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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY


    ENVIRONMENTAL HEALTH CRITERIA 99





    CYHALOTHRIN










    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, 1990


         The International Programme on Chemical Safety (IPCS) is a
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    International Labour Organisation, and the World Health
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    toxicology. Other activities carried out by the IPCS include the
    development of know-how for coping with chemical accidents,
    coordination of laboratory testing and epidemiological studies, and
    promotion of research on the mechanisms of the biological action of
    chemicals.

    WHO Library Cataloguing in Publication Data

    Cyhalothrin.

        (Environmental health criteria ; 99)

        1.Pyrethrins - adverse effects 2.Pyrethrins - toxicity
        I.Series

        ISBN 92 4 154299 3        (NLM Classification: WA 240)
        ISSN 0250-863X

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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR CYHALOTHRIN AND LAMBDA-CYHALOTHRIN

INTRODUCTION        

1. SUMMARY, EVALUATION, CONCLUSIONS, AND RECOMMENDATIONS       

    1.1. Summary and evaluation 
         1.1.1. Identity, physical and chemical properties, 
                analytical methods  
         1.1.2. Production and use  
         1.1.3. Human exposure  
         1.1.4. Environmental exposure and fate 
         1.1.5. Uptake, metabolism, and excretion   
         1.1.6. Effects on organisms in the environment 
         1.1.7. Effects on experimental animals and  in vitro 
                test systems   
         1.1.8. Effects on humans   
    1.2. Conclusions        
    1.3. Recommendations    

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS  

    2.1. Identity           
    2.2. Physical and chemical properties   
    2.3. Analytical methods 
         2.3.1. Sampling methods    
         2.3.2. Sample storage  
    2.4. Sample preparation 
    2.5. Gas chromatographic procedures for the determination of 
         cyhalothrin residues  
         2.5.1. Extraction  
         2.5.2. Clean-up    
         2.5.3. Determination   
         2.5.4. Limit of determination  
         2.5.5. Recoveries and interference 
         2.5.6. Confirmation of residue identity    

3. SOURCES AND LEVELS OF HUMAN AND ENVIRONMENTAL EXPOSURE  

    3.1. Production levels and processes    
    3.2. Uses               
    3.3. Residues in food   
    3.4. Levels in the environment  
         3.4.1. Air         
         3.4.2. Water       
         3.4.3. Soil        

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

    4.1. Transport and distribution between media   
    4.2. Abiotic degradation    
         4.2.1. Hydrolysis and photodegradation in water    
         4.2.2. Photodegradation in soil    

    4.3. Biodegradation in soil 
         4.3.1. Degradation rate    
         4.3.2. Degradation pathways    
    4.4. Metabolism in plants   
    4.5. Bioaccumulation and biomagnification   
         4.5.1.  n-Octanol-water partition coefficient   
         4.5.2. Bioaccumulation 

5. KINETICS AND METABOLISM 

    5.1. Absorption, distribution, and excretion    
         5.1.1. Rat         
         5.1.2. Dog         
         5.1.3. Cow         
    5.2. Metabolism         
         5.2.1. Rat         
         5.2.2. Dog         
         5.2.3. Cow         
         5.2.4. Goat        
         5.2.5. Fish        

6. EFFECTS ON ORGANISMS IN THE ENVIRONMENT 

    6.1. Aquatic organisms  
         6.1.1. Microorganisms  
         6.1.2. Invertebrates   
                6.1.2.1  Acute toxicity 
                6.1.2.2  Long-term toxicity 
         6.1.3. Fish        
                6.1.3.1  Acute toxicity 
                6.1.3.2  Long-term toxicity 
         6.1.4. Model ecosystem 
    6.2. Terrestrial organisms  
         6.2.1. Birds       
                6.2.1.1  Acute toxicity 
         6.2.2. Honey-bees  
         6.2.3. Earthworms  
         6.2.4. Higher plants   

7. EFFECTS ON EXPERIMENTAL ANIMALS AND  IN VITRO TEST SYSTEMS   

    7.1. Single exposures   
         7.1.1. Oral        
         7.1.2. Percutaneous    
         7.1.3. Intraperitoneal 
    7.2. Irritation and sensitization   
         7.2.1. Irritation  
         7.2.2. Sensitization   
    7.3. Short-term exposures   
         7.3.1. Oral        
                7.3.1.1  Rat    
                7.3.1.2  Dog    
         7.3.2. Dermal      
                7.3.2.1  Rabbit 

    7.4. Long-term exposures and carcinogenicity    
         7.4.1. Rat         
         7.4.2. Mouse       
    7.5. Reproduction, embryotoxicity, and teratogenicity   
         7.5.1. Reproduction    
         7.5.2. Embryotoxicity and teratogenicity   
                7.5.2.1  Rat    
                7.5.2.2  Rabbit 
    7.6. Mutagenicity and related end-points    
         7.6.1. Microorganisms  
         7.6.2.  In vitro mammalian cells    
         7.6.3.  In vivo mammalian assays    
    7.7. Mode of action     

8. EFFECTS ON HUMANS       

    8.1. General population exposure    
    8.2. Occupational exposure  
         8.2.1. Acute toxicity: poisoning incidents 
         8.2.2. Effects of short- and long-term exposure    
                8.2.2.1  Manufacture    
                8.2.2.2  Formulation and laboratory work    
                8.2.2.3  Field use  

9. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES            

REFERENCES          

APPENDIX                

RESUME, EVALUATION, CONCLUSIONS, ET RECOMMANDATIONS         

RESUMEN, EVALUACION, CONCLUSIONES Y RECOMENDACIONES         

WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR CYHALOTHRIN

 Members

Dr V. Benes, Toxicology and Reference Laboratory, Institute of 
   Hygiene and Epidemiology, Prague, Czechoslovakia 

Dr A.J. Browning, Toxicology Evaluation Section, Department of 
   Community Services and Health, Woden, ACT, Australia 

Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood 
   Experimental Station, Abbots Ripton, Huntingdon, United Kingdom 
    (Chairman) 

Dr P.  Hurley, Office of Pesticide Programme, US Environmental 
   Protection Agency, Washington, DC, USA 

Dr K.  Imaida, Section of Tumour Pathology, Division of Pathology, 
   National Institute of Hygienic Sciences, Setagaya-Ku, Tokyo, 
   Japan 

Dr S.K.  Kashyap, National Institute of Occupational Health, 
   (I.C.M.R.) Ahmedabad, India  (Vice-Chairman) 

Dr Yu.  I. Kundiev, Research Institute of Labour, Hygiene and 
   Occupational Diseases, Ul.  Saksaganskogo, Kiev, USSR 

Dr J.P.  Leahey, ICI Agrochemicals, Jealotts Hill Research Station, 
   Bracknell, United Kingdom  (Joint Rapporteur) 

Dr M. Matsuo, Sumitomo Chemical Company, Biochemistry and 
   Toxicology Laboratory, Kasugade-naka, Konohana-Ku, Osaka, Japan 

 Representatives of Other Organizations

Mr M. L'Hotellier, International Group of National Associations of 
   Manufacturers of Agricultural Products (GIFAP) 

Dr N. Punja, International Group of National Associations of 
   Manufacturers of Agricultural Products (GIFAP) 

 Secretariat

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

Dr R.  Plestina, Division of Vector Biology and Control, World 
   Health Organization, Geneva, Switzerland 

Dr J.  Sekizawa, Division of Information on Chemical Safety, 
   National Institute of Hygienic Sciences, Setagaya-Ku, Tokyo, 
   Japan  (Joint 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. 7988400 or 
7985850). 


                      * * *


    The proprietary information contained in this document cannot 
replace documentation 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 Second FAO Government 
Consultation (1982). 

ENVIRONMENTAL HEALTH CRITERIA FOR CYHALOTHRIN

    A WHO Task Group meeting on Environmental Health Criteria for 
Cyhalothrin was held in Geneva from 24 to 28 October 1988.  Dr M.  
Mercier, Manager, IPCS, opened the meeting and welcomed the 
participants on behalf of the three IPCS cooperating organizations 
(UNEP/ILO/WHO).  The group reviewed and revised the draft monograph 
and made an evaluation of the risks for human health and the 
environment from exposure to cyhalothrin. 

    The first draft was prepared by the IPCS Secretariat, based on 
material made available by ICI Agrochemicals, United Kingdom. 

    The second draft was also prepared by the IPCS Secretariat, 
incorporating comments received following circulation of the first 
draft to the IPCS contact points for Environmental Health Criteria 
monographs.  Dr K.W.  Jager and Dr P.G.  Jenkins, both members of 
the IPCS Central Unit, were responsible for the technical 
development and editing, respectively, of this monograph. 

    The assistance of ICI Agrochemicals in making available to the 
IPCS and the Task Group its toxicological proprietary information 
on cyhalothrin is gratefully acknowledged.  This allowed the Task 
Group to make its evaluation on the basis of more complete data. 

ABBREVIATIONS

ADI    acceptable daily intake

ai     active ingredient

APDM   aminopyrine- N-demethylase

EC     emulsifiable concentrate

ECD    electron capture detection

GC     gas chromatography

HPLC   high performance liquid chromatography

LOEL   lowest-observed-effect level

MS     mass spectrometry

MSD    mass selective detection

NOEL   no-observed-effect-level

SFS    subjective facial sensation

TLC    thin-layer chromatography

WP     wettable powder

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, cyfluthrin, 
    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, cyhalothrin, 
    lambda-cyhalothrin, 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 Elliott (1977), Miyamoto 
    (1981), Miyamoto & Kearney (1983), and Leahey (1985). 

1.  SUMMARY, EVALUATION, CONCLUSIONS, AND RECOMMENDATIONS

1.1.  Summary and evaluation

1.1.1.  Identity, physical and chemical properties, analytical methods

    Cyhalothrin is formed by esterifying 3-(2-chloro-3,3,3-
trifluoroprop-1-enyl)-2,2- dimethylcyclopropanecarboxylic acid 
with alpha-cyano-3-phenoxybenzyl alcohol, and it consists of a 
mixture of four stereoisomers.  Lambda-cyhalothrin consists of one 
enantiomeric pair of isomers and is the more biologically active 
form. 

    Technical grade cyhalothrin is a yellow-brown viscous liquid 
(melting point: approximately 10 °C) and contains more than 90% 
active material.  It is composed of four cis isomers in the ratio 
of 1:1:1:1.  Although it is insoluble in water, it is soluble in a 
range of organic solvents such as aliphatic and aromatic 
hydrocarbons.  It is stable to light and heat and has a low vapour 
pressure. 

    Technical grade lambda-cyhalothrin is a beige solid (melting 
point: 49.2 °C) and contains more than 90% active material.  The 
enantiomer ratio of the  (Z), (1R, 3R), S-ester to the  (Z), (1S, 
 3S), R-ester is 1:1.  It is sparingly soluble in water but soluble 
in a range of organic solvents and has a low vapour pressure.  Both 
cyhalothrin and lambda-cyhalothrin are rapidly hydrolysed under 
alkaline conditions but not in neutral or acidic media. 

    Well established methods for residue and environmental analysis 
of cyhalothrin and lambda-cyhalothrin are available (the minimum 
detectable concentration is 0.005 mg/kg). 

1.1.2.  Production and use

    Cyhalothrin was developed in 1977.  It is principally used to 
combat a wide range of pests in public health and animal health, 
but is also employed in agriculture against pests of pome fruit.  
Lambda-cyhalothrin is mainly used as an agricultural pesticide on a 
wide range of crops and is being developed for public health. 

    No data are available on production levels.

1.1.3.  Human exposure

    Residues in food arising from the use of cyhalothrin and 
lambda-cyhalothrin on crops and in animal health are low, usually 
less than 0.2 mg/kg. No results are available on the total dietary 
intake in humans, but it can be assumed that the dietary exposure 
of the general population will not exceed the ADI (0.02 mg/kg body 
weight). 

1.1.4.  Environmental exposure and fate

    On soil surfaces and in aqueous solutions at pH 5, lambda-
cyhalothrin degrades in sunlight with a half-life of approximately 

30 days.  The main degradation products are 3-(2-chloro-3,3,3-
trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropanecarboxylic acid, the 
amide derivative of cyhalothrin, and 3-phenoxybenzoic acid. 

    Degradation in soil occurs primarily by hydroxylation followed 
by cleavage of the ester linkage to give two main degradation 
products, which are further degraded to carbon dioxide.  The 
initial half-lives are in the range of 22 to 82 days. 

    Cyhalothrin and lambda-cyhalothrin are adsorbed on soil 
particles and are non-mobile in the environment. 

    On plants lambda-cyhalothrin degrades at a moderate rate (half-
life of up to 40 days), so that the major constituent of the 
residue on plants is usually the parent compound.  Lower levels of 
metabolites, resulting from a range of hydrolytic and oxidative 
reactions, are also found. 

    No data are available on actual levels in the environment, but 
with the low current use pattern and low application rates, these 
are expected to be low. 

1.1.5.  Uptake, metabolism, and excretion

    Metabolic studies have been carried out on the rat, dog, cow, 
and goat. In rats and dogs, cyhalothrin has been shown to be well 
absorbed after oral administration, extensively metabolized, and 
eliminated as polar conjugates in urine. Cyhalothrin levels in rat 
tissues declined upon cessation of exposure to the compound.  
Residues in rat carcasses were low (< 5% of the dose after 7 days) 
and were found to be almost entirely due to cyhalothrin contained 
in fats.  Residues in fats were eliminated with a half-life of 23 
days. 

    After oral administration to lactating cows, cyhalothrin was 
rapidly eliminated, an equilibrium between ingestion and 
elimination being reached after 3 days. Of the overall dose, 27% 
was excreted in the urine, 50% in the faeces, and 0.8% in the milk.  
Urinary material consisted entirely of ester cleavage metabolites 
and their conjugates, whereas 60-70% of the faecal [14C]-labelled 
material was identified as unchanged cyhalothrin.  Tissue 
residues, 16 h after the last dose, were low, the highest 
concentrations being detected in fat.  The [14C]-labelled residues 
in milk and fatty tissues were almost entirely unchanged 
cyhalothrin, no other component being detected. 

    In all mammalian species investigated, cyhalothrin has been 
found to be extensively metabolized as a result of ester cleavage 
to the cyclopropanecarboxylic acid and 3-phenoxybenzoic acid, and 
eliminated as conjugates. 

    In fish the main residue in tissues consists of unchanged 
cyhalothrin, and there are lower levels of the ester cleavage 
products. 

1.1.6.  Effects on organisms in the environment

    Under laboratory conditions of constant toxicant 
concentrations, cyhalothrin and lambda-cyhalothrin are highly toxic 
to fish and to aquatic invertebrates.  The 96-h LC50 values for  
fish range between 0.2 and 1.3 µg/litre, whereas for aquatic 
invertebrates the 48-h LC50 values range between 0.008 and 0.4 
µg/litre. 

    Accumulation studies conducted under laboratory conditions 
with constant concentration show that rapid uptake takes place in 
fish (accumulation factor approximately 1000-2000). However, in the 
presence of soil and suspended sediment, the bioaccumulation 
factors are greatly reduced (to 19 in the case of fish and 194 in 
the case of daphnids).  When exposed fish and daphnids were placed 
in clean water the residues declined rapidly, with half-lives of 7 
days and 1 day, respectively.  The concentrations of cyhalothrin 
and lambda-cyhalothrin that are likely to arise in water from 
normal agricultural application will be low.  Since the compound is 
rapidly adsorbed and degraded under natural conditions, there will 
not be any practical problems concerning the accumulation of 
residues or the toxicity of cyhalothrin or lambda-cyhalothrin in 
aquatic species. 

    Cyhalothrin and lambda-cyhalothrin are virtually non-toxic to 
birds; the single-dose LD50 was greater than 3950 mg/kg in all 
species tested and the lowest 5-day dietary LC50 was 3948 mg/kg 
(lambda-cyhalothrin fed to 8-day-old mallard ducks). 

    Under laboratory conditions, cyhalothrin and lambda-cyhalothrin 
are toxic to honey-bees; the oral LD50 for lambda-cyhalothrin is 
0.97 µg/bee.  However, in the field the hazard is lower since 
current formulations have a repellant action that causes a 
suspension of foraging activity in treated crops.  When foraging 
restarts there is no significant increase in bee mortality. 

1.1.7.  Effects on experimental animals and  in vitro 
test systems

    The acute oral toxicity of cyhalothrin is moderate in rats and 
mice and low in guinea-pigs and rabbits (LD50 values are as 
follows: rat, 144-243 mg/kg; mouse, 37-62 mg/kg; guinea-pig, 
> 5000 mg/kg; rabbit, > 1000 mg/kg). The acute oral toxicity of 
lambda-cyhalothrin is higher than that of cyhalothrin (LD50 values 
are: 56-79 mg/kg for the rat and 20 mg/kg for the mouse).  The 
dermal toxicities (LD50) are as follows: rat, 200-2000 mg/kg 
(cyhalothrin), 632-696 mg/kg (lambda-cyhalothrin); rabbit, > 2000 
mg/kg (cyhalothrin). Cyhalothrin and lambda-cyhalothrin are type 
II pyrethroids; clinical signs include ataxia, unsteady gait, and 
hyperexcitability. 

    In the rabbit, cyhalothrin is a moderate eye irritant and 
lambda-cyhalothrin is a mild eye irritant; both are mild skin 
irritants.  Cyhalothrin is not a skin irritant in the rat.  
However, it is a moderate skin sensitizer in the guinea-pig.  
Lambda-cyhalothrin is not a skin sensitizer. 

    In a 90-day feeding study in which rats were fed cyhalothrin at 
dose levels up to 250 mg/kg diet, reduced body weight gains were 
observed in males at 250 mg/kg diet.  Marginal effects on mean 
erythrocyte volumes were noted in some treated groups, as well as 
some liver changes, which were considered to be an adaptive 
response. In a 90-day feeding study in which rats were fed lambda-
cyhalothrin at dose levels up to 250 mg/kg diet, reduced body 
weight gain was observed in both sexes at 250 mg/kg diet. Some 
effects on clinical chemistry were observed, as well as liver 
effects similar to those noted with cyhalothrin.  The no-observed-
effect level was 50 mg/kg diet. 

    In a 26-week oral study in which cyhalothrin doses of up to 10 
mg/kg body weight per day were administered to dogs, signs of 
pyrethroid toxicity were observed at 10 mg per kg body weight per 
day.  The no-observed-effect level was 2.5 mg/kg body weight per 
day.  A similar study was conducted in which up to 3.5 mg lambda-
cyhalothrin/kg body weight per day was administered to dogs for 52 
weeks. Clinical signs of pyrethroid toxicity (neurological signs) 
were observed in all animals dosed with 3.5 mg/kg body weight per 
day. The no-observed-effect level was 0.5 mg/kg body weight per 
day. 

    In a 21-day dermal study on rabbits using cyhalothrin in 
polyethylene glycol at dose levels of up to 1000 mg/kg per day, 
clinical signs of toxicity were observed in some animals at the 
highest dose level.  Slight to severe skin irritation was observed 
in all groups, including controls. 

    Cyhalothrin was tested in two 104-week feeding studies, one on 
rats and one on mice.  In the rat study, no oncogenic effects were 
observed at dose levels up to 250 mg/kg diet (highest level 
tested).  The no-observed-effect level for systemic toxicity was 50 
mg/kg diet (1.8 mg/kg body weight per day). Decreased body weight 
gain was observed in both sexes at 250 mg/kg diet.  In the mouse 
study, no oncogenic effects were observed at dose levels up to 500 
mg/kg diet (highest level tested).  Clinical signs of pyrethroid 
toxicity were observed at 100 and 500 mg/kg diet, and reduced body 
weight gain was observed at 500 mg/kg diet.  The no-observed-effect 
level for systemic toxicity was 20 mg/kg diet (1.9 mg/kg body 
weight per day).  No histological evidence of damage to the nervous 
system was observed in either study. 

    Cyhalothrin and lambda-cyhalothrin gave negative results in a 
range of  in vivo and  in vitro assays designed to detect gene 
mutations, chromosomal damage, and other genotoxic effects. When 
orally administered to the rat and rabbit during the period of 
major organogenesis, cyhalothrin was neither embryotoxic nor 
teratogenic at dose levels that elicited maternal toxicity (15 
mg/kg per day for rats and 30 mg/kg per day for rabbits, both 
highest dose levels tested). 

    A three-generation reproduction study was conducted on rats 
with cyhalothrin at dose levels of up to 100 mg/kg diet.  Minor 
decreases in litter size and small reductions in weight gain were 

seen at 100 mg/kg diet.  The no-observed-effect level for 
reproductive effects was 30 mg per kg diet. 

1.1.8.  Effects on humans

    No cases of accidental poisoning have been described.

    In manufacturing, formulation, laboratory work, and field 
usage, symptoms of subjective facial sensation have been reported.  
This effect generally lasts only a few hours, but occasionally 
persists for up to 72 h after exposure; medical examination has not 
revealed any neurological abnormalities. 

    Subjective facial skin sensations, which may be experienced by 
people who handle cyhalothrin and lambda-cyhalothrin, are believed 
to be brought about by repetitive firing of sensory nerve 
terminals in the skin.  They may be considered as an early warning 
signal indicating that overexposure of the skin has occurred. 

    There are no indications that cyhalothrin and lambda-
cyhalothrin, used under the present recommended conditions and 
application rates, will have any adverse effect on humans. 

1.2.  Conclusions

(a)  General population: The exposure of the general population to 
cyhalothrin and lambda-cyhalothrin is expected to be very low and 
is not likely to present a hazard under recommended conditions of 
use. 

(b)  Occupational exposure: With good work practices, hygiene 
measures, and safety precautions, cyhalothrin and lambda-
cyhalothrin are unlikely to present a hazard to those 
occupationally exposed. 

(c)  Environment: It is unlikely that cyhalothrin and lambda-
cyhalothrin or their degradation products will attain levels of 
adverse environmental significance with recommended application 
rates. Under laboratory conditions cyhalothrin and lambda-
cyhalothrin are highly toxic to fish, aquatic arthropods, and 
honey-bees.  However, under field conditions, lasting adverse 
effects are not likely to occur under recommended conditions of 
use. 

1.3.  Recommendations

    Although dietary levels from recommended usage are considered 
to be very low, confirmation of this through inclusion of 
cyhalothrin and lambda-cyhalothrin in monitoring studies should be 
considered. 

    Although cyhalothrin and lambda-cyhalothrin have been used for 
several years and any effects from occupational exposure have been 
only transient, observations of human exposure should be 
maintained. 

2.  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

2.1.  Identity

Molecular formula: C23H19ClF3NO3

Chemical Structure

Chemical name:  alpha-cyano-3-phenoxybenzyl 3-(2-chloro-
                3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-
                cyclopropanecarboxylate

CAS Chemical    ( RS)-alpha-cyano-3-(phenoxyphenyl)methyl
name:           ( 1RS)-cis-3-( Z-2-chloro-3,3,3-tri-
                fluoroprop-1-enyl)-2,2-dimethylcyclopro-
                panecarboxylate

CAS registry:   cyhalothrin: 68085-85-8
number          lambda-cyhalothrin: 91465-08-6

Common          cyhalothrin: R114563, PP563
synonyms:       lambda-cyhalothrin: R119321, PP321

Trade names:    cyhalothrin: Grenade
                lambda-cyhalothrin: Karate, Matador, Icon

    Cyhalothrin was developed by ICI in 1977.  It is prepared by 
esterification of 3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-
dimethylcyclopropanecarboxylic acid chloride with alpha-cyano-3-
phenoxybenzyl alcohol. 

    Cyhalothrin has two asymmetric centres in the acid moiety and 
one in the alcohol moiety, as well as Z and E forms.  Thus, there 
are 16 possible isomeric forms (eight enantiomeric pairs).  
However, in practice cyhalothrin is produced only in the Z and cis 
forms, reducing the number of isomers to four.  These comprise two 
cis enantiomeric pairs: 

Enantiomer pair A:  ( Z), (1R, 3R ), R-alpha-cyano ( Z),
                    ( 1S, 3S) S-alpha-cyano;

Enantiomer pair B:  ( Z), (1R, 3R), S-alpha-cyano ( Z),
                    ( 1S, 3S) R-alpha-cyano.

FIGURE 1

    Lambda-cyhalothrin is manufactured by crystallization of the 
more active pair of enantiomers from cyhalothrin. The less active 
pair of enantiomers is recycled. 

    Pure lambda-cyhalothrin is a racemic mixture of the enantiomer 
pair B isomers.  The enantiomer pair A is present in low 
concentration in the commercial product. 

    Technical grade cyhalothrin contains more than 90% of the 
pesticide and is formulated in 5%, 10%, and 20% emulsifiable 
concentrates.  Technical grade lambda-cyhalothrin also contains 
more than 90% active ingredient. It is formulated as 2.5%, 5.0%, 
8.3%, and 12% emulsifiable concen-trates and as a 0.8% ultra-low 
volume concentrate. 

2.2.  Physical and chemical properties

    Some physical and chemical properties of cyhalothrin and 
lambda-cyhalothrin are listed in Table 1. 

Table 1.  Some physical and chemical properties of cyhalothrin and 
lambda-cyhalothrin
---------------------------------------------------------------------------
                                   Cyhalothrin          Lambda-cyhalothrin
---------------------------------------------------------------------------
Physical state                     viscous liquid       solid
Colour                             yellow-brown         beige
Odour                              mild                 mild
Relative molecular mass            449.9                449.9
Melting point                      glass-like           49.2 °C
                                   below 10 °C
Decomposes                         > 275 °C             > 275 °C
Water solubility                   4 x 10-3 mg/litre    5 x 10-3 mg/litre
Solubility in organic solvents     soluble              soluble
 n-octanol water-partition          6.9                  7.0
 coefficient (log Pow) at 20 °C
Relative density                   1.25                 1.33
Vapour pressure at 20 °C           1 x 10-9 kPa         2 x 10-10 kPa
Vapour pressure at 80 °C           4 x 10-6 kPa         3 x 10-6 kPa
---------------------------------------------------------------------------

    No boiling point data are available as both forms decompose on 
heating above 275 °C.  Cyhalothrin is highly stable to light and at 
temperatures below 220 °C. 

    Lambda-cyhalothrin is stable in water at pH 5. At pH 7 and pH 
9, there is racemization at the alpha-cyano carbon to yield a 1:1 
mixture of enantiomer pairs A and B.  At pH 9, the ester bond is 
fairly readily hydrolysed (half-life, 7 days) (Collis & Leahey, 
1984). 

    Dilute aqueous solutions are subject to photolysis at a 
moderate rate (Hall & Leahey, 1983; Curl et al., 1984a). 

2.3.  Analytical methods

    The most widely adopted procedures for analysing cyhalothrin 
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 by solvent-solvent 
partition and adsorption column chromatography, and determination 
of the residue using gas chromatography (GC) with electron capture 
detection (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. 

2.3.1.  Sampling methods

    Procedures for obtaining representative samples of crops, 
processed commodities, soil, and some animal products have been 
described in detail (GIFAP, 1981) and will not be discussed 
further. 

    Particular care is necessary when sampling water because 
cyhalothrin is extremely hydrophobic and rapidly adsorbs onto 
particulates or container walls from aqueous solution.  For this 
reason, the whole analytical sample should be taken for analysis 
and not subdivided in the field (Sapiets et al., 1984).  Collection 
of the sample in a clean glass container, with addition of the 
extraction solvent before sealing and shaking the bottle, gives 
good recoveries.  Crossland et al. (1982) described procedures for 
sampling surface water (using stainless steel fine mesh discs) and 
subsurface water from ponds for separate analysis of cypermethrin. 
Precautions were taken to avoid contamination during sampling 
(Crossland et al., 1982). These methods, developed for 
cypermethrin, are equally applicable to cyhalothrin and other 
pyrethroids. During the course of the pond studies, cypermethrin 
spray drift deposits were collected by means of horizontally placed 
aluminium foil plates and washed from the foils using acetone.  
Crossland also described the use of a core sampler to remove pond 
sediment for cypermethrin analysis (Crossland, 1982).  This method 
is equally applicable to cyhalothrin. 

    Sampling of air in agriculture work space for pyrethroid 
aerosol droplets using absorption onto exposed filter papers and 
porous glass slides has been described by Girenko & Klisenko 
(1984).  They quoted limits in the range of 0.05 to 0.5 mg/m3 for 
the concentrations of pyrethroid that could be detected without 
interference from organophosphorus or organochlorine insecticides.  
An alternative and more conventional approach would be to use a 
pumped device consisting of a filter (to trap droplets or 
particulates) in series with a packed tube (to trap vapour). 

    The use of a vacuum probe was described by Bengstone et al. 
(1983) to subsample pyrethroid-treated grain from several points 
within a silo for combination to give a composite sample.  However, 
care is needed to obtain a representative sample using this 
procedure (GIFAP, 1981). 

2.3.2.  Sample storage

    Storage stability experiments using untreated samples fortified 
with cyhalothrin (at 1.0 mg/kg) have shown that apples, cabbage, 
soil, and products of animal origin can be stored deep frozen at 
temperatures of -20 °C for periods of up to one year without 
residue loss (Sapiets, 1984a) 

    Particular problems in the handling of water samples have 
already been indicated and samples should be extracted and 
analysed as soon after sampling as possible. 

2.4.  Sample preparation

    Forbes & Dutton (1985) reported details of the procedures used 
to process crop and soil samples, which have been treated with 
pyrethroid insecticides, for sub-sampling before extraction.  Crops 
of high water content, e.g., fruit and vegetables, were chopped, 
dried, or puréed. Grain and oil seed crops (cotton seed and 
linseed) were frozen and ground to a powder, while crops of low 

water content, e.g., straw and tobacco, were finely divided in a 
rotary knife mill.  Soil samples were mixed thoroughly and stones 
and plant debris removed.  In all cases, care was taken to avoid 
localized overheating of the sample during processing.  Sapiets et 
al. (1984) used a similar processing procedure for high water 
content crops and also applied this to meat and eggs.  However, 
they draw attention to the importance of processing materials with 
high water content while still frozen to prevent separation of 
juice, which leads to sample inhomogeneity.  Milk was thoroughly 
mixed before subsampling. In the limited number of other studies 
where details for preparation of pyrethroid-treated samples have 
been given, none of the procedures differ markedly from those 
described above. All of the procedures are equally applicable to 
cyhalothrin and lambda-cyhalothrin. 

2.5.  Gas chromatographic procedures for the determination
of cyhalothrin residues

    Details of GC procedures are described in the following 
subsections (Sapiets, 1984b,c, 1985a,b, 1986a,b). 

2.5.1.  Extraction

    Representative subsamples of prepared crops or meat are blended 
for 2-5 min with a mixture of acetone and hexane (1 + 1 by volume).  
Dry materials are dampened with water.  Soil is similarly extracted 
by refluxing with acetonitrile for 1 h.  Extracts are then gravity 
filtered and partitioned with 5% sodium chloride solution to remove 
the acetone.  The hexane extract is dried over anhydrous sodium 
sulfate. 

    Eggs are extracted by homogenizing for 5 min with acetonitrile.  
An aliquot is evaporated to dryness and redissolved in hexane. 

    Milk is extracted by homogenizing for 2 min in acetone and 
hexane (1:1 by volume).  The solvent is dried over anhydrous sodium 
sulfate. 

2.5.2.  Clean-up

    Column absorption chromatography on Florisil is used for 
cleaning up extracts from crops and soils, and cyhalothrin 
residues are eluted with a mixture of diethyl ether in hexane. 

    Extracts from crops with high lipid content, animal products, 
and difficult matrices, e.g., tobacco and hops, require preliminary 
clean-up by liquid-liquid partition procedures. 

2.5.3.  Determination

    Residues of cyhalothrin in cleaned-up extracts are determined 
by GC/ECD using packed or capillary columns. 

    A variety of liquid phases have been found suitable for use 
with packed columns; these include OV-25, OV-101, OV-210, and OV-
202.  These are generally used at low loadings (3-5%) in the 
temperature range 230-250 °C, and retention times for cyhalothrin 
are normally less than 10 min.  Glass columns should be used.  On 
these packed columns cyhalothrin is eluted as a single peak. 

    Capillary columns will separate the two pairs of 
diastereoisomers (enantiomer pairs) of cyhalothrin to give two 
peaks.  Lambda-cyhalothrin under the same conditions gives a single 
peak.  Fused silica columns, 25 m long, coated with OV-101 have 
been found suitable when separate determination of diastereoisomers 
in the cyhalothrin residue is required. Retention times normally 
fall within the range of 10 to 30 min. 

2.5.4.  Limit of determination

    The limit of determination of the methods for cyhalothrin 
residues in crops and animal products is set at 0.01 mg/kg on the 
basis of recovery experiments at low fortification levels (0.005-
0.02 mg/kg) and background noise in the chromatograms.  The limit 
of determination for soils is set at 0.005 to 0.01 mg/kg and for 
water is 10 ng/litre (ppt). 

2.5.5.  Recoveries and interference

    The internal standardization procedure used in these methods 
determines the concentration of cyhalothrin or lambda-cyhalothrin 
relative to that of a known concentration of internal standard 
added to the sample prior to extraction.  Correction for percentage 
recovery is thereby inherent for each individual sample.  The 
repeatability of the procedure for most substrates is 2 to 3%.  The 
methods have been found to be applicable to the determination of 
cyhalothrin in a wide variety of substrates without interference 
from endogenous natural products in the GC determination. 

2.5.6.  Confirmation of residue identity

    Qualitative and quantitative confirmation of residue identity 
may be achieved by combined GC-MS operated in the selected ion 
monitoring mode. 

3.  SOURCES AND LEVELS OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1.  Production levels and processes

    No data on industrial production are available.

3.2.  Uses

    Cyhalothrin is a pyrethroid insecticide with a high level of 
activity (application rate up to 20 g/ha) against a wide range of 
 Lepidoptera, Hemiptera, Diptera, and  Coleoptera species.  It also 
has some miticidal activity. Lambda-cyhalothrin has the same 
spectrum of insecticidal activity as cyhalothrin but it is more 
active.  The compound is a stomach, contact, and residual 
insecticide.  It shows adulticidal, ovicidal and, particularly, 
larvicidal activity. 

    Like other photostable synthetic pyrethroids, cyhalothrin and 
lambda-cyhalothrin are relatively stable to degradation in 
sunlight.  This permits their use as practical tools in 
agriculture.  The compound is not plant-systemic and has very 
little fumigant or translaminar activity. 

    Owing, in part, to its short persistence in soil and lack of 
systemic effect, the compound is of only limited value when used as 
a soil insecticide.  It can, however, give useful control of 
cutworms when applied as a crop/ground spray. It has no 
molluscicidal or nematocidal activity. 

    Preventive treatments are generally more effective than 
curative treatments against major pests such as boring caterpillars 
or leaf miners. A programme of sprays is usually required, 
particularly during the more active growth stages of the plant and 
when the potential for re-infestation remains high. 

    Cyhalothrin has also found uses in public and animal health 
applications where it effectively controls a broad spectrum of 
insects, including cockroaches, flies, mosquitos, and ticks.  It 
has high activity as a residual spray on inert surfaces. 

3.3.  Residues in food

    Supervised trials have been carried out on a wide variety of 
crops, and comprehensive summaries of residue analysis in these 
trials can be found in the evaluation reports of the Joint FAO/WHO 
Meeting on Pesticide Residues (JMPR) (FAO/WHO 1985, 1986a). 

    Data reviewed by the JMPR showed that in studies on apples and 
on pears, when different rates of application were used in the same 
trial, initial residues reflected the different rates applied.  
When the spray programme was doubled from three to six applications 
per season, there was no increase in the lambda-cyhalothrin residue 
levels over those obtained with the three applications programme at 
the same rates.  Lambda-cyhalothrin residue levels on apples often 
declined relatively slowly, although this was not always the case.  

There were no obvious differences in residue levels arising from 
the use of the different strengths of emulsion concentrate 
formulations or from the use of either low volume or high volume 
rates of application (FAO/WHO, 1986a,b). 

3.4.  Levels in the environment

3.4.1.  Air

    No specific data on air concentrations are available. Since 
cyhalothrin and lambda-cyhalothrin are of low vapour pressure, 
atmospheric levels of their vapour will be negligible. 

3.4.2.  Water

    No specific data on water levels are available.  Since 
cyhalothrin and lambda-cyhalothrin are insoluble in water and not 
mobile in soil, they are very unlikely to reach ground water. 

3.4.3.  Soil

    No information on concentrations in soil is available.

4.  ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

4.1.  Transportation and distribution between media

    The very low vapour pressure of cyhalothrin means that this 
compound will not enter the atmosphere. 

    Studies have shown that cyhalothrin and its soil degradation 
products do not leach through soils. 14C-cyclopropane-labelled 
cyhalothrin was aerobically incubated for 30 days with a sandy loam 
(4.2% organic matter) and a loamy sand (2.0% organic matter).  The 
incubated soils (rates equivalent to 0.04 and 0.05 kg cyhalothrin 
equivalents per ha for the sandy loam and loamy sand, respectively) 
were then applied to soil columns (30 cm long) and leached during a 
period of 9 weeks with 66 cm "rain".  The radioactive residues more 
than 5 cm beneath the surface were below the limit of determination 
(i.e. < 0.47 ng cyhalothrin equivalents per g) in all the soil 
columns.  Radioactive residues in the leachate samples were also 
generally below the limit of determination (i.e. < 0.023 ng 
cyhalothrin equivalent per ml) and represented less than 0.3% of 
the applied radiocarbon.  Thus, cyhalothrin, lambda-cyhalothrin, 
and their degradation products have very low mobility in soil.  On 
the basis of these data it is concluded that the agricultural use 
of cyhalothrin or lambda-cyhalothrin will not result in the 
leaching of either the parent compounds or their degradation 
products into ground water (Stevens & Bewick, 1985). Furthermore, 
if soils containing cyhalothrin are flooded, there is no release of 
cyhalothrin into the water (Hamer & Hill, 1985).  Thus, residues of 
cyhalothrin in soil resulting from agricultural use will not be 
transported into other compartments of the environment. 

4.2.  Abiotic degradation

4.2.1.  Hydrolysis and photodegradation in water

    In studies by Collis & Leahey (1984), aqueous solutions of 14C-
cyclopropyl-labelled lambda-cyhalothrin, buffered at pH 5, 7, and 
9, were maintained in the dark at 25° C for periods of up to 30 
days.  Acetonitrile (1%) was used as a co-solvent to facilitate 
dissolution in the water.  Hydrolysis of lambda-cyhalothrin 
occurred rapidly in the pH 9 aqueous buffer solution (half-life, 
approxi-mately 7 days) via ester cleavage of the molecule to yield 
(1 RS)-cis-3-( Z-2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-
dimethylcyclopropanecarboxylic acid.  Rapid isomerization of the 
optical centre at the alpha-CN position also occurred at pH 9.  At 
pH 7 no hydrolysis was detected, but slow isomerization did occur.  
At pH 5 no hydrolysis or isomerization was observed (Collis & 
Leahey, 1984). 

    When quartz flasks containing 14C-cyclopropyl-labelled lambda-
cyhalothrin in pH 5 buffer were exposed to sunlight for 30 days, 
the compound underwent photodegradation with a half-life of 
approximately 30 days. (1 RS)-cis- and (1 RS)-trans-3-( ZE-2-chloro-
3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylic 

acids and ( RS)-alpha-amido-3-phenoxybenzyl (1 RS)-cis,trans-3-( ZE-2-
chloro-3,3,3-tri-fluoroprop-1-enyl)-2,2-dimethylcyclopropanecarb-
oxylate were the major degradation products formed.  Optical and 
geometrical isomerization of lambda-cyhalothrin occurred in the 
irradiated flasks.  No photodegradation or photoisomerization was 
observed in a dark control flask (Curl et al., 1984a). 

    In studies by Hall & Leahey (1983), 14C-cyhalothrin was 
incubated with two river water/sediment mixtures contained in 
quartz flasks.  The flasks were either exposed to sunlight or were 
maintained under dark conditions by covering them with aluminium 
foil.  In the dark, degradation of cyhalothrin was slow (over 80% 
remained unchanged after 32 days).  However, when exposed to 
sunlight the cyhalothrin degraded with a half-life of approximately 
20 days in both river water/sediment mixtures. The rate at which 
the parent compound was lost from the aqueous phase was, however, 
much faster than its rate of degradation in the whole 
water/sediment system.  This was due to the ready absorption of 
cyhalothrin onto the sediment.  The major degradation process was 
simple ester cleavage of the molecule, producing (1 RS)-cis- and 
(1 RS)-trans-3-( ZE-2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-
dimethylcyclopropanecarboxylic acids.  After 32 days of 
irradiation, these compounds together represented 36-47% of the 
radioactivity applied to the water/sediment systems. Some 
photoisomerization also occurred. 

4.2.2.  Photodegradation in soil

    When thin-layer soil plates were treated with 14C-cyclopropyl-
labelled lambda-cyhalothrin and irradiated in a xenon arc apparatus 
or in sunlight, the half-life of lambda-cyhalothrin was less than 2 
days in the xenon arc apparatus and less than 30 days in sunlight.  
(1 RS)-cis-3-( ZE-2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-
dimethylcyclopropane-carboxylic acid and ( RS)-alpha-amido-3-
phenoxybenzyl (1 RS)-cis,trans-3-( ZE-2-chloro-3,3,3-trifluoroprop-1-
enyl)-2,2-dimethylcyclopropanecarboxylate were the major 
degradation products (Curl et al., 1984b). 

4.3.  Biodegradation in soil

    Cyhalothrin degradation in the outdoor environment may occur by 
either biological or photochemical processes. In most cases, 
biological processes are by far the most important, although 
photochemical reactions can sometimes contribute to the degradation 
of residues on exposed surfaces. 

4.3.1.  Degradation rate

    At residue levels that are likely to occur under normal field 
conditions, cyhalothrin is degraded rapidly in soil. When a sandy 
loam soil was treated with 14C-cyclopropyl-labelled cyhalothrin, 
only 28% of the recovered radioactivity was present as cyhalothrin 
after five weeks of incubation under aerobic conditions; 30% was 
evolved as 14C-labelled carbon dioxide and 3.5% of the recovered 

radioactivity was due to 1 RS-cis-3-( Z-2-chloro-3,3,3-trifluoroprop-
1-enyl)-2,2-dimethylcyclopropanecarboxylic acid. Approximately 19% 
of the radioactivity was not extracted using acetonitrile at room 
temperature followed by soxhlet extraction with aqueous 
acetonitrile (Bewick & Zinner, 1981). 

    In a more recent and detailed study, 14C-cyclopropyl-labelled 
cyhalothrin was applied to two soils (a sandy loam and a loamy 
sand) at 100 g/ha and incubated under both aerobic and flooded 
conditions at 20 °C.  The sandy loam soil was also treated with 
cyhalothrin at 500 g/ha and, in a later experiment, treated 
separately with the two enantiomer pairs of cyhalothrin (one of 
which constitutes lambda-cyhalothrin). This soil was also 
incubated at 10 °C.  All the isomers of cyhalothrin, including 
those that constitute lambda-cyhalothrin, were readily degraded in 
soil under a range of conditions.  Half-lives for cyhalothrin at 
20 °C in the sandy loam and loamy sand soils were 22 and 82 days, 
respectively.  Degradation was somewhat slower in the sandy loam at 
higher rates (half-life: 42 days), lower temperature (half-life: 56 
days) and under flooded conditions (half-life: 74 days).  Lambda-
cyhalothrin was degraded at about 70% the rate of the other 
enantiomer pair of cyhalothrin in the aerobic soils but at 
approximately the same rate under flooded conditions.  In the 
aerobic soils, the principle degradative reactions were 
hydroxylation, yielding up to 11% of the applied radiocarbon as 
( RS)-alpha-cyano-3-(4-hydroxyphenoxy) benzyl  cis-3-( Z-2-chloro-
3,3,3-trifluoroprop-1-enyl)-2,2-di-methylcyclopropanecarboxylate 
(compound XV), and hydrolysis, yielding up to 7% as ( RS)-cis-3-( Z-
2-chloro-3,3,3-tri-fluoroprop-1-enyl)-2,2-dimethylcyclopropane-
carboxylic acid (compound Ia).  In the flooded soil, hydrolysis was 
the main degradative reaction (up to 18% of compound Ia in the soil 
phase), and hydroxylation was less important (only up to 1.4% of 
compound XV).  Compound Ia was the only compound detected (up to 
17%) in the aqueous phase of the flooded soils.  No isomerization 
of the parent esters or their hydrolysis product was detected. The 
initial degradation products of cyhalothrin and lambda-cyhalothrin 
in the aerobic soils were rapidly further degraded with extensive 
mineralization (up to 70% in 26 weeks) to 14CO2 (Bharti et al., 
1985).  Thus the acid moiety of cyhalothrin is readily mineralized 
in soil.  The alcohol moiety of this compound is identical to that 
of cypermethrin.  Studies with cypermethrin show that, after ester 
cleavage, the alcohol moiety released is readily mineralized to 
14CO2 (FAO/WHO, 1986a). 

    In a further study, when 14C-cyclopropyl-labelled cyhalothrin 
was applied (at 100 g/ha) to a Japanese upland soil (a volcanic 
ash) and incubated under aerobic conditions at 20 °C, the half-
life of cyhalothrin was approximately 100 days.  The principle 
degradative reactions were hydroxylation, yielding up to 7% of the 
applied radiocarbon as compound XV, and hydrolysis, yielding up to 
ca. 2% as compound Ia. The initial degradation products of 
cyhalothrin were further degraded with mineralization (up to 17% in 
26 weeks) to 14CO2 (Bharti & Bewick, 1986). 

    Four sites in the USA were treated with lambda-cyhalothrin 
(1.1 kg/ha), and soil was sampled and analysed at intervals up to 9 
months after treatment.  Residues remained in the top 15 cm of 
soil, except at one site where low residues immediately after 
treatment and at 2 days were attributed to contamination during 
sampling. Initial soil residues of 0.18 to 0.31 mg/kg declined to 
extremely low levels (< 0.01 to 0.02 mg/kg) during the course of 
the study, and at one site the residues were less than the limit of 
determination after 91 days (Fitzpatrick, 1985). 

4.3.2.  Degradation pathways

    Degradation pathways for cyhalothrin and lambda-cyhalothrin in 
soil are shown in Figure 2. 

FIGURE 2

4.4.  Metabolism in plants

    In studies by Leahey & French (1986a), soya bean plants were 
treated with 14C-cyclopropane-labelled and 14C-benzyl-labelled 
lambda-cyhalothrin. Two applications (18 days apart) were made by 
spraying an EC formulation at a rate of 20 g/ha.  The plants were 
analysed at maturity, 39 days after the second application, when 
radioactive residues on the leaves ranged from 1.2 mg/kg (benzyl-
labelled treatment) to 1.5 mg/kg (cyclopropane-labelled treatment).  
Very little radioactivity translocated into seeds (< 0.01 mg/kg). 
        
    In a similar experiment, in which cotton plants were treated 
with 14C-cyclopropane-labelled and 14C-benzyl-labelled lambda-
cyhalothrin, three applications at a rate of 66 g/ha were made (at 
flowering and 3 and 7 weeks after flowering). The plants were 
analysed, at maturity, 30 days after the final application. The 
radioactive residues on the leaves at harvest were 3.7 mg/kg for 
the benzyl-labelled treatment and 4.1 mg/kg for the cyclopropane-
labelled treatment.  Very little radioactivity (< 0.03 mg/kg) was 
detected in the cotton seeds (Leahey & French, 1986b,c). 

    At harvest, the major constituents of the radioactive residue 
on the leaves of both cotton and soya bean were lambda-cyhalothrin 
and other isomeric forms of lambda-cyhalothrin resulting from 
photochemically initiated interconversions (soya: 52% benzyl-
label, 45% cyclopropane-label; cotton: 52% benzyl-label, 37% 
cyclopropane-label). The metabolites detected on the leaves of both 
plants resulted from a range of hydrolytic and oxidative reactions. 
A metabolic pathway illustrating these reactions is shown in Fig. 3. 

FIGURE 3

4.5.  Bioaccumulation and biomagnification

4.5.1.   n-Octanol-water partition coefficient

    In common with other synthetic pyrethroids, the  n-octanol-water 
partition coefficient of cyhalothrin is high; values for log Pow of 
6.9 and 7.0 at 20 °C have been obtained for cyhalothrin and lambda-
cyhalothrin, respectively, using a generator column method 
(personal communication by ICI Agrochemicals to the IPCS). However, 

since the compound is insoluble in water (thus limiting exposures 
of aquatic species) and is rapidly metabolized in animal systems to 
the cyclopropanecarboxylic acid and 3-phenoxybenzoic acid, both of 
which are polar compounds, no problem of bioaccumulation will 
occur. 

4.5.2.  Bioaccumulation

    In a study consisting of a 28-day exposure and a 28-day 
depuration period, carp  (Cyprinus carpio) were exposed to 
cyhalothrin in a flow-through water system using 14C-labelled 
cyhalothrin at a nominal concentration of 0.02 µg cyhalothrin 
equivalent/litre. During the exposure period, the concentration of 
the total 14C-labelled cyhalothrin in the carp reached an 
equilibrium within 1-2 weeks.  The bioconcentration factors 
measured were: 4250-7340 in the viscera, 490-850 in the muscle, 
1020-2290 in the remainder of the body, and 1660-2240 in the whole 
fish.  Rapid depuration of residues was observed; the biological 
half-life of the total 14C-labelled cyhalothrin was 9 days in the 
viscera, muscle, and whole fish (Yamauchi et al., 1984a). 

    The accumulation of cyhalothrin and its degradation products in 
channel catfish and  Daphnia magna has been investigated in a soil-
water system.  14C-cyclopropane-labelled cyhalothrin was applied at 
50 g ai per ha and aerobically incubated in soil for 3 weeks prior 
to flooding. Channel catfish and  Daphnia magna were introduced for 
exposure periods of 31 and 28 days, respectively, after which the 
fish and daphnids were transferred to an uncontaminated system for 
depuration periods of 42 and 7 days, respectively.  Soil, water, 
fish, and daphnids were ana-lysed for 14C-residues.  Prior to 
flooding, 14C-labelled residues in soil decreased to 60-70% of that 
applied, 40% of which remained as extractable cyhalothrin.  
Following flooding of the soil, 14C-labelled residues in the water 
increased throughout the exposure period, reaching a level of 8% of 
the applied radioactivity.  No parent cyhalothrin was detected in 
the water; the only product comprising more than 1% of the applied 
radioactivity was  cis-3-( ZE-2-chloro-3,3,3-trifluoroprop-1-enyl-
2,2-dimethylcyclopropane-carboxylic acid, which represented up to 
5.3% of the applied radioactivity. During exposure, the maximum 
bio-concentration factors in whole fish and daphnids were 19 and 
194, respectively (Table 2). The concentration of 14C-residues in 
fish and daphnids decreased during the depuration period, the 
half-lives being approximately 7 days and 1 day, respectively 
(Table 3) (Hamer & Hill, 1985). 

Table 2.  Bioconcentration factors for 
cyhalothrin in  Daphnia and fish
---------------------------------------------
Exposure    Daphnia  Fish     Fish      Whole 
phase               muscle   viscera   fish
(days)
---------------------------------------------
1          93       2        20        17
3          194      3        28        7
7          158      6        45        10
14         62       7        66        19
21         47       5        28        10
28         29       7        49        8
31         NR       7        48        9
---------------------------------------------
From:   Hamer & Hill (1985)
NR = not recorded.

Table 3.  Concentration of 14C-residues in 
 Daphnia and fish tissues
--------------------------------------------
Depuration  % of tissue level on final day     
phase                of exposure            
(days)       Daphnia  Fish    Fish     Whole
                     muscle  viscera  fish
--------------------------------------------
1           56       105     60       80
3           29       66      53       64
4           NR       NR      NR       61
7           11       51      4        38
14          NR       32      4        37
21          NR       31      6        27
42          NR       20      2        14
--------------------------------------------
From: Hamer & Hill (1985)
NR = not recorded.

5.  KINETICS AND METABOLISM

5.1.  Absorption, distribution, and excretion

5.1.1.  Rat

    In studies by Harrison (1981, 1984a,b), groups of six male and 
six female Alderley Park rats received a single oral dose (1 or 25 
mg/kg) of radiolabelled cyhalothrin in corn oil.  As it was known 
that the metabolism of related pyrethroids involves extensive 
cleavage of the ester bond, duplicate experiments were performed 
using two forms of cyhalothrin labelled with 14C in the acid (14C-
cyclopropyl) or alcohol (14C-benzyl) portions of the ester. 
Excreta (urine, faeces and, in selected animals, expired air) were 
collected for up to 7 days after dosing and analysed for total 
radioactivity and metabolites by liquid scintillation counting and 
thin-layer chromatography. Blood samples were also collected at 
various times up to 48 h and analysed for total radioactivity and 
unchanged cyhalothrin. 

    Following oral administration of cyhalothrin, absorption was 
variable but accounted for about 55% of the dose. The proportions 
absorbed were similar at both dose levels. 

    Excretion was rapid for both 14C-cyclopropyl- and 14C-benzyl-
labelled cyhalothrin at both dose levels, although excretion rates 
were faster with the 14C-benzyl label than with the 14C-cyclopropyl 
label.  Urinary excretion accounted for approximately 20-40% of the 
dose and faecal excretion for 40-65% of the dose during the first 7 
days.  Peak blood concentrations of radioactivity were reached 
within 4-7 h, and by 48 h these concentrations had declined to 10% 
or less of peak values. A small proportion of an oral dose (2-3%) 
was retained in the animals after seven days; analysis of twelve 
different tissues indicated that this radioactivity was present 
mainly in white fat. 

    Results from a study in which rats were dosed subcutaneously 
indicated that some of the dose was excreted via the bile. 

    In a further experiment to study the excretion and tissue 
accumulation of cyhalothrin (1 mg/kg per day by gavage), groups of 
six male and six female rats received daily doses of 14C-benzyl-
labelled or 14C-cyclopropyl-labelled cyhalothrin for 14 days. Urine 
and faecal samples were collected every 24 h up to 7 days after the 
final dose. Groups of animals were killed 2, 5, and 7 days after 
the final dose and a range of tissues were removed for measurement 
of residual radioactivity.  Fat samples were analysed by HPLC for 
unchanged cyhalothrin.  The results demonstrated that the excretion 
of 14C-material after multiple oral dosing was similar to that 
which followed a single dose.  Slightly higher overall excretion in 
urine (up to 50% of the administered dose) was probably due to more 
consistent oral absorption in this study.  A large proportion of 
the oral dose of cyhalothrin was rapidly eliminated from the body.  
Analysis of tissue residues revealed that the small proportion 
(< 5%) of the dose retained in white fat was unchanged 
cyhalothrin, which was eliminated from this tissue with a half-life 
of about 23 days (Harrison, 1981, 1984a,b). 

    A further study was undertaken in the rat to explore the 
retention, in fat, of cyhalothrin and lambda-cyhalothrin.  Groups 
of male rats received daily oral doses of 14C-cyclopropyl-labelled 
cyhalothrin (1 mg/kg per day) for up to 119 days. At intervals 
during and after the dosing period, groups of three rats were 
killed and the concentrations of radioactivity in the liver, 
kidney, fat, and blood were determined.  Additionally the 
concentration in fat of lambda-cyhalothrin and its opposite 
enantiomer pair (enantiomer pair A) was measured by high-pressure 
liquid chromatography.  Levels of radioactivity in the blood 
remained fairly constant and low (approximately 0.2 µg cyhalothrin 
equivalents per g) throughout the dosing period.  In the liver and 
kidney, the radioactivity reached a plateau, after approximately 70 
days, at a level corresponding to approximately 2.5 µg cyhalothrin 
equivalents per g liver and 1.2 µg per g kidney.  The concentration 
of cyhalothrin in fat at the end of the dosing period was 
approximately 10 µg/g.  After the cessation of dosing, levels of 
radioactivity in the liver, kidney, and blood declined rapidly. In 
fat, the levels declined more slowly with an elimination half-life 
of 30 days.  The radioactive material in fat was unchanged 
cyhalothrin; the ratio of enantiomeric pairs, one of which was 
lambda-cyhalothrin, was not significantly different from that in 
the dosing solution, indicating that the rate of metabolism of 
lambda-cyhalothrin was the same as cyhalothrin and that there was 
no preferential accumulation of lambda-cyhalothrin (Prout, 1984). 

    A comparison of the absorption, distribution, excretion, and 
metabolism of lambda-cyhalothrin and cyhalothrin was made to 
establish whether the single enantiomer pair lambda-cyhalothrin 
differed from cyhalothrin (a 50:50 mixture of lambda-cyhalothrin 
and the opposite enantiomer pair A) (Prout & Howard, 1985).  One 
group of four male rats was given a single oral dose of 14C-
cyclopropyl-labelled lambda-cyhalothrin (1 mg/kg); a second group 
of four male rats was given 14C-cyclopropyl-labelled lambda-
cyhalothrin (1 mg/kg) plus the unlabelled enantiomeric pair A (1 
mg/kg); and a third group of four male rats was given a single oral 
dose of a 50:50 mixture of 14C-cyclopropyl-labelled lambda-
cyhalothrin and 14C-labelled enantiomeric pair A (i.e. 14C-
cyclopropyl-labelled cyhalothrin at 1 mg/kg).  The urinary and 
faecal excretion of radioactivity was monitored in all three groups 
for three days and the residual radioactivity was then determined 
in selected tissues. The metabolite profile of the excreta was 
determined by thin-layer chromatography.  The results of this study 
indicate that co-administration of enantiomer pair A with lambda-
cyhalothrin had little or no effect upon the absorption, 
distribution, or tissue retention of radioactivity, and there was 
no effect upon the metabolite profile of lambda-cyhalothrin.  
Similarly, the absorption, distribution, excretion, and metabolism 
of cyhalothrin was indistinguishable from that of lambda-
cyhalothrin, thus confirming the results of the bioaccumulation 
study of Prout (1984). 

5.1.2.  Dog

    The absorption, distribution, excretion, and metabolism of 
cyhalothrin have been studied in the dog.  As in the rat studies, 

the experiments were duplicated using cyhalothrin labelled either 
in the acid (14C-cyclopro-pyl) or alcohol (14C-benzyl) moieties of 
the molecule.  Groups of three male and three female beagle dogs 
were given a single oral dose of cyhalothrin (1 mg/kg or 10 mg/kg) 
and, after a 3-week interval, a further single intravenous 
administration of 0.1 mg/kg. Samples of blood and excreta were 
collected for 7 days after dosing and were analysed for total 
radioactivity.  The proportions of unchanged cyhalothrin and of 
metabolites in urine and faeces were determined by thin-layer 
chromatography. The identity of major metabolites was confirmed by 
mass spectrometry. 

    The absorption of cyhalothrin after oral administration was 
variable. The degree of absorption was difficult to assess but was 
within the range 48%-80%. Excretion of radioactivity after both 
oral and intravenous dosing was initially rapid, with most of the 
administered radioactivity being excreted in the first 48 h after 
dosing. After 7 days, a mean of 82-93% had been excreted (Harrison, 
1984c). 

5.1.3.  Cow

    After twice daily oral ingestion of 14C-benzyl- or 14C-
cyclopropyl-labelled cyhalothrin (1 mg/kg per day for 7 days), 
absorption of the insecticide by cows was apparently slow and 
incomplete.  Approximately 50% of the dosed radioactivity was 
excreted in the faeces, mainly as unchanged cyhalothrin, but only 
small amounts were detected in the bile.  With both labelled forms, 
most of the radioactive material was rapidly eliminated in the 
urine (27%) and faeces (49%) within 24 h of each daily dose.  Only 
a very small proportion of the dose was secreted in the milk (0.8%) 
and this was found to be unchanged cyhalothrin.  Tissue residues of 
radioactive material were low and were in the following order: fats 
> liver > kidney > blood > muscle.  Residues in fat consisted 
of unchanged cyhalothrin.  The liver and kidney contained small 
amounts of cyhalothrin, but the residues were largely due to a 
number of ester-cleavage metabolites that were probably present 
because the animals were still actively metabolizing and 
eliminating a significant fraction of the most recent day's intake 
of cyhalothrin.  The almost two-fold difference in the plasma 
levels of total radiolabelled components obtained with the 
different labelled forms suggests that little cyhalothrin was 
present in blood. The ester link must therefore be hydrolysed very 
rapidly, apart from a small fraction that is distributed into fatty 
tissues (Harrison, 1984d). 

    In studies by Sapiets (1985c), Friesian cows were fed for up to 
thirty consecutive days on diets containing lambda-cyhalothrin at 
1, 5, and 25 mg/kg. Lambda-cyhalothrin residues in milk correlated 
well with dietary inclusion rates, the mean plateau residue levels 
being 0.02 mg/kg, 0.09 mg/kg, and 0.52 mg/kg, respectively, for the 
three dietary inclusion rates.  Lambda-cyhalothrin residue levels 
in milk did not accumulate, and they declined when feeding of the 
treated diet ceased.  At the end of the 30 days, three cows from 
each group were sacrificed.  The remaining two cows from the high-

dose group were fed an untreated diet for a further 14 days before 
they too were slaughtered.  Lambda-cyhalothrin residue levels in 
the tissues of the sacrificed animals were as shown in Table 4. 
Table 4.  Lambda-cyhalothrin residues (mg/kg) in cow tissuesa
-----------------------------------------------------------------------------------------------
Dietary feeding  Abductor     Pectoral     Subcutaneous  Peritoneal   Liver        Kidney
rate (mg/kg)     muscle       muscle       fat           fat
-----------------------------------------------------------------------------------------------
1.0              < 0.01       < 0.01       0.01-0.21     0.07-0.50    < 0.01-0.03  0.01-0.02

5.0              0.01-0.03    0.03-0.07    0.44-0.81     0.95-1.8     < 0.01       0.01-0.07

25.0             0.08-0.14    0.02-0.41    1.3-4.6       3.9-7.9      0.06-0.10    0.09-0.43

25.0 + 14-day    < 0.01-0.05  < 0.01-0.03  0.03-1.1      0.47-2.6     < 0.01       0.10-0.20
recovery period  

Control          < 0.01       < 0.01       < 0.01-0.02   < 0.01-0.07  < 0.01       < 0.01
-----------------------------------------------------------------------------------------------
a   From: Sapiets (1985c).
5.2.  Metabolism

    The metabolic pathways that have been established for 
cyhalothrin in mammals are summarized in Fig. 4. 

FIGURE 4

5.2.1.  Rat

    Identification of the metabolites produced in the rat studies 
of Harrison (described in section 5.1.1) revealed that, following 
oral administration, unabsorbed cyhalothrin was eliminated 
unchanged via the faeces.  The absorbed material was rapidly and 
extensively metabolized and no unchanged cyhalothrin was present in 
urine or bile. The main route of metabolism was, as anticipated, 
via hydrolysis of the ester linkage (Fig. 4). The cyclopropane-
carboxylic acid moiety was subsequently excreted via the urine as 
the glucuronide conjugate.  This material accounted for about 50% 
of the radioactivity in urine following dosing with 14C-
cyclopropyl-labelled cyhalothrin.  The 3-phenoxybenzyl moiety was 
further metabolized by loss of the nitrile group, oxidation of the 
aldehyde formed to a carboxylic acid, aromatic hydroxylation at the 
4' position, and formation of the 4- O-sulfate conjugate of 3-(4-
hydroxyphenoxy)benzoic acid.  This conjugate accounted for 
approximately 75% of the urinary radioactivity following dosing 
with 14C-benzyl-labelled cyhalothrin.  No metabolite containing the 
ester function was detected (Harrison, 1983). 

5.2.2.  Dog

    The main route of metabolism after oral administration is, as 
in the rat, via cleavage of the ester bond.  After intravenous 
administration (0.1 mg/kg body weight), the patterns of metabolites 
in urine were very similar to those seen in the oral studies.  Very 
little unchanged compound was present in the faeces or urine. The 
phenoxy-benzyl moiety was further metabolized as in the rat; the 
main metabolites were  N-(3-phenoxybenzyl) glycine, 3-(4-
hydroxyphenoxy)benzoic acid and its sulfate conjugate, 3-
phenoxybenzoyl glucuronide, and a little free 3-phenoxybenzoic 
acid.  Other conjugated metabolites were also present.  The 
cyclopropane acid moiety was extensively metabolized to produce 11 
metabolites.  These included the cyclopropane acid glucuronide and 
other conjugated metabolites.  Thus, the metabolism of cyhalothrin 
is dominated by cleavage of the ester bond (Fig. 4). Subsequent 
metabolism of the products is similar both to that of other 
pyrethroids and to the fate of cyhalothrin in other species 
(Harrison, 1984c). 

5.2.3.  Cow

    In common with other structurally related pyrethroids, the main 
routes of metabolism of cyhalothrin in the cow have been found to 
be similar to those observed in rats and dogs, i.e cleavage of the 
ester bond with subsequent excretion of the cyclopropyl carboxylic 
moiety, either free, hydroxylated, or as a glucuronide conjugate.  
The phenoxybenzyl moiety was further metabolized by loss of the 
nitrile group and excreted as free 3-phenoxybenzoic acid and its 
amino acid conjugates, or after aromatic hydroxylation probably at 
the 4'position.  Cyhalothrin itself gives rise to residues in fats; 
this is consistent with the lipophilic properties of cyhalothrin 
compared to those of its more polar metabolites (Harrison, 1984d). 

5.2.4.  Goat

    In a study by Leahey et al. (1985), a goat was dosed orally for 
seven days with 14C-cyclopropyl-labelled lambda-cyhalothrin at a 
rate equivalent to approximately 11 mg/kg diet.  During dosing, the 
maximum residue level in the milk was 0.27 mg cyhalothrin 
equivalents/kg (mean value during days 3-7: 0.21 mg/kg), virtually 
all of which was characterized as lambda-cyhalothrin. When the goat 
was slaughtered 16 h after receiving the final dose, residues in 
the tissues, expressed in cyhalothrin equivalents, were: meat, 
0.024-0.028 mg/kg; fat, 0.13-0.44 mg/kg; liver, 0.34-0.35 mg/kg; 
kidney, 0.20 mg/kg.  The residues in meat and fat were due mainly 
to lambda-cyhalothrin. However, in the liver and kidney, intact 
pyrethroid accounted for only a small part of the residue. (1 RS)-
 cis-(Z-2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclo-
propanecarboxylic acid and 3-(2-chloro-3,3,3-trifluoro-prop-1-
enyl)-2-hydroxymethyl-2-methylcyclopropanecarboxylic acid were the 
major components of the residue identified in liver and kidney. 

5.2.5.  Fish

    In an accumulation study by Leahey & Parker (1985), carp were 
maintained in a flow-through water system con-taining 14C-
cyclopropyl-labelled cyhalothrin (at a level of 20 ng/g) for 28 
days.  Results showed that radioactive residues in muscle, head, 
and viscera were 0.035, 0.050, and 0.115 mg/kg, respectively.  The 
major part of the 14C-residue (50-65%) was characterized as 
cyhalothrin, a further 10-19% consisting of the compound 1a (Fig. 2). 

6.  EFFECTS ON ORGANISMS IN THE ENVIRONMENT

6.1.  Aquatic organisms

6.1.1.  Microorganisms

    It has been shown that lambda-cyhalothrin, at a concentration 
of 1.0 mg/litre, does not affect the growth of the single-celled 
green alga  Selenastrum capricornutum over a period of 96 h 
(Thompson & Williams, 1985). 

6.1.2.  Invertebrates

6.1.2.1 Acute toxicity

    Aquatic invertebrates show a wide range of susceptibility to 
cyhalothrin and lambda-cyhalothrin. The data are summarized in 
Table 5. 
Table 5.  Acute toxicity of cyhalothrin and lambda-cyhalothrin for aquatic invertebrates
-----------------------------------------------------------------------------------------
Species              Stage     Temper-  Test substance       Test     48-h    Reference
                               ature                         system   LC50
                               (°C)                                   (ng/
                                                                      litre)
-----------------------------------------------------------------------------------------
 Freshwater

Water flea           < 24 h    20       cyhalothrin          static   160     Yamauchi et 
 (Daphnia pulex)                         5% WP                                 al. (1984d)

Water flea           12 h      20       technical            static   380     Williams & 
 (Daphnia magna)      (± 12 h)           cyhalothrin                           Thompson 
                                                                              (1981)

Water flea           < 24 h    20       technical lambda-    static   360     Farrelly et 
 (Daphnia magna)                         cyhalothrin                           al. (1984)

                     < 24 h    20       lambda-cyhalothrin   static   90a     Farrelly et 
                                        5% EC                                 al. (1985)

                     < 24 h    20       lambda-cyhalothrin   static   90a     Farrelly et 
                                        13% EC                                al. (1985)

Freshwater shrimp    5 mm      15       14C-lambda-          flow-    8       Hamer et al. 
 (Gammarus pulex)                        cyhalothrin          through          (1985a)

 Marine

Mysid shrimp         < 48 h    25       14C-lambda-          flow-    7.5     Thompson 
 (Mysidopsis bahia)                      cyhalothrin          through          (1985)
----------------------------------------------------------------------------------------- 
a  Concentration of active ingredient.

6.1.2.2 Long-term toxicity

    The effects of lambda-cyhalothrin on the survival, growth, and 
reproduction of  Daphnia magna were investigated for a period of 21 
days in a static water test with daily renewal of test solutions.  
The nominal concentrations tested were 0, 2.5, 5.0, 10.0, 20.0, 
and 40.0 ng/litre.  Lambda-cyhalothrin affected all three parameters 
at a nominal concentration of 40 ng/litre, but no effects were 
noted at 2.5 ng/litre.  Chemical analysis suggested that the 
daphnids were exposed to about 60% of the nominal concentration.  
These results show that the life-cycle no-observed-effect level of 
lambda-cyhalothrin for daphnids is of the order of 2.5 ng/litre 
(Hamer et al., 1985b). 

6.1.3.  Fish

6.1.3.1 Acute toxicity

    Cyhalothrin and lambda-cyhalothrin are very toxic to fish in 
clean water under laboratory conditions.  The available data, 
summarized in Table 6, demonstrate a similar high acute toxicity 
for both cold and warm water species of fish. 

6.1.3.2  Long-term toxicity

    Sheepshead minnow  Cyprinodon variegatus embryos and larvae were 
continuously exposed (through 28 days post hatch) to mean measured 
lambda-cyhalothrin concentrations of 0.04, 0.07, 0.14, 0.25, and 
0.38 µg/litre, in a flow-through system.  The test was performed in 
duplicate. Assessments were made of percentage hatch and survival 
of embryos and of total length and weight of the larvae at the 
completion of the study. Hatchability was not affected (P < 0.05) 
at any concentration in the carrier dimethylformamide or dilution 
water controls, percentage hatch ranging from 81.3% to 100%.  
Larval survival was not significantly affected.  A significant 
effect (P < 0.05) was found on the weight of the larvae at the 
highest concen-tration tested, but not at any other concentration. 
On the basis of these data the NOEL was 0.25 µg/litre and the 
lowest-observed-effect level (LOEL) was 0.38 µg/litre (Hill et al., 
1985). 

6.1.4.  Model ecosystem

    Cyhalothrin is readily adsorbed onto soil and suspended 
particles, which in consequence significantly reduces its toxicity 
to aquatic organisms (Yamauchi et al., 1984c).   Daphnia pulex and 
 Cyprinus carpio were used in four different systems to test this 
experimentally (Table 7).  The median lethal concentrations (LC50) 
were calculated, immobilization being used as the end-point for 
 Daphnia pulex. 

Table 6.  Acute toxicity of cyhalothrin and lambda-cyhalothrin to fish
---------------------------------------------------------------------------------------------------
Species                  Weight      Test substance and vehicle     Temper-  96-h   Reference
                         (g)                                        ature    LC50  
                                                                    (°C)     (µg/  
                                                                             litre)
---------------------------------------------------------------------------------------------------
Rainbow trout            0.32-1.37   technical cyhalothrin          12       0.54   Hill (1981a)
 (Salmo gairdneri)                    dispersed via acetone
                         0.30-1.48   technical lambda-cyhalothrin   12       0.24   Hill (1984a)
                                     dispersed via acetone
                         0.99-2.32   lambda-cyhalothrin 2.5%        16       0.39   Hill (1985a)
                                     EC dispersed in water
                         1.28-4.78   lambda-cyhalothrin 13% EC      12       0.44   Hill (1985b)
                                     dispersed in water
                         0.87-4.09   lambda-cyhalothrin 5% EC       16       0.93   Hill (1985c)
                                     dispersed in water

Carp                     5.2         technical cyhalothrin          23-35    1.34a  Takeda Chemical 
 (Cyprinus carpio)                    dispersed via                                  Co. Ltd.
                                     dimethylformamide                              (1979)
                         5.4         cyhalothrin 5% WP              25       1.1    Yamauchi et al. 
                                                                                    (1984b)
                         1.48-5.8    lambda-cyhalothrin 2.5%        22       0.54   Hill (1985d)
                                     EC dispersed in water
                         3.92-7.28   lambda-cyhalothrin 5% EC       22       0.50   Hill (1985e)
                                     dispersed in water

Bluegill sunfish         0.23-0.84   technical cyhalothrin          22       0.46   Reynolds (1984)
 (Lepomis macrochirus)                dispersed via acetone
                         0.7-2.6     technical lambda-              22       0.21   Hill (1984b)
                                     cyhalothrin dispersed  
                                     via acetone
                         0.47-2.06   lambda-cyhalothrin 13%         22       0.28   Hill (1985f)
                                     EC dispersed in water
Sheephead minnow         0.32-0.91   technical lambda-              22       0.81   Hill (1985g)
 (Cyprinodon variegatus)              cyhalothrin dispersed 
                                     via acetone
---------------------------------------------------------------------------------------------------
a 72-h LC50.
Table 7.  Effect of soil on the toxicity (72-h LC50 in µg/
litre) of cyhalothrin to  Daphnia pulex and  Cyprinus carpioa
--------------------------------------------------------------
Conditions                       Daphnia pulex  Cyprinus carpio
--------------------------------------------------------------
Application to water surface    0.4            9
(without soil)

Application to water surface    1.0            32
(soil undisturbed)

Application to water surface    16             57
(soil suspended)

Application to soil             70             642
(soil undisturbed)
--------------------------------------------------------------
a From: Yamauchi et al (1984c).

6.2.  Terrestrial organisms

6.2.1.  Birds

6.2.1.1  Acute toxicity

    The toxicity of single oral doses of cyhalothrin and lambda-
cyhalothrin for birds is summarized in Table 8. 

    The 5-day dietary LC50 for cyhalothrin and lambda-cyhalothrin 
has been measured in  Anas platyrhynchos and  Colinus virginianus 
(Table 9). 
Table 8.  Oral toxicity of cyhalothrin and lambda-cyhalothrin for birds
---------------------------------------------------------------------------------------
Species               Age     Test substance      Observation  LD50 (mg/kg   References
                              and vehicle         period       body weight)
---------------------------------------------------------------------------------------
Domestic hen          adult   cyhalothrin in      14 days      > 10 000      Roberts 
 (Gallus domesticus)           corn oil                                       et al. 
                                                                             (1982)

Mallard duck          adult   cyhalothrin in      14 days      > 5000        Roberts & 
 (Anas platyrhynchos)          corn oil                                       Fairley 
                                                                             (1981)

Mallard duck          adult   lambda-cyhalothrin  14 days      > 3950        Roberts &  
 (Anas platyrhynchos)          in corn oil                                    Fairley 
                                                                             (1984)
---------------------------------------------------------------------------------------

Table 9.  Dietary LC50 of cyhalothrin and lambda-cyhalothrin for birds
---------------------------------------------------------------------------------------
Species                Age       Test substance      Observation   LC50     Reference
                                                     period (post  (mg/kg
                                                     treatment)    diet)
---------------------------------------------------------------------------------------
Mallard duck           10 days   cyhalothrin         3 days        14 000   Roberts et 
 (Anas platyrhynchos)                                                        al. (1981a)

Mallard duck           8 days    lambda-cyhalothrin  4 days        3948     Roberts et 
 (Anas platyrhynchos)                                                        al. (1985a)

Bobwhite quail         10 days   cyhalothrin         3 days        > 7530   Roberts et 
 (Colinus virginianus)                                                       al. (1981b)

Bobwhite quail         11 days   lambda-cyhalothrin  3 days        > 5300   Roberts et 
 (Colinus virginianus)                                                       al. (1985b)
---------------------------------------------------------------------------------------
6.2.2.  Honey-bees

    Cyhalothrin and lambda-cyhalothrin have been shown to be toxic 
to honey-bees  (Apis mellifera) in laboratory tests (Table 10). 

Table 10.  Toxicity of cyhalothrin and lambda-cyhalothrin for 
honey-bees (expressed as 24-h LD50 in µg ai per bee)
----------------------------------------------------------------------
Formulation                    Topical      Oral            Reference
                               application  administration
----------------------------------------------------------------------
Technical cyhalothrin          0.027        -               Smart & 
                                                            Stevenson 
                                                            (1982)

Technical lambda-cyhalothrin   0.051        0.97            Gough et 
                                                            al. (1984)

Lambda-cyhalothrin EC (5%)     0.095        0.57            Gough et 
                                                            al. (1984)
----------------------------------------------------------------------

    In common with other pyrethroids, the high laboratory toxicity 
of lambda-cyhalothrin is not translated into a significant field 
hazard to bees. In two trials on flowering rape, lambda-
cyhalothrin (JF 9509) EC was applied, at midday, by helicopter at a 
concentration of 10 g ai/ha to fields where hives of honey-bees 
were located.  A toxic standard and untreated control were used for 
comparison. Bees were actively foraging during spraying, and the 
hives were oversprayed.  Mortality, foraging activity, activity at 
the hive, and brood development were monitored before and after 
treatment, and pollen, honey, and wax were analyzed for residues.  
Apart from a suppression of foraging lasting up to 1.5 h, the 
lambda-cyhalothrin formulation had no effect on the bees, whereas 
the toxic standard killed large numbers.  Only low levels of 

residues were detected (pollen, 0.44 µg/g; honey, 0.01 µg/g; wax, 
0.01 µg/g).  It was concluded that, at 10 g ai/ha, lambda-
cyhalothrin formulation (JF 9509) EC is non-hazardous to honey-bees 
on flowering rape (Gough et al., 1985). 

6.2.3.  Earthworms

    Three annual applications of lambda-cyhalothrin at rates of up 
to 250 g ai/ha to field plots had no adverse effect on populations 
of individual species of earthworms or total earthworm numbers or 
weight (Coulson et al., 1986). 

6.2.4.  Higher plants

    No phytotoxic effects have been reported.

7.  EFFECTS ON EXPERIMENTAL ANIMALS AND  IN VITRO TEST SYSTEMS

7.1.  Single exposures

7.1.1.  Oral

    The acute oral toxicity of cyhalothrin and lambda-cyhalothrin 
in corn oil has been determined for several species (Table 11). The 
toxicity of cyhalothrin is moderate (LD50 values: rat, 144-243 
mg/kg; mouse, 37-62 mg/kg), whereas that of lambda-cyhalothrin is 
higher (LD50 values: rat, 56-79 mg/kg; mouse, 20 mg/kg). Signs of 
intoxication are characteristic of type II pyrethroid toxicity and 
included piloerection, subdued behaviour, ataxia, unsteady gait, 
salivation, incontinence, scouring, and chromodacryorrhoea. 

Table 11.  Acute oral toxicity of technical cyhalothrin and
lambda-cyhalothrin in corn oil
------------------------------------------------------------------
Species      Test substance      LD50 (mg/kg      Reference
                                 body weight)
------------------------------------------------------------------
Rat          cyhalothrin         243  (male)      Nixon & 
                                 144 (female)     Jackson (1981a)

Rat          lambda-cyhalothrin  79 (male)        Southwood (1985)
                                 56 (female)

Mouse        cyhalothrin         36.7  (male)     Nixon & 
                                 62.3  (female)   Jackson (1981a)

Mouse        lambda-cyhalothrin  19.9 (male)      Southwood (1984)
                                 19.9 (female)

Guinea-pig   cyhalothrin         > 5000 (male)    Nixon & 
                                                  Jackson (1981a)

Rabbit       cyhalothrin         > 1000 (female)  Nixon & 
                                                  Jackson (1981a)
------------------------------------------------------------------

7.1.2.  Percutaneous

    The percutaneous toxicity of cyhalothrin and lambda-cyhalothrin 
is summarized in Table 12. Signs of intoxication were similar to 
those seen after oral ingestion, and included incontinence, 
scouring, dehydration, subdued behaviour, curvature of the spine, 
unsteady gait, nervous appearance, piloerection, and increased 
vocalization when handled. 

Table 12.  Percutaneous toxicity of technical cyhalothrin and 
lambda-cyhalothrin in polyethylene glycol paste
-----------------------------------------------------------------
Species   Test substance      LD50 (mg/kg        Reference
                              body weight)
-----------------------------------------------------------------
Rat       cyhalothrin         1000-2000 (male)   Nixon & 
                              200-2000 (female)  Jackson (1981a)

Rat       lambda-cyhalothrin  632 (male)         Barber (1985)
                              696 (female)

Rabbit    cyhalothrin         > 2000 (male)      Nixon & 
                              > 2000 (female)    Jackson (1981a)
-----------------------------------------------------------------

7.1.3.  Intraperitoneal

    The intraperitoneal LD50 of cyhalothrin to rats is in the range 
of 250 to 750 mg/kg.  Responses of 0% or 100% mortality were 
observed at all but one dose, and so no precise value for the LD50 
could be given.  The highest dose with no mortality was 250 mg/kg 
and the lowest dose with 100% mortality was 750 mg/kg (Nixon & 
Jackson, 1981a). 

7.2.  Irritation and sensitization

7.2.1.  Irritation

    Undiluted technical cyhalothrin is a mild irritant to occluded 
rabbit skin (both intact and abraded) but is non-irritant to 
occluded rat skin (intact) (Jackson & Nixon, 1981).  Technical 
cyhalothrin is a moderate irritant to the rabbit eye without 
irrigation and is a mild irritant when irrigated for one minute, 20 
to 30 seconds after instillation of the material (Jackson, 1981). 

    Technical lambda-cyhalothrin is non-irritant to occluded 
rabbit skin without abrasion (Pritchard, 1985a). It is a mild 
irritant to the rabbit eye (Pritchard, 1985b). 

7.2.2.  Sensitization

    A skin sensitization test with cyhalothrin on guinea-pigs, 
using the procedure of Buehler, indicated that cyhalothrin has 
skin-sensitizing potential (Nixon & Jackson, 1981b).  In guinea-
pigs that had been previously induced with undiluted cyhalothrin 
technical material, using the Magnusson and Kligman maximization 
test, a moderate sensitization response was elicited.  When 
lambda-cyhalothrin was tested for skin sensitization on guinea-
pigs, using the maximization procedure of Magnusson and Kligmann, 
it was shown to have no sensitization potential (Pritchard, 1984). 

7.3.  Short-term exposures

7.3.1.  Oral

7.3.1.1 Rat

    When groups of male and female rats were fed diets containing 
cyhalothrin at levels up to 750 mg/kg for 28 days, symptoms of 
toxicity shown by animals receiving doses of 250 mg/kg diet or more 
included high stepping gait, ataxia, and hypersensitivity to 
external stimuli. These effects were dose related and some 
mortality occurred at the highest dose level.  The clinical signs 
were not accompanied by histopathological changes in the nervous 
system.  Thymic atrophy, adrenal enlargement with vacuolization, 
and incomplete spermatogenesis occurred with the highest dose.  An 
adaptive change was present in the liver as judged by an increase 
in liver weight, proliferation of smooth endoplasmic reticulum, 
and an increase in the activity of the xenobiotic-metabolizing 
enzyme, aminopyrine- N-demethylase (APDM). These effects occurred at 
doses of 100 mg/kg or more, and there was some evidence for this 
type of change at 20 mg/kg (Tinson et al., 1984). 

    When groups of 20 male and 20 female Wistar rats were fed 
cyhalothrin (89% pure) at dietary concentrations of 0, 10, 50, and 
250 mg/kg for 90 days, only male rats fed 250 mg/kg showed 
significantly reduced body weight gain.  No abnormal clinical signs 
were seen. Haemoglobin and haematocrit values were not affected by 
the treatment, but there were marginal effects on mean erythrocyte 
volume in some treated groups.  Male rats fed 50 or 250 mg/kg 
showed decreased plasma triglyceride levels and a dose-related 
increase in hepatic APDM activity.  The latter effect was also seen 
in females fed 250 mg/kg.  Small increases in urinary glucose 
excretion occurred in males fed 50 or 250 mg/kg after 13 weeks.  No 
treatment-related effects on organ weights and no significant 
histopathological changes were reported (Lindsay et al., 1981). 

    In studies by Lindsay et al. (1982), two groups of 32 male rats 
were fed either a control diet or a diet containing 250 mg 
cyhalothrin/kg for 28 days.  After this period eight rats per group 
were killed and examined.  The remaining rats were fed the control 
diet for periods of 7, 14, or 28 days after cessation of treatment, 
and a further eight rats per group were killed and examined at each 
of these time intervals.  A decrease in body weight gain was seen 
in the treated rats, which, although not statistically 
significant, was still much reduced at the end of the 28-day 
recovery period.  Proliferation of the hepatic smooth endoplasmic 
reticulum and elevated hepatic APDM activity were also seen in the 
treated animals.  These effects had reversed 7 days after the 
cessation of treatment with cyhalothrin and were considered to be 
physiological adaptive changes rather than a toxicological effect. 

    When groups of 20 male and 20 female Alderley Park rats 
received diets containing 0, 10, 50, or 250 mg lambda-
cyhalothrin/kg for 90 days, decreased body weight gain, accompanied 
by a reduction in food consumption, was seen in both male and 

female rats receiving the highest dose. No abnormal clinical signs 
were seen; in particular, there was no evidence of neurological 
effects.  There were no treatment-related effects on haematological 
parameters but reductions in the activities of plasma alanine 
trans-aminase (males only) and alkaline phosphatase (females only 
at 13 weeks) were apparent in animals fed the highest dose.  Plasma 
triglycerides were also reduced in males at this feeding level.  
Relative liver weights were increased in both sexes at 250 mg/kg 
and in males at 50 mg/kg, accompanied by increased activity of 
hepatic APDM.  No other changes in organ weight or histopathology 
were attributed to treatment with lambda-cyhalothrin. These two 
effects, particularly in view of the findings with cyhalothrin, 
were considered to be adaptive in nature and the toxicological NOEL 
was established at 50 mg/kg (equivalent to 2.5 mg/kg body weight 
per day (Hart et al., 1985). 

7.3.1.2 Dog

    In studies by Chesterman et al. (1980), groups of one male and 
one female dog (Alderley Park beagles) received 0, 2.5, or 10 mg 
cyhalothrin/kg body weight orally in corn oil by gelatine capsule 
daily for four weeks.  A further group initially received 30 mg/kg 
per day, but due to severe clinical signs after 10 days dosing, 
which were typical of pyrethroid toxicity (muscular trembling, 
unsteadiness, vomiting, and body weight loss), the animals were 
rested and then received 20 mg/kg per day for four weeks.  Similar 
clinical signs were seen, with the exception of body weight loss, 
in all animals receiving 10 mg/kg per day or more, the severity 
being dose related. Investigation of the sciatic and tibial nerves 
and the lumbricalis muscle with special histopathological stains 
indicated no changes that could be attributed to treatment with 
cyhalothrin.  Liquid faeces were produced by all animals receiving 
cyhalothrin, the incidence being dose related.  These changes were 
considered to be of no toxicological significance.  No other 
changes were observed that could be attributed to the treatment. 

    When groups of 6 male and 6 female dogs (Alderley Park beagles) 
were fed cyhalothrin in corn oil by gelatine capsule at 0, 1, 2.5, 
or 10 mg/kg body weight per day for 26 weeks, signs of pyrethroid 
toxicity were seen in some dogs at 10 mg/kg.  Although liquid 
faeces were produced by all animals in the study, including the 
controls, the incidence and frequency were higher in treated 
animals and were dose related.  These changes were considered to be 
of no toxicological significance.  Macroscopic postmortem 
examination, organ weights, and histological investigations 
revealed no treatment-related changes.  The oral NOEL in dogs was 
found to be 2.5 mg/kg per day (Chesterman et al., 1981). 

    In studies by Hext et al. (1986), groups of 6 male and 6 female 
dogs were dosed by gavage in corn oil with 0, 0.1, 0.5, or 3.5 mg 
lambda-cyhalothrin/kg body weight daily for 52 weeks. Clinical 
signs of neurological effects were evident in all animals fed the 
highest dose, which were unaccompanied by histological changes in 
the nervous system.  There was an increased incidence of fluid 
faeces at the highest dose and a slight increase in the group 

receiving 0.5 mg/kg per day. This effect was considered to be 
related to the method of administration and not to be 
toxicologically significant.  No histopathological changes 
attributable to lambda-cyhalothrin administration were observed at 
any of the dose levels employed, and the toxicological NOEL in 
this study was 0.5 mg lambda-cyhalothrin per kg per day. 

7.3.2.  Dermal

7.3.2.1 Rabbit

    Cyhalothrin in polyethylene glycol (PEG 300) (10, 100, or 1000 
mg/kg body weight per day) was applied to the skin of groups of 10 
male and 10 female New Zealand White rabbits and kept in contact 
with the skin 6 h/day, 5 days per week for 3 weeks (i.e.  a total 
of 15 applications) by means of an occlusive dressing.  A group of 
14 male and 14 female control rabbits was treated with polyethylene 
glycol (PEG 300) using the same procedure.  The skin of half the 
animals in each group was abraded prior to the application of 
cyhalothrin.  Repeated application of the vehicle alone 
(polyethylene glycol) and the vehicle plus cyhalothrin caused 
slight to severe skin irritation.  At the highest dose level there 
was an increased incidence of oedema and erythema.  A small number 
of animals given the highest dose showed pyrethroid-like symptoms, 
but only when the skin was unabraded. The NOEL was considered to be 
100 mg/kg per day (Henderson & Jackson, 1982). 

7.4.  Long-term exposures and carcinogenicity

7.4.1.  Rat

    In studies by Pigott et al. (1984), groups of 72 male and 72 
female Alpk/AP strain rats were fed diets containing cyhalothrin 
at levels of 0, 10, 50, or 250 mg/kg diet for up to 104 weeks. All 
the surviving animals were sacrificed, and histopathological and 
gross postmortem examinations were carried out.  Decreased body 
weight gain, accompanied by a small decrease in food consumption, 
was evident in rats of both sexes fed the highest dose.  This was 
accompanied by minor changes in blood biochemistry. Increased liver 
weight was seen in rats of both sexes fed cyhalothrin at 250 mg/kg 
at the interim sacrifice but this was not evident at termination.  
There was no histopathological evidence of a chronic toxic effect 
due to cyhalothrin. In particular clinical and histopathological 
evaluation gave no indication of an effect on the nervous system. 
There was no evidence for a carcinogenic effect of cyhalothrin.  
The toxicological NOEL for this study was 50 mg cyhalothrin/kg 
diet, corresponding to a minimum dose rate of approximately 1.7 
mg/kg body weight per day for male rats and 1.9 mg/kg per day for 
female rats. 

7.4.2.  Mouse

    Groups of 52 male and 52 female Charles River CD-1 mice were 
maintained for 104 weeks on diets containing 0, 20, 100, or 500 mg 
cyhalothrin/kg and further groups of 12 males and 12 females were 
designated for interim sacrifice after 52 weeks. During the study 

there were no deaths attributable to treatment with cyhalothrin. 
Signs of toxicity ascribable to cyhalothrin included piloerection 
and hunched posture in both sexes at 500 mg/kg and in males at 100 
mg/kg and reduced body weight gain, higher food intake, and 
reduced efficiency of food utilization in males receiving 500 
mg/kg. There was a statistically significant increase, compared to 
the controls, in the incidence of mammary adenocarcinoma in females 
at the two highest dose levels.  However, the frequency of these 
tumours was not unduly at variance with that normally seen in the 
strain of mouse used, and no dose relationship was apparent. Thus, 
there were no neoplastic findings that could be attributed to the 
long-term administration of cyhalothrin. There was a clear NOEL of 
20 mg/kg, corresponding to a mean calculated daily intake of 1.8 
mg/kg body weight per day in males and 2.0 mg/kg body weight per 
day in females (Colley et al., 1984). 

7.5.  Reproduction, embryotoxicity, and teratogenicity

7.5.1.  Reproduction

    In studies by Milburn et al. (1984), groups of 15 male and 30 
female (F0 parents) weaning Alderley Park rats were fed diets 
containing 0, 10, 30, or 100 mg cyhalothrin per kg.  After 12 
weeks, the animals were mated to produce the first (F1a) litter and 
subsequently re-mated to produce a second (F1b) litter.  The 
breeding programme was repeated with F1 parents selected from the 
F1b off-spring and F2 parents selected from the F2b offspring. 
Test diets were fed continuously throughout the study. There were 
minor effects on body weight gain of parents from all generations 
receiving 100 mg/kg, but no clinical signs of neurological effects 
were seen in either parents or offspring. No effects of treatment 
were seen on indices of male and female fertility, gestation 
period, live born index, or pup survival.  There was a small 
reduction in mean total litter weight of the F2 and F3 generations 
from rats receiving the highest dose, which was attributable to 
minor decreases in litter size and a small reduction in weight gain 
of the pups.  No effect was seen in litters from rats receiving 30 
mg/kg.  There was no evidence of gross or histopathological change 
attributable to the treatment.  The reproductive effects seen in 
rats receiving the highest dose were of a minor nature. A clear 
NOEL of 30 mg/kg (corresponding to a dosage in the range of 1.5 to 
1.9 mg/kg body weight per day) was established (Milburn et al., 
1984). 

7.5.2.  Embryotoxicity and teratogenicity

7.5.2.1 Rat

    When groups of 24 mated female rats (Charles River CD-1) were 
given cyhalothrin orally (in corn oil), at 0, 5, 10, or 15 mg/kg 
body weight per day, from day 6 to 15 inclusive of gestation and 
were killed on day 20, there was reduced body weight gain at the 
highest dose level and evidence of mild pyrethroid toxicity in two 
of these animals.  There were no other effects on the clinical or 
litter parameters attributable to treatment with cyhalothrin, and 

examination of the viscera and skeletons showed no effects of 
treatment.  At the highest dose level, there was maternal toxicity, 
but there was no effect on any aspect of fetal development at any 
dose level (Killick, 1981a). 

7.5.2.2 Rabbit

    In studies by Killick (1981b), groups of at least 18 pregnant 
New Zealand White rabbits received cyhalothrin orally in corn oil 
daily at 0, 3, 10, or 30 mg/kg body weight, from days 6 to 18 
(inclusive) of gestation and were killed on day 28.  There was 
reduced body weight gain at the highest dose, accompanied by 
reduced food intake during dosing. There were no clinical signs and 
no changes in pregnancy incidence or in litter parameters 
attributable to treatment with cyhalothrin.  Examination of the 
viscera and skeletons revealed no effects of treatment. At the 
highest dose level, there was maternal toxicity, but there was no 
effect on any aspect of fetal development at any dose level. 

7.6.  Mutagenicity and related end-points

7.6.1.  Microorganisms

    Five test strains, TA1535, TA1537, TA1538, TA98, and TA100, 
were employed to evaluate the mutagenic potential of cyhalothrin 
using the salmonella reverse mutation assay of Ames.  The assay was 
conducted in the presence and absence of metabolic activation (S9 
mix) with cyhalothrin at levels up to 2500 µg/plate.  The mean 
numbers of revertant colonies of Salmonella typhimurium observed in 
the five test strains indicated an unequivocal negative response 
(Trueman, 1981).  Lambda-cyhalothrin at dose levels of up to 5000 
µg/plate, both in the presence and absence of metabolic activation, 
gave a non-mutagenic response in the same test using the same 
strains (Callander, 1984). 

7.6.2.   In vitro mammalian cells

    When cyhalothrin was tested in a modification of the cell 
culture transformation test of Styles, using Syrian Hamster kidney 
cell line BHK21C13, the response in the presence of metabolic 
activation was unequivocally negative. In the absence of metabolic 
transformation there was an erratic increase in numbers of 
transformed colonies together with a poor dose response.  These 
data were not thought to indicate a significant positive response, 
and it was concluded that cyhalothrin does not appear to possess 
significant cell-transforming properties (Richold et al., 1981).  
In addition, the significance of the results from the BHK cell 
system is doubtful in view of the questionable interlaboratory 
reproducibility of this assay. 

    The mutagenic potential of lambda-cyhalothrin has been assessed 
 in vitro with L51787 mouse lymphoma cells, both in the presence and 
absence of auxiliary metabolic activation (S9) mix, using dose 
levels of 125-1000, 2000, and 4000 µg/ml.  There was no increase in 
mutation frequency either in the presence or absence of S9 mix 
(Cross, 1985). 

    Lambda-cyhalothrin, at dose levels of up to 1000 µg/ml, either 
in the presence or absence of metabolic activation, did not induce 
statistically significant increases in the incorporation of 
tritiated thymidine in cultured human (Hela) cells (Milone, 1986) 
or induce chromosomal damage in human lymphocytes stimulated by 
phytohaemagglutinin (Sheldon et al., 1985). 

7.6.3.   In vivo mammalian assays

    Male rats were given a single dose or five consecutive daily 
doses by gavage of cyhalothrin at levels of 1.5, 7.5, or 15 mg/kg, 
and bone marrow samples were taken and examined for chromosomal 
abnormalities. The results indicated that cyhalothrin has no 
clastogenic potential (Anderson et al., 1981). 

    In studies by Irvine (1981), three groups of male mice were 
dosed with cyhalothrin by gavage, at dose levels of 1, 5, or 10 
mg/kg daily, for 5 consecutive days. A further group received the 
known mutagen cyclophosphamide intraperitoneally at 200 mg/kg 
daily for five days. The animals were then mated with groups of 
females at weekly intervals for eight weeks.  Pregnancy incidence, 
pre- and post-implantation loss, clinical condition, body weight, 
and gross necropsy were assessed.  There was no evidence of an 
increase in the dominant lethal mutation frequency following 
treatment.  The NOEL was 10 mg/kg per day.  Although these studies 
showed no clastogenic or mutagenic effect, it is not clear whether 
sufficiently high dose levels were used. 

    When lambda-cyhalothrin was administered to mice at levels of 
up to 35 mg/kg and bone marrow preparations were examined for the 
formation of micronuclei in polychromatic erythrocytes, there was 
no statistically significant increase in the frequency of 
micronuclei, compared to control animals.  The positive control 
substance, cyclophosphamide, showed the expected response (Sheldon 
et al., 1984). 

7.7.  Mode of action

    The mode of action of cyhalothrin and lambda-cyhalothrin, both 
type II pyrethroids, is basically the same as that of the other 
pyrethroids (see Appendix). 

8.  EFFECTS ON HUMANS

8.1.  General population exposure

    No poisoning incidents with cyhalothrin or lambda-cyhalothrin 
have been reported.  There is no information on effects from short- 
or long-term exposure and no epidemiological information is 
available. 

8.2.  Occupational exposure

    Cyhalothrin is known to produce an effect described as 
subjective facial sensation (SFS) in some people working with this 
compound. SFS is a transient phenomenon; symptoms are not 
associated with objective physical signs and recovery appears to be 
complete.  It is likely that SFS arises from direct facial contact 
with the chemical particularly from touching the face with 
contaminated gloves or hands.  This would also help to explain the 
effect of formulation or concentration as these could affect the 
rate of dermal penetration and therefore access of the chemical to 
the nerve endings. 

    It appears unlikely that individual sensitivity is important 
in the development of symptoms following exposure. It is more 
likely to be related to the amount of the chemical that comes into 
contact with the facial skin. The information currently available 
(Hart, 1984) is summarized in section 8.2.2. 

8.2.1.  Acute toxicity: poisoning incidents

    No poisoning incidents involving cyhalothrin or lambda-
cyhalothrin have been reported. 

8.2.2.  Effects of short- and long-term exposure

    Laboratory workers and manufacturing plant and field operators 
handling natural and synthetic pyrethroids, including cyhalothrin 
and lambda-cyhalothrin, have noticed a transient skin sensation in 
the periorbital area of the face and other sites after direct skin 
exposure.  It has been suggested that these sensations are caused 
by spontaneous repetitive firing of sensory nerve fibres or nerve 
endings, whose threshold has been transiently lowered by the 
compound, localized around the sites of exposure. 

    Symptoms from exposure to a synthetic pyrethroid generally 
start 30 min to 1 h after exposure and last for several hours, 
sometimes up to 2 days. They almost always affect the facial area, 
producing a tingling, burning, or numb sensation that has been 
variously described as paraesthesia, dysaesthesia, or SFS.  The 
latter term appears most appropriate as no objective signs of 
abnormality of nerve function have been found in workers suffering 
from these effects and the facial area is by far the most commonly 
affected. 

8.2.2.1 Manufacture

    At least 12 workers involved in the manufacture of cyhalothrin 
have experienced symptoms of SFS. The symptoms were described as 
burning, tingling, or sunburn, but clinical examination revealed no 
abnormal neurological signs.  The areas of the face affected were 
the eyelids, cheeks, nostrils, forehead, and lips.  In one case the 
penis was affected, probably from contact with contaminated hands.  
The symptoms started between 5 min and 3 h from the onset of 
exposure and lasted from 5 to 30 h. Wind, washing, and temperature 
increase led to a worsening of the symptoms, and relief could be 
obtained by using a local anaesthetic. Barrier creams were 
relatively ineffective in preventing the symptoms. 

8.2.2.2 Formulation and laboratory work

    Two workers have been reported to have suffered from SFS.  Both 
were exposed to technical cyhalothrin and symptoms began 1-6 h 
after exposure.  The symptoms described were typical of SFS, 
consisting of tingling and burning around the eyes and facial area, 
and lasted 6-24 h. 

    Four reports involving three individuals have been received 
from laboratories involved with lambda-cyhalothrin.  The symptoms 
consisted of a facial tingling and burning sensation and in one 
case tingling on the tongue. Symptoms began within 30 min of 
exposure and lasted from 6 h to 2 days. All three workers were 
involved in handling either technical material or concentrated 
lambda-cyhalothrin solutions (10% w/v ai). 

8.2.2.3 Field use

    Virtually no reports have been received on the agricultural or 
public health use of cyhalothrin.  The only information that has 
become available is from the use of cyhalothrin in animal health 
products.  Skin itching has been reported following exposure to a 
5% emulsifiable concentrate of cyhalothrin, but dilutions of 0.1% 
and 0.005% (w/v of ai) were without significant effect.  More 
recently, several incidents of facial irritation have been reported 
following the use of cyhalothrin in sheep sprays (Hart, 1984).  The 
concentration used in these sprays was very low (0.002% w/v), but 
the characteristics of the spray used were unclear. 

    Out of 38 field trials staff who returned questionnaires, only 
four reported experiencing any adverse effects as a result of 
exposure to lambda-cyhalothrin. Three of these individuals 
experienced a burning sensation or irritation around the face, 
cheeks, or eyes, which started between 45 and 60 min after initial 
exposure and lasted, respectively, for 5, 18, and 72 h. In one case 
the symptoms were severe enough to prevent the individual from 
working.  The other field trials worker experienced a rash on the 
hands that started 24 h after exposure and lasted several days. All 
four field trials staff were involved in handling concentrated 
solutions of lambda-cyhalothrin (2.5% w/v ai) and three of the four 

sprayed diluted solutions.  None of the three workers experiencing 
the facial sensation had experienced similar symptoms before, but 
the worker who developed the rash had suffered a similar rash after 
exposure to permethrin, cypermethrin, and deltamethrin following 
their application to top fruit. Eight of the other 34 field trials 
staff returning questionnaires stated that they had previously 
suffered symptoms of facial tingling or burning. 

9.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    Cyhalothrin was discussed at the 1984 and 1986 FAO/WHO Joint 
Meetings on Pesticide Residues (JMPR), where an acceptable daily 
intake (ADI) for cyhalothrin of 0-0.02 mg/kg body weight was 
established (FAO/WHO, 1985, 1986a). 

    The JMPR (FAO/WHO, 1985, 1986a,b) has estimated maximum 
residue limits (MRLs) for cyhalothrin (sum of the isomers) as 
follows: 

---------------------------------------------------------
Commodity                 Maximum         Pre-harvest
                          residue limit   interval (days)
---------------------------------------------------------
Pome fruits               0.2             14
Cabbages, head            0.2             3-4
Potatoes                  0.02a           non specified
Cotton seed               0.02a           21
Cotton seed oil, crude    0.02a           non specified
Cotton seed oil, edible   0.02a           non specified
---------------------------------------------------------
a At or about the limit of detection.

REFERENCES

ANDERSON, D., RICHARDSON, C.R., HULME, A., MORRIS, J., BANHAM, P.B., &
GODLEY, M.J.  (1981)  Cyhalothrin: A cytogenic study in the rat (Unpublished
proprietary report No. CTL/P/664, submitted to WHO by ICI).

BARBER, J.E.  (1985)  PP321: Acute dermal toxicity study (Unpublished
proprietary report No. CTL/P/1119, submitted to WHO by ICI).

BENGSTONE, M., DAVIES, R.A.H., DESMARCHELIER, J.M., HENNING, R., MURRAY,
W., SIMPSON, B.W., SNELSON, J.T., STICKA, R., & WALLBANK, B.E.  (1983)
Organophosphorothioates and synergised synthetic pyrethroids as grain
protectants on bulk wheat.  Pestic. Sci., 14: 373-384.

BEWICK, D.W.  & ZINNER, C.K.J. (1981)  Cyhalothrin: Degradation in soil
(Unpublished proprietary report No. RJ0203B, submitted to WHO by ICI).

BHARTI, H.  & BEWICK, D.W. (1986)  Cyhalothrin: Degradation in a Japanese
 soil (Unpublished proprietary report No. RJ0491B, submitted to WHO by ICI).

BHARTI, H., BEWICK, D.W., & WHITE, R.D. (1985)  PP563 and PP321: Degradation
 in soil (Unpublished proprietary report No.  RJ0382B, submitted to WHO by
ICI).

CALLANDER, R.D.  (1984)  PP321: An evaluation in the Salmonella mutagenicity
 assay (Unpublished proprietary report No. CTL/P/1000, submitted to WHO by
ICI).

CHESTERMAN, H., HEYWOOD, R., ALLEN, T.R., STREET, A.E., PRENTICE, D.,
BUCKLEY, P., & OFFER, J. (1980)  PP563: Preliminary oral toxicity study in
 beagle dogs (Unpublished proprietary report of the Huntingdon Research
Centre No. 325/8074, submitted to WHO by ICI).

CHESTERMAN, H., HAYWOOD, R., ALLEN, T.R., STREET, A.E., KELLY, D.F.,
GOPINATH, C., & PRENTICE, D.E. (1981)  Cyhalothrin oral toxicity study in
 beagle dogs (Final report: Repeated daily dosing for 26 weeks) (Unpublished
proprietary report of the Huntingdon Research Centre No.  ICI/326/8162,
submitted to WHO by ICI).

COLLEY, J., DAWE, S., HEYWOOD, R., ALMOND, R., GIBSON, W.A., GREGSON, R., &
GOPINATH, C.  (1984)  Cyhalothrin potential tumorigenic and toxic effects in
 prolonged dietary administration to mice (Unpublished proprietary report of
the Huntingdon Research Centre No. ICI 395/83668, submitted to WHO by ICI).

COLLIS, W.M.D.  & LEAHEY, J.P. (1984)  PP321: Hydrolysis in water at pH 5, 7
 and 9 (Unpublished proprietary report No.  RJ0338B, submitted to WHO by
ICI).

COULSON, J.M., COLLINS, I.G., & EDWARDS, P.J. (1986)  PP321: Effects on
 earthworms Lumbricidae of repeated annual field applications (Unpublished
proprietary report No. RJ0511B, submitted to WHO by ICI).

CROSS, M.  (1985)  PP321: Assessment of mutagenic potential using L5178Y
 mouse lymphoma cells (Unpublished proprietary report No.  CTL/P/1340,
submitted to WHO by ICI).

CROSSLAND, N.O.  (1982) Aquatic toxicology of cypermethrin. II.  Fate and
biological effects in pond experiments.  Aquat. Toxicol., 2: 205-222.

CROSSLAND, N.O., SHIRES, S.W., & BENNETT, D. (1982) Aquatic toxicology of
cypermethrin. III.  Fate and biological effects of spray drift deposits in
freshwater adjacent to agricultural land.  Aquat. Toxicol., 2: 253-270.

CURL, E.A., LEAHEY, J.P., & LLOYD, S.J. (1984a)  PP321: Aqueous photolysis
 at pH 5 (Unpublished proprietary report No. RJ0362B, submitted to WHO by
ICI).

CURL, E.A., LEAHEY, J.P., & LLOYD, D. (1984b)  PP321: Photodegradation on a
 soil surface (Unpublished proprietary report No. RJ0358B, submitted to WHO
by ICI).

ELLIOTT, M. (1977)  Synthetic pyrethroids, Washington, DC, American Chemical
Society, pp. 229 (ACS Symposium Series 42).

EVANS, M.H.  (1976) End-plate potentials in frog muscle exposed to a
synthetic pyrethroid.  Pestic. Biochem. Physiol., 6: 547-550.

FAO (1982)  Report of the Second Government Consultation on International
 Harmonization of Pesticide Registration Requirements, Rome, 11-15 October,
Rome, Food and Agriculture Organization of the United Nations.

FAO/WHO (1985) Cyhalothrin. In:  1984 Evaluations of some pesticide residues
 in food, Rome, Food and Agricultural Organization of the United Nations,
pp. 173-185, 571-584 (FAO Plant production and protection Paper 67).

FAO/WHO (1986a) Cyhalothrin: In:  1986 Evaluations of some pesticide
 residues in food, Part 1: Residues, Rome, Food and Agriculture Organization
of the United Nations, pp. 95-138 (FAO Plant Production and Protection
Paper 78).

FAO/WHO (1986b)  Codex maximum limits for pesticide residues, 2nd ed., Rome,
Codex Alimentarius Commission, Food and Agriculture Organization of the
United Nations (CAC XIII).

FARRELLY, E., HAMER, M.J., & HILL, I.R. (1984)  PP321: Toxicity to first
 instar Daphnia magna (Unpublished proprietary report No. RJ0359B, submitted
to WHO by ICI).

FARRELLY, E., HAMER, M.J., & HILL, I.R.  (1985)  PP321: Toxicity of
 formulations JF9509 and GFU383C to first instar Daphnia magna (Unpublished
proprietary report No. RJ0426B, submitted to WHO by ICI).

FITZPATRICK, R.D.  (1985)  PP321 dissipation in US soils - 1983 (Unpublished
report No. TMU1809, submitted to WHO by ICI).

FLANNIGAN, S.A.  & TUCKER, S.B. (1985) Variation in cutaneous sensation
between synthetic pyrethroid insecticides.  Contact dermatitis, 13: 140-147.

FORBES, S. & DUTTON, A.J. (1985) A small scale method for the determination
of pyrethroid insecticide residues in crops and soils.  Pestic. Sci., 16:
404-408.

GAMMON, D.W.  & CASIDA, J.E. (1983) Pyrethroids of the most potent class
antagonize GABA action at the crayfish neuromuscular junction.  Neurosci.
 Lett., 40: 163-168.

GAMMON, D.W., BROWN, M.A., & CASIDA, J.E. (1981) Two classes of pyrethroid
action in the cockroach.  Pestic. Biochem. Physiol., 15: 181-191.

GAMMON, D.W., LAWRENCE, L.J., & CASIDA, J.E. (1982) Pyrethroid toxicology:
Protective effects of Diazepam and phenobarbital in the mouse and the
cockroach.  Toxicol. appl. Pharmacol., 66: 290-296.

GIFAP (1981)  Technical Monograph No. 4: Guidelines on pesticide residue
 trials to provide residue data for the registration of pesticides and the
 establishment of maximum residue limits, Brussels, International Group of
National Associations of Manufacturers of Agrochemical Products (GIFAP
D/1981/2537/3).

GIRENKO, D.B.  & KLISENKO, M.A. (1984) Concentration and determination of
trace quantities of synthetic pyrethroids in the air.  Gig. i Sanit., 3: 57-
59.

GLICKMAN, A.H.  & CASIDA, J.E. (1982) Species and structural variations
affecting pyrethroid neurotoxicity.  Neurobehav.  Toxicol. Teratol., 4(6):
793-799.

GOUGH, H.J., COLLINS, I.G., EVERETT, C.J., & WILKINSON, W. (1984)  PP321:
 Acute contact and oral toxicity to honey bees (Apis mellifera) (Unpublished
proprietary report No. RJ0390B, submitted to WHO by ICI).

GOUGH, H.J., COLLINS, I.G., & WILKINSON, W. (1985)  PP321: Field test of
 toxicity to honey bees (Apis mellifera)   on flowering oil-seed rape
(Brassica napus) (Unpublished proprietary report No. RJ0413B, submitted to
WHO by ICI).

HALL, J.S.  & LEAHEY, J.P.  (1983)  Cyhalothrin: Fate in river water
(Unpublished proprietary report No. RJ0320B, submitted to WHO by ICI).

HAMER, M.J.  & HILL, I.R.  (1985)  Cyhalothrin: The accumulation of
 cyhalothrin and its degradation products by channel catfish and 
 Daphnia magna in a soil/water system (Unpublished proprietary 
report No. RJ0427B, submitted to WHO by ICI). 

HAMER, M.J., FARRELLY, E., & HILL, I.R. (1985a)  PP321: Toxicity to Gammarus
 pulex (Unpublished proprietary report No. RJ0414B, submitted to WHO by
ICI).

HAMER, M.J., FARRELLY, E., & HILL, I.R. (1985b)  PP321: 21 day Daphnia magna
 life-cycle study (Unpublished proprietary report No. RJ0451B, submitted to
WHO by ICI).

HARRISON, M.P. (1981)  Cyhalothrin: The disposition and metabolism of [ 14 C]-
 146814 in rats (Unpublished proprietary report No. 10/HD/007325, submitted
to WHO by ICI).

HARRISON, M.P. (1983)  Cyhalothrin: The metabolism and disposition of 146814
 in the rat: Part IV. Isolation and identification of the major urinary
 metabolites derived from [14 C-benzyl]- or [14 C-cyclopropyl]-146814
 following oral administration (Unpublished proprietary report No.
6/HC/005683, submitted to WHO by ICI).

HARRISON, M.P. (1984a)  Cyhalothrin (146814): The metabolism and disposition
 of 146814 in rats: Part II.  Tissue residues derived from [14 C-benzyl] or
 [14 C-cyclopropyl]-146814, after a single oral dose of 1 or 25 mg/kg
(Unpublished proprietary report No. KMR 002/2, submitted to WHO by ICI).

HARRISON, M.P.  (1984b)  Cyhalothrin: The metabolism and disposition of
 [14 C]-146814 in rats: Part III. Studies to determine radioactive residues
 in the rat following 14 days repeated oral administration (Unpublished
proprietary report No. 146814 KMR 002/03, submitted to WHO by ICI).

HARRISON, M.P. (1984c) Cyhalothrin (146814):  The disposition and metabolism
 of [14 C]-146814 in the dog (Unpublished proprietary report No. 146814 KMD
005, submitted to WHO by ICI).

HARRISON, M.P.  (1984d)  Cyhalothrin (146814): The metabolism, excretion and
 residues in the cow after 7 days oral administration with two [14 C]-
 labelled forms of 146814 at 1 mg/kg/day (Unpublished proprietary report No.
146814 KMC 006/007, submitted to WHO by ICI).

HART, D., BANHAM, P.B., CHART, I.S., EVANS, D.P., GORE, C.W., STONARD,
M.D., MORELAND, S., GODLEY, M.J., & ROBINSON, M.  (1985)  PP321: 90-day
 feeding study in rats (Unpublished proprietary report No.  CTL/P/1045,
submitted to WHO by ICI).

HART, T.B.  (1984)  Review of adverse skin reactions associated with the use
 of synthetic pyrethroids (Unpublished proprietary report No.  TMF2530,
submitted to WHO by ICI).

HENDERSON, C.  & JACKSON, S.J. (1982)  Cyhalothrin: Subacute dermal toxicity
 study in rabbits (Unpublished proprietary report No. CTL/P/680, submitted
to WHO by ICI).

HEXT, P.M., BRAMMER, A., CHALMERS, D.T., CHART, I.S., GORE, C.W., PATE, I.,
& BANHAM, P.B. (1986)  PP321: 1 year oral dosing study in dogs (Unpublished
proprietary report No. CTL/P/1316, submitted to WHO by ICI).

HILL, R.W.  (1981)  Determination of the acute toxicity of cyhalothrin
 (PP563) to Rainbow trout (Salmo gairdneri) (Unpublished proprietary report
No. BL/B/2097, submitted to WHO by ICI).

HILL, R.W.  (1984a)  PP321: Determination of acute toxicity to Rainbow trout
(Salmo gairdneri) (Unpublished proprietary report No. BL/B/2405, submitted
to WHO by ICI).

HILL, R.W.  (1984b)  PP321: Determination of acute toxicity to Bluegill
 sunfish (Lepomis macrochirus) (Unpublished proprietary report No.
BL/B/2406, submitted to WHO by ICI).

HILL, R.W.  (1985a)  PP321: Determination of acute toxicity to Rainbow trout
(Salmo gairdneri)  of 2.5% w/w formulation (Unpublished proprietary report
No. BL/B/2603, submitted to WHO by ICI).

HILL, R.W.  (1985b)  PP321: Determination of acute toxicity of a 1 lb/US
 gallon EC formulation to Rainbow trout (Salmo gairdneri) (Unpublished
proprietary report No. BL/B/2609, submitted to WHO by ICI).

HILL, R.W.  (1985c)  PP321: Determination of acute toxicity to Rainbow trout
(Salmo gairdneri)   of a 5% EC formulation (Unpublished proprietary report
No. BL/B/2783, submitted to WHO by ICI).

HILL, R.W.  (1985d)  PP321: Determination of acute toxicity to Mirror carp
(Cyprinus carpio)  of a 2.5% w/w formulation (Unpublished proprietary report
No. BL/B/2604, submitted to WHO by ICI).

HILL, R.W.  (1985e)  PP321: Determination of acute toxicity to Mirror carp
(Cyprinus carpio)   of a 5% EC formulation (Unpublished proprietary report
No. BL/B/2784, submitted to WHO by ICI).

HILL, R.W.  (1985f)  PP321: Determination of acute toxicity of a 1 lb/US
 gallon EC formulation to Bluegill sunfish (Lepomis macrochirus)
(Unpublished proprietary report No. BL/B/2610, submitted to WHO by ICI).

HILL, R.W.  (1985g)  PP321: Determination of acute toxicity to Sheepshead
 minnow (Cyprinodon variegatus) (Unpublished proprietary report No.
BL/B/2615, submitted to WHO by ICI).

HILL, R.W., CAUNTER, J.E., & CUMMING, R.I. (1985)  PP321: Determination of
 the chronic toxicity to Sheepshead minnow (Cyprinodon variegatus)  embryos
 and larvae (Unpublished proprietary report No. BL/B/2677, submitted to WHO
by ICI).

IRVINE, L.F.H.  (1981)  Cyhalothrin: Oral (gavage) dominant lethal study in
 the male mouse (Unpublished proprietary report of the Hazleton Laboratories
No. 2647-72/213, submitted to WHO by ICI).

JACKSON, S.J.  (1981)  Cyhalothrin: Eye irritation study in the rabbit
(Unpublished proprietary report No. CTL/T/1502, submitted to WHO by ICI).

JACKSON, S.J.  & NIXON, J. (1981) C yhalothrin: Skin irritation studies in
 the rabbit and rat (Unpublished proprietary report No.  CTL/T/1504,
submitted to WHO by ICI).

KILLICK, M.E.  (1981a)  Cyhalothrin: Oral (gavage) teratology study in the
 rat (Unpublished proprietary report of the Hazleton Laboratories No. 2661-
72/208, submitted to WHO by ICI).

KILLICK, M.E.  (1981b)  Cyhalothrin: Oral (gavage) teratology study in the
 New Zealand white rabbit (Unpublished proprietary report of the Hazleton
Laboratories No. 2700-72/211, submitted to WHO by ICI).

LAWRENCE, L.J.  & CASIDA, J.E.  (1982) Pyrethroid toxicology: Mouse
intracerebral structure-toxicity relationship.  Pestic.  Biochem. Physiol.,
18: 9-14.

LAWRENCE, L.J. & CASIDA, J.E.  (1983) Stereospecific action of pyrethroid
insecticides on the gamma-aminobutyric acid receptor-ionophore complex.
 Science, 221: 1399-1401.

LAWRENCE, L.J., GEE, K.W., & YAMAMURA, H.I.  (1985) Interactions of
pyrethroid insecticides with chloride ionophore-associated binding sites.
 Neurotoxicology, 6: 87-98.

LEAHEY, J.P.  (1985)  The pyrethroid insecticides, London, Taylor & Francis
Ltd, 440 pp.

LEAHEY, J.P.  & FRENCH, D.A. (1986a)  Quantification and characterisation of
 radioactive residues found in soya leaves from plants treated with 14 C-
 PP321 (Unpublished proprietary report No. RJ0507B, submitted to WHO by
ICI).

LEAHEY, J.P.  & FRENCH, D.A. (1986b)  Quantification and characterisation of
 radioactive residues found in cotton leaves from plants treated with 14 C-
 cyclopropane-labelled PP321 (Unpublished proprietary report No.  JR0526B,
submitted to WHO by ICI).

LEAHEY, J.P.  & FRENCH, D.A. (1986c)  Quantification and characterisation of
 radioactive residues in cotton leaves from plants treated 14 C-benzyl-
 labelled PP321 (Unpublished proprietary report No.  RJ0497B, submitted to
WHO by ICI).

LEAHEY, J.P.  & PARKER, S. (1985)  Cyhalothrin: Characterisation of residues
 accumulated by carp continuously exposed to 14 C-cyhalothrin (Unpublished
proprietary report No. RJ0407B, submitted to WHO by ICI).

LEAHEY, J.P., FRENCH, D.A., & HEATH, J. (1985)  PP321: Metabolism in a goat
(Unpublished proprietary Report No. RJ0435B, submitted to WHO by ICI).

LINDSAY, S., CHART, I.S., GODLEY, M.J., GORE, C.W., HALL, M., PRATT, I.,
ROBINSON, M., & STONARD, M. (1981)  Cyhalothrin: 90-day feeding study in
 rats (Unpublished proprietary report No. CTL/P/629, submitted to WHO by
ICI).

LINDSAY, S., DOE, J.E., GODLEY, M.J., HALL, M., PRATT, I., ROBINSON, M., &
STONARD, M.D. (1982)  Cyhalothrin induced liver changes: Reversibility study
 in male rats (Unpublished proprietary report No. CTL/P/668, submitted to
WHO by ICI).

LUND, A.E.  & NARAHASHI, T. (1983) Kinetics of sodium channel modification
as the basis for the variation in the nerve membrane effects of pyrethroids
and DDT analogs.  Pestic. Biochem. Physiol., 20: 203-216.

MILBURN, G.M., BANHAM, P., GODLEY, M.J., PIGOTT, G., & ROBINSON, M. (1984)
 Cyhalothrin: Three generation reproduction study in the rat (Unpublished
proprietary report No. CTL/P/906, submitted to WHO by ICI).

MILONE, M.F. (1986)  PP321: Unscheduled DNA synthesis in cultured Hela cells
 (autoradiographic method) (Unpublished proprietary report of the Institute
di Ricerche Biomediche Antione Marxer No. M914, submitted to WHO by ICI).

MIYAMOTO, J.  (1981) The chemistry, metabolism and residue analysis of
synthetic pyrethroids.  Pure appl. Chem., 53: 1967-2922.

MIYAMOTO, J.  & KEARNEY, P.C. (1983)  Pesticide chemistry-human welfare and
 the environment.  Proceedings of the Fifth International Congress on
 Pesticide Chemistry, Kyoto, Japan, 29 August-4 September, 1982, Oxford, New
York, Pergamon Press (Vol. 1-4).

NIXON, J.  & JACKSON, S.J. (1981a)  Cyhalothrin: Acute toxicity (Unpublished
proprietary report No. CTL/T/1555, submitted to WHO by ICI).

NIXON, J.  & JACKSON, S.J. (1981b)  Cyhalothrin: Skin sensitisation study in
 the guinea-pig (Unpublished proprietary report No. CTL/T/1552, submitted to
WHO by ICI).

PIGOTT, G.H., CHART, I.S., GODLEY, M.J., GORE, C.W., HOLLIS, K.J.,
ROBINSON, M., TAYLOR, K., & TINSTON, D.J. (1984)  Cyhalothrin: Two year
 feeding study in rats (Unpublished proprietary report No.  CTL/P/980,
submitted to WHO by ICI).

PRITCHARD, V.K.  (1984)  PP321: Skin sensitisation study (Unpublished
proprietary report No. CTL/P/1054, submitted to WHO by ICI).

PRITCHARD, V.K.  (1985a)  PP321 and cyhalothrin: skin irritation study
(Unpublished proprietary report No. CTL/P/1139, submitted to WHO by ICI).

PRITCHARD, V.K.  (1985b)  PP321: Eye irritation study (Unpublished
proprietary report No. CTL/P/1207, submitted to WHO by ICI).

PROUT, M.S.  (1984)  Cyhalothrin: Bioaccumulation in the rat (Unpublished
proprietary report No. CTL/P/1014, submitted to WHO by ICI).

PROUT, M.S.  & HOWARD, E.F. (1985)  PP321: Comparative absorption study in
 the rat (1 mg/kg) (Unpublished proprietary report No. CTL/P/1214, submitted
to WHO by ICI).

REYNOLDS, L.F.  (1984)  Cyhalothrin: Determination of acute toxicity to
 Bluegill sunfish (Lepomis machrochirus) (Unpublished proprietary report No.
BL/B/2514, submitted to WHO by ICI).

RICHOLD, M., ALLEN, J.A., WILLIAMS, A., & RANSOME, S.J.  (1981)  Cell
 transformation test for potential carcinogenicity of Y00102/010/005
 (cyhalothrin (PP563)) (Unpublished proprietary report of the Huntingdon
Research Centre No. 391(B)/80948, submitted to WHO by ICI).

ROBERTS, N.L.  & FAIRLEY, C. (1981)  The acute oral toxicity (LD50) of
 cyhalothrin to the Mallard duck (Unpublished proprietary report of the
Huntingdon Research Centre No. 373WL/801024, submitted to WHO by ICI).

ROBERTS, N.L.  & FAIRLEY, C. (1984)  The acute oral toxicity (LD50) of PP321
 to the Mallard duck (Unpublished proprietary report of the Huntingdon
Research Centre No. 438BT/831011, submitted to WHO by ICI).

ROBERTS, N.L., FAIRLEY, C., & WOODHOUSE, R.N. (1981a)  The subacute dietary
 toxicity (LC50 ) of cyhalothrin to the Mallard duck (Unpublished proprietary
report of the Huntingdon Research Centre No. 377WL/8120, submitted to WHO
by ICI).

ROBERTS, N.L., FAIRLEY, C., & WOODHOUSE, R.N. (1981b)  The subacute dietary
 toxicity (LC50 ) of cyhalothrin to the Bobwhite quail (Unpublished
proprietary report of the Huntingdon Research Centre No.  378WL/8179,
submitted to WHO by ICI).

ROBERTS, N.L., FAIRLEY, C., HAKIN, B., PRENTICE, D.E., & WIGHT, D.G.D.
(1982)  The acute oral toxicity (LD50 ) and neurotoxic effects of cyhalothrin
 to the domestic hen (Unpublished proprietary report of the Huntingdon
Research Centre No. ICI/374 NT/81742, submitted to WHO by ICI).

ROBERTS, N.L., FAIRLEY, C., ANDERSON, A., & DAWE, I.S. (1985a)  The subacute
 dietary toxicity of PP321 to the Mallard duck (Unpublished proprietary
report of the Huntingdon Research Centre No. ISN 46BT/85171, submitted to
WHO by ICI).

ROBERTS, N.L., FAIRLEY, C., ANDERSON, A., & DAWE, I.S. (1985b)  The subacute
 toxicity of PP321 to the Bobwhite quail (Unpublished proprietary report of
the Huntingdon Research Centre No. ISN 45BT/841287, submitted to WHO by
ICI).

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.

SAPIETS, A.  (1984a)  Cyhalothrin: Storage stability of the residue on deep
 frozen apple, cabbage and soil samples (Unpublished proprietary report No.
M3843B, submitted to WHO by ICI).

SAPIETS, A. (1984b)  The determination of residues of PP321 in crops. A gas-
 liquid chromatographic method using an internal standard (Unpublished
proprietary residue analytical method No. PPRAM 81, submitted to WHO by
ICI).

SAPIETS, A.  (1984c)  The determination of residues of cyhalothrin
 metabolites in crops. A gas-liquid chromatographic method (Unpublished
proprietary residue analytical method No. PPRAM 74, submitted to WHO by
ICI).

SAPIETS, A.  (1985a)  The determination of residues of cyhalothrin in crops.
 A gas-liquid chromatographic method using an internal standard (Unpublished
proprietary residue analytical method No. PPRAM 70, submitted to WHO by
ICI).

SAPIETS, A.  (1985b)  The determination of residues of cyhalothrin in water.
 A gas-liquid chromatographic method using an internal standard (Unpublished
proprietary residue analytical method No. PPRAM 69, submitted to WHO by
ICI).

SAPIETS, A.  (1985c)  PP321: Residue transfer study with dairy cows fed on a
 diet containing the insecticide  (Unpublished proprietary report No. M3936B,
submitted to WHO by ICI).

SAPIETS, A.  (1986a)  The determination of residues of PP321 in products of
 animal origin.  A GLC method using an internal standard (Unpublished
proprietary residue analytical method No. PPRAM 86/1, submitted to WHO by
ICI).

SAPIETS, A.  (1986b)  The determination of residues of PP321 in soil. A GLC
 method using an internal standard (Unpublished proprietary residue
analytical method No. PPRAM 93, submitted to WHO by ICI).

SAPIETS, A., SWAINE, H., & TANDY, M.J. (1984) In:  Zweig, G. & Sherma, J.,
 ed. Cypermethrin (Chapter 2).  Analytical methods for pesticides and plant
 growth regulators: Vol XIII, Synthetic pyrethroids and other pesticides,
New York, London, San Francisco, Academic Press.

SHELDON, T., RICHARDSON, C.R., SHAW, J., & BARBER, G. (1984)  An evaluation
 of PP321 in the mouse micronucleus test (Unpublished proprietary report No.
CTL/P/1090, submitted to WHO by ICI).

SHELDON, T., HOWARD, C.A., & RICHARDSON, C.R. (1985)  PP321: A cytogenetic
 study in human lymphocytes in vitro (Unpublished proprietary report No.
CTL/P/1333, submitted to WHO by ICI).

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

SOUTHWOOD, J.  (1984)  PP321: Acute oral toxicity to the mouse (Unpublished
proprietary report No. CTL/P/1066, submitted to WHO by ICI).

SOUTHWOOD, J. (1985)  PP321: Acute oral toxicity studies (Unpublished report
No. CTL/P/1102, submitted to WHO by ICI).

STEVENS, J.E.B.  & BEWICK, D.W. (1985)  PP563 and PP321: Leaching of PP563
 and PP321 and their degradation products in soil columns (Unpublished
proprietary report No. RJ0408B, submitted to WHO by ICI).

TAKEDA CHEMICAL CO. LTD (1979)  Test result of fish toxicity of PP-563
(Unpublished proprietary report, submitted to WHO by ICI).

THOMPSON, R.S.  (1985)  PP321: Determination of acute toxicity to Mysid
 shrimps (Mysidopsis bahia) (Unpublished proprietary report No. BL/B/2635,
submitted to WHO by ICI).

THOMPSON, R.S.  & WILLIAMS, T.D. (1985)  PP321: Toxicity to the green alga
Selenastrum capricornutum (Unpublished proprietary report No.  BL/B2584,
submitted to WHO by ICI).

TINSON, D.J., BANHAM, P.D., CHART, I.S., GORE, C.W., PRATT, I., SCALES,
M.D.C., & WEIGHT, T.M. (1984)  PP563: 28-day feeding study in rats. Summary
 report (Unpublished proprietary report No. CTL/P/1056, submitted to WHO by
ICI).

TRUEMAN, R.W.  (1981)  Cyhalothrin: Results from the Salmonella reverse
 mutation assay (Unpublished proprietary report No. CTL/P/665, submitted to
WHO by ICI).

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) Voltage clamp studies on
the effects of allethrin and DDT on the sodium channels in frog myelinated
nerve membrane.  In:  Insect neurobiology and pesticide action, London,
Society of Chemical Industry, pp. 79-85.

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, pp. 183-210.

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

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 the frog node of Ranvier.  Biochem.
 Biophys. Acta, 728: 73-82.

WHO (1979)  Safe use of pesticides. Third report of the WHO Expert Committee
 on Vector Biology and Control, Geneva, World Health Organization (WHO
Technical Report Series, No. 634).

WILLIAMS, T.D.  & THOMPSON, R.S. (1981)  Determination of the acute toxicity
 of cyhalothrin (PP563) to Daphnia magna (Unpublished proprietary report No.
BL/B/2114, submitted to WHO by ICI).

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

YAMAUCHI, F., SHIGEOKA, T., YAMAGATA, T., & SAITO, H.  (1984a)  PP563
 (cyhalothrin): Accumulation in fish (carp) in a flow-through water system
(Unpublished proprietary report of MITES No.  58-367, submitted to WHO by
ICI).

YAMAUCHI, F., SHIGEOKA, T., YAMAGATA, T., & SATO, Y.  (1984b)  PP563
 (cyhalothrin) formulation (5% WP): Acute toxicity to carp (Unpublished
proprietary report of MITES No. 58-367, submitted to WHO by ICI).

YAMAUCHI, F., SHIGEOKA, T., YAMAGATA, T., & SATO, Y.  (1984c)  PP563
 (cyhalothrin): Toxicity to daphnia and fish (carp) in the presence and
 absence of soil (Unpublished proprietary report of MITES No.  58-367,
submitted to WHO by ICI).

YAMAUCHI, F., SHIGEOKA, T., YAMAGATA, T., & SATO, Y.  (1984d)  PP563
 (cyhalothrin) formulation (5% WP): Acute toxicity to daphnia (Unpublished
proprietary report of MITES No. 58-367, submitted to WHO by ICI).

APPENDIX

    On the basis of electrophysiological studies with peripheral 
nerve preparations of frogs  (Xenopus laevis; Rana temporaria, and 
 Rana escuelenta), 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-phenoxybenzyl 
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 intermittently, cause large 
depolarizing after-potentials, 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-dependant 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 
cray-fish, 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-
butylbicyclophosphorothionate [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,alpha]-fenval-erate 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, alphaS]-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 receptor-
ionophore 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). 
 
RESUME, EVALUATION, CONCLUSIONS, ET RECOMMANDATIONS

1.  Résumé et évaluation

1.1 Identité, propriétés physiques et chimiques, méthodes d'analyse

    La cyhalothrine s'obtient en estérifiant l'acide (chloro-2 
trifluoro-3,3,3 propényl-1)-3 diméthyl-2,2 cyclopropanecarb-
oxylique, par l'alcool alpha-cyanophénoxy-3 benzylique et elle 
consiste en un mélange de quatre stéréoisomères formant deux paires 
d'énantiomères.  La lambda-cyhalothrine est l'une de ces paires 
d'énantiomères et constitue la forme la plus active biologiquement. 

    La cyhalothrine de qualité technique est un liquide visqueux 
d'un jaune brunâtre (point de fusion environ 10 °C) qui contient 
plus de 90% de matière active.  Elle est constituée de quatre 
isomères cis dans la proportion de 1:1:1:1.  Elle est insoluble 
dans l'eau mais soluble dans divers solvants organiques, en 
particulier les hydrocarbures aliphatiques et aromatiques.  Elle 
est stable à la lumière et à la chaleur et possède une faible 
tension de vapeur. 

    La lambda-cyhalothrine technique est un solide beige (point de 
fusion 49,2 °C) contenant plus de 90% de matière active.  Le 
rapport des énantiomères (Z) (1R, 3R) de l'ester S aux énantiomères 
(Z) (1S, 3S) de l'ester R est de 1:1.  Peu soluble dans l'eau, ce 
produit est soluble dans divers solvants organiques et possède une 
faible tension de vapeur. La cyhalothrine et la lambda-cyhalothrine 
sont rapidement hydrolysées en milieu alcalin mais ne subissent 
aucune hydrolyse en milieu neutre ou acide. 

    On dispose de méthodes confirmées pour la recherche et le 
dosage des résidus de cyhalothrine et de lambda-cyhalothrine ainsi 
que pour l'analyse des prélèvements effectués dans l'environnement 
(limite inférieure de détection: 0,005 mg/kg). 

1.2 Production et usage

    La cyhalothrine a été mise au point en 1977. On l'utilise 
principalement pour détruire diverses espèces nuisibles en santé 
publique et santé publique vétérinaire ainsi qu'en agriculture 
contre les ravageurs des fruits à pépins.  La lambda-cyhalothrine 
est utilisée essentiellement en agriculture pour la protection des 
récoltes les plus variées et fait actuellement l'objet d'une mise 
au point en vue d'être utilisée en santé publique. 

    On ne dispose d'aucune donnée sur les quantités produites. 

1.3 Exposition humaine

    Les résidus dans les produits alimentaires, par suite du 
traitement des récoltes par la cyhalothrine et la lambda-
cyhalothrine ainsi que de leur utilisation en médecine vétérinaire 
sont faibles, généralement inférieurs à 0,2 mg/kg.  On ignore quel 
est l'apport total d'origine alimentaire chez l'homme mais on peut 
supposer que l'exposition de la population générale par cette voie 
ne dépasse pas la DJA (0,02 mg/kg de poids corporel). 

1.4 Exposition et destinée dans l'environnement

    A la surface du sol et en solution aqueuse à pH 5, la lambda-
cyhalothrine se décompose sous l'effet du rayonnement solaire avec 
une demi-vie d'environ 30 jours.  Les principaux produits de 
décomposition sont l'acide (chloro-2 trifluoro-3,3,3 propényl-1)-3 
diméthyl-2,2 cyclopropanecarboxylique, l'amide correspondant et 
l'acide phénoxy-3 benzoïque. 

    Dans le sol, la dégradation s'effectue principalement par 
hydroxylation puis rupture de la liaison ester aboutissant à deux 
produits principaux dont la dégradation se poursuit jusqu'à 
obtention de dioxyde de carbone. La demi-vie initiale varie de 22 à 
82 jours. 

    La cyhalothrine et la lambda-cyhalothrine sont adsorbées sur 
les particules du sol et ne se déplacent pas dans l'environnement. 

    Sur les végétaux, la lambda-cyhalothrine se décompose à vitesse 
modérée (demi-vie allant jusqu'à 40 jours) de sorte que les résidus 
sont principalement constitués du composé initial.  On trouve 
également des métabolites en faibles quantités qui résultent d'un 
certain nombre de réactions d'hydrolyse et d'oxydation. 

    On ne dispose d'aucune donnée sur les quantités effectivement 
présentes dans l'environnement mais compte tenu du fait que ce 
produit est relativement peu utilisé et à doses réduites, ces 
quantités sont vraisemblablement faibles. 

1.5 Absorption, métabolisme, et excrétion

    Des études métaboliques ont été effectuées sur des rats, des 
chiens, des vaches et des chèvres. Chez les rats et les chiens, on 
a montré que la cyhalothrine administrée par voie orale était bien 
absorbée, fortement métabolisée, puis éliminée sous forme de 
conjugués polaires dans les urines.  Chez le rat, on a constaté que 
le taux de cyhalothrine tissulaire diminuait après cessation de 
l'exposition.  Dans les carcasses, les résidus étaient faibles 
(moins de 5% de la dose au bout de sept jours) et consistaient 
presque entièrement en cyhalothrine accumulée dans le tissu 
adipeux.  Les résidus présents dans les tissus adipeux étaient 
éliminés avec une demi-vie de 23 jours. 

    Après administration par voie orale de cyhalothrine à des 
vaches en lactation, on a constaté que le produit était rapidement 
éliminé et qu'un état d'équilibre s'établissait au bout de trois 
jours entre ingestion et élimination.  Vingt-sept pour cent de la 
dose étaient excrétés dans les urines, 50% dans les matières 
fécales et 0,8% dans le lait.  Les produits retrouvés dans les 
urines étaient entièrement constitués de métabolites résultant du 
clivage de l'ester et de leurs conjugués, alors que 60 à 70% des 
produits marqués au 14C retrouvés dans les matières fécales 
consistaient en cyhalothrine non métabolisée.  Les résidus 
tissulaires, mesurés 16 heures après l'administration de la 
dernière dose, étaient faibles, la concentration la plus élevée 

étant enregistrée dans le tissu adipeux. Les résidus marqués au 14C 
retrouvés dans le lait et les tissus adipeux étaient presque 
entièrement constitués de cyhalothrine non métabolisée, à 
l'exclusion de tout autre composé. 

    Chez toutes les espèces mammaliennes étudiées, on a constaté 
que la cyhalothrine subissait une forte métabolisation par clivage 
de l'ester en acide cyclopropanecarboxylique et acide phénoxy-3 
benzoïque et qu'elle était éliminée sous forme de conjugués. 

    Chez les poissons, les principaux résidus tissulaires 
consistent en cyhalothrine non métabolisée à côté de quantités plus 
faibles de produits résultant du clivage de l'ester. 

1.6 Effets sur les êtres vivants dans leur milieu naturel

    Dans les conditions du laboratoire où la concentration est 
constante, la cyhalothrine et la lambda-cyhalothrine se révèlent 
très toxiques pour les poissons et les invertébrés aquatiques. Les 
valeurs de la CL50 à 96 heures pour les poissons vont de 0,2 à 1,3 
µg/litre, la CL50 à 48 heures pour les invertébrés aquatiques se 
situant entre 0,008 et 0,04 µg/litre. 

    En étudiant au laboratoire l'accumulation de la cyhalothrine à 
concentration constante, on a observé une absorption rapide par les 
poissons (facteur d'accumulation d'environ 1000 à 2000).  Toutefois 
lorsqu'il y a un sol et des sédiments en suspension, on constate 
une forte réduction du facteur de bioaccumulation, qui passe à 19 
pour les poissons et à 194 pour les daphnies.  Lorsqu'on remet les 
poissons et les daphnies dans de l'eau propre, on constate une 
diminution rapide des résidus, avec une demi-vie respective de 7 et 
1 jours.  Il est vraisemblable qu'en utilisation agricole normale, 
la cyhalothrine et la lambda-cyhalothrine subsistent à faible 
concentration dans l'eau.  Etant donné que ces composés sont 
rapidement adsorbés et dégradés dans les conditions naturelles, il 
ne se pose en pratique aucun problème d'accumulation de résidus ni 
de toxicité vis-à-vis des espèces aquatiques. 

    La cyhalothrine et la lambda-cyhalothrine sont pratiquement 
inoffensives pour les oiseaux; la DL50 (dose unique) s'est révélée 
supérieure à 3950 mg/kg pour toutes les espèces étudiées et la CL50 
alimentaire à cinq jours la plus faible a été de 3948 mg/kg pour 
des canards sauvages de huit jours qui recevaient de la lambda-
cyhalothrine dans leur alimentation. 

    Dans les conditions du laboratoire, la cyhalothrine et la 
lambda-cyhalothrine sont toxiques pour les abeilles; la DL50 par 
voie orale est de 0,97 µg de lambda-cyhalothrine par abeille.  
Toutefois, le risque est probablement moins élevé en pratique étant 
donné que les formulations actuellement en usage exercent une 
action répulsive qui empêche les abeilles de butiner sur les 
récoltes traitées. Lorsque les abeilles se remettent à butiner, on 
ne constate pas d'augmentation importante de la mortalité. 

1.7 Effets sur les animaux d'expérience et les systèmes d'épreuve 
 in vitro 

    La toxicité aiguë par voie orale de la cyhalothrine est modérée 
chez les rats et les souris et faible chez les cobayes et les 
lapins (les valeurs de la DL50 sont les suivantes: rat, 144-243 
mg/kg; souris, 37-62 mg/kg; cobaye, plus de 5000 mg/kg; lapin, plus 
de 1000 mg/kg). La toxicité aiguë par voie orale de la lambda-
cyhalothrine est plus forte que celle de la cyhalothrine (les 
valeurs de la DL50 sont les suivantes: 56-79 mg/kg pour le rat et 
20 mg/kg pour la souris). Par voie dermique, on obtient les 
toxicités suivantes exprimées par la DL50: rat, 200-2000 mg/kg 
(cyhalothrine), 632-696 mg/kg (lambda-cyhalothrine); lapin, plus 
de 2000 mg/kg (cyhalothrine).  La cyhalothrine et la lambda-
cyhalothrine sont des pyréthroïdes du type II avec pour signes 
cliniques d'intoxication une ataxie, une démarche chancelante et 
une hyperexcitabilité. 

    Chez le lapin, la cyhalothrine est modérément irritante pour 
l'oeil et la lambda-cyhalothrine peu irritante; les deux composés 
sont légèrement irritants pour la peau. La cyhalothrine n'est pas 
irritante pour la peau chez le rat.  Toutefois elle provoque une 
sensibilisation cutanée modérée chez le cobaye.  La lambda-
cyhalothrine n'a pas d'action sensibilisatrice sur la peau. 

    Lors d'une étude d'alimentation de 90 jours au cours de 
laquelle des rats ont reçu de la cyhalothrine à des doses allant 
jusqu'à 250 mg/kg de nourriture, on a observé une réduction du gain 
de poids chez les mâles à la dose la plus forte.  Des effets 
marginaux sur la valeur moyenne de l'hématocrite ont été 
enregistrés chez certains des groupes traités ainsi que quelques 
modifications au niveau du foie que l'on a considérées comme 
résultant d'une réaction d'adaptation.  Lors d'une étude de 90 
jours au cours de laquelle des rats ont reçu dans leur alimentation 
de la lambda-cyhalothrine à des doses allant jusqu'à 250 mg/kg de 
nourriture, on a observé une réduction du gain de poids chez les 
deux sexes à la dose la plus forte. On a observé un certain nombre 
d'effets sur le chimisme sanguin ainsi que des effets hépatiques 
analogues à ceux qui avaient été observés avec la cyhalothrine.  La 
dose sans effet observable était de 50 mg/kg de nourriture. 

    Lors d'une étude de 26 semaines au cours de laquelle de la 
cyhalothrine a été administrée par voie orale à des chiens à des 
doses quotidiennes allant jusqu'à 10 mg/kg de poids corporel, on a 
observé des signes d'intoxication de type pyréthroïde à la dose la 
plus forte.  La dose sans effet observable se situait à 2,5 mg/kg 
de poids corporel. Une étude du même genre a été menée sur d'autres 
chiens avec administration pendant 52 semaines de 3,5 mg de lambda-
cyhalothrine par kg de poids corporel et par jour. Des signes 
cliniques d'intoxication de type pyréthroïde (signes neurologiques) 
ont été observés chez tous les ani-maux à la dose quotidienne de 
3,5 mg/kg de poids corporel. La dose sans effet observable se 
situait à 0,5 mg/kg de poids corporel par jour. 

    Lors d'une étude de toxicité cutanée de 21 jours pratiquée sur 
des lapins au moyen d'une solution de cyhalothrine dans le 
polyéthylène-glycol à des doses quotidiennes allant jusqu'à 1000 
mg/kg de poids corporel, on a constaté des signes cliniques 
d'intoxication chez certains des animaux à la dose la plus forte.  
Dans tous les groupes, y compris les témoins, on a observé une 
irritation cutanée légère à sévère. 

    Deux études toxicologiques de 104 semaines ont été consacrées à 
la cyhalothrine, l'une sur des rats et l'autre sur des souris.  
L'étude sur le rat n'a révélé aucun effet oncogène à des doses 
allant jusqu'à 250 mg/kg de nourriture (dose la plus forte 
étudiée).  La dose sans effet observable en ce qui concerne la 
toxicité générale était de 50 mg/kg de nourriture (1,8 mg/kg de 
poids corporel par jour).  On a relevé une diminution du gain de 
poids corporel chez les deux sexes à la dose de 250 mg/kg de 
nourriture.  Aucun effet oncogène n'a été observé chez la souris à 
des doses allant jusqu'à 500 mg/kg de nourriture (dose la plus 
forte étudiée).  Les signes cliniques d'une intoxication de type 
pyréthroïde ont été observés aux doses de 100 et 500 mg/kg de 
nourriture, avec réduction du gain de poids corporel à cette 
dernière dose. En ce qui concerne la toxicité générale, la dose 
sans effet observable était de 20 mg/kg de nourriture (1,9 mg/kg de 
poids corporel par jour). Aucun signe histologique de lésion du 
système nerveux n'a été observé dans l'une ou l'autre de ces deux 
études. 

    Lors d'une série d'épreuves  in vivo et  in vitro visant à 
déceler des mutations géniques, des lésions chromosomiques et 
autres effets génotoxiques, on n'a observé aucun effet de ce type 
imputable à la cyhalothrine ou à la lambda-cyhalothrine.  
Administrée par voie orale à des rats et à des lapins au cours de 
la période cruciale de l'organogénèse, la cyhalothrine ne s'est 
révélée ni embryotoxique ni tératogène à des doses quotidiennes qui 
étaient toxiques pour la mère (15 mg/kg pour les rats et 30 mg/kg 
pour les lapins, c'est-à-dire les deux doses les plus fortes 
étudiées). 

    Lors d'une étude de reproduction portant sur trois générations, 
des rats ont reçu de la cyhalothrine dans leur alimentation à des 
doses allant jusqu'à 100 mg/kg de nourriture.  A la dose de 100 
mg/kg de nourriture on a observé une légère diminution de la taille 
des portées et une réduction peu importante du gain de poids.  En 
ce qui concerne les effets sur la reproduction, la dose sans effet 
observable était de 30 mg/kg de nourriture. 

1.8 Effets sur l'homme

    Aucun cas d'intoxication accidentelle n'a été décrit.

    Des sensations subjectives au niveau de la face ont été 
ressenties lors de la fabrication, de la formulation, du travail de 
laboratoire et de l'utilisation sur le terrain.  Cet effet ne dure 
en général que quelques heures mais il arrive qu'il se prolonge 
jusqu'à 72 heures après l'exposition; l'examen médical n'a pas 
révélé d'anomalies neurologiques. 

    Ces sensations cutanées subjectives au niveau de la face, qui 
sont ressenties par les personnes qui manipulent de la cyhalothrine 
ou de la lambda-cyhalothrine sont, semble-t-il, provoquées par 
l'excitation répétée des terminaisons nerveuses de la peau.  On 
peut les considérer comme un signal d'alarme qui indique une 
surexposition de l'épiderme. 

    Rien n'indique que la cyhalothrine et la lambda-cyhalothrine 
puissent avoir des effets nocifs pour l'homme lorsqu'on les utilise 
dans les conditions et aux doses qui sont recommandées 
actuellement. 

2.  Conclusions

a)  Population générale: l'exposition de la population générale à la 
cyhalothrine et à la lambda-cyhalothrine est vraisemblablement très 
faible et ne présente probablement aucun danger lorsque ces 
produits sont utilisés conformément aux recommandations. 

b)  Exposition professionnelle: moyennant de bonnes méthodes de 
travail, des mesures d'hygiène et pour peu que l'on respecte les 
précautions nécessaires, la cyhalothrine et la lambda-cyhalothrine 
ne présentent vraisemblablement aucun danger pour les personnes 
exposées de par leur profession. 

c)  Environnement: il ne semble pas que la cyhalothrine, la lambda-
cyhalothrine ou leurs produits de dégradation puissent atteindre 
des concentrations nocives pour l'environnement lorsqu'elles sont 
utilisées aux doses recommandées.  Dans les conditions du 
laboratoire, la cyhalothrine et la lambda-cyhalothrine sont très 
toxiques pour les poissons, les arthropodes aquatiques et les 
abeilles.  Toutefois, en pratique, il ne semble pas qu'il puisse se 
produire d'effets nocifs durables, lorsque ces insecticides sont 
utilisés conformément aux recommandations. 

3.  Recommandations

    Lorsque ces insecticides sont utilisés conformément aux 
recommandations, leurs concentrations dans les denrées alimentaires 
doivent être très faibles, toutefois il serait bon de le confirmer 
en soumettant la cyhalothrine et la lambda-cyhalothrine à une 
surveillance. 

    La cyhalothrine et la lambda-cyhalothrine sont utilisées 
depuis des années et seuls des effets passagers ont été observés 
lors d'expositions professionnelles; toute-fois il faut continuer à 
surveiller l'exposition humaine. 
 
RESUMEN, EVALUACION, CONCLUSIONES Y RECOMENDACIONES

1.  Resumen y evaluación

1.1 Identidad, propiedades físicas y químicas, y métodos 
analíticos

    La cihalotrina se obtiene esterificando ácido 3-(2-cloro-3,3,3-
trifluoroprop-1-enil)-2,2-dimetilciclopropanocarboxílico con 
alcohol alpha-ciano-3-fenoxibencílico y se compone de una mezcla de 
cuatro estereoisómeros. La lambda-cihalotrina se compone de un par 
enantiomérico de isómeros y es la forma más activa biológicamente. 

    La cihalotrina de calidad técnica es un líquido viscoso, de 
color entre amarillo y marrón (punto de fusión: aproximadamente 10 
°C), que contiene más del 90% de material activo.  Está compuesta 
por cuatro isómeros cis en proporción 1:1:1:1.  Aunque es insoluble 
en el agua, es soluble en toda una gama de disolventes orgánicos 
como los hidrocarburos alifáticos y aromáticos. Es estable respecto 
de la luz y la temperatura y tiene una baja tensión de vapor. 

    La lambda-cihalotrina de calidad técnica es un sólido de color 
café con leche (punto de fusión: 49,2 °C) que contiene más del 90% 
de material activo. La razón enantiomérica del ( Z), (1R, 3R), S-
éster y el ( Z), (1S, 3S), R-éster es 1:1. Es apenas soluble en el 
agua pero es soluble en toda una gama de disolventes orgánicos y 
tiene una baja tensión de vapor.  Tanto la cihalotrina como la 
lambda-cihalotrina se hidrolizan rápidamente en medio alcalino pero 
no en medio neutro o ácido. 

    Existen métodos bien establecidos para analizar la cihalotrina 
y la lambda-cihalotrina presentes en residuos y en el medio 
ambiente (la concentración detectable mínima es 0,005 mg/kg). 

1.2 Producción y utilización

    La cihalotrina comenzó a producirse en 1977.  Se utiliza sobre 
todo para combatir múltiples plagas en salud pública y en 
veterinaria, pero también se emplea en agricultura contra las 
plagas que atacan a los pomos.  La lambda-cihalotrina se usa 
principalmente como plaguicida agrícola aplicable a muy diversos 
cultivos y se está preparando para emplearla en salud pública. 

    No se dispone de datos sobre los niveles de producción.

1.3 Exposición humana

    Los residuos presentes en los alimentos de resultas de la 
aplicación de cihalotrina y lamba-cihalotrina a los cultivos y en 
veterinaria son bajos, por lo general inferiores a 0,2 mg/kg.  No 
se dispone de datos sobre la ingesta total en la dieta humana, pero 
se puede suponer que la exposición dietética de la población 
general no supera la IDA (0,02 mg/kg de peso corporal). 

1.4 Exposición y transformación en el medio ambiente

    En la superficie del suelo y en soluciones acuosas con un pH de 
5, la lambda-cihalotrina se degrada a la luz del sol con una 
semivida de unos 30 días.  Los principales productos de esa 
degradación son ácido 3-(2-cloro-3,3,3-trifluoroprop-1-enil)-2,2- 
dimetilciclopropanocarboxílico, el derivado amídico de la 
cihalotrina, y ácido 3-fenoxibenzoico. 

    La degradación en el suelo se produce primordialmente por 
hidroxilación seguida de la ruptura del enlace éster para dar lugar 
a dos principales productos de degradación, que siguen degradándose 
hasta convertirse en bióxido de carbono.  Las semividas iniciales 
oscilan entre 22 y 82 días. 

    La cihalotrina y la lambda-cihalotrina se adsorben a las 
partículas del suelo y no son móviles en el medio ambiente. 

    En las plantas, la lambda-cihalotrina se degrada a un ritmo 
moderado (semivida de hasta 40 días), por lo que el principal 
elemento constituyente de los residuos que en ellas se encuentran 
es por lo común el compuesto inicial. Se hallan también niveles más 
bajos de metabolitos, resultantes de diversas reacciones 
hidrolíticas y oxidantes. 

    No se dispone de datos sobre los niveles efectivos en el medio 
ambiente, pero dadas la escasa utilización habitual en la 
actualidad y las reducidas tasas de aplicación, se supone que son 
bajos. 

1.5 Incorporación, metabolismo y excreción

    Se han realizado estudios metabólicos en la rata, el perro, la 
vaca y la cabra.  En la rata y el perro se ha demostrado que la 
cihalotrina administrada por vía oral se absorbe y se metaboliza 
bien y se elimina en la orina, en forma de conjugados polares.  En 
los tejidos de las ratas, disminuyó la concentración de cihalotrina 
al interrumpirse la exposición al compuesto.  En los cadáveres de 
las ratas se encontraron niveles reducidos de residuos (< 5% de la 
dosis a los siete días), que se debían casi totalmente a la 
cihalotrina contenida en las grasas.  Los restos presentes en las 
grasas se eliminaron con una semivida de 23 días. 

    La cihalotrina administrada por vía oral a vacas lactantes se 
eliminó rápidamente, alcanzándose un equilibrio entre la ingestión 
y la eliminación a los tres días.  De la dosis total, el 27% se 
excretó en la orina, el 50% en las heces, y el 0,8% en la leche.  
El material presente en la orina estaba compuesto exclusivamente 
por metabolitos de la disociación de los ésteres y por sus 
conjugados, mientras que del 60% al 70% del material fecal marcado 
con [14C] se identificó como cihalotrina no alterada.  Dieciséis 
horas después de la última dosis, los residuos tisulares eran 
bajos, hallándose las concentraciones más elevadas en las grasas.  

Los residuos marcados con [14C] presentes en la leche y los tejidos 
adiposos constaban casi enteramente de cihalotrina no alterada, y 
no se detectó ningún otro componente. 

    En todas las especies de mamíferos investigadas, se ha 
descubierto que la cihalotrina se metaboliza ampliamente de 
resultas de la ruptura del enlace éster para dar ácido 
ciclopropanocarboxílico y ácido 3-fenoxibenzoico, y se elimina en 
forma de conjugados. 

    En los peces, el principal residuo presente en los tejidos es 
cihalotrina no alterada y hay niveles más bajos de los productos de 
la ruptura del éster. 

1.6 Efectos en los organismos del medio ambiente

    En condiciones de laboratorio con concentraciones tóxicas 
constantes, la cihalotrina y la lambda-cihalotrina son muy tóxicas 
para los peces y los invertebrados acuáticos. El valor de las CL50 
a las 96 horas para los peces oscila entre 0,2 y 1,3 µg/litro, 
mientras que en el caso de los invertebrados acuáticos los valores 
de la CL50 a las 48 horas van de 0,008 a 0,4 µg/litro. 

    Los estudios sobre la acumulación realizados en condiciones de 
laboratorio con concentraciones constantes indican que, en los 
peces, tiene lugar una rápida incorporación (factor de acumulación 
aproximado de 1000 a 2000). No obstante, en presencia de suelo y 
sedimentos en suspensión, los factores de bioacumulación quedan muy 
reducidos (a 19 en el caso de los peces y a 194 en el caso de los 
dáfnidos).  Cuando se colocó en agua limpia a los peces y dáfnidos 
expuestos, los residuos disminuyeron rápidamente, con semividas de 
siete días y un día, respectivamente. Las concentraciones de 
cihalotrina y lambda-cihalotrina que pueden hallarse en el agua de 
resultas de su aplicación normal con fines agrícolas serán bajas.  
Como el compuesto se adsorbe y se degrada rápidamente en 
condiciones naturales, la acumulación de residuos o la toxicidad de 
la cihalotrina y la lambda-cihalotrina para las especies acuáticas 
no plantearán problemas prácticos. 

    La cihalotrina y la lambda-cihalotrina son prácticamente 
inocuas para las aves; en todas las especies sometidas a prueba la 
DL50 con una dosis única fue superior a 3950 mg/kg y la CL50 
dietética más baja en cinco días fue de 3948 mg/kg (lambda-
cihalotrina administrada en el alimento a patos silvestres de ocho 
días de edad). 

    En condiciones de laboratorio, la cihalotrina y la lambda-
cihalotrina son tóxicas para la abeja; la DL50 de la lambda-
cihalotrina por vía oral es de 0,97 µg/abeja. No obstante, en la 
práctica, el riesgo es menor puesto que las formas actualmente 
utilizadas tienen un efecto repelente que hace que las abejas 
suspendan las actividades de búsqueda en los cultivos tratados.  
Cuando éstas vuelven a emprenderse, no hay un aumento significativo 
de la mortalidad de las abejas. 

1.7 Efectos en animales de experimentación y en sistemas de
prueba  in vitro 

    La toxicidad aguda de la cihalotrina administrada por vía oral 
es moderada para las ratas y los ratones y baja para las cobayas y 
los conejos (los valores de la DL50 son los siguientes: rata: 144-
243 mg/kg; ratón: 37-62 mg/kg; cobaya: > 5000 mg/kg; conejo: > 
1000 mg/kg).  La toxicidad aguda de la lambda-cihalotrina por vía 
oral es mayor que la de la cihalotrina (los valores de la DL50 son: 
56-79 mg/kg para la rata y 20 mg/kg para el ratón). La toxicidad 
por vía cutánea (DL50) alcanza los siguientes valores: rata: 200-
2000 mg/kg (cihalotrina), 632-696 mg/kg (lambda-cihalotrina); 
conejo: > 2000 mg/kg (cihalotrina).  La cihalotrina y la lambda-
cihalotrina son piretroides de tipo II; entre los signos clínicos 
figuran la ataxia, el andar vacilante y la hiperexcitabilidad. 

    En el conejo, la cihalotrina es un irritante ocular moderado y 
la lambda-cihalotrina un irritante ocular leve; ambos irritan 
levemente la piel.  La cihalotrina no irrita la piel de la rata. 
Sin embargo, sensibiliza moderadamente la piel de la cobaya. La 
lambda-cihalotrina no sensibiliza la piel. 

    En un estudio de alimentación de 90 días en el que se 
administró cihalotrina a ratas en dosis de hasta 250 mg/kg de 
alimento, se observó una disminución del aumento del peso corporal 
en los machos con la dosis de 250 mg.  En algunos de los grupos 
tratados, se señalaron efectos marginales en los volúmenes medios 
de eritrocitos, así como ciertas alteraciones hepáticas, que se 
consideraron una respuesta adaptativa.  En otro estudio de 
alimentación de 90 días, en el que se administró lambda-cihalotrina 
a ratas en dosis de hasta 250 mg/kg de alimento, se observó en 
ambos sexos una reducción del aumento del peso corporal con la 
dosis de 250 mg.  Se señalaron también algunos efectos en la 
química clínica, así como efectos hepáticos análogos a los 
observados con la cihalotrina.  El nivel sin efecto observado fue 
de 50 mg/kg de alimento. 

    En un estudio de 26 semanas en el que se administraron a perros 
por vía oral dosis diarias de cihalotrina de hasta 10 mg/kg de peso 
corporal, se observaron signos de toxicidad por piretroides con la 
dosis de 10 mg.  El nivel sin efecto observado fue de 2,5 mg/kg de 
peso corporal al día.  Se realizó otro estudio similar en el que se 
administraron a perros, durante 52 semanas, dosis diarias de 
lambda-cihalotrina de hasta 3,5 mg/kg de peso corporal. En todos 
los animales que recibieron la dosis de 3,5 mg se observaron signos 
clínicos de toxicidad por piretroides (signos neurológicos).  El 
nivel sin efecto observado fue de 0,5 mg/kg de peso corporal al 
día. 

    En un estudio cutáneo de 21 días con conejos a los que se 
aplicó cihalotrina en polietilénglicol en dosis diarias de hasta 
1000 mg/kg, se observaron en algunos animales signos clínicos de 
toxicidad con la dosis más alta.  En todos los grupos, incluidos 
los testigos, se señaló irritación de la piel de leve a grave. 

    Se realizaron dos estudios de alimentación de 104 semanas con 
cihalotrina, uno con ratas y otro con ratones. En el estudio con 
ratas, no se observaron efectos oncogénicos con dosis de hasta 250 
mg/kg de alimento (la dosis más alta ensayada).  En cuanto a la 
toxicidad sistémica, el nivel sin efecto observado fue de 50 mg/kg 
de alimento (1,8 mg/kg de peso corporal al día).  Con dosis de 250 
mg se señaló en ambos sexos una disminución del aumento del peso 
corporal. En el estudio con ratones, no se observaron efectos 
oncogénicos con dosis de hasta 500 mg/kg de alimento (la dosis más 
alta ensayada).  Con dosis de 100 y 500 mg/kg de alimento se 
apreciaron signos clínicos de toxicidad por piretroides y, con 
dosis de 500 mg, una disminución del aumento del peso corporal.  En 
cuanto a la toxicidad sistémica, el nivel sin efecto observado fue 
de 20 mg/kg de alimento (1,9 mg/kg de peso corporal al día). En 
ninguno de los dos estudios se obtuvieron datos histológicos que 
indicaran la presencia de lesiones del sistema nervioso. 

    En una serie de pruebas  in vivo e  in vitro destinadas a 
detectar mutaciones génicas, lesiones cromosómicas y otros efectos 
genotóxicos, se obtuvieron resultados negativos con la cihalotrina 
y la lambda-cihalotrina.  La cihalotrina administrada por vía oral 
a ratas y conejos durante el periodo de organogénesis principal no 
resultó embriotóxica ni teratogénica en dosis que provocaron 
reacciones tóxicas en las madres (15 mg/kg diarios para las ratas y 
30 mg/kg diarios para los conejos, en ambos casos los niveles más 
altos ensayados). 

    Se realizó un estudio sobre la reproducción en tres 
generaciones de ratas a las que se administró cihalotrina en dosis 
de hasta 100 mg/kg de alimento.  Con la dosis de 100 mg se 
observaron pequeñas reducciones del tamaño de las camadas y del 
aumento de peso.  En los aspectos relacionados con la reproducción, 
el nivel sin efecto observado fue de 30 mg/kg de alimento. 

1.8 Efectos en el ser humano

    No se ha descrito ningún caso de intoxicación accidental. 

    En las actividades de fabricación, formulación y laboratorio y 
durante el uso sobre el terreno, se han notificado sensaciones 
faciales subjetivas.  Este efecto sólo suele durar unas horas, pero 
ocasionalmente persiste hasta 72 horas después de la exposición; el 
examen médico no ha revelado ninguna anomalía neurológica. 

    Se cree que las sensaciones cutáneas faciales subjetivas que 
pueden experimentar las personas que manipulan cihalotrina y 
lambda-cihalotrina se deben a la repetida estimulación de las 
terminaciones nerviosas de la piel. Pueden considerarse una señal 
de alerta que indica que la piel ha sufrido una exposición 
excesiva. 

    No hay ninguna indicación de que la cihalotrina y la lambda-
cihalotrina, utilizadas en las condiciones y con arreglo a las 
tasas de aplicación actualmente recomendadas, tengan efectos 
adversos en los seres humanos. 

2.  Conclusiones

(a)  Población general: Se cree que la exposición de la población 
general a la cihalotrina y la lambda-cihalotrina es muy baja y que 
no es probable que represente un riesgo en las condiciones de uso 
recomendadas. 

(b)  Exposición ocupacional: Con prácticas de trabajo, medidas de 
higiene y precauciones de seguridad adecuadas, es poco probable que 
la cihalotrina y la lambda-cihalotrina representen un riesgo para 
las personas ocupacionalmente expuestas. 

(c)  Medio ambiente: No es probable que la cihalotrina y la lambda-
cihalotrina o los productos de su degradación alcancen niveles 
ambientales que puedan producir efectos adversos, si se respetan 
las tasas de aplicación recomendadas.  En condiciones de 
laboratorio, la cihalotrina y la lambda-cihalotrina son muy tóxicas 
para los peces, los artrópodos acuáticos y las abejas.  No 
obstante, en la práctica, no es probable que se produzcan efectos 
adversos duraderos en las condiciones de uso recomendadas. 

3.  Recomendaciones

    Aunque se cree que los niveles dietéticos según el uso 
recomendado son muy bajos, debe considerarse la posibilidad de 
confirmar este extremo incluyendo la cihalotrina y la lambda-
cihalotrina en estudios de vigilancia. 

    Pese a que ambas sustancias se llevan utilizando varios años y 
a que los efectos observados de la exposición ocupacional sólo han 
sido transitorios, debe continuar la observación de la exposición 
humana. 



See Also:
        Cyhalothrin (UK PID)
        Lambda-cyhalothrin (UK PID)