PESTICIDE RESIDUES IN FOOD - 1986 Sponsored jointly by FAO and WHO with the support of the International Programme on Chemical Safety (IPCS) EVALUATIONS 1986 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, 29 September - 8 October 1986 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. 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. M-84 ISBN 92-5 102598-3 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 1987 CONTENTS PART II - TOXICOLOGY List of those attending the Meeting Abbreviations Introduction Toxicology monographs and monograph addenda Carbosulfan Chlordane Clofentezine* Ethion Fenitrothion Folpet Glyphosate* Imazalil Isofenphos Mecarbam Methacrifos Methomyl* Paraquat* Phosphamidon Propamocarb Thiodicarb Triazophos Vinclozolin* Annex 1. 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 2. Acceptable daily intakes, residue limits, and guideline levels proposed at the 1986 Meeting *Full monograph 1986 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, 29 September - 8 October 1986 FAO Panel of Experts on Pesticide Residues in Food and the Environment Dr D.C. Abbott, formerly Deputy Director (Government Analyst), Laboratory of the Government Chemist, London, United Kingdom. (Chairman) Professor Dr A.F.H. Besemer, formerly Chair of Phytopharmacy, Agricultural University, Wageningen, The Netherlands. Dr E. Celma-Calamita, Ministerio de Agricultura, Pesca y Alimentacion, Madrid, Spain. Dr D.J. Hamilton, Assistant Director Agricultural Chemistry Branch, Department of Primary Industries, Brisbane, Australia. Mr N.F. Ives, Environmental Protection Agency, Office of Pesticide Programs, Washington, D.C., USA. Mr J.T. Snelson, Canberra, Australia, formerly Pesticides Co-Ordinator, Department of Primary Industry. (Rapporteur) Mr K. Voldum-Clausen, Division of Pesticides and Contaminants, National Food Agency, Soborg, Denmark. Observers invited by FAO Mr A.J. Pieters, Ministry of Welfare, Health and Cultural Affairs, Leidschendam, The Netherlands. Dr Sakdiprayoon Deema, Inspector General, Ministry of Agriculture and Cooperatives, Bangkok, Thailand. (Chairman of the CCPR ad hoc Working Group on Pesticide Residue Problems in Developing Countries) WHO Expert Group on Pesticide Residues Dr V. Benes, Chief, Department of Toxicology, Institute of Hygiene and Epidemiology, 10042 Prague 10, Czechoslovakia. Professor J.F. Borzelleca, Professor of Pharmacology & Toxicology, Medical College of Virginia, Richmond, VA., 23298 USA. Mr D.J. Clegg, Head, Pesticide Section, Toxicological Evaluation Division, Food Directorate, Health Protection Branch, Ottawa, Canada. (Vice-Chairman) Professor Mrs Julia Higa de Landoni, Professor of Toxicology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina. Professor M. Lotti, Professor of Industrial Toxicology, Istituto di Medicina del Lavoro, University of Padua Medical School, Padua, Italy. Professor R. Plestina, Head, Department of Toxicology, Institute for Medical Research and Occupational Health, Zagreb, Yugoslavia. Secretariat Mr H. Akagawa, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare, Japanese Government, Tokyo, Japan. (WHO Temporary Adviser) Professor Mrs Nabila M.S. Bakry, Professor of Pesticide Chemistry and Toxicology, Faculty of Agriculture, University of Alexandria, Alexandria, Egypt. (WHO Temporary Adviser) Professor C.L. Berry, Professor of Pathology and Chairman, Department of Morbid Anatomy, The London Hospital Medical College, London, UK. (WHO Temporary Adviser) Dr A.L. Black, Medical Adviser in Toxicology, Commonwealth Department of Health, Woden, A.C.T., Australia. (WHO Temporary Adviser) Dr J.L. Herrman, Food and Drug Administration, Washington, D.C., USA. (WHO Consultant) Dr E. Johnson, Scientist, Unit of Analytical Epidemiology, International Agency for Research on Cancer, Lyon, France. (WHO Temporary Adviser) Dr F.-W. Kopisch-Obuch, Pesticide Residue Specialist, Plant Protection Service, Food and Agriculture Organization, Rome, Italy (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, United Kingdom (FAO Consultant). Dr M. Manno, Istituto di Medicina del Lavoro, University of Padua Medical School, Padua, Italy. (WHO Temporary Adviser) Dr D.S. Saunders, Toxicologist, Toxicology Branch, Hazard Evaluation Division (TS 769c), US Environmental Protection Agency, Washington, D.C., USA. (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 Hygiene, Bilthoven, The Netherlands. (WHO Temporary Adviser) Dr G. Vettorazzi, Senior Toxicologist, International Programme on Chemical Safety, Division of Environmental Health, WHO, Geneva, Switzerland. (Joint Secretary). 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 b.w. body weight ChE cholinesterase CHO Chinese hampster 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 GC gas chromatography G.I. 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 dehydrogenase MCA 3-methylcholanthrene MCH mean corpuscular haemoglobin MCHC mean corpuscular haemoglobin concentration MCV mean corpuscular volume MMS methylmethane sulfonate MTD maximum tolerated dose NADPH nicotinamide adenine dinucleotide phosphate (reduced) 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 ppb parts per billion (1000 ppb = 1 ppm) ppm parts per million 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 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 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, 29 September to 8 October 1986. 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 1. 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. 77. 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 1986, Part I - Residues, as FAO Plant Production and Protection Paper No. 78. The toxicology monographs and monograph addenda contained in this volume are based upon working papers that were prepared by temporary advisers in advance of the 1986 Joint Meeting. A special acknowledgement is given to those who prepared these working papers, Professor N.S. Bakry, University of Alexandria, Alexandria, Egypt; Professor C.L. Berry, The London Hospital Medical College, London, UK; Dr A.L. Black, Commonwealth Department of Health, Woden, Australia; Dr M. Manno. University of Padua Medical School, Padua, Italy; Dr D.S. Saunders, U.S. Environmental Protection Agency, Washington, DC, USA; and Dr E.M. den Tonkelaar, National Institute of Public Health and Environmental Hygiene, Bilthoven, The Netherlands. 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