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Pesticide residues in food 2001

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, 17–26 September 2001

The summaries and evaluations contained in this book are, in most cases, based on unpublished proprietary data submitted for the purpose of the JMPR assessment.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

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 (2001: Geneva, Switzerland) Pesticide residues in food: 2001: toxicological evaluations / Joint Meeting of the FAO Panel of Experts on Pesticides Residues in Food and the Environment and the WHO Core Assessment Group, Geneva, 17-26 September 2001.

1. Pesticide residues – toxicity 2. No-observed-adverse-effect level

3. Food contamination I. FAO Panel of Experts on Pesticide Residues in Food and the Environment II. WHO Core Assessment Group on Pesticide Residues

ISBN 92 4 166517 3          (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.

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

© World Health Organization 2002

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.

TABLE OF CONTENTS

List of participants

Abbreviations

Introduction

Toxicological evaluations

Carbaryl (addendum)

Diazinon (addendum)

Diflubenzuron

Fenpropimorph (addendum)

Imazalil (addendum)

Imidacloprid*

Methomyl (addendum)

Methoprene and S-methoprene

Phosalone (addendum)

Prochloraz

Spinosad*

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

2001 Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group

Rome, 20–29 September 1999

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)

Professor B.-H. Chen, School of Public Health, Shanghai Medical University, Shanghai, China

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

Dr B.G. Priestly, Scientific Director, Chemicals and Non-prescription Medicines Branch, Therapeutic Goods Administration, Commonwealth Department of Health and Family Services, Woden, ACT, Australia

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, Central Laboratory of Public Health, Brasilia, Brazil (Rapporteur)

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

Mr D.J. Hamilton, Animal and 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, Bilthoven, The Netherlands

Secretariat

Dr M.C. Alonzo Romanelli, Departamento de Salud Ambiental y Seguridad Quimica, Ministerio de Salud Publica, Montevideo, Uruguay (WHO Temporary Adviser)

Dr A. Bartholomaeus, Therapeutic Goods Administration, Commonwealth Department of Health and Aged Care, Woden, ACT, Australia (WHO Temporary Adviser)

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

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

Dr H. Galal-Gorchev, Environmental Health Inc., Chevy Chase, MD, USA (WHO Temporary Adviser)

Dr J.L. Herrman, 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. van Hoeven-Arentzen, Centre for Substances and Risk Assessment, National Institute of Public Health and the Environment, Bilthoven, The Netherlands (WHO Temporary Adviser)

Mrs F. Jallow-NDoye, National Environment Agency, Banjul, The Gambia (WHO Temporary Adviser)

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

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

Dr J. Maskeliunas, Joint FAO/WHO Food Standards Programme, Food and Nutrition Division, FAO, Rome, Italy (FAO Food Standards Officer)

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

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

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 Institutes of Health Sciences, Tokyo, Japan (WHO Temporary Adviser)

Dr A.W. Tejada, Pesticide Management Group, Plant Protection Service, Plant Production and Protection Division, FAO, Rome, Italy (FAO Joint Secretary)

Dr G. Vaagt, Pesticide Management Group, Plant Protection Service, Plant Production and Protection Division, FAO, Rome, Italy

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

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

1 Unable to attend: Professor J.F. Borzelleca, Department of Pharmacology and Toxicology, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA, USA; Dr V.L. Dellarco, Office of Pesticide programs, Health Effects Division, Environmental protection Agency, Washington DC, USA; Dr H. Häkansson, Division of Risk Assessment and Organohalogen Pollutants, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden

Abbreviations used

ADI

acceptable daily intake

AUC

area under the curve

BrdU

5-bromo-2’-deoxyuridine

bw

body weight

CI

confidence interval

Cmax

maximal concentration

DMSO

dimethyl sulfoxide

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

GST

glutathione S-transferase

GST-P

glutathione S-transferase, placental form

HPLC

high-performance liquid chromatography

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

LOAEL

lowest-observed-adverse-effect level

M

male

M1

N-propyl-N-2-(2,4,6-trichlorophenoxy)ethylurea

M2

N-formyl-N’-propyl-N’-2-(2,4,6-trichlorophenoxy)ethylurea

MTD

maximum tolerated dose

NA

not analysed

NOAEL

no-observed-adverse-effect level

NOAEC

no-observed-adverse-effect concentration

ND

not determined

NR

not reported

OECD

Organisation for Economic Co-operation and Develeopment

PCNA

proliferating cell nuclear antigen

PEG

polyethylene glycol

ppm

parts per million

QA

quality assurance

RfD

reference dose

S9

9000 × g supernatant fraction of rodent liver

SMR

standardized mortality ratio

T3

triiodothyronine

T4

thyroxine

TSH

thyroid-stimulating hormone

UGT

UDP-glucuronidyl transferase

WAK 3839

1-(6-chloro-3-pyridylmethyl)-N-nitroso(imidazolidin-2-ylidene)amine

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 Geneva, Switzerland, on 17–26 September 2001.

Two of the substances evaluated by the Core Assessment Group at this Meeting, imidacloprid and spinosad, were evaluated for the first time. The other nine substances had been evaluated at earlier meetings. For six of these, carbaryl, diazinon, fenpropimorph, imazalil, methomyl and phosalone, only information received since the previous evaluations is summarized, in ‘monograph addenda’. Of these, diazinon, methomyl and phosalone were evaluated only for establishment of an acute reference dose. The appropriate earlier documents on the six compounds should be consulted in order to obtain full toxicological profiles of these chemicals. Toxicological monographs were prepared on diflubenzuron, methoprene and S-methoprene and prochloraz, 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 167. 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 2001, 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 2001 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