (c) World Health Organization 1994 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 Amitrole Bromopropylate Diazinon Dichlorvos Diquat Ethephon Ethylenethiourea (ETU) Etofenprox* Fenpropathrin* Mancozeb Maneb Metiram* Monocrotophos Phosalone Propineb Propylenethiourea (PTU) Triazophos Zineb 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 1993 JOINT MEETING OF THE FAO PANEL OF EXPERTS ON PESTICIDE RESIDUES IN FOOD AND THE ENVIRONMENT AND THE WHO EXPERT GROUP ON PESTICIDE RESIDUES Geneva, 20-29 September 1993 PARTICIPANTS WHO Expert Group on Pesticide Residues Professor U.G. Ahlborg, Division of Environmental Toxicology, Karolinska Institute, Institute of Environmental Medicine, Stockholm, Sweden Dr A.L. Black, Medical Services Adviser in Toxicology, Department of Health, Housing, Local Government and Community Services, Canberra, Australia Professor J.F. Borzelleca, Pharmacology, Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, USA (Chairman) Mr D.J. Clegg, Carp, Ontario, Canada Dr P.A. Fenner-Crisp, Director, Health Effects Division, Office of Pesticide Programs (H7509C), US Environmental Protection Agency, Washington, DC, USA (Rapporteur) Dr E.M. den Tonkelaar, Toxicologist, Toxicology Advisory Centre, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands Dr P. Yao, Professsor of Toxicology, Consultant of ICAMA, Institute of Occupational Medicine, CAPM, Ministry of Public Health, Beijing, China FAO Panel of Experts on Pesticide Residues in Food and the Environment Dr D.C. Abbott, AOAC International, Liaison Representative, Ashtead, Surrey, United Kingdom Dr A. Ambrus, Budapest Plant Health & Soil Conservation Station, Budapest, Hungary (Rapporteur) Dr U. Banasiak, Kleinmachnow, Germany Mr D.J. Hamilton, Senior Principal Scientist, Agricultural Chemistry, Queensland Department of Primary Industries, Indooroopilly, Brisbane, Queensland, Australia Mr N.F. Ives, Health Effects Division (H7509C), US Environmental Protection Agency, Washington, DC, USA (Vice-Chairman) Dr J.-R. Lundehn, Federal Biological Research Centre for Agriculture and Forestry (BBA), Braunschweig, Germany Mr K. Voldum-Clausen, VarlØse, Denmark Ms H.F. Yeoh, Residue Section, Pesticides Control Branch, Department of Agriculture, Kuala Lumpur, Malaysia Secretariat Mrs P.H. Arentzen, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands (WHO Temporary Adviser) Dr E. Bosshard, Federal Office of Public Health, Division of Food Science, c/o Institute of Toxicology, Schwerzenbach, Switzerland (WHO Temporary Adviser) Mrs M. Caris, Toxicological Evaluation Division, Bureau of Chemical Safety, Health and Welfare Canada, Tunney's Pasture, Ottawa, Ontario, Canada (WHO Temporary Adviser) Dr K. Fujimori, Division of Pharmacology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan (WHO Temporary Adviser) Dr H. Galal-Gorchev, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland Dr J.L. Herrman, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland (WHO Joint Secretary) Dr A. Kocialski, Health Effects Division, Office of Pesticide Programs (H7509C), US Environmental Protection Agency, Washington, DC, USA (WHO Temporary Adviser) Dr J.-J. Larsen, Head, Department of General Toxicology, Institute of Toxicology, National Food Agency of Denmark, S‚borg, Denmark (WHO Temporary Adviser) Professor M. Lotti, University of Padua, Institute of Occupational Medicine, Padua, Italy (WHO Temporary Adviser) Mr A.F. Machin, Boundary Corner, London, United Kingdom (FAO Consultant) Dr T.C. Marrs, Medical Toxicology and Environmental Health, Department of Health, Skipton House, Elephant and Castle, London, United Kingdom (WHO Temporary Adviser) Dr D. McGregor, Unit of Carcinogen Identification and Evaluation, International Agency for Research on Cancer, Lyon Cedex, France Dr A. Moretto, University of Padua, Institute of Occupational Medicine, Padua, Italy (WHO Temporary Adviser) Dr G. Moy, Food Safety, World Health Organization, Geneva, Switzerland Mr W.J. Murray, Plant Protection Service, Plant Production & Protection Division, Food and Agriculture Organization of the United Nations (FAO), Rome, Italy (FAO Joint Secretary) Dr R. Plestina, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland Dr A. Takanaka, Head, Division of Pharmacology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan (WHO Temporary Adviser) Dr W.H. van Eck, Chairman, Codex Committee on Pesticide Residues, Food and Product Safety Division, Ministry of Welfare, Health and Cultural Affairs, Rijswijk, The Netherlands Dr G. Vettorazzi, International Toxicology Information Centre (ITIC), San Sebastian, Spain (WHO Temporary Adviser) Mr M. Walsh, Principal Administrator EEC, Commission of the European Communities, Législation des produits végétaux et de nutrition animale, VI/B/II.1, Brussels, Belgium (WHO Temporary Adviser) Mr M. Watson, Head, Risk Evaluation Branch, Pesticide Safety Directorate, Ministry of Agriculture, Fisheries and Food, Rothamsted, Harpenden, Herts, United Kingdom (WHO Temporary Adviser) Dr Y. Yamada, Food Standards Officer, Joint FAO/WHO Food Standards Programme Group, Food and Agriculture Organization of the United Nations (FAO), Rome, Italy ABBREVIATIONS USED IN THE 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 BChE butyrylcholinesterase BUN blood urea nitrogen bw body-weight CCPR Codex Committee on Pesticide Residues CD caesarean-derived cf confer, compare to ChAT choline acetyltransferase ChE cholinesterase Ci Curie CHO Chinese hamster ovary CMC carboxymethylcellulose CNS central nervous system DCA dichloroacetaldehyde DEP diethyl phosphoric acid DETP diethyl thiophosphate DHPN dihydroxypropylnitrosamine DMSO dimethylsulfoxide DNA deoxyribonucleic acid DNCB 1-chloro-2,4-dinitrobenzene EBDC ethylene bisdithiocarbamate EBIS ethylene bis(isothiocyanate) sulfide ECG electrocardiogram EEG electroencephalogram EM electron microscopy ESR erythrocyte sedimentation rate ETU ethylenethiourea F female F₀ parental generation F₁ filial generation, first F₂ filial generation, second FMO flavin monooxygenase FTI free thyroxine index GC gas chromatography GGT gamma-glutamyltranspeptidase G.I. gastrointestinal GIT gastrointestinal tract GOT glutamate-oxalate transaminase GPT glutamate-pyruvate transaminase GSH glutathione-SH GSSG oxidized glutathione GST glutathione-S-transferase GTP (alpha)-glutamyltranspeptidase h hour ha hectare Hb haemoglobin HCT haematocrit HPLC high-performance liquid chromatography HPMC hydroxypropylmethyl cellulose Ht haematocrit I₅₀ inhibitory dose, median 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 MHEC methylhydroxyethylcellulose min minute ml milliliter MMD mass median diameter MMS methylmethanesulfonate mol mole MTD maximum tolerated dose NADPH nicotinamide adenine dinucleotide phosphate (reduced) NOAEL no-observed-adverse-effect level NOEL no-observed-effect level NSE non-specific esterase NTE neurotoxic esterase NZW New Zeeland white (rabbit) OP organophosphate 2-PAM (2-pyridine aldoxime methyl) chloride PAS periodic acid Schiff reagent PBI protein-bound iodine PCV haematocrit (packed corpuscular volume) PEG polyethylene glycol p.o. per os (by mouth) PI primary irritation ppm parts per million PSP phenolsulfophthalein PT prothrombin time PTT partial thromboplastin time PTU propylenethiourea PVC polyvinyl chloride RBC red blood cell RNA ribonucleic acid SAP serum alkaline phosphatase s.c. subcutaneous(ly) SCE sister chromatid exchange SDH sorbitol dehydrogenase SER smooth endoplasmic reticulum SGOT serum glutamic-oxaloacetic transaminase SGPT serum glutamic-pyruvic transaminase SPF specific pathogen free T₃ triiodothyronine T₄ thyroxin TBG thyroid binding globulin TEPP tetraethyl-pyrrophosphate TLC thin-layer chromatography TOCP tri- ortho-cresyl phosphate TSH thyroid-stimulating hormone (thyrotropin) UDS unscheduled DNA synthesis USEPA US Environmental Protection Agency -ve negative v/v volume per volume WBC white blood cell w/v weight per volume w/w weight per 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 Geneva, Switzerland, from 20 to 29 September 1993. 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. Monographs that summarize the data received since the previous evaluations as well as relevant data from the previous monographs were prepared on most of these compounds. Monograph addenda that summarize only the data received since the previous evaluations were prepared on monocrotophos and triazophos. The appropriate documents, which are referenced in Annex 1, should be consulted to obtain a full toxicological profile of these pesticides. 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. XXX. 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 1993, 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 1993 Joint Meeting. A special acknowledgement is given to those who prepared these working papers. 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