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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY



    ENVIRONMENTAL HEALTH CRITERIA 142





    ALPHA - CYPERMETHRIN








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

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

    First draft prepared by Dr E.A.H. van
    Heemstra-Lequin and Dr G.T. van Esch,
    Netherlands

    World Health Orgnization
    Geneva, 1992


         The International Programme on Chemical Safety (IPCS) is a
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    WHO Library Cataloguing in Publication Data

    Alpha-cypermethrin.

        (Environmental health criteria ; 142)

        1.Environmental exposure 2.Pyrethrins - adverse effects 
        3.Pyrethrins - toxicity       I.Series

        ISBN 92 4 157142 X        (NLM Classification: WA 240)
        ISSN 0250-863X

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    CONTENTS

    ENVIRONMENTAL HEALTH CRITERIA FOR ALPHA-CYPERMETHRIN

    INTRODUCTION

    1. SUMMARY AND EVALUATION; CONCLUSIONS AND RECOMMENDATIONS

         1.1. Summary and evaluation
                1.1.1. Identity, use, environmental fate and
                        environmental levels
                1.1.2. Kinetics and metabolism
                1.1.3. Effects on laboratory mammals and
                         in vitro test systems
                1.1.4. Effects on humans
                1.1.5. Effects on other organisms in the
                        laboratory and field
         1.2. Conclusions
                1.2.1. General population
                1.2.2. Occupational exposure
                1.2.3. Environment
         1.3. Recommendations

    2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
         METHODS

         2.1. Identity
                2.1.1. Primary constituent
                2.1.2. Technical product
         2.2. Physical and chemical properties
         2.3. Formulations
         2.4. Conversion factors
         2.5. Analytical methods
                2.5.1. Sampling
                        2.5.1.1   Air
                        2.5.1.2   Surface-wipe
                2.5.2. Methods for determination

    3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

         3.1. Natural occurrence
         3.2. Anthropogenic sources
                3.2.1. Production levels and processes
                3.2.2. Use

    4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION

         4.1. Transport and distribution between media
                4.1.1. Air
                4.1.2. Water
                4.1.3. Soil

         4.2. Biotransformation
                4.2.1. Biodegradation
                4.2.2. Bioaccumulation

    5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

         5.1. Environmental levels
                5.1.1. Soil
         5.2. Food
                5.2.1. Crops
                5.2.2. Fish
                5.2.3. Milk
         5.3. Human exposure

    6. KINETICS AND METABOLISM

         6.1. Absorption, elimination, retention and turnover
                6.1.1. Rats
                6.1.2. Domestic animals
                6.1.3. Humans
         6.2. Metabolic transformation
         6.3.  In vitro metabolic transformation
         6.4. Plants

    7. EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

         7.1. Single exposure
                7.1.1. Oral (technical product)
                7.1.2. Oral (formulations)
                7.1.3. Dermal
                7.1.4. Inhalation
                7.1.5. Other routes
         7.2. Short-term exposure
                7.2.1. Oral
                        7.2.1.1   Rat
                        7.2.1.2   Dog
         7.3. Skin and eye irritation; sensitization
                7.3.1. Skin irritation
                7.3.2. Eye irritation
                7.3.3. Sensitization
         7.4. Long-term and carcinogenicity studies
         7.5. Reproduction, embryotoxicity and teratogenicity
         7.6. Mutagenicity and related end-points
                7.6.1. Mutation
                7.6.2. Chromosomal effects
                7.6.3. DNA damage
                7.6.4. Conclusion
         7.7. Special studies
                7.7.1. Skin sensation
                7.7.2. Neurotoxicity
                7.7.3. Immunosuppressive action

         7.8. Mechanism of toxicity - mode of action

    8. EFFECTS ON HUMANS

         8.1. General population exposure
         8.2. Occupational exposure

    9. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

         9.1. Microorganisms
                9.1.1. Algae
                9.1.2. Bacteria
         9.2. Aquatic organisms
                9.2.1. Invertebrates
                        9.2.1.1   Laboratory studies
                        9.2.1.2   Field studies
                9.2.2. Fish
                        9.2.2.1   Laboratory studies
                        9.2.2.2   Small scale field or outdoor tank
                                  studies
         9.3. Terrestrial organisms
                9.3.1. Earthworms
                9.3.2. Invertebrates - field studies
                9.3.3. Honey-bees
                        9.3.3.1   Laboratory studies
                        9.3.3.2   Field studies
                9.3.4. Leaf-cutting bees
                9.3.5. Birds

    10. COMPARISON BETWEEN ALPHA-CYPERMETHRIN AND CYPERMETHRIN

         10.1. Use and residue levels
         10.2. Environmental impact
         10.3. Mammalian toxicity

    11. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    REFERENCES

    APPENDIX I

    RESUME ET EVALUATION; CONCLUSIONS ET RECOMMANDATIONS

    RESUMEN Y EVALUACION; CONCLUSIONES Y RECOMENDACIONES

    WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ALPHA-CYPERMETHRIN

     Members

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

    Dr R. Drew, Key Centre for Toxicology, Department of Applied Biology,
         Royal Melbourne Institute for Technology, Melbourne, Australia
          (Chairman)

    Dr S.K. Kashyap, National Institute of Occupational Health, Meghani
         Nagar, Ahmedabad, India

    Dr J.I. Kundiev, Research Institute of Labour, Hygiene and
         Occupational Diseases, Ul. Saksaganskogo, Kiev, USSR
          (Vice-Chairman)

    Dr K. Mitsumori, Division of Pathology, Biological Safety Research
         Center, National Institute of Hygienic Sciences, Setagaya-ku,
         Tokyo, Japan

    Dr R.F. Shore, Ecotoxicology and Pollution Section, Institute of
         Terrestrial Ecology, Monks Wood Experimental Station, Abbots
         Ripton, Huntingdon, Cambridgeshire, United Kingdom

    Dr G.J. van Esch, Bilthoven, Netherlands  (Joint Rapporteur)

    Dr E.A.H. van Heemstra-Lequin, Laren, Netherlands  (Joint Rapporteur)

    Dr S. Wong, Bureau of Chemical Hazards, Environmental Health
         Directorate, Department of National Health and Welfare, Tunney's
         Pasture, Ottawa, Ontario, Canada

     Observers

    Dr W.H. Gross, Fraunhofer Institute of Toxicology and  Aerosol
         Research, Hanover, Germany

    Dr J.R. Kielhorn, Fraunhofer Institute of Toxicology and Aerosol
         Research, Hanover, Germany

    Dr C.M. Melber, Fraunhofer Institute of Toxicology and Aerosol
         Research, Hanover, Germany

    Dr D.E. Owen, Shell Internationale Petroleum Maatschappij BV, The
         Hague, Netherlands

     Secretariat

    Dr R.F. Hertel, Fraunhofer Institute of Toxicology and Aerosol
         Research, Hanover, Germany

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

    Mrs C. Partensky, Unit of Carcinogen Identification and Evaluation,
         International Agency for Research on Cancer, Lyon, France

    NOTE TO READERS OF THE CRITERIA MONOGRAPHS

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


                           *     *     *


         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 monograph 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 ALPHA-CYPERMETHRIN

         A WHO Task Group on Environmental Health Criteria for
    Alpha-cypermethrin met at the Fraunhofer Institute of Toxicology and
    Aerosol Research, Hanover, Germany, from 16 to 20 September 1990, and
    was sponsored by the German Ministry of the Environment.  Dr R.F.
    Hertel welcomed the participants on behalf of the host institute.  Dr
    K.W. Jager, IPCS, welcomed the participants on behalf of Dr M.
    Mercier, Director of the IPCS, and the three IPCS cooperating
    organizations (UNEP/ILO/WHO).  The Group reviewed and revised the
    draft document and made an evaluation of the risks for human health
    and the environment from exposure to alpha-cypermethrin

         The first draft was prepared by Dr E.A.H. van Heemstra-Lequin and
    Dr G.J. van Esch of the Netherlands.  Dr van Esch prepared the second
    draft, incorporating the 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.

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

                                  *   *   *


         Partial financial support for the publication of this monograph
    was kindly provided by the United States Department of Health and
    Human Services through a contract from the National Institute of
    Environmental Health Sciences, Research Triangle Park, North Carolina,
    USA - a WHO Collaborating Centre for Environmental Health Effects.

    ABBREVIATIONS

    CPA       cyclopropane carboxylic acid

    EC        emulsifiable concentrate

    EEC       European Economic Community

    GC        gas chromatography

    MRL       maximum residue level

    MS        mass spectrophotometry

    NOEL      no-observed-effect level

    OECD      Organisation for Economic Co-operation and Development

    OSC       oil-enhanced suspension concentrate

    PBA       phenoxybenzoic acid

    SC        suspension concentrate

    ULV       ultra-low volume

    WP        wettable powder

    INTRODUCTION

         Cypermethrin (alpha-cyano-3-phenoxybenzyl-3-(2,2-dichloro-vinyl)
    -2,2-dimethylcyclopropanecarboxylate) is a racemic mixture of eight
    isomers. These eight isomers consist of two groups, those with a cis
    orientation across the cyclopropyl ring of the dichlorovinyl and ester
    groups and those with a trans orientation.

         Alpha-cypermethrin is a mixture of two of the four cis isomers
    present to approximately 25% in cypermethrin, i.e. the (1R, cis)S and
    the (1S, cis)R isomers. The structure of the eight isomers is
    summarized in Fig. 1.

         In this monograph the toxicological information specifically
    related to alpha-cypermethrin is summarized and compared with the data
    on cypermethrin. An evaluation of the full data on cypermethrin, which
    is also relevant for alpha-cypermethrin, is given in Environmental
    Health Criteria 82: Cypermethrin (WHO, 1989). The summary, evaluation,
    conclusions and recommendations of that monograph are added here as
    Appendix I.

    1.  SUMMARY AND EVALUATION; CONCLUSIONS AND RECOMMENDATIONS

    1.1  Summary and evaluation

    1.1.1  Identity, use, environmental fate and environmental levels

         Alpha-cypermethrin contains more than 90% of the insecticidally
    most active enantiomer pair of the four cis isomers of cypermethrin as
    a racemic mixture.

         It is a highly active pyrethroid insecticide, effective against
    a wide range of pests encountered in agriculture and animal husbandry.
    It is supplied as emulsifiable concentrate, ultra-low-volume
    formulation, suspension concentrate and in mixtures with other
    insecticides.

         The technical product is a crystalline powder with good
    solubility in acetone, cyclohexanone and xylene, but its solubility in
    water is low. It is stable under acidic and neutral conditions but
    hydrolyses at pH 12-13. It decomposes above 220 °C.

         No information on levels of alpha-cypermethrin in air is
    available.

         In water, alpha-cypermethrin is likely to be degraded by
    photochemical and biological processes. Surface and sub-surface water
    in a pond oversprayed with 15 g/ha active ingredient contained 5% and
    19% of the applied dose one day after spraying and 0.1% and 2% of the
    applied dose seven days later. About 5% of the applied dose was
    present in sediment 16 days after application.

         Alpha-cypermethrin is likely to be absorbed strongly onto soil
    particles. Residues in soil were below 0.1 mg/kg one year after
    treatment with 0.5 kg active ingredient per ha.

         The  n-octanol/water partition coefficient of alpha-cypermethrin
    is 1.4 x 105 (log Pow = 5.16).

         The recommended application rates of alpha-cypermethrin are lower
    than those of cypermethrin because the former is biologically more
    active. As a result, residues on crops are low, and following the use
    of recommended application rates the residues in crops are between
    0.05 and 1 mg/kg. Residues in marine catfish treated at between 0.001
    and 0.05% w/w active ingredient were 0.3-30 mg/kg one week after
    storage and 0.22-4.0 mg/kg after 15 weeks of storage.

    1.1.2  Kinetics and metabolism

         Alpha-cypermethrin administered orally to rats is eliminated, in
    the urine, as the sulfate conjugate of 3-(4-hydroxyphenoxy) benzoic
    acid and, in the faeces, partly as unchanged compound. Approximately

    90% of a single oral dose is eliminated from the body over a 4-day
    period, 78% within the first day. Residues in tissues are low except
    in fat tissue. The concentration in fat 3 days after a single oral
    dose of 2 mg/kg was 0.4 mg/kg. Elimination from the fat is biphasic;
    the half-life for the initial phase is 2.5 days and for the second
    phase 17-26 days.

         Alpha-cypermethrin is metabolized by cleavage of its ester bond.
    In the rat, the phenoxybenzyl alcohol portion of the molecule is
    hydroxylated and conjugated with sulfate; the cyclopropane carboxylic
    acid portion is also conjugated (probably as a glucuronide) prior to
    urinary excretion. Studies with liver microsomes from rats, rabbits
    and man have demonstrated that esteric hydrolysis and oxidative
    pathways can occur in all three species but esteric hydrolysis is the
    more prominent pathway for liver preparations from rabbit and man.

         In humans, 43% of an oral dose (0.25-0.75 mg) was excreted within
    24 h in the urine as free or conjugated  cis-cyclopropane carboxylic
    acid. The urinary excretion was not increased after five successive
    daily doses.

         High concentrations (up to 1156 mg/kg) of alpha-cypermethrin were
    found in the wool of sheep 14 days after the application of a dip or
    pour-on formulation. Low levels were found in subcutaneous fat (up to
    0.04 mg/kg). After treating calves along the mid-dorsal line with 10
    ml of a 1.6% formulation, no alpha-cypermethrin was found in muscle
    and liver. The maximum concentration in perirenal fat over a 14-day
    period was 0.26 mg/kg.

         After treating lactating cows along the mid-dorsal line with up
    to 0.2 g active ingredient, alpha-cypermethrin residues of 0.003 to
    0.005 mg/litre were found in the milk from 3 out of 15 treated
    animals.

    1.1.3  Effects on laboratory mammals and  in vitro test systems

         Alpha-cypermethrin has moderate to high acute oral toxicity to
    rodents. The LD50 values in mice and rats are highly variable and
    depend on the concentration of the compound and vehicle. For practical
    purposes an LD50 value of 80 mg/kg body weight is considered
    representative. However, some reported acute oral LD50 values are
    higher. Acute oral exposure results in clinical signs associated with
    central nervous system activity.

         Single dermal applications of alpha-cypermethrin to mice and rats
    at 100 and 500 mg/kg body weight, respectively, did not cause
    mortality or signs of intoxication. Similarly, a 4-h inhalation
    exposure of rats to an atmospheric concentration of 400 mg/m3 did
    not result in mortality or clinical signs.

         Technical alpha-cypermethrin has been reported to be minimally
    irritating to rabbit skin. Some alpha-cypermethrin formulations cause
    severe eye irritation. Technical alpha-cypermethrin is not a skin
    sensitizer. In guinea-pigs, alpha-cypermethrin caused stimulation of
    sensory nerve-endings in the skin.

         Short-term exposure of rats to alpha-cypermethrin at
    concentrations up to 200 mg/kg diet per day for 5 weeks or up to 180
    mg/kg diet per day for 13 weeks did not cause toxic effects. At higher
    dose levels, rats exhibited signs of intoxication associated with
    pathology of the nervous system, decreased growth, or increased liver
    and kidney weights. No clear haematological, clinical chemistry or
    histopathological effects were evident.

         In a 13-week oral dog study, the highest dose of 270 mg/kg diet
    caused signs of intoxication, but all other parameters examined
    (including haematology, clinical chemistry, urinalysis, organ weights,
    gross pathology and histopathology) were unaffected. The
    no-observed-effect level (NOEL) was 90 mg/kg diet (equivalent to 2.25
    mg/kg body weight per day).

         An oral study in rats demonstrated that alpha-cypermethrin
    induces neurotoxicity due to histopathological alterations of the
    tibial and sciatic nerves, axonal degeneration and increased
    beta-galactosidase activity.

         No data are available on long-term toxicity, reproductive
    toxicity, teratogenicity or immunotoxicity.

         From the available data on alpha-cypermethrin, it can be
    concluded that this compound is non-mutagenic in tests with
     Salmonella typhimurium, Escherichia coli and  Saccharomyces 
    cerevisiae, and  in vivo and  in vitro tests with rat liver cells
    for the induction of chromosome aberration and production of DNA
    single-strand damage. No increase in chromosomal aberrations was seen
    in rat bone marrow cells. 

         No data are available on the carcinogenicity of alpha-
    cypermethrin.

    1.1.4  Effects on humans

         Exposure of the general population to alpha-cypermethrin is
    negligible, provided its use follows good agricultural practice.
    Occupational dermal exposure in operators during mixing/loading,
    during spraying and washing of the equipment was found to be up to
    2.94 mg, 0.61 mg and 0.73 mg, respectively.

         In a study of exposure to alpha-cypermethrin during formulation,
    exposure levels were assessed by personal and static monitoring of
    atmospheric concentrations and measurement of urinary

    alpha-cypermethrin metabolites. The group mean personal exposure
    levels on the two days while formulating technical concentrates were
    2.8 and 4.9 mg/m3, whereas the group mean personal exposure to
    technical material on day 3 was 54.1 mg/m3. No metabolites could be
    detected in urine (limit of detection, 0.02 mg/litre). During
    formulation, skin sensations were reported but these were only mild.

         No poisoning incidents have been reported.

    1.1.5  Effects on other organisms in the laboratory and field

         The 48 and 96-h EC50 (growth) value for the freshwater alga
    Selenastrum capricornutum is above 100 µg/litre.

         Alpha-cypermethrin is highly toxic to aquatic invertebrates. The
    24- and 48-h EC50 (immobilization) values for  Daphnia magna are
    1.0 and 0.3 µg/litre, respectively, and the 24-h LC50 value for
     Gammarus pulex is 0.05 µg/litre. Alpha-cypermethrin is highly toxic
    to a number of aquatic arthropod taxa, but is of lower toxicity to
    molluscs. The short-term toxicity of the compound can be reduced by
    formulation of the product as an oil-enhanced suspension. Although
    spray drift may result in toxic effects on aquatic invertebrates, the
    rapid loss of alpha-cypermethrin from the water gives potential for
    recovery.

         Alpha-cypermethrin is highly toxic to fish. The 96-h LC50
    values range between 0.7 and 350 µg/litre depending upon the
    formulation. Emulsifiable concentrate formulations are much more toxic
    than suspension concentrate, wettable powder and micro-encapsulated
    formulations. The hazard of alpha-cypermethrin to aquatic
    invertebrates and fish lies in its acute toxicity. There is no
    evidence for the occurrence of cumulative effects as a result of
    long-term exposure.

         No data are available concerning the effects of alpha-
    cypermethrin on soil microbes. Sewage bacteria were not affected by a
    concentration of 3 mg/litre in a closed system.

         The toxicity of alpha-cypermethrin to certain Carabid beetles and
    neuropteran larvae is relatively low, and there is limited hazard to
    pre-adult stages of parasitoid Hymenoptera. Small-plot and large-scale
    field studies have demonstrated a low hazard of alpha-cypermethrin to
    Carabid and Staphylinid beetles but a relatively high hazard to
    Linyphiid spiders. The effects on populations were limited to a single
    growing season. Furthermore, alpha-cypermethrin has a low hazard to
    Syrphid larvae but has a significant effect on Coccinellids. However,
    the rapid dissipation of the residues on foliage gives the potential
    for these animals to recolonize rapidly.

         Field application of alpha-cypermethrin had no adverse effects on
    the relative abundance of entomophages within the arthropod

    communities. Its use in small grain cereals would not be associated
    with pest "resurgence" or the development of secondary pest
    infestations.

         In laboratory tests, the toxicity of alpha-cypermethrin to
    earthworms is low. No mortality was recorded after 14 days for worms
    exposed to up to 100 mg/kg of artificial soil.

         In laboratory acute toxicity tests, alpha-cypermethrin was found
    to be highly toxic to bees. Oral administration of an emulsifiable
    concentrate formulation gave a 24-h LD50 of 0.13 µg/bee, whereas the
    corresponding value for topical administration was 0.03 µg/bee
    (technical product) or 0.11 µg/bee (EC). The high toxicity of
    alpha-cypermethrin to bees did not manifest itself in field trials,
    probably as a result of the short-lived repellent effect of
    alpha-cypermethrin which causes a decline in bee foraging behaviour
    and, thus, in exposure.

         No data for the toxicity of alpha-cypermethrin to birds are
    available.

    1.2  Conclusions

    1.2.1  General population

         When applied according to good agricultural practice, exposure of
    the general population to alpha-cypermethrin is low and is unlikely to
    present a hazard.

    1.2.2  Occupational exposure

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

    1.2.3  Environment

         With recommended application rates, it is unlikely that
    alpha-cypermethrin will attain levels of environmental significance.
    It is highly toxic to aquatic arthropods, fish and honey-bees under
    laboratory conditions. Significant toxic effects on non-target
    invertebrates and fish are only likely to occur in cases of spillage,
    overspraying and misuse.

    1.3  Recommendations

    *    Contamination of surface waters with alpha-cypermethrin should be
         avoided.

    *    Alpha-cypermethrin binds strongly to particles. Further
         ecotoxicological studies on the effects of alpha-cypermethrin on
         sediment-dwelling organisms should be carried out, since this
         subject seems to have received little attention.

    *    The gastrointestinal absorption of alpha-cypermethrin should be
         investigated under various conditions.

    *    The fate of dermally applied alpha-cypermethrin should be
         investigated.

    *    Further information on the long-term toxicity/carcinogenicity and
         immunotoxicity of alpha-cypermethrin should be obtained.

    2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL METHODS

    2.1  Identity

    2.1.1  Primary constituent

    Chemical structure:      racemic mixture of the two stereoisomers
                             indicated by boxes in Fig. 1

    Empirical formula:       C22H19NO3Cl2

    Relative molecular
     mass:                   416.3

    Chemical name:
       (IUPAC)               a racemate comprising (S)-alpha-cyano-3-
                             phenoxybenzyl (1R,3R)-3-(2,2-dichloro-
                             vinyl)-2,2-dimethylcyclopropanecarboxy-late
                             and (R)-alpha-cyano-3-phenoxybenzyl
                             (1S,3S)-3-(2,2-dichlorovinyl)-2,2-dimethyl-
                             cyclopropanecarboxylate; a racemate
                             comprising (S)-alpha-cyano-3-phenoxybenzyl
                             (1R)- cis-3(2,2-dichloro-vinyl)-2,2-
                             dimethylcyclopropanecarboxylate and (R)-
                             alpha-cyano-3-phenoxybenzyl (1S)- cis-3-
                             (2,2-dichlorovinyl)-2,2-dimethylcyclopro-
                             panecarboxylate

       (Chemical             [1alpha(S*),3alpha}-(±)-cyano(3-phenoxy-
       Abstracts)            phenyl)methyl 3-(2,2-dichloroethenyl)-2,2-
                             dimethylcyclopropanecarboxylate (9CI)
                             (From: Worthing & Hance, 1991)

    Common name:             alpha-cypermethrin (alphamethrin and
                             alfoxylate are non-official names)

    Code numbers:            WL 85 871; OMS 3004

    CAS registry
     number:                 [67375-30-8] correct stereochemistry;
                             [52315-07-8] (formerly [69865-74-0],
                             [86752-99-0], [86753-92-6] cypermethrin (no
                             stereochemistry stated) were sometimes used
                             in Chemical Abstracts)

    FIGURE 1

    2.1.2  Technical product

    Common trade
     names:                  Fastac, Concord, Fendona, Renegade

    Purity:                  technical grade: > 90% pure (m/m)

    Impurities:              no data.

    2.2  Physical and chemical properties

         Alpha-cypermethrin is a racemic mixture of the two stereo-isomers
    (1:1) indicated by boxes in Fig. 1 and is a crystalline powder. Some
    physical and chemical properties of alpha-cypermethrin are given in
    Table 1.

    Table 1. Physical and chemical properties of alpha-cypermethrin (pure
    enantiomeric pair; purity > 99%)
                                                                        

    Boiling point            200 °C at 9.3 N/m2

    Melting point            80.5 °C

    Vapour pressure (20 °C)  170 nPa (1.7 x 107 N/m2)

    Density                  1.12 g/cm3 at 20 °C
                             1.28 g/cm3 at 22 °C

    Solubility (25 °C)       0.005-0.01 mg/litre water; 620 g/litre
                             acetone; 515 g/litre cyclohexanone; 7 g/kg
                             hexane; 351 g/litre xylene

    Stability                It is stable under acidic or neutral
                             conditions (pH 3-7) but hydrolyses in
                             strongly alkaline media (pH 12-13). It
                             decomposes above 220 °C. Field data indicate
                             that in practice it is stable to air and
                             light.

    Partition coefficient
      n-octanol/water        log Pow 5.16 (Pow = 1.4 x 105)
                                                                        

    From: Langner (1980); Shell (1983a); Worthing & Hance (1991).

         The water solubility of alpha-cypermethrin (98.0%), calculated as
    the sum of the cis-1 and the cis-2 isomer (ratio 2.6:97.4)
    concentrations, at 20 °C in 0.01 M buffers at pH values of
    approximately 4 to 9, ranges from 4.59 to 7.87 µg/litre, as measured
    by the OECD and EEC microcolumn techniques. In distilled water alone
    the solubility is slightly less, i.e. 2.06 µg/litre. The solubility is
    not strongly dependent on pH values within the range of 4 to 9. It is
    likely that ionic strength differences account for differences in
    solubility between values in pure water and in the buffer solutions
    (Baldwin, 1990).

    2.3  Formulations

         The following formulations exist:

         *    "Fastac", EC (20-100 g/litre), WP (50 g/kg), SC (15-250
              g/litre), ULV (6 to 15 g/litre);

         *    "Fendona" and "Renegade", EC (50 or 100 g/litre), SC (250
              g/litre), WP (50 g/kg).

         Combination with other active ingredients also exist, e.g.,
    "Azofas" (alpha-cypermethrin and monocrotophos) and combinations of
    alpha-cypermethrin with methomyl or Fenobucarb (Worthing & Hance,
    1991).

    2.4  Conversion factors

         1 ppm = 17.02 mg/m3
         1 mg/m3 = 0.059 ppm

    2.5  Analytical methods

    2.5.1  Sampling

    2.5.1.1  Air

         Samples are collected by drawing a measured volume of air through
    a 37-mm diameter silver membrane filter with a glass fibre pre-filter.
    They are analysed for total pyrethroid content ( cis- and
     trans-cypermethrin isomers) by gas chromatography with electron
    capture detection (ECD). The limit of determination is 0.01 µg/filter
    (see Table 2) (Armitage, 1984).

    2.5.1.2  Surface-wipe

         Surface-wipe samples are collected using a filter paper wetted
    with diethyl ether. These samples are analysed for total pyrethroid
    content ( cis- and  trans-cypermethrin isomers) by gas
    chromatography with flame ionization detection (FID). The limit of
    determination is 0.03 mg/filter (see Table 2) (Armitage, 1984).

    2.5.2  Methods for determination

         A method for the determination of alpha-cypermethrin in technical
    material and formulated products, excluding suspension concentrates,
    was described by Shell (1987a). This method is also used to determine
    the ratio of the enantiomer pairs cis 1 to cis 2.

         The alpha-cypermethrin content is determined by means of
    high-performance liquid chromatography (HPLC), using a column packed
    with Zorbax SIL, together with ultraviolet detection at 230 nm
    (Shell, 1987a).

         Methods have been described for the determination of
    alpha-cypermethrin in water, soil, crops, and animal tissues and
    fluids (see Table 2).


        Table 2.  Analytical methods for alpha-cypermethrin in air, soil, water and biological mediaa
                                                                                                                                           
    Sample    Extraction           Clean-up                 Detection and                      Recovery    Limit of         References
              quantification       determination
                                                                                                                                           
    Air       20% ethyl acetate    column chromatography    gas chromatography with                -       0.01 µg/filter   Armitage (1984)
              in hexane            chromosorb W.HP.         electron capture detection

    Surface   20% ethyl acetate    column chromatography    gas chromatography with                -       30 µg/filter     Armitage (1984)
     wipe     in hexane            chromosorb W.HP.         flame ionization detection

    Soil      anhydrous sodium     liquid-solid             packed column gas                  95-100%b    10 µg/kg         Shell (1990b)
              sulfate with         chromatography           chromatography, electron capture 
              acetone/hexane       using Florisil           detection; confirmation by 
                                                            capillary GC and packed column 
                                                            GC-MS

    Water     solvent partition    Florisil disposable      capillary gas-liquid               80-100%c    0.01 µg/litre    Shell (1990a)
              with hexane          cartridge                chromatography, electron-capture
                                                            detection; confirmation by GC-MS

    Crops     anhydrous sodium     partition between        packed column gas                  90-100%b    10 µg/kg         Shell (1989a)
              sulfate with         hexane and water/        chromatography, electron capture
              acetone/hexane       acetonitrile; liquid-    detection; confirmation by
                                   solid chromatography     capillary GC and packed
                                   using Florisil           column GC-MS

    Animal    acetone/hexane       partition with           gas-liquid chromatography,         80-100%d    10 µg/kg         Shell (1988a)
     tissues  mixture              acetonitrile or          electron capture detection;
                                   hexane-acetonitrile;     confirmation by GC-MS
                                   liquid-solid 
                                   chromatography on 
                                   Florisil

    Milk      diethyl ether/       cyano Bond Elut          gas-liquid chromatography,         90-100%e    1 µg/litre       Shell (1988b)
              hexane; Extrelut     cartridge                electron capture detection;
              extraction column                             confirmation by GC-MS
                                                                                                                                           

    Table 2 (continued)
                                                                                                                                           
    Sample    Extraction           Clean-up                 Detection and                      Recovery    Limit of         References
              quantification       determination
                                                                                                                                           
    Blood     acetone              partition with hexane    packed column gas                      -       10 µg/litre      Shell (1986)
     (rat)                         (washed with water);     chromatography, electron capture
                                   dried with sodium        detection; confirmation by
                                   sulfate; liquid-solid    capillary GC and GC-MS
                                   chromatography on
                                   Florisil
                                                                                                                                           
    a    Details of the analytical methods are available from Shell International Chemical Company, London.  These methods differentiate
         between alpha-cypermethrin and the other isomers.
    b    Over the concentration range 0.05-0.5 mg/kg
    c    Over the concentration range 0.05-0.5 µg/litre
    d    Concentrations 0.1-0.2 mg/kg
    e    Over the concentration range 0.005-0.02 mg/litre
    

    3.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    3.1  Natural occurrence

         Alpha-cypermethrin does not occur in nature.

    3.2  Anthropogenic sources

    3.2.1 Production levels and processes

         Alpha-cypermethrin is manufactured from  cis-2,2,dimethyl-3-
    (2",2"-dichlorovinyl)-cyclopropane carboxylate ( cis-DVO), 3-phenoxy
    benzaldehyde (POAL) and sodium cyanide.

         After removal of the solvent, the  cis-cypermethrin is
    epimerized into alpha-cypermethrin. Solid alpha-cypermethrin crystals
    separate and are filtered, washed and dried under vacuum before
    drumming-off1.

         No data are available on production levels.

    3.2.2  Use

         Alpha-cypermethrin has been available commercially since late
    1983. It is a potent insecticide effective against a wide range of
    pests, particularly  Lepidoptera and Coleoptera in citrus, cotton,
    forestry, fruit, rice, soybeans, tomatoes, vegetables, grapes and
    other crops, at a concentration of 5-30 g active ingredient per ha.
    Good control of plant-sucking  Hemiptera can also be obtained if the
    insecticide is applied before populations have become established. It
    also controls soil-dwelling  Lepidoptera.

         Alpha-cypermethrin can be used in most crops for either curative
    or preventive treatment. It can replace conventional insecticides in
    short-interval spray programmes, or the longer residual performance
    may be exploited to reduce the number of sprays per season. Either
    option may be chosen since no reports of phytotoxicity have been
    received even when sensitive crops have been involved in repeated
    applications. It controls ectoparasites ( Boophilus microplus at a
    concentration of 50 mg/litre), including strains resistant to
    organophosphorus pesticides, as well as sheep lice and  Melophagus
     ovinus.

                      

    1  Manufacturing process of alpha-cypermethrin; Shell International
         Chemical Company; letter dated 10 January 1989 (ref. CTMAR/4)

         Rapid knockdown and residual control of biting flies in and
    around animal housing have been obtained following direct spray
    application to animals or structural surfaces. Furthermore,
    alpha-cypermethrin controls  Blattellidae, Culicidae, flies and other
    nuisance or disease-carrying insects, at a level of 10-30 mg/m2,
    with good persistence on most surfaces (Fisher et al., 1983; Worthing
    & Hance, 1991).

         Alpha-cypermethrin is available as an emulsifiable concentrate,
    ultra-low-volume formulation and suspension concentrate (flowable
    formulations). Mixtures with organophosphorus and carbamate
    insecticides have also been developed. Details of formulations are
    given in section 2.3.

    4.  ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION

    4.1  Transport and distribution between media

         Data relevant to alpha-cypermethrin can be found in Environmental
    Health Criteria 82: Cypermethrin (WHO, 1989).

    4.1.1  Air

         No information on the transport of alpha-cypermethrin in air is
    available, but its volatility is very low.

    4.1.2  Water

         Alpha-cypermethrin as an emulsifiable concentrate (EC) was
    sprayed from the air (15 g active ingredient/ha) to a field along one
    side of which ran a freshwater ditch. The fate and biological effects
    of spray drift in the ditch were monitored for 7 weeks after the
    application (see sections 9.2.1.2 and 9.2.2.2). Deposition on the
    surface of the ditch was around 5 g active ingredient/ha (30% of the
    nominal application rate). Alpha-cypermethrin concentrations in the
    sub-surface water were 0.6 µg/litre shortly after the application and
    decreased to < 0.02 µg/litre within 2 to 4 days. No contamination of
    the water was found 200 m beyond either end of the treated field
    (Garforth & Woodbridge, 1984).

         Two freshwater ponds were treated with an EC formulation of
    alpha-cypermethrin in 1987. One pond was oversprayed with 15 g active
    ingredient/ha, while the other was treated with the same amount of
    alpha-cypermethrin but by direct incorporation into the water. A third
    pond served as a control. One day after the treatment, 5% of the
    applied substance was found in the surface film of the oversprayed
    pond and 19% in the sub-surface water. Residue levels in both
    compartments subsequently declined rapidly so that one week later only
    0.1 and 2% were still present, respectively. In the pond that received
    direct treatment, 37% of the applied alpha-cypermethrin was found in
    the sub-surface water one day after treatment. The concentration
    subsequently declined more rapidly than in the oversprayed pond so
    that one week later only 2% was present. The concentration of alpha-
    cypermethrin found in the sediment samples from both ponds 16 days
    after treatment indicated that approximately 5% of the
    alpha-cypermethrin applied was present at that time. Thereafter the
    concentration decreased and was less than 3% in the sediment 33 days
    after application. In a bioassay test, the water in both ponds was
    found to be acutely toxic to  Gammarus pulex for at least 4 days
    after application. After a further 29 days, the water was no longer
    acutely toxic. The sediment was not toxic to  Gammarus pulex
    (Pearson, 1990).

    4.1.3  Soil

         A trial in the United Kingdom (Reculver) investigated the decay
    of alpha-cypermethrin in sandy-clay soil treated with a diluted EC
    formulation at a dosage rate of 0.5 kg active ingredient per ha.
    Samples of soil were taken from the 0-15 cm layer of each plot at
    various intervals over a period of one year. Once a year a sample was
    also taken from the 15-30 cm layer. The residue immediately after the
    application was 0.07 mg/kg soil in the 0-15 cm layer, and within 2
    weeks this had declined by 50%. The residues of alpha-cypermethrin in
    samples from the 0-15 cm layer and 15-30 cm layer taken 40 weeks and
    52 weeks after application were below the limit of determination, i.e.
    0.01 mg/kg (Forbes & Knight, 1983).

         After one year, a second application to the bare soil was made
    and again a diluted EC formulation was applied at a dosage rate of 0.5
    kg active ingredient/ha. Samples were taken at various intervals
    during this second year. Residues of alpha-cypermethrin in the 0-15 cm
    soil layer declined from 0.19 mg/kg immediately after treatment to
    0.11 mg/kg after 2.1 weeks and < 0.01 mg/kg after 49 weeks. In
    samples from the 15-30 cm layer no residues (< 0.01 mg/kg) were
    detectable 23 and 49 weeks after application (Forbes & Burden, 1984).
    In the third year of the trial, another application to the same plots
    was made with the EC formulation at a dosage rate of 0.5 kg active
    ingredient/ha. Residues of alpha-cypermethrin in the 0-15 cm layer
    declined from 0.20 mg/kg immediately after treatment to 0.08 mg/kg
    after 18 weeks and 0.01 mg/kg after 52 weeks. Residues were not
    detectable in the 15-30 cm layer sampled after 32 and 52 weeks. Over
    the three years of the trial there was no indication of a build-up of
    alpha-cypermethrin residues in the surface soil layer or any evidence
    to suggest leaching of the compound into sub-surface soil layers
    (Forbes & Wales, 1985a).

         A further trial was carried out in the United Kingdom (Coates) to
    study the decay of alpha-cypermethrin applied to a peat type soil as
    a diluted EC formulation at a dosage rate of 0.5 kg active
    ingredient/ha. As in the Reculver study, residues were determined in
    the 0-15 cm layer at various intervals and in the 15-30 cm layer 32
    weeks after application. At the beginning of the second and third
    year, one application was made as at the beginning of the first year.
    The residue in the 0-15 cm layer immediately after the first
    application was 0.65 mg/kg declining to 0.36 mg/kg within 2 weeks and
    to 0.30 mg/kg after 8 weeks. After 16 weeks, the residue was 0.05
    mg/kg or less. In the 15-30 cm layer, no residues were found after 32
    weeks (Forbes & Mackay, 1983). Immediately after the second
    application, the residue in the 0-15 cm layer was 0.65 mg/kg; after
    two weeks the level was 0.36 mg/kg and declined to 0.07 mg/kg by 48
    weeks after application. No residues were found in the 15-30 cm layer
    (Forbes & Wales, 1985b).

         In the third year, a residue level of 0.55 mg/kg was found in the
    0-15 cm layer immediately after treatment, declining to 0.20 mg/kg
    within 8 weeks and to 0.09 mg/kg after 50 weeks. In the 15-30 cm
    layer, residues of 0.01 and 0.03 mg/kg were found after 40 and 50
    weeks respectively. In this 3-year trial there was no indication of a
    build-up of alpha-cypermethrin residues in the surface soil layers, or
    any evidence to suggest significant leaching into sub-surface soil
    layers (Coveney & Forbes, 1986).

    4.2  Biotransformation

    4.2.1  Biodegradation

         Alpha-cypermethrin has been tested for "ready biodegradability"
    in two tests: a) the closed bottle and modified Sturm test, and b)
    growth inhibition in a  Pseudomonas fluorescens growth test. In these
    tests, mineralization of alpha-cypermethrin was not detected. It was
    not degraded in these two tests and hence is not considered to be
    readily biodegradable (Stone & Watkinson, 1983).

         Maloney et al. (1988) studied the microbial transformation of
    technical alpha-cypermethrin (96.3% pure) in aerobic batch enrichment
    cultures. These microbial enrichments, which contained  Pseudomonas
     fluorescens (SM-1),  Achromobacter sp. and  Bacillus cereus, were
    able to transform alpha-cypermethrin with a half-life of 7 to 14 days
    at a concentration of 50 mg/litre in the presence of 0.05% Tween 80
    (v/v). One of the major transformation products was 3-phenoxybenzoic
    acid, which was further transformed to 4-hydroxy-3-phenoxybenzoic
    acid.

         McMinn (1983a) investigated the degradation under aerobic
    conditions of alpha-cypermethrin, labelled with 14C in the benzyl
    ring, in two types of soil, i.e. sandy clay loam and clay loam. The
    soils were treated with 1 mg of the labelled material and gently
    agitated to distribute the insecticide. Soils samples were removed for
    analysis 2.5, 6, 10, 20 and 42 weeks after treatment. The initial
    degradation half-lives were 27 and 13 weeks for sandy clay loam and
    clay loam, respectively. However, after 42 weeks the percentage of
    applied radioactivity remaining unchanged was 28.9 and 21.6%,
    respectively, for the two soils. The formation of total organo-soluble
    products after 42 weeks was 32.2 and 24.3% for sandy clay loam and
    clay loam, respectively. Total extractable and total non-extractable
    radioactivity for sandy clay loam was 32.5 and 18.0% and for clay loam
    25.3 and 32.0%, respectively. Metabolites were found in both cases at
    levels of 2 to 3%. Unchanged alpha-cypermethrin was present, and the
    degradation products had similar chromatographic mobilities to the
    previously identified major products of cypermethrin (McMinn, 1983b).

    4.2.2  Bioaccumulation

         The  n-octanol/water partition coefficient of alpha-cypermethrin
    is 1.4 x 105 (log Pow = 5.16), compared to a value for
    cypermethrin of 2 x 106 (log Pow = 6.3). The actual
    bioaccumulation in fish found experimentally for cypermethrin is lower
    than might be expected from the partition coefficient. This should
    also apply to alpha-cypermethrin, because the pathway and rate of
    metabolism are comparable with those of cypermethrin (Shell, 1983b;
    WHO, 1989).

    5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    5.1  Environmental levels

         Information relevant to alpha-cypermethrin was given in
    Environmental Health Criteria 82: Cypermethrin (WHO, 1989).

    5.1.1  Soil

         In a study on the deposition of alpha-cypermethrin on the orchard
    floor following commercial application to apple trees,
    alpha-cypermethrin (100 g EC/litre) was applied at a nominal dose rate
    of 26 g/ha using a tractor-driven "Kinkelder" mist-blower. Following
    normal practice, spray runs were made between each row of trees and
    then around the perimeter of the orchard. One hour after spraying,
    pesticide deposits were collected in foil-lined trays positioned on
    the orchard floor and analysed. Deposition was found to be variable,
    ranging from 10 to 76% of the nominal application rate (Hillaby,
    1988).

    5.2  Food

    5.2.1  Crops

         Residue data on cypermethrin have been evaluated by the Joint
    FAO/WHO Meeting on Pesticide Residues (FAO/WHO, l980, 1982).

         Alpha-cypermethrin application rates to crops range from 5 to 30
    g active ingredient/ha. Residue data have been obtained from
    supervised trials in many countries. The residue concentrations of
    alpha-cypermethrin derived from recommended application rates vary
    from 0.05 to 1.0 mg/kg product (Shell, 1984).

         A study was carried out to determine whether there was
    significant isomerization of alpha-cypermethrin after treatment of
    certain crops. Grapes were treated with 10% EC applied at a rate of 18
    g active ingredient/ha, and apples and lettuce with 10% EC at 15 g
    active ingredient/ha. Samples were taken 3 and 7 days (grapes), 7 days
    (apples) and 10 days (lettuce) after treatment. Residues of 0.17 and
    0.09 mg/kg were found on grapes, 0.05 mg/kg on apples and 0.17 mg/kg
    on lettuce, but none of the samples showed any significant isomer
    conversion of alpha-cypermethrin (Bosio, 1982).

         In 1983 two trials were carried out in Canada in which
    alpha-cypermethrin was applied with a knapsack sprayer to maize
    (sweetcorn). Five applications with diluted 10% EC formulations at a
    dosage rate of 20 g active ingredient/ha were made, samples were
    harvested 7 days after the last application, and the husks, grain and
    cobs were analysed separately. Alpha-cypermethrin residues of 0.38

    mg/kg were found in the husks, but no residues (limit of
    determination, 0.01 mg/kg) were found in the grain or the cobs (Forbes
    & Cole, 1986).

    5.2.2  Fish

         To reduce blow-fly infestations during the curing of marine
    catfish, the fish were dipped in EC solutions (15 g/litre) at various
    concentrations (0.001-0.05% active ingredient w/v) between the salting
    and drying stages of the curing process. Dipping after the salting
    stage in a 0.001% solution of the EC proved to be effective. The
    levels of residues in treated fish were dependent on the season (wet
    and dry season), storage time, concentration of the dip solution and
    the size of the fish. In the wet season, the range was from 0.9 to 2.8
    mg/kg, whereas in the dry season it was from 0.26 to 30.0 after one
    week of storage and 0.22 to 4.0 mg/kg (wet weight of homogenized fish)
    after 15 weeks of storage (Forbes, 1985).

    5.2.3  Milk

         A trial was carried out in 1987 in the United Kingdom where
    lactating cows were treated with pour-on formulations of
    alpha-cypermethrin. Two formulations were used containing either 10
    g/litre or 15 g/litre (see also section 6.1.2). Either 10 ml or 20 ml
    of formulation containing 0.1, 0.15 or 0.2 g active ingredient was
    applied along the mid-dorsal line of five cows for each treatment.
    Milk samples were taken 1, 2, 3, 4, 7, 14 and 21 days after treatment
    for the analysis of alpha-cypermethrin. The residues of
    alpha-cypermethrin in milk were at a maximum from 2 to 4 days after
    treatment. Generally, residues were highest in the 0.2 g group, the
    maximum concentration being 0.005 mg/litre (in two samples only). By
    day 21 the residues in the milk from all treated cows were < 0.002
    mg/litre (the limit of determination) (Sherren, 1988b).

    5.3  Human exposure

         In a study to quantify the maximum potential dermal exposure of
    operators to crop protection products, 13 exposure pads were mounted
    on each of three operators and chemicals adhering to gloves were
    analysed. The operation involved three distinct stages: mixing product
    and loading the tractor; spraying; and washing-up the equipment and
    tractor after the exercise. The total dermal exposure for the three
    operators was: mixing/loading, 2.45, 0.57 and 2.94 mg/operation;
    spraying, 0.38, 0.61 and 0.40 mg/h; and washing-up, 0.12, 0.29 and
    0.73 mg/operation (Senior & Lavers, 1990a,b).

    6. KINETICS AND METABOLISM

         Both cis and trans isomers of cypermethrin are metabolized via
    cleavage of the ester bond to phenoxybenzoic acid (PBA) and
    cyclopropane carboxylic acid (CPA). The PBA moiety is mainly excreted
    as a conjugate. The type of conjugate differs in a number of animal
    species. PBA is further metabolized to a hydroxy derivative and
    conjugated as a glucuronate or sulfate. The CPA moiety is mainly
    excreted as a glucuronate. Consistent with the lipophilic nature of
    cypermethrin, the highest tissue concentrations are found in body fat,
    skin, liver, kidneys, adrenals and ovaries. The elimination from fat
    is approximately 3 to 4 times slower for the cis isomers than for the
    trans isomers (WHO, 1989).

    6.1  Absorption, elimination, retention and turnover

    6.1.1  Rats

         Alpha-cypermethrin labelled in the 14C-benzyl moiety has been
    studied in Wistar rats at a concentration of approximately 2 mg/kg
    body weight in corn oil. The compound, which was given by stomach
    tube, was rapidly broken down and the radioactivity was mainly
    eliminated in the urine as the sulfate conjugate of
    3-(4-hydroxyphenoxy)benzoic acid (40-45% of the dose). Approximately
    35% of the dose was eliminated in the faeces, 20% of which was
    unchanged alpha-cypermethrin. The proportion of the dose excreted in
    the urine and faeces within the first 24 h was approximately 78% and
    within 4 days was 90%. Residues in major organs and tissues of rats 4
    days after a single oral dose were in general low: liver, 0.03 and
    0.05; skin, 0.04 and 0.02; adrenals, 0.03 and 0.06; and kidneys, 0.02
    and 0.02 (values are expressed as mg equivalent of
    alpha-cypermethrin/kg tissue for females and males, respectively).
    However, in body fat, higher residues were found (0.22 and 0.42
    mg/kg). The release from skin and fat was biphasic in nature. The
    half-life of elimination of radioactivity from fat was approximately
    2.5 days for the initial phase and 17-26 days for the slower phase
    (the half-life of elimination from fat for cis-cypermethrin was 18.9
    days). The half-life values for skin were 2 days for the initial phase
    and 40 days for the slower phase. The radioactivity in liver and
    kidneys was eliminated apparently by a monophasic process. More than
    95% of the residue in fat was present as unchanged alpha-cypermethrin
    (Hutson, 1982; Logan, 1983; Hutson & Logan, 1986).

    6.1.2  Domestic animals

         In a study by Francis & Gill (1991), a formulation containing a
    mixture of flufenoxuron and alpha-cypermethrin was applied to groups
    of three sheep. The formulation was applied once, either as a dip
    diluted at 1:1000 to give a solution of 80 mg flufenoxuron per litre
    and 60 mg alpha-cypermethrin/litre or as a pour-on solution applied
    directly to the backs of the sheep giving a dose of 0.15 g active

    ingredient flufenoxuron and 0.2 g alpha-cypermethrin per sheep. The
    sheep were killed at 3, 7 and 14 days after application and samples of
    subcutaneous fat, fleece and sheep skin were analysed. The residues of
    alpha-cypermethrin in fat ranged from < 0.01 to 0.04 mg/kg and in
    skin from 0.02 to 1.4 mg/kg over the three sampling periods, and they
    were lower for pour-on formulations than for the dip. Highest tissue
    residues were found in wool (sampled from the back); these were (for
    the 3, 7 and 14 day sampling periods, respectively) 730, 1020 and 360
    mg/kg for dip application and 360, 440 and 360 mg/kg for pour-on
    application. Wool sampled from the side of sheep treated with pour-on
    formulation were 10 to 30 times lower than wool sampled from the back
    region; with the dip solution, however, wool from the side region
    contained higher residues than that from the back. Pour-on application
    gave lower residues than after a dip.

         A trial was carried out during 1987 in the United Kingdom in
    which Friesian/Hereford calves (in total 17 female animals) were
    treated with an alpha-cypermethrin pour-on formulation. Ten ml of a 16
    g/litre formulation was applied to calves along the middorsal line
    from shoulder to tail. At 3, 7 and 14 days following treatment,
    animals were sacrificed for analysis of tissues, i.e. perirenal and
    subcutaneous fat, muscle, kidneys and liver. No residues were detected
    in muscle and liver samples at any time (limit of determination, 0.01
    mg/kg). In the kidneys a maximum of 0.03 mg/kg was found on day 7 but
    by day 14 the residues had decreased to 0.01 mg/kg or less. The fat
    tissues contained maximum levels on day 7, i.e. mean concentrations of
    0.26 mg/kg (perirenal fat) and 0.08 mg/kg (subcutaneous fat). By day
    14 these concentrations had decreased by about two and a half times
    (Sherren, 1988a) (see also section 5.2.3).

    6.1.3  Humans

         Six volunteers (two per dose level) received a single oral dose
    of 0.25, 0.5 or 0.75 mg alpha-cypermethrin and, after a period of 2-3
    weeks, five successive daily doses of 0.25, 0.5 or 0.75 mg to study
    the urinary excretion and bioaccumulation of alpha-cypermethrin. A
    parallel study with cypermethrin itself was carried out for comparison
    purposes. The metabolism and rate of excretion of a single oral dose
    of alpha-cypermethrin were similar to those of cypermethrin itself.
    The rate of excretion was dose-related, approximately 43% of the dose
    of alpha-cypermethrin being excreted in the urine as free or
    conjugated  cis-cyclopropane carboxylic acid ( cis-CPA) during the
    first 24 h. Urinary excretion did not increase with repeated oral
    dosing; an average of 49% of alpha-cypermethrin was excreted in the
    urine as free or conjugated  cis-CPA within 24 h (van Sittert et al.,
    1985; Eadsforth et al., 1988).

    6.2  Metabolic transformation

         In a study on Wistar rats using alpha-cypermethrin,
    14C-labelled in the benzyl moiety, (see section 6.1.1) no evidence

    was found for any racemization of the chiral centres of
    alpha-cypermethrin in the residues in intestines, faeces or fat. The
    major urinary metabolite was the sulfate conjugate of
    3-(4-hydroxyphenoxy)benzoic acid, and smaller amounts of
    3-phenoxybenzoic acid (II) and 3-(4-hydroxyphenoxy)benzoic acid (III)
    were identified. In the faeces, 75% of the radioactivity in the
    extract was unchanged alpha-cypermethrin; minor metabolites included
    a dihydroxy metabolite (V), 3-(4-hydroxyphenoxy)benzoic acid (III),
    3-phenoxybenzoic acid (II) and the 4-hydroxyphenoxy metabolite (IV).
    In the adipose tissue, the 14C label was mainly associated with
    unchanged alpha-cypermethrin, but a lipophilic metabolite of either
    alpha-cypermethrin or 3-phenoxybenzoic acid, probably a mixture of
    3-phenoxybenzoyl diacylglycerols, was also present (Hutson, 1982;
    Logan, 1983; Hutson & Logan, 1986) (see Fig. 2).

    6.3  In vitro metabolic transformation

         Creedy & Logan (1984) studied the  in vitro metabolism of
    cypermethrin and alpha-cypermethrin using liver microsomal
    preparations from rats, rabbits and humans. In order to obtain
    information on the relative importance of the oxidative and esteric
    pathways of degradation of these compounds, incubations were carried
    out both in the presence and absence of an NADPH-generating system.
    Both cypermethrin and alpha-cypermethrin were broken down via esteric
    and oxidative pathways by the liver preparations from the three
    species. For rabbit and human liver microsomes, oxidation was a minor
    metabolic route compared to esteric hydrolysis in the case of both
    compounds. Human liver microsomes were able to carry out the esteric
    hydrolysis of alpha-cypermethrin slightly faster than cypermethrin. In
    the liver preparations of all three species, cyclopropane carboxylic
    acid (mainly produced via the esteric pathway) was the main metabolite
    for both compounds (to the extent of approximately 90-99%). Via the
    oxidative route, mono-hydroxycypermethrins, dihydroxy-cypermethrin and
    small amounts of hydroxycyclopropane carboxylic acid (rat only) were
    also produced.

    FIGURE 2

    6.4  Plants

         The metabolism of cypermethrin in plants is described in WHO
    (1989).

         The degradation of alpha-cypermethrin and cypermethrin in
    cabbages grown to maturity outdoors has been studied. Eighteen days
    after transplanting, the cabbages were treated three times with
    14C-labelled alpha-cypermethrin or cypermethrin as an EC
    formulation. Each treatment consisted of 1.8 mg equivalent with a
    spray concentration of 36 g/litre. This treatment was repeated after
    11 and 27 days. Each box of cabbages received a total application of
    5.4 mg at a dose rate equivalent to 50 g active ingredient/ha. At
    harvest (3 months later) the plants were separated into old and new
    outer leaves, heart, stalk and roots. No major differences between the
    two compounds in distribution of radioactivity throughout the plants
    or in the metabolic profile were observed. The highest radioactive
    residues were present in the old outer leaves (23% for
    alpha-cypermethrin and 27% for cypermethrin), lower levels being found
    in new outer leaves, stalk, roots and heart. Very low levels (< 0.05
    mg/kg) of both compounds were found in the soil. The major radioactive
    residue at harvest was shown to be the pesticide, which was either in
    the unchanged form or had undergone cis/trans-isomerization,
    presumably photochemically. The profiles of the organosoluble
    metabolites were similar, and the major products of alpha-cypermethrin
    had chromatographic mobility similar to previously identified products
    of cypermethrin metabolism, such as 3-phenoxybenzoic acid and
    3-phenoxybenzyl alcohol, partly hydroxylated and/or conjugated. These
    compounds were found in minor quantities (McMinn, 1983a; WHO, 1989).

                                 Appraisal

          A wide range of studies in mice, rats, dogs, sheep, cows and
     humans has shown that cypermethrin is rapidly absorbed, distributed
     to a variety of organs and tissues, metabolized and rapidly excreted
     from the body (WHO, 1989). There are no major differences in the
     absorption, distribution, retention or excretion between the species.
     Differences, where they do occur, are related to the rate rather than
     the nature of the metabolites formed and the conjugation reactions.

          Cypermethrin, both the cis and trans isomers, and
     alpha-cypermethrin are primarily metabolized by cleavage of the ester
     bond. The metabolites PBA and CPA are mainly excreted as conjugates.
     The type of conjugate differs in a number of animal species dosed
     with cypermethrin, but humans and rats have the same pathway. Minor
     quantities of hydroxylated PBA (conjugated) may also be found. The
     terminal half-life of elimination of alpha-cypermethrin from the fat
     of rats is 17-26 days, compared to 18.9 days for cis-cypermethrin.

    7.  EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

    7.1  Single exposure

    7.1.1  Oral (technical product)

         Alpha-cypermethrin is moderately to highly toxic and 3-4 times
    more toxic than cypermethrin.

         The clinical signs of toxicity observed in the various acute
    toxicity studies on experimental animals with alpha-cypermethrin are
    typical for a cyano-containing pyrethroid intoxication. They included
    ataxia, abasia, gait abnormalities, choreoathetosis, "tip-toe" walk,
    and increased salivation, lacrimation, piloerection, tremor and clonic
    convulsions. The majority of the mortalities occurred within the first
    3 h and surviving animals recovered within 7 days (Rose, 1982, 1983a).

         In the study with alpha-cypermethrin administered in corn-oil
    (Rose, 1983a), clonic convulsions, piloerection, salivation and
    splayed hind-leg gait were found. The oral LD50 values for
    alpha-cypermethrin are summarized in Table 3.

    Table 3. Oral LD50 values for technical alpha-cypermethrin
                                                                        
    Species   Concentration and        LD50 in mg/kg body   Reference
    (strain)  vehicle                  weight (with 95%
                                       confidence limits)
                                                                        
    Mouse     5% in corn oil               35 (26-48)       Rose (1982)
    (CD)      40% in DMSO                 762 (514-912)     Rose (1982)
              50% aqueous suspension     798 (568-1074)     Rose (1982)

    Rat       5% in corn oil               79 (63-98)       Dewar (1981)
    (Wistar)  40% in DMSO              approximately 4000   Rose (1982)
              50% aqueous suspension         > 5000         Rose (1982)

    Rat       10% in corn oil                 40-80         Rose (1983a)
    (Wistar)  20% in corn oil             368 (282-487)     Rose (1983a)
                                                                        

         Woollen et al. (1991) noted a higher degree of absorption of
    cypermethrin when it was applied in corn oil. This could be the
    explanation for the higher toxicity of alpha-cypermethrin administered
    in corn oil.

    7.1.2  Oral (formulations)

         Formulations of alpha-cypermethrin have moderate acute oral
    toxicity (Table 4). The clinical signs observed after oral
    administration to rats are characteristic of cyano-containing
    pyrethroid intoxication (see section 7.1.1.). The majority of the

    mortalities occurred within 3 days of dosing. The degree of acute oral
    toxicity of formulations containing mixtures with other active
    ingredients depended on the toxicity of the latter ingredients.

    7.1.3  Dermal

         Alpha-cypermethrin has low dermal toxicity. No deaths or signs of
    intoxication were observed in rats (Dewar, 1981; Shell, 1983a) and
    mice (Rose, 1982; Shell, 1983a) receiving a single 24-h dermal
    exposure of 500 mg/kg body weight (25% in DMSO) and 100 mg/kg body
    weight (5% in corn oil), respectively.

         The dermal LD50 values in rats of formulations of
    alpha-cypermethrin and of alpha-cypermethrin mixed with another active
    ingredient are summarized in Table 4. In all cases, the maximum dose
    that could be applied was tested.

         With the pour-on formulations, no clinical signs were observed.
    Blood around the nose and eyes was the only sign seen in the case of
    SC formulations. Clinical signs observed after the application of EC
    or ULV formulations of alpha-cypermethrin included increased
    lacrimation, chromodacryorrhoea and unkempt appearance, aggressiveness
    and diarrhoea. The Fastac/BPMC formulation caused the same signs of
    intoxication and also oedema at the application site. With the
    Fastac/methomyl formulation, fasciculation, lethargy, salivation,
    piloerection, hunched back, chromodacryorrhoea and cyanosis were
    observed. Animals treated with Fastac/Azodrin formulation showed the
    above-mentioned symptoms, and some additionally showed ataxia, abasia,
    hypothermia, eye pallor and prostration/coma.

    7.1.4  Inhalation

         Groups of five male and five female albino Fischer-344 rats were
    exposed for 4 h to a dust atmosphere containing 30% (m/m)
    alpha-cypermethrin on silica powder at an average concentration of 1.3
    g/m3 (equivalent to 0.4 g active ingredient/m3). The mass media
    diameter of the dust particles was 4.2 µm (geometric standard
    deviation 6.4). The animals were observed for 14 days after the
    exposure but there were no signs of intoxication. Macroscopic
    examination of the lungs did not reveal any effects. Thus, the acute
    LC50 was > 1.3 g 30% silica powder dust/m3 or > 0.4 g active
    ingredient/m3 (Blair, 1984).

        Table 4. Oral and dermal LD50 values for formulated alpha-cypermethrin in rats (Fischer-344)
                                                                                 

    Formulationa        LD50 in mg total formulation per kg          Reference
                        body weight (with 95% confidence limits)
                                   Oral            Dermal
                                                                                 
    100 g/litre EC           101 (82-119)          > 1800            Rose (1984d)

    100 g/litre EC           136 (98-186)          > 1800            Rose (1984e)

    100 g/litre EC           174 (125-327)         > 2000            Price (1985a)

    30 g/litre EC            229 (178-292)         > 2000            Rose (1984f)

    30 g/litre EC            673 (597-753)         > 2000            Rose (1985)

    15 g/litre pour-on          > 2000             > 2000            Price (1988)

    10 g/litre pour-on          > 2000             > 2000            Price (1988)

    100 g/litre SC         1804 (1507-2168)        > 2000            Price (1985b)

    60 g/litre SC               > 5000             > 2000            Gardner (1991)

    15 g/litre SC               > 5000             > 2000            Price (1986)

    15 g/litre ULV         5838 (5130-6665)        > 2000            Rose (1984c)

     Mixtures with other active ingredients

    Fastac/methomyl EC       58-97 (males)         > 1900            Rose (1984h)
    15/120 g/litre       73 (51-89) (females)      > 1900

    Fastac/BPMCb EC          310 (215-462)         > 2000            Price (1987)
    10/400 g/litre

    Fastac/Azodrin EC         25 (18-34)           > 2000            Gardner (1989)
    20/400 g/litre
                                                                                 

    a  EC = emulsifiable concentrate; SC = suspension concentrate; ULV = ultra-low volume
    b  BPMC = 2 sec-butylphenyl methylcarbamate (fenobucarb)
    
    7.1.5  Other routes

         The acute intraperitoneal LD50 for rats of a 10% solution of
    alpha-cypermethrin in corn oil was 3.39 (3.03-3.83) ml/kg body weight,
    or 339 mg active ingredient per kg body weight. The surviving animals
    showed characteristic pyrethroid signs of intoxication, e.g., ataxia,

    abasia, choreoathetosis, gait abnormalities, "tip-toe" walk and
    salivation (Rose, 1984a).

    7.2  Short-term exposure

    7.2.1  Oral

    7.2.1.1  Rat

         Groups of Wistar rats (10 of each sex at each dose level and 20
    of each sex as controls) were fed 0, 25, 100, 200, 400 or 800 mg
    alpha-cypermethrin/kg diet (equivalent to 0, 1.25, 5, 10, 20 or 40
    mg/kg body weight) for 5 weeks. At 400 and 800 mg/kg diet, signs of
    intoxication, such as abnormal gait and hypersensitivity were
    observed, and food intake and body weight were decreased in both sexes
    compared with the control group. Changes in blood chemistry, e.g.,
    decreases in protein and increases in urea levels, were observed in
    both sexes of rats fed 800 mg/kg diet and in males fed 400 mg/kg. The
    weights of livers and kidneys of both sexes of rats fed 800 mg/kg diet
    and livers of male rats fed 400 mg/kg were increased. No
    histopathological changes were observed except in the case of one
    severely intoxicated male animal fed 800 mg/kg diet, which showed
    sparse axonal degeneration in the sciatic nerve. No effects were seen
    in the animals fed 200 mg/kg diet for five weeks (Pickering, 1982).

         In a 13-week study, Wistar rats (30 males and 30 females per test
    group, and a control group consisting of 60 males and 60 females),
    which were initially 5 weeks old, were fed 0, 20, 60, 180 or 540 mg
    alpha-cypermethrin/kg diet (equivalent to 0, 1, 3, 9 or 27 mg/kg body
    weight). After six weeks of feeding, one third of the animals were
    killed for interim haematological, clinical chemical and gross
    post-mortem examination. The remaining animals were killed after 13
    weeks. Signs of intoxication, such as abnormal gait with splayed hind
    limbs, were found in 3 out of 20 males fed 540 mg/kg diet. Several
    instances of transient skin sores and fur loss were observed
    particularly in the rats fed 540 mg/kg. There was decreased growth,
    which correlated with decreased food intake, in both sexes fed 540
    mg/kg from the first week onwards. No clear effects on the
    haematological and clinical chemical parameters were found. Organ
    weights were comparable with those of the control animals. No
    histopathological abnormalities were found except sparse axonal
    degeneration in the sciatic nerve, without clinical signs of toxicity,
    in two males fed 540 mg/kg. No axonopathy was observed in the three
    animals with abnormal gait. There were marginal effects (decreased
    growth during week one and from week 10 onwards) in the males fed 180
    mg/kg diet. No effects were found in the 60-mg/kg group (Clark, 1982).

    7.2.1.2  Dog

         Beagle dogs (one male and one female) were fed alpha-cypermethrin
    in the diet at the following concentrations: 200 mg/kg diet for 7

    days, 400 mg/kg diet for 2 days, and 300 mg/kg diet for 7 days. With
    200 mg/kg no signs of intoxication were observed, whereas dosing with
    300 mg/kg or more caused weight loss, ataxia, subdued behaviour, head
    nodding, food regurgitation, inflammation of gums and tongue, body
    tremors and diminished response to stimuli. Haematological, clinical
    chemical and gross pathological examination showed no effects
    (Greenough & Goburdhun, 1984).

         In a further study, Beagle dogs (one male and one female)
    received 300 mg/kg diet for 3 days (male dog) or 4 days (female dog)
    and 250 mg/kg diet for 7 days. Both animals showed the above-mentioned
    signs of intoxication, the only difference being that when it was
    being fed the 250-mg/kg diet the female animal showed these signs more
    frequently than the male animal. There were no effects on haematology,
    clinical chemical parameters, urinalysis, faecal occult blood test or
    gross pathology (Greenough & Goburdhun, 1984).

         In a study by Greenough et al. (1984), 36 pure bred Beagle dogs
    (18 males and 18 females) received a diet containing
    alpha-cypermethrin at 0, 30, 90 or 270 mg/kg diet for 13 weeks. The
    group dosed at the highest concentration comprised six males and six
    females while the other groups consisted of four males and four
    females. All animals fed 270 mg/kg diet exhibited signs of
    intoxication, such as whole body tremors, head nodding, "lip-licking",
    subduedness, ataxia, agitation and a high-stepping gait. These signs
    increased in both intensity and duration as the study progressed. Food
    consumption, body weight gain, organ weights, ophthalmoscopy,
    haematological and clinical chemical parameters, urinalysis, gross
    pathology and microscopy of 18 organs and tissues of all test groups
    showed no dose-related effects. In this study, the no-observed-effect
    level was considered to be 90 mg/kg diet (equivalent to 2.25 mg/kg
    body weight).

    7.3  Skin and eye irritation; sensitization

    7.3.1  Skin irritation

         Undiluted technical alpha-cypermethrin was minimally irritating
    when applied as a single occluded dose for 24 h to intact and abraded
    rabbit skin (Dewar, 1981).

         New Zealand white rabbits were used to study the primary skin
    irritation of a number of alpha-cypermethrin formulations. The test
    duration was 4 h, the observation period was 7-21 days, and the
    formulations tested were 30 and 100 g/litre EC, 15 g/litre ULV, 10 and
    15 g/litre pour-on formulation, 15 and 100 g/litre SC, and
    Fastac/methomyl (15/120) EC. The EC formulations caused mild to
    moderate skin irritation. Superficial necrosis was observed in one or
    two animals treated with 100 g/litre EC, but there was no permanent
    in-depth skin damage. The effects persisted for up to 7 days. The EC
    formulations and the 100 g/litre SC formulation were classified as

    mildly irritating. All other formulations tested were either
    non-irritating or only slightly irritating (Rose, 1984c,d,e,f,h, 1985;
    Price, 1985a,b, 1986, 1988).

    7.3.2  Eye irritation

         Undiluted formulations were tested for their eye irritancy
    potential in groups of six rabbits using the Draize test. All the EC
    formulations tested (30 or 100 g/litre) caused severe eye irritation,
    including corneal opacity and damage to the iris (Rose, 1984d,e,f,
    1985).

         When an EC formulation (100 g/litre) and its components, both in
    the undiluted form and at typical in-use dilutions (1 in 400 and 1 in
    1333 aqueous dilution), were tested for eye irritancy potential, the
    undiluted formulation was severely irritating, with or without
    irrigation, while the undiluted blank formulations were mildly to
    severely irritating. The diluted test formulations, with or without
    alpha-cypermethrin or with emulsifier, were non-irritating. It was
    concluded that the eye irritation resulted from the combined
    formulation ingredients (especially the emulsifier) and that
    alpha-cypermethrin  per se gave only slight irritation, if any
    (Dewar, 1981; Rose, 1984b). In-use dilutions (0.0075%) of another 100
    g/litre EC formulation and its blank formulation were non-irritating
    (Rose, 1984g).

         Two pour-on formulations (10 and 15 g/litre) caused moderate and
    slight conjunctival inflammation, respectively. The 10 g/litre
    formulation was considered to be an eye irritant (Price, 1988). Two SC
    formulations (15 and 100 g/litre) were mildly irritating, causing
    slight conjunctival redness and chemosis (Price, 1985b, 1986). A 15
    g/litre ULV formulation was mildly irritating to rabbit eyes and there
    was a moderate initial pain response (Rose, 1984c). An EC formulation
    containing Fastac/methomyl (15:120 g/litre) was a severe eye irritant.
    The vascularization of the cornea and iritis were considered to be
    irreversible (Rose, 1984h).

    7.3.3  Sensitization

         Technical alpha-cypermethrin was tested in the guinea-pig
    maximization test of Magnusson and Kligman using groups of 10 male and
    10 female guinea-pigs and a control group of 55 animals of each sex.
    The following concentrations were used: intradermal injection, 0.05%
    (v/v) in corn oil; topical application and challenge, 50% (m/m) in
    vaseline. On the basis of the negative results it was concluded that
    alpha-cypermethrin is not a skin sensitizer in guinea-pigs (Dewar,
    1981).

          An EC formulation (100 g/litre) and its corresponding blank were
    tested, as a 50% solution in corn oil, in the Buehler guinea-pig
    sensitization test. The topical challenge was carried out with a 30%

    solution in corn oil. None of the animals showed positive responses at
    24 or 48 h after the challenge (Rose, 1984g).

    7.4  Long-term and carcinogenicity studies

         No long-term or carcinogenicity studies have been conducted with
    alpha-cypermethrin.

    7.5  Reproduction, embryotoxicity and teratogenicity

         Alpha-cypermethrin has not been tested for reproductive effects
    or teratogenicity.

         From the available reproduction and teratogenicity studies with
    cypermethrin it is clear that no influence on reproduction performance
    occurs at a level of 100 mg/kg diet, nor are there any teratogenic
    effects even with dose levels high enough to cause maternal toxicity
    (WHO, 1989). Furthermore, the no-observed-effect level of cypermethrin
    for reproduction and teratogenicity is comparable with the
    no-observed-effect levels based on other parameters of toxicity. In
    consequence, there is no reason to believe that alpha-cypermethrin,
    consisting of two cis isomers also present in cypermethrin, would
    behave differently.

    7.6  Mutagenicity and related end points

    7.6.1  Mutation

         The results of the various mutagenicity studies with
    alpha-cypermethrin are summarized in Table 5.

         Alpha-cypermethrin (in DMSO) at concentrations of 31.25, 62.5,
    125, 250, 500, 1000, 2000 or 4000 µg/ml did not increase reverse gene
    mutation (at the arg 4-17, trp 5-48 or hom 3-10 markers) in log- or
    stationary-phase cultures or forward mutation (to cyclo-heximide
    -resistance) in log-phase cultures of  Saccharomyces cerevisiae XV
    185-14C, either in the presence or absence of rat-liver S9 fraction.
    Concentrations of 10 and 50 µg/ml 4-nitroquinoline- N-oxide and 1250
    and 5000 µg/ml cyclophosphamide were used as positive controls
    (Brooks, 1984).

         Alpha-cypermethrin (in DMSO) at concentrations of 31.25, 62.5,
    125, 250, 500, 1000, 2000 or 4000 µg/plate, both with and without
    microsomal activation, did not increase reverse mutation rates in
     Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538 or in
    Escherichia coli WP2 and WP2 uvr A. Mitotic gene conversion was not
    induced in liquid suspension cultures of log-phase cells of
     Saccharomyces cerevisiae JD 1, dosed with solutions of
    alpha-cypermethrin at concentrations of 10, 100, 500, 1000 or 5000
    µg/ml, both in the presence or absence of a rat liver S9 fraction.

    These studies were carried out in comparison with four positive
    control compounds (Brooks, 1982).

    7.6.2  Chromosomal effects

         In a study by Clare & Wiggins (1984), groups of five male and
    five female Wistar rats were administered a single oral dose of 2, 4
    or 8 mg alpha-cypermethrin in 5% corn oil/kg body weight and killed 24
    h after dosing. The control group received corn oil alone.
    Cyclophosphamide was used as a positive control. Alpha-cypermethrin
    caused no increase in the incidence of chromatid or chromosome
    aberrations or polyploidy in bone marrow cells.

         Alpha-cypermethrin in aqueous carboxymethylcellulose at
    concentrations of up to 40 µg/ml did not increase the frequency of
    chromatid gaps, chromatid breaks or total chromatid aberrations in rat
    liver (RL4) cell cultures (Brooks, 1982).

    7.6.3  DNA damage

         Alpha-cypermethrin in DMSO (20%) was administered to Wistar rats
    as a single oral dose of 40 mg/kg body weight. The exposure time was
    6 h. Alpha-cypermethrin failed to produce any detectable DNA
    single-strand damage using alkaline elution profiles of liver DNA.
    Methylmethane sulfonate was used as a positive control and DMSO as the
    solvent control (Wooder, 1982).

    7.6.4  Conclusion

         From the available data on alpha-cypermethrin, it can be
    concluded that this compound is non-mutagenic in tests with
     Salmonella typhimurium, Saccharomyces cerevisiae, and  in vivo and
     in vitro tests with rat liver cells for the induction of chromosome
    aberration and production of DNA single-strand damage.


        Table 5.  Mutagenicity tests on microorganisms
                                                                                                                        
    Organism/strain               Dose                   Type of test         Metabolic    Result       Reference
                                                                              activation
                                                                                                                        
     Salmonella typhimurium       up to 4000 µg/plate    plate                with or      negative     Brooks (1982)
    TA98, TA100, TA1535,                                                      without
    TA1537, TA1538

     Escherichia coli             up to 4000 µg/plate    plate                with or      negative     Brooks (1982)
    WP2, WP2 uvrA                                                             without

     Saccharomyces cerevisiae     up to 5000 µg/ml       liquid suspension    with or      negative     Brooks (1982)
    JDI                                                  culture              without

    Saccharomyces cerevisiae      up to 4000 µg/ml       liquid suspension    with or      negative     Brooks (1984)
    XV 185-14C                                           culture              without

    Rat liver cells (RL4)         up to 40 µg/ml                                           negative     Brooks (1982)
    (chromatid gaps, breaks or
    aberrations)

    Rat liver DNA                 one oral dose of                                         negative     Wooder (1982)
    (DNA single strand damage)    40 mg/kg body weight

    Rat bone marrow               one oral dose of                                         negative     Clare & Wiggins
    chromosome study              up to 8 mg/kg body                                                    (1984)
                                  weight
                                                                                                                        
    

    7.7  Special studies

    7.7.1  Skin sensation

         It is known that exposure to certain types of pyrethroids can
    result in a transient skin sensation in humans (Le Quesne et al.,
    1980).

         Guinea-pigs received 0.1 ml of a 0.01, 0.1 or 1.0% solution of
    alpha-cypermethrin in ethanol or a 1, 10 or 20% solution of
    alpha-cypermethrin (w/v) in corn oil on the skin. Sensory stimulation
    was quantified by counting the number of times each animal turned to
    lick or bite its treated flank in preference to the non-treated flank.
    Skin stimulation was observed during a 2-h period at all dose levels
    except the lowest. In the groups of guinea-pigs treated with 10% and
    20%, some animals exhibited an exaggerated hopping movement and a
    repeated head shaking activity at the time of maximum skin stimulation
    (40-60 min after treatment). This behaviour was not seen with the 1%
    solution or more dilute ones (Hend, 1983).

    7.7.2  Neurotoxicity

         Large oral doses of alpha-cypermethrin and other synthetic
    pyrethroids (WHO, 1989) have been shown to produce minor
    histopathological lesions in the sciatic nerve of rats, described as
    sparse axonopathy in peripheral nerves.

         Rose (1983b) conducted a two-phase study. In the first phase, the
    time-course for development and recovery from pyrethroid-induced nerve
    lesions was investigated by measuring biochemical correlates of
    neuropathological change (the enzymes beta-glucuronidase and
    beta-galactosidase) in groups of Wistar rats (five of each sex per
    group) at periods of 2-12 weeks after the start of dosing. The daily
    doses of alpha-cypermethrin (96.6%), administered by stomach tube,
    were 37.5 mg/kg body weight for the first 11 doses and 25.0 mg/kg body
    weight for the subsequent 9 doses over a 4-week period (5 times/week).
    DMSO was used as the solvent for 10 doses and then arachis oil. In
    all, 21% of the animals died and more than 80% of the treated animals
    showed clinical signs of intoxication. Maximum enzyme activities in
    the sciatic posterior tibial nerves were found 5 weeks after the start
    of the experiment and had returned to control values by 12 weeks. In
    the trigeminal nerve and trigeminal ganglia, a slight but not
    significant increase in enzyme activities was found.

         In the second phase of the study, 10 male and 10 female Wistar
    rats were given 20 oral doses of alpha-cypermethrin in DMSO (0, 10, 20
    or 40 mg/kg body weight per day) over a period of 4 weeks (5
    times/week). Only two animals died, one given 10 mg/kg and one given
    20 mg/kg. In the 40-mg/kg group, 75% of the animals developed clinical
    signs, whereas in the 20-mg/kg group only 25% of the animals showed
    these clinical effects. In the 10-mg/kg group, the animals showed no

    differences from the controls. No clear influence of
    alpha-cypermethrin on growth was found. Five weeks after the initial
    dose, which corresponded to the period of maximal enzyme changes,
    biochemical changes (increases of up to 60%) indicative of a mild
    axonal degeneration were found in both the distal and proximal
    sections of the sciatic posterior tibial nerve in animals administered
    40 mg/kg body weight. In the 20-mg/kg group, only a small (up to 20%)
    increase in beta-galactosidase activity was found in the proximal
    sections of the sciatic posterior nerve. The same trends were found in
    the trigeminal nerve and ganglia. No changes were found in the
    10-mg/kg group (Rose, 1983b).

    7.7.3  Immunosuppressive action

         No data on the immunosuppressive action of alpha-cypermethrin are
    available.

    7.8  Mechanism of toxicity - mode of action

         The mechanism of toxicity and mode of action of cypermethrin (and
    other pyrethroids) are extensively described in section 8.8 of the
    Environmental Health Criteria 82: Cypermethrin (WHO, 1989). Recently
    Vijverberg & van den Bercken (1990) and Aldridge (1990) summarized
    current knowledge of the neurotoxicity and mode of action of the
    different pyrethroids (see also Appendix 1).

         Pyrethroids induce toxic signs that are characteristic of a
    strong excitatory action on the nervous system. Toxic doses generally
    cause hypersensitivity to sensory stimuli, and a number of compounds
    may induce tingling sensations in the skin. Two distinct toxic
    syndromes have been described in mammals. The T-syndrome is induced by
    pyrethrins and non-cyano pyrethroids, and the CS-syndrome, induced by
    cyano-pyrethroids such as cypermethrin and alpha-cypermethrin, is
    characterized by choreoathetosis and salivation.

         The available data 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 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 (for instance cypermethrin and alpha-cypermethrin) 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 (with no alpha-cyano
    group) and the two insecticides cypermethrin and alpha-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 between the symptoms of poisoning
    by alpha-cyano pyrethroids and those of 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.

         Because of the universal character of the processes underlying
    nerve excitability, the action of pyrethroids should not be considered
    to be 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 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.

    8.  EFFECTS ON HUMANS

    8.1  General population exposure

         No data concerning the exposure of the general population to
    alpha-cypermethrin are available.

    8.2  Occupational exposure

         A study of alpha-cypermethrin exposures was carried out during
    formulation using both technical concentrate and technical material at
    Durban, South Africa. The oil-damped solid, crystalline, dry technical
    concentrate contained a minimum of 90% (m/m) alpha-cypermethrin.
    Exposures were assessed by personal and static monitoring of
    atmospheric alpha-cypermethrin concentrations, urinary
    alpha-cypermethrin metabolite concentrations and by medical
    examination. Four individuals were exposed during 3 days of operation.
    The group mean personal exposures for the two days whilst formulating
    technical concentrate were 2.8 and 4.9 µg/m3 and the group mean
    personal exposure to technical material on day 3 was 54.1 µg/m3.
    Urinary alpha-cypermethrin metabolites could not be identified (limit
    of detection, 0.02 mg/litre). Formulation was successfully completed,
    only minor skin sensations being reported by two of the
    non-operational personnel, possibly resulting from particles of
    alpha-cypermethrin settling directly on the skin, face and neck. Dust
    concentrations were up to 30 times greater during handling the
    technical material compared with oil-damped technical concentrate, and
    local exhaust dust extraction reduced dust emission by a factor of up
    to 17 (Western, 1984).

    9.  EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

                                 Appraisal

          The acute toxicity of alpha-cypermethrin to Daphnia magna and
     Gammarus pulex is similar to that of cypermethrin. However, in a
     reproduction study with Daphnia magna, alpha-cypermethrin seemed to
     be slightly more toxic than cypermethrin. Comparison of the results
     of a reproduction study in Daphnia magna with the results of acute
     tests shows that the hazard of alpha-cypermethrin lies in its acute
     toxicity. There is no significant potential for cumulative effects
     occurring as a result of long-term exposure to lower concentrations.

          Alpha-cypermethrin is highly toxic to a number of aquatic
     arthropod taxa but of low toxicity to molluscs. The short-term
     toxicity of the compound can be reduced by formulating the product as
     an OSC. Contamination through spray drift from commercial
     applications will generally be low, and so the effects on susceptible
     taxa will be limited. The rapid loss of alpha-cypermethrin from the
     water gives the potential for complete recovery of affected
     populations.

          Laboratory studies show that values for the acute toxicity and
     the toxicity to the early-life stages of fish are similar for
     alpha-cypermethrin and cypermethrin. A comparison of the results from
     both alpha-cypermethrin studies reveals that the hazard of the
     compound results from its acute toxicity, and there is no significant
     potential for additional effects occurring as a result of long-term
     exposure to lower concentrations. Laboratory and field studies have
     shown that the toxicity of alpha-cypermethrin to fish is greatly
     influenced by the formulation, particulate formulations showing
     significantly less toxicity than emulsifiable concentrates.

          Field studies demonstrate that the high toxicity of
     alpha-cypermethrin to fish observed in laboratory studies is not
     realized under field conditions. Contamination of water bodies by
     inadvertent overspraying or spray drift does not present a hazard to
     fish.

    9.1  Microorganisms

    9.1.1  Algae

         The acute toxicity of alpha-cypermethrin to a single-celled green
    alga,  Selenastrum capricornutum, at 24 °C has been determined. The
    pesticide was dispersed using acetone, and the 2- to 4-day EC50 for
    growth was above 100 µg/litre (Stephenson, 1982).

    9.1.2  Bacteria

         The effects of cypermethrin on microbial activity in the soil
    have been investigated in a series of studies. Cypermethrin was
    applied to sandy loam at concentrations of 2.5 and 250 mg/kg. No
    effects on the rates of carbon dioxide evolution or oxygen uptake were
    observed at the lower rate, but significant inhibition of carbon
    dioxide evolution and a decrease in oxygen uptake were observed at the
    higher rate of application. There were no effects at either
    concentration on nitrogen fixation, ammonification, nitrification or
    glucose utilization (WHO, 1989).

         Sewage bacteria were unaffected by the presence of
    alpha-cypermethrin (3 mg/litre) in a closed system test, while the
    growth of Pseudomonas fluorescens was unaffected at 100 mg/litre
    (Stone & Watkinson, 1983).

    9.2  Aquatic organisms

    9.2.1  Invertebrates

    9.2.1.1  Laboratory studies

         Acute toxicity studies with  Daphnia magna (aged < 24 h) showed
    that at 20 °C technical alpha-cypermethrin, dispersed in acetone under
    static conditions (daily renewal), has effects at concentrations below
    1 µg/litre. The 24-h and 48-h EC50 values (immobilization) were 1.1
    and 0.3 µg/litre, respectively (Stephenson, 1982).

         Water samples taken from field enclosures 24 h after treatment
    with an EC formulation were analysed for alpha-cypermethrin and
    bioassayed with  Gammarus pulex. The 24-h LC50 value for this
    organism was 0.05 µg/litre (Garforth, 1982a; Shires, 1982).

         The effect of technical alpha-cypermethrin on survival, growth
    and reproduction of  Daphnia magna was studied over a period of 21
    days by Garforth (1982b). The test solution was renewed daily and the
    temperature ranged between 18.5 and 20.2 °C. The results are
    summarized in Table 6.

    Table 6. Effects of alpha-cypermethrin on the reproductive cycle of
    Daphnia magnaa
                                                                        
    Effect                              Nominal concentration (µg/litre)
                                        LOEL                    NOEL
                                                                        
    Survival of parent generation       0.3                     0.1

    Growth of parent generation         0.1                     0.03

    Production of young                 0.1                     0.03
                                                                        

    a    From: Garforth (1982b)
         LOEL = Lowest-observed-effect level; NOEL = No-observed-effect
         level

    9.2.1.2  Field studies

         Garforth (1982a) studied the effects of alpha-cypermethrin on a
    range of aquatic invertebrates in metal enclosures, each containing
    about 1 m3 water, placed in an outdoor experimental pond. A diluted
    EC formulation was sprayed onto the water surface at concentrations of
    1, 3, 10, 30 and 100 g active ingredient/ha, and samples were taken up
    to 7 days after application. The concentration of alpha-cypermethrin
    was around 50% of the nominal level 24 h after application and
    decreased to 10 to 20% of the nominal level 7 days after application.
    The lowest concentration was toxic to  Asellidae. Thirteen families
    of aquatic arthropods were tested; most were killed at 1 g/ha except
    one species of  Coenagriidae, which tolerated about 3 g/ha. Three
    families of molluscs were tested and were found to be unaffected at
    100 g/ha.

         Studies to investigate the relative toxicity of two formulations
    of alpha-cypermethrin (a 100-g/litre EC and a 100-g/litre oil-enhanced
    suspension concentrate (OSC) with and without anti-evaporant agents)
    to aquatic invertebrates have been carried out. Water samples were
    taken from field enclosures treated with a range of doses (0.1-5 g/ha
    for the EC and 0.1-10 g/ha for the two OSC formulations) and
    bioassayed with  Gammarus pulex. The 24-h LD50 values (in g
    alpha-cypermethrin/ha equivalents) of water samples taken 24 h after
    application were 0.9 for the EC, 6.3 for the OSC without
    anti-evaporant, and 2.8 for the OSC plus anti-evaporant formulation.
    Thus, one day after treatment, both OSC formulations were less toxic
    to  Gammarus pulex than the EC formulation. However, the EC
    formulation lost its toxicity more rapidly than either of the OSC
    formulations (see also section 4.1.2). The effects on other aquatic
    invertebrate communities could not be accurately assessed, since the
    results for macro-arthropods and zooplankton were inconclusive.
     Coenagriidae, Chironomidae and zooplankton seemed to be relatively
    tolerant. The residues in water and sediment, 22 days after treatment
    with the EC at 2 g alpha-cypermethrin/ha or with both OSC formulations

    at 5 g/ha, were < 0.004 µg/litre and < 0.01 mg/kg, respectively, for
    all three formulations (Inglesfield, 1985b).

         The hazard to aquatic invertebrates resulting from spray drift
    from the aerial application of an EC (15 g alpha-cypermethrin/ha) has
    been investigated by Garforth & Woodbridge (1984). Details of the
    study are described in section 9.2.2.2. The sub-surface water
    concentration was 0.6 µg alpha-cypermethrin/litre shortly after
    application and decreased to < 0.02 µg/litre within 2 to 4 days. The
    contamination initially caused a significant reduction in the
    abundance of several groups of aquatic arthropods, including beetles,
    chironomids, corixids, mites and zooplankton. However, within 4 to 7
    weeks the affected fauna had completely recovered.

         In a study by Pearson (1990), two freshwater ponds were treated
    with alpha-cypermethrin as an emulsifiable concentrate in 1987. One
    pond was oversprayed at 15 g active ingredient/ha, while the other was
    treated with the same amount of alpha-cypermethrin but by direct
    incorporation into the water (see section 4.1.2). Indigenous
    populations of zooplankton nauplii and of copepods ( Cyclops spp.)
    were significantly reduced in both ponds by the treatment but
    recovered within 26-45 days. Other zooplankton were not plentiful but
    appeared to be less severely affected in the oversprayed pond than in
    the pond treated by incorporation. Populations of phantom midge larvae
    ( Chaoborus spp) were killed by both treatments. However, within 47
    days after treatment, populations of young larvae had developed in the
    oversprayed pond to almost pre-treatment numbers, and to a lesser
    extent in the pond with direct incorporation.

    9.2.2  Fish

    9.2.2.1  Laboratory studies

         The available acute 96-h LC50 values for two fish species are
    summarized in Table 7.

         The effects of the type of formulation on the acute toxicity to
    fish are summarized in Table 8. Suspension concentrate, wettable
    powder and micro-encapsulated formulations were 10 to 70 times less
    acutely toxic to rainbow trout than the EC formulation (Shires,
    1983b).


        Table 7. Acute toxicity of technical alpha-cypermethrin in fish
                                                                                                                                     
    Species                 Mean weight     Vehicle             Test system     Temperature   96-h LC50            Reference
                                (g)                                                (°C)       (µg/litre) (95%
                                                                                              confidence limits)
                                                                                                                                     
    Rainbow trout               3.3         dispersed via       static water;       15              2.8            Stephenson (1982)
     (Oncorhynchus mykiss)                  acetone             12 h renewal of                  (2.1-3.5)
                                                                test solutions

    Fathead minnow              0.76        adsorbed onto       continuous         23-25           0.93            Stephenson (1983)
     (Pimephales promelas)                  pumice              flow-through                    (0.78-1.2)
                                                                                                                                     

    Table 8. Effect of type of formulation on the toxicity of alpha-cypermethrin to fish in laboratory studies
                                                                                                                           
    Species               Weight            Tempera-            Formulation                   96-h LC50      Reference
                            (g)             ture (°C)                                         (µg/litre)
                                                                                                                           
    Rainbow trout         0.8-2.5              15               100 g/litre EC                  5.6          Shires (1983b)
      (Oncorhynchus                                             250 g/litre SC                  350
      mykiss)                                                   100 g/kg WP                     120
                                                                50 g/kg WP                      220
                                                                50 g/kg ME                    > 100
                                                                50 g/kg CD                      65

    Rainbow trout        0.11-0.25             15               15 g/litre OSC                  10a          Pearson (1986)
      (Oncorhynchus                                             15 g/litre OSC                  71
      mykiss)                                                   100 g/litre OSC                 16a
                                                                100 g/litre OSC                 56

    Common carp            3.5-4              24-30             100 g/litre OSC                 11           Stephenson
      (Cyprinus carpio)                                         15 g/litre EC                   0.8          (1986)
                                                                50 g/kg WP                      60

     Puntius              0.3-0.5             24-30             100 g/litre OSC                 3.2          Stephenson
      gonionotus                                                15 g/litre EC                   0.7          (1986)
                                                                50 g/kg WP                      22
                                                                                                                           

    a  Denotes daily renewal of test solutions. All other tests were carried out without renewal of the test solutions.
       EC = emulsifiable concentrate; SC = suspension concentrate; OSC = oil-enhanced suspension concentrate; WP= wettable powder;
       ME = micro-encapsulated;
       CD = ß-cyclodextrin.
    

         The toxicity of alpha-cypermethrin to the early-life stages of
    fish has been studied in a 34-day continuous-flow embryo-larval test
    with the fathead minnow  (Pimephales promelas). Eggs less than 24 h
    old were exposed to nominal concentrations of 0.03 to 1.0 µg/litre.
    Pre-hatch, post-hatch and overall mortality and final body weight were
    recorded. On the basis of the most sensitive parameter (overall
    survival) and measured exposure concentrations, the lowest
    concentration of alpha-cypermethrin producing an adverse effect was
    0.09 µg/litre and the highest concentration producing no effect (NOEL)
    was 0.03 µg/litre (Stephenson, 1983).

    9.2.2.2  Small scale field or outdoor tank studies

         The acute effect of formulation on the toxicity of
    alpha-cypermethrin to fish under field conditions was investigated in
    studies using stainless steel enclosures placed in an experimental
    pond. In the first study (Shires, 1983b), the rainbow trout (13-32 g)
    was the test species and the results are summarized in Table 9. The EC
    formulation was at least 30 times more toxic than any of the other
    formulations. The number of fish used was not reported.

    Table 9. Effect of formulation on the toxicity of alpha-cypermethrin
    to rainbow trout in field studies
                                                                        
              Formulation                   14-day LD50 (g active
                                            ingredient/ha equivalent)
                                                                        
    100 g/litre emulsifiable concentrate           29

    250 g/litre suspension concentrate           > 1000

    100 g/kg wettable powder                     > 1000

    50 g/kg micro-encapsulated                   > 1000
                                                                        

         In the second study, Stephenson (1987c) tested an 1.5%
    oil-enriched SC formulation of alpha-cypermethrin in outdoor tanks
    containing carp ( Cyprinus carpio; 6.3 g). The application rate was
    approximately 4, 8 and 15-16 g active ingredient/ha applied by hand
    sprayer. The water temperature ranged from 23-26 °C, the water was
    aerated and the duration of the experiment was 7 days. There was 20%
    mortality at all treatment rates, which was comparable with the
    control group. The number of fish used was not reported.

         In the third study (Shires, 1985b), rainbow trout ( Oncorhynchus
     mykiss; 2-5 g) were introduced into open-ended stainless steel
    enclosures placed in a mature experimental pond. Different volumes of
    alpha-cypermethrin (as a diluted EC containing 100 g active
    ingredient/litre) were applied with a hand-held sprayer onto the water
    surface. The dose rates were equivalent to 5-500 g active

    ingredient/ha. The concentrations in the water samples were dependent
    on the dose applied and the time after the treatment that the samples
    were taken. For instance, with a dose of 5 g alpha-cypermethrin/ha the
    concentration in the water was 0.4 µg/litre or less after 96 h,
    whereas with a dose of 500 g/ha residues of up to 30 µg/litre were
    found. Alpha-cypermethrin was toxic to the rainbow trout at a
    concentration of about 2-5 µg/litre water. In terms of nominal
    application rate, the no-observed-effect level for alpha-cypermethrin
    lies between 50 and 100 g alpha-cypermethrin/ha. These dose rates are
    much higher than those used for crop protection purposes.

         In a further study, 20 rainbow trout were placed in stainless
    steel enclosures in a shallow pond. The diluted EC and SC formulations
    were sprayed onto the surface of the water and the fish were monitored
    for mortality over 8 days. The SC formulation did not cause mortality,
    even at an application rate equivalent to 300 g active ingredient/ha.
    However, high mortality (90%) occurred with the EC formulation at 30
    g/ha alpha-cypermethrin, but application of 10 g active ingredient/ha
    did not cause mortality. From these results it is clear that the SC
    formulation has a lower toxicity than the EC formulation (Stephenson,
    1987b).

         The hazard to fish caused by spray drift from aerial applications
    of alpha-cypermethrin to agricultural land has been investigated by
    Garforth & Woodbridge (1984). The trial site was a cereal field
    bordered on one side by a freshwater ditch. The water's edge was
    generally less than 2 m from the crop margin. Four days prior to
    application, two cages, each containing 15 common carp ( Cyprinus
     carpio; 30-50 cm) were placed in the ditch. The ditch was known to
    contain a good stock of different types of fish, macroinvert-ebrates
    and zooplankton. An alpha-cypermethrin EC containing 100 g/litre was
    applied by air at 15 g active ingredient/ha to the crop when a gentle
    breeze was blowing from the crop over the ditch. The
    alpha-cypermethrin concentration in the sub-surface water was 0.6
    µg/litre shortly after the application and decreased to < 0.02
    µg/litre within 2 to 4 days (see section 4.1.2.). None of the fish
    died and no adverse effects were observed either on the carp placed in
    the cages or on the indigenous species. It was concluded that
    inadvertent contamination of water bodies by spray drift resulting
    from the normal commercial use of alpha-cypermethrin does not present
    a hazard to fish.

         Several field tests in rice paddies have examined the toxicity of
    alpha-cypermethrin to fish.

         Stephenson (1986, 1987b) investigated the acute toxicity of 15
    g/litre EC, 100 g/litre OSC and 50 g/kg WP formulations to fish in
    plots of rice paddy in West Java. The application rates were 7.5, 15,
    and 30 g alpha-cypermethrin/ha for the EC and OSC formulations and 30
    g alpha-cypermethrin/ha for the WP formulation. Each of the
    insecticide treatments was applied to the same plot on two separate

    occasions; once 12 days after transplantation of the rice seedlings
    and again 57 days after the transplantation. Prior to application, two
    cages each containing 20 carp  (Cyprinus carpio) (2.5-5 g) and two
    cages each containing 20 specimens of  Puntius gonionotus (1.4-5 g)
    were placed in trenches cut in each plot. In addition, before the
    first experiment, 30 fish of each of these two species were released
    to swim freely in each plot. Survival of the fish was monitored daily
    up to 7 days after each treatment. The water temperature was between
    25 and 36 °C. Following the first application, only the EC formulation
    at 15 and 30 g/ha resulted in significant mortality of caged and
    free-swimming carp and  Puntius gonionotus. The same was true for
    carp following the second application, but no results were available
    for Puntius gonionotus following the second application due to an
    outbreak of disease among these fish.

         Two other field studies were carried out in West Java to examine
    the effects of an OSC formulation on the growth and survival of
    free-swimming carp (6-8 g) in rice paddies. Experimental conditions
    were similar to those described above for the acute studies. The water
    temperature was 23-32 °C. In the first experiment, treatments with 15
    g active ingredient/ha were carried out 21 and 33 days after
    transplantation of the rice seedlings. In the second experiment, the
    same dose rate was applied 51 and 64 days after transplanting. The
    fish were monitored over periods of 3 to 4 weeks in each experiment.
    No adverse effects on survival and growth of the carp were observed
    (Stephenson, 1987a,b).

    9.3  Terrestrial organisms

    9.3.1  Earthworms

         The toxicity of technical alpha-cypermethrin to the red
    earthworm,  Eisenia foetida, has been assessed in laboratory tests.
    In the filter paper contact toxicity test, 50% mortality occurred
    within 48 h at a dose of about 0.01 mg/cm2 of filter paper. However,
    increases in the dose up to 1 mg/cm2 did not result in a significant
    increase in mortality. In the artificial soil test no significant
    mortality occurred within a period of 14 days in earthworms exposed to
    up to 100 mg alpha-cypermethrin/kg soil (Inglesfield & Sherwood,
    1983).

    9.3.2  Invertebrates - field studies

         In a study designed to investigate the effects of
    alpha-cypermethrin on non-target arthropod fauna in Italian vineyards,
    two formulations of alpha-cypermethrin were tested, i.e. an
    emulsifiable concentrate (100 g active ingredient/litre) and a
    suspension concentrate (250 g active ingredient/litre). Both were
    diluted to 1.25 g active ingredient/ha and sprayed to run-off. The
    effect on predators and parasites (crop foliage fauna) such as
    parasitoid  Hymenoptera, Heteroptera and  Chrysopa carnea, soil

    surface predators such as  Coleoptera and  Araneae, phytophagous
    arthropods such as  Homoptera, Thysanoptera and  Acari, and other
    invertebrates such as nematocerous, Diptera and epigeal fauna was
    inconclusive but in most cases negative. Spiders were the only group
    significantly affected by alpha-cypermethrin. The abundance of major
    phytophagous insect taxa  (Homoptera, Thysanoptera and Acari) was
    markedly reduced by both treatments although neither treatment had any
    long-term adverse effects (Inglesfield, 1984).

         An emulsifiable concentrate (EC) of alpha-cypermethrin was tested
    on the non-target arthropod fauna of maize in France at 20 and 30 g
    active ingredient/ha and applied using tractor-mounted boom and nozzle
    equipment at different stages of crop development. Organisms from the
    following taxa were collected: phytophagous arthropods  (Aphidoidea),
     Thysanoptera (Thripidae), Cicadellidae and entomophagous arthropods;
    predatory  Coleoptera (Coccinellidae, Cantharidae, Carabidae and
     Staphylinidae); parasitoid  Hymenoptera (Braconidae, Chalcidoidea);
    and predatory  Diptera, Neuroptera and  Aranea. In addition, the
    effects on community structure were studied. The two treatments
    reduced transiently the numbers of some of the entomophagous taxa,
    especially  Coccinellidae (Coleoptera), Carabidae (Coleoptera),
     Neuroptera and  Araneae. Alpha-cypermethrin at a concentration of
    20 g/ha promoted some late-season resurgence of aphid populations
    (Inglesfield, 1985a).

         A large-scale replicated field experiment was carried out in
    Indonesia to investigate the effects of an EC (10 g and 20 g
    alpha-cypermethrin/ha) and an OSC (10 g and 20 g alpha-cypermethrin
    per ha), applied at 17 and 62 days after transplanting using a single
    fan-jet nozzle knapsack sprayer, on rice pests and their natural
    enemies. Alpha-cypermethrin was applied at two crop stages, and
    populations of both pests and beneficial arthropods were monitored
    throughout the season. Alpha-cypermethrin produced good control of
    stemborers, grasshoppers, leafhoppers and stinkbugs, the most numerous
    pests found during the trial. It had a significant but short-lived
    effect on spiders and, generally, no effect on either dragon-flies or
    other beneficial arthropods (Shires & Inglesfield, 1986).

         A study was initiated in England in 1982 to compare the effects
    on entomophagous arthropods of annual applications of an EC of
    alpha-cypermethrin (at a rate of 10 g active ingredient/ha in the
    first year and 15 g active ingredient/ha in subsequent years) with
    those resulting from the use of non-pyrethroid products. The study was
    carried out on a range of crops (oilseed rape, wheat and barley) over
    the duration of a 5-year arable crop rotation. A field of 8 ha was
    divided into two equal areas, and each year alpha-cypermethrin was
    applied to one of the areas and other products to the other area. All
    treatments were carried out with standard tractor-driven boom and
    nozzle spraying equipment. The crop rotation was as follows: winter
    rape in 1982, winter wheat in 1983 and 1984, and winter barley in
    1985. Organisms from a variety of taxa were collected during the

    study, such as parasitoid  Hymenoptera, predatory  Diptera,
    predatory  Coleoptera, Araneae, phytophagous insects and other
    arthropods. The results indicated that any difference between the
    effects of alpha-cypermethrin and the reference compounds on
    entomophagous arthropods was generally short-lived. There is no
    evidence that alpha-cypermethrin treatments had any long-term effects
    on any of the taxa studied. In addition, there appeared to be no
    long-term effects on the relative abundance of entomophages within the
    arthropod communities or on the structure and integrity of the
    arthropod communities of which they form a part (Inglesfield, 1985c,
    1988, 1989).

         The results of these studies have been reviewed by Inglesfield
    (1991). They showed that field application of alpha-cypermethrin and
    cypermethrin had no adverse effects on the relative abundance of
    entomophages within the arthropod communities and that the use of
    these two pesticides in small grain cereals would not be associated
    with pest "resurgence" or the development of secondary pest
    infestations.

    9.3.3  Honey-bees

    9.3.3.1  Laboratory studies

         The oral administration of alpha-cypermethrin in acetone produced
    a 24-h LD50 of 0.06 µg/bee, whereas an EC formulation (100 g/litre)
    of the pesticide yielded a 24-h LD50 of 0.13 µg formulation/bee.
    After topical application, 24-h LD50 values of 0.03 µg (technical)
    and 0.11 µg (EC) per bee were obtained (Murray, 1985).

         The mortality of honey-bees  (Apis mellifera) exposed to
     Phacelia flowers 30 min after they had been treated with an EC
    formulation (15 g active ingredient/ha) in a residual test was low
    (15%) within 48 h. However, the foraging activity was reduced (Murray,
    1985).

         The residual toxicity to the honey-bee of alpha-cypermethrin as
    EC, OSC, and EC/fungicide mixtures has been investigated. Bees were
    exposed for 48 h to flowering  Phacelia campanularia plants that had
    been sprayed with each formulation at a rate of 10 or 20 g active
    ingredient/ha, and the mortality was assessed 24 and 48 h after
    initial exposure to the treated plants. Although there was great
    variation in the results, there appeared to be no difference in the
    residual toxicity of the EC and OSC formulations at a rate of 10 g
    active ingredient/ha. However, at 20 g active ingredient/ha the OSC
    appeared to be more toxic than the EC. Application of the EC in
    admixtures did not appear to significantly increase bee mortality
    (Hillaby & Inglesfield, 1986).

    9.3.3.2  Field studies

         Alpha-cypermethrin, applied as an EC (10 and 20 g active
    ingredient/ha) by tractor-mounted boom and nozzle equipment to small
    plots of flowering mustard in France, caused a sharp decline in
    foraging activity of bees immediately after application, but there was
    a return to normal activity within a few hours. No effect on bee
    survival or hive development was observed (Shires, 1983a; Shires et
    al., 1984b; Shires, 1985a).

         In a further study, the same EC formulation was applied at the
    same concentration on large isolated fields of flowering oilseed rape
    during peak foraging activity of honey-bees in France. No increase in
    bee mortality was found, but foraging activity declined for a few
    hours after application at a rate of 10 g active ingredient/ha. With
    a rate of 20 g active ingredient/ha a more prolonged decline in
    foraging activity occurred. No effects on the overall condition of the
    hives were seen at the end of the season and very low or undetectable
    residues were found in dead bees, pollen, honey and wax (Shires et
    al., 1984c; Shires, 1985a).

         Two large and two small plots of winter wheat were enclosed
    beneath large mesh-covered tunnels. A small bee-hive was placed in
    each tunnel and sucrose solution was sprayed onto all of the wheat in
    order to simulate aphid honey dew. Alpha-cypermethrin (an EC at 10, 15
    or 30 g active ingredient/ha) was applied to the larger plots of wheat
    when the bees were actively foraging the sugar deposits. No increase
    in bee mortality, compared with that in the pre-treatment period, was
    observed. Foraging activity in the plots declined sharply after
    treatment and remained at a reduced level, probably because of its
    repellent effect. Examination of the hives about 2 weeks after the
    trial showed that the hives, both the control and the
    alpha-cypermethrin-treated, were in excellent condition with strong
    adult populations and large areas of developing brood. In
    post-treatment samples, alpha-cypermethrin residues of 0.03 mg/kg of
    honey and 0.01 mg/kg of wax were found. In live and dead bees
    collected from the tunnel treated with 15 g/ha, a concentration of
    0.026 µg/bee was found (Shires et al., 1984a; Le Blanc, 1985).

         In a study by Inglesfield & Forbes (1986), alpha-cypermethrin was
    applied as an OSC (10 g active ingredient/ha) and an EC (10 g active
    ingredient/ha) to three fields of flowering winter-sown oilseed rape
    in Germany while bees were actively foraging the crops. None of the
    treatments had any significant effect on adult bee survival or on the
    longer-term development of the experimental colonies. The number of
    bees actively foraging in the crops declined following application.
    This reduction in activity can probably be partly attributed to the
    repellent effects of these treatments. Both the OSC and EC
    formulations of alpha-cypermethrin had similar effects on bee
    behaviour. Residues of alpha-cypermethrin in post-treatment samples of

    pollen, honey and wax were below 0.01 mg/kg. In dead bees, the residue
    on the day of application with the OSC was 1.8 mg/kg and in the case
    of the EC was 0.12 mg/kg.

         A diluted EC formulation of alpha-cypermethrin (mixed with the
    fungicide vinclozolin, 100 g active ingredient/ha) was applied by a
    tractor-driven boom and nozzle sprayer, at a rate of 20 g active
    ingredient/ha, to a 206-ha block of flowering oilseed rape situated in
    Kent, England. Shortly before spraying, which took place over a 3-day
    period, five beehives were positioned at each of two sites adjacent to
    the crop. At each site the hives were either fitted with pollen traps
    or with traps to collect dead bees as they were removed from the hive.
    The hives were observed daily before and for ten days after spraying.
    Hive activity was recorded at intervals each day, and, on days when
    bees were flying, pollen traps were set and samples of pollen
    collected. Following the application of alpha-cypermethrin the bees
    foraged normally. At least 90% of the pollen returned to the hives
    during the immediate post-treatment period was found to be from
    oilseed rape, showing that the bees had continued to forage on the
    treated crop. The number of dead bees collected remained low
    throughout the study and did not increase after application of the
    alpha-cypermethrin. After the study, all hives were in good condition
    and subsequently yielded a good crop of honey. A local beekeeper with
    many hives adjacent to the same block of oilseed rape reported no
    effects amongst his hives. It was concluded that the application of
    alpha-cypermethrin at 20 g active ingredient/ha to flowering oilseed
    rape had no direct effects on honey-bee survival and hive development
    (Brown, 1989).

    9.3.4  Leaf-cutting bees

         Laboratory trials using 15 male adult alfalfa leaf-cutting bees
    ( Megachile rotundata F.) per group, exposed to treated filter papers
    for 4 h, showed that alpha-cypermethrin EC (100 g/litre) at the rate
    of 10 or 15 g active ingredient/ha caused 12 and 30% mortality,
    respectively, and 42 and 100% mortality after 24 h of contact (Tasei
    et al., 1987).

         In a study by Tasei et al. (1987), populations of about 400
    female alfalfa leaf-cutting bees were reared in three flowering
    lucerne fields. One field was left untreated, while the two others
    were treated with alpha-cypermethrin as an EC (10 or 15 g active
    ingredient/ha), applied by a tractor-mounted fan-jet sprayer. Two days
    after the treatments, counts of live females in artificial nesting
    sites showed the losses due to 10 and 15 g active ingredient/ha to be
    21 and 12%, respectively. After hibernation and incubation of the
    progeny larvae, little effect of the treatments could be observed. The
    maximum residue in leaves collected from nests was 1 mg
    alpha-cypermethrin/kg. The mean values after 5, 10 and 27 days in leaf
    pieces capping the nests of the bees were 0.75, 0.48, and 0.19 mg/kg
    at the lower application rate and 0.59, 0.53, and 0.10 mg/kg at the

    higher rate. No residues (limit of determination, 0.01 mg/kg) were
    detected in live larvae but 0.07 mg/kg was found in pollen provisions
    (Tasei et al., 1987).

    9.3.5  Birds

         Cypermethrin is practically non-toxic to birds; acute oral LD50
    values are greater than 2000 mg/kg body weight. The dietary LC50
    value is above 10 000 mg/kg diet (see WHO, 1989). However, studies
    with alpha-cypermethrin have not been carried out.

    10.  COMPARISON BETWEEN ALPHA-CYPERMETHRIN AND CYPERMETHRIN

         Alpha-cypermethrin comprises one quarter of the racemic mixture
    cypermethrin, with which an extensive agricultural, ecological and
    (eco)toxicological programme has been carried out (WHO, 1989). It
    contains more than 90% of the insecticidally most active enantiomer
    pair of the four cis isomers of cypermethrin, i.e. the two cis isomers
    (IRcis)S and (IScis)R (see Fig. 1).

    10.1  Use and residue levels

         Alpha-cypermethrin is used to control the same pests in
    agriculture as cypermethrin. Its rate of application to crops (5-30 g
    active ingredient/ha) is lower than that of cypermethrin (10-200 g
    active ingredient/ha) since alpha-cypermethrin is biologically more
    active than cypermethrin.

         Residue data for alpha-cypermethrin have been obtained from a
    large number of supervised trials carried out worldwide. These trials
    cover the most important crop groupings for which alpha-cypermethrin
    is recommended, including oilseeds, pome fruits, peaches, fruiting
    vegetables, berries, leafy vegetables, maize and speciality crops such
    as hops and tobacco (Shell, 1984). Residues in a variety of these
    crops resulting from application of alpha-cypermethrin at the
    recommended rate ranged between 0.05 and 1.0 mg/kg (Shell, 1984). In
    comparison, residues of cypermethrin in crops were higher and ranged
    between 0.05 and 2.0 mg/kg. In comparative trials where
    alpha-cypermethrin was applied at half the dose rate of cypermethrin,
    alpha-cypermethrin residues in general averaged 40% (20-50%) of those
    in cypermethrin-treated samples (Shell, 1984; WHO, 1989).

         The residue data on cypermethrin have been evaluated by the Joint
    FAO/WHO Meeting on Pesticide Residues and recommended MRLs (1979/1981)
    have been published (FAO/WHO, 1980, 1982) (see Table 10). From the
    available residue data obtained with good agricultural practice and
    using the MRLs set for cypermethrin, suggested MRLs for
    alpha-cypermethrin can be extrapolated (Table 10).

         It can be concluded that alpha-cypermethrin, since it is
    biologically more active, is always used at a lower application rate
    than cypermethrin and, as a result, the residues on crops are
    approximately half those of cypermethrin.

    Table 10. Comparison of current MRLs in mg/kg product for cypermethrin
    recommended by the FAO/WHO Joint Meeting on Pesticides Residues (JMPR)
    with those which may be proposed for alpha-cypermethrin
                                                                     

    Commodity                     Cypermethrin    Alpha-cypermethrin
                                     (JMPR)a        (extrapolated)
                                                                     

    Cotton seed                        0.2            0.05
    Rapeseed                           0.2            0.05
    Pome fruits                        2              0.5
    Peaches                            2              0.5
    Grapes                             1              0.5
    Citrus fruits                      2              1
    Tomatoes                           0.5            0.1
    Brassica, leafy vegetables         1              1
    Lettuce                            2              1
    Peas, kidney beans (less pod)      0.05           0.05
    Soyabeans (less pod)               0.05           0.05
    Potatoes                           0.05           0.05
    Sugarbeet (roots)                  0.05           0.05
    Maize grain                        0.05           0.05
                                                                     

    a  From: FAO/WHO (1980, 1982)
    For analytical reasons, 0.05 mg/kg is considered the minimum practical
    MRL.

    10.2  Environmental impact

         Because its physico-chemical properties are similar to those of
    cypermethrin, alpha-cypermethrin is expected to have a similar
    environmental fate to that of cypermethrin. The potential of
    alpha-cypermethrin to bioaccumulate may therefore be estimated from
    experimental data on the bioaccumulation of cypermethrin. This is
    because the octanol/water partition coefficients of alpha-cypermethrin
    (1.4 x 105; log Pow = 5.16) and cypermethrin (2 x 106; log Pow
    = 6.3) are relatively similar. In fish, the bioaccumulation of
    cypermethrin determined experimentally was lower than might have been
    expected from its partition coefficient, presumably because it was
    rapidly metabolized. This would also be expected for
    alpha-cypermethrin because both the route of metabolism and its rate
    are similar to those of cypermethrin (Shell, 1983b; WHO, 1989).

         In the area of environmental toxicology, results available for
    green algae, aquatic invertebrates, fish and bees show that the acute
    toxicity of alpha-cypermethrin is slightly higher than, but broadly
    similar to that of cypermethrin (Table 11). This is because the
    toxicity of cypermethrin results largely from its alpha-cypermethrin
    component. No toxicity data are available concerning the effects of

    alpha-cypermethrin on soil microbes, but little or no effect on carbon
    dioxide evolution, oxygen uptake and nitrogen fixation would be
    expected if alpha-cypermethrin acts on soil microbes in a similar way
    to cypermethrin (WHO, 1989). There are also no toxicity data for
    alpha-cypermethrin in birds. However, cypermethrin has a low toxicity
    to birds. Since alpha-cypermethrin constitutes 25% of the active
    ingredients of cypermethrin and is used at lower application rates, it
    is expected that alpha-cypermethrin will also have a low toxicity to
    birds (Shell, 1983b).

         Overall, in the natural environment, the more biologically active
    alpha-cypermethrin is likely to have a similar toxicity to that of
    cypermethrin. This is because alpha-cypermethrin is used at a lower
    application rate than cypermethrin.

    10.3  Mammalian toxicity

         In acute oral toxicity studies, alpha-cypermethrin is either
    equally toxic or two to three times more toxic than cypermethrin (WHO,
    1989), depending on the vehicle and the concentrations used.

         In Table 12, the no-observed-effect levels and
    lowest-observed-effect levels of the various mouse, rat and dog
    studies are compared for cypermethrin,  cis-cypermethrin and
    alpha-cypermethrin. Short- and long-term studies with the racemic
    mixture cypermethrin (containing four cis and four trans isomers),
     cis-cypermethrin (four cis isomers) and alpha-cypermethrin (two cis
    isomers) have shown similar toxicological effects.

         The data from the short-term toxicity studies indicate that
    alpha-cypermethrin is approximately 2 to 3 times more toxic than
    cypermethrin in rats and dogs. This reflects the amount of
    alpha-cypermethrin present in cypermethrin.

         The signs of intoxication, the effects on target organs and
    tissues, and the metabolic pathway of alpha-cypermethrin are similar
    to those of  cis-cypermethrin. The mode of action of
    alpha-cypermethrin is similar to that of cypermethrin.

         Cypermethrin has been tested in a rodent multigeneration
    reproduction study and for embryotoxicity and teratogenicity in two
    species. There were no effects on either reproductive performance or
    on fetal development, even at doses producing systemic toxicity (WHO,
    1989). Alpha-cypermethrin has not been tested for reproductive
    toxicity or teratogenicity, but there is no indication that it would
    have effects on these parameters since it is a component of
    cypermethrin.


        Table 11. Comparison of environmental toxicology of cypermethrin and alpha-cypermethrin
                                                                                                                                              
    Species                  Life stage/      Water        Administration     Measured                     Values for              Reference 
                             age              temper-      route or vehicle   end-point          cypermethrin     alpha-
                                              ature (°C)                                                          cypermethrin
                                                                                                                                              
    Green alga
     (Selenastrum                -              24         dispersal          2- to 4-day        > 100 µg/litre   > 100 µg/litre  Stephenson
     capricornutum)                                        via acetone        EC50 (growth)                                       (1982)

    Aquatic invertebrates
    Water flea               up to 24 h         20         dispersal          EC50                                                Stephenson
     (Daphnia magna)           old                         via acetone        (immobilization)                                    (1982)
                                                                              24 h               1.2 µg/litre     1.1 µg/litre
                                                                              48 h               0.3 µg/litre     0.3 µg/litre

    Fish
    Rainbow trout              3.3 g            15         dispersal          96-h LC50          2.8 µg/litre     2.8 µg/litre    Stephenson
     (Oncorhynchus mykiss)                                 via acetone                                                            (1982)

    Fathead minnow           0.74-0.76 g       23-25       absorbed on        96-h LC50          1.2 µg/litre     0.93 µg/litre   Stephenson
     (Pimephales promelas)   (juvenile)                    to pumice                                                              (1983)

    Earthworm
     (Eisenia foetida)           -               -         filter paper       48-h LD50          26.1 µg/cm2      10 µg/cm2       Rob
                                                           contact                                                                & Dorough
                                                           toxicity                                                               (1984);
                                                                                                                                  Inglesfield
                                                                                                                                  & Sherwood
                                                                                                                                  (1983)
                                                                                                                                             

    Table 11 (continued)
                                                                                                                                             
    Species                  Life stage/      Water        Administration     Measured                     Values for              Reference
                             age              temper-      route or vehicle   end-point          cypermethrin     alpha-
                                              ature (°C)                                                          cypermethrin
                                                                                                                                             

    Bees
     (Apis mellifera)          worker           -          oral               24-h LD50          0.035 µg/bee     0.06 µg/bee      Badmin
                                                           adminis-                                                                & Twydell
                                                           tration                                                                 (1976);
                                                                                                                                   Murray
                                                                                                                                   (1985)
                                                                                                                                             
    

    Table 12. Comparison between short- and long-term oral studies with
    cypermethrin,  cis-cypermethrin and alpha-cypermethrin
                                                                        
    Animal    Number of   Duration of     Dose level in mg/kg diet
    species   studies     experiment    No-observed-    Lowest-observed-
                                        effect level    effect level
                                                                        

    Cypermethrin (4 cis and 4 trans isomers)a

    Mouse     1            2 years           400             1600
    Rat       1            5 weeks           750             1500
              2            13 weeks        100/150            400
              1            2 years           100             1000
    Dog       1            13 weeks          500             1500
              1            2 years           300            750/600

    cis-cypermethrin (4 cis isomers)a

    Rat       1            5 weeks           100              300

    Alpha-cypermethrin (2 cis isomers)

    Rat       1            5 weeks           200              400
              1            13 weeks          60               180
    Dog       2            2-7 days          200              250
              1            13 weeks          90               270
                                                                        

    a  See WHO (1989)

         The WHO Task Group on Environmental Health Criteria for
    Cypermethrin, which met in 1986, concluded that cypermethrin was
    without mutagenic activity. Available data on alpha-cypermethrin
    indicate that this compound also is non-mutagenic in tests with
     Salmonella typhimurium, Saccharomyces cerevisiae, and  in vivo and
     in vitro tests with rat liver cells for the induction of chromosome
    aberration and production of DNA single-strand damage.

         Alpha-cypermethrin has not been tested for carcinogenicity, but
    the long-term toxicity studies in mice and rats did not indicate any
    carcinogenic potential for cypermethrin. Because cypermethrin contains
    the two cis isomers present in alpha-cypermethrin, it is unlikely that
    these two isomers would have a carcinogenic potential. This
    supposition is supported by the fact that all the mutagenicity studies
    on alpha-cypermethrin have yielded negative results.

         Near lethal doses of alpha-cypermethrin and cypermethrin produce
    sparse axonopathy in the peripheral nerves of rats (see section
    7.7.2). Similar signs of intoxication were observed with both
    compounds, and increases in beta-glucuronidase and beta-galactosidase
    activities, consistent with an axonal degeneration, could only be

    detected in severely intoxicated animals. The magnitude of the enzyme
    changes was substantially less than for other known neurotoxic
    compounds, thereby confirming the minor nature of the lesion. The
    short time period needed to produce ataxia and/or abnormal gait rules
    out a causal relationship between ataxia and axonopathy. The signs of
    intoxication are consistent with a pharmacologically-mediated effect.
    No biochemical changes indicative of axonopathy were detected in rats
    given 20 oral doses of 20 mg alpha-cypermethrin/kg body weight per day
    or 75 mg cypermethrin/kg body weight per day. From these comparative
    studies, it is clear that the neurotoxic potential of
    alpha-cypermethrin and cypermethrin is qualitatively similar, but
    alpha-cypermethrin is 3 to 4 times more potent. This reflects the fact
    that alpha-cypermethrin constitutes the active ingredient and 25% of
    cypermethrin.

                                 Appraisal

          The effects of alpha-cypermethrin on vertebrates and
     invertebrates are qualitatively and, in a number of cases, even
     quantitatively similar to those of cypermethrin, reflecting the fact
     that alpha-cypermethrin is composed of two of the four cis isomers
     present in cypermethrin (these two being the most active components
     of cypermethrin). Therefore, the toxicological information of
     cypermethrin can be used to evaluate the effects of
     alpha-cypermethrin where certain important toxicity studies for
     alpha-cypermethrin are lacking.

          Alpha-cypermethrin has a higher toxicity (lower
     no-observed-effect level) than cypermethrin but its application rate
     is at most only half that of cypermethrin (5-30 g active
     ingredient/ha for alpha-cypermethrin and 10-200 g active
     ingredient/ha for cypermethrin). Therefore, residue levels of
     alpha-cypermethrin in crops are less than half those of cypermethrin.

    11.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

         The toxicological and residue data on cypermethrin have been
    evaluated by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR)
    (FAO/WHO, 1980, 1982), but alpha-cypermethrin has not yet been
    evaluated by the JMPR.

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    Francis WP & Gill JP (1991) Flufenoxuron/alpha-cypermethrin - residues
    in sheep tissues following treatment with PAMPASS/RENEGADE mixtures by
    dip or pour-on. London, Shell International Chemical Company, Ltd
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    Gardner JR (1989) "Fastac/Azodrin" 20/400 g/litre emulsifiable
    concentrate: Acute oral and dermal toxicity. London, Shell
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    Gardner JR (1991) Fastac 60 G/l SC (SF07396); acute oral and dermal
    toxicity in rat. Sittingbourne, Shell Research (SBGR 91.020).

    Garforth BM (1982a) A comparison of the toxicities of WL85871 and
    Ripcord to freshwater invertebrates in small field enclosures.
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    Garforth BM (1982b) WL85871 and cypermethrin; chronic toxicity to
     Daphnia magna. Sittingbourne, Shell Research (SBGR 82.119).

    Garforth BM & Woodbridge AP (1984) Spray drift from an aerial
    application of Fastac; fate and biological effects in an adjacent
    freshwater ditch. Sittingbourne, Shell Research (SBGR 84.055).

    Greenough RJ & Goburdhun R (1984) WL85871; Oral (dietary) maximum
    tolerated dose study in dogs. Musselburgh, Inveresk Research
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    Research).

    Greenough RJ, Cockrill JB, & Goburdhun R (1984) WL85871; 13-week oral
    (dietary) toxicity study in dogs. Musselburgh, Inveresk Research
    International (Unpublished report No. 3197, submitted to WHO by Shell
    Research).

    Hend RW (1983) Toxicology of pyrethroids; skin stimulation studies
    using guinea-pigs. Sittingbourne, Shell Research (SBGR 83.197).

    Hillaby JM (1988) Deposition of pesticide on the orchard floor
    following a commercial mistblower application to apples. London, Shell
    International Chemical Company, Ltd (Internal report SBGR 88.106).

    Hillaby JM & Inglesfield C (1986) The residual toxicity of "Fastac"
    formulations and "Fastac"/fungicide mixtures to the honey bee,  Apis
     mellifera L. Sittingbourne, Shell Research (SBGR 86.018).

    Hutson DH (1982) WL85871; metabolism of a single oral dose in the rat.
    Sittingbourne, Shell Research (SBGR 82.205).

    Hutson DH & Logan CJ (1986) The metabolic fate in rats of the
    pyrethroid insecticide WL85871, a mixture of two isomers of
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    Inglesfield C (1984) The effects of two formulations of Fastac on the
    beneficial arthropod fauna of grape vines. Sittingbourne, Shell
    Research (SBGR 84.039).

    Inglesfield C (1985a) A field study on the effects of Fastac on the
    beneficial arthropod fauna of maize in France. Sittingbourne, Shell
    Research (SBGR 85.069).

    Inglesfield C (1985b) A pond enclosure study of the effects of Fastac
    formulations on aquatic invertebrates. Sittingbourne, Shell Research
    (SBGR 85.083).

    Inglesfield C (1985c) The effects of the pyrethroid insecticide
    WL85871 on non-target arthropods: Field studies. Pestic Sci, 16(2):
    211.

    Inglesfield C (1988) Effects of "Fastac" on non-target arthropods; an
    overview of a five-year arable crop rotation study. Sittingbourne,
    Shell Research (SBGR 87.149).

    Inglesfield C (1989) A long-term field study to investigate the
    effects of alpha-cypermethrin on predatory and parasitic arthropods.
    Meded Fac Landbouwwet Rijksuniv Gent, 54(3a): 895-904.

    Inglesfield C (1991) Effects of alpha-cypermethrin (Fastac) on
    entomophagous organisms and game-bird chick-food insects in summer
    cereals. The Hague, Shell Internationale Petroleum Maatschappij B.V.
    (Report Series HSE 91.008).

    Inglesfield C & Forbes S (1986) A field trial to assess the effects of
    "Fastac" 100 g/litre OSC on foraging honey bees in oilseed rape.
    Sittingbourne, Shell Research (SBGR 86.087).

    Inglesfield C & Sherwood CM (1983) Toxicity of cypermethrin and
    WL85871 to the earthworm, Eisenia foetida L.
     (Oligochaeta:Lumbriculidae) in laboratory tests. Sittingbourne,
    Shell Research (SBGR 83.071).

    Langner EJ (1980) Determination of the vapour pressure of WL 43467 and
    WL 85871 at 20 °C. Sittingbourne Shell Research (Research Note No.
    FCDN 80.137).

    Le Blanc J (1985) Field experiments on the effects of a new pyrethroid
    insecticide WL85871 on bees foraging artificial aphid honey-dew on
    winter wheat. Pestic Sci, 16(2): 206.

    Le Quesne PM, Maxwell IC, & Butterworth STG (1980) Transient facial
    sensory symptoms following exposure to synthetic pyrethroids; a
    clinical and electrophysiological assessment. Neurotoxicology, 2:
    1-11.

    Logan CJ (1983) WL85871; depletion from tissues of female rats after
    a single oral dose. Sittingbourne, Shell Research (SBGR 83.075).

    McMinn AL (1983a) The degradation of the pyrethroid insecticides
    WL85871 (Fastac) and WL43481 in cabbage. Sittingbourne, Shell Research
    (SBGR 83.396).

    McMinn AL (1983b) The degradation of the pyrethroid insecticides
    WL85871 and WL43481 in soil. Sittingbourne, Shell Research (SBGR
    83.395).

    Maloney SE, Maule A, & Smith ARW (1988) Microbial transformation of
    the pyrethroid insecticides: Permethrin, deltamethrin, fastac,
    fenvalerate and fluvalinate. Appl Environ Microbiol, 54(11):
    2874-2876.

    Murray A (1985) Acute and residual toxicity of a new pyrethroid
    insecticide WL85871, to honey-bees. Bull Environ Contam Toxicol, 34:
    560-564.

    Pearson N (1986) Fastac oil-enriched suspension concentrates; acute
    toxicities of two formulations to the rainbow trout,  Salmo gairdneri.
    Sittingbourne, Shell Research (SBGR 85.290).

    Pearson N (1990) The fate of "Fastac" in experimental ponds.
    Sittingbourne, Shell Research (SBGR 88.177).

    Pickering RG (1982) A 5-week feeding study with WL85871 in rats.
    Sittingbourne, Shell Research, vol 1 and 2 (SBGR 81.212).

    Price JB (1985a) Toxicology of Fastac (WL85871); the acute oral and
    percutaneous toxicity and skin irritancy of a Fastac 10% EC (SF
    06510). Sittingbourne, Shell Research (SBGR 85.087).

    Price JB (1985b) Toxicology of pyrethroids; the acute oral and
    percutaneous toxicity, skin and eye irritancy of a Fastac 100 g/litre
    suspension concentrate (SF 06378). Sittingbourne, Shell Research (SBGR
    84.298).

    Price JB (1986) Toxicology of pyrethroids; the acute oral and
    percutaneous toxicity, skin and eye irritancy of SF 06615, a 15
    g/litre suspension concentrate of WL85871 ("Fastac", "Fendona").
    Sittingbourne, Shell Research (SBGR 85.224).

    Price JB (1987) Toxicology of pyrethroids; the acute oral and
    percutaneous toxicity of Fastac/BPMC 10/400 g/litre EC (SF 06717).
    Sittingbourne, Shell Research (SBGR 86.253).

    Price JB (1988) Toxicology of animal health products; the acute oral
    and percutaneous toxicity, skin and eye irritancy of two pour-on
    formulations of Renegade, SF 06954 (10 g/litre) and SF 06977 (15
    g/litre). Sittingbourne, Shell Research (SBGR 87.161).

    Roberts BL & Dorough HW (1984) Relative toxicities of chemicals to the
    earthworm  Eisenia foedita. Environ Toxicol Chem, 3(1): 67-68.

    Rose GP (1982) Toxicology of pyrethroids; the acute oral and
    percutaneous toxicity of WL85871 ( cis-2-Ripcord) comparison with
    Ripcord. Sittingbourne, Shell Research (SBGR 82.130).

    Rose GP (1983a) Toxicology of pyrethroids; the acute oral toxicity of
    WL85871 in comparison with WL43467. Sittingbourne, Shell Research
    (SBGR 83.101).

    Rose GP (1983b) Neurotoxicity of WL85871 in comparison with WL43467;
    the effect of twenty oral doses of WL85871 or WL43467 over a period of
    4 weeks on the rat sciatic/posterior tibial nerve, trigeminal nerve
    and trigeminal ganglion. Sittingbourne, Shell Research (SBGR 83.185).

    Rose GP (1984a) Toxicology of pyrethroids; the acute intraperitoneal
    toxicity of technical Fastac. Sittingbourne, Shell Research (SBGR
    84.085).

    Rose GP (1984b) Toxicology of Fastac; the eye irritancy potential of
    the Fastac 100 g/litre emulsifiable concentrate formulation DF 05898
    and its formulation components. Sittingbourne, Shell Research (SBGR
    84.053).

    Rose GP (1984c) Toxicology of pyrethroids; the acute oral and
    percutaneous toxicity, skin and eye irritancy of the Fastac 15 g/litre
    ULV formulation SF 06363. Sittingbourne, Shell Research (SBGR 84.145).

    Rose GP (1984d) Toxicology of pyrethroids; the acute oral and
    percutaneous toxicity, skin and eye irritancy of the Fastac 10 EC
    formulation, 5835 B. Sittingbourne, Shell Research (SBGR 84.077).

    Rose GP (1984e) Toxicology of pyrethroids; the acute oral and
    percutaneous toxicity, skin and eye irritancy of the Fastac 10 EC
    formulation 5898 B. Sittingbourne, Shell Research (SBGR 84.078).

    Rose GP (1984f) Toxicology of pyrethroids; the acute oral and
    percutaneous toxicity, skin and eye irritancy of the Fastac 3 EC
    formulation, DF 06353. Sittingbourne, Shell Research (SBGR 84.084).

    Rose GP (1984g) Toxicology of pyrethroids; the eye irritancy and skin
    sensitizing potential of the 100 g/litre Fastac emulsifiable
    concentrate formulation EF 5835. Sittingbourne, Shell Research (SBGR
    84.086).

    Rose GP (1984h) Toxicology of pyrethroids; the acute oral and
    percutaneous toxicity, skin and eye irritancy of the 15:120 g/litre
    Fastac/methomyl emulsifiable concentrate formulation, FD 9148.
    Sittingbourne, Shell Research (SBGR 84.104).

    Rose GP (1985) Toxicology of insecticides; the acute oral and
    percutaneous toxicity, skin and eye irritancy of the 30 g/litre Fastac
    EC formulation SF 06446. Sittingbourne, Shell Research (SBGR 84.209).

    Senior PL & Lavers A (1990a) Fastac - Potential dermal exposure. The
    Hague, Shell Internationale Petroleum Maatschappij B.V. (Report Series
    HSE 90.016).

    Senior PL & Lavers A (1990b) A field study of operator exposure to
    Fastac during crop spraying at Shell Research Ltd, Sittingbourne
    Research Centre. The Hague, Shell Internationale Petroleum
    Maatschappij B.V. (Report Series HSE 90.014).

    SHELL (1983a) Review of mammalian and human toxicology; Fastac. The
    Hague, Shell Internationale Petroleum Maatschappij B.V. (Review Series
    MDT 83.001).

    SHELL (1983b) Review of environmental toxicology; Fastac. The Hague,
    Shell Internationale Petroleum Maatschappij B.V. (Review Series MDT
    83.005).

    SHELL (1984) Review of residue information; Fastac. London, Shell
    International Chemical Company Ltd.

    SHELL (1986) Determination of residues of alpha-cypermethrin in rat
    blood - Gas chromatographic method. Sittingbourne, Shell Research
    (Analytical Method Series, No. SAMS 436-1).

    SHELL (1987a) Determination of WL 85871 and the ratio of the
    enantiomer pairs in technical material and formulated products -
    liquid chromatographic method. Sittingbourne, Shell Research
    (Analytical Methods Series, No. SAMS 346-4).

    SHELL (1987b) Intereg residues section: Ripcord residues in crops.
    London, International Chemical Company, Ltd (Internal report).

    SHELL (1987c) Intereg residues section: Fastac residues in crops.
    London, International Chemical Company, Ltd (Internal report).

    SHELL (1988a) Determination of residues of alpha-cypermethrin in
    animal tissues - Gas-liquid chromatographic method. Sittingbourne,
    Shell Research (Analytical Method Series, No. SAMS 461-1).

    SHELL (1988b) Determination of residues of alpha-cypermethrin in milk
    - Gas-liquid chromatographic method. Sittingbourne, Shell Research
    (Analytical Method Series, No. SAMS 456-1).

    SHELL (1989a) Determination of residues of alpha-cypermethrin in crops
    - Gas chromatographic method. Sittingbourne, Shell Research
    (Analytical Method Series, No. SAMS 351-2).

    SHELL (1989b) Review of environmental toxicology; Fastac. The Hague,
    Shell Internationale Petroleum Maatschappij B.V. (Review Series HSE
    89.008).

    SHELL (1990a) Determination of residues of alpha-cypermethrin in water
    - Gas chromatographic method. Sittingbourne, Shell Research
    (Analytical Method Series, No. SAMS 469-2).

    SHELL (1990b) Determination of residues of alpha-cypermethrin in soils
    - Gas chromatographic method. Sittingbourne, Shell Research
    (Analytical Method Series, No. SAMS 354-2).

    Sherren AJ (1988a) Residues of alpha-cypermethrin in cattle tissues
    following topical treatment of calves with "Renegade" pour-on in the
    UK. London, Shell International Chemical Company, Ltd (Internal report
    SBGR 88.036).

    Sherren AJ (1988b) Residues of alpha-cypermethrin in milk following
    topical treatment of cows with "Renegade" pour-on in the UK. London,
    Shell International Chemical Company, Ltd (Internal report SBGR
    88.037).

    Shires SW (1982) A comparison of the toxicity of WL85871 and Ripcord
    to rainbow trout ( Salmo gairdneri, Richardson) in small field
    enclosures. Sittingbourne, Shell Research (SBGR 82.089).

    Shires SW (1983a) Pesticides and honey bees; case studies with Ripcord
    and Fastac. Span, 26(3): 118-120.

    Shires SW (1983b) Effect of formulation type on the toxicity of
    insecticides to fish. Sittingbourne, Shell Research (SBGR 83.015).

    Shires SW (1985a) A step-wise evaluation of the effects of a new
    pyrethroid insecticide WL85871 on honey bees. Pestic Sci, 16(2):
    205-216.

    Shires SW (1985b) Toxicity of a new pyrethroid insecticide WL85871 to
    rainbow trout. Bull Environ Contam Toxicol, 34: 134-137.

    Shires SW & Inglesfield C (1986) A field study of the effects of
    "Fastac" (WL85871) on rice pests and their natural enemies.
    Sittingbourne, Shell Research (SBGR 86.003).

    Shires SW, Le Blanc J, Debray P, Forbes S, & Louveaux J (1984a) Field
    experiments on the effects of a new pyrethroid insecticide WL85871 on
    bees foraging artificial aphid honey-dew on winter wheat. Pestic Sci,
    15: 543-552.

    Shires SW, Murray A, Debray P, & Le Blanc J (1984b) The effects of a
    new pyrethroid insecticide WL85871 on foraging honey bees ( Apis
     mellifera L.) Pestic Sci, 15: 491-499.

    Shires SW, Le Blanc J, Murray A, Forbes S, & Debray P (1984c) A field
    trial to assess the effects of a new pyrethroid insecticide WL85871 on
    foraging honey bees in oilseed rape. J Agric Res, 23(4): 217-226.

    Stephenson RR (1982) WL85871 and cypermethrin; a comparison of their
    acute toxicity to  Salmo gairdneri, Daphnia magna and  Selenastrum
     capricornutum. Sittingbourne, Shell Research (SBGR 81.277).

    Stephenson RR (1983) WL85871 and cypermethrin; a comparative study of
    their toxicity to the fathead minnow,  Pimephales promelas
    (Rafinesque). Sittingbourne, Shell Research (SBGR 82.298).

    Stephenson RR (1986) "Fastac"; the acute toxicity of different
    formulations to fish in rice paddies. Sittingbourne, Shell Research
    (SBGR 85.201).

    Stephenson RR (1987a) The effects of "Fastac" (OSC) on fish survival
    and growth following its application to paddy rice. Sittingbourne,
    Shell Research (SBGR 87.054).

    Stephenson RR (1987b) An insecticide formulation that spares fish.
    Span, 30(2): 75-77.

    Stephenson RR (1987c) The effects of "Fastac" (OSC) on fish following
    its application to outdoor tanks. Sittingbourne, Shell Research (SBGR
    86.227).

    Stone CM & Watkinson RJ (1983) WL85871; an assessment of ready
    biodegradability. Sittingbourne, Shell Research (SBGR 83.206).

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    the pyrethroid insecticide WL85871 and Phosalone on adults and progeny
    of the leaf-cutting bee,  Megachile rotundata F., pollinator of
    lucerne. Pestic Sci, 21: 119-128.

    Van Sittert NJ, Eadsforth CV, & Bragt P (1985) Human oral
    dose-excretion study with Fastac. The Hague, Shell Internationale
    Petroleum Maatschappij B.V. (Report Series HSE 85.010).

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    and the mode of action of pyrethroid insecticides. Crit Rev Toxicol,
    21(2): 105-126.

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    formulation of technical concentrate (TC) and technical material (TM)
    at Durban, South Africa, September 1983. The Hague, Shell
    Internationale Petroleum Maatschappij B.V. (Report Series HSE 84.003).

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    World Health Organization, 154 pp.

    Wooder MF (1982) Studies on the effect of WL85871 on the integrity of
    rat liver DNA  in vivo. Sittingbourne, Shell Research (SBGR 81.225).

    Woollen BH, Marsh JR, & Chester G (1991) Metabolite profiles of a
    pyrethroid insecticide following oral and dermal absorption in man.
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    210-211.

    APPENDIX I

         Cypermethrin: Summary, Evaluation, Conclusions, and
    Recommendations (Reprint from EHC 82 on Cypermethrin, WHO/IPCS, 1989)

    1.  Summary

    1.1  General

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

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

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

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

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

    1.2  Environmental transport, distribution and transformation

         Unlike the natural pyrethrins, cypermethrin is relatively stable
    to sunlight and, though it is probable that photodegradation plays a
    significant role in the degradation of the product on leaf surfaces

    and in surface waters, its effects in soils are limited. The most
    important photodegradation products, 2,2-dimethyl-3-
    (2,2-dichlorovinyl) cyclopropane carboxylic acid (CPA),
    3-phenoxy-benzoic acid (PBA) and, to some extent, the amide of the
    intact ester, do not differ greatly from those resulting from
    biological degradation.

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

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

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

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

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

    1.3  Environmental levels and human exposure

         Cypermethrin is used in a wide range of crops. In general, the
    maximum residue limits are low, ranging from 0.05 to 2.0 mg/kg in the
    different food commodities. The residues will be further reduced
    during food processing. In food of animal origin, residues may range

    between 0.01 and 0.2 mg/kg product. Residues in non-food commodities
    are generally higher, ranging up to 20 mg/kg product.

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

    1.4  Kinetics and metabolism

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

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

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

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

    as a glucuronide conjugate, hydroxylation of the methyl group only
    occurring to a limited extent.

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

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

    1.5  Effects on organisms in the environment

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

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

         Cypermethrin is not very toxic for birds. Signs of cypermethrin
    intoxication were seen at dose levels of 3000 mg/kg body weight or
    more. Administration of 1000 mg cypermethrin/kg body weight to laying
    hens over a 5-day period did not cause signs of intoxication. However,
    cypermethrin was highly toxic for honey bees in laboratory tests, the
    oral LD50 ranging from 0.03 to 0.12 µg/bee. Under field conditions,
    the hazard is considerably lower, because of the repellent effect of
    cypermethrin on worker honey bees, which lasts for at least 6 h after
    spraying.

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

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

    field. However, care should be taken where predatory mites are
    important in pest management.

    1.6  Effects on experimental animals and  in vitro test systems

         The acute oral toxicity of cypermethrin is moderate. While LD50
    values differed considerably among animal species depending on the
    vehicle used and the cis/trans isomeric ratios, the toxic responses in
    all species were found to be very similar. The acute toxicity of the
    trans isomer in the rat (LD50 > 2000 mg/kg body weight) was lower
    than that of the cis isomer (LD50, 160-300 mg/kg body weight). The
    onset of toxic signs of poisoning was rapid and they disappeared
    within several days in survivors. The toxic signs are characterized by
    salivation, tremors, increased startle response, sinuous writhing of
    the whole body (choreoathetosis), and clonic seizures. Myelin and axon
    degeneration were noted in the sciatic nerve at near lethal dose
    levels.

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

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

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

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

         Repeated oral administration of cypermethrin to rats and other
    animal species at levels sufficiently high to produce significant
    mortality in one group of animals, produced biochemical changes in the
    peripheral nerves, consistent with sparse axonal degeneration.
    Histopathological changes (swelling and/or disintegration of axons of

    the sciatic nerve) were observed. There was no cumulative effect. The
    magnitude of the change was substantially less than that encountered
    with established neurotoxic agents. The neurotoxic effects seem to be
    reversible; presumably the clinical signs are not related to the
    induction of neuropathological lesions.

         Further evidence to support the minor nature of the nerve lesions
    has been afforded by electrophysiological studies on rats.
    Measurements of the maximal motor conduction velocities of the sciatic
    and tail nerves of rats were made before, and at intervals of up to 5
    weeks after, exposure to a single dose or repeated high doses of
    cypermethrin. It was concluded from the results that, even at
    near-lethal doses, cypermethrin did not cause any effects on maximal
    motor conduction velocities and conduction velocities of the slower
    motor fibres in rat peripheral nerves. No delayed neurotoxicity was
    observed in domestic hens.

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

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

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

         Cypermethrin did not show any mutagenic activity in bacteria or
    in yeast, with or without metabolic activation, or in V79 Chinese
    hamster cells. Furthermore, cypermethrin gave negative results in an
     in vivo chromosomal aberration test with Chinese hamsters and in
    dominant lethal studies on mice. In a host-mediated assay with mice,
    no increase in the rate of mitotic gene conversion in  Saccharomyces
     cerevisae was found. In a chromosome study using the bone marrow
    cells of Chinese hamsters, cypermethrin did not increase the number of
    chromosome abnormalities. However, in a micronucleus test with mouse
    bone marrow cells, an increase in the frequency of polychromatic
    erythrocytes with micronuclei was found after oral and dermal
    applications of cypermethrin. Intraperitoneal application gave a
    negative result. A sister chromatid exchange study using bone marrow
    cells of mice showed a dose-response related increase in sister
    chromatid exchanges of dividing cells.

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

    1.7  Mechanism of toxicity

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

    1.8  Effects on man

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

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

    2.  Evaluation

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

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

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

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

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

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

         The toxicity of cypermethrin for birds is low. Bees appear to be
    very sensitive in laboratory tests. Under field conditions, the effect
    on bees is minimal, because cypermethrin seems to have a repellent
    effect for bees. Absorption and elimination of cypermethrin has been
    rapid in the different mammalian species tested. The major metabolic
    reaction is cleavage of the ester bond followed by hydroxylation and
    conjugation of the cyclopropane and phenoxybenzyl moiety. The highest
    levels are found in body fat, which is consistent with the lipophilic
    nature of cypermethrin. The half-life in the fat of the rat is about

    12-19 days for the cis isomer and 3-4 days for the trans isomer.
    Breakdown products in plants are bound as glucosides.

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

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

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

    3.  Conclusions

         It can be concluded that:

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

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

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

    4.  Recommendations

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

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

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

    RESUME ET EVALUATION; CONCLUSIONS ET RECOMMANDATIONS

    1.  Résumé et évaluation

    1.1  Identité, emploi, destinée et concentrations dans l'environnement

         L'alpha-cyperméthrine est constituée à plus de 90% de
    l'énantiomère le plus actif du point de vue insecticide parmi les
    quatre isomères cis qui entrent dans la composition de la
    cyperméthrine racémique.

         C'est un pyréthrinoïde extrêmement actif, qui agit contre de
    nombreux parasites auxquels on a affaire dans l'agriculture et
    l'élevage. Il est commercialisé sous forme de concentrés
    émulsionnables, de formulations à très bas volume, de concentrés pour
    suspension ou en mélange avec d'autres insecticides.

         Le produit technique se présente sous la forme d'une poudre
    cristalline facilement soluble dans l'acétone, la cyclohexanone et le
    xylène mais peu soluble dans l'eau. Il est stable en milieu acide ou
    neutre mais s'hydrolyse à pH 12-13. Il se décompose au-dessus de 120
    °C.

         On ne dispose d'aucune donnée sur la concentration de
    l'alpha-cyperméthrine dans l'air.

         Dans l'eau, il est probable que l'alpha-cyperméthrine est
    décomposée par voie photochimique et biologique. On a constaté que,
    après avoir traité un étang à raison de 15 g de matière active par
    hectare, les eaux de surface et les couches plus profondes contenaient
    respectivement 5% et 19% de la dose appliquée une journée après
    l'épandage et 0,1% et 2% respectivement de cette dose sept jours plus
    tard. Environ 5% de la dose appliquée se retrouvaient dans les
    sédiments 16 jours après l'épandage.

         Il est probable que l'alpha-cyperméthrine est fortement adsorbée
    aux particules du sol. Une année après un épandage à raison de 0,5 kg
    de matière active par hectare, on retrouvait dans le sol des résidus
    inférieurs à 0,1 mg/kg.

         Le coefficient de partage de l'alpha-cyperméthrine entre le
    n-octanol et l'eau est égal à 1,4 x 105 (log de Pow = 5,16).

         La dose d'emploi recommandée pour l'alpha-cyperméthrine est
    moindre que pour la cyperméthrine car elle est biologiquement plus
    active. Il en résulte moins de résidus sur les récoltes et si l'on se
    conforme aux doses recommandées, ils se situent entre 0,05 et 1 mg/kg.
    Chez des poissons-chats d'eau de mer traités à raison de 0,01 à 0,05%
    p/p de matière active, on a mesuré des résidus de 0,3 à 30 mg/kg une
    semaine après l'entreposage et entre 0,22 et 4,0 mg/kg 15 semaines
    plus tard.

    1.2  Cinétique et métabolisme

         Après avoir été administrée par voie orale à des rats,
    l'alpha-cyperméthrine est éliminée dans les urines sous forme du
    sulfo-conjugué de l'acide 3-(4-hydroxyphénoxy)benzoïque ainsi que dans
    les matières fécales, en partie sans modification. Environ 90% d'une
    dose orale unique sont éliminées de l'organisme en quatre jours, dont
    78% au cours du premier jour. Les résidus sont faibles dans les
    tissus, sauf dans les tissus lipidiques. Trois jours après
    administration d'une dose orale unique de 2 mg/kg, la concentration
    dans les graisses était de 0,4 mg/kg. L'élimination à partir des
    graisses est biphasique; la demi-vie relative à la phase initiale est
    de 2,5 jours, et de 17 à 26 jours pour la deuxième phase.

         L'alpha-cyperméthrine est métabolisée par coupure de la liaison
    ester. Chez le rat, la fraction alcool phénoxybenzylique est
    hydroxylée et transformée en sulfo-conjugué; la fraction acide
    cyclopropane-carboxylique subit également une conjugaison,
    probablement sous forme de glucuronide, avant d'être excrétée par la
    voie urinaire. Des études portant sur des microsomes hépatiques de
    rats, de lapins et d'origine humaine ont montré que chez ces trois
    espèces, il pouvait y avoir hydrolyse de l'ester et métabolisation
    oxydative mais que l'hydrolyse de l'ester prédominait dans le cas des
    préparations de foie provenant de lapins ou de sujets humains.

         Chez l'homme, 43% d'une dose orale (0,25-0,75 mg/litre) ont été
    excrétés dans les 24 heures par la voie urinaire sous forme d'acide
     cis-cyclopropane-carboxylique libre ou conjugué. Après
    l'administration de cinq doses quotidiennes successives, l'excrétion
    urinaire n'a pas augmenté.

         On a trouvé de fortes concentrations (jusqu'à 1156 mg/kg)
    d'alpha-cyperméthrine dans la laine de mouton, 14 jours après avoir
    traité les animaux par des bains ou des aspersions. De faibles
    quantités ont été retrouvées dans la graisse sous-cutanée (jusqu'à
    0,04 mg/kg). Après avoir traité des veaux le long de l'épine dorsale
    avec 10 ml d'une formulation à 1,6%, on n'a pas retrouvé
    d'alpha-cyperméthrine dans les muscles ni le foie. La concentration
    maximale dans la graisse périrénale était de 0,25 mg/kg au bout de 14
    jours.

         Après avoir traité des vaches en lactation le long de l'épine
    dorsale avec des formulations contenant jusqu'à 0,2 g de matière
    active on a retrouvé dans le lait de 3 des 15 animaux traités, des
    résidus d'alpha-cyperméthrine compris entre 0,003 et 0,005 mg/litre.

    1.3  Effets sur les mammifères de laboratoire et les systèmes
         d'épreuves  in vitro

         L'alpha-cyperméthrine présente une toxicité orale aiguë modérée
    à forte pour les rongeurs. La DL50 varie beaucoup chez la souris et

    le rat et dépend de la concentration du composé et du véhicule
    utilisé. En pratique, on considère qu'une DL50 de 80 mg/kg de poids
    corporel est représentative. Toutefois, on a fait état de valeurs plus
    élevées pour la DL50 par voie orale dans des conditions
    d'intoxication aiguë. Une intoxication aiguë par voie orale entraîne
    des signes cliniques qui traduisent une action au niveau du système
    nerveux central.

         Une application cutanée d'alpha-cyperméthrine à des rats et des
    souris aux doses respectives de 100 et 500 mg/kg de poids corporel,
    n'a entraîné ni mortalité ni signes d'intoxication. De même, des rats
    à qui l'on avait fait inhaler pendant quatre heures de
    l'alpha-cyperméthrine à une concentration de 400 mg/m3, n'ont
    présenté aucune mortalité ni signes cliniques d'intoxication.

         L'alpha-cyperméthrine technique ne provoquerait qu'une irritation
    minimale de la peau chez le lapin. En revanche, certaines formulations
    de ce composé peuvent déterminer une très forte irritation oculaire.
    L'alpha-cyperméthrine technique n'a pas d'effet sensibilisant cutané.
    Chez le cobaye, elle provoque une stimulation des terminaisons
    nerveuses sensorielles de l'épiderme.

         Exposés pendant une courte période à de l'alpha-cyperméthrine à
    des concentrations quotidiennes allant jusqu'à 200 mg/kg de nourriture
    pendant cinq semaines ou jusqu'à 100 mg/kg de nourriture pendant 13
    semaines, des rats n'ont pas présenté d'effets toxiques. Aux doses les
    plus élevées, on notait des signes d'intoxication traduisant une
    atteinte du système nerveux, ainsi qu'une réduction de la croissance
    et une augmentation du poids du foie et des reins. Aucun effet bien
    net n'a été observé en ce qui concerne les paramètres hématologiques
    ou histopathologiques.

         Lors d'une étude de 13 semaines au cours de laquelle des chiens
    ont reçu de l'alpha-cyperméthrine par voie orale, on a observé que la
    dose la plus forte (270 mg/kg de nourriture) produisait des signes
    d'intoxication; en revanche tous les autres paramètres étudiés (NFS,
    biochimie du sang, urines, poids des organes, anatomopathologie et
    histopathologie) sont restés normaux. La dose sans effet observable
    était de 90 mg/kg de nourriture (soit l'équivalent de 2,25 mg/kg de
    poids corporel par jour).

         Le même genre d'étude menée sur des rats a montré que
    l'alpha-cyperméthrine provoquait des effets neurotoxiques imputables
    à des lésions histopathologiques des nerfs tibial et sciatique, une
    dégénérescence des axones et un accroissement de l'activité de la
    bêta-galactosidase.

         On ne dispose d'aucune donnée sur la toxicité à long terme, la
    toxicité pour la fonction de reproduction, la tératogénicité ou
    l'immunotoxicité.

         En se basant sur les données disponibles, on peut conclure que
    l'alpha-cyperméthrine n'est pas mutagène, comme le montrent les tests
    effectués sur  Salmonella typhimurium, Escherichia coli et
     Saccharomyces cerevisiae ainsi que les épreuves  in vivo et  in
     vitro sur des cellules de foie de rat, qui n'ont révélé ni
    aberration chromosomique ni lésion de l'ADN monobrin. On n'a pas non
    plus observé d'augmentation du nombre d'aberrations chromosomiques
    dans des cellules de moelle osseuse de rat.

         On ne dispose d'aucune donnée sur la cancérogénicité de
    l'alpha-cyperméthrine.

    1.4  Effets sur l'homme

         Dans la mesure où l'alpha-cyperméthrine est utilisée conformément
    aux règles de bonne pratique agricole, l'exposition de la population
    générale reste négligeable. On a constaté que l'exposition
    professionnelle cutanée des opérateurs procédant à la préparation des
    mélanges, au chargement des pulvérisateurs, à l'épandage de
    l'insecticide ou au lavage du matériel, pouvait atteindre des valeurs
    respectivement égales à 2,94 mg, 0,61 mg et 0,73 mg.

         Lors d'une étude sur l'exposition à l'alpha-cyperméthrine au
    cours de la préparation de formulations à base de cet insecticide, on
    a évalué les niveaux d'exposition par surveillance personnelle et
    statique de la concentration atmosphérique de ce composé et dosage de
    ses métabolites urinaires. Au cours des deux jours pendant lesquels
    les personnes exposées procédaient à la formulation de concentrés
    techniques, l'exposition individuelle moyenne dans le groupe a été
    respectivement de 2,8 et 4,9 mg/m3, l'exposition individuelle
    moyenne du groupe au produit technique étant de 50,1 mg/m3 le
    troisième jour. On n'a pas pu déceler la présence de métabolites dans
    les urines (limite de détection 0,02 mg/litre). Au cours de la
    préparation des diverses formulations, les ouvriers ont fait état de
    sensations au niveau de l'épiderme mais en précisant qu'elles étaient
    légères.

         Aucune intoxication n'a été signalée.

    1.5  Effets sur d'autres organismes au laboratoire et dans leur milieu
         naturel

         La CE50 à 48 et 96 heures (pour la croissance) chez une algue
    d'eau douce,  Selenastrum capricornutum, dépasse 100 µg/litre.

         L'alpha-cyperméthrine est très fortement toxique pour les
    invertébrés aquatiques. Les valeurs de la CE50 à 24 et 48 heures
    (pour l'immobilisation de la daphnie) sont respectivement égales à 1,0
    et 0,3 µg/litre, et celle de la CL50 à 24 heures (pour  Gammarus
     pulex) est égale à 0,05 µg/litre. L'alpha-cyperméthrine est
    également très toxique pour un certain nombre d'arthropodes aquatiques

    mais sa toxicité est moindre pour les mollusques. La toxicité à court
    terme de ce composé peut être réduite lorsqu'il est présenté sous la
    forme d'une suspension dans l'huile. Les pertes à l'épandage peuvent
    provoquer des effets toxiques sur les invertébrés aquatiques, mais
    comme l'alpha-cyperméthrine disparaît rapidement de l'eau, ceux-ci ont
    la possibilité de récupérer. L'alpha-cyperméthrine est très fortement
    toxique pour les poissons. La valeur de la CL50 à 96 heures oscille
    entre 0,7 et 350 µg/litre selon le type de formulation. Les concentrés
    émulsionnables sont beaucoup plus toxiques que les concentrés en
    suspension, les poudres mouillables et les formulations
    micro-encapsulées. Le danger de l'alpha-cyperméthrine pour les
    invertébrés aquatiques et les poissons tient à sa toxicité aiguë. Rien
    n'indique toutefois qu'une exposition prolongée entraîne des effets
    cumulatifs.

         On ne dispose d'aucune donnée concernant les effets de
    l'alpha-cyperméthrine sur les microbes terricoles. Les bactéries
    présentes dans les effluents n'ont pas paru affectées par une
    concentration de 3 mg/litre en système fermé.

         La toxicité de l'alpha-cyperméthrine pour certains carabides et
    les larves de neuroptères est relativement faible et elle ne présente
    guère de danger pour les stades pré-imaginaux des hyménoptères
    parasitoïdes. Des études menées sur des champs de grande superficie ou
    de petites parcelles ont montré que l'alpha-cyperméthrine était peu
    dangereuse pour les carabides et les staphylinides mais qu'elle
    présentait un risque relativement important pour les linyphiides. Les
    effets sur ces populations d'insectes se sont limités à une seule
    saison de croissance. En outre, l'alpha-cyperméthrine ne présente
    guère de risque pour les larves de syrphides mais n'est pas dénuée
    d'effets sur les coccinellides. Malgré tout, la dissipation rapide des
    résidus présents sur le feuillage permet à ces animaux de reconstituer
    rapidement leurs colonies.

         L'épandage d'alpha-cyperméthrine n'a pas d'effets indésirables
    sur l'abondance relative des arthropodes entomophages. Son utilisation
    sur les céréales à petits grains n'entraînerait donc pas la
    réapparition des ravageurs ou le déclenchement d'infestations
    secondaires.

         Des études de laboratoire ont montré que l'alpha-cyperméthrine
    était peu toxique pour les lombrics. Des vers placés pendant 14 jours
    dans un sol artificiel contenant ce composé à des concentrations
    allant jusqu'à 100 mg/kg, n'ont présenté aucune mortalité.

         Des études de toxicité aiguë également effectuées en laboratoire
    ont montré que l'alpha-cyperméthrine était extrêmement toxique pour
    les abeilles. Administré par voie orale, un concentré émulsionnable
    d'alpha-cyperméthrine a donné une DL50 à 24 heures de 0,13
    µg/abeille, la valeur correspondante pour l'administration topique
    étant de 0,03 µg/abeille (de produit technique) ou 0,11 µg/abeille (de

    concentré émulsionnable). La forte toxicité de l'alpha-cyperméthrine
    pour les abeilles ne s'est pas manifestée au cours des épreuves de
    plein champ, probablement du fait que le composé a un bref effet
    répulsif qui réduit le butinage et, par voie de conséquence,
    l'exposition des insectes.

         On ne dispose d'aucune donnée sur la toxicité de
    l'alpha-cyperméthrine pour les oiseaux.

    2.  Conclusions

    2.1  Population générale

         Lorsque l'épandage de l'alpha-cyperméthrine s'effectue
    conformément aux règles de bonne pratique, son utilisation en
    agriculture n'expose guère la population générale à ce composé et il
    y a peu de danger pour elle.

    2.2  Exposition professionnelle

         Moyennant de bonnes méthodes de travail ainsi que des mesures
    d'hygiène et de sécurité, l'utilisation de l'alpha-cyperméthrine ne
    devrait pas présenter de danger pour les personnes qui y sont exposées
    de par leur profession. L'apparition de sensations au niveau de la
    face indique une contamination. Dans ces circonstances, il est bon de
    revoir les méthodes de travail.

    2.3  Environnement

         Aux doses d'emploi recommandées, il n'est guère probable que
    l'alpha-cyperméthrine puisse être libérée dans l'environnement à des
    concentrations écologiquement dangereuses. Elle est fortement toxique
    pour les arthropodes aquatiques, les poissons et les abeilles dans les
    conditions du laboratoire. On ne peut envisager la probabilité
    d'effets toxiques importants sur les invertébrés non visés et les
    poissons qu'en cas de déversement accidentel, d'épandage excessif ou
    d'erreur de manipulation.

    3.  Recommandations

    *    Il convient d'éviter la contamination des eaux superficielles par
         l'alpha-cyperméthrine.

    *    L'alpha-cyperméthrine se lie fortement aux particules. D'autres
         études écotoxicologiques sont à effectuer à propos des effets de
         l'alpha-cyperméthrine sur les organismes qui vivent dans les
         sédiments car il s'agit d'un aspect qui n'a guère retenu
         l'attention jusqu'ici.

    *    L'absorption dans les voies digestives de l'alpha-cyperméthrine
         est à étudier dans diverses conditions expérimentales.

    *    Il faudrait également étudier la destinée de
         l'alpha-cyperméthrine après application sur l'épiderme.

    *    Il faudrait obtenir des données supplémentaires sur la toxicité
         à long terme, la cancérogénicité et l'immunotoxicité de
         l'alpha-cyperméthrine.

    RESUMEN Y EVALUACION; CONCLUSIONES Y RECOMENDACIONES

    1.  Resumen y evaluación

    1.1  Identificación, uso, destino y niveles en el medio ambiente

         La alfa-cipermetrina contiene más del 90% del par de
    enantió-meros con mayor actividad insecticida de los cuatro isómeros
    cis de la cipermetrina en mezcla racémica.

         Se trata de un insecticida piretroide sumamente activo contra una
    gran variedad de plagas habituales en agricultura y ganadería. Existe
    como concentrado emulsionable, formulacion de volumen ultra-bajo,
    concentrado en suspensión y en mezcla con otros insecticidas.

         El producto técnico es un polvo cristalino, con buena solubilidad
    en acetona, ciclohexanona y xileno, y con baja solubilidad en agua. Es
    estable en condiciones ácidas o neutras, pero se hidroliza a pH 12-13.
    Se descompone por encima de los 220 °C.

         No se dispone de información acerca de los niveles de
    alfa-cipermetrina en el aire. 

         Es probable que la degradación de la alfa-cipermetrina en agua se
    deba a procesos fotoquímicos y biológicos. El agua superficial y
    subsuperficial de un estanque rociado con 15 g/ha de principio activo
    contenía el 5% y el 19% de la dosis aplicada un día después del
    rociamiento, y 0.1% y 2% siete días más tarde. A los 16 días de la
    aplicación se encontró en el sedimento alrededor del 5% de la dosis
    utilizada.

         Es probable que la alfa-cipermetrina se adsorba con fuerza a las
    partículas del suelo. Un año después del tratamiento con 0.5 kg de
    principio activo por hectárea se encontraron en el suelo residuos
    inferiores a 0.1 mg/kg.

         El coeficiente de reparto n-octanol/agua de la alfa-cipermetrina
    es 1.4 x 105 (log Poa = 5.16).

         Las tasas de aplicación recomendadas de alfa-cipermetrina son
    inferiores a las de cipermetrina, porque la primera es biológicamente
    más activa. En consecuencia, los residuos en los cultivos son escasos,
    y utilizando las tasas de aplicación recomendadas estos residuos
    oscilan entre 0.05 y 1 mg/kg. Los residuos en peces siluroideos
    marinos tratados con dosis entre el 0.001 y el 0.05% p/p de principio
    activo eran de 0.3-30 mg/kg una semana después del almacenamiento, y
    de 0.22 a 4.0 mg/kg tras 15 semanas de almacenamiento.

    1.2  Cinética y metabolismo

         La alfa-cipermetrina administrada por vía oral a ratas se elimina
    por la orina como sulfato conjugado del ácido 3-(4-hidroxifenoxi)
    benzoico y en parte como compuesto inalterado por las heces. De una
    dosis oral única alrededor del 90% se elimina del cuerpo en un período
    de cuatro días, y el 78% en el primer día. Los residuos en los tejidos
    son escasos, excepto en el adiposo. La concentración en la grasa tres
    días después de una dosis oral única de 2 mg/kg fue de 0.4 mg/kg. La
    eliminación a partir de la grasa es bifásica: en la fase inicial tiene
    una vida media de 2.5 días y en la segunda de 17 a 26 días.

         La alfa-cipermetrina se metaboliza mediante la ruptura de su
    enlace éster. En la rata, el alcohol fenoxibencílico de la molécula se
    hidroxila y se conjuga con sulfato, y el ácido
    ciclopropano-carboxílico también se conjuga (probablemente en forma de
    glucurónido) antes de la excreción urinaria. En estudios con
    microsomas hepáticos de ratas, conejos y seres humanos se ha
    demostrado que la hidrólisis en el ester y rutas oxidativas se dan en
    las tres especies, si bien la primera es la ruta predominante en las
    preparaciones hepáticas de conejo y de ser humano.

         En el ser humano, el 43% de una dosis oral (0.25-0.75 mg) se
    excreta en la orina en un plazo de 24 h en forma de ácido  cis-
    ciclopropano-carboxílico libre o conjugado. La excreción urinaria no
    aumentó tras la administración de 5 dosis diarias sucesivas.

         En la lana de las ovejas se detectaron concentraciones altas
    (hasta 1156 mg/kg) de alfa-cipermetrina 14 días después de la
    aplicación por inmersión o por lavado. En la grasa subcutánea se
    encontraron niveles bajos (hasta 0.04 mg/kg). Después de tratar
    terneros a lo largo del dorso con 10 ml de una preparación al 1.6%, no
    se detectó alfa-cipermetrina en los músculos ni en el hígado. La
    máxima concentración en la grasa perirrenal durante un período de 14
    días fue de 0.26 mg/kg.

         Tras la aplicación de hasta 0.2 ml de principio activo a lo largo
    del dorso de vacas lecheras, se encontraron en la leche de tres en 15
    animales tratados residuos de alfa-cipermetrina en concentraciones que
    oscilaban entre 0.003 y 0.005 mg/ml.

    1.3  Efectos en mamíferos de laboratorio y en sistemas de prueba
          in vitro

         En roedores, la toxicidad aguda oral de la alfa-cipermetrina es
    entre moderada y alta. Los valores de la DL50 en ratones y ratas son
    muy variables y dependen de la concentración del compuesto y del
    excipiente. A efectos prácticos, se considera representativo un valor
    de la DL50 de 80 mg/kg de peso corporal. Sin embargo, se han
    notificado valores más altos de DL50 aguda por vía oral. La

    exposición oral aguda produce síntomas clínicos relacionados con la
    actividad del sistema nervioso central.

         Las aplicaciones cutáneas aisladas de alfa-cipermetrina a ratones
    y ratas en concentraciones de 100 y 500 mg/kg de peso corporal,
    respectivamente, no produjeron mortalidad ni síntomas de intoxicación.
    La exposición de ratas por inhalación durante 4 h a una concentración
    atmosférica de 400 mg/m3 tampoco ocasionó mortalidad ni signos
    clínicos.

         Se ha reportado que la alfa-cipermetrina de calidad técnica
    produce una irritación cutánea mínima en el conejo. Algunas de las
    preparaciones provocan irritación ocular grave. La alfa-cipermetrina
    de calidad técnica no produce sensibilización cutanea. En cobayos
    ocasionó la excitación de las terminaciones neuro-sensoriales de la
    piel.

         La exposición breve de ratas a concentraciones de
    alfa-cipermetrina de hasta 200 mg/kg en dieta diaria durante 5 semanas
    o hasta 180 mg/kg en dieta diaria durante 13 semanas no produjo
    efectos tóxicos. Con dosis más elevadas, las ratas mostraron signos de
    intoxicación asociados a la patología del sistema nervioso,
    disminución del crecimiento o aumento del peso del hígado y los
    riñones. No se pusieron de manifiesto efectos hematológicos,
    bioquímicos o histopatológicos claros.

         En un estudio de toxicidad oral en perros durante 13 semanas, la
    dosis más alta, de 270 mg/kg causó síntomas de intoxicación, pero
    todos los demás parámetros examinados (relativos a la hematología,
    bioquímica clínica, análisis de orina, peso de los órganos, anatomía
    patológica e histopatología) se mantuvieron inalterados. El nivel sin
    efectos observados (NOEL) fue de 90 mg/kg de dieta (equivalente a 2.25
    mg/kg de peso corporal al día).

         En un estudio de toxicidad oral en ratas se demostró que la
    alfa-cipermetrina induce neurotoxicidad a causa de alteraciones
    histopatológicas de los nervios tibial y ciático, degeneración axonal
    y aumento de la actividad de la beta-galactosidasa.

         Se carece de datos sobre toxicidad a largo plazo, toxicidad en la
    reproducción, teratogenicidad e inmunotoxicidad.

         Con los datos disponibles sobre la alfa-cipermetrina, se puede
    deducir que se trata de un compuesto no mutagénico en las pruebas con
     Salmonella typhimurium, Escherichia coli y  Saccaromyces cerevisiae,
    y en las pruebas  in vivo e  in vitro con hepatocitos de rata, con
    respecto a la inducción de aberraciones cromosómicas y producción de
    lesiones en cadenas simples de ADN. No se observó aumento de las
    aberraciones cromosómicas en las células de médula ósea de rata.

         Se carece de datos sobre la carcinogenicidad de la
    alfa-cipermetrina.

    1.4  Efectos en el ser humano

         La exposición de la población general a la alfa-cipermetrina es
    insignificante siempre que en su utilización se apliquen buenas
    prácticas agrícolas. Se comprobó que la exposición cutánea profesional
    de los trabajadores durante la mezcla/carga, el rociado y el lavado
    del equipo era de hasta 2.94 mg, 0.61 mg y 0.73 mg, respectivamente.

         En un estudio de exposición a la alfa-cipermetrina durante la
    formulación, se evaluaron los niveles de exposición mediante el
    monitoreo personal y estático de las concentraciones atmosféricas y la
    medición de los metabolitos en la orina. Los niveles de exposición
    personal media del grupo durante los dos días de la formulación de los
    concentrados de calidad técnica fueron de 2.8 y 44.9 mg/m3, mientras
    que la exposición personal media del grupo al material técnico el
    tercer día fue de 54.1 mg/m3. No se detectaron metabolitos en la
    orina (límite de detección, 0.02 mg/litro). Durante la formulación se
    informó de reacciones cutáneas ligeras.

         No se han comunicado casos de envenenamiento.

    1.5  Efectos en otros organismos en el laboratorio y en el medio
         ambiente

         El valor de la CE50 (crecimiento) en las 48 y 96 horas para el
    alga de agua dulce  Selenastrum capricornutum es superior a 100
    µg/litro.

         La alfa-cipermetrina es muy tóxica para los invertebrados
    acuáticos. Los valores de la CE50 (inmovilización) a las 24 y 48 h
    para  Daphnia magna son de 1.0 y 0.3 µg/litro, respectivamente, y el
    valor de la CL50 a las 24 h para  Gammarus pulex es de 0.05
    µg/litro. La alfa-cipermetrina es muy tóxica para varios grupos de
    artrópodos acuáticos, pero lo es menos para los moluscos. Se puede
    reducir la toxicidad a corto plazo del compuesto formulando el
    producto como suspensión con mayor cantidad de aceite. Aunque el
    arrastre del rociado puede producir efectos tóxicos en los
    invertebrados acuáticos, la desaparición rápida de la
    alfa-cipermetrina del agua facilita la recuperación.

         La alfa-cipermetrina es muy tóxica para los peces. El valor de la
    CL50 a las 96 h oscila entre 0.7 y 350 µg/litro, segun la
    formulación. Las formulaciones de concentrados emulsionables son mucho
    más tóxicas que el concentrado en suspensión, el polvo humectable y
    las formulaciones microencapsuladas. El peligro del compuesto para los
    invertebrados acuáticos y los peces radica en su toxicidad aguda. No

    hay pruebas de que se produzcan efectos acumulativos debido a una
    exposición prolongada.

         No se dispone de datos acerca de los efectos de la
    alfa-cipermetrina en los microorganismos del suelo. En un sistema
    cerrado, no se observaron efectos en las bacterias de aguas residuales
    con concentraciones de 3 mg/litro.

         La toxicidad de la alfa-cipermetrina para determinados
    coleopteros carábidos y larvas de neurópteros es relativamente baja,
    y representa un peligro limitado en las fases preadultas de los
    himenópteros parasitoides. En estudios de campo en pequeñas parcelas
    y en gran escala se ha puesto de manifiesto que la alfa-cipermetrina
    es poco peligrosa para los coleopteros carábidos y estafilínidos, pero
    es un peligro relativamente grande para las arañas linifíidas. Los
    efectos sobre las poblaciones se limitaron a una sola temporada de
    crecimiento. Además, la alfa-cipermetrina es de bajo riesgo para las
    larvas de sírfidos, pero tiene efectos considerables en los
    coccinélidos. Sin embargo, la rápida desaparición de los residuos de
    las hojas permite a estos animales recolonizar en poco tiempo las
    zonas tratadas.

         La utilización de alfa-cipermetrina en el campo no diminuye la
    abundancia relativa de entomófagos en las comunidades de artrópodos.
    Su utilización en cultivos de cereales de grano pequeño no iría
    acompañada de la "reaparición" de plagas o de infestaciones de plagas
    secundarias.

         En las pruebas de laboratorio, la toxicidad de la
    alfa-cipermetrina para las lombrices de tierra es baja. No se registró
    mortalidad tras 14 días de exposición de las lombrices a
    concentraciones de hasta 100 mg/kg de suelo artificial.

         En pruebas de toxicidad aguda en el laboratorio se observó que la
    alfa-cipermetrina es muy tóxica para las abejas. La administración
    oral de una solución concentrada emulsionable dio una DL50 a las 24
    h de 0.13 µg/abeja, mientras que el valor correspondiente para la
    administración tópica fue de 0.03 µg/abeja (producto técnico) ó 0.11
    µg/abeja (CE). La elevada toxicidad de la alfa-cipermetrina para las
    abejas no se manifestó claramente en los ensayos de campo,
    probablemente a causa del breve efecto repelente del producto, que
    hace disminuir la actividad libadora de las abejas y, por
    consiguiente, su exposición.

         No se dispone de datos acerca de la toxicidad del
    alfa-cipermetrina para las aves.

    2.  Conclusiones

    2.1  Población general

         Cuando la alfa-cipermetrina se aplica correctamente, la
    exposición de la población general al producto es baja y probablemente
    no supone riesgos.

    2.2  Exposición ocupacional

         Con buenas prácticas de trabajo, medidas de higiene y
    precauciones de seguridad, es improbable que la alfa-cipermetrina
    suponga un peligro para las personas expuestas en forma laboral. La
    aparición de "sensaciones faciales" es un síntoma de exposición. En
    estas circunstancias se deben re-examinar las prácticas de trabajo.

    2.3  Medio ambiente

         Con las cantidades recomendadas para la aplicación es improbable
    que la alfa-cipermetrina alcance niveles de importancia ecológica. En
    condiciones de laboratorio es muy tóxica para los artrópodos
    acuáticos, los peces y las abejas. Hay cierta probabilidad de que se
    produzcan efectos tóxicos importantes en invertebrados a los que no
    está destinado y en peces en casos de derrame, rociado excesivo o mala
    utilización del producto.

    3.  Recomendaciones

    *    Se debe evitar la contaminación de aguas superficiales.

    *    La alfa-cipermetrina se une fuertemente a las partículas. Se
         deberían llevar a cabo nuevos estudios ecotoxicológicos sobre los
         efectos del compuesto en los microorganismos de los sedimentos,
         puesto que este aspecto parece haber recibido poca atención.

    *    Hay que investigar la absorción gastrointestinal de
         alfa-cipermetrina en distintas circunstancias.

    *    Se debe investigar el destino final de la alfa-cipermetrina
         aplicada por vía cutánea.

    *    Hay que obtener nueva información acerca de la
         toxicidad/carcinogenicidad a largo plazo y de la inmunotoxicidad
         de la alfa-cipermetrina.


    See Also:
       Toxicological Abbreviations
       Cypermethrin, alpha- (UKPID)