Pesticide residues in food -- 1999
Sponsored jointly by FAO and WHO
with the support of the International Programme
on Chemical Safety (IPCS)
Toxicological evaluations
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
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 15 7
(c) World Health Organization 2000
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concerning the legal status of any country, territory, city or area or
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TABLE OF CONTENTS
List of participants
Abbreviations
Introduction
Toxicological evaluations
Chlormequat (addendum)
Chlorpyrifos
Dimethipin
Ethoprophos
Glufosinate-ammonium (addendum)
Permethrin
2-Phenylphenol and its sodium salt
Propargite
Propylene thiourea (addendum)
Pyrethrum extract (Pyrethrins) (addendum)
Pyriproxyfen*
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
1999 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 Group
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 and Toxicology,
Virginia Commonwealth University, Medical College of Virginia,
Richmond, VA, 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 A. Moretto, Istituto di Medicina del Lavoro, Università 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
Medicines Branch, Therapeutic Goods Administration, Commonwealth
Department of Health and Family Services, Woden, ACT, Australia
(Rapporteur)
Professor S.A. Soliman, Department of Pesticide Chemistry, Faculty of
Agriculture, Alexandria University, El-Shatby, Alexandria, Egypt
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, Pharmaceutical Sciences Department, College of
Health Sciences, University of Brasilia, Brasilia, Brazil
(Rapporteur)
Dr S. Funk, Health Effects Division, Environmental Protection Agency,
Washington DC, United States
Mr D.J. Hamilton, Principal Scientific Officer, Animal and Plant
Health Service, Department of Primary Industries, Brisbane,
Queensland, Australia (Chairman)
Secretariat
Dr A. Ambrus, Agrochemicals Unit, Joint FAO/IAEA Division of Nuclear
Techniques in Food and Agriculture, IAEA, Vienna, Austria
(FAO Consultant)
Dr R. Bhula, Chemistry and Residue Evaluation Section, National
Registration Authority for Agricultural and Veterinary Chemicals,
Kingston, ACT, Australia (FAO Consultant)
Dr E. Bosshard, Section Crop Protection Products, Federal Office of
Agriculture, Bern, Switzerland (WHO Temporary Adviser)
Dr S.M.F. Calumpang, National Crop Protection Center, University of
the Philippines, Los Baños, Laguna, Philippines (FAO
Consultant)
Dr I.C. Dewhurst, Pesticides Safety Directorate, Ministry of
Agriculture, Fisheries and Food, York, United Kingdom
(WHO Temporary Adviser)
Dr W.G. Dykstra, Office of Pesticide Programs, Environmental
Protection Agency, Washington DC, United States (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 K. Fujimori, Division of Xenobiotics, Metabolism and Disposition,
National Institute of Health Sciences, Tokyo, Japan (WHO
Temporary Adviser)
Professor J. Hajslova, Institute of Chemical Technology, Department of
Food Chemistry and Analysis, Prague, Czech Republic (WHO
Temporary Adviser)
Mrs C. Harris, Pesticides Safety Directorate, Ministry of Agriculture,
Fisheries and Food, York, United Kingdom (FAO Consultant)
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)
Dr M. Hirose, Head, Division of Pathology, National Institute of
Health Sciences, Tokyo, Japan (WHO Temporary Adviser)
Dr J.-J. Larsen, Head, Department of General Toxicology, Institute of
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 Safety and Standards Group, London, United
Kingdom (WHO Temporary Adviser)
Dr D.B. McGregor, Unit of Carcinogen Identification and Evaluation,
International Agency for Research on Cancer, Lyon, France
Dr G. Moy, Food Safety, World Health Organization, Geneva, Switzerland
Mr N. Nakashima, International Programme on Chemical Safety, World
Health Organization, Geneva, Switzerland
Mr K. Ogura, Agricultural Chemicals Inspection Station, Tokyo, Japan
(FAO Consultant)
Dr B.C. Ossendorp, Centre for Substances and Risk Assessment, National
Institute of Public Health and the Environment, Bilthoven,
Netherlands (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, Food and Agriculture
Organization of the United Nations, Rome, Italy (FAO Joint
Secretary)
Dr G. Vaagt, Pesticide Management Group, Food and Agriculture
Organization of the United Nations, Rome, Italy
Dr J. van Engelen, Centre for Substances and Risk Assessment, National
Institute of Public Health and the Environment, Bilthoven,
Netherlands (WHO Temporary Adviser)
Mr D. Wagner, Chemicals Review and International Harmonisation
Section, Chemical and Non-prescription Drugs Branch, Commonwealth
Department of Health and Family Services, Canberra, ACT,
Australia (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
AUC area under the curve
BrdU 5-bromo-2'-deoxyuridine
bw body weight
CI confidence interval
CYP cytochrome P450
DMBA 7,12-dimethylbenz[ a]anthracene
DMSO dimethyl sulfoxide
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)
GABA gamma-aminobutyric acid
GLP good laboratory practice
HPLC high-performance liquid chromatography
IARC International Agency for Research on Cancer
IC50 median inhibitory concentration
IPCS International Programme on Chemical Safety
IU international unit
JMPR Joint FAO/WHO Meeting on Pesticide Residues
LC50 median lethal concentration
LD limit of detection
LD50 median lethal dose
LOAEL lowest-observed-adverse-effect level
M male
MRL maximum residue limit
NA not analysed
NBHBA N-nitrosobutyl- N-(4-hydroxybutyl)amine
NOAEL no-observed-adverse-effect level
NOAEC no-observed-effect concentration
NR not reported
OECD Organisation for Economic Co-operation and Develeopment
PEG polyethylene glycol
ppm parts per million
QA quality assurance
S9 9000 × g supernatant fraction of rodent liver
SD Sprague-Dawley
SPF specific pathogen-free
TBPC 1-[4-(1,1-dimethylethyl)phenoxy]-2-cyclohexanol
TCP 3,5,6-trichloro-2-pyridinol
TLC thin-layer chromatography
TMRL tolerable maximum residue limit
TPA 12- O-tetradecanoylphorbol 13-acetate
USEPA US Environmental Protection Agency
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 20-29 September 1999.
One of the substances evaluated by the Core Assessment Group at
this Meeting, pyriproxyfen, was evaluated for the first time. The
other 10 substances had been evaluated at earlier meetings. For four
of these, chlormequat, glufosinate ammonium, propylene thiourea, and
pyrethrum extract, 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 chlorpyrifos, dimethipin, ethoprophos, permethrin,
2-phenylphenol and its sodium salt, and propargite, 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 153. 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 1999, 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 1999 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