PESTICIDE RESIDUES IN FOOD - 1985
Sponsored jointly by FAO and WHO
with the support of the International Programme
on Chemical Safety (IPCS)
EVALUATIONS 1985
PART II - TOXICOLOGY
Joint meeting of the
FAO Panel of Experts on Pesticide Residues
in Food and the Environment
and the
WHO Expert Group on Pesticide Residues
Geneva, 23 September - 2 October 1985
The designations employed and the presentation of material in this
publication do not imply the expression of any opinion whatsoever on
the part of the Food and Agriculture Organization of the United
Nations concerning the legal status of any country, city or area or of
its authorities, or concerning the delimitation of its frontiers or
boundaries.
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.
INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
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).
The International Programme on Chemical Safety (IPCS) is a joint
venture of the United Nations Environment Programme, the International
Labour Organisation, and the World Health Organization. One of the
main objectives of the IPCS is to carry out and disseminate
evaluations of the effects of chemicals on human health and the
quality of the environment.
M-84
ISBN 92-5-102485-5
All rights reserved. No part of this publication may be reproduced,
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reproduction, should be addressed to the Director, Publications
Division, Food and Agriculture Organization of the United Nations, Via
delle Terme di Caracalla, 00100 Rome, Italy.
(c) FAO 1986
CONTENTS
PART II: TOXICOLOGY
List of those attending the meeting
Abbreviations
Introduction
Toxicology monographs and monograph addenda
Binapacryl
Carbendazim
Chlordimeform
Chlorothalonil
Diflubenzuron
Dimethipin*
Fenamiphos
Flucythrinate*
Imazalil
Methamidophos
Omethoate
Oxamyl
2-Phenylphenol and its sodium salt
Phorate
Propineb
Thiodicarb*
Triadimefon
Vamidothion
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. Acceptable daily intakes (ADIs), Maximum residue limits
(MRLs), and Guideline levels proposed at the 1985 Meeting
* Full monograph
1985 JOINT MEETING OF THE FAO PANEL OF EXPERTS ON PESTICIDE RESIDUES
IN FOOD AND THE ENVIRONMENT AND A WHO EXPERT GROUP ON PESTICIDE
RESIDUES
Geneva, 23 September - 2 October 1985
FAO Panel of Experts on Pesticide Residues in Food and the
Environment
Dr D.C Abbott, Ashtead, United Kingdom.
Mr J.A.R. Bates, Head, Pesticide Registration Department, Ministry of
Agriculture, Fisheries and Food, Harpenden, United Kingdom
(Chairman).
Professor A.F.H. Besemer, formerly Chair of Phytopharmacy,
Agricultural University, Wageningen, The Netherlands.
Dr E. Celma-Calamita, Ministerio de Agricultura, Pesca y Alimentación,
Madrid, Spain.
Mr N.F. Ives, Environmental Protection Agency, Office of Pesticide
Programmes, Washington, D.C., USA.
Mr K. Voldum-Clausen, Division of Pesticides and Contaminants,
National Food Agency, Soborg, Denmark.
Observers invited by FAO
Dr W. Bosse, GTZ Pesticide Residue Laboratory, Darmstadt, West
Germany.
Mr A.J. Pieters, Ministry of Welfare, Health and Cultural Affairs,
Leidschendam, The Netherlands.
WHO Expert Group on Pesticide Residues
Dr V. Benes, Chief, Department of Toxicology, Institute of Hygiene and
Epidemiology, Prague, Czechoslovakia.
Dr D.J. Clegg, Head, Pesticide Section, Toxicological Evaluation
Division Food Directorate, Health Protection Branch, Ottawa,
Canada (Chairman).
Dr A.H. El-Sebae, Chairman, Pesticides Division, Faculty of
Agriculture, Alexandria University, Alexandria, Egypt.
Professor M. Lotti, Assistant Professor of Occupational Medicine,
Istituto di Medicina del Lavoro, Padua, Italy.
Dr O.E. Paynter, Chief Scientist, Hazard Evaluation Division, US
Environmental Protection Agency, Washington, D.C., USA.
Professor T.J. Pekkanen, Department of Food Hygiene, College of
Veterinary Medicine, Helsinki, Finland.
Dr R. Plestina, Director, Institute for Medical Research and
Occupational Health, Zagreb, Yugoslavia.
Professor Dr F.G. Reyes, Departamento Ciencias de Alimentos, Faculdade
de Engenharia de Alimentos e Agrícola, Universidade Estadual de
Campinas, Campinas SP, Brazil.
Secretariat
Dr A.L. Black, Medical Services Adviser, Commonwealth Department of
Health Woden, Australia (WHO Temporary Adviser).
Dr E. Budd, Supervisory Toxicologist, Hazard Evaluation Division, US
Environmental Protection Agency, Washington, D.C., USA (WHO
Temporary Adviser).
Dr J.R.P. Cabral, Unit of Mechanisms of Carcinogenesis, International
Agency for Research on Cancer, Lyon, France (WHO Temporary
Adviser).
Dr A. Di Muccio, Research Officer, Laboratorio Tossicologia Applicata,
Istituto Superiore di Sanitŕ, Rome, Italy (WHO Temporary
Adviser).
Dr M. Gilbert, Scientific Affairs Officer, IRPTC/UNEP, Geneva,
Switzerland (WHO Temporary Adviser).
Dr H. Galal Gorchev, Food Safety, Division of Environmental Health,
WHO, Geneva, Switzerland.
Dr J.L. Herman, Center for Food Safety and Applied Nutrition, Food and
Drug Administration, Washington, D.C., USA (WHO Consultant).
Mr G. van den Hurk, Technical Officer, International Programme on
Chemical Safety, Division of Environmental Health, WHO, Geneva,
Switzerland.
Dr R.B. Jaeger, Section Head, Toxicology Branch, Hazard Evaluation
Division, US Environmental Protection Agency, Washington, D.C.,
USA (WHO Temporary Adviser).
Dr F.K. Kaeferstein, Manager, Food Safety, Division of Environmental
Health, WHO, Geneva, Switzerland.
Dr F-W. Kopisch-Obuch, Pesticide Residues Specialist, Plant Protection
Service, Food and Agriculture Organization, Rome, Italy (Joint
Secretary).
Dr L.G. Ladomery, Food Standards Officer, Joint FAO/WHO Food Standards
Programme, Food and Agriculture Organization, Rome, Italy.
Mr. A.F. Machin, London, United Kingdom.
Dr M. Mercier, Manager, International Programme on Chemical Safety,
Division of Environmental Health, WHO, Geneva, Switzerland.
Dr A. Pelfrčne, Pesticides Development and Safe Use, Division of
Vector Biology and Control, WHO, Geneva, Switzerland.
Dr J.R. Plimmer, Head, Agrochemicals and Residues Section, Joint
FAO/IAEA Division, IAEA, Vienna, Austria.
Professor A. Rico, Director, I.N.R.A., Ecole National Vétérinaire,
Toulouse, France (WHO Temporary Adviser).
Professor V. Silano, Director, Department of Comparative Toxicology
and Ecotoxicology, Istituto Superiore di Sanitŕ, Rome, Italy (WHO
Temporary Adviser).
Dr A. Takanaka, Head, Division of Pharmacology, Biological Safety
Research Center, National Institute of Hygienic Sciences, Tokyo,
Japan (WHO Temporary Adviser).
Professor K. Topsy, Member Pesticide Control Board, Ministry of
Health, Beau Bassin, Mauritius (WHO Temporary Adviser).
Dr G. Vettorazzi, Senior Toxicologist, International Programme on
Chemical Safety, Division of Environmental Health, WHO, Geneva,
Switzerland (Joint Secretary).
Dr D. Wu-Lau, Scientific Adviser, Toxicological Evaluation Division,
Food Directorate, Health Protection Branch, Ottawa, Canada (WHO
Temporary Adviser).
Mr J.R. Wessel, Director, Contaminants Policy Staff, Office of
Regulatory Affairs, Food and Drug Administration, Rockville,
Maryland, USA.
ABBREVIATIONS USED IN THE MONOGRAPHS
AchE acetylcholinesterase
ADI acceptable daily intake
a.i. active ingredient
ALD acute lethal dose
ALP alkaline phosphatase
BBN N-butyl-N-(4-hydroxybutyl) nitrosamine
BSP bromosulfophathalein
BUN blood urea nitrogen
c-AMP cyclic adenosine monophosphate
c-GMP cyclic guanosine monophosphate
ChE cholinesterase
CHO Chinese hampster ovary
CNS central nervous system
DMBA 7, 12-dimethylbenz(a)anthracene
DMCF dimethylcyanoformamide
DMSO dimethylsulfoxide
ETU ethylene thiourea
FAO Food and Agriculture Organization of the United Nations
G.I. gastrointestinal
GLDH glutamate dehydrogenase
GOT glutamate-oxoloacetate transaminase
GPT glutamate-pyruvate transaminase
GSH glutathione
Hb haemoglobin
hr. hour
I50 inhibition, median
IARC International Agency for Research on Cancer
IBT Industrial Bio-test Laboratories, Inc.
i.m. intramuscular
i.p. intraperitoneal
IPCS International Programme on Chemical Safety
i.v. intravenous
JMPR Joint FAO/WHO Meeting on Pesticide Residues (Joint Meeting
of the FAO Panel of Experts on Pesticide Residues in Food
and the Environment and a WHO Expert Group on Pesticide
Residues)
kg kilogram
LD50 lethal dose, median
LDH lactate dehydrogenase
MFO mixed function oxidase
µg microgram
µl microlitre
µM micromolar
mg milligram
ml millilitre
mM millimolar
MTD maximum tolerated dose
NADPH nicotinamide adenine dinucleotide phosphate
NCI National Cancer Institute (United States)
NOEL no-observed-effect-level
NTE neurotoxic esterase
OP organophosphate
OPP 2-phenylphenol (o-phenylphenol)
2-PAM 2-pyridine aldoxine melthiodide (pralidoxime)
PBI protein-bound iodine
PEG polyethylene glycol
PN papillary/nodulary hyperplasia
ppm parts per million
PSP phenosulfophthalein
PTU propylene thiourea
RBC red blood cell
SCE sister chromatid exchange
SOPP sodium 2-phenylphenate (sodium o-phenylphenol)
T3 triiodothyronine
T4 tetraiodothyronine
TADI temporary acceptable daily intake
TOCP tri-o-cresyl phosphate
TOTP tri-o-tolyl phosphate
TPA 12-o-tetradecanoylphorbol-13-acetate
UDS unscheduled DNA synthesis
USDA United States Department of Agriculture
WBC white blood cell
WHO World Health Organization
w/v weight/volume
INTRODUCTION
The toxicology monographs and monograph addenda contained in this
volume were prepared by a WHO Expert Group on Pesticide Residues 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, 23 September to 2 October 1985. These monographs
summarize the safety data on those pesticide residues for which
sufficient information was provided to the WHO Expert Group for it to
make decisions regarding acceptable daily intakes.
Most of the compounds considered by the WHO Expert Group at this
Meeting had been evaluated at previous meetings and monographs on them
have been published previously. In such cases, only new information is
summarized in the relevant "monograph addenda". Reference is made to
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, which are
listed in Annex 1. The appropriate documents should be consulted to
obtain a full toxicological profile of the chemicals under
consideration.
The report of the Joint Meeting has been published by the Food
and Agriculture Organization (FAO) of the United Nations as the FAO
Plant Production and Protection Paper No. 68. The report contains
brief comments on the compounds under consideration, acceptable daily
intakes established by the WHO Expert Group, and maximum residue
limits or guideline levels established by the FAO Panel of Experts.
Residues monographs prepared by the FAO Panel of Experts have been
published as a companion volume to this one, Evaluations 1985, Part I
- Residues, as the FAO Plant Production and Protection Paper No. 72/1
The toxicology monographs and monograph addenda contained in this
volume are based upon working papers that were prepared by temporary
advisers in advance of the 1985 Joint Meeting. A special
acknowledgement is given to those who prepared these working papers,
Dr A.L. Black, Commonwealth Department of Health, Woden, Australia;
Dr E. Budd, U.S. Environmental Protection Agency, Washington, DC, USA;
Dr A. DiMuccio, Istituto Superiore di Sanitŕ, Rome, Italy; Dr R.B.
Jaeger, U.S. Environmental Protection Agency, Washington, DC, USA; and
Dr D. Wu-Lau, Food Directorate, Health Protection Branch, Ottawa,
Ontario, Canada.
The preparation and editing of the monographs included in this
volume have been made possible through the technical and financial
contributions of the lead Institutions of the International Programme
on Chemical Safety (IPCS), which support the activities of 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 its authorities, or
concerning the delimitation of its frontiers or boundaries. The
mention of specific companies or of certain maufacturers' 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 biological or
toxicological data on the compounds reported in this document 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.