Cypermethrin (EHC 82, 1989)

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

ENVIRONMENTAL HEALTH CRITERIA 82

CYPERMETHRIN

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policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization.

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the International Labour Organisation,
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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR CYPERMETHRIN

INTRODUCTION

1. SUMMARY

1.1. General
1.2. Environmental transport, distribution, and transformation
1.3. Environmental levels and human exposure
1.4. Kinetics and metabolism
1.5. Effects on organisms in the environment
1.6. Effects on experimental animals and in vitro test systems
1.7. Mechanism of toxicity
1.8. Effects on man

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

2.1. Identity
2.2. Physical and chemical properties
2.3. Analytical methods

3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1. Industrial production
3.2. Use patterns

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

4.1. Transport and distribution between media
4.1.1. Transport from soil to water
4.1.2. Transport within water bodies
4.2. Abiotic degradation
4.2.1. Photodegradation
4.2.1.1 Basic studies
4.2.1.2 Photodegradation
4.3. Biological degradation in soil
4.3.1. Mechanism
4.3.2. Degradation pathways (separate isomers)
4.3.3. Rates of degradation
4.3.3.1 Laboratory studies (separate isomers)
4.3.3.2 Field studies
4.4. Degradation in water and sediments
4.4.1. Laboratory studies
4.4.2. Field studies
4.5. Bioaccumulation and biomagnification
4.5.1. n-Octanol water-partition coefficient
4.5.2. Bioaccumulation in fish
4.5.3. Bioaccumulation in aquatic invertebrates

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

5.1. Environmental levels
5.1.1. Air
5.1.2. Water
5.1.3. Soil
5.1.4. Food
5.1.4.1 Residues in food commodities from
treated crops
5.1.4.2 Residues in food of animal origin
5.2. General population exposure
5.3. Occupational exposure

6. KINETICS AND METABOLISM

6.1. Absorption, excretion, and distribution
6.1.1. Oral
6.1.1.1 Rat
6.1.1.2 Mouse
6.1.1.3 Dog
6.1.1.4 Cow
6.1.1.5 Sheep
6.1.1.6 Chicken
6.1.1.7 Man
6.1.2. Dermal
6.1.2.1 Cow
6.1.2.2 Sheep
6.1.2.3 Man
6.2. Metabolic transformation
6.2.1. In vitro studies
6.2.2. In vivo studies
6.2.3. Metabolism of the glucoside conjugate of
3-phenoxybenzoic acid
6.3. Metabolism in plants
6.4. Metabolism in fish

7. EFFECTS ON ORGANISMS IN THE ENVIRONMENT

7.1. Microorganisms
7.2. Aquatic organisms
7.2.1. Fish
7.2.1.1 Acute toxicity
7.2.1.2 Long-term toxicity
7.2.2. Invertebrates
7.2.2.1 Acute toxicity
7.2.2.2 Long-term toxicity
7.2.3. Field studies
7.2.3.1 Deliberate overspraying
7.2.3.2 Monitoring of drift from ground
and aerial applications
7.3. Terrestrial organisms
7.3.1. Laboratory studies
7.3.1.1 Acute toxicity
7.3.1.2 Short-term toxicity

7.3.2. Field studies
7.3.2.1 Applications for tsetse fly control in
Nigeria
7.3.2.2 Honey bees
7.3.2.3 Soil fauna
7.3.2.4 Foliar predators and parasites

8. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS

8.1. Single exposures
8.1.1. Oral
8.1.2. Dermal
8.1.3. Intraperitoneal
8.1.4. Inhalation
8.1.5. Skin and eye irritation
8.1.6. Sensitization
8.2. Short-term exposures
8.2.1. Oral
8.2.1.1 Rat
8.2.1.2 Dog
8.2.2. Dermal
8.2.2.1 Rabbit
8.2.3. Intravenous
8.2.3.1 Rat
8.3. Long-term exposures
8.3.1. Rat
8.3.2. Mouse
8.3.3. Dog
8.4. Special studies
8.4.1. Synergism/potentiation studies
8.4.1.1 Organophosphate mixture
8.4.1.2 Organochlorine mixture
8.4.2. Neurotoxicity
8.4.2.1 Characterization of the neurotoxic
effects
8.4.2.2 Neuropathological studies
8.4.2.3 Biochemical and electro-physiological
studies
8.4.2.4 Appraisal
8.4.3. Immunosuppressive action
8.5. Reproduction, embryotoxicity, and teratogenicity
8.5.1. Reproduction
8.5.2. Embryotoxicity and teratogenicity
8.5.2.1 Rat
8.5.2.2 Rabbit
8.6. Mutagenicity and related end-points
8.6.1. In vitro studies
8.6.1.1 Microorganisms
8.6.1.2 Mammalian cells
8.6.2. In vivo studies
8.6.2.1 Host-mediated assay
8.6.2.2 Dominant lethal assay
8.6.2.3 Bone marrow chromosome study
8.6.2.4 Micronucleus test
8.7. Carcinogenicity
8.7.1. Oral
8.7.1.1 Rat
8.7.1.2 Mouse
8.8. Mechanisms of toxicity - mode of action

9. EFFECTS ON MAN

9.1. General population exposure
9.1.1. Acute toxicity: poisoning incidents
9.1.2. Controlled human studies
9.1.3. Epidemiological studies
9.2. Occupational exposure
9.2.1. Acute toxicity: poisoning incidents
9.2.2. Effects of short- and long-term exposure

10. EVALUATION OF HEALTH RISKS FOR MAN AND EFFECTS ON THE
ENVIRONMENT

10.1. Evaluation
10.2. Conclusions

11. RECOMMENDATIONS

12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

REFERENCES

APPENDIX

WHO TASK GROUP MEETING ON ENVIRONMENTAL HEALTH CRITERIA FOR CYPERMETHRIN

Members

Dr L. Albert, Environmental Pollution Programme, National
Institute of Biological Resource Research, Veracruz, Mexico

Dr E. Budd, Office of Pesticide Programs, US Environmental
Protection Agency, Washington DC, USA

Mr T.P. Bwititi, Ministry of Health, Causeway, Harare, Zimbabwe

Dr S. Deema, Ministry of Agriculture and Cooperatives, Bangkok
Thailand

Dr I. Desi, Department of Hygiene & Epidemiology, Szeged
University Medical School, Szeged, Hungary

Dr A.K.H. El Sebae, Pesticides Division, Faculty of
Agriculture, Alexandria University, Alexandria, Egypt

Dr R. Goulding, Keats House, Guy's Hospital, London, United
Kingdom (Chairman)

Dr J. Jeyaratnam, National University of Singapore, Department
of Social Medicine & Public Health, Faculty of Medicine,
National University Hospital, Singapore (Vice-Chairman)

Dr Y. Osman, Occupational Health Department, Ministry of Health
Khartoum, Sudan

Dr A. Takanaka, Division of Pharmacology, National Institute
of Hygienic Sciences, Tokyo, Japan

Representatives of Other Organizations

Dr Nazim Punja, European Chemical Industry, Ecology &
Toxicology Centre, (ECETOC), Brussels, Belgium

Miss J. Shaw, International Group of National Associations
of Manufacturers of Agrochemical Products (GIFAP), Brussels,
Belgium

Secretariat

Dr M. Gilbert, United Nations Environment Programme,
International Register of Potentially Toxic Chemicals,
Geneva, Switzerland

Dr T. Ng, Office of Occupational Health, World Health
Organization, Geneva, Switzerland

Dr G. Quélennec, Pesticides Development & Safe Use Unit,
World Health Organization, Geneva, Switzerland

Secretariat (contd.)

Dr G.J. van Esch, Bilthoven, The Netherlands (Temporary
Adviser) (Rapporteur)

Dr E.A.H. van Heemstra-Lequin, Laren, The Netherlands
(Temporary Adviser)

Dr K.W. Jager, International Programme on Chemical Safety,
Division of Environmental Health, World Health Organization
Geneva, Switzerland (Secretary)

Dr R.C. Tincknell, Beaconsfield, Buckinghamshire, United
Kingdom (Temporary Adviser) (Rapporteur)

NOTE TO READERS OF THE CRITERIA DOCUMENTS

Every effort has been made to present information in the
criteria documents as accurately as possible without unduly
delaying their publication. In the interest of all users of the
environmental health criteria documents, readers are kindly
requested to communicate any errors that may have occurred to the
Manager of the International Programme on Chemical Safety, World
Health Organization, Geneva, Switzerland, in order that they may be
included in corrigenda, which will appear in subsequent volumes.

* * *

A detailed data profile and a legal file can be obtained from
the International Register of Potentially Toxic Chemicals, Palais
des Nations, 1211 Geneva 10, Switzerland (Telephone No. 988400 -
985850).

* * *

NOTE:

The proprietary information contained in this document cannot
be used in place of the documentation required for registration
purposes, because the latter has to be closely linked to the
source, the manufacturing route, and the purity/impurities of the
substance to be registered. The data should be used in accordance
with paragraphs 82-84 and recommendations paragraph 90 of the 2nd
FAO Government Consultation (1982).

ENVIRONMENTAL HEALTH CRITERIA FOR CYPERMETHRIN

A WHO Task Group on Environmental Health Criteria for
Cypermethrin met in Geneva from 1 to 5 December 1986.
Dr M. Mercier, Manager, IPCS, opened the meeting and welcomed the
participants on behalf of the heads of the three IPCS co-sponsoring
organizations (UNEP/ILO/WHO). The group reviewed and revised the
draft criteria document and made an evaluation of the risks for
human health and the environment from exposure to cypermethrin.

The first draft of the criteria document was prepared by
Dr G.J. van Esch of the Netherlands on the basis of two data
sources:

1. A draft document based on published literature prepared by
Dr J. Miyamoto and Dr M. Matsuo of Sumitomo Chemical Co., Ltd.
with the assistance of the staff of the National Institute of
Hygienic Sciences, Tokyo, Japan. Dr I. Yamamoto of the Tokyo
University of Agriculture and Dr M. Eto of Kyushu University,
Japan assisted in the finalization of this draft.

2. A review of all studies on Cypermethrin, including the
proprietary information, made available to the IPCS by Shell
International Chemical Company Limited, London, United Kingdom.

The second draft of the criteria document was prepared by
Dr van Esch, incorporating comments received following the
circulation of the first draft to the IPCS contact points for
Environmental Health Criteria documents.

The efforts of all who helped in the preparation and
finalization of the document are gratefully acknowledged.

* * *

Partial financial support for the publication of this criteria
document was kindly provided by the United States Department of
Health and Human Services, through a contract from the National
Institute of Environmental Health Sciences, Research Triangle Park,
North Carolina, USA - a WHO Collaborating Centre for Environmental
Health Effects. The United Kingdom Department of Health and Social
Security generously supported the cost of printing.

INTRODUCTION

SYNTHETIC PYRETHROIDS - A PROFILE

1. During investigations to modify the chemical structures of
natural pyrethrins, a certain number of synthetic pyrethroids
were produced with improved physical and chemical properties
and greater biological activity. Several of the earlier
synthetic pyrethroids were successfully commercialized,
mainly for the control of household insects. Other more
recent pyrethroids have been introduced as agricultural
insecticides because of their excellent activity against a
wide range of insect pests and their non-persistence in the
environment.

2. The pyrethroids constitute another group of insecticides in
addition to organochlorine, organophosphorus, carbamate, and
other compounds. Pyrethroids commercially available to date
include allethrin, resmethrin, d-phenothrin, and tetramethrin
(for insects of public health importance), and cypermethrin,
deltamethrin, fenvalerate, and permethrin (mainly for
agricultural insects). Other pyrethroids are also available
including furamethrin, kadethrin, and tellallethrin (usually
for household insects), fenpropathrin, tralomethrin,
cyhalothrin, lambda-cyhalothrin, tefluthrin, cufluthrin,
flucythrinate, fluvalinate, and biphenate (for agricultural
insects).

3. Toxicological evaluations of several synthetic pyrethroids
have been performed by the FAO/WHO Joint Meeting on Pesticide
Residues (JMPR). The acceptable daily intake (ADI) has been
estimated by the JMPR for cypermethrin, deltamethrin,
fenvalerate, permethrin, d-phenothrin, cyfluthrin,
cyhalothrin, and flucythrinate.

4. Chemically, synthetic pyrethroids are esters of specific
acids (e.g., chrysanthemic acid, halo-substituted
chrysanthemic acid, 2-(4-chlorophenyl)-3-methylbutyric
acid) and alcohols (e.g., allethrolone, 3-phenoxybenzyl
alcohol). For certain pyrethroids, the asymmetric centre(s)
exist in the acid and/or alcohol moiety, and the commercial
products sometimes consist of a mixture of both optical
(1R/1S or d/1) and geometric ( cis/trans) isomers. However,
most of the insecticidal activity of such products may reside
in only one or two isomers. Some of the products (e.g.,
d-phenothrin, deltamethrin) consist only of such active
isomer(s).

5. Synthetic pyrethroids are neuropoisons acting on the axons in
the peripheral and central nervous systems by interacting
with sodium channels in mammals and/or insects. A single
dose produces toxic signs in mammals, such as tremors,
hyperexcitability, salivation, choreoathetosis, and
paralysis. The signs disappear fairly rapidly, and the
animals recover, generally within a week. At near-lethal

dose levels, synthetic pyrethroids cause transient changes in
the nervous system, such as axonal swelling and/or breaks and
myelin degeneration in sciatic nerves. They are not
considered to cause delayed neurotoxicity of the kind induced
by some organophosphorus compounds. The mechanism of
toxicity of synthetic pyrethroids and their classification
into two types are discussed in the Appendix.

6. Some pyrethroids (e.g., deltamethrin, fenvalerate,
flucythrinate, and cypermethrin) may cause a transient
itching and/or burning sensation in exposed human skin.

7. Synthetic pyrethroids are generally metabolized in mammals
through ester hydrolysis, oxidation, and conjugation, and
there is no tendency to accumulate in tissues. In the
environment, synthetic pyrethroids are fairly rapidly
degraded in soil and in plants. Ester hydrolysis and
oxidation at various sites on the molecule are the major
degradation processes. The pyrethroids are strongly adsorbed
on soil and sediments, and hardly eluted with water. There
is little tendency for bioaccumulation in organisms.

8. Because of low application rates and rapid degradation in the
environment, residues in food are generally low.

9. Synthetic pyrethroids have been shown to be toxic for fish,
aquatic arthropods, and honey-bees in laboratory tests. But,
in practical usage, no serious adverse effects have been
noticed because of the low rates of application and lack of
persistence in the environment. The toxicity of synthetic
pyrethroids in birds and domestic animals is low.

10. In addition to the evaluation documents of FAO/WHO, there are
several good reviews and books on the chemistry, metabolism,
mammalian toxicity, environmental effects, etc. of synthetic
pyrethroids, including those by Elliot (1977), Miyamoto
(1981), Miyamoto & Kearney (1983), and Leahey (1985).

1. SUMMARY

1.1. General

Cypermethrin was initially synthesized in 1974 and first
marketed in 1977 as a highly active synthetic pyrethroid
insecticide, effective against a wide range of pests in
agriculture, public health, and animal husbandry. In agriculture,
its main use is against foliage pests and certain surface soil
pests, such as cutworms, but because of its rapid breakdown in
soil, it is not recommended for use against soil-borne pests below
the surface.

In 1980, 92.5% of all the cypermethrin produced in the world
was used on cotton; in 1982, world production was 340 tonnes of the
active material. It is mainly used in the form of an emulsifiable
concentrate, but ultra low volume concentrates, wettable powders,
and combined formulations with other pesticides are also available.

Chemically, cypermethrin is the alpha-cyano-3-phenoxy-benzyl
ester of the dichloro analogue of chrysanthemic acid, 2,2-dimethyl-
3-(2,2-dichlorovinyl) cyclopropanecarboxylic acid. The molecule
embodies three chiral centres, two in the cyclopropane ring and one
on the alpha cyano carbon. These isomers are commonly grouped into
four cis- and four trans-isomers, the cis-group being the more
powerful insecticide. The ratio of cis- to trans-isomers varies
from 50:50 to 40:60. Cypermethrin is the racemic mixture of all
eight isomers and, in this appraisal, cypermethrin refers
exclusively to the racemic mixture (ratio 50:50) unless otherwise
stated.

Most technical grades of cypermethrin contain more than 90% of
the active material. The material varies in physical form from a
brown-yellow viscous liquid to a semi-solid.

Cypermethrin has a very low vapour pressure and solubility in
water, but it is highly soluble in a wide range of organic
solvents. Analytical methods are available for the determination
of cypermethrin in commercially available preparations. In
addition, methods for the determination of residues of cypermethrin
in foods and in the environment are well established. In most
substrates, the practical limit of determination is 0.01 mg/kg.

1.2. Environmental Transport, Distribution, and Transformation

Unlike the natural pyrethrins, cypermethrin is relatively
stable to sunlight and, though it is probable that photo-
degradation plays a significant role in the degradation of the
product on leaf surfaces and in surface waters, its effects in
soils are limited. The most important photodegradation products,
2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane-carboxylic acid
(CPA), 3-phenoxybenzoic acid (PBA) and, to some extent, the amide
of the intact ester, do not differ greatly from those resulting
from biological degradation.

Degradation in the soil occurs primarily through cleavage of
the ester linkage to give CPA, PBA, and carbon dioxide. Some of
the carbon dioxide is formed through the cleavage of both the
cyclopropyl and phenyl rings under oxidative conditions. The half-
life of cypermethrin in a typical fertile soil is between 2 and 4
weeks.

Cypermethrin is adsorbed very strongly on soil particles,
especially in soils containing large amounts of clay or organic
matter. Movement in the soil is therefore extremely limited and
downward leaching of the parent molecule through the soil does not
occur to an appreciable extent under normal conditions of use. The
two principal degradation products show, on the scale of Helling,
"intermediate mobility".

Cypermethrin is also relatively immobile in surface waters and,
when applied to the surface of a body of water at rates typical of
those used in agriculture applications, it is largely confined to
the surface film and does not reach deeper levels or the sediment
in appreciable concentrations. Cypermethrin also degrades readily
in natural waters with a typical half-life of about 2 weeks. It is
probable that both photochemical and biological processes play a
part. It has been shown that spray drift reaching surface waters
adjacent to sprayed fields does not result in long-term residues in
such waters.

Accumulation studies have shown that cypermethrin is rapidly
taken up by fish (accumulation factor approximately 1000); the
half-life of residues in rainbow trout was 8 days. In view of the
low concentrations of cypermethrin that are likely to arise in
water bodies and their rapid decline, it has been concluded that,
under practical conditions, residues in fish will not reach
measurable levels.

The results of field studies have shown that, when applied at
recommended rates, the levels of cypermethrin and its degradation
products in soil and surface waters are very low. Thus, it is
unlikely that the recommended use of cypermethrin will have any
effects on the environment.

1.3. Environmental Levels and Human Exposure

Cypermethrin is used in a wide range of crops. In general, the
maximum residue limits are low, ranging from 0.05 to 2.0 mg/kg in
the different food commodities. The residues will be further
reduced during food processing. In food of animal origin, residues
may range between 0.01 and 0.2 mg/kg product. Residues in non-food
commodities are generally higher, ranging up to 20 mg/kg product.

Total dietary intake values for man are not available, but it
can be expected that the oral exposure of the general population is
low to negligible.

1.4. Kinetics and Metabolism

Absorption of cypermethrin from the gastrointestinal tract and
its elimination are quite rapid. The major metabolic reaction is
cleavage of the ester bond. Elimination of the cyclopropane moiety
in the rat, over a 7-day period, ranged from 40 to 60% in the urine
and from 30 to 50% in the faeces; elimination of the phenoxybenzyl
moiety was about 30% in the urine and 55 to 60% in the faeces.
Biliary excretion is a minor route of elimination for the
cyclopropane moiety and small amounts are exhaled as carbon
dioxide. In principle, these absorption and elimination rates and
metabolic pathways hold for all animal species studied, including
domestic animals. In cows fed 100 mg cypermethrin/day, the highest
level found in milk was 0.03 mg/litre; levels of up to 0.1 mg/kg
tissue were found in subcutaneous fat. Under practical conditions,
the oral intake of cypermethrin with feed will be much lower.
Cypermethrin used as a spray or dip to combat parasites, may give
rise to maximum residues of 0.05 mg/kg tissue and 0.01 mg/litre
milk.

Laying hens exposed orally to 10 mg cypermethrin/kg diet for 2
weeks, showed cypermethrin levels of up to 0.1 mg/kg in the fat,
and up to 0.09 mg/kg in the eggs (predominantly in the yolk).

Consistent with the lipophilic nature of cypermethrin, the
highest mean tissue concentrations are found in body fat, skin,
liver, kidneys, adrenals, and ovaries. Only negligible
concentrations are found in the brain. The half-life of cis-
cypermethrin in the fat of the rat ranges from 12 to 19 days and
that of the trans-isomer, from 3 to 4 days. In mice, these half-
lives are 13 days and 1 day, respectively.

Overall, the metabolic transformation has been similar in the
different animals studied, including man. Differences that occur
have been related to the rate of formation rather than to the
nature of the metabolites formed and to conjugation reactions.
Cypermethrin (both the cis- and trans-isomers) is metabolized via
the cleavage of the ester bond to phenoxybenzoic acid and
cyclopropane carbolic acid. The fact that thiocyanate has been
identified in in vivo studies, indicates that the cyanide moiety
is further metabolized. The 3-phenoxybenzoic acid is mainly
excreted as a conjugate. The type of conjugate differs in a number
of animal species. Phenoxybenzoic acid is further metabolized to a
hydroxy derivative and conjugated with glucuronic acid or sulfate.
The cyclopropyl moiety is mainly excreted as a glucuronide
conjugate, hydroxylation of the methyl group only occurring to a
limited extent.

Ester cleavage is much slower in certain fish species than in
other animal species, the main metabolic pathway being
hydroxylation of the phenoxybenzoic and the cyclopropyl moieties.

Ester cleavage also takes place in plants. The phenoxybenzyl
and cyclopropyl moieties are readily converted into glucoside
conjugates. In mammals, these conjugates are hydrolysed into the
original acids and metabolized.

1.5. Effects on Organisms in the Environment

High doses of cypermethrin may exert transient minor effects on
microflora activity in the soil. However, no influence on
ammonification and nitrification has been found.

Cypermethrin is very toxic for fish (in laboratory tests
96-h LC₅₀s were generally within the range of 0.4-2.8 µg/litre),
and aquatic invertebrates (LC₅₀s in the range of 0.01-> 5
µg/litre). The presence of suspended solids decreases the toxicity
by at least a factor of 2, because of adsorption of cypermethrin to
the solids.

Cypermethrin is not very toxic for birds. Signs of
cypermethrin intoxication were seen at dose levels of 3000
mg/kg body weight or more. Administration of 1000 mg
cypermethrin/kg body weight to laying hens over a 5-day period did
not cause signs of intoxication. However, cypermethrin was highly
toxic for honey bees in laboratory tests, the oral LD₅₀ranging
from 0.03 to 0.12 µg/bee. Under field conditions, the hazard is
considerably lower, because of the repellent effect of cypermethrin
on worker honey bees, which lasts for at least 6 h after spraying.

Earthworms are not sensitive to cypermethrin. No deaths
occurred in worms exposed to levels of 100 mg/kg soil for 14 days.

In studies involving deliberate overspraying of experimental
ponds under field conditions, peak concentrations of 2.6 µg
cypermethrin/litre were measured in the water. Fish were not
affected, but populations of crustaceae, mites, and surface-
breathing insects were severely reduced. Most of these populations
returned to normal levels after 15 weeks. Free-swimming dipterous
larvae and bottom-dwelling invertebrates, snails, flatworms, etc.,
were not affected. Under normal agricultural conditions (during
which drifts may reach adjacent ditches or streams), the only
effects seen in surface-breathing or -dwelling insects were
hyperactivity or immobilization.

The relative toxicity of cypermethrin for pests and their
parasites and predators is such that the balance between host/prey
and parasites/predator may not be adversely affected in the field.
However, care should be taken where predatory mites are important
in pest management.

1.6. Effects on Experimental Animals and In Vitro Test Systems

The acute oral toxicity of cypermethrin is moderate. While LD₅₀
values differed considerably among animal species depending on the
vehicle used and the cis-/ trans-isomeric ratios, the toxic
responses in all species were found to be very similar. The acute

toxicity of the trans-isomer in the rat (LD₅₀> 2000 mg/kg body
weight) was lower than that of the cis-isomer (LD₅₀, 160 - 300
mg/kg body weight). The onset of toxic signs of poisoning was
rapid and they disappeared within several days in survivors. The
toxic signs are characterized by salivation, tremors, increased
startle response, sinuous writhing of the whole body
(choreoathetosis), and clonic seizures. Myelin and axon
degeneration were noted in the sciatic nerve at near lethal dose
levels.

Cypermethrin was moderately to severely irritating, when
applied to the skin or the eye of the rabbit. The severity was
partly dependent on the vehicle used. In guinea-pigs, a mild skin
sensitizing potential was found using the maximization test.

No toxic effects were observed in rats, fed cypermethrin at 100
mg/kg diet for 3 months. Furthermore, prolonged feeding of
cypermethrin (2 years) to dogs at a level of 300 mg/kg feed did not
produce any toxicological effects. A level of 600 mg/kg diet
resulted in reduced body weight gain, but no gross pathological or
histopathological effects were seen.

Two long-term studies on rats and one on mice were carried out.
The dose levels in the rat studies ranged up to 1500 mg/kg
diet, equivalent to 75 mg/kg body weight. No effects were seen at
150 mg/kg diet. At the highest dose level, reduced body weight
gain, increased liver weights (accompanied by increased smooth
endoplasmatic reticulum), and some haematological and biochemical
changes were observed. No increase in tumour incidence was noted.
The same type of effects were seen in the mouse study at 1600 mg
cypermethrin/kg diet. No effects were seen in the 400 mg/kg diet
group.

The effect of cypermethrin on the immune system was studied in
rats. The results showed the possibility of immunesuppression by
pyrethroids. More attention should be paid to this aspect, but, at
present, no opinion can be given about its relevance in the
extrapolation of these data for man.

Repeated oral administration of cypermethrin to rats and other
animal species at levels sufficiently high to produce significant
mortality in one group of animals, produced biochemical changes in
the peripheral nerves, consistent with sparse axonal degeneration.
Histopathological changes (swelling and/or disintegration of axons
of the sciatic nerve) were observed. There was no cumulative
effect. The magnitude of the change was substantially less than
that encountered with established neurotoxic agents. The
neurotoxic effects seem to be reversible; presumably the clinical
signs are not related to the induction of neuro-pathological
lesions.

Further evidence to support the minor nature of the nerve
lesions has been afforded by electrophysiological studies on rats.
Measurements of the maximal motor conduction velocities of the
sciatic and tail nerves of rats were made before, and at intervals
of up to 5 weeks after, exposure to a single dose or repeated high

doses of cypermethrin. It was concluded from the results that,
even at near-lethal doses, cypermethrin did not cause any effects
on maximal motor conduction velocities and conduction velocities of
the slower motor fibres in rat peripheral nerves. No delayed
neurotoxicity was observed in domestic hens.

The ability of the major metabolite of cypermethrin,
3-phenoxybenzoic acid, to produce axonal changes has been
investigated and found to be negative.

In a multigeneration reproduction study on rats, dose levels up
to 500 mg/kg feed were tested. The parent animals at the highest
dose level showed decreased food intake and reduction in body
weight gain. No influence on reproductive performance or on
survival of the offspring was found. However, at the highest dose
level, reductions in litter size and total litter weights were
seen. The pooled body weights of weaning pups of the 500 mg/kg
group were decreased over 3 generations. No effect was found with
100 mg cypermethrin/kg diet.

Embryotoxic and teratogenic effects were not found in rats
administered dose levels of up to 70 mg/kg body weight and clear
teratogenic effects were not observed in rabbits given dose levels
of up to 30 mg/kg body weight during days 6 - 18 of gestation.

Cypermethrin did not show any mutagenic activity in bacteria or
in yeast, with or without metabolic activation, or in V₇₉Chinese
hamster cells. Furthermore, cypermethrin gave negative results in
an in vivo chromosomal aberration test with Chinese hamsters and
in dominant lethal studies on mice. In a host-mediated assay with
mice, no increase in the rate of mitotic gene conversion in
Saccharomyces cerevisae was found. In a chromosome study using the
bone marrow cells of Chinese hamsters, cypermethrin did not
increase the number of chromosome abnormalities. However, in a
micronucleus test with mouse bone marrow cells, an increase in the
frequency of polychromatic erythrocytes with micronuclei was found
after oral and dermal applications of cypermethrin. Intraperitoneal
application gave a negative result. A sister chromatid exchange
study using bone marrow cells of mice showed a dose-response
related increase in sister chromatid exchanges of dividing cells.

In long-term/carcinogenicity studies, oral administration of
cypermethrin to rats did not induce an increase in the incidence of
tumours. In a mouse study, dose levels of up to 1600 mg
cypermethrin/kg diet did not produce any increase in tumours of
types not commonly associated with the mouse strain employed. The
incidence of tumours was similar in all groups with the exception
of a slight increase in the incidence of benign alveolar lung
tumours in the females in the 1600 mg/kg diet group. However, the
increased incidence, when compared with concurrent and historical
control incidence, was not sufficient to warrant concern. There
was no suggestion of increased malignancy and no evidence of a
decrease in the latency of the tumours. Furthermore, there was no
evidence of a carcinogenic response in the male mice in this study

and, as the results of mutagenicity studies on cypermethrin have
been mainly negative, it is concluded that there is no evidence for
the carcinogenic potential of cypermethrin.

1.7. Mechanism of Toxicity

Extensive studies have been carried out to explain the
mechanism of toxicity of cypermethrin, especially with regard to
the effects on the nervous system. The results strongly suggest
that the primary target site of cypermethrin (and of pyrethroid
insecticides in general) in the vertebrate nervous system is the
sodium channel in the nerve membrane. The alpha-cyano pyrethroids,
such as cypermethrin, cause a long-lasting prolongation of the
normally transient increase in sodium permeability of the nerve
membrane during excitation, resulting in long-lasting trains of
repetitive impulses in sense organs and a frequency-dependent
depression of the nerve impulse in nerve fibres. Since the
mechanisms responsible for nerve impulse generation and conduction
are basically the same throughout the entire nervous system,
pyrethroids may well act in a similar way in various parts of the
central nervous system. It is suggested that the facial skin
sensations that may be experienced by people handling cypermethrin
are brought about by repetitive firing of sensory nerve terminals
in the skin, and may be considered as an early warning signal that
exposure has occurred.

1.8. Effects on Man

No cases of accidental poisoning have been reported as a result
of occupational exposure.

Skin sensations, reported by a number of authors to have
occurred during field studies, generally lasted only a few hours
and did not persist for more than one day after exposure.
Neurological signs were not observed. General medical and
extensive clinical blood-chemistry studies, and
electrophysiological studies on selected motor and sensory nerves
in the legs and arms did not show any abnormalities.

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

2.1. Identity

IUPAC chemical name (RS)-alpha-cyano-3-phenoxybenzyl(1RS)-
cis-, trans-3-(2,2-dichlorovinyl)-2,2-
dimethylcyclopropane carboxylate

CAS chemical name (RS)-cyano(3-phenoxyphenyl)methyl(1RS)-
cis- trans-3-(2,2-dichloroethenyl)-2.2-
dimethylcyclopropane carboxylate

CAS registry number 52315-07-8 (formerly 69865-47-0)

RTECS registry number GZ1250000

Common synonyms NRDC 149, WL43467, PP 383, CG-A 55186

Common trade names Ammo, Avicade, Barricade, CCN 52,
Cymbush, Folcord, Imperator, Kafil
Super, Polytrin, Ripcord, Stockade

The asymmetric carbons are marked with an arrow and give rise
to the 8 isomers shown in Fig. 1. Conventionally, the 4 isomers
where the dichlorovinyl group is trans in relation to the
phenoxybenzyl group are referred to as trans-isomers, and the
other 4 as cis-isomers.

Cypermethrin is the ISO name for the pure racemic compound.
The technical products commonly available contain more than 90%
cypermethrin and the ratio of cis- to trans-isomers varies from
50:50 to 40:60. The data presented in this document refer to
products within this range of composition, unless otherwise stated.

2.2. Physical and Chemical Properties

Some physical and chemical properties of cypermethrin are given
in Table 1.

Cypermethrin is highly stable to light and at temperatures
below 220 °C. It is more resistant to acidic than to alkaline
media, with an optimum stability at pH 4. Cypermethrin is
hydrolysed under alkaline conditions in the same way as simple
aliphatic esters: the rate-determining step is the nucleophilic
attack by a hydroxyl group (Camilleri, 1984). Dilute aqueous

solutions are subject to photolysis, which occurs at a moderate
rate (Martin & Worthing 1977; FAO/WHO, 1980b; Meister et al., 1983;
Worthing & Walker, 1983).

Table 1. Some physical and chemical properties of cypermethrin^a
--------------------------------------------------------------------
Physical state varies from a viscous yellow liquid
to a semi-solid crystalline mass at
ambient temperatures

Relative molecular mass 416.3

Melting point up to 80 °C depending on purity
and cis: trans ratio

Boiling point decomposes at 220 °C

Density (22 °C) 1.12 g/ml

Solubility in water (20 °C) 0.009 mg/litre

Solubility in organic solvents:
hexane 103 g/litre
xylene > 450 g/litre
also comparable solubility in
cyclohexanone, ethanol, acetone,
and chloroform

Vapour pressure (20 °C) 1.9 x 10^-7Pa (1.4 x 10^-9mmHg)

n-octanol/water partition 2 x 10⁶(log P_ow6.3)
coefficient
--------------------------------------------------------------------
^a From: FAO/WHO (1980b); Grayson et al (1982); Working & Walker (1983).

2.3. Analytical Methods

The most widely adopted procedures for the determination of
cypermethrin residues in crops, soil, animal tissues and products,
and environmental samples are based on extraction of the residue
with organic solvent, clean-up of the extract, as necessary, by
means of solvent-solvent partition and adsorption column
chromatography, followed by determination of the residue using gas
chromatography with electron capture detector (GC/ECD). The
identity of residues can be confirmed by GC with mass selective
detection (GC-MSD) or by thin-layer chromatography (TLC) followed
by GC/ECD.

Methods using these procedures have been applied for the
determination of cypermethrin residues in the presence of other
synthetic pyrethroids or other classes of pesticides, including
organochlorine insecticides.

Alternative procedures, based on high-performance liquid
chromatography with UV detection (HPLC/UV) and TLC with a
colorimetric end point, have been described, but have not been
widely adopted, because of the simplicity and sensitivity of the
GC/ECD methods. This is also true for more elaborate procedures
based on hydrolysis and derivatization.

Procedures have also been developed for the determination of
the more important cypermethrin metabolites, 3-phenoxybenzoic acid
(PBA), the cyclopropane carboxylic acid (CPA), and the amide.
Following extraction and clean-up, these materials are determined
by HPLC/UV or by GC procedures, after derivatization in the case of
the two acids.

The Codex Committee on Pesticide Residues lists recommended
methods for the determination of cypermethrin residues (FAO/WHO
1986).

The methods for residue, environmental, and product analysis
for cypermethrin are summarized in Table 2.

Table 2. Published analytical methods for cypermethrin
---------------------------------------------------------------------------------------------------------
Sample Sample preparation Method of determination LD^b Reference
Extraction Partition Clean-up GLC or HPLC condition^a (mg/kg)
solvent Column/elution
---------------------------------------------------------------------------------------------------------
Residue
analysis

Apple n-hexane:acetone extraction silica gel/ electron capture 0.01 Baker &
Pear (1:1) solvent:H₂O CH₂Cl₂ detection-gas 0.01 Bottomley
Cabbage chromatography 0.01 (1982)
Potato 0.01

Apple n-hexane:acetone extraction silica gel/ high-performance liquid 0.2 Baker &
Pear (1:1) solvent:H₂O CH₂Cl₂ chromatography 0.2 Bottomley
Cabbage 0.2 (1982)
Potato 0.2

Onion CH₃CN:H₂O CH₂Cl₂ Florisil/ electron capture Frank et
Carrot (2:1) ether: n- detection-gas al. (1982)
hexane chromatography

Celery CH₃CN n-hexane:2% Florisil/ electron capture 0.005 Braun &
NaCl CH₃CN/CH₂Cl₂: detection-gas Stanek
n-hexane chromatography (1982)

Wheat n-hexane:acetone 2% NaCl:extrac- Florisil/ electron capture 0.02 Joia et
grain (1:1) tion solvent benzene detection-gas al. (1981,
flour chromatography 1985a)
bran
middling

Beef CH₃CN:H₂O n-hexane:2% Florisil/ electron capture 0.005 Braun &
muscle (85:15) NaCl solution CH₃CN/CH₂Cl₂: detection-gas Stanek
n-hexane chromatography (1982)

Egg yolk CH₃CN:H₂O n-hexane:2% Florisil/ electron capture 0.005 Braun &
(85:15) NaCl solution CH₃CN/CH₂Cl₂: detection-gas Stanek
n-hexane chromatography (1982)
---------------------------------------------------------------------------------------------------------

Cotton n-hexane Florisil/ n- electron capture Estesen et
foliage hexane:EtOAc detection-gas al. (1982)
(dislodgable chromatography
residue)

Environmental
analysis

Fish n-hexane:acetone alumina/ n- electron capture McLeese et
Shrimp (1:1) hexane:benzene detection-gas al. (1980)
chromatography

Water XAD-2 resin: extraction sol- electron capture McLeese et
Seawater acetone vent: n-hexane detection-gas al. (1980)
chromatography

Soil acetone sat. Na₂SO₄: electron capture Harris et
n-hexane detection-gas al. (1981)
chromatography

Soil CH₃CN:H₂O CH₂Cl₂ Florisil/ electron capture Frank et
(2:1) ether: n-hexane detection-gas al. (1982)
chromatography
Product
analysis

Technical n-hexane flame ionization Chapman &
grade detection-gas Simmons
chromatography (1977)
---------------------------------------------------------------------------------------------------------

Table 2. (contd.)
---------------------------------------------------------------------------------------------------------
Sample Sample preparation Method of determination LDb Reference
Extraction Partition Clean-up GLC or HPLC condition^a (mg/kg)
solvent Column/elution
---------------------------------------------------------------------------------------------------------
Technical methylene flame ionization Bland
and chloride (con- detection-capillary gas (1985)
formulated taining as chromatography
material internal stan-
dard dicyclo-
hexylphthalate)
---------------------------------------------------------------------------------------------------------
^a GLC = gas-liquid chromatography.
HPLC = high-performance liquid chromatography.
^b LD = limit of determination. (The lower practical limit of determination for most of the analytical
methods based on GLC is usually 0.01 mg/kg. The actual level achievable, however, depends to some
extent on the substrate and to a great extent on the intensity of the clean-up steps in the
procedure).
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1. Industrial Production

Cypermethrin was synthesized by Elliott et al. in 1974. It was
prepared by the esterification of a chloro analogue of chrysanthemic
acid (1R, 1S or 1RS, 3R, 3S, or cis-, trans-)-2,2-dimethyl-3-(2,2-
dichlorovinyl)cyclopropanecarboxylic acid with (alphaR, alphaS, or
alphaRS)-alpha-cyano-3-phenoxybenzyl alcohol. Today there are many
other methods of preparation.

Cypermethrin has been marketed since 1977. Recent global
production figures are given in Table 3.

Table 3. Global production of cypermethrin
-------------------------------------------------
Year Production Reference
(tonnes)
-------------------------------------------------
1979 200 Wood, Mackenzie, & Co. (1980)
1980 380 Wood, Mackenzie, & Co. (1981)
1981 375 Wood, Mackenzie, & Co. (1982)
1982 340 Wood, Mackenzie, & Co. (1983)
-------------------------------------------------

3.2. Use Patterns

Cypermethrin is a highly active synthetic pyrethroid
insecticide, effective against a wide range of pests in many crops.
According to Battelle (1982), global consumption of cypermethrin
amounted to 159 tonnes in 1980. Fifty-eight tonnes were consumed
in Africa and 9 tonnes in western Europe. Global production in
1982 was 340 tonnes. Cypermethrin was mainly (92.5%) used on
cotton, the major consumer areas being Turkey (47 tonnes), Central
America (44 tonnes), and Egypt (25 tonnes) (Battelle, 1982). Other
agricultural uses included the treatment of hop, vegetables, and
maize. Cypermethrin is also used for the control of veterinary and
public health insects, such as flies, lice, and mites and, in the
United Kingdom, it is used as a wood preservative.

Cypermethrin is formulated as emulsifiable concentrates (100
and 250 g/litre), ultra-low-volume concentrate (10 - 50 g/litre),
wettable powder (125 g/kg), and animal dip concentrate (5 - 15%).

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSPORTATION

4.1. Transport and Distribution between Media

Because of its physical and chemical characteristics,
cypermethrin is comparatively immobile in the outdoor environment
and transport between media is restricted. It has a very low
vapour pressure and water solubility and is strongly adsorbed from
aqueous solutions by solid surfaces. This drastically restricts
its movement in air and water, and particularly in soils.

4.1.1. Transport from soil to water

Kaufman et al. (1981), working in the laboratory with radio-
labelled cypermethrin in soil columns, down which a volume of water
equivalent to their moisture equivalent was allowed to percolate,
reported virtually no movement of radioactivity below the top
2.5 cm. Using the procedure introduced by Helling & Turner (1968),
where the mobility was studied using thin layer chromatographic
(TLC) plates, very little movement of cypermethrin occurred in
soils. However, radio-labelled PBA leached down the soil columns
to a level of about 8 cm and CPA reached a maximum concentration at
this level. On the basis of the Helling nomenclature for soil
TLC, CPA and PBA were of "intermediate mobility" to "mobile".
While the mobilities of CPA and PBA were relatively little affected
by the organic matter content of the soil, pH appeared to be a most
important factor, mobility being greatest in soils of highest pH,
presumably because of increased dissociation.

Stevens & Hill (1980) studied the leaching of cypermethrin in
the laboratory in 4 different soil types, a clay loam, a loamy
sand, a coarse sand, and a fen peat. The compound was incubated
for three weeks with each soil under aerobic conditions. The soils
were then packed into glass columns and leached with 67.5 cm water
over a 10-week period. At the end of the period of incubation, a
substantial proportion of the cypermethrin had been lost as ¹⁴CO₂
(up to a third in one case), and only minor amounts of degradation
products had been formed. It was found that, after the leaching
period, more than 99% of the ¹⁴C residue remained within the top
5 cm in all the soils. Radioactivity in the leachate was below the
limit of determination in all cases.

In laboratory studies using labelled cypermethrin and soil
columns, Jackson (1977) found little penetration of cypermethrin
below the top 2-cm layer, even after the percolation of 1.35 metres
of water.

In a further study on the percolation of distilled water
through sandy loam soils containing ¹⁴C-benzyl cypermethrin from
spent sheep-dip baths, Standen (1977) reported that up to 0.3% of
the applied radioactivity was leached out. However, most of the
radioactivity was associated with fine soil particles in the
leachate and could not be extracted with organic solvents. The
water contained small amounts of unchanged cypermethrin and PBA.
Most (89%) of the radioactivity was contained in the top 14 cm of
the columns, mainly as cypermethrin itself.

Sakata et al. (1986) studied the leaching with distilled water
of radio-labelled cypermethrin through columns of 4 different types
of soil in the laboratory. The water flow was at a rate of 3 ml/h
and was continued for 3 weeks at 25 °C, so that the total flow
through the column was equivalent to about 3 metres. Cypermethrin
was relatively resistent to leaching but radioactivity was found in
the leachate, especially in one sandy soil where, after 30 days of
incubation, about 30% of the cyclopropyl label first added was
collected in the leachate. The major products associated with
radioactivity in the leachates were either CPA or PBA, depending on
the position of the label. Unchanged cypermethrin was present only
in trace amounts in sand containing less than 0.1% organic matter.

4.1.2. Transport within water bodies

Cypermethrin moves slowly in water bodies. In the experimental
overspraying of ponds carried out by Crossland (1982) and described
in detail in section 4.4.2, it was calculated that 48 h after
treatment with 100 g cypermethrin/ha, only about 8 - 16% of the
amount applied could be found underneath the surface film of 0.05
mm depth. In all of Crossland's studies, the levels of
cypermethrin residues in the sediment at the bottom of the ponds
were below 7 µg/kg.

With spray levels applied according to normal agricultural
practice, Crossland et al. (1982) found that water bodies adjacent
to sprayed arable fields in the United Kingdom received only four-
five orders of magnitude less cypermethrin per m²than the land
itself and that the initial concentration in the surface film of
water was between 6 and 20 µg/litre. Residues in the water below
the surface film did not reach more than 0.1 µg/litre and within
24 h the levels had nearly all fallen to below the limit of
determination of 0.01 µg/litre. A similar study in French
vineyards showed comparable results, though the initial
concentrations reached in the surface films were higher, probably
because conditions in the area were more favourable for spray drift
than those in the British study.

Shires & Bennett (1985) reported similar results concerning
water in drainage ditches adjacent to cereal fields in the United
Kingdom treated with an aerial spray application of 25 g
cypermethrin/ha.

From the available studies, it can be concluded that
contamination of water bodies by overspray is likely to be very
superficial and of comparatively short duration.

4.2. Abiotic Degradation

4.2.1. Photodegradation

4.2.1.1. Basic studies

According to Ruzo et al. (1977), cypermethrin is one of the
more light-stable pyrethroids. Thus, when exposed in the solid
phase to sunlight for 30 h, no loss of cypermethrin was detected.

When exposed in methanol solution to light of wavelength > 290 nm
for about 2 days, 55% of cypermethrin was recovered, but no data on
the photodecomposition products formed were reported. According to
Ruzo & Casida (1980), the reaction quantum yield at 300 nm in
methanol was low, at 0.022. Ruzo (1983) further demonstrated the
comparative resistance of cypermethrin to irradiation in his
studies on the involvement of oxygen in the photodegradation of
pyrethroids.

Cypermethrin is more susceptible to radiation of lower
wavelengths; Lauren & Henzel (1977) reported that under ultra-
violet radiation, 90% of cypermethrin on a glass petri dish was
decomposed after 3 days, but only 45% was decomposed after 3 days
when the cypermethrin was deposited on grass and placed under an
UV-lamp.

4.2.1.2. Photodegradation

(a) Water

Day & Leahey (1980) studied the effects of sunlight on dilute
aqueous solutions of cypermethrin. In their studies, ¹⁴C-labelled
cis- or trans-isomers were used with the label in either the
cyclopropyl or the benzyl ring. They were dissolved in sterile
aqueous acetonitrile at a concentration of 1 mg/litre, irradiated
in sunlight for 32 days and the irradiated solutions compared with
controls stored for the same length of time in the dark. The
degree of photodegradation was very limited. At the end of the
study, 89.4% of the cypermethrin remained in the case of the
irradiated benzyl label, compared with 97.4% in the dark control.
Corresponding figures for the cyclopropyl label were 92.3 and
96.8%. Six of the 8 photodegradation products separated by
chromatography were positively identified; cis- and trans-CPA,
phenoxybenzyl alcohol, aldehyde and acid, and alpha-cyano-3-
phenoxybenzyl alcohol.

The effects of natural sunlight on aqueous solutions of the
(1R, cis-, alpha RS) and (1R, trans-, alpha RS) isomers were
studied by Takahashi et al. (1985a,b). The products were labelled
with ¹⁴C in either the cyclopropyl ring, the benzyl ring, or the
cyano carbon. The aqueous solutions were made from distilled
water, 2% acetone, aqueous humic acid, sea water, or natural river
water (both of which had been filtered). The isomers were added to
the water in the form of a stabilized suspension using Tween 20 to
give 50 µg/litre test suspension. The rates of degradation of the
isomers were very rapid compared with those reported by other
authors, however, a large part of the changes involved
transformation to other isomers. The degradation was more rapid in
river or sea water (half-life of cis-isomer, 0.6 - 0.7 days) than
in distilled water or humic acid (half-life of cis-isomers, 2.3 -
2.6 days), but the most rapid change of all occurred in the
presence of acetone. Presumably the differences were due to the

well known effect of photosensitizaton by the acetone or organic
constituents of the natural waters. The main degradation products,
in addition to the different isomers, were CPA, PBA together with
smaller amounts of the corresponding aldehyde, and carbon dioxide,
especially in the case of the cyano label. There was evidence of
further degradation of CPA and PBA.

(b) Soil

Hall et al. (1981) studied the photodegradation of cypermethrin
on the soil surface. Labelled cypermethrin, as used by Day &
Leahey, was applied to very thin soil plates (0.5 mm) at a rate
equivalent to about 200 g/ha. The plates were exposed to sunlight
in the open air protected against rain by polythene sheeting, when
necessary; the sheeting was transparent to the UV component of
sunlight. The plates were extracted after an exposure period of 32
days and the extracts chromatographed. In the case of the
cyclopropyl label, 63% of the radioactivity initially applied to
the irradiated plate was recovered, compared with 103.5% from the
plate that had been kept in the dark. The half-life of the
cyclopropyl-labelled cypermethrin was reduced from > 32 days to 8
- 16 days by irradiation with natural light. The main degradation
products appear to have been the amide, together with cis- and
trans-CPA, and some unidentified (partly volatile) products. In
the case of the benzyl label, the degradation products identified
were mainly the amide analogue of cypermethrin and various
phenoxybenzyl derivatives, such as the alcohol, aldehyde, and acid.
In these studies, the amide was the most prominent, even in the
unirradiated sample, and in this respect, the results differ
somewhat from those obtained in other soil incubation studies,
where the main metabolite from benzyl-labelled cypermethrin was
PBA, with the amide occurring only as a very minor product.

Takahashi et al. (1985a,b), working with the same products as
they used for their study on water, applied the labelled products
at 1.1 µg/cm²to half-millimetre layers of 3 different soils and
found very rapid degradation in the irradiated soils compared with
those kept in the dark. The half-lives ranged from between 0.6 and
1.9 days with sunlight and > 7 days in the dark. With regard to
degradation products, the results were rather similar to those
reported by Hall et al. (1981) in that the main degradation product
was the amide of the otherwise intact isomers. In addition, they
found smaller amounts of PBA, virtually no CPA, but occasionally
small amounts of alpha carbamoyl- and alpha carboxyphenoxybenzyl
alcohol. In one of the soils in which degradation was the
highest, nearly half of the radio-labelled carbon was unextractable
at the end of the exposure period. In contrast with the water
study, there was very little evidence of isomerization of the
parent isomers.

There is no obvious explanation for the different rates of
degradation under the influence of irradiation and it is difficult
to extrapolate the results of these studies to the practical
situation. It appears likely that photochemical reactions will

hasten the degradation of deposits of cypermethrin on exposed
surfaces and possible residues in water, but there is little
indication that they greatly change the degradation pathways.

4.3. Biological Degradation in Soil

Cypermethrin degrades relatively quickly in soils, primarily by
biological processes involving cleavage of the ester linkages, to
give the two main degradation products, CPA and PBA. These
products are themselves subsequently mineralized. There is also
evidence for the formation, as an intermediate, of the amide of the
intact molecule and occasionally the 4-hydroxy phenoxy analogue.
Neither of the latter products appears to persist in the soil
(Leahey 1979; Sakata et al., 1986).

4.3.1. Mechanism

Chapman et al. (1981), who studied the effects of sterilization
of soils on the rate of cypermethrin degradation in the laboratory,
demonstrated that degradation in the soil was essentially a
biological process. Cypermethrin was added at 1 mg/kg to the soils
(either untreated or sterilized) and the soils incubated for 16
weeks, by which time the sterilized soils were considered to have
become contaminated. The experiment was conducted under strictly
aerobic conditions. It was found that 84% of the added material
had degraded in natural organic soil compared with only 8% in the
sterilized organic soil. The corresponding values for the mineral
soil were 96% and 7%. The small amounts of degradation in the
sterilized soils presumably resulted from residual microbial
activity, especially in the later stages of the study.

4.3.2. Degradation pathways (separate isomers)

In order to study degradation pathways, Roberts & Standen
(1977, 1981) carried out a series of soil studies in the laboratory
using either the racemic cis- or trans-isomers of cypermethrin or
mixtures of the two. The compounds were ¹⁴C-radio-labelled in
either the benzyl or the cyclopropyl ring and were added to the
soil at a rate of 2.5 mg/kg moist soil. Incubation with 3
different soils was carried out under either aerobic or anaerobic
conditions, initially for 16 weeks and subsequently for a total of
52 weeks. Experiments were also conducted using biometer flasks,
in order to measure the output of radio-labelled carbon dioxide.
In the case of the cis-isomer, the main degradation products
extracted from the soils were PBA, cis-CPA with small amounts of
trans-CPA, and limited amounts of the 4-hydroxy derivative of
cypermethrin. Between 25% and 30% of the added radioactivity could
not be extracted with acetonitrile/water. A similar spectrum of
degradation products was extracted in the trans-isomer experiments,
except that the cis-isomer was absent. Some of the remaining
radioactivity was identified in a further degradation product of
CPA, the dicarboxylic acid.

A further study was undertaken by Roberts & Standen (1981) in
which ring-labelled cis- and trans-isomers of CPA were added to a
sandy loam soil at 2.5 - 13.5 mg/kg. In most cases, the soils were

contained in loosely stoppered vessels but, in one experiment, a
biometer flask fitted with a caustic potash trap was used, in order
to measure carbon dioxide (CO₂) production. In spite of the
production of labelled CO₂in the initial study with cyclopropyl-
labelled cypermethrin, very little was produced in the latter study
and most of the radioactivity was shown to be still present in the
soil. At the end of the 8-week exposure period, it was found that
the greater part of the radioactivity in the soil was still
associated with unchanged CPA, 33 - 65% in the case of the trans-
acid and 78% in the case of the cis-acid. There was also evidence
that some of the trans-CPA was transformed to the cis-isomer, but
not vice-versa. This finding was analogous to that with the parent
compound where a certain amount of cis-CPA was produced from trans-
cypermethrin.

A similar series of studies was carried out by Sakata et al.
(1986) who incubated 2 Japanese soils with the 1R cis-RS alpha and
1R trans-RS alpha isomers of cypermethrin for up to 168 days at
25 °C. While ester cleavage was the principal pathway of
degradation, limited production of the amides of the intact esters
and production of the 4-hydroxy derivatives (on the phenoxy group)
were also reported. The latter were often present in greater
amounts than the PBA or CPA fragments. The authors also reported
the presence of small amounts of the desphenoxy derivative derived
from ether cleavage, not previously reported for cypermethrin.
However, the level of ¹⁴C associated with extractable breakdown
products was low (1 - 17% of the amount initially added, at 56
days) compared with that of bound radio carbon (14 - 58% at 56
days), the actual levels being very dependent on the type of soil
under study. Since the trans-isomers degraded more readily than
the cis-isomers and since the level of free degradation products
was considerably lower for the trans- than the cis-isomers, it is
possible that a substantial proportion of the bound radio carbon
had reverted to the general carbon pool of the soil organic matter.
A major proportion of the added label was recovered as carbon
dioxide (16 - 48% at 56 days) and the amount was highest when the
label was on the benzyl carbon, indicating, as Roberts & Standen
had found, that the PBA was mineralized more readily than the CPA.
Sakata et al. also found that, under comparable circumstances, the
cis-isomers produced carbon dioxide more slowly than the trans-
isomers.

The principal degradation products in soils, prior to breakage
of the benzyl and cyclopropane rings, are shown in Fig. 2.

4.3.3. Rates of degradation

4.3.3.1. Laboratory studies

(a) Separate isomers

In the laboratory studies carried out by Roberts & Standen
(1977, 1981), the half-lives of the cis-isomers were around 4
weeks, except in the inactive Los Palacios soils, where the figure
was nearer to 10 - 12 weeks. The trans-isomer generally exhibited
a much shorter half-life of less than 2 weeks and less than 4 weeks

on the less active soil. After a year, the amounts of unchanged
material left in the soils were very low and nearly always below
10% of the amount applied. But, even at the low levels remaining
after such a long interval, residues of the trans- were still
substantially less than those of the cis-product.

Sakata et al. (1986) in their incubation studies reported half-
lives of between 4.1 and 17.6 days for trans-cypermethrin and 12.5
and 56.4 days for the cis-isomer, under aerobic upland conditions.
Degradation was much slower in one of the soils than in the other,
as was also shown by Roberts & Standen (1977, 1981). Miyamoto &
Mikami (1983) reported data on the half-lives in soil incubation
tests for all 4 of the 1R isomers of cypermethrin. The alpha S
isomers of both cis- and trans-isomers degraded much more rapidly
than the alpha R isomers, sometimes nearly twice as fast. Again,
the cis-isomers were slower to degrade than the trans-isomers.
The greater readiness of the trans-isomers to degrade has been
observed extensively by other workers, i.e., Kaufman et al. (1978),
Chapman et al. (1981), Chapman & Harris, (1981), Harris et al.
(1981). The Japanese studies did not produce data for the 1S
isomers, but Chapman & Harris did not detect appreciable
differences between the rates of degradation of the 1R and 1S
isomers, either trans or cis. On the other hand, Harris et al.
(1981) reported a substantial decrease in the 1S/1R ratio for trans-
cypermethrin, as degradation in the soil proceeded suggesting
that, in these studies, the 1S trans-isomers degraded more quickly
than the 1R trans-isomers.

4.3.3.2. Field studies

(a) Cypermethrin, and separate isomers

Roberts & Standen (1981) showed that the rates of degradation
of cypermethrin observed in the laboratory and in the field did not
differ greatly. On the basis of their data, 2 - 4 weeks in the
growing season would appear to be a typical half-life for the

parent racemic cypermethrin, bearing in mind that the half-lives of
the cis-isomers were often approximately twice those of the trans-
isomers.

Shorter half-lives of less than 2 weeks on a mineral soil and
about 3 weeks on a peat soil were reported by Chapman & Harris
(1981). Harris et al. (1981) reported a half-life for cypermethrin
in Plainfield sand of about 2.5 weeks. The persistence of the
insecticidal activity of surface applications of cypermethrin, as
measured by toxicity for cutworms was studied by Cheng (1984).
Although these data cannot be expressed in terms of the half-life
of cypermethrin, it is interesting to note that initial
applications, giving 100% mortality, were only producing about 50%
mortality after 12 days.

However, Chapman & Harris (1981) warned that a simple half-life
expression was not necessarily a valid way of defining the rates of
degradation of cypermethrin, because these tend to decrease with
time. A possible explanation for this effect is that there is a
gradual increase in the proportion of cis-isomers in the residues.
Since these degrade more slowly, overall degradation rates are
bound to decrease with time. But the results of Harris et al.
(1981) cast doubt on whether this change in isomer ratio provides
the sole explanation. These authors reported that, in their
studies, the ratio of cis- to trans-isomers increased during the
early part of their studies, but decreased substantially
afterwards.

Chapman & Harris (1981) also reported that the degradation was
slowed down by high soil contents of organic matter or clay (c.f.,
the slow rates of degradation reported by Roberts & Standen (1977,
1981) on the very high clay soil, Los Palacios) and by anaerobic
conditions. Contrary to what might be expected in light of the
behaviour of other pesticides, they reported that cypermethrin
degraded more quickly on dry than on wet soils. They also
identified the level of cypermethrin in the soil as a very
important factor. Thus, degradation, expressed on a proportionate
basis, was 2 - 3 times slower with an initial concentration in the
soil of 10 mg/kg, than that with an initial concentration of
0.5 mg/kg. Kaufman et al. (1978) also reported faster degradation
with lower rates of application.

(b) Metabolites

In studies on the 2 metabolites (PBA and CPA), Roberts &
Standen (1977, 1981) reported that PBA was quicker to degrade than
CPA.

In the Leiston soil, only about 2% of applied radioactivity
was recovered as PBA after 16 weeks, though in the soil from Los
Palacios, the figure was just under 30% for the soil treated with
cis-cypermethrin and some 50% for the soil treated with trans-
cypermethrin. The higher figure for PBA derived from trans-
cypermethrin was, presumably, due to the more rapid rate of
degradation of this parent isomer.

The degradation of PBA is an oxidative process and, under
anaerobic conditions, its degradation was greatly retarded (Roberts
& Standen, 1977).

The data of Roberts & Standen (1977) on CPA showed that, in
Brenes soil treated with the parent cypermethrin cis-isomers,
radioactivity recovered as CPA reached a maximum (about 17% of the
total radioactivity initially added) at the 8th week. The maximum
level of CPA from the trans-cypermethrin was reached at about the
same time, but constituted nearly 50% of the radioactivity
originally applied. Moreover, by the 52nd week, whilst CPA from
the cis-product had practically disappeared, there was still a
residue of CPA from the trans-isomers, equivalent to some 10% of
the radioactivity originally applied.

The rate of decay of the unextractable radioactivity in soils
previously treated by Roberts & Standen (1977) with labelled
cypermethrin, as described above, was studied by incubating some of
the soils (Brenes & Leiston soils) for a further 26 weeks in
admixture with fresh soil. Substantial additional losses of radio
carbon were observed. At the end of this time, 25 - 45% of the
"bound" radioactivity initially present was lost. Perhaps
unexpectedly, the losses from cypermethrin labelled in the
cyclopropyl ring was almost double that from product labelled in
the benzyl ring. It is clear from these studies that the binding
of residues of breakdown products did not prevent their continued
degradation. Although some of the evidence of Roberts & Standen
relating to the rate of degradation of CPA itself appears to be
anomalous, it can be inferred that cypermethrin degrades rapidly in
the soil and that the subsequent degradation products are
mineralized, as shown by the liberation of labelled carbon dioxide
from cypermethrin labelled in either the cyclopropyl or benzyl
rings. As Miyamoto (1981) concluded, there appears to be little
likelihood of cypermethrin or its metabolites persisting for
lengthy periods in soils.

4.4. Degradation in Water and Sediments

4.4.1. Laboratory studies

(a) Cypermethrin and separate isomers

Camilleri (1984), using 10-5mol/litre solutions of the cis-2
isomer pair of enantiomers in dioxan-water, showed that, at
alkaline pH values, cypermethrin is readily degraded by ester
cleavage to give CPA and PBA. The alternative route of
degradation, hydrolysis of the cyano group to amide, required a
much higher energy of activation and could not be detected.

Takahashi et al. (1985a) demonstrated the effects of pH on the
hydrolysis of 1R cis- or 1R trans-cypermethrin in abiotic
buffered aqueous solutions. At acidic pH values, the half-life of
the isomers was one or more years, but it was appreciably shorter
at pH 7 and had fallen to a matter of minutes at pH 11 (all at

25 °C). In natural waters, sterilized by filtration and having a
pH of about 8, the half-life was about 3 weeks at 25 °C. The trans-
isomers were hydrolysed more readily than the cis-isomers.

The fate of cypermethrin under biotic conditions, simulating
those in rivers and ponds, was studied by Rapley et al. (1981)
using a radio-labelled product, with the label in either the
cyclopropyl or benzyl ring. Samples of water and sediments from 3
rivers and a pond were used in a laboratory experiment in which
mixtures of water and sediment were placed in pairs of glass
cylinders. The insecticide was added at a rate equivalent to 140
g/ha and the vessels incubated at 16 °C for up to 60 weeks,
periodic determinations being made of the level of cypermethrin
remaining and the amount of labelled CO₂evolved. One series of
vessels was aerated and the other left undisturbed. Degradation
was rapid in all cases, even in the non-aerated series. Some 50%
of cypermethrin was lost in less than 2 weeks and 90% within 2 - 9
weeks. After approximately one year, 40-70% of the ¹⁴C label from
the benzyl-labelled material was lost as ¹⁴CO₂, but only 4% from
the cyclopropyl-labelled material, though this proportion rose to
10% after 63 weeks. In the case of the cyclopropyl-labelled
material, the main degradation product detected was CPA with a
small amount of dicarboxylic acid. Subsequent degradation of the
CPA was slow. When the label was in the benzyl ring, the main
product was PBA though, in the sediment, precursors (aldehyde and
to some extent the alcohol) were the most prominent, possibly
because aeration was defective.

Muir et al. (1985) studied the behaviour of cis- and trans-
cypermethrin isomers, labelled with ¹⁴C in the cyclopropyl ring, in
3 bottom sediments (sand, a river silty clay, and a pond bottom
clay). In each case, 0.064 or 0.64 mg of the trans-isomers/kg or
0.012, 0.017, or 0.17 mg of the cis-isomers/kg was added to the
sediment. Each sediment was covered with dechlorinated tap water
and allowed to equilibrate for 24 h. The system was sampled at 6
and 24 h and the level of radioactivity determined in the sediment,
pore water from the sediment (in a separate study), and in the
supernatant water. The radioactivity was much less strongly
absorbed on sediment treated with the trans-isomer than on that
treated with cis-isomer, indicating that a substantial proportion
of the radioactivity was associated with degradation products
rather than with the parent compound, because it is unlikely that
major differences in adsorption between the cis- and trans-isomers
of the parent molecule would have been noticed.

4.4.2. Field Studies

(a) Cypermethrin

Crossland (1982) studied the effects of deliberately
overspraying experimental ponds with cypermethrin at the rate of
100 g/ha. Water was sampled either from the surface (2.5 - 10 cm)
or from a depth of 50 cm. Approximately 4 h after treatment, the
concentration of cypermethrin in the surface was 0.1 mg/litre, but
it fell to about a tenth of this value in 24 h. By 13 days, the

surface concentration had fallen to 0.0007 mg/litre. Concentrations
at a depth of 50 cm rose to a plateau of 0.0023 - 0.0026 mg/litre,
4 h after treatment, and then started to fall. By 13 days after
treatment, the concentration had decreased to 0.0009 mg/litre.
Residues were also found in the sediment at the bottom of the pond;
these reached a concentration of 0.006 mg/kg by the thirteenth day.

In a second study with similar treatment, a procedure for
surface sampling was introduced that enabled water films of only
0.05 mm to be sampled. In this extremely thin surface film, the
initial concentration reached 24 mg/litre. There was a very rapid
fall to around 50 µg/litre after the first week, and by the third
week, none could be detected (the limit of determination was 1 - 2
µg/litre). In the subsurface water, where the limit of
determination was only 0.1 µg/litre, concentrations reached 1
µg/litre shortly after treatment but fell rapidly to about a fifth
of this value by the end of the first week. By the end of the
fourth week, the concentration was below the limit of
determination. Sporadic amounts were found in the sediments, but
most had disappeared by the end of the study (16 weeks).

The effects of overspraying ponds or streams adjacent to arable
fields in the United Kingdom and of treating vineyards in France
with cypermethrin were studied by Crossland et al. (1982). The
fields in the United Kingdom were treated with a tractor-drawn
sprayer at the rate of 70 g/ha and the French vineyards with
mistblowers at the rate of 30 - 45 g/ha. One objective of this
work was to determine the possible occurrence of the insecticide in
the water as a result of spray drift from the treated areas. In
the United Kingdom study, deposits on the soil where the spray had
been applied were in the range of 4 - 7 mg/m², but those on the
surface of the water of the adjacent pond were 4 - 5 orders of
magnitude less. The concentration of cypermethrin in the surface
layer of water (0.06 mm) was between 6 and 20 µg/litre but, after
24 h, only one of the 14 surface samples showed any cypermethrin,
the concentration in this sample being 6 µg/litre. Residues in
the subsurface layers reached between 0.01 and 0.07 µg/litre after
5 h but then declined; after 24 h, levels in most samples were
below the limit of determination (0.01 µg/litre) with only the
occasional sample reaching 0.03 µg/litre.

In the French vineyards, deposits on the surface of the water
were considerably higher (0.04 - 0.5 mg/m²). Concentrations in the
surface water were initially between 0.14 and 1 mg/litre falling to
0.02 mg/litre within 3 h. Even in the subsurface samples,
concentrations of up to 2 µg/litre were occasionally reached, but
they fell rapidly and had generally decreased to 0.1 µg/litre or
less within a few hours.

Further experiments along similar lines were carried out by
Shires & Bennett (1985) who used a fixed wing aircraft to apply
cypermethrin at 25 g/ha to a large field of winter wheat that was
bordered on 3 sides by drainage ditches.

The deposit on the land was about 60% of the nominal rate of
application, while on the water it was only about a tenth of this
value (equivalent to 1.5 g/ha). Analysis of subsurface water
showed that any spray drift reaching the ditches resulted only in
very low levels ranging from below the level of determination of
0.01 µg/litre to a maximum of 0.03 µg/litre. By the fourth day,
none could be detected.

It appears unlikely that spray drift during properly conducted
spray operations will give rise to high concentrations of
cypermethrin in adjacent surface waters. It is also evident that
if cypermethrin residues do occur in natural waters, they are
relatively short lived.

4.5. Bioaccumulation and Biomagnification

4.5.1. n-Octanol/water partition coefficient

In common with those of other synthetic pyrethroids, the
n-octanol/water partition coefficient of cypermethrin is high; a
value of 2 x 10⁶(log P_ow= 6.3) was obtained by extrapolation from
chromatographic data (Gray & Grayson, 1980). McLeese et al. (1980)
reported a calculated log n-octanol/water partition coefficient of
2.44.

4.5.2. Bioaccumulation in fish

The accumulation by fish of cypermethrin from water and its
subsequent elimination have been studied. In a preliminary study,
rainbow trout were exposed to ¹⁴C-benzyl-labelled cypermethrin in
water at 14 °C for a period of 22 days. The initial concentration
each day of 0.165 µg/litre decreased over the 24-h period to 0.064
µg/litre. Radioactivity in whole fish rose to a plateau equivalent
to 0.083 mg cypermethrin/kg wet weight after approximately 11 days.
During the steady state, at least 67% of the radioactivity was
unchanged cypermethrin, but unidentified materials were also
present. When the fish were transferred to clean water after 22
days, the concentration of radioactivity decreased to half the
plateau level in about 11 days. According to this study, allowing
for the cyclical nature of the exposure concentration, the best
estimate of the accumulation factor is approximately 1000 (Baldwin
& Lad, 1978b).

In a follow-up study, 2 groups of rainbow trout of different
sizes were exposed to steady, low concentrations of unlabelled
cypermethrin in a continuous-flow system. When exposed to a mean
concentration of 0.19 µg cypermethrin/litre, residues in small
trout (2-13 g) increased rapidly to approximately 0.15 mg/kg wet
weight over 10 days and 0.23 mg/kg wet weight in 10 - 18 days.
After 18 days, the fish were placed in clean water and depuration
followed. Using a one-compartment mathematical model, it was
calculated that the bioaccumulation factor at equilibrium was 1200.
The calculated depuration half-life was approximately 8 days. In
the larger trout (130 - 160 g), exposed to a mean concentration of
0.18 µg cypermethrin/litre in a continuous-flow system, the uptake

was slower, and residues in whole fish reached 0.12 mg/kg wet
weight after 24 days. Cypermethrin residues in fish were fairly
uniformly distributed (mean values 1 - 2 mg/kg tissue), when
expressed on a lipid-weight rather than a wet-weight basis, except
that the brain contained lower residues than the other tissues
(Bennett, 1981a).

Rainbow trout and common carp were exposed to cypermethrin
concentrations of 0.4 - 1.9 µg/litre in a continuous-flow study for
up to 21 days. It was found that residues in both species were
very similar on a wet- and on a lipid-weight basis, but that there
was only a small difference in residue burden between the fish that
died and those that survived. The mean residue concentrations
(mg/kg tissue) for trout and carp were respectively: 0.91 (died)
and 0.67 (survived), 0.68 (died) and 0.72 (survived), on a wet-
weight basis and 44 (died) and 29 (survived), and 43 (died) and 25
(survived) on a lipid-weight basis, (Bennett, 1981b).

McLeese et al. (1980) studied the concentration factors for
cypermethrin in salmon from various toxicity tests. The results
are given in Table 4.

Table 4. Concentration factors for
cypermethrin in salmon^a
-------------------------------------------
Concentration Exposure Concentration CF^b
in water time fish
(µg/litre) (h) (mg/kg)
-------------------------------------------
12 12 0.04 3.5
7.8 21 0.02 3.6
3.0 62 0.02 6.7
1.4 96 0.01 7.1
-------------------------------------------
^aFrom: McLeese et al. (1980).
^bCF = Concentration in fish/concentration
in water.

The low CFs for cypermethrin may indicate rapid metabolism and
elimination of the compound by salmon.

Accumulation of cypermethrin by fish exposed under field
conditions was studied in rudd taken at various time intervals from
a pond treated with 100 g cypermethrin a.i./ha (Table 5).

These results show a rapid uptake of cypermethrin in the fish
followed by elimination from the fish as the compound is lost from
the water in the pond system. In such a dynamic situation, it is
not possible to give a definite accumulation factor (Crossland et
al., 1978).

Table 5. Residues of cypermethrin in rudd and water from a
pond treated at 100 g active ingredient/ha
---------------------------------------------------------------
Time after treatment Concentration of cypermethrin in:
subsurface water rudd (µg/kg wet weight)
(µg/litre) (individual values)
---------------------------------------------------------------
1 day 1.0 50 and 41
1 week 0.21 45 and 49
2 weeks 0.06 42 and 65
4 weeks 0.01 26 and 30
8 weeks 0.01 19 and 5
16 weeks - 5^a
---------------------------------------------------------------
^aAverage of 8 fish.

In view of the very low concentrations of cypermethrin that are
likely to arise in water from normal agricultural use and the
rapidity with which concentrations decline, fish in the wild will
not contain measurable residues of cypermethrin, in spite of the
concentration factors reported.

4.5.3. Bioaccumulation in aquatic invertebrates

Muir et al. (1985) studied the accumulation of cypermethrin in
sediment-dwelling larvae of the midge Chironomus tentans. These
were allowed to establish themselves in the sediments or were kept
suspended in the water under the conditions of the study described
in section 4.4.1. Bioaccumulation factors were calculated for both
the water and sediment larvae; these varied from 43 to 245 for the
trans-compound and from 34 to 385 for the cis-, expressed as the
ratios of total radioactivity per gram of larvae to that per ml of
water.

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

5.1. Environmental Levels

5.1.1. Air

No data are available.

5.1.2. Water

No data are available.

5.1.3. Soil

See section 4.3.

5.1.4. Food

Cypermethrin is used to control insect pests on a very wide
range of crops, and residues of the parent compound can sometimes
be found in agricultural commodities from treated crops. Foods of
animal origin can also contain limited residues arising either from
the use of the product for the control of ectoparasites or from the
occurrence of residues in the animal feed.

5.1.4.1. Residues in food commodities from treated crops

A large body of information on the levels of residues arising
in crop commodities where cypermethrin has been used according to
Good Agricultural Practice (GAP), was available to the Task Group.
The data had already been comprehensively reviewed by the FAO/WHO
Joint Meeting on Pesticide Residues and summarized in their
published Monographs of the meetings in 1979, 1981, 1982, and 1984.
(FAO/WHO 1980b, 1982b, 1983b, and 1985c). As a consequence of
their reviews, the JMPR were able to propose a series of Maximum
Residue Limits (MRLs) for cypermethrin in a wide range of food
commodities (treated according to GAP) below which the actual
residue levels would be expected to fall. They range from 0.05 to
2 mg/kg. These MRLs are now at various steps in the Codex
procedure and many have already been fully adopted by the Codex
Alimentarious Commission, shown as step "CLX" in Table 6 (Codex
Alimentarius Commission, 1986).

Dried tea is an exception to this range of levels in food
commodities in that the level proposed is 20 mg/kg, but it was
shown that only 0.1% of the residues in dried tea enter the
infusion so that the brew, as drunk, will only contain negligible
amounts (FAO/WHO 1985b). Cereal straws also fall outside this
range in that the MRL is 5 mg/kg, but these are not foodstuffs.

Table 6. Codex limits for cypermethrin
residues in treated crops
--------------------------------------------
Crop MRL (mg/kg) Step
--------------------------------------------
Brassica leafy vegetables 1 CLX
Citrus 2 CLX
Lettuce 2 8
Oil seeds except peanuts 0.2 8
Peas 0.05 CLX
Root and tuber vegetables 0.05 CLX
Tomatoes 0.5 CLX
Wheat grain 0.2 8
--------------------------------------------

In addition to these data, limited information on residues have
been published by Lauren & Henzel (1977), Braun et al. (1982),
Frank et al. (1982), and Awasthi & Anand (1983).

Research has also been carried out on the fate of residues in
stored grain treated experimentally (Joia et al., 1985b; Noble &
Hamilton, 1985). Residues proved to be relatively persistent and a
knowledge of storage times and conditions would be required to
estimate the levels that would occur in the grain trade, should
this use of cypermethrin become accepted practice.

5.1.4.2. Residues in food of animal origin

Residues of cypermethrin can arise in foods of animal origin
(milk or milk products, eggs, meat or meat products), either from
topical application to livestock for the control of ecotoparasites
or from residues in livestock rations. In the USA, the actual
residues in meat and milk are expected to be less than the
tolerances of 0.05 mg/kg per litre product (US EPA, 1984). By
referring to available residue data, the JMPR was able to propose
MRLs for carcass meat and meat products, eggs, and milk.
Subsequently, the following Codex Limits (CLXs) were established
(Codex Alimentarius Commission-1986) (Table 7).

Table 7. Codex limits for cypermethrin residues
in foodstuffs
-------------------------------------------------
Commodity Maximum Residue Limit
mg/kg
-------------------------------------------------
Carcass meat (carcass fat) 0.2
Meat products 0.2
Eggs 0.05
Milk (whole milk) 0.01
-------------------------------------------------

5.2. General Population Exposure

Taking into consideration: (a) the levels of cypermethrin
residues that may occur in food commodities from crops or in foods
of animal origin, where cypermethrin has been used according to
GAP; (b) the contribution of the relevant commodities to the diet;
and (c) the losses that occur during the processing of these
commodities, it can confidently be inferred that the daily intake
of cypermethrin in the human diet will be well below the officially
adopted Acceptable Daily Intake. However, no total diet or market
basket studies are available.

5.3. Occupational Exposure

See section 9.2.2.

6. KINETICS AND METABOLISM

6.1. Absorption, Excretion, and Distribution

6.1.1. Oral

6.1.1.1. Rat

(a) Cypermethrin mixture

Three rats of each sex were given a single oral dose of 0.5 mg
(approximately 1.2 mg/kg body weight for males and 2.1 mg/kg body
weight for females) of a cis/trans mixture of ¹⁴C-cyclopropyl-
labelled cypermethrin. Three days after dosing, low concentrations
of radioactivity were found for both sexes in the kidneys, muscle,
brain, and blood. The level in the liver of male rats was 3 times
higher than that in the liver of female rats (0.37 and 0.12 mg/kg
tissue, respectively). The residues in the fat of the female rats
were 2 - 3 times higher than those in the male rats (0.72 and 0.31
mg/kg tissue respectively). Concentrations in muscle, brain, and
blood were < 0.05 mg/kg. The mean percentage recovery of the
administered dose was more than 100% (Crawford, 1977; Crawford et
al., 1981a).

Urinary excretion of the compound was rapid in both sexes;
approximately 50 - 65% of the dose being excreted in 48 h.
Elimination via the faeces was slower, the mean rate being
approximately 30% of the dose in 3 days. The amount of
radioactivity excreted via expired CO₂, measured in a separate
study using one rat of each sex, was up to 0.1% of the dose in 15
days.

Studies with ¹⁴C-cyclopropyl-labelled cypermethrin indicated
that biliary excretion of the cyclopropyl moiety is a minor route
of elimination (up to 2% in 4 h) (Crawford et al., 1981a).

The metabolism of cypermethrin in maize oil was studied in male
and female Wistar rats following a single toxic oral dose of 200
mg/kg body weight of 2 radio-labelled forms (¹⁴C-benzyl and ¹⁴C-
cyclopropyl) of the insecticide. Minimal amounts of ¹⁴CO₂were
expired from both types of labelled cypermethrin: viz < 0.005 -
0.06% of dose. The elimination of radioactivity within 7 days was
29 - 33% (¹⁴C-benzyl label) and 41-56% (¹⁴C-cyclopropyl label) in
the urine and 55 - 59% and 34 - 46%, respectively, in the faeces.
The differences between the sexes were small (Rhodes et al., 1984).

The distribution and tissue retention of cypermethrin was
studied in 5 male and 5 female Wistar rats receiving daily oral
doses of 2 mg (¹⁴C-benzyl)-labelled cypermethrin/kg body weight for
28 days. Consistent with the lipophilic nature of cypermethrin,
the highest mean tissue concentration was found in the fat (4.1
mg/kg in males and 5.1 mg/kg in females). Concentrations in the
liver, kidneys, adrenals, gut, ovaries, and skin were of the order
of 0.4 - 0.9 mg/kg tissue. Small amounts of radioactivity (0.04 -
0.07 mg/kg) were detected in the muscle, spleen, and bone.

Negligible concentrations (< 0.01 mg/kg) were detected in the
brain (Rhodes et al., 1984). In a further study, the tissues
identified as containing the highest concentrations of ¹⁴C-benzyl-
labelled cypermethrin (fat, liver, kidneys, skin, and ovaries) as
well as whole blood and plasma were used to study the extent of
accumulation and rate of elimination of cypermethrin. A total of
60 female rats were dosed orally with ¹⁴C-benzyl-labelled
cypermethrin at 2 mg/kg body weight per day, for up to 70
consecutive days. Levels in all tissues reached a plateau after 56
days of dosing. The extent of accumulation, expressed as mg
equivalents of cypermethrin per kg tissue, was: fat, 3.91; liver,
0.97; kidneys, 0.69; ovaries, 0.03; skin, 1.89; whole blood, 0.35;
and plasma 0.64. Analysis of fat samples, 24 h after the final
dose, revealed that higher levels of the cis-isomer of cypermethrin
had been retained than of the trans-isomer. The rate of
elimination of radioactivity from fat was biphasic in nature, with
rapid elimination of trans-cypermethrin (half-life = 3.4 days) and
slower elimination of the less-readily hydrolysed cis-cypermethrin
(half-life = 18.9 days). Levels of ¹⁴C residues in the liver,
kidneys, and blood reached control background levels within 29, 8,
and 15 days, respectively, of the final dose. Apart from fat, the
only other tissue that contained radioactivity was the skin; the
rate of elimination of radioactivity from the skin was similar to
that for fat. Accumulation in the sciatic nerve was also studied
in rats dosed for 26 days. No appreciable bioaccumulation was
found to occur (Jones, 1981; Rhodes et al., 1984).

Three Wistar rats of each sex, given a single oral dose of
(¹⁴C-cyano)-cypermethrin (4.3 mg/kg body weight), eliminated 30 -
66% of the dose in the faeces over 3 days. Urinary excretion of
¹⁴CN-label was slow, accounting for 6 - 12% of the dose and
elimination of expired ¹⁴CO₂accounted for only 1.2 - 1.5% of the
dose. Tissue retention in major organs apart from fat, was higher
than that in similar studies involving ¹⁴C-benzyl or ¹⁴C-
cyclopropyl labelling, thus reflecting metabolism typical of the
¹⁴C-labelled cyanide moiety (Crawford et al., 1981a).

(b) Separate isomers

The fates of both cis- and trans-isomers have been studied
separately. Groups of 3 - 6 Wistar rats of each sex were given
single oral doses (approximately 2.5 mg/kg body weight) of either
the cis-isomer or the trans-isomer, both ¹⁴C-labelled in the
benzyl ring. Both isomers were rapidly eliminated. The greater
part of the administered dose was excreted in the urine; 40% and
60% for males and females, respectively, of the cis-isomer and 70%
and 80% of the trans-isomer within 48 h. Elimination of the cis-
isomer in the faeces amounted to 26% and 48% for male and females,
respectively; elimination of the trans-isomer was 24%. The
results for the cis-isomer show a clear sex difference in the route
of elimination. After 72 h, less than 5% of the administered dose
of either isomer remained in the animal tissues with the exception
of the intestines and skin. Fat and skin contained the highest
concentrations (Crawford, 1976a,b; Crawford et al., 1981a). It has

been demonstrated (Crawford & Hutson, 1977a, Crawford et al.,
1981a) that the residue derived from cis-cypermethrin is
eliminated more slowly from fat than from other tissues. In one
study, 8 female rats were given (¹⁴C-benzyl)- cis-cypermethrin at
2.5 mg/kg body weight orally, and elimination of radioactivity was
measured in fat samples from 8 up to 42 days after dosing. The
radioactivity was calculated to have a half-life of 11.7 (3.4 -
16.7) days. Ninety to 100% of the radioactivity still remaining in
the fat at 25 days was present as unchanged cypermethrin. The
residues in the liver and kidneys were much lower than those in the
fat but were eliminated at a similar rate (Crawford et al., 1981a).

6.1.1.2. Mouse

(a) Separate isomers

Elimination of radioactivity was measured in male Swiss-Webster
mice, dosed once orally with cis- or trans-cypermethrin, ¹⁴C-
labelled in either the benzyl (8 mg/kg body weight) or cyclopropyl
(7 mg/kg body weight) moiety. The ¹⁴C-benzyl-dosed mice eliminated
22% and 34% of the administered dose of cis-isomer in the urine
and faeces, respectively, in one day; values for the trans-isomer
were 41% and 16%, respectively. The ¹⁴C-cyclopropyl-dosed mice
eliminated 20% of the administered dose of cis-isomer in the urine
and 50% in the faeces in one day; the values for the trans-isomer
were 55% and 16%, respectively. Thus, radioactivity from the
trans-isomer was mainly eliminated in the urine and that from the
cis-isomer in the faeces. The ¹⁴C-benzyl-treated mice were killed
1, 3, or 8 days after dosing; the ¹⁴C-cyclopropyl-treated mice, 3
days after dosing. Residues of radioactivity from both labels, 3
days after dosing, were low in all tissues except for the fat. The
sequence of the residues in different organs was fat > liver ~
kidneys > blood ~ muscle > brain. Residues fell rapidly during
the ¹⁴C-benzyl study, with the exception of the residues derived
from the cis-isomer in fat, which did not decrease during the
study period (Hutson, 1978a; Hutson et al., 1981). However, in a
further study, radioactivity was measured in fat samples from 10
male mice taken up to 42 days after a single oral dose of
approximately 8.8 mg/kg body weight (¹⁴C-benzyl)- cis-cypermethrin.
The residue was eliminated exponentially with a half-life of 13.1
(3.6 - 18.4) days. At 8 and 22 days after dosing, approximately
90% of the radioactivity present in two pooled fat samples was
attributable to unchanged cis-cypermethrin (Crawford & Hutson,
1978; Crayford et al., 1980; Hutson et al., 1981).

6.1.1.3. Dog

(a) Cypermethrin mixture

Two male beagle dogs were given single oral doses of (¹⁴C-
cyclopropyl)-cypermethrin at 2 mg/kg body weight (Crawford, 1979a).
Elimination of labelled material was rapid in both dogs, though a
variable distribution between urine and faeces was observed between
the 2 dogs, i.e., 21 and 57% in urine and 78 and 48%, respectively,
in faeces. In a further study, one dog was dosed orally with

(¹⁴C-benzyl)-cypermethrin at 2 mg/kg body weight (Crawford, 1979b).
Over 4 days, 80% of the radioactivity was recovered in the faeces
and 11% in the urine. Analysis of tissues, 4 days after dosing,
revealed that the gall bladder (1.5 mg/kg tissue) and renal fat
(0.3 mg/kg tissue) contained the highest levels of radioactivity
expressed as cypermethrin. Negligible amounts were detected in the
brain (0.006 mg/kg tissue) and sciatic nerve (0.09 mg/kg tissue).
In the liver, adrenals, bone marrow, pituitary gland, and
mesenteric fat, levels of cypermethrin of 0.1 - 0.2 mg/kg tissue
were found.

(b) Separate isomers

Administration of (¹⁴C-benzyl)- cis-cypermethrin or
(¹⁴C-benzyl)- trans-cypermethrin separately to groups of 2 male
dogs as a single (2 mg/kg body weight) oral dose resulted in
83.4% of cis-isomer and 88% of trans-isomer being recovered in
the urine plus faeces over 6 - 7 days (Crawford, 1979b).
Quantitative differences existed between the amounts eliminated
via the 2 routes. As already mentioned, a variable distribution
was found. These data are consistent with the results of the study
involving ¹⁴C-cyclopropyl-labelled cypermethrin (Crawford, 1979a),
and the variation in amounts according to the route of elimination
probably reflects the inter-group differences in rates of
absorption of labelled material.

6.1.1.4. Cow

Three studies were carried out on lactating cows fed diets
containing 0.2, 5, or 10 mg ¹⁴C-benzyl and/or ¹⁴C-cyclo-propyl-
cypermethrin/kg feed, respectively, twice daily, for 7 or 21 days.
The estimated daily intake was 2, 50, or 100 mg cypermethrin/cow.
The radioactivity was rapidly eliminated following ingestion.
Equilibrium between ingestion and elimination was reached after
about 4 days. The amounts eliminated via the major routes were
similar for both labels, i.e., approximately 50% in the urine, and
approximately 40% in the faeces (mainly unchanged cypermethrin).
Polar and acidic components were found in the urine. Up to 0.2% of
the administered radioactivity was found in the milk, mainly in the
cream phase (about 88%). Feeding 0.2, 5, or 10 mg/kg feed, the
residues in the milk were 0.0006, 0.012, or 0.03 mg cypermethrin
/litre, respectively. Radioactivity (expressed as mg cypermethrin
/kg tissue) in the carcasses of the animals of the 3 groups at
slaughter was not detectable in muscle and brain (< 0.001- < 0.04
mg/kg). Levels in other tissues were: blood < 0.04 - 0.07 mg/kg,
liver 0.004 - 0.21 mg/kg, kidneys 0.003 - 0.11 mg/kg, and
subcutaneous and renal fat 0.01 - 0.1 mg/kg (Croucher et al.,
1985).

Swaine & Sapiets cf. FAO/WHO (1982b) dosed cows daily with 0.2,
5, or 50 mg cypermethrin (43% cis-isomers, 35% trans-isomers) per
kg feed for up to 29 days. Residues in milk and tissues were
comparable to those reported by Croucher et al. (1985).

6.1.1.5. Sheep

The elimination pattern in a single sheep, given one oral
dose of a mixture consisting of unlabelled cypermethrin with ¹⁴C-
benzyl- and ¹⁴C-cyclopropyl-labelled material (3.9 mg/kg body
weight) in a gelatin capsule, showed that 41% of the administered
dose was excreted in the urine and 20% was eliminated in faeces,
within 48 h. Tissue residues, 2 days after treatment, were muscle,
0.04 mg/kg; and liver, kidneys, and renal fat approximately 0.4
mg/kg tissue (Crawford & Hutson, 1977b).

6.1.1.6. Chicken

¹⁴C-phenoxy-labelled cypermethrin ( cis:trans, 55:45) was
administered orally to laying hens, daily for 14 days, at a rate
equivalent to 10 mg/kg diet (about 0.7 mg/kg body weight).
Radioactivity in the eggs reached a plateau, equivalent to about
0.05 mg cypermethrin/kg, after 8 days. Most of the radioactivity
was found in the yolk (up to 0.19 mg/kg) and about half of it was
identified as cypermethrin. The rest was closely associated with
neutral lipids and phosphatidyl cholines. Residues in the
carcasses, at slaughter, were low; values were between 0.01 and
0.02 mg/kg in muscle tissue, about 0.08 mg/kg in the subcutaneous
and peritoneal fat, and 0.37 mg/kg in the liver. The composition
of residues in the liver was not conclusively established. Apart
from small amounts of unchanged cypermethrin, the radioactivity was
also associated with highly polar material. However, it is evident
that the hen has a very effective mechanism for the metabolism of
cypermethrin (Hutson & Stoydin, 1987).

Comparable results were obtained from non-labelled studies with
laying hens in which dietary levels of up to 40 mg cypermethrin/kg
diet were fed for 28 days (Wallace et al., 1982).

6.1.1.7. Man

Male volunteers were each given a single oral dose of 0.25,
0.5, 1, or 1.5 mg cypermethrin in corn oil in a capsule. Urinary
excretion of cypermethrin metabolites was rapid. The subjects
excreted an average 78% of the dose of trans-isomer and 49% of the
cis-isomer within 24 h. These values did not differ from the
results in rats. The ester cleavage was a major route of
metabolism of cypermethrin in man. As reported in other animal
species, the trans-isomer was metabolized more readily than the
cis-isomer. Concentrations of both isomers excreted in the urine
between 2 and 5 days after dosing 0.5 or 1 mg cypermethrin were
below the limit of detection of 0.01 mg/litre (Eadsforth & Baldwin,
1983).

Groups of 2 male subjects were given cypermethrin in daily oral
doses of 0.25, 0.75, or 1.5 mg/man, by capsule, for 5 consecutive
days. During the dosing period and the following 5 days, 24-h
urine samples were collected daily and analysed for the
concentration of the cyclopropane carboxylic acid metabolite. The
results showed that the respective percent-ages of the cis- and

trans-isomers of cypermethrin, excreted in the 24-h period
following each of the oral doses, were similar to the percentage
excretion of these isomers measured in the single oral dose study.
Therefore, no accumulation in the body occurred (van Sittert et
al., 1985a).

6.1.2. Dermal

6.1.2.1. Cow

Two lactating cows were sprayed 3 times with 1.1 g
cypermethrin/animal, with 2-week intervals between treatments.
Milk samples were analysed during this period. Tissue samples
were analysed approximately three weeks after the final spraying.
The residues were: in whole milk, < 0.01 mg/litre; muscle, liver,
and kidneys, < 0.01 mg/kg tissue and in fat samples, 0.02 mg/kg
tissue or less (Baldwin et al., 1977).

Comparable results were obtained when 2 barns were sprayed with
either 0.05% or 0.1% of cypermethrin prepared from a 10% a.i.
formulation. Cows were present during spraying. Milk was
collected up to 4 weeks after spraying (0.05% application) or 4
days after spraying (0.1% application). Only the samples collected
4 days after the 0.05% treatment and 2 days after the 0.1%
treatment contained detectable residues (0.005 mg/kg milk). No
residues were found (< 0.002 mg/kg milk) in any of the other
samples (Baldwin & Lad, 1978a).

Cows were dipped twice in approximately 170 mg cypermethrin
/litre with a 10-week interval between treatments. The animals
were sacrificed 4 or 14 days after the second dipping. Residues in
muscle and liver did not exceed 0.01 mg/kg tissue. Fat samples
contained detectable residues. The highest was 0.13 mg/kg in renal
fat. The fat residue did not decline between 4 and 14 days after
treatment (Baldwin, 1977a).

Cattle sprayed once with 0.1 and 0.2% a.i. showed the same
level of residues (< 0.005 mg/kg tissue) in muscle, liver, and
kidneys, and a level of < 0.01 mg/kg in fat samples, 1, 3, 8, and
15 days after treatment. In cattle treated twice, fat samples
contained residues ranging from 0.01 to 0.05 mg/kg tissue (Bosio,
1979).

Many trials in which cows were sprayed with, or dipped in,
cypermethrin solutions were carried out in Australia. The milk
from cows sprayed with 0.1% cypermethrin did not contain any
detectable residues. The highest residue (0.03 mg/kg) in butterfat
was found one day after spraying. When the cows were dipped in a
dipwash containing 75 mg cypermethrin/litre, residues in the milk
determined 1, 3, and 7 days after dipping ranged from 0.01 to <
0.002 mg/litre. Omental fat contained the highest residue level
(0.02 mg/kg) 3 and 4 days after dipping. Liver, kidneys, and
muscle did not contain any detectable residues. A second dipping,
7 days after the first, did not cause any build-up of cypermethrin
in the tissues of the cattle (FAO/WHO, 1982b).

Detectable residues of cypermethrin of up to 0.01 mg/kg
butterfat were found in milk samples taken over 21 days from 5 of
10 cows wearing cypermethrin-integrated ear tags (Braun et al.,
1985).

Taylor et al. (1985) found cypermethrin in the hair of cattle,
in concentrations of up to 2.8 mg/kg, after application of
impregnated ear tags.

6.1.2.2. Sheep

Two sheep were each treated dermally with a mixture consisting
of unlabelled cypermethrin mixed with ¹⁴C-benzyl-and ¹⁴C-
cyclopropyl-labelled material at 22 mg/kg body weight. The
cypermethrin was slowly absorbed. Less than 0.5% of the dose was
excreted in the urine within 24 h and only 2% over a 6-day period.
Faecal elimination was also slow, 0.5% of the dose being eliminated
in 6 days. Approximately 30% of the dose was recovered from the
application area. Tissue residues, 6 days after treatment, were:
muscle, 0.04; renal fat, 0.3; and liver and kidneys 0.12 mg/kg
tissue (Crawford & Hutson, 1977b).

6.1.2.3. Man

A male subject was given a single dermal application of a ULV
formulation of cypermethrin (50 mg cypermethrin in hexylene
glycol/Shellsol AB) on the underside of the forearm. The majority
of this application (35 mg) was removed from the skin after 4 h.
Urine was monitored for residues of the acid metabolite [3-(2,2-
dichlorovinyl)-2,2-dimethylcyclo-propane-carboxylic acid] and its
glucuronide, for a 96-h period after dosing. The metabolites were
not detected over this period (Coveney & Eadsforth, 1982).

In a study by van Sittert et al. (1985b), 2 male volunteers
were given a single dermal application of a ULV formulation, 25 mg
cypermethrin in hexylene glycol/Shellsol A, on the underside of the
forearm. An average