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cases, based on unpublished proprietary data submitted for the purpose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
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that has obtained permission from the owner of the data for this
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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.
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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 13 0
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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.