IPCS INCHEM Home

Pesticide residues in food - 2002 - Joint FAO/WHO Meeting on Pesticide Residues

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 Core Assessment Group

Rome, 16–25 September 2002

The summaries and evaluations contained in this book are, in most cases, based on unpublished proprietary data submitted for the purpose of the JMPR assessment.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.

WORLD HEALTH ORGANIZATION

Geneva, 2003

WHO Library Cataloguing-in-Publication Data

Joint Meeting of the FAO Panel of Experts on Pesticides Residues in Food and the Environment and the WHO Core Assessment Group (2002 : Rome, Italy) Pesticide residues in food : 2002 : toxicological evaluations / Joint Meeting of the FAO Panel of Experts on Pesticides Residues in Food and the Environment and the WHO Core Assessment Group, Rome, 16-25 September 2002.

1.Pesticide residues - toxicity 2.Food contamination 3.No-observed-adverse-effect level I.FAO Panel of Experts on Pesticide Residues in Food and the Environment II.WHO Core Assessment Group on Pesticide Residues III.Title.

ISBN 92 4 166518 1          (NLM classification: WA 240)

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.

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 Nations 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 in the field of chemical safety. The purpose of the IOMC is to promote 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.

© World Health Organization 2003

All rights reserved. Publications of the World Health Organization can be obtained from Marketing and Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: bookorders@who.int). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to Publications, at the above address (fax: +41 22 791 4806; email: permissions@who.int).

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 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. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.

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.

The World Health Organization does not warrant that the information contained in this publication is complete and correct and shall not be liable for any damages incurred as a result of its use.

TABLE OF CONTENTS

List of participants

Abbreviations

Introduction

Toxicological evaluations

Acephate

Carbofuran (addendum)

Esfenvalerate*

Ethephon (addendum)

Fenamiphos (addendum)

Flutolanil*

Lindane

Metalaxyl and metalaxyl-M*

Methamidophos

Oxamyl

Oxydemeton-methyl (addendum)

Tolyfluanid

Triazophos

Studies of developmental neurotoxicity and their use in establishing acute reference doses and acceptable daily intakes

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

* First full evaluation

2002 Joint Meeting of the FAO Panel of Experts on
Pesticide Residues in Food and the Environment
and the WHO Core Assessment Group

Rome, 16–25 September 2002

PARTICIPANTS

Toxicological Core Assessment Group1

Professor A.R. Boobis, Section on Clinical Pharmacology, Division of Medicine, Imperial College School of Medicine, London, United Kingdom (Rapporteur)

Dr L. Davies, Scientific Director, Chemicals & Non-Prescription Medicines Branch, Therapeutic Goods Administration, Commonwealth Department of Health and Ageing, Woden, ACT, Australia

Dr V.L. Dellarco, Environmental Protection Agency, Office of Pesticide Programs, Health Effects Division, Washington DC, USA

Dr H. Häkansson, Institute of Environmental Medicine, Karolinska Institutet, Division of Risk Assessment and Organohalogen Pollutants, Stockholm, Sweden

Dr A. Moretto, Dipartimento Medicina Ambientale e Sanità Pubblica, Università di Padova, Padova, Italy (Chairman)

Dr M. Tasheva, Associate Professor of Toxicology, National Center of Hygiene, Medical Ecology and Nutrition, Sofia, Bulgaria

FAO Panel of Experts on Pesticide Residues in Food and the Environment

Dr U. Banasiak, Federal Biological Research Centre for Agriculture and Forestry, Kleinmachnow, Germany

Dr E. Dutra Caldas, University of Brasilia, College of Health Sciences, Pharmaceutical Sciences Department, Campus Universitàrio Darci Ribeiro, and Central Laboratory of Public Health of Federal District, Brasília DF, Brazil (Rapporteur)

Dr S. Funk, Health Effects Division, Environmental Protection Agency, Washington DC, USA

Mr D.J. Hamilton, Principal Scientific Officer, Animal & Plant Health Service, Department of Primary Industries, Brisbane, Queensland, Australia (Vice-Chairman)

Dr B.C. Ossendorp, Centre for Substances and Risk Assessment, National Institute of Public Health and the Environment (RIVM), Bilthoven, Netherlands

Dr Y. Yamada, Research Planning and Coordination Division, National Food Research Institute, Tsukuba, Japan

Secretariat

Dr A. Ambrus, Head, Agrochemicals Unit, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, IAEA, Vienna, Austria

Mr B. Declercq, Ministère de l'Economie et des Finances, Laboratoire interrégional de la DGCCRF, Massy, France (FAO Consultant)

Dr I. Dewhurst, Pesticides Safety Directorate, King’s Pool, York, England (WHO Temporary Adviser)

Dr K. Hamernik, Environmental Protection Agency, Washington DC, USA (WHO Temporary Adviser)

Dr J.L. Herrman, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland (WHO Joint Secretary)

Dr A.R.C. Hill, Department for Environment, Food and Rural Affairs, Central Science Laboratory, Sand Hutton, York, England (FAO Consultant)

Dr H. Jeuring, Chairman, Codex Committee on Pesticide Residues, Senior Public Health Officer Food Inspectorate for Health Protection and Veterinary Public Health Ministry of Health, Welfare and Sport, The Hague, Netherlands

Dr S. Khan, Department of Chemistry, George Mason University, Fairfax, Virginia, USA (FAO Editor)

Dr J.-J. Larsen, Head, Department of General Toxicology, Institute of Toxicology, Danish Veterinary and Food Administration, Søborg, Denmark (WHO Temporary Adviser)

Dr S.J. Logan, Therapeutics Goods Administration, Department of Health & Aged Care, Woden, ACT, Australia (WHO Temporary Adviser)

Mr D. Lunn, Programme Manager (Residues-Plants), Dairy and Plant Products Group, New Zealand Food Safety Authority, Wellington, New Zealand (FAO Consultant)

Mr A.F. Machin, London, England (FAO Consultant)

Dr D. MacLachlan, Australian Quarantine and Inspection Service, Department of Agriculture, Forestry and Fisheries, Australia, Kingston, ACT, Australia (FAO Consultant)

Dr T.C. Marrs, Food Standards Agency, London, England (WHO Temporary Adviser)

Ms S. Malezieux, Ministère de L’Agriculture, Paris, France (FAO Consultant)

Dr D.B. McGregor, Lyon, France (WHO Temporary Adviser)

Dr J. Maskeliunas, Food Standards Officer, Joint FAO/WHO Food Standards Programme, Food and Nutrition Division, Food and Agriculture Organization of the United Nations (FAO), Rome, Italy

Dr E. Mendez, Health Effects Division, Office of Pesticide Programs, Environmental Protection Agency, Washington DC, USA (WHO Temporary Adviser)

Dr S.W. Page, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland

Dr Whang Phang, Health Effects Division, Office of Pesticide Programs, Environmental Protection Agency, Washington DC, USA (WHO Temporary Adviser)

Dr F. Rodrigues Puga, Instituto Biológico, Secretariat of Agriculture of the State of São Paulo, São Paulo, Brazil (WHO Temporary Adviser)

Ms N. Scheidegger, Food Safety, European Centre for Environment and Health, World Health Organization, Rome, Italy

Dr R. Solecki, Pesticides and Biocides Division, Federal Institute for Health Protection of Consumers and Veterinary Medicine, Berlin, Germany (WHO Temporary Adviser)

Dr A. Takagi, Department of Toxicology, National Institute of Health Sciences, Tokyo, Japan (WHO Temporary Adviser)

Dr A.W. Tejada, Pesticide Management Group, Food and Agriculture Organization of the United Nations (FAO), Rome, Italy (FAO Joint Secretary)

Dr G. Vaagt, Senior Officer, Pesticide Management Group, Food and Agriculture Organization of the United Nations (FAO), Rome, Italy

Dr C. Vleminckx, Toxicology Division, Scientific Institute of Public Health, Ministry of Social Affairs, Public Health and Environment, Brussels, Belgium (WHO Temporary Adviser)

Dr G. Wolterink, Centre for Substances & Risk Assessment, National Institute of Public Health and the Environment (RIVM), Bilthoven, Netherlands (WHO Temporary Adviser)

1 Unable to attend: Professor J.F. Borzelleca, Department of Pharmacology and Toxicology, Virginia Commonwealth University, Medical College of Virginia, Richmond, Virginia, USA

Abbreviations used

ADI

acceptable daily intake

AUC

area under the curve

bw

body weight

Cmax

maximal concentration

CMC

carboxymethylcellulose

CPIA

2-(4-chlorophenyl)isovaleric acid

CYP

cytochrome P450

DMCF

N,N-dimethyl-2-nitriloacetamide

DMOA

dimethylamino(oxo)acetic acid

DMSO

dimethyl sulfoxide

DMTO

methyl 2-(dimethylamino)-N-hydroxy-2-oxo-ethanimidothioate

EDTA

ethylenediamine tetraacetic acid

EEC

European Economic Community

EPA

Environmental Protection Agency (USA)

F0

parental generation

F1 (1a, 1b, 1c...)

first filial generation (succeeding litters)

F2 (2a, 2b, 2c...)

second filial generation (succeeding litters)

F3

third filial generation

FIFRA

Federal Insecticide, Fungicide and Rodenticide Act (USA)

FOB

functional observational battery

GD

gestation day

GLP

good laboratory practice

HDT

highest dose tested

HID

highest ineffective dose

IC50

median inhibitory concentration

ID50

median inhibitory dose

IPCS

International Programme on Chemical Safety

JMPR

Joint FAO/WHO Meeting on Pesticide Residues

LC50

median lethal concentration

LD50

median lethal dose

LED

lowest effective dose

LOAEL

lowest-observed-adverse-effect level

LOD

limit of detection

LOQ

limit of quantification

NADPH

nicotinamide adenine dinucleotide phosphate (reduced form)

NOAEL

no-observed-adverse-effect level

NOAEC

no-observed-adverse-effect concentration

ND

not determined

NK

natural killer

NR

not reported

NS

no sample collected

NTE

neuropathy target esterase

OECD

Organisation for Economic Co-operation and Development

OPPTS

Office of Prevention, Pesticides and Toxic Substances (US Environmental Protection Agency)

p

probability

PND

postnatal day

ppm

parts per million

QA

quality assurance

RfD

reference dose

S9

9000 × g supernatant fraction of rodent liver

TLC

thin-layer chromatography

Tmax

time to maximal plasma concentration

TOCP

tri-ortho-cresyl phosphate

TSH

thyroid-stimulating hormone

v/v

volume per volume

wt

weight

w/v

weight per volume

Introduction

The toxicological monographs and monograph addenda 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 Rome, Italy, on 16–25 September 2002.

Three of the substances evaluated by the Core Assessment Group at this Meeting, esfenvalerate, flutolanil and metalaxyl-M, were evaluated for the first time. The other 11 substances had been evaluated at earlier meetings. For four of these, carbofuran, ethephon, fenamiphos and oxydemeton-methyl, only information received since the previous evaluations is summarized, in ‘monograph addenda’. Of these, carbofuran, fenamiphos and oxydemeton-methyl were evaluated for establishment of an acute reference dose. The appropriate earlier documents on the four compounds should be consulted in order to obtain full toxicological profiles. Toxicological monographs were prepared on acephate, esfenvalerate, flutolanil, lindane, metalaxyl-M and metalaxyl, methamidophos, oxamyl, tolyfluanid and triazophos, 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.

In order to address questions regarding the adequacy of the usual toxicological databases for assessing the safety of pesticides to developing fetuses, infants and children, the 1999 JMPR agreed that it would be useful to compare the critical NOAELs identified in developmental neurotoxicity studies with those identified from conventional data packages. The results of studies on developmental neurotoxicity with 14 pesticides were reviewed by the present Meeting and compared with those of related studies of prenatal effects on development, reproduction and fertility and studies of neurotoxicity in both acute and 90-day studies in adult rats in order to evaluate the use of studies of developmental neurotoxicity in the establishment of acute reference doses and ADIs.

The report of the Joint Meeting has been published by the FAO as FAO Plant Production and Protection Paper 172. That report contains comments on the compounds considered, acceptable daily intakes established by the WHO Core Assessment Group, and maximum residue limits 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 2002, Part I, Residues, in the FAO Plant Production and Protection Paper series.

The toxicological monographs and addenda contained in this volume are based on working papers that were prepared by temporary advisers before the 2002 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 biological properties or toxicity 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