PESTICIDE RESIDUES IN FOOD - 1996
Sponsored jointly by FAO and WHO
with the support of the International Programme
on Chemical Safety (IPCS)
EVALUATIONS - 1996
PART II - TOXICOLOGY
Joint meeting of the
FAO Panel of Experts on Pesticide Residues
in Food and the Environment
and the
WHO Core Assessment Group
Rome 15-25 September, 1996
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 and environmental
evaluations of pesticides carried out by the WHO Core Assessment Group
for consideration by the Joint FAO/WHO 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.
IPCS gratefully acknowledges the assistance of Mrs. E. Heseltine, St.
Léon-sur-Vézère, France, for editing these monographs.
The summaries and evaluations contained in this books are, in most
cases, based on unpublished data submitted for the purpose of the
JMPR assessment. A registration authority should not grant a
registration on the basis on 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.
ISBN 92 4 1665 12 2
(c) World Health Organization 1997
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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.
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products does not imply that they are endorsed or recommended by the
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TABLE OF CONTENTS
List of participants
Abbreviations
Introduction
Toxicological evaluations
Carbaryl
Carbofuran
2,4-Dichlorophenoxyacetic acid (2,4-D)
Dimethoate
Ferbam
Flumethrin*
Maleic hydrazide
Mevinphos
Phorate (addendum)
Tebufenozide*
Ziram
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
1996 Joint Meeting of the FAO Panel of Experts on Pesticide Residues
in Food and the Environment and the WHO Core Assessment Group
Rome, 16-25 September 1996
PARTICIPANTS
Toxicological Core Assessment Group
Professor J.F. Borzelleca, Pharmacology, Toxicology, Medical College
of Virginia, Virginia Commonwealth University, Richmond, VA, United
States (Vice-Chairman)
Dr P. Fenner-Crisp, Deputy Director, Office of Pesticide Programs, US
Environmental Protection Agency, Washington DC, United States
(Vice-Chairman)
Dr M. Joffe, Department of Epidemiology and Public Health, Imperial
College of Medicine at St Mary's, London, United Kingdom
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 (Rapporteur)
Professor A. Rico, Biochemistry-Toxicology, Physiopathology and
Experimental Toxicology Laboratory (INRA), Ecole Nationale
Vétérinaire, Toulouse, France
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
Mr S. Crossley, Pesticide Safety Directorate, Ministry of Agriculture,
Fisheries and Food, Kings Pool, York, United Kingdom
Mr D.J. Hamilton, Department of Natural Resources, Resource Sciences
Centre, Indooroopilly, Brisbane, Queensland, Australia
(Rapporteur)
Mr N.F. Ives, Health Effects Division, US Environmental Protection
Agency, Washington DC, United States (Chairman)
Mrs E. Masoller, Servicios de Laboratorios, Ministerio de Ganadería,
Agricultura y Pesca, Montevideo, Uruguay
Mr T. Sakamoto, Agricultural Chemicals Inspection Station, Ministry of
Agriculture, Forestry and Fisheries, Tokyo, Japan
Secretariat
Dr A. Ambrus, Pesticide Group, Plant Protection Service, Food and
Agricultural Organization, Rome, Italy (FAO Joint Secretary)
Dr E. Bosshard, Wettswil, Switzerland (WHO Temporary Adviser)
Dr W.H. van Eck, Public Health Division, 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, Ministry of Health
and Welfare, Tokyo, Japan (WHO Temporary Adviser)
Dr D.L. Grant, Health Evaluation Division, Health Canada, Tunney's
Pasture, Ottawa, Ontario, Canada (WHO Temporary Adviser)
Dr R.J. Hance, Pesticides Section, Joint FAO/IAEA Division, Vienna,
Austria
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 Consultant)
Mrs P.H. van Hoeven-Arentzen, National Institute of Public Health and
Environment, Bilthoven, Netherlands (WHO Temporary Adviser)
Dr F.-W. Kopisch-Obuch, Pesticide Group, Plant Protection Service,
Food and Agricultural Organization, Rome, Italy
Dr J.-J. Larsen, Department of General Toxicology, Institute of
Toxicology, National Food Agency of Denmark, 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, Food Safety Unit, Division of Food and Nutrition, World
Health Organization, Geneva, Switzerland
Dr J.C. Rowland, Toxicology Branch II, Health Effects Division, US
Environmental Protection Agency, Washington DC, USA (WHO
Temporary Adviser)
Dr G. Vettorazzi, International Toxicology Information Centre, San
Sebastian, Spain (WHO Temporary Adviser)
Mr M. Walsh, Commission of the European Communities, Législation des
produits végétaux et de nutrition animale, VI/B/II.1, Brussels,
Belgium
Mr M. Watson, Risk Evaluation Branch, Pesticides Safety Directorate,
Ministry of Agriculture, Fisheries and Food, Kings Pool, York,
United Kingdom (WHO Temporary Adviser)
Dr Y. Yamada, 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
ADP adenosine diphosphate
AMP adenosine monophosphate
ATP adenosine triphosphate
AUC area under the curve
bw body weight
CCPR Codex Committee on Pesticide Residues
CI confidence interval
DMSO dimethyl sulfoxide
EEG electroencephalogram
EMG electromyogram
F0 parental generation
F1 first filial generation
F2 second filial generation
GC-MS gas chromatography-mass spectrometry
HPLC high-performance liquid chromatography
hprt hypoxanthine-guanine phosphoribosyl transferase gene
IC50 median inhibitory dose
IPCS International Programme on Chemical Safety
JECFA Joint FAO/WHO Expert Committee on Food Additives
JMPR Joint FAO/WHO Meeting on Pesticide Residues
LC50 median lethal concentration
LD50 median lethal dose
LOAEL lowest-observed-adverse-effect level
NAD nicotinamide adenine dinucleotide
NADH+ reduced nicotinamide adenine dinucleotide
NADP nicotinamide adenine dinucleotide phosphate
NADPH+ reduced nicotinamide adenine dinucleotide phosphate
NOAEL no-observed-adverse-effect level
NR not reported
OECD Organisation for Economic Co-operation and Development
OR odds ratio
P450 cytochrome P450
ppm parts per million
RR relative risk
S9 9000 × g supernatant fraction
SD standard deviation
TLC thin-layer chromatography
TOCP tri-ortho-cresyl phosphate
v/v volume per volume
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 Rome,
Italy, on 16-25 September 1996.
Nine of the compounds considered by the WHO Core Assessment
Group at this Meeting had been evaluated at earlier meetings. For
one of these, phorate, only information received since the previous
evaluation is summarized, in a 'monograph addendum'. The appropriate
earlier documents should be consulted in order to obtain a full
toxicological profile of this chemical. Toxicological monographs
were prepared on carbaryl, carbofuran, 2,4-D, dimethoate, ferbam,
flumethrin, maleic hydrazide, mevinphos, tebufenozide, and ziram,
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 will be published by the FAO
in the FAO Plant Production and Protection Paper series. The 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 1996, Part I,
Residues, in the FAO Plant Production and Protection Paper series.
The toxicological monographs and addendum contained in this
volume are based on working papers that were prepared by temporary
advisers before the 1996 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