Pesticide residues in food 2000

Toxicological evaluations

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

Geneva, 20-29 September 2000

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.

IPCS gratefully acknowledges the assistance of Mrs E. Heseltine, St Léon-sur-Vézère, France, for editing these monographs.

ISBN 92 4 1665 16 5

© World Health Organization 2001

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 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, 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 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 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.

TABLE OF CONTENTS

List of participants

Abbreviations

Introduction

Toxicological evaluations

Chlorpropham

DDT (addendum)

Deltamethrin

Dodine

Fenitrothion

Fipronil (addendum)

Imazalil

Thiodicarb

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

2000 Joint FAO/WHO Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group

Geneva, 20–29 September 2000

WHO Members

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

Professor J.F. Borzelleca, Department of Pharmacology, Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA

Dr P. Fenner-Crisp, Senior Science Advisor to the Director, Office of Pesticide Programs, Environmental Protection Agency, Washington DC, USA

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

Professor J. Hajslova, Institute of Chemical Technology, Department of Food Chemistry and Analysis, Prague, Czech Republic

Dr A. Moretto, Department of Environmental Medicine and Public Health, University of Padua, Padua, Italy (Chairman)

Dr B.G. Priestly, Scientific Director, Chemicals & Non-Prescription Medicines Branch, Therapeutic Goods Administration, Commonwealth Department of Health and Aged Care, Woden, ACT, Australia (Rapporteur)

Professor S.A. Soliman, Department of Pesticide Chemistry, Faculty of Agriculture, Alexandria University, Alexandria, Egypt

FAO Members

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

Dr S.M.F. Calumpang, National Crop Protection Center, University of the Philippines, Los Baños, Laguna, Philippines

Dr E. Dutra Caldas, Pharmaceutical Sciences Department, College of Health Sciences, University of Brasilia, Brasília DF, Brazil (Rapporteur)

Dr S. Funk, Health Effects Division, US 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)

Mr K. Ogura, Agricultural Chemicals Inspection Station, Tokyo, Japan

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

Secretariat

Dr F. Aguilar, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland

Dr I.C. Dewhurst, Pesticides Safety Directorate, Ministry of Agriculture, Fisheries and Food, York, United Kingdom (WHO Temporary Adviser)

Dr V.A. Dobozy, Health Effects Division, Office of Pesticide Programs, US Environmental Protection Agency, Washington DC, USA (WHO Temporary Adviser)

Dr W.H. van Eck, Chairman, Codex Committee on Pesticide Residues, Division of Public Health, Ministry of Health and Welfare and Sport, The Hague, Netherlands

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

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

Dr M. Hirose, Head, Division of Pathology, National Institute of Health Sciences, Tokyo, Japan (WHO Temporary Adviser)

Dr D. MacLachlan, Chemistry & Residues Evaluation Section, National Registration Authority for Agricultural & Veterinary Chemicals, Kingston, ACT, Australia (FAO Consultant)

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

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

Dr G. Moy, Food Safety, World Health Organization, Geneva, Switzerland

Dr U.W. Mueller, Chemicals & Non-Prescription Medicines Branch, Therapeutic Goods Administration, Commonwealth Department of Health and Aged Care, Woden, ACT, Australia (WHO Temporary Adviser)

Ms B. Röstel, Chef d’unité Relations internationals, ANMV–AFSSA, Fougères, France (FAO Consultant)

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

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

Dr Y. Yamada, Food Standards Officer, Joint FAO/WHO Standards Programme, Food and Nutrition Division, Food and Agriculture Organization of the United Nations, Rome, Italy

Abbreviations used

ADI

acceptable daily intake

AUC

area under the curve

bw

body weight

CFR

Code of Federal Regulations (United States)

CI

confidence interval

Cmax

maximum plasma concentration

CYP

cytochrome P450

DDD

1,1’-Dichloro-2,2-bis(para-chlorophenyl)ethane

DDE

1,1’-(2,2-Dichloroethylenylidene)-bis(para-chlorobenzene)

DDT

1,1,1-Trichloro-2,2-bis(para-chlorophenyl)ethane

DMBA

7,12-dimethylbenz[a]anthracene

DMSO

dimethyl sulfoxide

EC50

median effective concentration

ED50

median effective dose

F

female

F0

parental generation

F1

first filial generation

F2

second filial generation

FIFRA

Federal Insecticide, Fungicide and Rodenticide Act (United States)

FOB

functional observational battery

GLP

good laboratory practice

HID

highest ineffective dose

HPLC

high-performance liquid chromatography

IARC

International Agency for Research on Cancer

IC50

median inhibitory concentration

Ig

immunoglobulin

IPCS

International Programme on Chemical Safety

IU

international unit

JMPR

Joint FAO/WHO Meeting on Pesticide Residues

LC50

median lethal concentration

LD50

median lethal dose

LED

lowest effective dose

LOAEC

lowest-observed-adverse-effect concentration

LOAEL

lowest-observed-adverse-effect level

LSC

liquid scintillation counting

mRNA

messenger RNA

M

male

MRL

maximum residue limit

NA

not analysed

NADPH2

reduced nicotine adenine dinucleotide phosphate

NC

not confirmed

NOAEC

no-observed-effect concentration

NOAEL

no-observed-adverse-effect level

NR

not reported

OECD

Organization for Economic Co-operation and Development

PEG

polyethylene glycol

ppm

parts per million

PTDI

provisional tolerable daily intake

QA

quality assurance

S9

9000 × g supernatant fraction of rodent liver

SD

Sprague-Dawley

TLC

thin-layer chromatography

Tmax

time to achieve maximum plasma concentration

TRR

% total residues

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 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 Geneva, Switzerland, on 20–29 September 2000.

All eight substances on which monographs were prepared by the Core Assessment Group at this Meeting had been evaluated at earlier meetings. For two of these, DDT and fipronil, 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 chlorpropham, deltamethrin, dodine, fenitrothion, imazalil, and thiodicarb, 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.

The report of the Joint Meeting has been published by the FAO as FAO Plant Production and Protection Paper 163. 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 2000, 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 2000 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