PESTICIDE RESIDUES IN FOOD - 1997 Sponsored jointly by FAO and WHO with the support of the International Programme on Chemical Safety (IPCS) TOXICOLOGICAL AND ENVIRONMENTAL EVALUATIONS 1994 Joint meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group Lyon 22 September - 1 October 1997 The summaries and evaluations contained in this book are, in most cases, based on unpublished proprietary data submitted for the purpose of the JMPR assessment. A registration authority should not grant a registration on the basis of an evaluation unless it has first received authorization for such use from the owner who submitted the data for JMPR review or has received the data on which the summaries are based, either from the owner of the data or from a second party that has obtained permission from the owner of the data for this purpose. 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. 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) within the framework of the Inter- Organization Programme for the Sound Management of Chemicals. The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the United Nations Environment Programme (UNEP), the International Labour Organisation (ILO), and the World Health Organization (WHO). The overall objectives of the IPCS are to establish the scientific basis for assessing the risk to human health and the environment from exposure to chemicals, through international peer-review processes as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals. The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO, the United Nationals Industrial Development Organization, and the Organisation for Economic Co-operation and Development (Participating Organizations), following recommendations made by the 1992 United Nations Conference on the Environment and Development to strengthen cooperation and increase coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment. IPCS gratefully acknowledges the assistance of Mrs. E. Heseltine, St Léon-sur-Vézère, France, for editing these monographs. Health & Environment International Ltd, by agreement with WHO, performed independent literature searches on some of the substances on which data are summarized in this document in order to ensure that all relevant toxicological and related information was reviewed. ISBN 92 4 1665 13 0 (c) World Health Organization 1998 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 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. TABLE OF CONTENTS List of participants Abbreviations Introduction Toxicological evaluations Abamectin (addendum) Amitrole (addendum) Aminomethylphosphonic acid (AMPA) Chlormequat (addendum) Fenamiphos Fenbuconazole* Fenthion (addendum) Fipronil* Guazatine Lindane (addendum) Malathion Methidathion (addendum) Phosalone (addendum) Triforine Environmental evaluations 2,4-Dichlorophenoxyacetic acid (2,4-D), salts and esters Mevinphos 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. Corrigenda to previous editions of JMPR toxicological and environmental evaluations ____________ * First full evaluation 1997 Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group Lyon, 22 September-1 October 1997 PARTICIPANTS Toxicological Core Assessment Group1 Dr P. Fenner-Crisp, Acting Director, Office of Science Coordination and Policy, US Environmental Protection Agency, Washington DC, United States (Chairman) Dr D.L. Grant, Director, Health Evaluation Division, Health Canada, Tunney's Pasture, Ottawa, Ontario, Canada (Rapporteur) Dr A. Moretto, Istituto di Medicina del Lavoro, Universita di Padova, Padova, Italy Professor O. Pelkonen, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland Dr B.G. Priestly, Scientific Director, Chemicals and Non-prescription Drug Branch, Therapeutic Goods Administration, Commonwealth Department of Health and Family Services, Woden, ACT, Australia Dr P. Yao, Professor of Toxicology, Institute of Occupational Medicine, Ministry of 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 Dr U. Banasiak, Federal Biological Research Centre for Agriculture and Forestry, Kleinmachnow, Germany Mr S. Crossley, Pesticides Safety Directorate, Ministry of Agriculture, Fisheries and Food, Kings Pool, York, United Kingdom Mr D.J. Hamilton, Principal Scientific Officer, Animal and Plant Health Service, Department of Primary Industries, Brisbane, Queensland, Australia (Rapporteur) 1 Invited but unable to attend: Professor J.F. Borzelleca, Pharmacology, Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, United States Mr N.F. Ives, Health Effects Division, US Environmental Protection Agency, Washington DC, United States (Vice-Chairman) Mrs E. Masoller, Servicios de Laboratorios, Ministerio de Ganader'a, Agricultura y Pesca, Montevideo, Uruguay Mr T. Sakamoto, Head of Technical Research Section, Agricultural Chemicals Inspection Station, Ministry of Agriculture, Forestry and Fisheries, Tokyo, Japan Secretariat Dr E. Dutra Caldas, Instituto de Saude do DF/Gerência de Bromatologia e Quimica, Brasilia, Brazil (FAO Temporary Adviser) Dr P.J. Campbell, Pesticides Safety Directorate, Ministry of Agriculture, Fisheries and Food, Kings Pool, York, United Kingdom (WHO Temporary Adviser) Mr D.J. Clegg, Carp, Ontario, Canada (WHO Temporary Adviser) Dr I.C. Dewhurst, Pesticides Safety Directorate, Ministry of Agriculture, Fisheries and Food, Kings Pool, York, United Kingdom (WHO Temporary Adviser) Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood, Abbots Ripton, Huntindon, Cambridgeshire, United Kingdom (WHO Temorary Adviser) Dr W.H. van Eck, Division of Public Health, Ministry of Health, Welfare and Sport, Rijswijk, Netherlands (Chairman, Codex Committee on Pesticide Residues) Dr K. Fujimori, Division of Pharmacology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan (WHO Temporary Adviser) Dr S. Funk, Health Effects Division, US Environmental Protection Agency, Washington DC, USA (FAO Consultant) Dr S. Geertsen, Insecticide Toxicological Evaluation Section, Health Evaluation Division, Pest Management Regulatory Agency, Ottawa, Ontario, Canada (WHO Temporary Adviser) Professor J. Hajslova, Institute of Chemical Technology, Department of Food Chemistry and Analysis, Prague, Czech Republic (FAO Temporary Adviser) Dr K. Hamernik, Toxicology Branch II, Health Effects Division, Office of Pesticide Programs, US Environmental Protection Agency, Washington DC, USA (WHO Temporary Adviser) Dr J.L. Herrman, Assessment of Risk and Methodologies, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland (WHO Joint Secretary) Mrs E. Heseltine, Communication in Science, St Léon-sur-Vézère, France (WHO Editor) Mrs P.H. van Hoeven-Arentzen, Centre for Substances and Risk Assessment, National Institute of Public Health and the Environment, Bilthoven, Netherlands (WHO Temporary Adviser) Dr F.-W. Kopisch-Obuch, Senior Officer, Pesticide Group, Plant Protection Service, Food and Agricultural Organization of the United Nations, Rome, Italy Dr J.-J. Larsen, Head, Department of General Toxicology, Institute of Toxicology, Danish Veterinary and Food Administration, Soborg, Denmark (WHO Temporary Adviser) Mr A.F. Machin, London, United Kingdom (FAO Consultant) Dr T.C. Marrs, Medical Toxicology and Environmental Health, Department of Health, London, United Kingdom (WHO Temporary Adviser) Dr D. McGregor, Unit of Carcinogen Identification and Evaluation, International Agency for Research on Cancer, Lyon, France (WHO Temporary Adviser) Dr G. Moy, Programme of Food Safety and Food Aid, Division of Food and Nutrition, World Health Organization, Geneva, Switzerland Dr E. Smith, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland Dr G. Vettorazzi, International Toxicology Information Centre, San Sebastian, Spain (WHO Temporary Adviser) Mr M. Watson, Ricerca Inc., Painesville, Ohio, USA (WHO Temporary Adviser) Dr Y. Yamada, Food Standards Officer, Joint FAO/WHO Food Standards Programme, Food and Nutrition Division, Food and Agriculture Organization of the United Nations, Rome, Italy Abbreviations used ADI acceptable daily intake AMPA aminomethylphosphonic acid bw body weight CCPR Codex Committee on Pesticide Residues CoA coenzyme A CoE Council of Europe CYP cytochrome P450 D decedents DMSO dimethyl sulfoxide EBOB 1-[(4-ethyl)phenyl]-4- n-propyl-2,6,7- trioxacicyclo[2.2.2]octane EPPO European Plant Protection Organization F female F0 parental generation F1 first filial generation F2 second filial generation GABA gamma-aminobutyric acid HPLC high-performance liquid chromatography hprt hypoxanthine-guanine phosphoribosyl transferase gene IARC International Agency for Research on Cancer IPCS International Programme on Chemical Safety JMPR Joint FAO/WHO Meeting on Pesticide Residues LC50 median lethal concentration LD50 median lethal dose lambdamax maximum wavelength LOAEL lowest-observed-adverse-effect level M male MRL maximum residue limit NOAEL no-observed-adverse-effect level NOEC no-observed-effect concentration NR not reported PEC predicted environmental concentration ppm parts per million RFLP restriction fragment length polymorphism S9 9000 × g supernatant fraction of rodent liver T terminally killed animals T3 triodothyronine T4 thyroxine Tmax time of maximum concentration TBPS tert-butylbicyclophosphorothionate TER toxicity:exposure ratio TSH thyroid-stimulating hormone w/w weight per weight Introduction The toxicological monographs and monograph addenda and the environmental monographs contained in this volume were prepared by a WHO Core Assessment Group 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 Lyon, France, on 22 September-1 October 1997. Two of the substances evaluated by the Core Assessment Group at this Meeting, fipronil and aminomethylphosphonic acid (AMPA), the primary degradation product of glyphosate in plants, soil, and water, were evaluated for the first time. Twelve of the substances had been evaluated at earlier meetings. For seven of these, abamectin, amitrole, chlormequat, fenthion, lindane, methidathion, and phosalone, only information received since the previous evaluations is summarized, in 'monograph addenda'. The appropriate earlier documents should be consulted in order to obtain full toxicological profiles of these chemicals. Toxicological monographs were prepared on AMPA, fenamiphos, fenbuconazole, fipronil, guazatine, malathion, and triforine, summarizing new data and, where relevant, incorporating information from previous monographs and addenda. Reports and other documents resulting from previous Joint Meetings on Pesticide Residues are listed in Annex 1. Two environmental monographs are included, on 2,4-dichlorophenoxyacetic acid (2,4-D) salts and esters and on mevinphos. These monographs were prepared by a Core Assessment Group that met in Leicester, United Kingdom, in March 1997. The report of the Joint Meeting has been published by the FAO as FAO Plant Production and Protection Paper 145. That report contains brief comments on the compounds considered, acceptable daily intakes established by the WHO Core Assessment Group, and maximum residue limits or guideline levels established by the FAO Panel of Experts. Monographs on residues prepared by the FAO Panel of Experts are published as a companion volume, as Evaluations 1997, Part I, Residues, in the FAO Plant Production and Protection Paper series. The toxicological monographs and addenda and the environmental monographs contained in this volume are based on working papers that were prepared by temporary advisers before the 1997 Joint Meeting. A special acknowledgement is made to those advisers. The monographs were edited by Mrs E. Heseltine, St Léon-sur-Vézère, France. The preparation and editing of this volume were made possible by the technical and financial contributions of the lead institutions of the International Programme on Chemical Safety (IPCS), which supports the activities of the 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 of its authorities, nor 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 biology or toxicology of the compounds included in this volume 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