PESTICIDE RESIDUES IN FOOD - 1988 Sponsored jointly by FAO and WHO with the support of the International Programme on Chemical Safety (IPCS) EVALUATIONS 1988 PART II - TOXICOLOGY 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, 19-28 September 1988 The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Food and Agriculture Organization of the United Nations concerning the legal status of any country, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. This report contains the collective views of two international groups of experts and does not necessarily represent the decisions or 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. M-84 ISBN 92-5 102815-X All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying or otherwise, without the prior permission of the copyright owner. Applications for such permission, with a statement of the purpose and extent of the reproduction, should be addressed to the Director, Publications Division, Food and Agriculture Organization of the United Nations, Via delle Terme di Caracalla, 00100 Rome, Italy. (c) FAO 1989 CONTENTS PART II - TOXICOLOGY List of those attending the Meeting Abbreviations Introduction Toxicology monographs and monograph addenda Acephate Bromide ion Dimethipin Ethylenethiourea (ETU) Fenitrothion Methacrifos *Paclobutrazol d-Phenothrin *Tolylfluanid Vamidothion Vinclozolin Corregenda to 1982 and 1986 Evaluations 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 Annex II. Acceptable daily intakes, residue limits, and guideline levels proposed at the 1988 Meeting * First full evaluation 1988 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, 19-28 September 1988 FAO Panel of Experts on Pesticide Residues in Food and the Environment Mr J.A.R. Bates, formerly Head, Pesticide Registration and Surveillance Department, Ministry of Agriculture, Fisheries and Food, Harpenden, UK. Professor Dr A.F.H. Besemer, formerly Chair of Phytopharmacy, Agricultural University, Wageningen, The Netherlands. Dr R. Greenhalgh, Plant Research Centre, Agriculture Canada, Ottawa, Canada. Mr D.J. Hamilton, Assistant Director, Agricultural Chemistry Branch, Department of Primary Industries, Brisbane, Australia. Professor E.D. Magallona, Department of Entomology, College of Agriculture, University of the Philippines at Los Banos College, Laguna, Philippines. Mr K. Voldum-Clausen, Division of Chemical Contaminants in Food, National Food Agency, Soborg, Denmark. WHO Expert Group on Pesticide Residues Prof. N.M.S. Bakry, Head, Professor of Pesticide Chemistry and Toxicology, Faculty of Agriculture, University of Alexandria, El-Shatby, Alexandria, Egypt. Dr V. Benes, Chief, Department of Toxicology, Institute of Hygiene and Epidemiology, 10042 Prague 10, Czechoslovakia. Dr A.L. Black, Medical Adviser in Toxicology, Department of Community Services and Health, Woden, Australia. Mr D.J. Clegg, Head, Agricultural Chemicals Section, Toxicological Evaluation Division, Food Directorate, Health Protection Branch, Tunneys Pasture, Ottawa, Ontario, KIA 0L2 Canada. Prof. M. Lotti, Università di Padova, Istituto di Medicina del Lavoro, Via Facciolati 71, 35127 Padova, Italy. Dr O.E. Paynter, Chief Scientist, Hazard Evaluation Division, US Environmental Protection Agency, Washington, D.C., USA. Secretariat Dr Mrs E.P. Arnold, Toxicologist, Agricultural Chemicals Section, Toxicological Evaluation Division, Health Protection Branch, Health & Welfare Canada, Ottawa, KIA 0L2 Canada. (WHO Temporary Adviser) Prof. C.L. Berry, Department of Morbid Anatomy, The London Hospital Medical College, Whitechapel, London E1 1.BB, UK. (WHO Temporary Adviser) Dr G. Burin, Office of Pesticide Programs, US Environmental Protection Agency, TS-769 Washington, D.C., 20460 USA. (WHO Consultant) Dr J.L. Herrman, International Programme on Chemical Safety, World Health Organization, 1211 Geneva 27, Switzerland. (WHO Joint Secretary) Dr R.B. Jaeger, Toxicologist, Section Head, Special Analyses and Coordination Branch, Health Effects Division, US Environmental Protection Agency, Washington, D.C., USA. (WHO Temporary Adviser) Dr J. van der Kolk, Foodstuffs Division, Ministry of Welfare, Health and Cultural Affairs, Rijswijk, Netherlands. (Chairman of the CCPR) Dr F.-W. Kopisch-Obuch, Plant Protection Service, Food and Agriculture Organization, Rome, Italy. (FAO Joint Secretary) Dr L.G. Ladomery, Food Standards Officer, Joint FAO/WHO Food Standards Programme, Food and Agriculture Organization, Rome, Italy. Mr A.F. Machin, London, England. (FAO Consultant) Dr A. Moretto, Università di Padova, Istituto di Medicina del Lavoro, Padova, Italy. (WHO Temporary Adviser) Dr R. Plestina, Division of Vector Biology and Control, World Health Organization, 1211 Geneva 27, Switzerland. Dr L. Shuker, Unit of Carcinogen Identification and Evaluation, International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon, Cedex 08 France. (WHO Temporary Adviser) Dr A. Takanaka, Head, Division of Pharmacology, Biological Safety Research Center, National Institute of Hygienic Sciences, Tokyo, Japan. (WHO Temporary Adviser) Dr Mrs. E.M. den Tonkelaar, Toxicology Advisory Center, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands. (WHO Temporary Adviser) Mr M. Walsh, Administrator, E.E.C., Législation des produits végétaux et de nutrition animale, Brussels, Belgium. (WHO Temporary Adviser) ABBREVIATIONS USED IN THESE MONOGRAPHS 2-AAF 2-acetylaminofluorine AChE acetylcholinesterase ADI acceptable daily intake a.i. active ingredient ALD acute lethal dose ALP alkaline phosphatase ALT alanine aminotransferase AMP aminomethylphosphonic acid AST aspartate aminotransferase BUN blood urea nitrogen bw body weight CD caesarian derived ChE cholinesterase CHO Chinese hamster ovary CMC carboxymethylcellulose CNS central nervous system EMS ethylmethanesulfonate F1 filial generation, first F2 filial generation, second FAO Food and Agriculture Organization of the United Nations FSH follicle stimulating hormone GC gas chromatography GH growth hormone GI gastrointestinal GLC gas-liquid chromatography GMP guanosine monophosphate GOT glutamate-oxoloacetate transaminase GPT glutamate-pyruvate transaminase GSSG glutathione, oxidized Hb haemoglobin HGPRT hypoxanthine-guanine phosphoribosyl transferase HPLC high pressure liquid chromatography IARC International Agency for Research on Cancer IBT Industrial Bio-Test Laboratories, Inc. i.m. intramuscular i.p. intraperitoneal IPCS International Programme on Chemical Safety i.v. intravenous JMPR Joint FAO/WHO Meeting on Pesticide Residues (Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and a WHO Expert Group on Pesticide Residues) LC50 lethal concentration, median LD50 lethal dose, median LDH lactate dehydrogensase MCA 3-methylcholanthrene MCH mean corpuscular haemoglobin MCHC mean corpuscular haemoglobin concentration MCV mean corpuscular volume mmol/l millimoles/liter MMS methylmethane sulfonate MTD maximum tolerated dose NADPH nicotinamide adenine dinucleotide phosphate (reduced) ng nanogram NOAEL no-observed-adverse-effect level NOEL no-observed-effect level NPMG N-nitrosophosphonomethyl glycine NTE neurotoxic esterase OECD Organization for Economic Cooperation and Development op organophosphate 2-PAM 2-pyridine aldoxine methyl (pralidoxime) p.c. post-coitum p.o. per oral ppb parts per billion (1000 ppb = 1 ppm) ppm parts per million PRL prolactin RBC red blood cell RER rough endoplasmic reticulum s.a. specific activity SAP serum alkaline phosphatase s.c. subcutaneous SCE sister chromatid exchange SER smooth endoplasmic reticulum T3 triiodothyronine T4 thyroxin TADI temporary acceptable daily intake TBG thyroxine binding globulin TEM triethylenemelamine TLC thin layer chromatography TLV threshold limit value TOCP tri-o-cresyl phosphate TSH thyrotropin UDS unscheduled DNA synthesis WBC white blood cell WHO World Health Organization w/v weight/volume < less than < less than or equal to > greater than > greater than or equal to INTRODUCTION The toxicology 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, 19-28 September 1988. 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 and monographs on them have been published previously. In such cases, only new information is summarized in the relevant "monograph addenda". 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 I. 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. 92. 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 1988, Part I Residues (FAO Plant Production and Protection Paper No. 93/1). The toxicology monographs and monograph addenda contained in this volume are based on working papers that were prepared by temporary advisers in advance of the 1988 Joint Meeting. A special acknowledgement is given to those who prepared these working papers: Dr A. Moretto, University of Padua Medical School, Padua, Italy; Dr R.B. Jaeger, U.S. Environmental Protection Agency, Washington, DC, USA; Dr E.M. den Tonkelaar, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands; and Dr E.P. Arnold, Health & Welfare Canada, Ottawa, 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.
See Also: Toxicological Abbreviations