PESTICIDE RESIDUES IN FOOD - 1995
Sponsored jointly by FAO and WHO
with the support of the International Programme
on Chemical Safety (IPCS)
EVALUATIONS 1995
PART II - TOXICOLOGY AND ENVIRONMENTAL
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, 18-27 September 1995
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.
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
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.
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TABLE OF CONTENTS
List of participants
Abbreviations
Introduction
Toxicological evaluations
Benomyl
Captan (addendum)
Carbendazim
Fenarimol*
Fenpyroximate*
Fenthion
Flusilazole
Folpet
Haloxyfop*
Iprodione (addendum)
Monocrotophos (addendum)
Parathion (addendum)
Parathion-methyl (addendum)
Piperonyl butoxide
Quintozene
Thiophanate-methyl
Vinclozolin
Environmental evaluations
Carbendazim, benomyl, and thiophanate-methyl
Fenarimol
Fenthion
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
Annex II. Corrigenda to previous JMPR toxicological evaluations
* First full evaluation
1995 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, 18-27 September 1995
PARTICIPANTS
Toxicological Core Assessment Group
Dr A.L. Black, Medical Services Adviser in Toxicology, Department of
Human Services and Health, Canberra ACT, Australia
Professor J.F. Borzelleca, Pharmacology, Toxicology, Medical College
of Virginia, Virginia Commonwealth University, Richmond, VA,
United States (Chairman)
Dr P. Fenner-Crisp, Acting Deputy Director, Office of Pesticide
Programs, US Environmental Protection Agency, Washington DC,
United States (Rapporteur)
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
Professor A. Rico, Biochemistry-Toxicology, Physiopathology and
Experimental Toxicology Laboratory, Ecole Nationale Vétérinaire,
Toulouse, France
Dr P.-P. Yao, Professor of Toxicology, Institute of Occupational
Medicine, Ministry of Health, Beijing, China
Environmental Core Assessment Group
Professor D. Calamari, III Faculty of Sciences, University of Milan,
Varese, Italy
Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood,
Huntingdon, Cambridgeshire, United Kingdom (Vice-Chairman)
Dr P.E.T. Douben, Her Majesty's Inspectorate of Pollution, London,
United Kingdom (Rapporteur)
Dr J. Herkovits, Programa Seguridad Quimica, Instituto de Ciencias
Ambientales y Salud, Buenos Aires, Argentina
Dr L. Samsoe-Petersen, VKI Water Quality Institute, Horsholm, Denmark
Dr J.H.M. Temmink, Department of Toxicology, Wageningen Agricultural
University, Wageningen, Netherlands
FAO Expert Group on Pesticide Residues
Dr A. Ambrus, Budapest Plant Health and Soil Conservation Station,
Budapest, Hungary (Rapporteur)
Dr U. Banasiak, Federal Biological Research Centre for Agriculture and
Forestry, Kleinmachnow, Germany
Mr S. Crossley, Pesticide Safety Division, Kings Pool, York, United
Kingdom
Mr D.J. Hamilton, Department of Primary Industries, Indooroopilly,
Brisbane, Queensland, Australia
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 Ganaderia,
Agricultura y Pesca, Montevideo, Uruguay
Dr D. Murphy, National Registration Authority, Canberra ACT, Australia
Mr T. Sakamoto, Plant Protection Division, Ministry of Agriculture,
Forestry and Fisheries, Tokyo, Japan
Secretariat
Dr E. Bosshard, Federal Office of Public Health, Food Science
Division, Schwerzenbach, Switzerland (WHO Temporary Adviser)
Dr G. Burin, Technology Sciences Group, Washington DC, United States
(WHO 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 W.H. van Eck, Food and Product Safety 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 R. Hailey, Environmental Toxicology Program, National Institute of
Environmental Health Sciences, Research Triangle Park, North
Carolina, United States (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 Consultant)
Mrs P.H. van Hoeven-Arentzen, National Institute of Public Health and
Environmental Protection, Bilthoven, Netherlands (WHO Temporary
Adviser)
Dr F.-W. Kopisch-Obuch, Pesticide Group, Plant Protection Service,
Food and Agricultural Organization, Rome, Italy (FAO Joint
Secretary)
Dr J.-J. Larsen, Head, Department of General Toxicology, Institute of
Toxicology, National Food Agency of Denmark, Soborg, Denmark
(WHO Temporary Adviser)
Dr J.B.H.J. Linders, National Institute of Public Health and
Environmental Protection, Bilthoven, Netherlands (WHO Temporary
Adviser)
Dr S. Ma, Health Evaluation Division, Pest Management Regulatory
Agency, Tunney's Pasture, Ottawa, Ontario, Canada (WHO
Temporary Adviser)
Mr A.F. Machin, London, United Kingdom (FAO Consultant)
Dr D. McGregor, Unit of Carcinogen Identification and Evaluation,
International Agency for Research on Cancer, Lyon, France
Dr M. Morrow, Health Effects Division, Office of Pesticide Programs,
Environmental Protection Agency, Washington DC, United States
(WHO Temporary Adviser)
Dr G. Moy, Food Safety Unit, Division of Food and Nutrition, World
Health Organization, Geneva, Switzerland
Mr R.C. Petrie, Ecological Effects Branch, Environmental Fate and
Effects Division, Environmental Protection Agency, Washington DC,
United States (WHO Temporary Adviser)
Dr R. Plestina, Poisonings Prevention and Treatment, International
Programme on Chemical Safety, World Health Organization, Geneva,
Switzerland
Dr E.M.B. Smith, Assessment of Risk and Methodologies, International
Programme on Chemical Safety, World Health Organization, Geneva,
Switzerland
Mrs A. Sundén-Byléhn, International Register of Potentially Toxic
Chemicals, United Nations Environment Programme, Châtelaine,
Switzerland
Dr G. Vettorazzi, International Toxicology Information Centre, San
Sebastian, Spain (WHO Temporary Adviser)
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, 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
a.i. active ingredient
BrDU 5-bromo-2'- deoxyuridine
bw body weight
CCPR Codex Committee on Pesticide Residues
CKD cyclin-dependent kinase
DMSO dimethyl sulfoxide
DT50 dissipation half-life
EC50 median effective concentration in relation to a 50% change
in a parameter or to a concentration causing a particular
effect in 50% of the tested population
F0 parental generation
F1 first filial generation
F2 second filial generation
5-HBC 5-hydroxybenzimidazol-2-ylcarbamate
hCG human chorionic gonadotropin
HPLC high-performance liquid chromatography
hprt hypoxanthine-guanine phosphoribosyl transferase gene
IIPCS 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
MATC maximal acceptable toxicant concentration
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
NOEC no-observed-effect concentration
NR not reported
P450 cytochrome P450
PCNA proliferating cell nuclear antigen
PEC predicted environmental concentration
ppm parts per million
S9 9000 × g supernatant fraction
SD standard deviation
TER toxicity:exposure ratio
TLC thin-layer chromatography
TOCP tri- ortho-cresol phosphate
Tween 80 polyoxyethylenesorbitan monooleate
v/v volume per volume
WP wettable powder
w/v weight per volume
w/w weight per weight
Introduction
The toxicological and environmental 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 Geneva, Switzerland, on 18-27 September 1995.
Fourteen of the compounds considered by the WHO Expert Group at
this Meeting had been evaluated at earlier meetings. For five of
these, captan, iprodione, monocrotophos, parathion, and parathion-
methyl, only information received since the previous evaluation is
summarized, in 'monograph addenda'. The appropriate earlier documents
should be consulted in order to obtain a full toxicological profile of
these chemicals. In the cases of benomyl, carbendazim, fenthion,
flusilazole, folpet, piperonyl butoxide, quintozene, thiophanate-
methyl, and vinclozolin, toxicological monographs were prepared,
summarizing new data and incorporating information from previous
monographs and addenda. 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 are listed in Annex I. Toxicological monographs
summarizing all of the available information were prepared on the
pesticides evaluated for the first time (fenarimol, fenpyroximate, and
haloxyfop).
For the first time, environmental evaluations were made for
certain of the pesticides covered in this document. An Environmental
Core Assessment Group thus met concurrently with the other two groups
to evaluate the related compounds carbendazim, benomyl, and
thiophanate-methyl, and also fenarimol and fenthion for environmental
effects.
The report of the Joint Meeting has been published by the FAO as
FAO Plant Production and Protection Paper No. 133. 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 1995, 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 1995 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 ad dressed 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