PESTICIDE RESIDUES IN FOOD - 1991
JOINT FAO/WHO MEETING ON PESTICIDE RESIDUES
EVALUATIONS 1991
PART II - TOXICOLOGY
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 Expert Group on Pesticide Residues
Geneva, 16-25 September 1991
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.
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.
IPCS gratefully acknowledges the assistance of Dr. G. Burin, and Mr.
D. Schutz U.S. Environmental Protection Agency, for editing these
monographs.
ISBN 92 4 166507 6
(c) World Health Organization 1992
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The designations employed and the presentation of the material in
this publication do not imply the impression of any opinion whatsoever
on the part of the Secretariat of the World Health Organization
concerning the legal status of every country, territory, city, or area
or of its authorities, or 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
World Health Organization in preference to others of a similar nature
that are not mentioned. Errors and omissions excepted, the names of
proprietary products are distinguished by initial capital letters.
TABLE OF CONTENTS
List of those attending the meeting
Abbreviations
Introduction
The Monographs
Azinphos-methyl
* Bentazone
Bioresmethrin
* Buprofezin
* Cadusafos
Chlorpyrifos-methyl
Cyhexatin
Daminozide
Disulfoton
Fentin
* Glufosinate-ammonium
Heptachlor
* Hexythiazox
Imazalil
Monocrotophos
Triazophos
ANNEX I 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
1991 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, 16-25 September 1991
PARTICIPANTS
WHO Expert Group on Pesticide Residues
Prof. U.G. Ahlborg, Head, Unit of Toxicology, Karolinska Institute,
Institute of Environmental Medicine, Stockholm, Sweden
Dr A.L. Black, Medical Services Adviser in Toxicology, Department
of Health, Housing and Community Services, Canberra, Australia
(Rapporteur)
Dr J.F. Borzelleca, Professor, Pharmacology, Toxicology, Medical
College of Virginia, Virginia Commonwealth University, Richmond,
Virginia, USA
Mr D.J. Clegg, Head, Agricultural Chemicals Section, Toxicological
Evaluation Division, Health Protection Branch, Health and
Welfare Canada, Ottawa, Ontario, Canada (Chairman)
Prof. M. Lotti, Universitŕ di Padova, Istituto di Medicina del Lavoro,
Padua, Italy
Dr F.R. Puga, Head, Section of Toxicology, Instituto Biolňgico, Sao
Paulo, Brazil
Dr P. Yao, Vice-Director, Professor of Toxicology, Institute of
Occupational Medicine, CAPM, Ministry of Public Health, Beijing,
China
FAO Members
Dr A. Ambrus, Budapest Plant Health and Soil Conservation Station,
Budapest, Hungary (Rapporteur)
Prof. A.F.H. Besemer, Formerly Chair of Phytopharmacy, Agricultural
University, Wageningen, Netherlands
Dr D. Hamilton, Assistant Director, Agricultural Chemistry Branch,
Agricultural Research Laboratories, Department of Primary
Industries, Brisbane, Queensland, Australia (Chairman)
Mr F. Ives, Health Effects Division, US Environmental Protection
Agency, Washington, D.C., USA
Dr J.-R. Lundehn, Federal Biological Research Centre for
Agriculture and Forestry, Braunschweig, Germany
Dr K. Voldum-Clausen, Ministry of Health, National Food Agency of
Denmark, Soborg, Denmark
Mr W. Zhuang, Associate Professor, Head of the Department of
Research Chemicals, China Import & Export, Commodity Inspection
Institute, Beijing, China
Secretariat
Dr E. Bosshard, Fed. Office of Public Health, Division of Food
Science, c/o Institute of Toxicology, Zürich, Switzerland
(WHO Temporary Adviser)
Dr G. Burin, Health Effects Division, Office of Pesticide Programs,
US Environmental Protection Agency, Washington, D.C., USA
(WHO Temporary Adviser)
Dr S. Caroldi, Universitŕ di Padova, Istituto di Medicina del
Lavoro, Padua, Italy (WHO Temporary Adviser)
Dr E. Casadei, Joint FAO/WHO Food Standards Programme, Food and
Agriculture Organization, Rome, Italy
Dr W.H. van Eck, Food and Product Safety Division, Ministry of
Welfare, Health and Cultural Affairs, Rijswijk, Netherlands
(Chairman, Codex Committee on Pesticide Residues)
Dr P. Fenner-Crisp, Director, Health Effects Division, Office of
Pesticide Programs, Environmental Protection Agency, Washington,
D.C., USA (WHO Temporary Adviser)
Dr H. Galal-Gorchev, International Programme on Chemical Safety,
Division of Environmental Health, World Health Organization,
Geneva, Switzerland
Dr J.L. Herrman, International Programme on Chemical Safety,
Division of Environmental Health, World Health Organization,
Geneva, Switzerland (WHO Joint Secretary)
Dr F.-W. Kopisch-Obuch, Pesticide Residues Specialist, Plant
Protection Service, Food and Agriculture Organization, Rome,
Italy (FAO Joint Secretary)
Mr A.F. Machin, London, UK (FAO Consultant)
Dr T.C. Marrs, Medical Toxicology and Environmental Health,
Department of Health, London, UK (WHO Temporary Adviser)
Dr D. McGregor, Unit of Carcinogen Identification and Evaluation,
International Agency for Research on Cancer, Lyon, France
Dr O. Meyer, Ministry of Health, National Food Agency of Denmark,
Institute of Toxicology, Soborg, Denmark (WHO Temporary
Adviser)
Mr B. Murray, Bureau of Chemical Safety, Health Protection Branch,
Health and Welfare Canada, Ottawa, Ontario, Canada
(FAO Consultant)
Dr W. Phang, Senior Toxicologist, Health Effects Division, Office
of Pesticide Programs, US Environmental Protection Agency,
Washington, D.C., USA (WHO Temporary Adviser)
Dr R. Plestina, International Programme on Chemical Safety,
Division of Environmental Health, WHO, Geneva, Switzerland
Mr D. Schutz, Office of Toxic Substances, US Environmental
Protection Agency, Washington, D.C. USA (WHO Consultant)
Dr A. Takanaka, Head, Division of Pharmacology, Biological Safety
Research Center, National Institute of Hygienic Sciences, Tokyo,
Japan (WHO Temporary Adviser)
Dr E.M. den Tonkelaar, Toxicologist, Toxicology Advisory Centre,
National Institute of Public Health and Environmental
Protection, Bilthoven, The Netherlands (WHO Temporary Adviser)
Mr M. Walsh, Administrator EEC, Législation des produits végétaux
et de nutrition animale, Brussels, Belgium
Mr M. Watson, Head, Risk Evaluation Branch, Pesticide Safety
Division, Ministry of Agriculture Fisheries and Food,
Rothamsted, Harpenden, Herts, UK (WHO Temporary Adviser)
ABBREVIATIONS USED IN THESE MONOGRAPHS
ACH acetylcholine
AChE acetylcholinesterase
ADP adenosine diphosphate
A/G albumin/globulin ratio
a.i. active ingredient
ALAT alanine aminotransferase
ALD50 approximate median lethal dose, 50%
ALP alkaline phosphatase
ASAT aspartate aminotransferase
ATP adenosine triphosphate
BSP bromosulfophthalein
BUN blood urea nitrogen
cf confer, compare to
ChE cholinesterase
CMC carboxymethylcellulose
CNS central nervous system
DMPT dimethyl phosphorothioate
DMSO dimethylsulfoxide
DNA deoxyribonucleic acid
DOTDC dioctyltindichloride
DTH delayed-type hypersensitivity
EC emulsifiable concentrate
EL emulsifiable liquid
F0 parental generation
F1 filial generation, first
F2 filial generation, second
GGT alpha-glutamyltransferase
G.I. gastrointestinal
GIT gastrointestinal tract
GOT glutamate-oxoloacetate transaminase
GPT glutamate-pyruvate transaminase
GSH reduced glutathione
GSSG oxidized glutathione
GST glutathione-S-transferase
GTP alpha-glutamyltranspeptidase
Hb haemoglobin
HCG human chorionic gonadotropin
HGRPT hypoxanthine-guanine phosphoribosyl transferase
HPLC high pressure liquid chromatography
Ht haematocrit
I50 inhibitory dose, 50%
IBT Industrial Bio-Test Laboratories, Inc.
i.m. intramuscular
inh inhalation
i.p. intraperitoneal
LC50 lethal concentration, median
LD50 lethal dose, median
LOAEL lowest-observed-adverse-effect-level
m metre
M molar
MCH mean corpuscular haemoglobin
MCHC mean corpuscular haemoglobin concentration
MCV mean corpuscular volume
MFO mixed function oxidase(s)
ml milliliter
MTD maximum tolerated dose
n.d.r. not dose-related
NOAEL no-observed-adverse-effect level
NTE neurotoxic target esterase
2-PAM 2-pralidoxime
PCV haematocrit (packed corpuscular volume)
p.o. by mouth
POSO disulfoton oxygen analog sulfoxide
POSO2 disulfoton oxygen analog sulfone
PSP phenolsulfophthalein
PrT prothrombin time
PSSO2 disulfoton sulfone
PT thromboplastin time
PTT partial thromboplastin time
PTU propyl-thionracil
RBC red blood cell
RNA ribonucleic acid
SAP serum alkaline phosphatase
SGOT serum GOT
SGPT serum GPT
SPF specific pathogen free
T3 tri-iodothyronine
T4 thyroxine
TLC thin layer chromatography
TMPO trimethylphosphate
TOCP tri-ortho-cresyl phosphate
TPTA triphenyltinacetate
TPTCl triphenyltinchloride
TPTH triphenyltinhydroxide
TWA time weighted average
UDS unscheduled DNA synthesis
WBC white blood cell
WD wettable dust
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, 16 September to 25 September 1991. 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 only new
information is summarized in the relevant "monograph addenda". In the
case of coumaphos, a previously prepared monograph addendum which was
not published has been included with new information. In the case of
terbufos, the monograph prepared for the 1989 meeting is published in
its entirety. 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 FAO Plant
Production and Protection Paper No. 111. 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 1991, Part I
Residues, in the FAO Plant Production and Protection Paper series.
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 1991 Joint Meeting. A special
acknowledgement is given to those who prepared these working papers.
The monographs were edited by Dr G. Burin of US Environmental
Protection Agency, Washington D.C.
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 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 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.