Pesticide residues in food -- 1998
Toxicological and environmental
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
Rome, 21-30 September 1998
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cases, based on unpublished proprietary data submitted for the purpose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 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
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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 149
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TABLE OF CONTENTS
List of participants
Abbreviations
Introduction
Toxicological evaluations
Amitraz
Bentazone (addendum)
Bitertanol
Dicloran
Dinocap
Diphenylamine (addendum)
Endosulfan
Ethoxyquin
Kresoxim-methyl*
Methiocarb
Phosmet (addendum)
Thiophanate-methyl (addendum)
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
1998 Joint Meeting of the FAO Panel of Experts on Pesticide Residues
in Food and the Environment and the WHO Core Assessment Group
Rome, 21-30 September 1998
PARTICIPANTS
Toxicological Core Assessment Group
Professor J.F. Borzelleca, Pharmacology, Toxicology, Medical College
of Virginia, Richmond, Virginia, United States (Vice-Chairman)
Dr P. Fenner-Crisp, Senior Science Advisor to the Director, Office of
Pesticide Programs, US Environmental Protection Agency, Washington DC
United States
Dr D. L. Grant, Director, Health Evaluation Division, Pest Management
Regulatory Agency, Ottawa, Ontario, Canada (Rapporteur)
Dr A. Moretto, Laboratorio di Tossicologia Industriale, Istituto di
Medicina del Lavoro, Università di Padova, Padova, Italy
Dr B.G. Priestly, Scientific Director, Chemicals & Non-Prescription
Drug Branch, Therapeutic Goods Administration, Commonwealth Department
of Health and Family Services, Woden, ACT, Australia
Professor A. Rico, Biochemistry-Toxicology, Physiopathology and
Experimental Toxicology Laboratory, Ecole Nationale Vétérinaire,
Toulouse, France
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, Food and Environmental Protection Section, Joint
FAO/IAEA Division of Nuclear Techniques in Food and Agriculture,
International Atomic Energy Agency, Vienna, Austria
Dr U. Banasiak, Federal Biological Research Centre for Agriculture and
Forestry, Kleinmachnow, Germany
Mr S. Crossley, Pesticide Safety Directorate, Ministry of Agriculture,
Fisheries and Food, Kings Pool, York, United Kingdom (Rapporteur)
Dr E. Dutra Caldas, Instituto de Saúde do DF/Gerência de Bromatologia
e Químicam and Department of Pharmaceutical Sciences, University of
Brasilia, Brasília, Brazil
Dr S. Funk, Health Effects Division, US Environmental Protection
Agency, Washington DC, United States
Mr D.J. Hamilton, Principal Scientific Officer, Animal & Plant Health
Service, Department of Primary Industries, Brisbane, Australia
(Chairman)
Ms E. Masoller, Dirección General Servicios Agrícolas, División
Analisis y Diagnósticos, Ministerio de Ganadería, 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 R. Bhula, National Registration Authority, Chemistry and Residue
Evaluation Section, Kingston, ACT, Australia (FAO Consultant)
Dr K. Fujimori, Division of Xenobiotics, Metabolism and Disposition,
National Institute of Health Sciences, Tokyo, Japan (WHO Temporary
Adviser)
Dr W.H. van Eck, Chairman, Codex Committee on Pesticide Residues,
Division of Public Health, Ministry of Health Welfare and Sport, The
Hague, Netherlands
Professor J. Hajslová, Institute of Chemical Technology, Department of
Food Chemistry and Analysis, Prague, Czech Republic (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, Lajarthe ,
Saint-Léon-sur-Vézère, France
Mrs J. Jempson, London, United Kingdom (FAO Consultant)
Dr J.-J. Larsen, Head, Department of General Toxicology, Institute of
Food Safety and Toxicology, Danish Veterinary and Food Administration,
Sœborg, Denmark (WHO Temporary Adviser)
Mr A.F. Machin, London, United Kingdom (FAO Consultant)
Dr T. C. Marrs, Joint Food Standards and Safety Group, 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 C. Moase, Health Evaluation Division, Pest Management Regulatory
Agency, Health Canada, Ottawa, Ontario, Canada (WHO Temporary
Adviser)
Dr G. Moy, Food Safety Unit, Programme of Food Safety and Food Aid,
World Health Organization, Geneva, Switzerland
Mr N. Nakashima, International Programme on Chemical Safety, World
Health Organization, Geneva, Switzerland
Dr A. Protzel, Health Effects Division, US Environmental Protection
Agency, Washington DC, United States (WHO Temporary Adviser)
Dr R. Solecki, Bundesinstitut für gesundheitlichen Verbraucherschutz
und Veterinärmedizin, Berlin, Germany (WHO Temporary Adviser)
Dr G. Vaagt, Senior Officer, Pesticide Management Group, Food and
Agriculture Organization of the United Nations, Rome, Italy (FAO
Joint Secretary)
Mr S. Warren, Pesticides Safety Directorate, Ministry of Agriculture,
Fisheries and Food, King's Pool, York, United Kingdom (WHO
Temporary Adviser)
Mr G. Wyrwal, Pesticide Group, Plant Protection Service, Food and
Agriculture Organization of the United Nations, Rome, Italy
Abbreviations used
ADI acceptable daily intake
ALAT alanine aminotransferase
AP alkaline phosphatase
ASAT aspartate aminotransferase
BrdU 5-bromo-2'-deoxyuridine
bw body weight
CCPR Codex Committee on Pesticide Residues
CMC carboxymethyl cellulose
CYP cytochrome P450
DMSO dimethyl sulfoxide
DNHCP methyl heptyl isomer of dinocap
F female
F0 parental generation
F1 first filial generation
F2 second filial generation
GABA gamma-aminobutyric acid
GGT gamma-glutamyl transferase
GLP good laboratory practice
GST-P placental form of glutathione S-transferase
gamma-GT gamma-glutamyl transpeptidase
H&E haematoxylin and eosin
HID highest ineffective dose
HPLC high-performance liquid chromatography
hprt hypoxanthine-guanine phosphoribosyl transferase gene
Ig immunoglobulin
ip intraperitoneally
IPCS International Programme on Chemical Safety
JMPR Joint FAO/WHO Meeting on Pesticide Residues
LED lowest effective dose
LC50 median lethal concentration
LD50 median lethal dose
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
po orally
ppm parts per million
S9 9000 × g supernatant fraction of rodent liver
SPF specific pathogen-free
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 Rome,
Italy, on 21-30 September 1998.
One of the substances evaluated by the Core Assessment Group at
this Meeting, kresoxim-methyl, was evaluated for the first time. The
other substances had been evaluated at earlier meetings. For five of
these, bentazone, dinocap, diphenylamine, phosmet, and thiophanate-
methyl, 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 amitraz,
bitertanol, dicloran, endosulfan, ethoxyquin, kresoxim-methyl, and
methiocarb, 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 148. 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 1998, 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 1998 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.