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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY


    ENVIRONMENTAL HEALTH CRITERIA 82







    CYPERMETHRIN








    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    World Health Orgnization
    Geneva


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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. Qulennec, 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 g/litre), 
and aquatic invertebrates (LC50s in the range of 0.01-> 5 
g/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 LD50 ranging 
from 0.03 to 0.12 g/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 g 
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 V79 Chinese 
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

Chemical Structure

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 cypermethrina
--------------------------------------------------------------------
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 10-7 Pa (1.4 x 10-9 mmHg)

 n-octanol/water partition        2 x 106 (log Pow 6.3)
 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. 

FIGURE 1

    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  LDb     Reference
            Extraction        Partition       Clean-up        GLC or HPLC conditiona   (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)
---------------------------------------------------------------------------------------------------------

Table 2.  (contd.)
---------------------------------------------------------------------------------------------------------
Sample                      Sample preparation                Method of determination  LDb     Reference
            Extraction        Partition       Clean-up        GLC or HPLC conditiona   (mg/kg)
            solvent                           Column/elution
---------------------------------------------------------------------------------------------------------
Milk        CH3CN              n-hexane:2%     Florisil/       electron capture         0.005   Braun & 
                              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 conditiona   (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 g/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 m2 than the land 
itself and that the initial concentration in the surface film of 
water was between 6 and 20 g/litre.  Residues in the water below 
the surface film did not reach more than 0.1 g/litre and within 
24 h the levels had nearly all fallen to below the limit of 
determination of 0.01 g/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 g/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 g/cm2 to 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 CO2 in 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. 

FIGURE 2

    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 CO2 evolved.  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 g/litre after the first week, and by the third 
week, none could be detected (the limit of determination was 1 - 2 
g/litre).  In the subsurface water, where the limit of 
determination was only 0.1 g/litre, concentrations reached 1 
g/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 g/litre but, after 
24 h, only one of the 14 surface samples showed any cypermethrin, 
the concentration in this sample being 6 g/litre.  Residues in  
the subsurface layers reached between 0.01 and 0.07 g/litre after 
5 h but then declined; after 24 h, levels in most samples were
below the limit of determination (0.01 g/litre) with only the 
occasional sample reaching 0.03 g/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 g/litre were occasionally reached, but 
they fell rapidly and had generally decreased to 0.1 g/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 g/litre to a maximum of 0.03 g/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 Pow = 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 g/litre decreased over the 24-h period to 0.064 
g/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 g 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 g 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 g/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 salmona
-------------------------------------------
Concentration  Exposure  Concentration  CFb
in water       time      fish        
(g/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
-------------------------------------------
a From:  McLeese et al. (1980).
b CF = 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 (g/kg wet weight)
                      (g/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              -                 5a
---------------------------------------------------------------
a Average 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 14CO2 were 
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 14CO2 accounted 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 of 53% of the original amount of cypermethrin 
applied was removed from the skin, 4 h after application.  
Approximately 0.1% was excreted as the urinary metabolite, 
cyclopropane carboxylic acid, during a 72-h period.  Measurements 
were made using gas liquid chromatography - mass spectrometry, a 
method with a higher sensitivity and selectivity than gas liquid 
chromatography - electron capture detection, which was used in the 
previous study. 

6.2.  Metabolic Transformation

6.2.1.   In vitro studies

     In vitro studies on mouse liver homogenates have shown that 
ester cleavage is more extensive for the  trans-isomer than for the 
 cis-isomer.  One mg of each of (1RS,trans)- and (1RS,  cis)-
cypermethrin was incubated with 2.2 ml of approximately 10% mouse 
microsome substrate at 37 C for 30 min, under the following 
conditions:  (a) tetraethyl pyrophosphate (TEPP)-treated microsomes 

(neither esterase nor oxidase activity); (b) normal microsomes 
(esterase activity); (c) TEPP-treated microsomes plus NADPH 
(oxidase activity); and (d) normal microsomes plus NADPH (esterase 
plus oxidase activity).  Each esterase preparation hydrolysed about 
twice as much  trans-cypermethrin as  cis-cypermethrin.  In contrast, 
 cis-cypermethrin was metabolized more rapidly in an oxidation 
system than  trans-cypermethrin.  The major site of ring 
hydroxylation was the 4' position and the secondary site was the 5 
position.  The  trans-methyl group was an important site of 
hydroxylation in the ester metabolites and  cis-methyl oxidation was 
predominant in the ester-cleaved acid metabolites.  The 
hydroxymethyl derivatives were further oxidized to the 
corresponding aldehydes and carboxylic acids. 

    3-Phenoxybenzaldehyde-cyanohydrin was detected as a minor 
metabolite.  The preferred sites of hydroxylation were:  with 
 trans-cypermethrin,  cis-methyl > 4' position >  trans-methyl > 5 
position; with  cis-cypermethrin, trans > cis > 4' position > 5 
position (Shone & Casida, 1978; Shone et al., 1979).  With  cis-
cypermethrin, at least, cleavage of cypermethrin to cyanohydrin may 
result from both hydrolytic and oxidative mechanisms, since large 
amounts of the cleavage products were also evident in the oxidase 
system, which lacks esterase activity (Shono & Casida, 1978; Shono 
et al., 1979).  However, at approximately 35-times higher substrate 
levels, the hydrolysis rate of cypermethrin isomers was depressed 
(Sderlund & Casida, 1977). 

    In studies on the metabolism of 14C-cypermethrin by rat liver 
microsomes, the overall rates of metabolism of  cis- and  trans-
cypermethrin were similar, though their metabolic routes differed.  
The  cis-isomer was metabolized almost exclusively by an NADPH-
dependent oxidative pathway to 4'hydroxy- cis-cypermethrin with 
subsequent oxidative ester cleavage.  The predominant route for the 
metabolism of the  trans-isomer was hydrolysis to the  trans-acid by 
microsomal carboxylesterase (Crawford, 1979c).  The  in vitro 
esteratic capacity was determined in rat, rabbit, and human liver 
microsomes using  p-nitrophenyl acetate and cypermethrin as 
substrate.  The relative ability to hydrolyse cypermethrin was 
rabbit > man > rat.  Rabbit and rat microsomes metabolized the 
 trans-isomer 6 times faster than the  cis-isomer.  Human 
microsomes showed a similar capacity for metabolizing both  cis- 
and  trans-isomers (Croucher et al., 1982a,b). 

6.2.2.   In vivo studies

    The identification of the metabolites of cypermethrin has been 
studied in mice (Hutson, 1978b, Casida et al., 1979; Hutson et al., 
1981), rats (Crawford & Hutson, 1977a; Casida et al., 1979; Hutson, 
1979a,b; Crawford et al., 1981b; Rhodes et al., 1984), dogs 
(Crawford, 1979d,e), and cows (Swaine & Sapiets, 1980a,b; Croucher 
et al., 1985). 

    Overall, metabolism in these species is similar.  Differences 
that occur are related to the rate of metabolite formation rather 
than to the nature of the metabolites formed.  The only major 
differences between species relate to conjugation reactions. 

    Cypermethrin (both isomers) is metabolized via cleavage of the 
ester bond.  The cyclopropane carboxylic acid moiety is mainly 
excreted as the glucuronide conjugate; hydroxylation of the methyl 
group occurs only to a limited extent (Crawford, 1979e; Rhodes et 
al., 1984).  The 3-phenoxy-benzyl product of the ester hydrolysis 
is converted to PBA.  The cyanide moiety is metabolized to 
thiocyanate (Hutson, 1979b).  The PBA moiety is mainly excreted as 
a glutamic acid conjugate in the cow (Croucher et al., 1985), as a 
taurine conjugate ( N-(3-phenoxy-benzoyl)taurine) in 2 strains of 
mouse (Hutson & Casida, 1978; Hutson, 1978b, 1979a; Hutson et al., 
1981), and as a glycine conjugate in the rat and dog (Crawford & 
Hutson, 1977a; Crawford, 1979d) and in the sheep, cat, and gerbil 
(Huckle et al., 1981a).  PBA is further metabolized (rat > 
mouse > dog) via the 4'-hydroxylation to 3-(4'-hydroxyphenoxy)
benzoic acid and its sulfate conjugate (Crawford & Hutson, 1977a; 
Hutson, 1978b; Crawford, 1979d).  Glucuronic acid conjugates of PBA 
and its 4'hydroxy derivative are the major urinary metabolites in 
the marmoset, rabbit, guinea-pig, and hamster.  The rat was unique 
among the animal species tested in utilizing sulfuric acid for the 
conjugation of the 4'-hydroxy derivative (Huckle et al., 1981a).  
The major route of excretion for cypermethrin metabolites is via 
the urine; unchanged cypermethrin accounted for the majority of 
radioactivity found in faeces in radiolabel studies.  The amount of 
cyclopropyl-radioactivity eliminated in the bile (1%) suggests that 
the biliary-intestinal-faecal route is of minor importance for this 
moiety (Crawford & Hutson, 1977a; Crawford, 1979e; Rhodes et al., 
1984).  Biliary excretion of PBA occurred as glucuronide and that 
of 4'-OH-PBA as ether and ester glucuronic acid conjugates.  Very 
little was eliminated in the faeces, indicating that the biliary 
glucuronides decompose and/or are enzymatically cleaved in the 
gastro-intestinal tract to the respective benzoic acids.  The 
latter are subsequently reabsorbed and undergo further metabolism, 
principally to the sulfate ester, which is excreted in the urine 
(Huckle et al., 1981b).  As already noted, the major urinary 
metabolite of cypermethrin in cows is  N-(3-phenoxy-benzoyl)glutamic 
acid.  This metabolite is also found in the organs and tissues with 
only a small quantity of unchanged cypermethrin.  The residues in 
body fat consist mainly of cypermethrin.  An unidentified polar 
metabolite, present in the liver and kidneys, is suspected of being 
a conjugate of 3-(4'-hydroxyphenoxy)benzoic acid.  The small 
portion  of radioactivity appearing in milk was associated with 
lipid components and consisted mainly of unchanged cypermethrin 
(Croucher et al., 1985).  The metabolic pathway of cypermethrin is 
shown in Fig. 3. 

    As in other mammals, ester cleavage and elimination of the 
cyclopropyl acid moieties in the free and glucuronidated form is a 
major route of metabolism of cypermethrin in man (Eadsforth & 
Baldwin, 1983). 

6.2.3.  Metabolism of the glucoside conjugate of 3-phenoxy-benzoic 
acid

    Studies have been carried out on rats on the metabolism of the 
glucoside conjugate of 3-phenoxybenzoic acid, which occurs 
occasionally as a metabolite in plants (Crayford, 1978).  The 

results indicated that the rat hydrolyses the glucoside and then 
metabolizes the 3-phenoxybenzoic acid in virtually the same way as 
it would metabolize PBA liberated during the metabolism of 
cypermethrin. 

FIGURE 3

    The same conclusion was also reached by Mikami et al. (1985).  
During this study involving the metabolism of the glucoside 
conjugate of PBA, it was noticed that the skin and carcasses 
contained high residues (4 - 7% of the administered dose) of 
radioactivity.  To characterize the metabolites of PBA in the skin 
and carcasses, rats were given (14C-benzyl) 3-PBA in a single oral 
dose (0.8 mg/kg body weight) or a higher dose (totalling 
approximately 750 mg/kg body weight) for 7 consecutive days.  Two 
components were identified in the skin:  unchanged PBA and a 
mixture of 3-phenoxybenzoyl-dipalmitins.  The components were 
present in the skin of the high-dose animals in the approximate 
ratio of 3:7 and in the carcasses at 9:1 (Crayford & Hutson, 1979, 
1980). 

6.3.  Metabolism in Plants

    Lettuce plants were sprayed outdoors with 14C cypermethrin 
labelled in the cyclopropyl ring (Wright et al., 1980; Roberts, 
1981).  The plants were sprayed twice, at a rate equivalent to 0.3 
kg/ha, and harvested for analysis 21 days after the last treatment.  
Most of the residue was in the form of unchanged cypermethrin (33% 
of the total label present) and polar materials (54%), which were 
shown to be mainly conjugates of  trans-CPA.  One of these 
conjugates was identified as the  beta-D-glucopyranose ester.  
Evidence for this was obtained from studies on abscised cotton 
leaves.  The acid,  trans-CPA was shown to be readily converted 
into a mixture of the  beta-D-glucopyranose ester, an acidic 
derivative of this, and disaccharide derivatives, including the 
glucosyl arabinose ester and the glucosylxylose ester. 

    Small apple trees were grown in cages outdoors (Roberts, 1981) 
and the  cis- or  trans-isomers, labelled in either the cyclopropyl 
or the benzyl rings, were applied to either the leaves or fruit.  
In the leaves, it was shown that the main component of the residue 
was cypermethrin itself with smaller amounts of sugar conjugates 
that gave rise on hydrolysis to the 3-phenoxybenzyl alcohol, 
3-phenoxybenzyl aldehyde, or PBA.  A small amount of 4-hydroxy 
cypermethrin was also detected.  There was also evidence that some 
30% of the  cis-cypermethrin was converted to the  trans-isomer, 
though the conversion of  trans- to  cis- was not observed.  Less 
extensive metabolism occurred in the apple fruit.  More than 98% of 
the total label recovered was associated with the peel.  Of this, 
up to 77% was cypermethrin.  Small amounts of the other free 
compounds, together with polar compounds, were detected (Roberts, 
1981). 

    Furuzawa et al. (1986) treated young cabbage plants in the 
greenhouse with known amounts of either  cis- or  trans-
cypermethrin labelled in either the cyclopropyl or benzyl rings.  
After 42 days, 4 - 6% of the applied dose was found on the surface 
of the leaves, 57 - 63% in the acetone extract of the whole leaves, 
and 13 - 26% was present as a bound residue.  The observed half-
lives were 4 - 5 days for the  trans- and 7 - 8 days for the  cis-
cypermethrin.  Isomerization was carefully followed in these 
studies.  First, there was practically no change in the ratio of 
alpha-R to alpha-S isomers.  On the other hand, both of the 1R 
isomers ( cis and  trans) were converted, in part, to the 
corresponding 1S isomers, though the transformation appeared 
greater where  cis- had been the starting material, compared with 
 trans-cypermethrin.  However, the position was complicated by the 
simultaneous conversion of trans to  cis-isomers.  Apparently, these 
changes were much less in the case of the extracts from the whole 
leaf and the authors considered that this isomerization, as well as 
the 1R-1S epimerization, were probably photochemical.  These 
findings on the conversion of  cis to  trans are consistent with the 
formation of  trans-cypermethrin from  cis- reported by Cole et al. 
(1982) in bean and cotton leaves in the greenhouse.  These authors 
also considered this to be a photochemical reaction.  Roberts 
(1981) reported the conversion of  cis- to  trans-cypermethrin on 
apple leaves, but not of trans to cis. 

    The results of studies by Furuzawa et al. (1986) showed that, 
in the intact ester, there was some hydration of the cyano group to 
the amide, and subsequently to the corresponding acid, as well as 
hydroxylation at the 4-benzyl or one of the  gem methyl groups in 
the cyclopropyl moiety.  However, by far the most important 
metabolites were glycoside conjugates of 4'-OH-PBA and CPA (with a 
limited degree of isomerization from  cis to  trans and  vice versa).  
Hydroxylated CPA, either free or conjugated, was a relatively minor 
metabolite. 

    More et al. (1978) studied the uptake of 14C radio-labelled PBA 
in the abscised leaves of a range of different plants, which were 
dipped in aqueous solutions.  The PBA was labelled in the benzyl 
ring.  Mainly cotton plants and vines were studied, but broad 
beans, tomatoes, lettuce, peas, and soybeans were also included.  
In the case of cotton, some of the leaves were exposed to 13C-
labelled CO2 and allowed to take up the labelled PBA after a 2-h 
period of photosynthesis; the 13C label was used to assist 
identification by mass spectroscopy.  A large part of the PBA in 
the cotton leaves was conjugated within a few hours; it was shown 
that most of the conjugated material was the glucose ester.  It was 
also shown, in the 13CO2 study, that at least a part of the glucose 
moiety had been derived from recent photosynthesis.  On more 
prolonged exposure, other conjugates were formed.  In the case of 
vine leaves, these proved to be a series of disaccharides that 
contained pentose sugars as well as glucose.  The evidence 
suggested that these had been formed by the addition of the pentose 
sugar to the glucose conjugate rather than by the PBA becoming 
conjugated with the preformed disaccharide.  The conjugates in the  
other plant species were not always positively identified, but the 
authors commented that the interspecies differences were likely to 
be mainly of degree rather than of any fundamental differences in 
process. 

    Mikami et al. (1984) studied the metabolism of PBA in abscised 
leaves of cabbage, cotton, cucumber, kidney bean, and tomato 
plants.  PBA was rapidly converted into more polar products by 
esterification with glucose, malonylglucose, gentiobiose, 
cellobiose, glycosylxylose, and tri-glucose.  The main metabolites 
were malonyl glucoside in cabbage, kidney bean, and cucumber, and 
the glucosylxylose ester in cotton. The gentiobiose and tri-glucose 
esters were predominant in tomato.  The metabolism of cypermethrin 
in plants is summarized in Fig. 4. 

6.4.  Metabolism in Fish

    The metabolism of  cis-cypermethrin (14C-labelled in either the 
acid or the alcohol moiety) in trout was studied by Edwards & 
Millburn (1985a).  In contrast with that in other animals (frogs, 
mice, and quail), ester cleavage of cypermethrin was very slow, 
and the main metabolic pathway was hydroxylation to give the 4-
hydroxyphenoxy derivative, which was excreted in the bile as the 
glucuronide.  Edwards & Millburn (1985b) identified the glucuronide 
of CPA and the ether glucuronide and sulfate of 4-hydroxy PBA, but 
only as minor metabolites. 

FIGURE 4

    Trout liver microsomes metabolize both  cis- and  trans-isomers 
of cypermethrin to the 4'-hydroxy derivatives of the intact esters 
and their corresponding ether glucuronic acid conjugates at 
comparable rates.  There are indications, derived from studies with 
other pyrethroids, that the liver microsomes of the carp are more 
able to metabolize pyrethroids than those of the salmonids (Edwards 
& Millburn, 1985b). 

7.  EFFECTS ON ORGANISMS IN THE ENVIRONMENT

    Leahey (1985) and Smith & Stratton (1986) give extensive 
reviews on this matter. 

7.1.  Microorganisms

    Effects of cypermethrin on microbial activity in the soil have 
been investigated under laboratory conditions.  Cypermethrin was 
applied to a sandy loam soil at a rate of 2.5 or 250 mg/kg soil.  
No effect was found on the rate of carbon dioxide evolution (Cook, 
1978a) or oxygen uptake (Loveridge & Cook, 1978a) at the lower 
rate.  With 250 mg/kg, slight, but significant, inhibition of the 
CO2 evolution and a decrease in oxygen uptake were noted after long 
incubation periods.  Nitrogen fixation was assessed by the 
acetylene reduction method (Loveridge & Cook, 1978b).  No 
significant effects were found.  Ammonification and nitrification 
were studied in soils, either alone, or amended with urea or 
ammonium chloride.  Again, no significant effects were found, even 
at the high rate of application (Cook, 1978b).  Finally, glucose 
utilization was studied in the short term (2 days) and after pre-
incubation with cypermethrin for up to 38 weeks.  No significant 
effects were noted, even at the high rate (Bromley & Cook, 1979). 

    A second series of experiments, in which cypermethrin was 
applied to a sandy loam at 0.5 or 5 mg/kg soil has been reported.  
Antimicrobial activity was observed in the early stages of 
incubation with fungal population numbers returning to normal 
within 2 - 4 weeks, and with a subsequent stimulation of microbial 
growth.  There was no inhibition of acetylene reduction activity at 
either dosage.  Nitrification and microbial respiration were 
increased at both dosages, suggesting microbial degradation of 
cypermethrin.  Dehydrogenase activity was not affected, while 
urease activity was stimulated.  This study indicates that 
cypermethrin may exert transient effects on the populations and 
activities of microflora, but they are short-lived and minor in 
nature (Tu, 1980). 

    The toxicity of cypermethrin for 4 pathogens of soybean and for 
the nodulation organism  Rhizobium has been investigated.  In a 
paper disc inhibition test, cypermethrin proved non-toxic for 
 Rhizobium, the EC50 exceeding 10 000 mg/litre.  The toxicity for 
the pathogens was higher, EC50 values ranging from 390 to 1700 
mg/litre (Tu, 1982). 

7.2.  Aquatic Organisms

7.2.1.  Fish

7.2.1.1.  Acute toxicity

    In common with other pyrethroids, cypermethrin is very toxic 
for fish in clean water under laboratory conditions. The available 
data are summarized in Table 8.  The data demonstrate a similar 
high acute toxicity for both cold- and warm-water species of fish.  
Certain of these data have been reviewed by Stephenson (1982e). 

    There is no evidence of a significant effect of temperature on 
toxicity, though a negative temperature coefficient has been 
claimed for certain pyrethroids (Kumaraguru & Beamish, 1981).  
Furthermore, the toxicity of pyrethroids for fish was not 
influenced by the hardness or pH of the water (Mauck et al., 1976). 

    To determine the acute toxicity of cypermethrin for  Tilapia 
 nilotica, an EC formulation of cypermethrin (25 g/litre) was 
sprayed on the surface of static water held in stainless steel 
tanks in a glasshouse.   The concentration of cypermethrin in the 
water was determined over a 96-h period.  Depending on the 
application rate, the concentration of cypermethrin in the water 
rose rapidly during the first 24 h after application and decreased 
slowly over the following 3 days.  The tanks each contained 5 fish 
and water to a depth of 30 cm.  Water temperatures were 23 - 26 C.  
No fish deaths occurred when the peak concentration of cypermethrin 
was less than 1.5 g/litre, while all fish died when the 
concentration exceeded approximately 5 g/litre (Stephenson, 
1981a). 

    To study the influence of suspended solids on water 
concentrations and the toxicity for fish of cypermethrin, Rainbow  
trout  were exposed to nominal concentrations of 2 or 5 g 
cypermethrin/litre, which was added to microfiltered mains water or 
to pond water containing 14.5 mg suspended solids/litre.  The 
actual concentrations were measured for water samples taken 30 min 
after initial mixing.  Two samples of pond water were taken.  One 
was analysed as such while the second was centrifuged (60 min at 
3000 rev/min) to precipitate the suspended solids; the clear 
supernatant liquid was then analysed.  The results are summarized 
in Table 9. 

    The data from this study show that suspended solids absorb 40% 
of the cypermethrin initially present.  Fish exposed to an actual 
concentration of 4.9 g cypermethrin/litre in mains water died 
within 24 h, those in pond water containing an actual concentration 
of 2.5 - 4 g/litre survived (Reiff, 1978a). 

    The high degree of adsorption of cypermethrin on soils was 
demonstrated by Riley & Hill (1983) in their studies on the 
toxicity of cypermethrin for  Daphnia and other aquatic organisms.  
The addition of soil to the system reduced the toxicity of the 
aqueous solution by 200 - 350 times. 

    The stainless steel tank study with  Tilapia nilotica was 
repeated with the water initially containing 100 mg suspended 
solids/litre.  In this study too, the presence of suspended solids 
reduced the toxic effects of cypermethrin (about 2-fold) 
(Stephenson, 1982a). 


Table 8.  Acute toxicity of cypermethrin for fish
---------------------------------------------------------------------------------------------------------
Species            Weight (g)  Vehicle                   Temperature  96-h LC50         Reference
                   (or age)                              (C)         (g a.i./litre)
---------------------------------------------------------------------------------------------------------
Brown trout        5 - 8       technical, dispersed via  15           2 - 2.8           Reiff (1976)
 (Salmo trutta)                 DMSO

                   5 - 8       technical, absorbed on    15           1.2a,b            Reiff (1976)
                               pumice

Rainbow trout      1 - 11      technical, absorbed on    10 - 15      0.5a,b,c          Reiff (1978b)
 (Salmo gairdneri)              pumice

                   1 - 2       technical, via acetone    10           0.5               Stephenson 
                                                                                        (1982b)

                   3.3         technical, via acetone    15           2.8               Stephenson 
                                                                                        (1982b)

                   3           emulsifiable concentrate  10           11d,g             Coats & 
                               (40% ai)                                                 O'Donnell-Jeffery
                                                                                        (1979)

                   3           technical, dispersed via  10           55d               Coats & 
                               acetone                                                  O'Donnell-Jeffery 
                                                                                        (1979)

Common carp        4 - 10      technical, absorbed on    10           0.9a,b,c          Reiff (1978b)
 (Cyprinus carpio)              pumice

                   4 - 10      technical, absorbed on    20 - 25      1.1a,b,c          Reiff (1978b)
                               pumice

                   8 - 10      technical, via acetone    10           0.9               Stephenson 
                                                                                        (1982c)

                   2.1         emulsifiable concentrate  22 - 26      3.4f              Stephenson 
                               (5% a.i.)                                                (1982c) 
                                                                                        Stephenson et
                                                                                        al. (1984)
---------------------------------------------------------------------------------------------------------

Table 8.  (contd.)
---------------------------------------------------------------------------------------------------------
Species            Weight (g)  Vehicle                   Temperature  96-h LC50         Reference
                   (or age)                              (C)         (g a.i./litre)
---------------------------------------------------------------------------------------------------------
Rudd  (Scardinius   9 - 10      technical, absorbed on    15           0.4a,b,c          Reiff (1978b)
 erythrophthalmus)              pumice

Atlantic salmon    5.3         technical, dispersed via  10           2 - 2.4b          McLeese et al. 
( Salmo salar)                  ethanol                                                  (1980)

                   9.4         1-R- cis-                  10           0.74              Zitko et al. 
                                                                                        (1979)

 Tilapia nilotica   1 - 3       technical, absorbed on    25           2.0a,b,c          Stephenson 
                               pumice                                                   (1981b)  
                                                                                        Stephenson et
                                                                                        al. (1984)

Fathead minnow     0.74        technical, absorbed on    23 - 25      1.2a,b            Stephenson 
 (Pimephales        (juvenile)  pumice                                                   (1982d)
 promelas)

 Mugil cephalus     0.1         30% EC                    ?            24g               Tag El-Din et al. 
                   30 days                                                              (1981)

 Gambusia affinis   4 weeks     30% EC                    25           6.6g              El-Sebae et al. 
                                                                                        (1983)
---------------------------------------------------------------------------------------------------------
a Flow-through system. Otherwise, static test.
b Measured concentration. Otherwise, nominal.
c The data quoted have been recalculated from the primary data given in the original reports following 
  current statistical methods.
d 24-h LC50.
e Lethal threshold value (geometric mean of lowest concentration with and highest concentration without 
  mortality).
f 48-h LC50.
g Formulation.

 Remark:  In most tests, the pH of the water was 7.5 - 8.5; the hardness was 260 mg/litre as CaCO3 (except 
         for a few cases).
Table 9.  Influence of suspended solids on the toxicity of cypermethrin 
for Rainbow trout
-------------------------------------------------------------------------
Source         Suspended  Initial cypermethrin      Response of Rainbow
               solids     concentration (g/litre)  trout
               (mg/litre)              actual     
                          nominal  total  in water
-------------------------------------------------------------------------
Microfiltered  0          2        1.7    1.7       1/6 fish dead at 48 h
mains water               5        4.9    4.9       6/6 fish dead at 24 h

Pond water     14.5       2        1.2    0.65      no symptoms or deaths
                          5        4.0    2.5       at 7 days
-------------------------------------------------------------------------

7.2.1.2.  Long-term toxicity

    The effects of cypermethrin on the most sensitive stage in the 
life cycle of the Fathead minnow  (Pimephales promelas) were 
investigated using a flow-through system.  Total hardness, pH, 
concentration of dissolved oxygen, and temperature were controlled.  
Within 24 h of fertilization, eggs were exposed to nominal 
concentrations of 0, 0.03, 0.1, 0.3, or 1.0 g/litre (mean exposure 
concentration 0, 0.03, 0.12, 0.17, and 0.79 g cypermethrin/litre), 
for a total of 34 days.  Hatching occurred between the 3rd and 6th 
day, while egg hatch was not affected at the highest concentration.  
No fry survived day 34.  Survival was reduced at concentrations of 
0.3 and 0.1 g/litre but not at 0.03 g/litre.  On the basis of the 
most sensitive parameter, i.e., survival of young fry, the no-
observed-adverse-effect level for cypermethrin lay between 0.03 and 
0.12 g/litre (Stephenson, 1982d). 

7.2.2.  Invertebrates

7.2.2.1.  Acute toxicity

    Aquatic invertebrates show a wide range of susceptibility to  
cypermethrin.  The  data in Table 10 are from static, clean water 
test systems and some of these data have been reviewed by 
Stephenson (1982e).  It can be seen that snails do not show any 
effects at 5 g/litre (close to the water solubility of 
cypermethrin), while some insects show behavioural changes, but no 
mortality at this level.  Crustacea, particularly marine decapod 
Crustacea, are highly susceptible to cypermethrin, mortality 
occurring at levels below 0.05 g/litre.  Water mites are also very 
susceptible (Zitko et al., 1979). 

    In addition to these static water tests, continuous-flow tests 
in clean water have been undertaken with 2 sensitive species 
(Stephenson, 1980b) (Table 11). 

    It can be concluded that effects can be expected when 
concentrations of cypermethrin of the order of 0.01 g/litre are 
maintained in the water phase for more than 96 h. 

    It has been shown that, at 100 g/litre, cypermethrin does not 
affect the growth of the single-celled green alga  Selenastrum 
 capricornutum, over a period of 2 - 4 days (Stephenson, 1982b). 

7.2.2.2.  Long-term toxicity

    The effects of cypermethrin on the survival, growth, and 
reproduction of  Daphnia magna were investigated, over 21 days, in 
a static water test with daily renewal of test solutions.  The 
nominal concentrations tested were 0, 0.003, 0.01, 0.03, 0.1, and 
0.3 g/litre.  Cypermethrin affected all 3 parameters at a nominal 
concentration of 0.3 g/litre, but no effects were noted at 0.1 
g/litre.  Chemical analysis suggested that the  Daphnia were 
exposed to about 50% of the nominal concentration, two-thirds in 
solution, the remainder adsorbed on suspended solids.  These 
results show that the no-observed-adverse-effect level of 
cypermethrin throughout the life cycle for  Daphnia is of the order 
of 0.05 g/litre (Garforth, 1982). 

7.2.3.  Field studies

7.2.3.1.  Deliberate overspraying

    This subject has received wide attention, and various aspects 
have been reviewed in a number of publications (Crossland & 
Stephenson, 1979; Crossland, 1982; Crossland et al., 1982; 
Crossland & Elgar, 1983; Shires, 1983a; Stephenson, 1983). 

    The effects of field applications of cypermethrin on fish were 
studied in a preliminary study by Crossland & Bennett (1976).  A 
small pond was deliberately oversprayed with 100 g cypermethrin/ha 
as an EC formulation.  The peak concentration of cypermethrin in 
the water was 2.6 g/litre.  Wild populations of fish and amphibia 
were not affected by this treatment.  Large numbers of young fish 
seen during the 2 weeks following treatment did not appear to be 
affected. 

    In a second study at the same rate of application, the peak 
concentration of cypermethrin was 1.4 g/litre.  There was no 
observed mortality among 12 small rudd that had been placed in the 
pond 12 days before treatment, and no effects of treatment were 
noted in wild populations of rudd or newts (Crossland et al., 
1978). 


Table 10.  Acute toxicity of cypermethrin for aquatic invertebrates in static tests
---------------------------------------------------------------------------------------------------------
Species              Stage       Temperature  Solvent  24-h EC50    24-h LC50        Reference
                                 (C)                  (g/litre)a  (g a.i./litre)
---------------------------------------------------------------------------------------------------------
Fresh-water

Crustacea

Water flea           up to 24 h  22           acetone               4.2              Reiff (1977)
 (Daphnia magna)      old         18           water    2            2                Stephenson (1980a)b
                                 20           acetone  1.2          -                Stephenson (1982b)
                                 20           acetone  0.3c         -                Stephenson (1982b)

Water hog louse      3 - 8 mm    15           water    0.02         0.2              Stephenson (1980a)
 (Asellus spp.)

Freshwater shrimp    3 - 8 mm    15           id       0.04         0.1              Stephenson (1980a)
 (Gammarus pulex)

Insecta

Mayfly               larvae      15           id       0.07         0.6              Stephenson (1980a)
 (Cloeon dipterum)

Whirligig beetle     adult       15           id       0.07         > 5             Stephenson (1980a)
 (Gyrinus natator)

Bloodworm            larvae      15           id       0.2          > 5             Stephenson (1980a)
 (Chironomus thummi)

Mosquito             larvae      18           id       0.03         1                Stephenson (1980a)
 (Aedes aegypti)

Midge  (Chaoborus     larvae      15           id       0.03         0.2              Stephenson (1980a)
 crystallinus)

Water boatman        adult       15           water    0.7          > 5             Stephenson (1980a)
 (Corixa punctata)

Water boatman        adult       15           id       0.3          > 5             Stephenson (1980a)
 (Notonecta spp.)
---------------------------------------------------------------------------------------------------------

Table 10.  (contd.)
---------------------------------------------------------------------------------------------------------
Species              Stage       Temperature  Solvent  24-h EC50    24-h LC50        Reference
                                 (C)                  (g/litre)a  (g a.i./litre)
---------------------------------------------------------------------------------------------------------
Arachnida

Water mite           adult       15                    0.02         0.05             Stephenson (1980a)
 (Piona carnea)

Mollusca

Snail  (Lymnaea       < 8 mm      15           id       > 5         > 5               Stephenson (1980a)
 peregra)

Marine

Crustacea

Lobster  (Homarus     450 g       10           ethanol  -            0.04g            McLeese et al. 
 americanus)                                                                          (1980)
                     450 g       10           id       -            0.003d,f,g       Zitko et al. (1979)

Shrimp  (Crangon      1.3 g       10           id       -            0.01d,e          McLeese et al. 
 septemspinosa)                                                                       (1980)
---------------------------------------------------------------------------------------------------------
a   EC50 values are based on effects, usually immobilization, other than death.
b   Stephenson (1980a) used cypermethrin (85% a.i.) dissolved in acetone and absorbed on pumice.
c   48-h EC50.
d   96-h LC50.
e   Dispersed via ethanol.
f   1-R- cis-.
g   Salinity, 30%.

 Remark:  In most tests, the pH of the water was 7.5 - 8.5; and the hardness, 260 mg/litre as CaCO3.
Table 11.  Acute toxicity of cypermethrin for aquatic invertebrates in
continuous-flow tests
------------------------------------------------------------------------
Species            Stage       Temperature  EC50           LC50
                   size        (C)         (g/litre)     (g/litre)  
                                            24-h   96-h    24-h    96-h
------------------------------------------------------------------------
Freshwater shrimp  3 - 8 mm    15           0.005  0.004   0.030   0.009
 (Gammarus pulex)

Mayfly             larvae      15           0.008  0.004   0.070a  0.020
 (Cloeon dipterum)  0.5 - 1 cm
------------------------------------------------------------------------
a 48-h LC50.

    Observations on invertebrates were included in these two pond 
studies.  In the first study, which lasted 2 weeks, populations of 
Crustacea, mites, and insects were severely reduced.  Surface 
breathing insects were affected most rapidly, within hours of 
treatment.  Free-swimming dipterous larvae were not noticeably 
affected for 24 h, while zooplankton were killed between 1 and 2 
days after treatment.  Bottom dwelling invertebrates, including 
chironomid larvae, snails, leaches, and flatworms, did not appear 
to be affected, though the numbers in the last 2 groups were low in 
pre-treatment samples. 

    The second study was continued for 15 weeks after treatment.  
Initial results were similar to those reported above.  Macro-
invertebrates were markedly reduced in numbers, 2 weeks after 
treatment.  However, both numbers and diversity returned to normal 
levels after 15 weeks.  Snails and flat-worms (again numbers low in 
this group in pretreatment counts) were unaffected, but no 
arthropods were present in the samples taken at 2 weeks.  
Recolonization by flying insects (beetles and chironomids) 
commenced 4 weeks after treatment.  The Crustacean  Asellus had not 
reappeared by the end of the study. 

    No daphnids or copepods were found in the zooplankton samples, 
1 week after treatment, and they only reappeared in the 8-week 
post-treatment sample.  Populations returned to normal levels in 
10 - 12 weeks.  Some 2 weeks after treatment, an increase in 
filamentous algae was noted, and this persisted until the end of 
the study.  It was inferred that this was a secondary effect 
following from the elimination of known feeders on algae, for 
instance, the mayfly,  Cloeon dipterum, and the daphnid, 
 Simocephalus sp. (Crossland & Bennett, 1976; Crossland et al., 
1978). 

7.2.3.2.  Monitoring of drift from ground and aerial applications

    Two field studies were undertaken to assess the fate and 
effects in adjacent waters of spray drift from ground-based 
agricultural applications of cypermethrin. 

    (a)  Mistblower applications on vines (France)

    Three sites were chosen, each with vines planted up to the 
banks of adjacent streams.  One application of cypermethrin was 
monitored at each site and a second application at one of the 
sites.  A diluted EC formulation of cypermethrin was applied at 
30 g a.i./ha using a backpack, swinging-head mistblower, and at 
45 g a.i./ha using a tractor-mounted, fixed-head mistblower. 

    The deposition on the ground and an adjacent stream of 0.37 - 
4.5 g/ha led to peak concentrations in the subsurface water ranging 
from 0.17 to 1.7 g/litre during the first hour after spraying; the 
concentrations decreased to less than 0.1 g/litre within a few 
hours.  No effects on fish, tadpoles, or frogs were observed.  Some 
aquatic invertebrates in adjacent streams were seen to be 
hyperactive or immobilized during the first 2 h after application.  
This was most obvious with mayfly larvae, water boatmen, water 
beetles, pond skaters, and syrphid larvae.  During the first 3 h 
following application, there was an increase in the number of 
invertebrates caught in drift nets.  However, there were no 
significant population effects in zooplankton or macro-
invertebrates (Bennett et al., 1980). 

    (b)  Boom-and-nozzle applications to row crops (United Kingdom)

    Two sites were chosen each with row crops (potatoes or 
sugarbeet or both) planted up to within 1 - 3 m of the edge of 
ponds.  Two applications of cypermethrin were monitored at each of 
3 ponds.  In each case, a diluted EC formulation of cypermethrin 
was applied at 70 g a.i./ha using tractor-mounted, boom-and-nozzle 
equipment.  Deposition on the ground and over the pond was 
estimated.  The deposition led to peak concentrations in subsurface 
water in the range of 0.01 - 0.05 g/litre.  In one case, the 
concentration in subsurface waters after 24 h was 0.02 - 0.03 
g/litre.  In all other cases, this value was at, or below, 0.01 
g/litre, the limit of detection.  No effects on fish were 
observed.  No residues of cypermethrin were found in fish (limit of 
detection, 5 g/kg wet weight).  The only effects on invertebrates 
in adjacent waters were noted in the corner of 1 pond.  Some pond 
skaters, one water-boatman, and 2 syrphid larvae were found 
immobilized.  They had recovered by the next day.  There was no 
evidence from zooplankton or sweep-net samples of any effects on 
invertebrate populations (Shires et al., 1980). 

    (c)  Aerial application to winter wheat (United Kingdom)

    A large field of winter wheat was chosen, which was surrounded 
on 3 sides by drainage ditches.  An EC formulation of cypermethrin 
was applied at 25 g a.i./ha by fixed-wing aircraft.  Up to 6% of 
the nominal dose was deposited on the water surfaces, resulting in 
maximum levels in subsurface waters of 0.03 g/litre, which 
declined rapidly after spraying.  No effects were observed on caged 
or wild fish, and no significant residues of cypermethrin were 
found in the fish.  A few air-breathing water boatmen and water 
mites, which are very susceptible, showed minor short-term 
reductions in abundance (Shires & Bennett, 1982, 1985). 

    (d)  Application for rice insect control (Korea, Spain)

    An EC formulation of cypermethrin was applied to rice paddies 
in Korea, in which carp had been caged, by hand-spraying at 15 or 
40 g a.i./ha.  Mortality at the higher rate was significantly 
higher than that in the control, i.e., 15 and 7%, respectively 
(Stephenson, 1982c). 

    Another field study was carried out in Spain.  Cypermethrin was 
applied by air to paddy rice and also to caged fish  (Cyprinus 
 carpio) within the area.  The application rate was 15 - 40 g 
a.i./ha.  The limited toxic effects of cypermethrin on fish under 
field conditions were confirmed in this study. Aerial  overspraying 
of the rice paddies at 25 g a.i./ha did not produce any mortality 
(Stephenson et al., 1984). 

    (e)  Applications for tsetse fly control (Nigeria)

    Field studies have been reported on the assessment of the 
environmental impact of the application of cypermethrin for tsetse  
fly control in Nigeria.  Searches for affected fish were made in 
areas that had been selectively sprayed from the ground with an EC 
formulation of cypermethrin at 2 - 3 g a.i./litre, or sprayed from 
the air with an oil-based solution of cypermethrin at 100 g a.i./ha 
in 1977 and at 60 and 150 g a.i./ha in 1978.  The ground spray 
application was successful in controlling the tsetse fly, but only 
the highest rate applied from the air approached a satisfactory 
level of tsetse control.  None of these searches revealed any dead 
fish in the rivers within the areas sprayed with cypermethrin.  
Pre- and post-treatment net samples of aquatic invertebrates were 
taken in an area sprayed at 100/150 g a.i./ha.  Acute mortality 
occurred in terrestrial and aquatic arthropods, such as the water 
beetle and Crustaceans.  Shrimps and mayfly larvae disappeared from 
river benthos after spraying, but reappeared one year later (Smies 
et al., 1980). 

7.3.  Terrestrial Organisms

7.3.1.  Laboratory studies

7.3.1.1.  Acute toxicity

    (a)  Birds

    The acute oral toxicity of cypermethrin for birds is summarized 
in Table 12. 

    In the first study (Coombs et al., 1976), 4 birds of each 
species were observed for a 3-week period after dosing; no deaths 
or toxic signs were noted at the highest dosages applied.  In the 
second study (Rose, 1981), clinical signs of cypermethrin 
intoxication, including ataxia and lethargy, were noted at dosages 
of 3000 mg/kg body weight and above.  One male duckling, out of 28 
of each sex, died at the top dosage of 10 000 mg/kg body weight. 

7.3.1.2.  Short-term toxicity

    (a)  Birds

    Six laying hens were given 5 successive daily oral doses of 
1000 mg cypermethrin/kg body weight in DMSO followed after 3 weeks 
by a second 5-day dosing regime and were observed for a further 3 
weeks.  Control hens did not receive any treatment.  No signs of 
intoxication or histological changes in nervous tissue were noted 
at any time (Owen & Butterworth, 1977). 

Table  12.  Acute oral toxicity of cypermethrin for birds
--------------------------------------------------------------------------
Species           Age     Vehicle      Observation  LD50     Reference
                                       period       (mg/kg
                                                    body 
                                                    weight)
--------------------------------------------------------------------------
Domestic fowl     adult   40% DMSO     21 days      > 2000    Coombs et al.
 (Gallus                                                      (1976)
 domesticus)

French partridge  adult   40% DMSO     21 days      > 3000    Coombs et al.
 (Allectoris                                                  (1976)
 rufa)

Mallard duck      2 - 6   40% emul-    14 days      > 10 000  Rose (1981)
 (Anas             months  sifiable
 platyrhynchos)            concentrate
--------------------------------------------------------------------------

    Cypermethrin was administered for 5 consecutive days to Mallard 
ducks at dosages of 5000 or 10 000 mg/kg diet.  No deaths or 
clinical signs of intoxication were noted during the feeding period 
or over a subsequent 40-day holding period.  Food intake and body 
weights were slightly depressed during the feeding period, though 
most ducks had regained or exceeded their initial body weights by 
the end of the holding period (Rose, 1981). 

    Riviere et al. (1983) studied the influence of cypermethrin on 
the microsomal drug metabolizing enzymes in Japanese quail 
 (Coturnix coturnix).  Cypermethrin had no or only a very weak 
inducing effect. 

    (b)  Honey bees

    Cypermethrin was highly toxic for worker honey bees  (Apis 
 mellifera) in laboratory tests (24-h oral LD50 0.035 g a.i. per 
bee) (Table 13).  Cypermethrin applied on the dorsal side of the 
thorax was more toxic for honey-bees at lower breeding 
temperatures, i.e., at 12 - 20 C, the toxic level was 0.01 - 0.02 
g/bee and at 32 C, 0.02 - 0.03 g/bee.  In addition, the 
sensitivity of the bees to cypermethrin increased with age (Delabie 
et al., 1985). 

    An aqueous dispersion of cypermethrin was sprayed directly on  
worker  honey bees.  Only 5% of the bees sprayed with a 0.01 
g/litre solution were killed.  All bees sprayed with 0.1 and 1 
g/litre died (Harris & Turnbull, 1978). 

    First indications that cypermethrin might not be hazardous for 
bees under field conditions were obtained in cage tests.  Worker 
honey bees were exposed for 2 h to residues produced by treating 
flowering  Solidago (Golden rod) to run-off with a spray containing 
0.5 g cypermethrin/litre and aging the residue for 1 h.  Some 
knock-down of the bees (up to 9%) was noted during the first 8 h 
following initial exposure.  However, most bees recovered, and 
mortality after 1 day and 10 days did not differ from that in 
untreated control bees.  Higher mortality had been noted in an 
earlier study using the same technique but with a higher dosage 
rate of 1.5 g cypermethrin/litre (Gerig, 1979, 1981). 

Table 13.  Toxicity of cypermethrin for worker honey bees
-------------------------------------------------------------------------
Formulation               24-h LD50 (mg/bee)            Reference
              Topical application  Oral administration
-------------------------------------------------------------------------
Technical     0.02                 0.035                Badmin & Twydell
                                                        (1976)
Technical     0.053                0.12                 Knight (1982)
Technical     0.056                -                    Smart & Stevenson
                                                        (1982), Westlake
                                                        et al. (1985)
Emulsifiable  -                    0.031                Badmin & Twydell
concentrate                                             (1976)
(40%)
-------------------------------------------------------------------------

    (c)  Predatory and parasitic species

    Cypermethrin has also been evaluated against a number of 
predatory or parasitic insects and mites.  Laboratory data are 
available for a number of predators (Coleoptera) and parasites 
(Hymenoptera) of insect pests. 

    The available data indicate that cypermethrin can show useful 
selectivity between insect predators and parasites and the relevant 
pest species (Mulla et al., 1978; du Toit, 1978; Waddill, 1978; 
Abdel-Aal et al., 1979; Coats et al., 1979; Holden, 1979; Leake et 
al., 1979; McDonald, 1979; European Patent Office, 1980; Harris & 
Turnbull, 1980; Hagley et al., 1981; Jordan & Chang, 1981; Saad et 
al., 1981; Ascher et al., 1982; Baicu, 1982; Bayoumi, 1982; Chang & 
Jordan, 1982; Osman et al., 1982; Rajakulendran & Plapp, 1982; 
Surulivelu & Menon, 1982; Brempong-Yeboah et al., 1983; Chang & 
Jordan, 1983; El-Guindy et al., 1983; El-Minshawy et al., 1983; 
El-Sebae et al., 1983; Ho et al., 1983; Ishaaya et al., 1983; 
Watters et al., 1983; Abbassy et al., 1984; Bariola & Lingren, 
1984; Brempong-Yeboah et al., 1984a,b,c; Cheng & Hanlon, 1984; Dai 
& Sun, 1984; El-Sayed & Knowles, 1984; Ewen et al., 1984; Fabellar 
& Heinrichs, 1984; Hopkins et al., 1984; Liu et al., 1984; Mani & 

Krishnamoorthy, 1984; Meisner et al., 1984; Le Patourel & Singh, 
1984; Riskallah, 1984; Scott & Georghiou, 1984; Wilde et al., 1984; 
Zohdy et al., 1984; Ahmed et al., 1985; Abou-Awad & El-Banhawy, 
1985; Bostanian & Belanger, 1985; Bostanian et al., 1985; Corbitt 
et al., 1985; Edwards et al., 1985; El-Sebae et al., 1985; Harris 
et al., 1985; Knapp et al., 1985; Knowles & El-Sayed, 1985; McKee & 
Knowles, 1985; Pree & Hagley, 1985; Suhas & Devaiah, 1985; Tewari & 
Krishnamoorthy, 1985; Vekaria & Vyas, 1985; Barlow et al., 1986). 

    (d)  Earthworms

    The toxicity of cypermethrin for the earthworm  (Eisenia 
 foetida) has been assessed in an artificial soil test system.  Worms 
were exposed to dosages of 0, 0.1, 1.0, 10, or 100 mg/kg soil for 
14 days.  No mortality was found (Inglesfield & Sherwood, 1983; 
Inglesfield, 1984). 

    The LC50 for cypermethrin in  Eisenia foetida was found to be 
26.1 g/cm2 (16.3 - 44.4 g/cm2) (Roberts & Dorough, 1984). 

    (e)  Higher plants

    In studies on effects of cypermethrin on seed germination in 
the soybean, seedling emergence and survival were not reduced by 
levels of up to 5000 mg/litre (Tu, 1982).  Cypermethrin has been 
demonstrated not to be phytotoxic for crops when applied at 
recommended dosages (Hargreaves & Cooper, 1979). 

7.3.2.  Field Studies

7.3.2.1.  Applications for tsetse fly control in Nigeria

    Field trials in Nigeria of cypermethrin against Tsetse flies 
( Glossina palpalis (RD) and  Glossina tachnoides Westw.) were 
carried out, over a 2-year period by Spielberger et al. (1979).  
Ground applications of cypermethrin (0.3%) were made on fly-resting 
sites in vegetation using pressurized knapsack sprayers.  
Populations of both species were eradicated after a single 
application.  Levels of over 150 g/ha were needed for complete 
eradication by residual spraying from a helicopter. 

    The effects on the general insect population of aerial 
applications of cypermethrin for tsetse fly control were studied by 
Smies et al. (1980).  Within a few hours of application, dead and 
dying insects were found, exemplifying the rapid knockdown effect 
of cypermethrin.  Insect fallout, as assessed by funnel traps, was 
markedly increased for 1 day by 100 g cypermethrin a.i./ha, and for 
3 days by 150 g a.i./ha.  General insect activity as assessed by 
Malaise trap catches was not affected by 150 g cypermethrin a.i./ha 
(Smies et al., 1980). 

7.3.2.2.  Honey bees

    This subject has been reviewed by Shires & Debray (1982) and 
Shires (1983b). 

    The hazard of practical field applications of cypermethrin for 
worker honey bees was assessed in 2 field trials.  In both trials, 
cypermethrin was applied to flowering oilseed rape, by helicopter, 
at a time when the crops were being actively worked by bees from 
nearby colonies, thus representing a worst case exposure of the 
bees.  The rate of application in both trials was 25 g a.i./ha.  Of 
the 8 hives, placed adjacent to the treated crops, 6 had been 
fitted with dead bee traps and 2 with pollen traps.  Observations 
were made on bee mortality, pollen collection, foraging activity, 
hive populations, and brood areas.  In addition, in the second 
trial, cypermethrin residues were determined in the bees, pollen, 
wax, honey, and in the leaves and flowers of the treated crop 
(Pearson & Shires, 1981; Shires, 1982b). 

    In the first trial, only a small increase in bee mortality was 
noted, following the cypermethrin treatment (Table 14). 
Cypermethrin appeared to be repellent to honey bees foraging the 
crop, but the duration of this effect could not be established 
because of poor weather during the first few days following 
treatment.  Cypermethrin did not have any effects on hive 
populations of adult bees or brood areas. 

    In the second trial, a slight increase in bee mortality was 
found at the time of treatment (Table 14).  Cypermethrin had a 
repellent effect on honey bees for up to 24 h after application.  
Following this period, foraging activity and pollen collection 
returned to normal.  Cypermethrin residues in dead bees, collected 
on the day of spraying and on the following morning, were higher 
than would be expected to be lethal.  However, residue levels in 
dead bees collected after this period were considerably lower than 
those required to produce toxic effects, confirming that they 
represented the natural mortality level.  Very low levels of 
cypermethrin were found in live bees and levels in honey and wax 
were close to the limit of detection.  Concentrations of 
cypermethrin in flowers and pollen declined rapidly after 
treatment.  Again, cypermethrin did not have any effects on hive 
populations of adult bees or of brood areas (Shires, 1982b). 

Table 14.  Mean number of dead bees per hive during large-scale 
field trials with cypermethrina
-----------------------------------------------------------------
Treatment                        Time from treatment             
compound           -2 to -1  -1 to 0  0 to +4  +1 to +2  +3 to +4
(dosage)           days      days     h        days      days
-----------------------------------------------------------------
Winter-sown rape;  65        6        260      40        2
cypermethrin
(25 g a.i./ha)

water control      75        17       0        26        15

Spring-sown rape   9         36       310      2         13
cypermethrin
(25 g a.i./ha)
-----------------------------------------------------------------
a From:  Shires (1983b).

    In glasshouse studies, in which insecticide treatment was 
carried out during foraging by spraying the rape with 0.12 ml of 
Cymbush in 100 ml water (equivalent to 50 g a.i./ha), high 
mortality was observed 2 days after treatment, but no residual 
mortality appeared during the following 2-month period.  In this 
study, oilseed rape flowers were not attractive to bees for at 
least 2 days following treatment. 

    A field test was carried out on a 38-ha field of oilseed rape.  
The insecticide was sprayed on a central area of 13 ha during the 
morning, at a rate of 50 g a.i./ha.  The weather was sunny and the 
temperature about 18 C.  A high level of mortality occurred only 
on the 3 days following treatment.  The results also showed that the 
bees avoided visiting the flowers as soon as the treatment was 
made, especially during the first 2 days.  From the third day after 
the treatment, the repellent effect decreased, and the visits to 
the rape flowers increased reaching normal on the fifth day.  It 
was suggested by the authors that the repellent effect appeared to 
be due to the formulation ingredients. 

    No residues of cypermetherin were found in hive products 
(pollen, wax, or honey) (Delabie et al., 1985). 

    In a study by Gerig (1981), cypermethrin was repellent to 
worker honey bees for a short period after spraying.  Flowering 
 Phaselia plants, within a flight tent, were treated with a spray 
containing 0.5 g cypermethrin/litre.  Honey bee visits to the 
treated flowers were very few over the first 0.5 h following 
treatment and remained at a reduced level during the remaining 
5.5 h of observation on the day of treatment.  Flower visits 
returned to normal levels on the following day (Gerig, 1981). 

7.3.2.3.  Soil fauna

    This topic has been reviewed by Shires (1980).

    In an initial study on the effects of cypermethrin on the soil 
surface fauna and earthworms, cypermethrin was applied at 100 g 
a.i./ha to small plots of spring wheat.  This treatment did not 
have any effect on earthworm populations or on leaf litter 
breakdown, which is an indirect indicator of earthworm activity.  
The general population of soil surface predators, mainly beetles 
and spiders, was reduced to about 50% of the control value soon 
after treatment, but increased to a higher level than that in the 
controls after 5 weeks.  A subsequent secondary decrease in 
predator populations was probably related to the efficiency of 
control of cereal aphids by cypermethrin (Shires et al., 1979).  In 
a second study, cypermethrin was applied at 25 g a.i./ha to newly-
emerged winter barley to control the aphid vectors of barley yellow 
dwarf virus.  Populations of non-target arthropods were assessed 
using pitfall and water traps.  Populations of soil  Collembola  
were only slightly affected by cypermethrin.  Populations of 
predators (beetles, spiders, and centipedes) were already declining 
because of the season, but there were significantly fewer predators 

in the cypermethrin plots compared with the controls at the end of 
the trial.  Cypermethrin treatment did not affect the numbers of 
invertebrates collected from the water traps (Sherwood & Shires, 
1981). 

    Two studies have been reported on the summer application of 
cypermethrin for aphid control in winter wheat.  In France, ground 
applications of cypermethrin at 50 and 75 g a.i./ha were made in 
June and effects on the fauna in the air, on the crop, and on the 
soil surface were studied.  Cypermethrin proved effective against 
the phytophagous (pest) species.  Effects on non-target organisms 
were only minor, with the exception of spiders.  In the second 
study in the United Kingdom, cypermethrin was applied in June using 
a fixed-wing aircraft at 25 g a.i./ha.  Again, cypermethrin proved 
effective against the pest species, while, generally, effects on 
non-target organisms were minor and short-lived (Shires, 1982a,c). 

    Similar results have been obtained in studies on the aerial 
application of cypermethrin at 25 g a.i./ha on oilseed rape and at 
50 and 75 g a.i./ha on maize, in France (Inglesfield, 1982; 
Garforth, 1983). 

7.3.2.4.  Foliar predators and parasites

    The relative toxicity of cypermethrin for pests and their 
parasites and predators is such that the balance between host/prey 
and parasites/predators may not be adversely affected in the field.  
However, care should be taken where predatory mites are important 
in pest management.  The high toxicity of cypermethrin for 
predatory mites has been confirmed under field conditions (Wong & 
Chapman, 1979; Aliniazee & Cranham, 1980; Shires & Tipton, 1982). 

    The effects of cypermethrin treatments, included in a spray 
programme for cotton insect control, on white fly parasitism have 
been studied in the Sudan.  The treatment regime that gave the 
consistently highest level of control of parasitism included 
cypermethrin at 40 g a.i./ha in 4 early season sprays (Shires & 
Tipton, 1982). 

8.  EFFECTS ON EXPERIMENTAL ANIMALS AND  IN VITRO TEST SYSTEMS

    Leahey (1985) and Smith & Stratton (1986) have reviewed the 
available literature on this subject. 

8.1.  Single Exposures

8.1.1.  Oral

    The acute oral toxicity of cypermethrin (mixture of  cis-/ trans-
isomers) in experimental animals is of a moderate order (Tables 15, 
16).  Signs of intoxication, indicative of an action on the central 
nervous system consist of sedation, ataxia, splayed gait, tip-toe 
walk, with occasional tremors and convulsions.  These signs of 
toxicity appear within a few hours following dosing, and survivors 
show clinical recovery within 3 days (Coombs et al., 1976). 

    Table 16 shows the effects of the ratio of  cis-: trans-isomers 
on the acute oral toxicity (FAO/WHO, 1980b). 

    Factors known to influence the oral LD50 value of cypermethrin 
include concentration, vehicle, temperature, age of the animals, 
and the animal strain used (Coombs et al., 1976; Dewar & Owen, 
1979).  The acute toxicity of cypermethrin was approximately 3 
times greater in 3-week-old, than in 12-week-old rats (Rose & 
Dewar, 1978).  The  cis-: trans-ratio plays a role in determining 
acute toxicity, the  cis-isomers being more toxic than the  trans-
isomers.  The oral LD50 of the  cis-isomers in rats (Carworth Farm 
E strain) was 229 mg/kg body weight while, with the  trans-isomers, 
no deaths were found at 2000 mg/kg body weight (Brown, 1979a,b). 

8.1.2.  Dermal

    The acute dermal toxicity of technical cypermethrin is of a low 
order.  There were no deaths in CFE rats at any dose level tested 
up to 1600 mg/kg body weight using 20% w/v xylene as the vehicle 
(Coombs et al., 1976).  The dermal LD50 for the  cis-isomer of 
cypermethrin, applied to the skin of rats as a 10% solution in 
DMSO, was 219 mg/kg body weight (Brown, 1979a). 

    The acute dermal toxicity of cypermethrin for the rabbit 
is > 2460 mg/kg body weight (US EPA 1984). 

8.1.3.  Intraperitoneal

    The intraperitoneal (ip) LD50 (20% w/v solution in corn oil) 
for technical cypermethrin in CFI mice is 485 mg/kg body weight 
(Coombs et al., 1976).  In rats, the LD50 is between 198 and 315 
mg/kg body weight (administered as 5% solution in DMSO) (Price, 
1981a). 

Table 15.  Oral LD50 values for technical cypermethrin
-----------------------------------------------------------------------
Species    Concentration and     LD50 value (mg a.i./    Reference
           vehicle               kg body weight) (with
                                 95% confidence limits)
-----------------------------------------------------------------------
rat        5% in corn oil        251 (203 - 295)         Coombs et al.
                                                         (1976)

rat        5% in dimethylsulf-   303 (277 - 329)         Coombs et al.
           oxide                                         (1976)

rat        5% in dimethylsulf-   570 (485 - 823)         Price (1981a)
           oxide

rat        40% in dimethylsulf-  approximately 4000      Rose (1982)
           oxide

rat        5% in glycerol        200 - 400 (male);       Coombs et al.
           formal                approximately 200       (1976)
                                 (female)

rat        10% in aqueous        400 - 800 (male);       Coombs et al.
           suspension            approximately 400       (1976)
                                 (female)

rat        50% in aqueous        3423 (2815 - 4328)a     Rose (1982)
           suspension

mouse      5% in corn oil        82 (68 - 116)           Rose (1982)

mouse      5% in dimethylsulf-   138 (105 - 199)         Coombs et al.
           oxide                                         (1976)

mouse      50% in aqueous        657 (439 - 1003)        Rose (1982)
           suspension

Syrian     10% in corn oil       approximately 400       Coombs et al.
 hamster                         (male and female)       (1976)

Chinese    5% in corn oil        203 (144 - 255)         Coombs et al.
 hamster                                                 (1976)

guinea-    20% in corn oil       approximately 500       Coombs et al.
 pig                             (male); > 1000          (1976)
                                 (female)

bovine     15% formulation in    142 - 284 (male)        Cassidy (1979)
 calves    Shellsol A

piglets    15% formulation in    > 600 (male)            Cassidy (1979)
           Shellsol A
-----------------------------------------------------------------------

Table 15.  (contd.)
-----------------------------------------------------------------------
Species    Concentration and     LD50 value (mg a.i./    Reference
           vehicle               kg body weight) (with
                                 95% confidence limits)
----------------------------------------------------------------------
lamb       15% formulation in    283 - 567 (male)        Cassidy (1979)
           Shellsol A


domestic   40% in dimethylsulf-  > 2000                 Coombs et al.
 fowl      oxide                                         (1976)

partridge  40% in dimethylsulf-  > 3000                 Coombs et al.
           oxide                                         (1976)
-----------------------------------------------------------------------
a 40:60 cis/trans.

Table 16.  Effects of  cis-: trans-ratio on the acute toxicity of
cypermethrina
------------------------------------------------------------------
Species  Sex     Vehicle             cis-: trans-ratio  LD50 (mg/kg)
------------------------------------------------------------------
rat      male,   dimethylsulfoxide   cis-only          160 - 300
         female

rat      male,   dimethylsulfoxide   trans-only        > 2000
         female

rat      female  corn oil           90:10             367

rat      female  corn oil           40:60             891
------------------------------------------------------------------
a From:  FAO/WHO (1980b).

8.1.4.  Inhalation

    Groups of CD rats (4 of each sex) were exposed for 4 h to an 
aqueous spray of cypermethrin as a 400 g/litre emulsifiable 
concentrate.  The liquid phase contained 3 g cypermethrin/litre and 
the atmospheric concentration of droplets  in  the vicinity of the 
rats was calculated to be 0.7 mg/litre.  The median droplet size 
was 130 m with a geometric standard deviation of 1.6 m, 
comparable with the droplet spectrum of a field-spraying device.  
(It should be noted that this droplet size is nearly not 
inhalable).  The rats became thoroughly soaked during the exposure, 
thereby indicating a significant dermal exposure with probable oral 
exposure during post-exposure grooming.  Immediately after the 
exposure, the female rats showed the abnormal gait and urinary 
incontinence typical of pyrethroid intoxication.  Recovery took 
place within 3 days.  No deaths or other adverse signs occurred 
during the exposure period or the subsequent 14-day observation 
period (Blair & Roderick, 1976). 

    In another study on possible effects on the peripheral nerves, 
rats (8 of each sex) were exposed for 4 h to an aqueous spray of 
cypermethrin as a 400 g/litre emulsifiable concentrate under 
conditions similar to those in the previous study.  Half of the 
rats were necropsied immediately after exposure and the others 
after 66 h.  Examination of the sciatic nerves from all of the rats 
did not reveal any abnormalities, even though signs of intoxication 
had been observed (Blair et al., 1976). 

8.1.5.  Skin and eye irritation

    Technical cypermethrin was moderately irritant to occluded 
rabbit skin (both intact and abraded) and to the eyes of New 
Zealand white rabbits.  In both cases, recovery was complete in a 
few days.  The severity of the irritation depended on the 
formulation and the solvent used (Hine & Zuidema, 1970; Coombs et 
al., 1976). 

    The skin on the backs of guinea-pigs was treated with 
cypermethrin.  The animals responded by licking, rubbing, 
scratching, or biting the sides tested.  This reaction may be 
associated with skin sensory effects characterized by transient 
itching and tingling sensations (Cagen et al., 1984). 

8.1.6.  Sensitization

    A skin sensitization test on guinea-pigs (maximization 
procedure of Magnusson & Kligman) indicated that technical 
cypermethrin may have a mild skin sensitizing potential (Coombs et 
al., 1976; US EPA, 1984). 

8.2.  Short-Term Exposures

8.2.1.  Oral

8.2.1.1.  Rat

    Groups of 6 male and 6 female Charles River rats were fed diets 
containing 0, 25, 100, 250, 750, or 1500 mg cypermethrin/kg feed 
for 5 weeks.  In the 1500 mg/kg group, reduced body weight gain and 
food intake, piloerection, nervousness, incoordinated movement, 
increased liver weight, and increases in blood urea and haemoglobin 
concentrations were observed, but there were no pathological 
changes.  No changes were detected in the groups receiving 750 
mg/kg or less (Coombs et al., 1976). 

    Groups of Charles River rats, 12 of each sex (24 of each sex as 
controls), were fed dietary concentrations of 0, 25, 100, 400, or 
1600 mg cypermethrin/kg feed for 3 months.  Signs of intoxication, 
such as hypersensitivity and abnormal gait, were observed in the 
1600 mg/kg group, during the first 5 weeks, and one animal died.  
The survivors showed clinical recovery in the second half of the 
study.  However, body weight gain was reduced, liver and kidney 
weights increased, and there were increases in plasma-urea 
concentrations and plasma-alkaline phosphatase activity, and 

decreases in haemoglobin concentrations and the red blood cell 
count in females, and in the kaolin cephalin clothing time in males 
and packed cell volume were observed.  Two out of 4 male rats, 
killed prematurely, showed axonal breaks and vacuolization of 
myelin in the sciatic nerve.  None of the survivors showed nerve 
lesions, and no other pathological effects were found. In the 
400 mg/kg group, males showed increased kidney weights but no 
histopathological changes.  No effects were found in the 100 mg/kg 
group (Hend & Butterworth, 1976). 

    Male and female rats (20 in each group) were fed cypermethrin 
( cis-: trans- = 44:56) with a purity of 92% in the diet at levels 
of 0, 75, 150, or 1500 mg/kg diet, for 90 days.  Haematology and 
the results of urinalysis were normal. Both males and females 
receiving 1500 mg/kg diet showed reduced body weight and reduced 
food consumption during the first month of the study.  Increased 
liver microsomal oxidase activity was noted in both males and 
females in the 1500 mg/kg group and in the males in the 150 mg/kg 
group.  These changes were substantially reversed within the 4-week 
recovery period.  Gross and microscopic (including electron 
microscopic) examination of the tissues and organs did not reveal 
any signficant differences between the treated groups and the 
controls.  Examination of the sciatic nerve of animals in the 
control and the 1500 mg/kg groups did not reveal any changes that 
could be directly attributed to cypermethrin (Glaister et al., 
1977b). 

    Groups of rats (6 male and 6 female rats per group and 14 of 
each sex as controls) were fed  trans-isomer at concentrations of 
0, 30, 100, 1000, or 3000 mg/kg diet, for 5 weeks.  No gross or 
microscopic findings were observed and mortality did not occur.  
Changes in several haematological parameters, alkaline phosphatase 
activity, and liver, spleen, and kidney weight were observed at the 
2 highest dose levels. Special histopathological studies of the 
sciatic nerve did not show any damage (Hend & Butterworth, 1977a). 

    Groups of rats (6 male and 6 female rats per group and 10 of 
each sex used as controls) were fed concentrations of the  cis-
isomer at 0, 30, 100, 300, 750, or 1500 mg/kg diet for 5 weeks 
(protocol similar to that described above).  Mortality was observed 
at the 1500 mg/kg level as well as neurotoxic signs of poisoning.  
Growth was reduced at the 750 mg/kg level.  Significant reductions 
in food intake were also noted at doses of 300 mg/kg or more, 
during the initial phase of the study.  Relative kidney weights 
showed a statistically-significant increase at doses of 300 mg/kg 
or more and an increase in liver weight was observed at 750 mg/kg.  
Histopathological examinations revealed substantial degeneration 
in both the liver and sciatic nerve at 1500 mg/kg.  No lesions were 
observed in the brain or spinal cord (Hend & Butterworth, 1977b). 

8.2.1.2.  Dog

    Beagle hounds (4 of each sex per dose level) were fed diets 
containing 0, 5, 50, 500, or 1500 mg cypermethrin/kg diet for 13 
weeks.  At 1500 mg/kg, severe signs of intoxication consisting of 

diminished food intake, weight loss, diarrhoea, anorexia, licking 
and chewing of the paws, whole body tremors, a stiff exaggerated 
gait, ataxia, incoordination, and hyperaesthesia were observed.  
Half of the dogs in this group were necropsied because of severe 
clinical signs of intoxication.  However, no changes in 
haematology, organ weight, or histopathology were observed and 
despite the severe signs of intoxication, no lesions of the sciatic 
nerves were observed in the dogs.  No effects were seen at 500 
mg/kg feed (Buckwell & Butterworth, 1977). 

8.2.2.  Dermal

8.2.2.1.  Rabbit

    Groups of 10 male and 10 female New Zealand white rabbits 
received occluded dermal applications (abraded and non-abraded 
skin) of 2, 20, or 200 mg cypermethrin/kg body weight in 
polyethylene glycol (PEG 300) for 6 h per day, 5 days per week,  
for 3 weeks.  A control group was similarly treated with the 
vehicle only (PEG 300).  Slight-to-moderate skin irritation was 
observed in rabbits receiving 2 and 20 mg/kg body weight; those 
receiving 200 mg/kg body weight showed slight-to-severe irritation.   
In  the  rabbits  treated at 200 mg/kg, reductions were observed in 
food intake, body weight gain, and weight of gonads.  No other 
changes were noticed.  No such effects were found at 20 mg/kg body 
weight (Henderson & Parkinson, 1981). 

8.2.3.  Intraveneous

8.2.3.1.  Rat

    Lock & Berry (1981) found biochemical changes in the rat 
cerebellum after a single iv administration of 25 mg 
cypermethrin/kg body weight.  Signs of toxicity included: 
salivation, clonic convulsions, and sinuous writhing movements.  
The concentrations of cerebellar amino acids and cyclic nucleotides 
were determined at these stages of toxicity.  Treatment with 
cypermethrin resulted in an increase in cerebellar cyclic GMP at 
the earliest stage, without changing cyclic AMP.  Levels of blood- 
and cerebellar-glucose, lactate, and ammonia were also increased in 
most of the stages of toxicity.  No changes were seen in 
concentrations of glutamate, glutamine, gamma-aminobutyrate, 
creatine, phosphate, or ATP in the cerebellum.  The increase in 
cerebellar cyclic GMP did not appear to be related to the 
convulsive state of the animal or to the muscarinic cholinergic 
stimulation. 

8.3.  Long-Term Exposures

8.3.1.  Rat

    Wistar rats (24 of each sex per dose level and 48 of each sex 
as controls) were fed dietary concentrations of 0, 1, 10, 100, or 
1000 mg cypermethrin/kg diet for 2 years.  Additional groups (6 or 
12 rats of each sex per dose level) were fed the diets for only 6, 
12, or 18 months. 

    Throughout the 2-year study, the control and cypermethrin-
treated animals were similar in terms of behaviour; no compound-
related clinical signs were observed, except for a significantly-
reduced growth rate in both males and females fed 1000 mg/kg diet.  
Survival was not affected by cypermethrin.  No clinical-chemical, 
haematological, or histopathological changes were observed.  The 
sciatic nerves from a number of animals of all groups, sacrificed 
after 6, 12, 18, or 24 months, showed a small number of nerve 
fibres exhibiting Wallerian degeneration.  The incidence increased 
with age, but there was no difference in severity between the 
control and treated groups.  It is concluded that doses of 100 mg 
cypermethrin/kg diet or less did not produce significant 
toxicological effects in rats over a 2-year period (McAusland et 
al., 1978). 

    Assays of liver microsomal enzyme activity in 6 rats of each 
sex fed 0 or 1000 mg cypermethrin/kg feed for 2 years showed 
cypermethrin to be a weak inducer of the microsomal enzyme hepatic 
 p-nitroanisole- O-dimethylase (PNOD), used as an index of 
monooxygenase activity (Potter & McAusland, 1980). 

    Five groups of Wistar rats, each composed of 52 males and 52 
females, were given diets containing 0 (2 groups), 20, 150, or 1500 
mg/kg diet (equivalent to 0, 1, 7.5, and 75 mg/kg body weight) for 
2 years.  Satellite groups of 12 male and 12 female rats were 
sacrificed at 52 weeks.  For the first 6 weeks of the study, the 
rats in the 1500 mg/kg group received 1000 mg/kg.  The purity of 
the cypermethrin was between 88% and 93% ( cis-: trans-ratio; 
55:45).  After 104 weeks at the highest dose level, body weight 
loss, increased liver weight, increased smooth endoplasmatic 
reticulum in hepatocytes, and some haematological and other slight 
clinical changes were observed.  No other changes or increase in 
the incidence of tumours were found.  The dose of 150 mg/kg diet 
was considered to be the no-observed-adverse-effect level in this 
study (only a summary is given) (US-EPA, 1984). 

8.3.2.  Mouse

    The effects of cypermethrin were investigated in groups of 70 
male and 70 female Swiss mice fed diets containing 0 (2 groups), 
100, 400, or 1600 mg/kg feed (equivalent to 0, 15, 60, or 240 mg/kg 
body weight) for up to 101 weeks.  The purity of the cypermethrin 
was between 91.5 and 94.2%;  cis-: trans-ratio; 53:47 or 54:46.  
Ten males and 10 females per group were killed at 52 weeks for 
interim haematological evaluation.  Appearance, behaviour, and 
survival were similar in all groups.  Body weight gain was reduced 
in mice fed 1600 mg cypermethrin/kg diet compared with the combined 
control groups.  Food intake of both males and females was not 
significantly changed.  Several haematological changes, consistent 
with a mild anaemia, were found in the 1600 mg/kg group of animals 
at the interim kill (decreased haemoglobin, haematocrit, and red 
blood cell counts in males; decreased mean cell volume and mean 
cell haemoglobin concentration in females) but were not found at 
termination.  Thrombocytosis and increased liver weight were also 
observed in this group, at both the interim and terminal kills.  

There were no accompanying histopathological changes (for 
carcinogenic potential, see section 8.7).  No effects were observed 
at dose levels of 400 mg/kg diet or less (Lindsay et al., 1982). 

8.3.3.  Dog

    Cypermethrin (dissolved in corn oil) was administered to 4 
groups of 8 beagle dogs of each sex at dose levels of 0, 1, 5, or 
15 mg/kg body weight per day, by capsule, for a period of 52 weeks.  
The purity of the cypermethrin was 90.6% ( cis-: trans-ratio; 
54:46).  The dogs in the highest dose group exhibited loss of 
appetite, tremors, gait changes, incoordination, disorientation, 
and hypersensitivity.  No other abnormalities were found in the 
composition of the blood or urine or in organ weights.  Dogs 
receiving 5 mg/kg or more showed liquid stools by this mode of 
administration.  However, this effect was not found when 
cypermethrin was fed in the diet for 2 years.  No effects were seen 
at 1 mg/kg (but only a summary is given) (US-EPA, 1984). 

    Groups of 4 male and 4 female Beagle hounds were fed diets 
containing 0, 3, 30, or 300 mg cypermethrin/kg feed for 2 years.  
An additional group received 1000 mg/kg feed but, because of severe 
intoxication signs, the dose was decreased to 750 mg/kg.  The signs 
of intoxication consisted of licking and chewing of the paws, a 
stiff high-stepping gait, whole body tremors, head shaking, 
incoordination, ataxia, and convulsions.  After 3 weeks of feeding 
at 750 mg/kg, the animals received the control diet, until signs of 
intoxication could no longer be seen.  The dogs were then fed a 
diet containing 600 mg cypermethrin/kg from week 8 until 
termination at 2 years.  No signs of intoxication were observed in 
dogs fed diets containing 0, 3, 30, or 300 mg/kg during the course 
of the study.  There was reduced body weight gain in male dogs in 
the 600 mg/kg group.  Clinical chemistry and haematological 
investigations, performed at 6-week intervals for 2 years, did not 
reveal any consistent differences between treated groups and 
controls.  The minor changes in absolute organ weight observed in 
the brain and thyroid in the 300 mg/kg group were not present when 
the differences were corrected for terminal body weight.  
Furthermore, a dose relationship was not apparent, and there were 
no accompanying histopathological changes.  Opthalmological 
observations performed during the course of the study did not 
reveal any ocular differences between treated groups and control.  
No abnormalities were found in the sciatic nerves, brain, or spinal 
cord in any of the treated groups.  The feeding of diets containing 
up to 600 mg cypermethrin/kg diet to dogs for 2 years did not 
reveal any treatment-related gross or histopathological effects, 
although the dogs receiving diets containing 1000 mg/kg decreased 
to 600 mg cypermethrin/kg showed reduced body weight gain.  
Cypermethrin did not produce any toxicological effects in dogs fed 
dietary concentrations of 300 mg/kg feed or less, over 2 years 
(Buckwell, 1981). 

8.4.  Special Studies

8.4.1.  Synergism/potentiation studies

8.4.1.1.  Organophosphate mixture

    In a study on rats, designed to determine whether an 
organophosphate insecticide, monocrotophos, potentiated the 
neurotoxic effect of cypermethrin, 5 groups of 7 or 8 male and 7 or 
8 female rats were given 7 consecutive oral doses of monocrotophos 
(100 g/litre), cypermethrin (25g/litre), or a mixture  of  
monocrotophos and cypermethrin (100 g/litre and 25 g/litre, 
respectively).  Signs of intoxication and neurotoxic effects 
(biochemical changes consistent with very sparse axonal 
degeneration in sciatic/tibial nerves) were found to be wholly 
attributable to the monocrotophos component of the mixture, and 
there was no evidence of potentiation of neurotoxic effects (Rose & 
Dewar, 1979a). 

8.4.1.2.  Organochlorine mixture

    The oral and dermal toxicities of cypermethrin and endosulfan 
for rats were determined both individually and combined.  No 
evidence for enhancement of toxicity was found for either 
cypermethrin or endosulfan when administered as a 1:1 mixture in 
corn oil (Price, 1981b). 

8.4.2.  Neurotoxicity

8.4.2.1.  Characterization of the neurotoxic effects

    During preliminary short-term studies on cypermethrin, 2 
observations were made: 

    (a)  high doses of cypermethrin given orally to rats
         caused an unusual gait in intoxicated animals; and

    (b)  at lethal or near-lethal dermal or oral doses,
         histopathological changes (swelling and/or 
         disintegration of axons of the sciatic nerve of 
         rats) were observed; such observations have been 
         reported to occur with other synthetic pyrethroids 
         (Okuno et al., 1976a) and natural pyrethrins (Okuno 
         et al., 1976b).

    As a consequence of these findings, an extensive programme of 
work has been undertaken to characterize the neurotoxic effects of 
cypermethrin. 

8.4.2.2.  Neuropathological studies

    (a)  Rat

    Single oral doses of cypermethrin in corn oil were given to 
groups of 6 - 12 rats of each sex at 100, 200, or 400 mg/kg body 
weight.  All rats showed signs of intoxication, which varied in 
severity according to the dose level.  At 400 mg/kg, severe  
clinical signs were seen within 2 days of dosing.  Most of the  
animals showed swelling of the myelin sheaths and breaks of some of 
the axons of the sciatic nerves.  At 200 mg/kg, 8 rats of each sex 
died or were killed within 48 h of dosing, and the remaining 4 of 
each sex survived the 9 days of the study.  Nearly half of the 
animals showed lesions of the sciatic nerve.  At 100 mg/kg, all 
rats survived 9 days of the trial.  Only one female out of 12 
showed minimal lesions of the sciatic nerve.  Neuropathological 
changes were found in a number of animals dosed with 200 mg 
cypermethrin/kg body weight or more.  Dose-related increases in 
signs of intoxication and neuropathy were observed; however, 
neuropathy was not detected in all the animals showing signs of 
intoxication (Carter & Butterworth, 1976). 

    Groups of rats (10 males per group) were fed dietary levels of 
cypermethrin ( cis-: trans- = 45:55) at 0, 1250, 2500, or 5000 
mg/kg diet for 14 days.  Mortality was observed at the 2 higher 
doses and growth inhibition was seen in all treated groups.  
Clinical signs of neurotoxicity were characterized by an impaired 
ability to walk, splayed hind limbs, ataxia, and paralysis.  Other 
clinical signs were hypersensitivity, gross disorientation, and 
convulsions.  The neurotoxic signs of poisoning observed at 1250 
mg/kg diet were reversible.  Remission of ataxia at 2500 mg/kg diet 
was also noted.  Ultrastructural changes in the sciatic nerve were 
observed in a small number of animals at the 2 highest dose levels.  
Some evidence of axonal damage in the myelinated nerves was 
observed, mainly in these groups (Glaister et al., 1977a). 

    In another study, rats were fed dietary concentrations of 0, 1, 
10, 100, or 1000 mg cypermethrin/kg diet for 2 years (section 8.3).  
At the 12-month interim kill, part of the sciatic nerve was removed 
from 6 males and 6 females in both the control and 1000 mg/kg 
group.  The dissected nerves were divided and teased into a fan 
shape, allowing each fibre to be examined.  No significant 
difference was found in the incidence of abnormal nerve fibres  in 
the control and the 1000 mg/kg group (Trigg et al., 1977; McAusland 
et al., 1978). 

    (b)  Hamster

    Groups of 6 male and 6 female Syrian hamsters were given single 
oral doses of cypermethrin in corn oil at 0, 794, 1000, and 1260 
mg/kg body weight.  Signs of intoxication (generally tiptoe 
walking, tremors, irregular movements) occurred in all groups 
receiving cypermethrin.  Animals died or were killed at times 
varying from a few hours to 9 days after dosing.  Of the 31 animals 
of the different test groups that were examined, 3 had nerve 

lesions, axonal swelling, and axonal breaks in the sciatic and 
posterior tibial nerves (many animals died within a few hours) 
(Butterworth & Clark, 1977). 

    (c)  Chicken

    In a delayed neurotoxicity study on 6 adult domestic hens, 
cypermethrin in DMSO did not cause histological lesions in the 
nervous system (brain, spinal cord, and sciatic nerves) or signs of 
intoxication at an oral dose of 1000 mg/kg body weight per day for 
5 days, compared with a positive control group.  No delayed 
neurotoxicity was observed (Owen & Butterworth, 1977). 

8.4.2.3.  Biochemical and electrophysiological studies

    Biochemical and electrophysiological studies have been carried 
out because the sparse axonal degeneration described above is 
difficult to demonstrate by conventional histopathological 
techniques.  Furthermore, evidence was required to quantify the 
neurological dysfunction attributable to cypermethrin.  The 
rationale for measuring the activities of beta-glucuronidase and 
beta-galactosidase in conjunction with an assessment of "mean slip 
angle" and "mean landing foot spread" as markers for axonal 
degeneration has been described by Dewar (1977a,b). 

    (a)  Rat

    Using biochemical markers, it has been shown that, at high oral 
doses of cypermethrin, sparse axonal degeneration occurs in the 
sciatic/posterior tibial nerves (Dewar, 1977b; Rose & Dewar, 1983), 
and the trigeminal nerve and trigeminal ganglion of Wistar rats 
(Dewar & Moffett, 1978a). 

    Three studies involving repeated oral administration of 
cypermethrin to rats at 150 mg/kg body weight for 5 or 7 days and 
0, 25, 50, 100, or 200 mg/kg body weight for 5 or 7 days have been 
carried out.  Mortality occurred from 100 mg/kg body weight 
onwards.  A dose-related transient functional impairment, assessed 
by means of the inclined plane test, was found in the first week.  
Significant increases in beta-glucuronidase or beta-galactosidase 
activity of the sciatic, tibial, or trigeminal nerves only occurred 
with 5 or 7 doses of 150 or 200 mg/kg body weight.  The sensitivity 
of these nerves is comparable.  Complete functional recovery 
occurred within 26 days.  Increased activity of the enzymes in the 
distal portion of nerves was found but, even in the most severely 
intoxicated animals, the magnitude of the increases was less than 
that induced by the known neurotoxic agent methylmercury chloride 
(Dewar, 1977b; Dewar & Moffett, 1978a; Rose & Dewar, 1983). 

    Biochemical changes, consistent with primary axonal 
degeneration, were detected in rats aged 3, 6, or 12 weeks. 
Cypermethrin was more acutely toxic for 3-week-old rats than for 
12-week-old rats and the dose required to cause a sparse axonal 
degeneration, as demonstrated by biochemical changes, was 
proportionally smaller for the younger rats (Rose & Dewar, 1978). 

    The time-course for development and recovery from axonopathy 
was investigated in groups of rats (5 of each sex) at periods of 
2 - 12 weeks after the start of dosing.  The daily doses were 150 
mg/kg body weight for the first 11 doses and 100 mg/kg body weight 
for the subsequent 9 doses, over a period of 4 weeks.  More than 
half of the animals died and more than 80% of the treated animals 
showed clinical signs of intoxication, characterized by abnormal 
gait, ataxia, salivation, lethargy, chromodacryorrhoea, 
piloerection, and hypersensitivity to external stimuli.  Maximum 
enzyme activities in the sciatic posterior tibial nerves were found 
after 5 weeks and had returned to control values by 12 weeks.  In a 
second phase of the study, 10 male and 10 female rats were given  
20 oral doses of cypermethrin at 37.5, 75, or 150 mg/kg body weight 
per day, (concurrent control group dosed with DMSO), over a 4-week 
period.  The animals given 75 and 150 mg/kg showed clinical signs 
of intoxication.  Mortality also occurred at the highest dose 
level.  The behaviour and appearance of animals in the 37.5 mg/kg 
body weight per day group were similar to those of the controls.  
Five weeks after the initial dose, biochemical changes, which were 
indicative of a mild axonal degeneration, were observed in animals 
in the highest dose group.  No consistent or biologically 
significant neurobiochemical changes were found in the 37.5 or 75 
mg/kg body weight groups.  The results of this study demonstrated 
that 20 oral doses of cypermethrin at 75 mg/kg body weight per day 
administered over a 4-week period, produced mild clinical signs of 
intoxication; however, no biochemical changes which were indicative 
of peripheral neuropathy were seen (Rose, 1983). 

    Further evidence to support the minor nature of the nerve 
lesions has been afforded by electrophysiological studies on rats.  
In these studies, measurements of the maximal motor conduction 
velocities and conduction velocity of slower fibres in the sciatic 
and tail nerves of Wistar rats were made before, and at intervals 
of up to 5 weeks after, exposure to single (200 mg/kg body weight) 
or repeated doses (7 doses of 150 mg/kg body weight) of 
cypermethrin.  Even at near-lethal doses, cypermethrin did not 
cause any effects on these parameters (Dewar & Deacon, 1977). 

    The ability of the major metabolite of cypermethrin, PBA, to 
produce axonal changes has been investigated.  Four groups of 8 
male and 8 female rats given 7 consecutive daily oral doses of 0, 
25, 77, or 375 mg/kg body weight did not show any biochemical 
changes indicative of peripheral nerve damage.  The sparse axonal 
degeneration observed with high doses of cypermethrin is, 
therefore, not caused by PBA (Rose & Dewar, 1979b). 

    (b)  Hamster

    In  3 studies, Chinese hamsters were given oral doses of 
5 - 30 mg cypermethrin/kg body weight per day, for 5 consecutive 
days.  Clinical signs of intoxication were observed and tests 
made to assess whether the compound produced degenerative changes 
in peripheral nerves and sensory ganglia.  Beta-glucuronidase, 
and beta-galactosidase activities were measured in the 

sciatic/posterior tibial nerves and trigeminal ganglion.  A 
positive control group received 7.5 mg methylmercury chloride/kg 
body weight per day, for 5 consecutive days. 

    The most striking feature in the hamsters treated with doses 
exceeding 5 times 20 mg/kg body weight was a marked loss of fur in 
the facial area, neck, and back, due to repeated scratching.  The 
results of the enzyme determinations suggest that the Chinese 
hamster like the rat developed sparse axonal degeneration following 
oral doses in excess of 5 times 10 mg/kg body weight (Dewar & 
Moffet, 1978b) 

    (c)  Rabbit

    Rabbits were administered capsules with 0 (corn oil), 75, 
150, or 300 mg cypermethrin (93.5%)/kg body weight in corn oil, 
5 times a week, for 6 weeks.  At the end of the 6th week, 
electroencephalographic records were taken.  The waves of the 
complex EEG activity as well as the performance of the 6 
constituting bands of different frequency were computer analysed.  
No significant alterations were found (Desi et al., 1986a). 

8.4.2.4.  Appraisal

    Repeated oral administration of cypermethrin to rats, at doses 
sufficiently high to produce significant mortality in a group of 
animals, produced biochemical changes in peripheral nerves that 
were consistent with sparse axonal degeneration.  The magnitude of 
the biochemical changes was similar to that of changes produced 
with either a single (Dewar, 1977b) or repeated doses of shorter 
duration (Dewar & Moffet, 1978a), thus demonstrating a lack of 
cumulative effect.  The magnitude of change was substantially less 
than that encountered with established neurotoxic agents and the 
site of maximal enzyme change (distal portion of the nerve) 
suggests that the degeneration is more likely to be of a Wallerian 
type rather than segmental demyelination.  The short time required 
to produce ataxia and/or abnormal gait rules out a causal 
relationship between ataxia and axonopathy.  The clinical signs are 
consistent with a pharmacologically-mediated effect whereas the 
axonopathy is a minor reversible lesion that occurs several days 
after exposure and has also been detected in animals that do not 
show clinical signs. 

    Histopathological lesions of some fibres of the sciatic nerve 
have only been demonstrated in rats or hamsters receiving extremely 
high, lethal or near lethal, oral doses of cypermethrin (Carter & 
Butterworth, 1976; Butterworth & Clark, 1977).  Compound related 
histopathological changes have not been observed in rats exposed to 
cypermethrin through inhalation (Blair et al., 1976) or in rats fed 
diets containing 1000 mg cypermethrin/kg over a 1 - 2 year period 
(Trigg et al., 1977; McAusland et al., 1978).  Furthermore, dogs 
fed 1500 or 600 mg cypermethrin/kg diet for 3 or 24 months, 
respectively, did not have any compound-related lesions of the 
sciatic nerve (Buckwell & Butterworth, 1977; Buckwell, 1981). 

    The results of biochemical studies, used as sensitive 
indicators of change, confirmed that minor changes that occur after 
massive exposure to cypermethrin are reversible and are not 
necessarily associated with clinical signs (Dewar, 1977b; Dewar & 
Moffet, 1978a; Rose, 1983).  There was no direct correlation 
between the time course of the neuromuscular dysfunction and the 
neurobiochemical changes (Rose & Dewar, 1983).  The metabolite of 
cypermethrin, PBA, did not produce any biochemical changes in 
peripheral nerves (Rose & Dewar, 1979b). 

8.4.3.  Immunosuppressive action

    Stelzer & Gordon (1984) studied the  in vitro effects of 
pyrethroids on the mitogenic responsiveness of murine splenic 
lymphocytes to concornavalin A and lipopolysaccharide.  The results 
of these studies showed that at concentrations of the order of 1 - 
10 mol/litre, inhibition of murine splenic lymphocytes to both B 
and T cell mitogens was found.  These results support the 
possibility of immune suppression by pyrethroid (cypermethrin) 
exposure. 

    Desi et al., (1985, 1986a) studied the short-term effects of 
6.25, 12.5 or 25 mg cypermethrin (93.5%)/kg body weight in rats, on 
the immune system by measuring the autologous rosette formation of  
T-lymphocytes and determining the ovalbumin titre.  These studies 
were performed over a period of 6 or 12 weeks. 

    The humoral immune response after vaccination with  Salmonella 
 typhimurium and the cell-mediated immune response were determined 
in rabbits.  The antibody titre was measured by tube-agglutination 
and complement-binding tests and the tuberculin skin test was used 
for the immune response test.  The dose levels in this study were 
75, 150, or 300 mg/kg body weight, for 7 weeks.  A significant 
dose-dependent decrease was observed in both the anti-ovalbumin 
titre of the blood-serum and in the autologous rosette formation of 
the T-lymphocytes.  In rabbits, the 2 highest dose levels induced a 
significant dose-dependent decrease in serum antibody titres and 
the tuberculin skin test showed the same dose-dependent tendency. 

8.5.  Reproduction, Embryotoxicity, and Teratogenicity

8.5.1.  Reproduction

    Cypermethrin  was fed to Wistar rats (30 male and 30 female per 
group) at dietary concentrations of 0, 10, 100, or 500 mg/kg for 5 
weeks, after which the males and females (10 weeks of age) from 
each treatment group were mated.  Two successive litters were 
produced from each pair.  The first of these litters was discarded, 
and randomly-selected male and female pups of the second litters 
were mated to produce the next generation.  The study was continued 
until 2 litters from each of 3 successive generations had been 
bred.  The parent animals in the 500 mg/kg group consumed less food 
than the controls and this was accompanied by a reduction in body 
weight.  Otherwise, the parent animals of control and treatment 
groups behaved similarly.  Cypermethrin did not cause any adverse 
effects on the reproductive performance of the rats or on the 

survival of the offspring.  No consistent changes were observed in 
mean litter weight between birth and weaning in any treatment 
group, with the exception of a reduction in total litter weights in 
the 500 mg/kg F1a litters on days 4, 14, and 21.  There was also a 
statistically-significant decrease compared with controls in total 
litter weights and size in the F1b litters at 500 mg 
cypermethrin/kg diet.  In the 500 mg/kg Fo group, one animal showed 
a squamous cell carcinoma of the skin.  However, this was 
considered not to be related to the compound, because no increase 
in tumour incidence was found in the long-term studies on rats and 
mice.  No changes were observed in rats administered 100 mg/kg diet 
(Hend et al., 1978). 

8.5.2.  Embryotoxicity and teratogenicity

8.5.2.1.  Rat

    Groups of pregnant female Sprague Dawley CD rats (25 animals 
per group) were administered cypermethrin orally as a 1% solution 
in corn oil at doses of 0, 17.5, 35, or 70 mg/kg body weight per 
day, from days 6 to 15 (inclusive) of gestation.  Cypermethrin at 
17.5 mg/kg body weight per day did not affect maternal performance 
or fetal survival and development.  At the higher doses of 35 and 
70 mg/kg body weight, respectively, slight and significant 
retardation of maternal body weight gain was recorded.  In 
addition, at 70 mg/kg per day, slight to severe neurological 
disturbances were observed in nearly half of the females including: 
slight splaying of the hind legs while walking ranging to severe 
splaying of all limbs, involuntary movements of the jaws, 
convulsive spasms, and hypersensitivity to noise.  Despite this 
maternal toxicity, there were no indications of any embryotoxic or 
teratogenic effects of cypermethrin (Tesh et al., 1978). 

8.5.2.2.  Rabbit

    Groups of pregnant female Banded Dutch rabbits (30 controls and 
20 for each dose group) were dosed orally with 0, 3, 10, or 30 mg 
cypermethrin/kg body weight per day in corn oil (by gelatin 
capsule) during days 6 - 18 (inclusive) of gestation.  No influence 
was found on growth, pre-implantation losses, resorptions, fetal 
deaths, or numbers and sizes of fetuses.  The incidence of fetal 
visceral and/or skeletal abnormalities was comparable to that in 
the vehicle control group, except for a slight increase in the mean 
percentages of fetuses showing visceral and/or skeletal 
abnormalities in the group receiving 30 mg/kg body weight per day.  
No teratogenic effects were found in this study (Dix, 1978). 

8.6.  Mutagenicity and Related End-Points

8.6.1.   In vitro studies

8.6.1.1.  Microorganisms

    Using bacterial assays, no increases in the reversion rates of 
 Escherichia coli WP2,  E. coli WP2 uvrA,  Salmonella typhimurium 
TA 1535, TA 1537, TA 1538, TA 98, and TA 100 were detected with 
cypermethrin (concentrations of up to 2 mg per plate) in the 
presence or absence of a rat liver microsomal activation system.  
Exposing  Saccharomyces cerevisiae JD1 in liquid culture to  
cypermethrin  at concentrations of up to 5 mg/ml, both in the 
presence and absence of a rat liver microsomal activation system, 
did not result in any increase in the rate of mitotic gene 
conversion (Brooks, 1980). 

    In a study in which cypermethrin was tested for mutagenicity in 
 Salmonella typhimurium TA 100 or TA 98, in the presence or absence 
of a rat liver activation system, using the plate incorporation 
assay, concentrations of up to 1 mg/plate gave negative results.  
The same was true with the fluctuation test, with concentrations of 
up to 10 g/ml (Pluymen et al., 1984). 

8.6.1.2.  Mammalian cells

    Cypermethrin was tested for mutagenicity in V79 Chinese hamster 
cells.  No cytotoxicity was observed when the assay was carried out 
in the presence of rat hepatocytes.  Cypermethrin was found not to 
be mutagenic for either genetic locus (OUA' and TG') in V79 cells, 
when tested in concentrations up to 20 g/ml, in the presence or 
absence of rat hepatocytes (Pluymen et al., 1984). 

8.6.2.   In vivo studies

8.6.2.1.  Host-mediated assay

    There was no increase in the rate of mitotic gene
conversion in  Saccharomyces cerevisiae JD1 harvested from male
mice following a single oral dose of cypermethrin at 25 or 50 mg/kg 
body weight for 2 days (Brooks, 1980). 

8.6.2.2.  Dominant lethal assay

    No evidence of dominant lethality was found when male CD1 mice 
(3 groups of 12 animals and a control group with 36 animals) were 
given single oral doses of 6.25, 12.5, or 25 mg cypermethrin/kg 
body weight.  Two other groups were given 5 consecutive daily oral 
doses of 2.5 or 5 mg/kg body weight (controls received the vehicle 
DMSO).  A significant reduction in fetal implants during the second 
week of mating was noted and a marginal increase in early fetal 
deaths was observed at 5 mg/kg per day.  This effect was not 
confirmed in a second study using oral doses of 2.5, 5, 7.5, or 
10 mg/kg body weight for 5 consecutive days, when no effects were 
found on reproductive capability or the histopathology of the 

testes and epididymis.  The marginal differences found in the 
5 mg/kg per day group in the second study were considered not to 
be related to the compound. 

    In summary, cypermethrin did not show detectable dominant 
lethality after administration of doses of up to 10 mg/kg body 
weight per day, for 5 days, or as a single oral dose of 25 mg/kg 
body weight (Dean et al., 1977). 

8.6.2.3.  Bone marrow chromosome study

    Chinese hamsters (12 of each sex per group) were orally dosed 
with 20 or 40 mg cypermethrin/kg body weight, in DMSO, for 2 
successive days.  The incidence of chromosome abnormalities in 
bone marrow cells, 8 and 24 h after dosing, did not differ from 
that in the DMSO control animals.  The positive control group 
(100 mg/kg cyclophosphamide) showed many chromosomal aberrations 
(Dean, 1977). 

    The effects of cypermethrin on sister chromatid exchange were 
studied in the bone marrow cells of 3-month-old mice.  Cypermethrin  
was injected subcutaneously at 0.75, 1.5, or 3 mg/kg body weight 
or 2.5, 5.0, or 10 mg Ripcord/kg body weight.  Both the technical 
and the formulated products showed a dose-related increase in 
sister chromatid exchanges in the dividing cells at all dose 
levels.  The highest doses of both cypermethrin and Ripcord 
completely inhibited mitotic division (Seehy et al., 1983). 

8.6.2.4.  Micronucleus test

    The induction of micronuclei was studied in mouse bone marrow.  
Cypermethrin was administered by 3 routes:  intraperitoneal, oral, 
and dermal.  Cypermethrin showed mutagenic potential after oral 
administration of 900 mg/kg diet for 7 and 14 consecutive days.  No 
effects were seen after ip administration of a single injection of 
60 or 180 mg/kg body weight or double and triple injections of 60 
mg/kg body weight. 

    Up to 4 dermal treatments with 360 mg cypermethrin/kg body 
weight resulted in a significant increase in the frequency of 
polychromatic erythrocytes with micronuclei (Amer & Aboul-Ela, 
1985). 

8.7.  Carcinogenicity

8.7.1.  Oral

8.7.1.1.  Rat

    Wistar rats (24 of each sex per dose level and 48 of each sex 
as controls) (section 8.3) were fed dietary concentrations of 0, 1, 
10, 100, or 1000 mg cypermethrin/kg for up to 2 years in a combined 
long-term/carcinogenicity study.  No evidence for carcinogenicity 
was found in this study (McAusland et al., 1978) (section 8.3.1). 

    No increase in tumour incidence was seen when Wistar rats were 
given diets containing 0, 20, 150, or 1500 mg cypermethrin/kg diet 
(equivalent to 0, 1, 7.5, or 75 mg/kg body weight) for 2 years.  
The purity of the cypermethrin ( cis-: trans- ratio; 55:45) was 
between 88% and 93% (section 8.3.1) (US EPA, 1984). 

8.7.1.2.  Mouse

    Swiss mice (70 male and 70 female) were fed diets containing 0 
(2 groups), 100, 400, or 1600 mg cypermethrin/kg feed for up to 101 
weeks.  Effects consisted of increased liver weights at 400 and 
1600 mg/kg diet and decreased body weight, thrombocytosis, and mild 
anaemia at 1600 mg/kg diet (section 8.3.2). 

    There were no compound-related changes in non-neoplastic 
histopathology or increases in tumours of types that are not 
commonly associated with the mouse strain used.  The incidence of 
tumours was similar in all groups with the exception of a slightly 
increased incidence of benign alveolar lung tumours in the females 
in the 1600 mg/kg group.  However, the magnitude of this increased 
incidence was insufficient when compared with concurrent and 
historical control incidence, to warrant concern.  There was no 
evidence for a decreased latency of benign alveolar lung tumours in 
the female mice receiving the highest dose, and this tumour type 
was not accompanied by any increase in malignancy.  There was also 
no evidence of a carcinogenic response in the male mice in this 
study.  Furthermore, benign alveolar lung tumours are know to occur 
in both sexes at a high and variable incidence in this strain of 
mouse.  Therefore, it is considered that the occurrence of benign 
alveolar lung tumours in the female mice receiving the highest dose 
was not related to treatment with cypermethrin.   Feeding  
cypermethrin at levels of up to 1600 mg/kg diet to mice for a life-
time did not produce any evidence of carcinogenicity (Lindsay et 
al., 1982). 

8.8.  Mechanisms of Toxicity - Mode of Action

    In the classification in the Appendix, cypermethrin is 
classified among the Type II compounds, which cause toxic signs of 
choreoathetosis with salivation (CS-syndrome) in the rat 
(Verschoyle & Aldridge, 1980) and bursts of spikes in the cercal 
motor nerve of the cockroach (Gammon et al., 1981).  Pyrethroids 
having alpha-cyano-3-phenoxy-benzyl alcohol, such as cypermethrin, 
do not induce repetitive firing in the cercal sensory nerves of the 
cockroach  in vivo or  in vitro, but cause different signs including 
a pronounced convulsive phase (Gammon et al., 1981). 

    The intravenous toxicity of 1RS- cis-, and 1RS- trans-
cypermethrin for the rat has been examined.  Both compounds cause 
the CS-syndrome, which is characterized by initial pawing and 
burrowing behaviour, followed within 2 - 5 min by profuse 
salivation, coarse whole-body tremor, increased startle response 
and abnormal locomotion involving the hind limbs.  The coarse 
tremor progresses into sinuous writhing (choreoathetosis) of the 
whole body, which gradually becomes more violent and is enhanced by 

sensory stimuli.  Clonic seizures are occasionally observed as a 
terminal event.  No increase in core temperature occurs and, in 
fact, it may fall.  In the electroencephalogram (EEG) during the 
CS-syndrome, poisoned rats showed generalized spike and wave 
discharges, prior to choreoathetosis (Verschoyle & Aldridge, 1980).  
The primary site of action resulting in the CS-syndrome has not yet 
been decided. 

    It has been suggested (Van den Bercken, personal communication, 
1981) that the facial skin sensations experienced by people who 
handle cypermethrin or other pyrethroids (section 9.2.2) are 
brought about by repetitive firing of sensory nerve terminals in 
the skin.  In the opinion of the author, this is a strictly local 
effect that may occur as soon as the pyrethroid concentration on or 
in the skin reaches a certain level and is not a sign of general 
intoxication.  It is considered by the author that the occurrence 
of these skin sensations are a warning signal indicating that 
exposure has occurred.  No undue hazard is likely, provided the 
pyrethroid does not reach the blood in any significant 
concentration.  In this connection, it was stressed that, although 
cypermethrin is among the least toxic insecticides when 
administered orally, it may become highly toxic, whenever it 
reaches the nervous system in sufficient concentrations. 

    The question remains whether there is a causal relation between 
the intense repetitive activity induced by alpha-cyano pyrethroids 
(of which cypermethrin is an example) and the nerve damage that 
occurs in experimental animals after prolonged exposure to nearly 
lethal concentrations of these compounds.  Because of the large 
number of different chemicals, most of which do not cause 
repetitive activity in the nervous system but are known to cause 
serious nerve damage, such a correlation is hardly expected.  
Furthermore, the extensive literature on DDT (which causes the same 
type of repetitive activity in sense organs and in sensory nerve 
terminals as the non-cyano pyrethroids) does not contain any 
indication that this insecticide may cause axonal degeneration.  
However, in theory, there is a possibility that repeated occurrence 
of intense repetitive firing will eventually lead to dysfunction of 
sensory nerve terminals and sense organs, and, finally, to 
degeneration of sensory nerve fibres (Van den Bercken, personal 
communication, 1981; Van den Bercken & Vijverberg, 1980a). 


-------------------------------------------------------------------
a  Van den Bercken, J. & Vijverberg, H.P.M.  (1980)  Letter
   (personal communication) to WHO concerning "Mode of action of
   pyrethroid insecticides in the vertebrate nervous system"
   (dated April, 1980).

9.  EFFECTS ON MAN

9.1.  General Population Exposure

9.1.1.  Acute toxicity: poisoning incidents

    One report of accidental intoxication has been described.  A 
family who ate food cooked in 10% cypermethrin developed nausea, 
prolonged vomiting with colicky pain, tenesmus, and diarrhoea 
within minutes of ingestion.  One male adult had convulsions, 
passed into coma, and died due to respiratory paralysis.  The 
symptoms were less severe in other members of the family (Poulos et 
al., 1982).  There is some doubt whether this was a cypermethrin 
intoxication (Suthers, personal communication). 

9.1.2.  Controlled human studies

    Flannigan & Tucker (1985) studied the differences in the extent 
of paraesthesia induced by a number of pyrethroids.  Field strength 
formulated cypermethrin (0.13 mg/cm2) was applied (0.05 ml) to a 
4 cm2 area of the earlobe of volunteers on 5 occasions.  Distilled 
water was applied to the opposite earlobe.  Participant evaluation 
after each application continued for 48 h and involved description 
of the cutaneous sensations.  Each participant was treated after 
each application with one of the other pyrethroids.  Cypermethrin 
(as the other pyrethroids) induced sensation.  The paraesthesia 
developed with a latency period of approximately 30 min, peaked by 
8 h and deteriorated as early as 24 h.  Dl-alpha tocopheryl acetate 
markedly inhibited the occurrence of the paraesthesia. 

9.1.3.  Epidemiological studies

    No information is available.

9.2.  Occupational Exposure

9.2.1.  Acute toxicity: poisoning incidents

    No information is available.

9.2.2.  Effects of short- and long-term exposure

    Laboratory workers and field operators handling natural and 
synthetic pyrethroids, including cypermethrin, have noticed a 
transient sensation (described as "tingling" or "burning" 
sensations) of the skin in the periorbital area of the face and of 
other sites after direct skin exposure.  The skin sensations have 
been interpreted (section 8.8) as being caused by spontaneous 
repetitive firing of local sensory nerve fibres or nerve endings, 
with thresholds that have been transiently lowered by the compound 
(Wouters & Van den Bercken, 1978).  There is a delay of about 
30 min before onset of these symptoms following pyrethroid 

exposure; the sensation generally lasts only a few hours and does 
not persist for more than one day after exposure (Van den Bercken & 
Vijverberg, 1980a, Le Quesne et al., 1980). 

    In a clinical and electrophysiological assessment of these skin 
sensations (paraesthesia), 23 laboratory workers, who had been 
exposed to synthetic pyrethroids during the preceding months, were 
examined.  Nineteen of the 23 workers had experienced at least one 
or more episodes of facial sensations.  Neurological signs were not 
observed and electrophysiological studies of selected motor and 
sensory nerves in the legs and arms of the 23 subjects showed no 
abnormalities (Le Quesne et al., 1980). 

    Field studies have been performed in the Cte d'Ivoire in which 
cypermethrin was sprayed on cotton using a hand-held, ultra-low-
volume (ULV) commercial spraying machine.  This method of 
application represented a situation of high potential exposure.  
The first study, in which 17 workers were involved, concerned a 
single exposure to cypermethrin (Prinsen & Van Sittert, 1978), 
while a second study was conducted in which 7 workers took part in 
7 consecutive spray sessions (Prinsen & Van Sittert, 1979).  Skin 
exposure to cypermethrin was assessed by quantitative measurement 
of the compound deposited on aluminium foil pads on the body of the 
sprayer during the spraying operation.  The rate of dermal exposure 
of the operators during spraying ranged from 1.5 to 46.1 mg/h. 
Total absorption of cypermethrin in the body was monitored by 
urinary analysis for 2,2-dichlorovinyl-3,3-dimethyl-cyclopropane-
1-carboxylic acid, a metabolite of cypermethrin.  In most of the 
samples, the excretion was below the limit of detection 
(0.05 mg/litre), indicating a low level of absorption.  It was 
estimated that approximately 3% of the total dermal dose was 
absorbed.  General medical, extensive clinical blood chemistry, and 
electrophysiological examinations were carried out of selected 
motor and sensory peripheral nerves in the legs and arms, of the 
trigeminal nerve, and of the facial nerve.  No effects were found. 

    In another field study in India, 18 workers, including spraymen 
(spraying an emulsifiable concentrate formulation by mist-blower or 
knap-sack), mixers, and loaders, handled cypermethrin daily for 5 
consecutive days.  Medical examination, with special attention to 
the sensory function of the peripheral nervous system, was carried 
out before, during, and after spraying (Suthers & Marlow, 1981).  
No compound-related adverse clinical effects of peripheral 
neuropathy were noticed in any of the workers.  The urinary 
excretion of the cypermethrin metabolite (methyl ester of the 
cyclopropane carboxylic acid moiety) increased from day 1 to 5 of 
the study, but decreased 24 h after spraying had ceased.  On the 
fifth day, concentrations of up to 0.18 mg (average 0.1 mg) were 
found in the 24-h urine of workers using the mist-blower.  
Concentrations were lower in workers using the knap-sack sprayer. 
-------------------------------------------------------------------
a  Van den Bercken, J. & Vijverberg, H.P.M.  (1980)  Letter
   (personal communication) to WHO concerning "Mode of action of
   pyrethroid insecticides in the vertebrate nervous system"
   (dated April, 1980).

    A field study was carried out on Indian workers in the Satara 
district in India prior to, during, and after spraying cotton with 
the synthetic pyrethroid formulations, permethrin (Ambush) and 
cypermethrin (Cymbush).  The formulations were applied using a 
mist-blower or knap-sack spray.  Exposure of 7 spraymen and 2 
loaders/mixers was monitored by measuring the 24-h urinary 
excretion of 3-(4'-hydroxyphenoxy)-benzoic acid, and medical 
assessments were carried out by 4 medical doctors.  The sensory 
function of the peripheral nervous system was also assessed.  The 
formulations were applied at the recommended rates; Ambush, 150 g 
a.i./ha and Cymbush, 70 g a.i./ha.  Average exposure was 
approximately 8 h per day for 5 days.  No compound-related adverse 
clinical effects were noticed.  The average urinary excretion of 
3-(4'-hydroxy-phenoxy)-benzoic acid increased from day 1 to day 5, 
but then decreased 24 h after spraying had ceased (Hart et al., 
1982). 

    In another study, two agricultural pilots and five 
mixer/loaders were monitored for dermal exposure during aerial 
"ultra-low-volume" (ULV) applications of cypermethrin in vegetable 
oil to cotton.  This study was conducted in Greenwood, Mississippi.  
The mixer/loaders wore protective equipment.  The actual dermal 
exposure for pilots was 0.67 mg/8 h and for mixer/loaders 2.43 
mg/8h.  The exposure of pilots was predominantly of the hands, 
whereas that of mixer/loaders was more uniform (hands were 
protected).  The urinary excretion of cypermethrin metabolites was 
very low; between 4 and 22 g cypermethrin equivalents/day.  This 
study demonstrates that exposure of pilots and mixer/loaders during 
the aerial ULV applications of cypermethrin is minimal and that 
skin absorption is very slight (Chester et al., 1986). 

    Desi et al. (1986b) carried out a biological monitoring and 
health surveillance study on 11 workers spraying organophosphate 
carbamate and pyrethroid pesticides in greenhouses during the whole 
year in comparison with 10 control persons.  During the work, 
protective clothing and masks were worn before and after a regular 
spraying period with pyrethroids (including cypermethrin).  
Extensive medical examinations, such as urinalysis, haematology, 
immunoglobulin levels, whole blood cholinesterase activity, serum-
gamma-glutamyltransferase activity, chromosome analysis and 
electro-cardiography were performed over a period of 3 months.  The 
amount of cypermethrin in the blood was just at the limit of 
detection.  No health injuries or other significant changes in the 
parameters studied were found. 

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

10.1.  Evaluation

    Cypermethrin, an alpha-cyano pyrethroid consisting of a mixture 
of 8 stereo-isomers, is a highly active insecticide effective 
against a wide range of pests in many food and non-food 
commodities. 

    It is stable to light and heat, it has a low vapour pressure 
and is more stable in acidic than in alkaline media.  Sensitive 
analytical methods for the determination of residues in food and 
the environment are available. 

    When cypermethrin is applied to crops, residues may occur in 
soils and surface waters, but biological degradation is fairly 
rapid and residues do not accumulate in the environment.  
Photodegradation is unlikely to play an important role.  The main 
route of degradation is cleavage of the ester linkage to give 2 
main degradation products containing the cyclopropane, and the 
phenoxybenzyl moiety.  The half-lives in the soil are determined by 
many factors, but are in the range of 2 - 4 weeks.  Cypermethrin is 
strongly adsorbed by soil and downward leaching is negligible.  
Because of its rather fast breakdown forming less toxic products, 
and the low dose rates used in good agricultural practice, it is 
unlikely that cypermethrin will attain significant levels in the 
environment. 

    Bioaccummulation in certain organisms, such as fish, took place 
under laboratory conditions, but levels declined on cessation of 
exposure and there are indications that, under natural conditions, 
fish will not contain measurable residues. 

    When applied according to good agricultural practice, the 
levels of cypermethrin residues in food commodities are generally 
low.  Total diet studies are not available, but from the available 
residue information, it can be inferred that the oral intake by man 
is well below the ADI. 

    High dose levels of cypermethrin may exert transient effects on 
the soil microflora.  Earthworms and other soil organisms are 
generally rather resistant to cypermethrin, while fish and other 
aquatic invertebrates are very sensitive.  Because of its strong 
adsorption on soil, only low levels of cypermethrin may leak into 
surface water.  These may have transient effects, mainly on surface 
breathing insects. 

    The toxicity of cypermethrin for birds is low.  Bees appear to 
be very sensitive in laboratory tests.  Under field conditions, the 
effect on bees is minimal, because cypermethrin seems to have a 
repellent effect for bees. 

    Absorption and elimination of cypermethrin has been rapid in 
the different mammalian species tested.  The major metabolic 
reaction is cleavage of the ester bond followed by hydroxylation 
and conjugation of the cyclopropane- and phenoxybenzyl moiety.  The 
highest levels are found in body fat, which is consistent with the 
lipophilic nature of cypermethrin.  The half-life in the fat of the 
rat is about 12 - 19 days for the  cis-isomer and 3 - 4 days for the 
 trans-isomer.  Breakdown products in plants are bound as 
glucosides. 

    The acute toxicity of cypermethrin for mammals is of a moderate 
order.  The oral LD50 for the rat ranges from 200 to 4000 mg/kg 
body weight.  Short-term and long-term toxicity studies on rats, 
mice, and dogs have shown effects on growth, on the liver and 
kidneys, and the nervous system, and on haematology.  A no-
observed-adverse-effect level of 7.5 mg/kg body weight has been 
adopted by the Task Group. 

    Cypermethrin was not carcinogenic for mice or rats fed diets 
containing high levels of the material over a 2-year period.  
Cypermethrin did not induce teratogenic effects in either rats at 
70 mg/kg body weight or rabbits at 30 mg/kg body weight.  It was 
also shown not to have any effects on reproductive performance 
during a 3-generation reproduction study in rats administered 
100 mg/kg diet.  In a variety of mutagenicity studies, cypermethrin 
was shown to be mainly without mutagenic activity. 

    The mechanism of the action on the nervous system has been 
extensively studied.  From these studies and the occupational 
studies available, it seems that the skin sensation seen in workers 
handling cypermethrin, generally lasts only a few hours and does 
not persist for more than one day after exposure.  Other 
neurological signs were not observed.  These skin sensations can be 
considered to be an early warning that exposure has occurred and 
that work practice should be reviewed.  Cypermethrin may cause eye 
irritation and may be a sensitizer for certain persons. 

10.2.  Conclusions

    It can be concluded that:

     General population:  When applied according to good 
agricultural practice, exposure of the general population to 
cypermethrin is negligible and is unlikely to present a hazard. 

     Occupational exposure:  With reasonable work practices,
hygiene measures, and safety precautions, the use of cypermethrin 
is unlikely to present a hazard to those occupationally exposed to 
it.  The occurrence of "facial sensations" is an indication of 
exposure.  Under these circumstances work practice should be 
reviewed. 

     Environment:  With recommended application rates it is
unlikely that cypermethrin or its degradation products will attain 
levels of environmental significance.  Notwithstanding its high 
toxicity for fish and honey bees, this is only likely to cause a 
problem in the case of spillage and overspraying. 

11.  RECOMMENDATIONS

-   Cypermethrin should be included among the residues looked for 
    in surveillance, market-basket, or total diet studies. 

-   Attention should be paid to the implications for the welfare of 
    human beings of animal studies indicating immune suppression. 

-   Further follow-up studies into the facial effects in human 
    beings should be conducted, in order to better understand this 
    phenomenon. 

12.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    Cypermethrin was discussed at meetings of the Joint FAO/WHO 
Meeting on Pesticide Residues (JMPR) during the period 1979-84 
(FAO/WHO, 1980a,b; 1982a,b; 1983a,b; 1984; 1985a,b,c; Vettorazzi & 
Van den Hurk, 1984).  In 1981, the JMPR established an Acceptable 
Daily Intake (ADI) for cypermethrin of 0 - 0.05 mg/kg body weight. 

    The Pesticide Development and Safe Use Unit, Division of Vector 
Biology and Control, WHO, classified cypermethrin as "irritant to 
eyes and sensitizer of skin" in the list of "technical products 
unlikely to present an acute hazard in normal use" (Plestina, 1984; 
WHO, 1979; WHO, 1985).  The same division published a data sheet on 
cypermethrin, No. 84.58 (WHO/FAO, 1975-85). 

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M.A.  (1984)  Toxicological and histopathological studies on 
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ABDEL-AAL, Y.A.I., EL-SAYED, A.M.K., NEGM, A.A., HUSSEIN, 
M.H., & EL-SEBAE, A.H.  (1979)  The relative toxicity of 
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82.

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AHMED, Y.M., MOSTAFA, A.M.A., & ELEWA, M.A.  (1985)  Toxicity 
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some pyrethroids.  J. environ. Sci. Health, B20(6): 689-699.

ALINIAZEE, M.T. & CRANHAM, J.E.  (1980)  Effect of four 
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AMER, S.M. & ABOUL-ELA, E.I.  (1985)  Cytogenetic effects of 
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ASCHER, K.R.S., ELIYAHU, M., NEMNY, N.E., & ISHAAYA, I.  
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AWASTHI, M.D. & ANAND, L.  (1983)  Dissipation and persistence 
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BADMIN, J.S. & TWYDELL, R.S.  (1976)   Evaluation of the 
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BAICU, T.  (1982)  Toxicity of some pesticides to  Trichoderma 
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BAKER, P.G. & BOTTOMLEY, P.  (1982)  Determination of residues 
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BALDWIN, M.K.  (1977a)   Residues of the pyrethroid insecticide 
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BALDWIN, M.K. & LAD, D.D.  (1978a)   Residue data for milk 
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BALDWIN, M.K. & LAD, D.D.  (1978b)   The accumulation and 
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BALDWIN, M.K., BUCKWELL, A.C., & LAD, D.D.  (1977)   Residue 
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BARIOLA, L.A. & LINGREN, P.D.  (1984)  Comparative toxicities 
of selected insecticides against pink bollworm (Lepidoptera: 
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BARLOW, F., HADAWAY, A.B., FLOWER, L.S., & TURNER, C.R.  
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BATTELLE  (1982)   Pesticide programme of research and market 
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BAYOUMI, O.C.  (1982)  The susceptibility of Myzus persicae 
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BENNETT, D.  (1981a)   The accumulation, distribution, and 
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BENNETT, D.  (1981b)   Residues of RIPCORD in Rainbow trout 
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BENNETT, D., CROSSLAND, N.O., & SHIRES, S.W.  (1980)   Spray 
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BLAIR, D. & RODERICK, H.R.  (1976)   Toxicity studies on the 
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BLAIR, D., BUTTERWORTH, S.T.G., & RODERICK, H.R.  (1976)  
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BLAND, P.D.  (1985)  Capillary gas chromatographic 
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BOSIO, P.G.  (1979)   Residues of Barricade (cypermethrin) in 
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BOSTANIAN, N.J. & BELANGER, A.  (1985)  The toxicity of three 
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BRAUN, H.E. & STANEK, J.  (1982)  Application of the AOAC 
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BRAUN, H.E., FRANK, R., & MILLER, L.A.  (1985)  Residues of 
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BREMPONG-YEBOAH, C.Y., SAITO, T., & MIYATA, T.  (1983)  
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BREMPONG-YEBOAH, C.Y., SAITO, T., & MIYATA, T.  (1984a)  
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BREMPONG-YEBOAH, C.Y., SAITO, T., & MIYATA, T.  (1984b)  
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BREMPONG-YEBOAH, C.Y., SAITO, T., & MIYATA, T.  (1984c)  The 
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BROMLEY, S. & COOK, K.A.  (1979)   Determination of the effects 
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BROOKS, T.M.  (1980)   Toxicity studies with agricultural 
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BROWN, V.K.  (1979a)   Toxicology of WL 43467 isomers: acute 
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BROWN, V.K.  (1979b)   Toxicology of WL 43467 isomers: acute 
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BUCKWELL, A.C.  (1981)   A 2-year feeding study in dogs on WL 
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BUTTERWORTH, S.T.G. & CLARK, D.G.  (1977)   Toxicity studies on 
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CAGEN, S.Z., MALLEY, L.A., PARKER, C.M., GARDINER, T.H., VAN 
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CASIDA, J.E., GAUGHAN, L.C., & RUZO, L.O.  (1979)  Comparative 
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CASSIDY, S.L.  (1979)   Acute oral toxicity of the spray 
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CHANG, C.K. & JORDAN, T.W.  (1982)  Penetration and metabolism 
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CHANG, C.K. & JORDAN, T.W.  (1983)  Insecticide handling 
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CHAPMAN, R.A. & HARRIS, C.R.  (1981)  Persistence of four 
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CHAPMAN, R.A. & SIMMONS, H.S.  (1977)  Gas-liquid chromato- 
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CHAPMAN, R.A., TU, C.M., HARRIS, C.R., & COLE, C.  (1981)  
Persistence of five pyrethroid insecticides in sterile and 
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CHENG, H.H.  (1984)  Residual toxicity of six pyrethroid and 
two organophosphorus insecticides on the soil surface against 
dark-sided cutworm (Lepidoptera: Noctuidae) on tobacco in 
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CHENG, H.H. & HANLON, J.J.  (1984)  Residual toxicity of six 
insecticides and a herbicide applied sequentially or in tank 
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CHESTER, G., HATFIELD, L.D., HART, T.B., LEPPERT, B.C., 
SWAINE, H., & TUMMON, O.J.  (1986)   Worker exposure to, and 
 absorption of cypermethrin during aerial application of an 
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COATS, S.A., COATS, J.R., & ELLIS, C.R.  (1979)  Selective 
toxicity of three synthetic pyrethroids to eight coccinellids, 
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CODEX ALIMENTARIUS COMMISSION  (1986)   Guide to Codex 
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COLE, L.M., CASIDA, J.E., & RUZO, L.O.  (1982)  Comparative 
degradation of the pyrethroids tralomethrin, tralocythrin, 
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COOK, K.A.  (1978a)   Determination of the effects of WL 43467 
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COOK, K.A.  (1978b)   Determination of the effects of WL 43467 
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COOMBS, A.D., CARTER, B.I., HEND, R.W., BUTTERWORTH, S.G., & 
BUCKWELL, A.C.  (1976)   Toxicity studies on the insecticide WL 
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CORBITT, T.S., WRIGHT, D.J., & GREEN, A.St.J.  (1985)  The 
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COVENEY, P.C. & EADSFORTH, C.V.  (1982)   The metabolism of 
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CRAWFORD, M.J.  (1976a)   The metabolism of WL 43467 in 
 mammals. The fate of a single oral dose of (14 C-benzyl)WL 
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CRAWFORD, M.J.  (1976b)   The metabolism of WL 43467 in 
 mammals. The fate of a single oral dose of 14 C-WL 42641 
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CRAWFORD, M.J.  (1977)   The metabolism of WL 43467 in mammals. 
 The fate of a single oral dose of (14 C-cyclopropyl)WL 43467 in 
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CRAWFORD, M.J.  (1979a)  The metabolism of cypermethrin (WL 
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CRAWFORD, M.J.  (1979b)   The metabolism of cypermethrin (WL 
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CRAWFORD, M.J.  (1979c)   The metabolism of 14 C-cypermethrin by 
 rat liver microsomes, Sittingbourne, Shell Research 
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CRAWFORD, M.J.  (1979d)   The metabolic fate of the cis- and 
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CRAWFORD, M.J.  (1979e)   The metabolism of cypermethrin (WL 
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CRAWFORD, M.J. & HUTSON, D.H.  (1977a)   The metabolic fate of 
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 Metabolism and elimination of 14 C-aryl-labelled cis- and 
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CRAWFORD, M.J. & HUTSON, D.H.  (1977b)   The elimination and 
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CRAWFORD, M.J. & HUTSON, D.H.  (1978)   The elimination of 
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CRAWFORD, M.J., CROUCHER, A., & HUTSON, D.H.  (1981a)  
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CRAWFORD, M.J., CROUCHER, A., & HUTSON, D.H.  (1981b)  The 
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CRAYFORD, J.V.  (1978)   A study of the metabolism of 
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CRAYFORD, J.V. & HUTSON, D.H.  (1979)   The identification of 
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CRAYFORD, J.V. & HUTSON, D.H.  (1980)  Xenobiotic triglyceride 
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CRAYFORD, J.V., HUTSON, D.H., & THORPE, E.  (1980)   The 
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CROSSLAND, N.O.  (1982)  Aquatic toxicology of cypermethrin. 
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CROSSLAND, N.O. & BENNETT, D.  (1976)   A field trial to assess 
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CROSSLAND, N.O. & ELGAR, K.E.  (1983)  Fate and biological 
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CROSSLAND, N.O. & STEPHENSON, R.R.  (1979)  The role of pond 
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CROSSLAND, N.O., BENNETT, D., KANE, D.F., & STEPHENSON, R.R.  
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CROSSLAND, N.O., SHIRES, S.W., & BENNETT, D.  (1982)  Aquatic 
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CROUCHER, A., HUTSON, D.H., & LOGAN, C.J.  (1982a)   Hepatic 
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CROUCHER, A., HUTSON, D.H., & LOGAN, C.J.  (1982b)   In vitro 
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CROUCHER, A., HUTSON, D.H., & STOYDIN, G.  (1985)  Excretion 
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DEAN, B.J.  (1977)   Toxicity studies with SL 43467: chromosome 
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DEAN, B.J., PAUW, C.L, VAN DER, & BUTTERWORTH, S.T.B.  (1977)  
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DELABIE, J., BOS, C., FONTA, C., & MASSON, C.  (1985)  Toxic 
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DESI, I., VARGA, L., DOBRONYI, I., & SZKLENARIK, G.  (1985)  
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REIFF, B.  (1976)   The acute toxicity of the pyrethroid 
 insecticide WL43467 to Brown trout (S. trutta), Sittingbourne, 
Shell Research (TLBR.0096.76).

REIFF, B.  (1977)   The acute toxicity of the pyrethroid WL 
 43467 to Daphnia magna, Sittingbourne, Shell Research (TLGR. 
0155.77).

REIFF, B.  (1978a)   The effect of suspended solids on the 
 toxicity of WL 43467 to Rainbow trout (Salmo gairdneri), 
Sittingbourne, Shell Research (TLGR.0007.78).

REIFF, B.  (1978b)   The acute toxicity of the pyrethroid 
 insecticide WL 43467 to Rainbow trout (Salmo gairdneri), 
 Common carp (Cyprinus carpio),  and Rudd (Scardinius 
erythrophthalmus), Sittingbourne, Shell Research (TLGR.0067. 
78).

RHODES, C., JONES, B.K., CROUCHER, A., HUTSON, D.H., LOGAN, 
C.J., HOPKINS, R., HALL, B.E., & VICKERS, J.A.  (1984)  The 
bioaccumulation and biotransformation of  cis, trans- 
cypermethrin in the rat.  Pestic. Sci., 25: 471-480.

RILEY, D. & HILL, I.R.  (1983)  Adsorption reduces activity of 
pesticides in soil and water. In:  Proceedings of the 10th 
 International Congress on Plant Protection, Brighton, 20-25 
 November, 1983, Vol. 2, pp. 728 (4B-R18).

RISKALLAH, M.R.  (1984)  Influence of posttreatment 
temperature on the toxicity of pyrethroid insecticides to 
susceptible and resistant larvae of the Egyptian cotton 
leafworm,  Spodoptera littoralis (Boisd.)  Experientia (Basel), 
40(2): 188-190.

RIVIERE, J.L., BACH, J., & GROLLEAU, G.  (1983)  Effect of 
pyrethroid insecticides and  N-(3,5-dichlorophenyl) 
dicarboximide fungicides on microsomal drug metabolizing 
enzymes in the Japanese quail  (Coturnix coturnix). Bull. 
 environ. Contam. Toxicol., 31: 479-485.

ROBERTS, B.L. & DOROUGH, H.W.  (1984)  Relative toxicities of 
chemicals to the earthworm  Eisenia foetida. Environ. Toxicol. 
 Chem., 3(1): 67-68.

ROBERTS, T.R.  (1981)  The metabolism of the synthetic 
pyrethroids in plants and soils. In: Hutson, D.H. & Roberts, 
T.R., ed.  Progress in pesticide biochemistry, New York, John 
Wiley and Sons, Vol. 1, pp. 115-146.

ROBERTS, T.R. & STANDEN, M.E.  (1977)  Degradation of the 
pyrethroid cypermethrin NRDC 149()-alpha-cyano-3-phenoxy- 
benzyl()- cis,trans-3-(2,2-dichlorovinyl-2,2-dimethylcyclo- 
propanecarboxylate and the respective  cis-(NRDC 160) and the 
 trans-(NRDC 159) isomers in soils.  Pestic. Sci., 8: 305-319.

ROBERTS, T.R. & STANDEN, M.E.  (1981)  Further studies of the 
degradation of the pyrethroid insecticide cypermethrin in 
soils.  Pestic. Sci., 12: 285-296.

ROSE, B.  (1981)   A dietary toxicity study of WL 43467 in 
 Mallard ducks, Sittingbourne, Shell Research (TLGR.80.033).

ROSE, G.P.  (1982)   Toxicology of pyrethroids: the acute oral 
 and percutaneous toxicity of WL 85871 (cis-2-RIPCORD) 
 comparison with RIPCORD, Sittingbourne, Shell Research 
(SBGR.82.130).

ROSE, G.P.  (1983)   Neurotoxicity of WL 85871 comparison with 
 WL 43467: the effect of twenty oral doses of WL 85871 or WL 
 43467 over a period of 4 weeks on the rat sciatic/posterior 
 tibial nerve, trigeminal nerve, and trigeminal ganglion, 
Sittingbourne, Shell Research (SBGR.83.185).

ROSE, G.P. & DEWAR, A.J.  (1978)   Toxicity studies on the 
 insecticide WL 43467: the effect of age on the neurotoxicity 
 of WL 43467 to rats, Sittingbourne, Shell Research 
(TLGR.0039.78).

ROSE, G.P. & DEWAR, A.J.  (1979a)   Toxicity studies on the 
 RIPCORD/AZODRIN formulation EF 5254: biochemical and 
 functional studies on the neurotoxicity of the formulation EF 
 5254 in the rat, Sittingbourne, Shell Research (TLGR.79.027).

ROSE, G.P. & DEWAR, A.J.  (1979b)   A neurotoxicity study on 
 the pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA), 
Sittingbourne, Shell Research (TLGR.79.076).

ROSE, G.P. & DEWAR, A.J.  (1983)  Intoxication with four 
synthetic pyrethroids fails to show any correlation between 
neuromuscular dysfunction and neurobiochemical abnormalities 
in rats.  Arch. Toxicol., 53: 297-316.

RUIGT, G.S.F. & VAN DEN BERCKEN, J.  (1986)  Action of 
pyrethroids on a nerve - muscle preparation of the clawed 
frog,  Xenopus laevis. Pestic. Biochem. Physiol., 25: 176-187.

RUZO, L.O.  (1983)  Involvement of oxygen in the 
photoreactions of cypermethrin and other halogenated 
pyrethroids.  J. agric. food Chem., 31: 1113-1115.

RUZO, L.O. & CASIDA, J.E.  (1980)  Pyrethroid photochemistry: 
mechanistic aspects in reactions of the (dihalogenovinyl)- 
cyclopropanecarboxylate substituent.  J.C.S. Perkin Trans. I, 
728-732.

RUZO, L.O., HOLMSTEAD, R.L., & CASIDA, J.E.  (1977)  
Pyrethroid photochemistry: decamethrin.  J. agric. food Chem., 
25(6): 1385-1389.

SAAD, A.S.A., ELEWA, M.A., ALY, N.M., AUDA, M., & EL-SEBAE, 
A.H.  (1981)  Toxicological studies on the Egyptian cotton 
leafworm  Spodoptera littoralis. I. Potentiation and antagonism 
of synthetic pyrethroid, organophosphorus and urea derivative 
insecticides.  Meded. Fac. Landbouwwet. Rijksuniv. Gent, 46(2): 
559-571.

SAKATA, S., MIKAMI, N., MATSUDA, T., & MIYAMOTO, J.  (1986)  
Degradation and leaching behaviour of the pyrethroid 
insecticide cypermethrin in soils.  J. Pestic. Sci., 11: 71-79.

SCOTT, J.G. & GEORGHIOU, G.P.  (1984)  Influence of 
temperature on knockdown, toxicity and resistance to 
pyrethroids in the housefly,  Musca domestica. Pestic. Biochem. 
 Physiol., 21: 53-62.

SEEHY, M.A., SHALABI, H.G., SHAKER, N., & BADR, E.  (1983)   In 
 vivo induction of sister chromatid exchanges in mice by 
cypermethrin.  Proceedings of the International Conference on 
 Environmental Hazards of Agrochemicals, 1982, Vol. 1, 659-673.

SHERWOOD, C.M. & SHIRES, S.W.  (1981)   The effect of RIPCORD 
 on the invertebrate fauna of winter barley in France, 
Sittingbourne, Shell Research (SBGR.81.070).

SHIRES, S.W.  (1980)  Soil surface predators in arable land: 
the effects of farming practices.  Span, 23(2): 62-64.

SHIRES, S.W.  (1982a)   The effect of RIPCORD on the 
 invertebrate fauna of winter wheat in France, Sittingbourne, 
Shell Research (SBGR.81.303).

SHIRES, S.W.  (1982b)   A field study in France of the effects 
 on honey bees of an aerial application of RIPCORD in spring- 
 grown oil seed rape, Sittingbourne, Shell Research 
(SBGR.82.066).

SHIRES, S.W.  (1982c)   A study of the effects of an aerial 
 application of RIPCORD on the invertebrate fauna of winter 
 wheat, Sittingbourne, Shell Research (SBGR.82.304).

SHIRES, S.W.  (1983a)  The use of small enclosures to assess 
the toxic effects of cypermethrin in fish under field 
conditions.  Pestic. Sci., 14: 475-480.

SHIRES, S.W.  (1983b)  Pesticides and honey bees. Case studies 
with RIPCORD and FASTAC.  Span, 26(3): 118-120.

SHIRES, S.W. & BENNETT, D.  (1982)   Spray drift from aerial 
 application of RIPCORD to winter wheat in Kent, UK: fate and 
 effects in adjacent drainage ditches, Sittingbourne, Shell 
Research (SBGR.82.274).

SHIRES, S.W. & BENNETT, D.  (1985)  Contamination and effects 
in freshwater ditches, resulting from an aerial application of 
cypermethrin.  Ecotoxicol. environ. Saf., 9: 145-158.

SHIRES, S.W. & DEBRAY, P.  (1982)  Pyrethroids and the bee 
problem.  Shell Agric., May: 1-3.

SHIRES, S.W. & TIPTON, J.D.  (1982)   A study of the effects of 
 BIRLANE and RIPCORD on the hymenopterous parasites of white 
 flies on cotton in the Sudan, Sittingbourne, Shell Research 
(SBGR.82.342).

SHIRES, S.W., BENNETT, D., & KANE, D.F.  (1979)   The effects 
 of WL 43467 on soil surface fauna, earthworms, and litter 
 composition, Sittingbourne, Shell Research (TLGR.79.074).

SHIRES, S.W., BENNETT, D., & CROSSLAND, N.O.  (1980)   Spray 
 drift from RIPCORD applications to arable crops in Suffolk, 
 UK: fate and effects in adjacent farm ponds, Sittingbourne, 
Shell Research (TLGR.80.150).

SHONO, T. & CASIDA, J.E.  (1978)  Species-specificity in 
enzymatic oxidation of pyrethroid insecticides: 
3-phenoxybenzyl and alpha-cyano-3-phenoxybenzyl 3-(2,2-dihalo- 
vinyl)-2,2-dimethylcyclopropanecarboxylates.  J. Pestic. Sci., 
3: 165-168.

SHONO, T., OHSAWA, K., & CASIDA, J.E.  (1979)  Metabolism of 
 trans- and  cis-permethrin and  trans- and  cis-cypermethrin, and 
decamethrin by microsomal enzymes.  J. agric. food Chem., 
27(2): 316-325.

SMART, L.E. & STEVENSON, J.H.  (1982)  Laboratory estimation 
of toxicity of pyrethroid insecticides to honey bees: 
relevance to hazard in the field.  Bee World, 63(4): 150-152.

SMIES, M., EVERS, R.H.J., PEIJNENBURG, F.H.M., & KOEMAN, J.H.  
(1980)  Environmental aspects of field trials with pyrethroids 
to eradicate tsetse fly in Nigeria.  Ecotoxicol. environ. Saf., 
4: 114-128.

SMITH, T.M. & STRATTON, G.W.  (1986)  Effects of synthetic 
pyrethroid insecticides on non-target organisms.  Residue Rev., 
97: 93-120.

SODERLUND, D.M. & CASIDA, J.E.  (1977)  Effects of pyrethroid 
structure on rates of hydrolysis and oxidation by mouse liver 
microsomal enzymes.  Pestic. Biochem. Physiol., 7: 391-401.

SPIELBERGER, U., NA'ISA, B.K., KOCH, K., MANNO, A., SKIDMORE, 
P.R., & COUHS, H.H.  (1979)  Field trials with the synthetic 
pyrethroids permethrin, cypermethrin, and decamethrin against 
 Glossina (Diptera: gloninidae) in Nigeria.  Bull. entomol. 
 Res., 69: 667-689.

STANDEN, M.E.  (1977)   The leaching and degradation of the 
 insecticide WL43467 when applied in sheep-dip solution to 
 soil, Sittingbourne, Shell Research (BLGR.0141.77) 
(Unpublished report).

STELZER, K.J. & GORDON, M.A.  (1984)  Effects of pyrethroids 
on lymphocyte mitogenic responsiveness.  Res. Commun. chem. 
 Pathol. Pharmacol., 46(1): 137-150.

STEPHENSON, R.R.  (1980a)   The acute toxicity of WL 43467 to 
 some freshwater invertebrates in static water tests, 
Sittingbourne, Shell Research (TLGR.80.040).

STEPHENSON, R.R.  (1980b)   The acute toxicity of cypermethrin 
 (WL 43467) to the freshwater shrimp (Gammarus pulex)  and 
 larvae of the mayfly (Cloeon dipterum)  in continuous-flow 
 tests, Sittingbourne, Shell Research (TLGR.80.079).

STEPHENSON, R.R.  (1981a)   RIPCORD: the acute toxicity of an 
 EC formulation to Tilapia nilotica in the laboratory, 
Sittingbourne, Shell Research (SBGR.81.028).

STEPHENSON, R.R.  (1981b)   Cypermethrin: acute toxicity to 
Tilapia nilotica  in a continuous-flow test, Sittingbourne, 
Shell Research (SBGR.81.080).

STEPHENSON, R.R.  (1982a)   RIPCORD: a laboratory study of the 
 acute toxicity of an EC formulation to Tilapia nilotica in the 
 presence of suspended solids, Sittingbourne, Shell Research 
(SBGR.81.235).

STEPHENSON, R.R.  (1982b)   WL 85871 and cypermethrin: a 
 comparison of their acute toxicity to Salmo gairdneri, Daphnia 
 magna, and Selenastrum capricornutum, Sittingbourne, Shell 
Research (SBGR.81.277).

STEPHENSON, R.R.  (1982c)   RIPCORD, BIRLANE, and FURADAN: 
 acute toxicity to common carp (Cyprinus carpio L.)  in the 
 laboratory and in rice paddies, Sittingbourne, Shell Research 
(SBGR.82.030).

STEPHENSON, R.R.  (1982d)   WL 85871 and cypermethrin: a 
 comparative study of their toxicity to the Fathead minnow 
 Pimephales promelas (Rafinesque), Sittingbourne, Shell 
Research (SBGR.82.298).

STEPHENSON, R.R.  (1982e)  Aquatic toxicology of cypermethrin. 
I. Acute toxicity to some freshwater fish and invertebrates in 
laboratory tests.  Aquat. Toxicol., 2: 175-185.

STEPHENSON, R.R.  (1983)  Pesticides and freshwater animals. A 
case study with RIPCORD.  Span, 26(3): 121-122.

STEPHENSON, R.R., CHOI, S.Y., & OLMOS-JEREZ, A.  (1984)  
Determining the toxicity and hazard to fish of a rice 
insecticide.  Crop Prot., 3(2): 151-165.

STEVENS, J.E.B. & HILL, I.R.  (1980)   Mobility of cypermethrin 
 and its degradation products in soil columns, Fernhurst, 
Imperial Chemical Industries (Report No. RJ/0166-B) 
(Unpublished ICI data).

SUHAS, Y. & DEVAIAH, M.C.  (1985)  Studies on the effect of 
insecticides sprayed mulberry leaves to silkworm,  Bombyx mori 
 L. Pesticides, 19(10): 53-54, 57.

SUNDARARAJAN, R. & CHAWLA, R.P.  (1983)  Simple, sensitive 
technique for detection and separation of halogenated 
synthetic pyrethroids by thin layer chromatography.  J. Assoc. 
 Off. Anal. Chem., 66(4): 1009-1012.

SURULIVELU, T. & MENON, M.V.  (1982)  Contact toxicity of 
synthetic pyrethroids, organophosphorus and carbamate 
insecticides to adults of the parasite  Chelonus blackburni 
Cameron.  J. Agric. Sci. Camb., 98: 331-334.

SUTHERS, J.R. & MARLOW, R.G.  (1981)   A study of the exposure 
 and health of Indian workers spraying RIPCORD on cotton over 
 five consecutive days using mistblower and knapsack 
 applicators, The Hague, Shell Internationale Research Mij (TOX 
81-003).

SWAINE, H. & SAPIETS, A.  (1980a)   Residue transfer study with 
 dairy cows fed on a diet containing the insecticide.  
Fernhurst, Imperial Chemical Industries (Unpublished Report 
No. RJ/0186-B).

SWAINE, H. & SAPIETS, A.  (1980b)   Residue levels of the major 
 metabolites of the insecticide in the milk and tissues of 
 dairy cows fed on a diet containing cypermethrin at 50 mg/kg, 
Fernhurst, Imperial Chemical Industries (Unpublished Report 
No. RJ/0198-B).

TAG EL-DIN, A., ABBAS, M.M., ALY, H.A., TANTAWY, G., & ASKAR, 
A.  (1981)  Acute toxicities to  Mugil cephalus fry caused by 
some herbicides and new pyrethroids.  Meded. Fac. Landbouwwet. 
 Rijksuniv. Gent, 46(1): 387-391.

TAKAHASHI, N., MIKAMI, N., MATSUDA, T., & MIYAMOTO, J.  
(1985a)  Hydrolysis of the pyrethroid insecticide cypermethrin 
in aqueous media.  J. Pestic. Sci., 10: 643-648.

TAKAHASHI, N., MIKAMI, N., MATSUDA, T., & MIYAMOTO, J.  
(1985b)  Photodegradation of the pyrethroid insecticide 
cypermethrin in water and on soil surface.  J. Pestic. Sci., 
10: 629-642.

TAYLOR, S.M., ELLIOTT, C.T., & BLANCHFLOWER, J.  (1985)  
Cypermethrin concentrations in hair of cattle after 
application of impregnated ear tags.  Vet. Rec., 116(23): 620.

TESH, J.M., TESH, S.A., & DAVIES, W.  (1978)   WL 43467: 
 effects upon the progress and outcome of pregnancy in rat, 
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TEWARI, G.C. & KRISHNAMOORTHY, P.N.  (1985)  Selective 
toxicity of some synthetic pyrethroids and conventional 
insecticides to aphid predator,  Menochilus sexmaculatus 
Fabricius.  Indian J. agric. Sci., 55(1): 40-43.

TRIGG, C.E., BUTTERWORTH, S., & HUNT, P.F.  (1977)  
 Neurotoxicity of pyrethroids: a study of teased nerves from 
 rats fed WL 43467 for 12 months, Sittingbourne, Shell Research 
(TLGR.0137.77).

TU, C.M.  (1980)  Influence of five pyrethroids insecticides 
on microbial populations and activities in soil.  Microbiol. 
Ecol., 5: 321-327.

TU, C.M.  (1982)  Effects of some pesticides on  Rhizobium 
 japonicum and on the seed germination and pathogens of 
soybean.  Chemosphere, 11(10): 1027-1033.

US EPA  (1984)  Cypermethrin: tolerances for residues in or on 
raw agricultural commodities: final rule. Part III.  Fed. Reg., 
49(117): 24865-24872.

VAN DEN BERCKEN, J.  (1977)  The action of allethrin on the 
peripheral nervous system of the frog.  Pestic. Sci., 8: 
692-699.

VAN DEN BERCKEN, J. & VIJVERBERG, H.P.M.  (1980)   Effects of 
 insecticides on the sensory system of Xenopus. Insect neurobiology 
 and pesticide action, London, Society of Chemical 
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VAN DEN BERCKEN, J., AKKERMANS, L.M.A., & VAN DER ZALM, J.M.  
(1973)  DDT-like action of allethrin in the sensory nervous 
system of  Xenopus laevis. Eur. J. Pharmacol., 21: 95-106.

VAN DEN BERCKEN, J., KROESE, A.B.A., & AKKERMANS, L.M.A.  
(1979)  Effects of insecticides on the sensory nervous system. 
In: Narashashi, T., ed.  Neurotoxicology of insecticides and 
 pheromones, New York, London, Plenum Publishing Corporation, 
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VAN SITTERT, N.J., EADSFORTH, C.V., & BRAGT, P.C.  (1985a)  
 Human oral dose-excretion study with RIPCORD, The Hague, Shell 
Internationale Petroleum Maatschappy (HSE.85.008).

VAN SITTERT, N.J., EADSFORTH, C.V., & BRAGT, P.C.  (1985b)  
 Human dermal dose-excretion study with RIPCORD, The Hague, 
Shell Internationale Petroleum Maatschappy (HSE.85.009).

VEKARIA, M.V. & VYAS, H.N.  (1985)  Studies on ovicidal 
toxicity of certain insecticides against the eggs of  Heliothis 
 armigera Hubner.  Pesticides, 19(10): 43-44.

VERSCHOYLE, R.D. & ALDRIDGE, W.N.  (1980)  Structure-activity 
relationships of some pyrethroids in rats.  Arch. Toxicol., 45: 
325-329.

VETTORAZZI, G. & VAN DEN HURK, G.W.  (1984)   Pesticides 
 reference index. JMPR 1961-84, Geneva, World Health 
Organization.

VIJVERBERG, H.P.M. & VAN DEN BERCKEN, J.  (1979)  Frequency- 
dependent effects of the pyrethroid insecticide decamethrin in 
frog myelinated nerve fibres.  Eur. J. Pharmacol., 58: 501-504.

VIJVERBERG, H.P.M. & VAN DEN BERCKEN, J.  (1982)  Action of 
pyrethroid insecticides on the vertebrate nervous system. 
 Neuropathol. appl. Neurobiol., 8: 421-440.

VIJVERBERG, H.P.M., RUIGT, G.S.F., & VAN DEN BERCKEN, J.  
(1982a)  Structure-related effects of pyrethroid insecticides 
on the lateral-line sense organ and on peripheral nerves of 
the clawed frog,  Xenopus laevis. Pestic. Biochem. Physiol., 
18: 315-324.

VIJVERBERG, H.P.M., VAN DER ZALM, J.M., & VAN DEN BERCKEN, J.  
(1982b)  Similar mode of action of pyrethroids and DDT on 
sodium channel gating in myelinated nerves.  Nature (Lond.), 
295: 601-603.

VIJVERBERG, H.P.M., VAN DER ZALM, J.M., VAN KLEEF, R.G.D.M., & 
VAN DEN BERCKEN, J.  (1983)  Temperature- and 
structure-dependent interaction of pyrethroids with the sodium 
channels in frog node of Ranvier.  Biochim. biophys. Acta, 728: 
73-82.

WADDILL, V.H.  (1978)  Contact toxicity of four synthetic 
pyrethroids and methomyl to some adult insect parasites. 
 Florida Entomol., 61(1): 27-30.

WALLACE, B.G., ROBERTS, T.R., & MCKERRELL, E.H.  (1982)  
 Cypermethrin. A residue transfer study with laying hens, 
Sittingbourne, Shell Research (SBTR.82.059).

WATTERS, F.L., WHITE, N.D.G., & COTE, D.  (1983)  Effect of 
temperature on toxicity and persistence of three pyrethroid 
insecticides applied to fir plywood for the control of the red 
flour beetle (Coleoptera: Tenebrionidae).  J. econ. Entomol., 
76: 11-16.

WHO  (1979)  WHO Technical Report Series, No. 634  (Safe use of 
 pesticides. Third Report of the WHO Expert Committee on Vector 
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WHO  (1985)  WHO Technical Report Series, No. 720  (Safe use of 
 pesticides. Ninth Report of the WHO Expert Committee on Vector 
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WHO/FAO  (1984)   Cypermethrin, Geneva, World Health 
Organization (Data Sheets on Pesticides, No. 84.58).

WILDE, G., KADOUM, A., & MIZE, T.  (1984)  Absence of 
synergism with insecticides combinations used on chinch bugs 
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WONG, S.W. & CHAPMAN, R.B.  (1979)  Toxicity of synthetic 
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15: 3-27.

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21: 3-17.

WOOD, MACKENZIE, & CO.  (1983)  Pyrethroids.  Agrochem. Monit., 
27: 3-12.

WORTHING, C.R. & WALKER, S.B.  (1983)   The pesticide manual, 
7th ed., Croydon, British Crop Protection Council, pp. 150-151.

WOUTERS, W. & VAN DEN BERCKEN, J.  (1978)  Action of 
pyrethroids.  Gen. Pharmacol., 9: 387-398.

WRIGHT, A.N., ROBERTS, T.R., DUTTON, A.J., & DOIG, M.V.  
(1980)  The metabolism of cypermethrin in plants: the 
conjugation of the cyclopropyl moiety.  Pestic. Biochem. 
 Physiol., 13: 71-80.

ZITKO, V., MCLEESE, D.W., METCALFE, C.D., & CARSON, W.G.  
(1979)  Toxicity of permethrin, decamethrin, and related 
pyrethroids to salmon and lobster.  Bull. environ. Contam. 
 Toxicol., 21: 338-343.

ZOHDY, G.I., OSMAN, A.A., & MOMEN, F.M.  (1984)  Toxicity of 
some pyrethroid compounds to the predatory mite,  Amblyseius 
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 Acarology VI, Chichester, Ellis Horwood Ltd., Vol. 2, pp. 
659-662.

APPENDIX

    On the basis of electrophysiological studies with peripheral 
nerve preparations of frogs  (Xenopus laevis; Rana temporaria, and 
 Rana esculenta), it is possible to distinguish between 2 classes 
of pyrethroid insecticides:  (Type I and Type II).  A similar 
distinction between these 2 classes of pyrethroids has been made on 
the basis of the symptoms of toxicity in mammals and insects (Van 
den Bercken et al., 1979; WHO, 1979; Verschoyle & Aldridge, 1980; 
Glickman & Casida, 1982; Lawrence & Casida, 1982).  The same 
distinction was found in studies on cockroaches (Gammon et al., 
1981). 

    Based on the binding assay on the gamma-aminobutyric acid 
(GABA) receptor-ionophore complex, synthetic pyrethroids can also 
be classified into two types:  the alpha-cyano-3-phenoxy-benzyl 
pyrethroids and the non-cyano pyrethroids (Gammon et al., 1982; 
Gammon & Casida, 1983; Lawrence & Casida, 1983; Lawrence et al., 
1985). 

     Pyrethroids that do not contain an alpha-cyano group (allethrin, 
 d-phenothrin, permethrin, tetramethrin, cismethrin, and 
 bioresmethrin) (Type I: T-syndrome) 

    The pyrethroids that do not contain an alpha-cyano group give 
rise to pronounced repetitive activity in sense organs and in 
sensory nerve fibres (Van den Bercken et al., 1973).  At room 
temperature, this repetitive activity usually consists of trains of 
3 - 10 impulses and occasionally up to 25 impulses.  Train duration 
is between 10 and 5 milliseconds. 

    These compounds also induce pronounced repetitive firing of the 
presynaptic motor nerve terminal in the neuromuscular junction (Van 
den Bercken, 1977).  There was no significant effect of the 
insecticide on neurotransmitter release or on the sensitivity of 
the subsynaptic membrane, nor on the muscle fibre membrane.  
Presynaptic repetitive firing was also observed in the sympathetic 
ganglion treated with these pyrethroids. 

    In the lateral-line sense organ and in the motor nerve 
terminal, but not in the cutaneous touch receptor or in sensory 
nerve fibres, the pyrethroid-induced repetitive activity increases 
dramatically as the temperature is lowered, and a decrease of 5 C 
in temperature may cause a more than 3-fold increase in the number 
of repetitive impulses per train.  This effect is easily reversed 
by raising the temperature.  The origin of this "negative 
temperature coefficient" is not clear (Vijverberg et al., 1983). 

    Synthetic pyrethroids act directly on the axon through 
interference with the sodium channel gating mechanism that 
underlies the generation and conduction of each nerve impulse.  The 
transitional state of the sodium channel is controlled by 2 
separately acting gating mechanisms, referred to as the activation 
gate and the inactivation gate.  Since pyrethroids only appear to 
affect the sodium current during depolarization, the rapid opening 

of the activation gate and the slow closing of the inactivation 
gate proceed normally. However, once the sodium channel is open, 
the activation gate is restrained in the open position by the 
pyrethroid molecule.  While all pyrethroids have essentially the 
same basic mechanism of action, however, the rate of relaxation 
differs substantially for the various pyrethroids (Flannigan & 
Tucker, 1985). 

    In the isolated node of Ranvier, allethrin causes prolongation 
of the transient increase in sodium permeability of the nerve 
membrane during excitation (Van den Bercken & Vijverberg, 1980).  
Evidence so far available indicates that allethrin selectively 
slows down the closing of the activation gate of a fraction of the 
sodium channels that open during depolarization of the membrane.  
The time constant of closing of the activation gate in the 
allethrin-affected channels is about 100 milliseconds compared with 
less than 100 microseconds in the normal sodium channel, i.e., it 
is slowed down by a factor of more than 100.  This results in a 
marked prolongation of the sodium current across the nerve membrane 
during excitation, and this prolonged sodium current is directly 
responsible for the repetitive activity induced by allethrin 
(Vijverberg et al., 1983). 

    The effects of cismethrin on synaptic transmission in the frog 
neuromuscular junction, as reported by Evans (1976), are almost 
identical to those of allethrin, i.e., presynaptic repetitive 
firing, and no significant effects on transmitter release or on the 
subsynaptic membrane. 

    Interestingly, the action of these pyrethroids closely 
resembles that of the insecticide DDT in the peripheral nervous 
system of the frog.  DDT also causes pronounced repetitive activity 
in sense organs, in sensory nerve fibres, and in motor nerve 
terminals, due to a prolongation of the transient increase in 
sodium permeability of the nerve membrane during excitation.  
Recently, it was demonstrated that allethrin and DDT have 
essentially the same effect on sodium channels in frog myelinated 
nerve membrane.  Both compounds slow down the rate of closing of a 
fraction of the sodium channels that open on depolarization of the 
membrane (Van den Bercken et al., 1973, 1979; Vijverberg et al., 
1982b). 

    In the electrophysiological experiments using giant axons of 
crayfish, the type I pyrethroids and DDT analogues retain sodium 
channels in a modified open state only intermittantly, cause large 
depolarizing afterpotentials, and evoke repetitive firing with 
minimal effect on the resting potential (Lund & Narahashi, 1983). 

    These results strongly suggest that permethrin and cismethrin, 
like allethrin, primarily affect the sodium channels in the nerve 
membrane and cause a prolongation of the transient increase in 
sodium permeability of the membrane during excitation. 

    The effects of pyrethroids on end-plate and muscle action 
potentials were studied in the pectoralis nerve-muscle preparation 
of the clawed frog  (Xenopus laevis).  Type I pyrethroids 
(allethrin, cismethrin, bioresmethrin, and 1R,  cis-phenothrin) 
caused moderate presynaptic repetitive activity, resulting in the 
occurrence of multiple end-plate potentials (Ruigt & Van den 
Bercken, 1986). 

     Pyrethroids with an alpha-cyano group on the 3-phenoxybenzyl
 alcohol (deltamethrin, cypermethrin, fenvalerate, and  fenpropanate) 
 (Type II: CS-syndrome) 

    The pyrethroids with an alpha-cyano group cause an intense 
repetitive activity in the lateral line organ in the form of long-
lasting trains of impulses (Vijverberg et al., 1982a).  Such a 
train may last for up to 1 min and contains thousands of impulses.  
The duration of the trains and the number of impulses per train 
increase markedly on lowering the temperature.  Cypermethrin does 
not cause repetitive activity in myelinated nerve fibres.  Instead, 
this pyrethroid causes a frequency-dependent depression of the 
nervous impulse, brought about by a progressive depolarization of 
the nerve membrane as a result of the summation of depolarizing 
after-potentials during train stimulation (Vijverberg & Van den 
Bercken, 1979; Vijverberg et al., 1983). 

    In the isolated node of Ranvier, cypermethrin, like allethrin, 
specifically affects the sodium channels of the nerve membrane and 
causes a long-lasting prolongation of the transient increase in 
sodium permeability during excitation, presumably by slowing down 
the closing of the activation gate of the sodium channel 
(Vijverberg & Van den Bercken, 1979; Vijverberg et al., 1983).  The 
time constant of closing of the activation gate in the 
cypermethrin-affected channels is prolonged to more than 100 
milliseconds.  Apparently, the amplitude of the prolonged sodium 
current after cypermethrin is too small to induce repetitive 
activity in nerve fibres, but is sufficient to cause the long-
lasting repetitive firing in the lateral-line sense organ. 

    These results suggest that alpha-cyano pyrethroids primarily 
affect the sodium channels in the nerve membrane and cause a long-
lasting prolongation of the transient increase in sodium 
permeability of the membrane during excitation. 

    In the electrophysiological experiments using giant axons of 
crayfish, the Type II pyrethroids retain sodium channels in a 
modified continuous open state persistently, depolarize the 
membrane, and block the action potential without causing repetitive 
firing (Lund & Narahashi, 1983). 

    Diazepam, which facilitates GABA reaction, delayed the onset of 
action of deltamethrin and fenvalerate, but not permethrin and 
allethrin, in both the mouse and cockroach.  Possible mechanisms of 
the Type II pyrethroid syndrome include action at the GABA receptor 
complex or a closely linked class of neuroreceptor (Gammon et al., 
1982). 

    The Type II syndrome of intracerebrally administered 
pyrethroids closely approximates that of the convulsant picrotoxin 
(PTX).  Deltamethrin inhibits the binding of [3H]-dihydropicrotoxin 
to rat brain synaptic membranes, whereas the non-toxic R epimer of 
deltamethrin is inactive.  These findings suggest a possible 
relation between the Type II pyrethroid action and the GABA 
receptor complex.  The stereospecific correlation between the 
toxicity of Type II pyrethroids and their potency to inhibit the 
[35S]-TBPS binding was established using a radioligand, [35S]- t-
butyl-bicyclophosphoro-thionate [35S]-TBPS.  Studies with 37 
pyrethroids revealed an absolute correlation, without any false 
positive or negative, between mouse intracerebral toxicity and  in 
 vitro inhibition:  all toxic cyano compounds including 
deltamethrin, 1R, cis-cypermethrin, 1R,  trans-cypermethrin, and 
[2S, alphaS]-fenvalerate were inhibitors, but their non-toxic 
stereoisomers were not; non-cyano pyrethroids were much less potent 
or were inactive (Lawrence & Casida, 1983). 

    In the [35S]-TBPS and [3H]-Ro 5-4864 (a convulsant 
benzodiazepine radioligand) binding assay, the inhibitory potencies 
of pyrethroids were closely related to their mammalian toxicities.  
The most toxic pyrethroids of Type II were the most potent 
inhibitors of [3H]-Ro 5-4864 specific binding to rat brain 
membranes.  The [3H]-dihydropicrotoxin and [35S]-TBPS binding 
studies with pyrethroids strongly indicated that Type II effects of 
pyrethroids are mediated, at least in part, through an interaction 
with a GABA-regulated chloride ionophore-associated binding site.  
Moreover, studies with [3H]-Ro 5-4864 support this hypothesis and, 
in addition, indicate that the pyrethroid-binding site may be very 
closely related to the convulsant benzodiazepine site of action 
(Lawrence et al., 1985). 

    The Type II pyrethroids (deltamethrin, 1R,  cis-cypermethrin 
and [2S,alpha S]-fenvalerate) increased the input resistance of 
crayfish claw opener muscle fibres bathed in GABA.  In contrast, 
two non-insecticidal stereoisomers and Type I pyrethroids 
(permethrin, resmethrin, allethrin) were inactive.  Therefore, 
cyanophenoxybenzyl pyrethroids appear to act on the GABA 
receptorionophore complex (Gammon & Casida, 1983). 

    The effects of pyrethroids on end-plate and muscle action 
potentials were studied in the pectoralis nerve-muscle preparation 
of the clawed frog  (Xenopus laevis).  Type II pyrethroids 
(cypermethrin and deltamethrin) induced trains of repetitive muscle 
action potentials without presynaptic repetitive activity.  
However, an intermediate group of pyrethroids (1R-permethrin, 
cyphenothrin, and fenvalerate) caused both types of effect.  Thus, 
in muscle or nerve membrane the pyrethroid induced repetitive 
activities due to a prolongation of the sodium current.  But no 
clear distinction was observed between non-cyano and alpha-cyano 
pyrethroids (Ruigt & Van den Bercken, 1986). 

Appraisal

    In summary, the results strongly suggest that the primary 
target site of pyrethroid insecticides in the vertebrate nervous 
system is the sodium channel in the nerve membrane.  Pyrethroids 
without an alpha-cyano group (allethrin, d-phenothrin, permethrin, 
and cismethrin) cause a moderate prolongation of the transient 
increase in sodium permeability of the nerve membrane during 
excitation.  This results in relatively short trains of repetitive 
nerve impulses in sense organs, sensory (afferent) nerve fibres, 
and, in effect, nerve terminals.  On the other hand, the alpha-
cyano pyrethroids cause a long-lasting prolongation of the 
transient increase in sodium permeability of the nerve membrane 
during excitation.  This results in long-lasting trains of 
repetitive impulses in sense organs and a frequency-dependent 
depression of the nerve impulse in nerve fibres.  The difference in 
effects between permethrin and cypermethrin, which have identical 
molecular structures except for the presence of an alpha-cyano 
group on the phenoxybenzyl alcohol, indicates that it is this 
alpha-cyano group that is responsible for the long-lasting 
prolongation of the sodium permeability. 

    Since the mechanisms responsible for nerve impulse generation 
and conduction are basically the same throughout the entire nervous 
system, pyrethroids may also induce repetitive activity in various 
parts of the brain.  The difference in symptoms of poisoning by 
alpha-cyano pyrethroids, compared with the classical pyrethroids, 
is not necessarily due to an exclusive central site of action.  It 
may be related to the long-lasting repetitive activity in sense 
organs and possibly in other parts of the nervous system, which, in 
a more advance state of poisoning, may be accompanied by a 
frequency-dependent depression of the nervous impulse. 

    Pyrethroids also cause pronounced repetitive activity and a 
prolongation of the transient increase in sodium permeability of 
the nerve membrane in insects and other invertebrates.  Available 
information indicates that the sodium channel in the nerve membrane 
is also the most important target site of pyrethroids in the 
invertebrate nervous system (Wouters & Van den Bercken, 1978; WHO, 
1979). 

    Because of the universal character of the processes underlying 
nerve excitability, the action of pyrethroids should not be 
considered restricted to particular animal species, or to a certain 
region of the nervous system.  Although it has been established 
that sense organs and nerve endings are the most vulnerable to the 
action of pyrethroids, the ultimate lesion that causes death will 
depend on the animal species, environmental conditions, and on the 
chemical structure and physical characteristics of the pyrethroid 
molecule (Vijverberg & Van den Bercken, 1982). 








    See Also:
       Toxicological Abbreviations
       Cypermethrin (HSG 22, 1989)
       Cypermethrin (ICSC)
       Cypermethrin (PDS)
       CYPERMETHRIN (JECFA Evaluation)
       Cypermethrin (PIM 163)
       Cypermethrin (Pesticide residues in food: 1981 evaluations)
       Cypermethrin (Pesticide residues in food: 1982 evaluations)
       Cypermethrin (Pesticide residues in food: 1983 evaluations)
       Cypermethrin (Pesticide residues in food: 1984 evaluations)