IPCS INCHEM Home


    PESTICIDE RESIDUES IN FOOD - 1981


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1981







    Food and Agriculture Organization of the United Nations
    Rome

    FAO PLANT PRODUCTION AND PROTECTION PAPER 42

    pesticide residues in food:
    1981 evaluations

     the monographs

    data and recommendations
    of the joint meeting
    of the
    FAO panel of experts on pesticide residues
    in food and the environment
    and the
    WHO expert group on pesticide residues

    Geneva, 23 November-2 December 1981

    FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS
    Rome 1982

    CYPERMETHRIN

    Explanation

         Cypermethrin was evaluated by the 1979 JMPR,* and a temporary ADI
    was estimated at that time. Lack of data on tissue residue storage and
    release and on human experience with cypermethrin were instrumental in
    making this temporary. Further toxicological data were required on
    potential bioaccumulation of cypermethrin and/or its metabolites in
    adipose tissue and on humans exposed to the pesticide, especially
    those with a high level of occupational exposure. Such data were
    submitted to this Meeting for evaluation.

         Temporary maximum residue limits were recommended for several
    crops in 1979 and the Meeting considered that further information was
    desirable on residue data on known fruits from supervised trials,
    selective surveys of residues in crops known to have been treated
    under practical circumstances, and use patterns for animal health use
    and residues in foods of animal origin deriving from the recommended
    application.

         At the 13th Session of the Codex Committee on Pesticide residues,
    the appropriateness of the MRLs for wheat and alfalfa was questioned.

         Since cypermethrin was evaluated by the JMPR in 1979, new data
    have become available. These are summarized in this monograph and
    cover the following categories: new food crop uses, including coffee,
    fruiting vegetables with edible peel, nectarines and apricots;
    additional data for crops previously evaluated by the JMPR, including
    wheat grain, cherries and plums; and residue data on fodder crops,
    cattle tissues and milk.

    DATA FOR THE ESTIMATION OF ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution, biotransformation and excretion

    Rats

         The fate of orally administered cis- and trans-isomers of
    cypermethrin was studied in rats at levels of 1 to 5 mg/kg, using
    three forms of radio labelling, e.g. benzyl-14C; cyclopropyl-14C and
    cyano-14C (Crawford  et al 1981). Radioactivity derived from the

              

    *  See Annex II for FAO and WHO documentation.

    benzyl-14C and cyclopropyl-14C labelling was rapidly eliminated,
    mostly in the urine. Tissue residues were generally very low, e.g.
    0.01 µg/g in brain, with the exception of fat (about 1 µg/g). Residues
    derived from the cis-isomer tended to be higher them those derived
    from the trans-isomer. The rate of depletion of the residues derived
    from (benzyl-14C)-cis-cypermethrin was rapid (t 1/2 was less than
    about 1 day) from all tissues except fat (t 1/2 of 11 to 12 days).
    This residue consisted largely of unchanged cis-cypermethrin. The
    rapid elimination of cypermethrin from rats is due primarily to the
    efficient cleavage of the ester bond giving rise to polar metabolites,
    which are further oxidized and conjugated before excretion (Crawford
     et al 1981).

         The kinetics of cypermethrin in the blood of rats following
    single oral doses of 2 mg/kg and 200 mg/kg in male and female Wistar
    rats utilizing 14C-benzyl-, and 14C-cyclopropyl-labelled cypermethrin
    (50:50 of cis:trans) have been described (Climie 1980). In the low
    dose studies (2 mg/kg) the half-lives for the elimination of
    radioactivity from the blood of rats following an oral dose of
    14C-labelled cypermethrin were:

         14C-benzyl label: male, 2.78 h; female 4.36 h.

         14C-cyclopropyl label: male, 4.30 h; female, 4.74 h.

         The mean peak blood concentrations of cypermethrin equivalents
    derived from the benzyl label were 1.8 and 1.4 µg/ml, both at about
    3 h after dosing for male and female rats respectively. The equivalent
    figures from the cyclopropyl label study were 0.7 and 0.6 µg/ml at
    about 3 and 3 to 4 h after dosing respectively. This difference could
    be attributed to a rapid clearance of the labelled chemical from the
    body or to inter-animal variation. The mean peak plasma concentrations
    of cypermethrin in the benzyl-labelled study were 0.19 and 0.18 µg/ml
    for male and female rats respectively. The equivalent figures for the
    cyclopropyl label were 0.04 and 0.02 µg/ml. The difference between the
    two studies can only be accounted for by inter-animal variation.

         The high dose studies with 200 mg/kg (50:50 of cis:trans) showed
    a high inter-animal variation. Each animal behaved differently from
    the others, both with respect to the toxic effect of the compound and
    to the amount of labelled chemical in the blood at any given time. The
    mean peak blood concentrations of cypermethrin equivalents from the
    benzyl-label were 41.9 and 39.7 µg/ml at about 16 and 23 h after
    dosing for females and male rats respectively. The equivalent figures
    from the cyclopropyl study were 6.7 and 10.3 µg/ml blood at about 8
    and 24 h respectively. The peak plasma concentration of cypermethrin
    equivalents in the cyclopropyl metabolite study for female rats,
    however, occurred at 24h and not at 8h after dosing. The mean peak

    plasma concentrations of cypermethrin in the benzyl labelled study
    were 5.4 µg/ml for both male and female rats. The equivalent figures
    for the cyclopropyl label were 0.43 and 0.42 µg/ml for male and female
    rats respectively (Climie 1980).

         The elimination of radioactivity after a large (200 mg/kg)
    single oral dose of radio-labelled cypermethrin (50:50 of cis:trans)
    to groups of male and female rats was rapid (Logan 1980). Cypermethrin
    was partially absorbed and rapidly metabolized, principally by
    ester cleavage, to give the cyclopropanecarboxylic acid and the
    3-phenoxybenzyl moiety, which was excreted mostly as the
    sulphate conjugate of 3-(4'hydroxyphenoxy) benzoic acid. The
    cyclopropanecarboxylic acid was transformed mainly to the ester
    glucuronide prior to elimination. The overall excretion of
    cypermethrin and its metabolites was very rapid, with more than 75% of
    the dose in the case of males and 85% in the case of females being
    eliminated within three days. The residues in the tissues at seven
    days were low with, on average, less than 1% of the total dose being
    retained in the whole body. The residues in fat were the highest of
    all tissues (21 to 14 µg/g) but they were considerably less than 100
    times as large as the residues found in fat when rats were dosed at
    about 2 mg/kg (Crawford and Hutson 1977; Crawford 1977), and suggests
    than an appreciable portion of the dose was not absorbed.

         The presence of a large proportion of the dose as untransformed
    cypermethrin in the faeces, 26 to 51%, is a further indication of the
    poor absorption of this insecticide at this dose level. The absorbed
    cypermethrin, however, was rapidly cleaved at the ester bond to
    produce 2,2-dimethyl-3-(2', 2'-dichlorovinyl)cyclopropane carboxylic
    acid and a 3-phenoxy-benzoyl moiety that was mostly further
    metabolized by oxidation at the 4' position. The resultant phenol
    was almost totally conjugated with sulphate, the identical result to
    that observed in low dose studies (Crawford and Hutson 1977). The
    4'-hydroxy sulphate forms the major aryl metabolite (16% of the dose)
    with 3-phenoxybenzoic acid as the second most important (5%). The
    other identified aryl metabolites are 3-(4 -hydroxyphenoxy) benzoic
    acid (1%) and the glycine conjugate, N-(3-phenoxybenzoyl) glycine
    (1%).

         The cyclopropyl acid is almost exclusively conjugated as the
    ester glucuronide (30% of the dose in males, 47% in females) with some
    free acid (twice as much trans as cis) being found in the urine (4%)
    together with traces of the trans-hydroxymethyl cyclopropyl acids
    (2%).

         The bioaccumulation of radioactivity in the rat was investigated
    following 28 consecutive daily oral doses of (14C)-cypermethrin
    (50:50 of cis: trans) at a dose level of 2 mg/kg bw/day (Hall
     et al 1980).

         Twenty-four hours after the 28th daily dose, the tissue
    distribution of radioactivity was similar in male and female rats. The
    highest mean concentrations of radioactivity were found in fat (4 100
    and 5 100 ng equivalents of (14C-cypermethrin/g tissue in males and
    females respectively), skin (636 and 712 ng equivalents/g of tissue),
    gastrointestinal tract (547 and 578 ng equivalents/g tissue), liver
    (566 and 672 ng equivalents/g tissue), kidney (495 and 535 ng
    equivalents/g tissue), adrenal glands (913 and 665 ng equivalents/g
    tissue) and ovaries (710 ng equivalents/g tissue).

         Low mean concentrations were found in heart (67.6 and 88.7 ng
    equivalents/g tissue in males and females respectively), spleen
    (64.2 and 63.6 ng equivalents/g tissue), muscle (35.2 and 51.7 ng
    equivalents/g tissue) and bone (72.8 and 44.4 equivalents/g tissue).
    There was no detectable radioactivity in the brain of female rats and
    only a very low concentration in that of males (mean = 13.4 ng
    equivalents/g tissue). Of the individual organs examined, the highest
    residual radioactivity was found in the gastrointestinal tract
    (mean = 6 405 ng equivalents/g tissue), liver, (mean = 5 820 ng
    equivalents/g tissue) and kidney (mean = 795 ng equivalents/g tissue).

         The high concentration of radioactivity found in fat, skin,
    ovaries and adrenal glands is consistent with the lipophilic nature of
    cypermethrin. The pyrethroid group of insecticides is known to undergo
    extensive metabolism in mammals (Casida and Ruzo 1980) resulting in
    metabolites of a less lipophilic nature that will therefore be more
    rapidly excreted than the parent compound.

         The accumulation of radioactivity in the liver and kidney found
    in this study is consistent with these processes of metabolism and
    excretion. High levels of radioactivity were also found in the
    gastrointestinal tract, reflecting its role in absorption. The
    remaining tissues that were studied accumulated less radioactivity,
    the lowest levels being located in the brain (Hall  et al 1980).

         A bioaccumulation study was undertaken to establish the rate of
    extent of accumulation of cypermethrin-derived 14-C label in a
    selected range of tissues during a daily oral dosing regime and also
    the rate of elimination of any 14C-residues following the attainment
    of steady state tissue levels. Sixty female rats were dosed orally
    with 14C-benzyl-labelled cypermethrin (50:50 of cis: trans), 2 mg/kg
    (2 µCi/kg) bw, in maize oil (2 ml/kg) for up to 70 consecutive days. A
    group of treated (3) and untreated (1) animals were sacrificed at
    prescribed intervals during the dosing regime in order to monitor the
    rate and extent of bioaccumulation of 14C-radioactivity in liver,
    kidney, adipose tissue (fat), blood (whole blood and plasma), skin and
    ovaries (Jones 1981).

         The elimination of radioactivity from fat demonstrated biphasic
    characteristics. This was associated with a rapid elimination of

    residues of trans-cypermethrin coupled with a slower elimination of
    the cis-isomer. These elimination characteristics did not allow a
    simple half life value for elimination of radioactivity from fat to be
    calculated. However, as the relative proportions of cis- and trans-
    isomers in fat were monitored from day 70 of the study, it was
    possible to determine the independent half lives for both isomers. At
    the termination of dosing, the relative proportions of cis-and trans-
    isomers in fat were 88.25% to 11.75%. The half lives of elimination of
    cis- and trans-cypermethrin from fat were calculated by linear
    regression analysis to be 18.24 and 3.43 days respectively.

         Daily dosing was continued for 70 consecutive days, by which
    time the extent of bio-accumulation of radioactivity in each
    tissue analysed had been shown to reach a plateau. The extent of
    accumulation, expressed as µg equivalents of cypermethrin per gram of
    tissue (as mean ± S.D. values from a group of 3 rats), was: liver
    0.97 ± 0.31; kidneys 0.65 ± 0.24; fat 3.91 ± 0 25, blood 0.35 ± 0.13;
    plasma 0.64 ± 0.28; skin 1.86 ± 0.14 and for each ovary 0.03 ± 0.01 µg
    equivalents. Such levels of radioactivity in ovaries were similar to
    background values.

         In addition, the degree of accumulation of 14C-label in the
    sciatic nerve was determined by analysing nerves isolated from treated
    animals given 56 to 70 daily doses of cypermethrin. The extent of
    accumulation of radioactivity did not exceed 0.05 µg equivalents of
    cypermethrin per nerve, representing a level of radioactivity similar
    to the background value.

         Following the termination of dosing, the remaining groups of
    treated and untreated rats were sacrificed at prescribed intervals
    during a period of 50 days. Tissue residue levels of radioactivity
    were monitored and the rate of elimination of 14C-label from each
    tissue was determined. After the cessation of dosing the liver, kidney
    and blood 14C-residue levels fell rapidly and reached control
    background levels within 29, 8 and 15 days respectively. With regard
    to skin, a much slower elimination of radioactivity was observed, with
    half of the radioactivity being eliminated by 18.7 days after dosing
    (Jones 1981).

    Dog

         The metabolites derived from a single oral dose of
    (14C-cyclopropyl) cypermethrin (1:1 cis/trans-WL 43467), administered
    orally to two male beagle dogs, have been studied. The rapid
    elimination of cypermethrin in dogs was due to the efficient cleavage
    of the ester linkage of both the cis- and trans-isomers and the
    urinary excretion of the cyclopropane carboxylic acid moiety, largely
    as its glucuronic acid conjugate. This metabolite comprised 18% and
    51% of the respective doses administered to dogs 1 and 2. Absorption

    of the orally administered cypermethrin was not complete, i.e. 65.6%
    of the dose was excreted as unchanged cypermethrin in the faeces of
    dog 1 and 32.1% in the faeces of dog 2.

         The results of this study confirmed those derived from a similar
    study in which dogs were dosed with (14C-aryl) cypermethrin, in that
    most of the excreted metabolites were ester-cleavage products of
    cypermethrin. Whereas the 3-phenoxybenzyl moiety was mostly
    hydroxylated in the 4'-position before excretion, most of the
    cyclopropane carboxylic acids (cis- and trans-) were excreted without
    further metabolism other than glucuronide conjugation (Crawford and
    Croucher 1979).

         The results of these studies show that the metabolic fate of
    cypermethrin in dogs is similar to that in rats and mice with the
    following exceptions: absorption from the gut is limited and somewhat
    erratic, and hydroxylation reaction(s) do not occur as readily as in
    rats and mice (Crawford and Croucher 1979).

    Cow

         The metabolic fate of (14C-benzyl)cypermethrin (cis-47% and
    trans-53%) (49.4 mg), administered orally to one lactating cow twice a
    day for 7 days, has been elaborated. This dosage was equivalent to
    approximately 10 ppm of cypermethrin in the total diet. Milk, urine
    and faeces were collected daily and the animal was sacrificed 16h
    after the last dose. A second control cow was fed an untreated diet
    over this period.

         Elimination and ingestion of radioactivity were in balance at
    about day 4 after the start of dosing. Urine and faeces were equally
    the major routes of elimination. Although the metabolites in the urine
    and faeces were not analysed in this study, it was noted that the
    major urinary metabolite of the 3-phenoxybenzyl moiety of the related
    insecticide permethrin in the cow has previously been identified as
    N-(3-phenoxybenzoyl)glutamic acid (Gaughan  et al 1978). Although
    radioactivity was detected in milk, it was equivalent to only about
    0.03 µg of cypermethrin/ml (<0.2% of the ingested dose) and was
    located mostly in the lipophilic component (cream or butterfat).

         Radioactive residues retained in the tissues were generally low
    and were in the order: liver > kidney > fat > blood > muscle.
    Tissue residues (expressed as µg cypermethrin/per g tissue) were liver
    0.21; kidney 0.11; renal fat 0.1; subcutaneous fat 0.08; blood
    0.04 and muscle 0.01. The major residue in liver and kidney was
    N-(3-phenoxybenzoyl)glutamic acid. Another polar metabolite was
    detected in both liver and kidney and, although not identified,
    it was suggested that it could be an acid-label conjugate of
    3-(4'-hydroxyphenoxy)benzoic acid. Unchanged cypermethrin formed only

    a very small proportion of the residue in liver and kidney. Residues
    in lean muscle could not be identified as they were very low (Hutson
    1980.

         A study designed to examine the residue transfer into milk and
    tissues of Fresian cows following oral administration of cypermethrin
    was reported. Three groups of three Fresian cows were fed for up to
    29 consecutive days on a diet containing 0.2, 5.0 or 50 mg/kg of
    cypermethrin (calculated on a whole diet, e.g. grass, nuts, plug, hay,
    basis). (Cypermethrin used was of 78.5% purity, isomer ratio: cis A
    21.7%; cis B 21.6%; trans C19.1% and trans D 16.1%.) At the end of the
    treatment period, two cows from each group were slaughtered. The
    remaining cow from each group was fed an untreated diet for a further
    7 to 8 days before being slaughtered. No effects on milk yields or
    general health of the animals were observed throughout the period of
    the trial.

         Cypermethrin residues found in the milk did not accumulate and
    declined rapidly when feeding of treated diet ceased. Levels
    correlated well with dose rate. Residues resulting from the 0.2 mg/kg
    dose rate remained <0.005 mg/kg and reached mean plateau values of
    0.021 and 0.249 mg/kg for the 5.0 and 50 mg/kg groups respectively.

         Cypermethrin residue levels in tissues were generally in the
    order peritoneal fat > subcutaneous fat > kidney > muscle> liver,
    and these again correlated well with dose level. Cows from the two
    lower dosage groups had tissue residues that were around or below the
    limit of determination of 0.01 mg/kg in all but the fat of the
    5.0 mg/kg group, which contained 0.09 to 0.34 mg/kg. Cypermethrin
    residue levels in the tissues of the high rate group ranged from
    <0.05 mg/kg in liver samples, approximately 0.5 mg/kg in muscle and
    kidney samples and up to approximately 5.0 mg/kg in a peritoneal fat
    sample.

         Examination of the isomer ratios of cypermethrin residues in milk
    and fat showed some cis enrichment compared to the cypermethrin
    originally incorporated into the diet.

         The residue levels of two major metabolites of cypermethrin,
    namely 3-(2,2-dichloro-vinyl)-2,2-dimethylcyclopropane carboxylic acid
    (DCVA) and 3-phenoxybenzoic acid (3-PB acid) have been quantitatively
    measured in the milk and tissues of dairy cows fed for up to 29 days
    on a diet containing 50 mg/kg of cypermethrin (Swaine and Saprets
    1980b), Analysis was also carried out on the milk and tissues of a cow
    that was returned to untreated diet for seven days following the
    treatment period. Residue levels of both metabolites in milk were
    extremely low; measurable residues at about the limit of determination
    of the methodology used (e.g. 0.01 mg/kg) were found in only isolated
    samples and none were found in the post-treatment "recovery" period.
    Tissue analysis indicated residue levels in different organs in the

    general order liver - kidney > muscle > fat, with the maximum
    metabolite residues not exceeding 0.5 mg/kg. Residue levels in the
    "recovery" cow were significantly lower, indicating that the
    metabolites were readily excreted (Swaine and Sapiets 1980a).

         A two-year feeding study has been carried out in which beagle
    dogs, groups of four males and four females, were fed diets containing
    0, 3, 30, 300 and (initially) 1 000 ppm of WL 43467 (cypermethrin).
    When severe signs of intoxication were observed in the groups fed
    1 000 ppm WL 43467, this top dose level was reduced to 750 ppm, and
    when signs of intoxication persisted it was further reduced to 600 ppm
    of the insecticide.

         The results of the study were as follows:

         1.   Signs of intoxication consisted of licking and chewing of
    the paws, a stiff high-stepping gait, whole body tremors, head
    shaking, incoordinate ataxia and, in some cases, convulsions. Some
    dietary inappetence was observed in males fed 1 000 ppm WL 43467.
    These signs were observed in the group fed 1 000 ppm and 750 ppm, but
    not when the dietary level of WL 43467 was reduced to 600 ppm. No
    signs of intoxication were observed in groups of dogs fed 3, 30 and
    300 ppm WL 43467.

         2.   A reduction in body Weight was observed in the top dose
    group males in the main feeding study. This is considered to be a
    consequence of the dietary inappetence observed early in the study
    when the dogs were fed 1 000 ppm WL 43467. No effect on body weight
    (attributable to feeding of the compound) was observed in dogs fed 3,
    30 and 300 ppm WL 43467.

         3.   Significant but small differences between controls and
    treated dogs were observed randomly throughout the study. Sodium
    levels in the blood plasma of male dogs at the 600 ppm treatment level
    showed a significant decrease in some weeks, but were always within
    the normal physiological range. Three dogs tended to have high
    alkaline phosphatase activity throughout most weeks of the study, this
    made the 300 ppm treatment level in male dogs significantly higher
    than in controls. This effect was not observed at 600 ppm. No similar
    effect was observed in female dogs. This observation was not therefore
    considered to be of toxicological significance. Overall, no
    significant differences were detected in clinical chemistry and
    haematological estimations that could be attributed to the feeding of
    WL 43467 for two years.

         4.   No compound-related pathological abnormalities were found. A
    small number of minor organ weight changes were found in intermediate
    dose groups, but were not considered to be due to the feeding of dogs
    with WL 43467 for 2 years (Shell Research Ltd. 1980d).

    Special studies on exposure of spray applicators

         A study was carried out in humans at the Institut de Recherches
    du Coton et des Textiles Exotiques (IRCT), Bouake, Ivory Coast, after
    hand-held ULV application to cotton of the pyrethroid Ripcord (WL
    43467) during one season of spraying.

         The operators were 7 indigenous Africans. Six of them had no
    previous pesticide application history; One had very limited
    experience. They sprayed the formulation EF 4922 (25 g Ripcord/l in
    a 50/50 (v/v) hexylene glycol and Shellsol AB mixture) on an area of
    1 ha at the rate of 2 l/ha in 6 spray sessions at fortnightly
    intervals under the supervision of IRCT staff. In a seventh spray
    session, the same amount was sprayed under the supervision of the
    Exposure Monitoring Group. The operators wore their normal clothes and
    no special protective devices were used.

         Exposure to Ripcord was monitored by collecting the total amount
    of urine passed during the first 24 h after each spray session and the
    determination of the excretion levels of the urinary metabolite trans
    WL 44776 3-(2,2-dichlorovinyl-2,2-dimethyl-cyclopropane-1-carboxylic
    acid). In many samples the excretion was below the limit of detection,
    indicating a low level of absorption. Skin contamination and
    inhalational exposure were monitored only in the seventh spray
    session. Skin and inhalational measurements did not correlate well
    with the urinary excretion. Inhalational exposure was about 1% of skin
    exposure. Skin exposure, as measured with aluminum foil, reflected the
    working procedures. It was concluded that exposures were low, in
    particular when the spraying recommendations are observed.  The
    absorption was calculated to be substantially less than the equivalent
    of an oral dose of 1 mg Ripcord per spray session.

         General medical and extensive clinical and neurological
    examinations, blood biochemistry and peripheral nerve function tests
    (including the trigeminal nerve) did not show abnormalities either
    before or after the series of 6 spray sessions nor after the seventh
    spray session. In some electroneurophysiological tests (motor
    conduction velocity, slow fibre conduction velocity and cornea reflex)
    a statistically significant change within the normal range appeared to
    exist for the group of sprayers between pre- and post-exposure
    measurements. There is no evidence that these changes are compound
    related; they probably reflect seasonal variations.

         The general conclusion is that under the conditions of this study
    the application of Ripcord caused no detectable adverse health effects
    (Prinsen and Van Sittert 1979).

         Transient facial sensory symptoms following exposure to
    synthetic pyrethroids (e.g. cypermethrin, permethrin, fenvalerate
    and fenpropathin) in some workers has been reported (LeQuesne
     et al 1980). Among 23 workers exposed to synthetic pyrethroids,
    19 had experienced one or more episodes of abnormal facial sensation
    that developed between 30 min and 3 h after exposure and persisted
    for 30 min to 8 h. There were no abnormal neurological signs and
    electrophysiological studies were normal in the arms and legs. It was
    concluded that the symptoms are most likely to be due to transient
    lowering of the threshold of sensory nerve fibres or sensory nerve
    endings following exposure of the facial skin to pyrethroids, similar
    to the phenomena that have been described following exposure of animal
    nerves to pyrethroids (Wouters and van den Bercken 1978).

         Skin sensations experienced by those handling cypermethrin or
    other pyrethroids are believed to arise by repetitive firing of
    sensory nerve terminals in the skin. It is said to be a strictly local
    effect, which may occur as soon as the pyrethroid concentration on or
    in the skin reaches a certain level and is not considered as a sign of
    general intoxication (provided the pyrethroid does not reach the blood
    in any significant concentration). A possibility exists, however, that
    repeated occurrence of intense repetitive firing can perhaps
    eventually lead to dysfunction of sensory nerve terminals and sense
    organs and finally to degeneration of sensory nerve fibres (van den
    Bercken 1980).

    Special studies on photodecomposition

         The decomposition of a number of pyrethroids, e.g. cypermethrin,
    fenvalerate, NRDC 161, permethrin, phenothrin and S-3206 on glass by
    radiation of 305 nm has been reported (Barlow  et al 1977). A
    comparison of permethrin and cypermethrin (e.g. insecticide half lives
    of 4.5 and 1.9 days respectively) indicates that the presence of an
    alpha-cyano group in the alcohol reduces stability, while the
    phenothrin-permethrin pair illustrates the stabilizing effect of
    chlorines replacing the methyl groups in the acid position of the
    molecule (Barlow  et al 1977).

    RESIDUES IN FOOD

    USE PATTERN

         Recommendations for the use of cypermethrin on peaches, wheat and
    maize covered in this document were described in papers submitted to
    the 1979 JMPR. Corresponding information for those crops discussed
    herein, and not previously considered by the JMPR, are listed in
    Table 1.

        TABLE 1.  Recommendations for the use of cypermethrin on crops and in animal treatment
                                                                                               
    Crop                Pest                          Application rate (g/ha)       PHI1
                                                                                               

    Cucumber            Trialeurodes vaporariorum     50-80                         1-2 days
    Aubergine           Epilachna sp.                 50                            "
                        Leucinodes orbonalis          60
    Pepper              Heliothis sp.                 30-50                         "
                        Gnorimoschema sp.             50-75
    Coffee              Leucoptera coffeella          10-15                         3 weeks
                                                      37.5-70
    Sorghum2            Diatraea sp.
                        Euxoa sp.                     35-70
                        Heliothis armigera            30-50
                        Busseola fusca                70-80
                        Chilo partellus               50-70
                        Spodoptera frugiperda         50-75
                        Contarinia sorghicola         40
                        Autoba silicula               40

    Alfalfa2            Colias lesbia                 60
                        Spodoptera frugiperda         60-70
                        Acyrthosiphon                 30

    Animal              Pest                          Application rate (mg/l)

    Cattle              HaematoDia irritans           900 mg/1-200 ml/animal =
                        (Buffalo fly)                 180 mg/animal

                                                      WHP - meat 3 days
                                                      milk nil

                        Boophilus microplus           100 mg/l as dip
                        (Cattle tick)

                        Haematobia irritans           "       "
                                                      WHP - meat - 3 days
                                                      milk - nil

    Sheep               Linognathus ovillus           18 g/l
                        Linognathus pedalis           WHP- 7 days
                        Damalinia ovis
                        (Sheep lice)

                        Melophagus ovinus
                        (Sheep ked)
                                                                                               

    1  Interval shown is current minimum required for good agricultural practice;

    2  Owing to the nature of uses, PHIs tend to be indeterminate.
    
    RESIDUES RESULTING FROM SUPERVISED TRIALS

    New food crop uses

    Fruiting vegetables with edible peel

         The available residue data are summarized in Table 2. In some
    instances, crops were grown in greenhouses but, where comparable
    outdoor data are available, it may be seen that residue levels for
    cypermethrin, resulting from the two situations, were similar. As can
    also be seen from Table 2, residue levels for cucumbers and sweet
    peppers were not very different for the two crops, even where a large
    number of applications were made at frequent intervals. Results from a
    single trial with eggplants are included in Table 2, as this crop is
    within the same vegetable classification group. The residue levels
    reported indicate that levels are likely to be generally similar to
    those for cucumbers and sweet peppers and for all three crops are
    unlikely to exceed 0.5 mg/kg following recommended treatments. Data
    for chilli peppers are also included in Table 2. These data tend to be
    somewhat higher than those for the other crops in this group mentioned
    previously; residues up to 1 mg/kg were found at harvest 1 week after
    treatment.

    Coffee

         Residue data have been obtained from a number of trials in
    Brazil. Although treatment according to recommendations gave rise to
    residues in the whole cherries (Imperial Chemical Industries 1981c) of
    up to 0.10 mg/kg, no residues (limit of determination of 0.01 mg/kg)
    were found in samples of coffee beans obtained from either 'green' or
    air-dried cherries. These latter and other data on beans are given in
    Table 3. As coffee is exported only as dried, 'green' beans, without
    the skin or flesh of the fruit, it is considered that residues are
    unlikely to occur in the exported commodity at levels in excess of
    0.05 mg/kg.

    Peach, nectarine and apricot

         Some additional data on peaches, obtained since the 1979
    evaluation, are summarized in Table 4. These support the MRL proposed
    by the 1979 JMPR. The close similarity between nectarines and
    peaches suggests that residue data obtained for peaches could be
    applied equally well to nectarines (both are  Prunus persicae 
    varieties). Moreover, the latter fruit have somewhat smoother skins,
    are likely to retain less spray deposit than peaches and, hence,
    contain somewhat lower residues. The very close physical similarity of
    apricots to peaches also suggests that apricots could also be covered
    by peach residue data.

        TABLE 2.  Residues of cypermethrin in fruiting vegetables with edible peel
                                                                                                                                              

                                                                      Application         Time                                    References
                                                                     Rate                 Between         PHI        Residues
    Crop                Variety      Country          Formulation    (g/ha)     No.       treatment       (Days)     (mg/kg)
                                                                                                                                              

    Cucumber            Evadan       Denmark          10% EC           67       2         10 days           1         0.03        Shell Chimie
    (glasshouse)                                                                                            3         0.02        S.A. 1980a
                                                                                                            7         0.02

                        Amazone      Germany          10% EC           60       3         2 weeks           0         0.07
                                                                                                            1         0.05        ibid 1980b
                                                                                                            3         0.10
                                                                                                            4         0.04
                                                                                                            7         0.02

                        Uniflora     Germany          10% EC           60       3         2 weeks           0         0.05        ibid
                                                                                                            1         0.03
                                                                                                            3         0.02
                                                                                                            4         0.02
                                                                                                            7        <0.01

                        Sandra       Germany          10% EC           60       3         2 weeks           0         0.05
                                                                                                            1         0.07        ibid
                                                                                                            3         0.05
                                                                                                            4         0.05
                                                                                                            7         0.03

                        Corona       The Netherlands  10% EC          125       3         1 week            0         0.02,
                                                                                                                      0.04        ICI 1981c
                                                                                                            3         0.01,
                                                                                                                      0.01
                                                                                                            7         0.01,
                                                                                                                      0.01
                                                                                                           14         0.01,
                                                                                                                      0.01
                                                                                                                                              

    TABLE 2.  (con't)
                                                                                                                                              

                                                                      Application         Time                                    References
                                                                     Rate                 Between         PHI        Residues
    Crop                Variety      Country          Formulation    (g/ha)     No.       treatment       (Days)     (mg/kg)
                                                                                                                                              

    Cucumber            Hokus        Germany          10% EC           60       3         2 weeks           0         0.02        Shell Chimie
    (outdoor)                                                                                               1         0.04        S.A. 1980b
                                                                                                            3         0.01
                                                                                                            4        <0.01
                                                                                                            7        <0.01

                        Hokus        Germany          10% EC           60       3         2 weeks           0         0.05
                                                                                                            1         0.07        ibid
                                                                                                            3         0.04
                                                                                                            4         0.03
                                                                                                            7         0.02

                        Mervita      Germany          10% EC           60       3         2 weeks           0         0.03
                                                                                                            1         0.01        ibid
                                                                                                            3        <0.01
                                                                                                            4        <0.01
                                                                                                            7        <0.01

    Pepper              Sweet        Canada           40% EC           70       9         4-6 days          1         0.28        ibid 1978a
                        (Stoddons                                                                           3         0.25
                        select)                                                                             7         0.22
                                                                                                           14         0.19

                        Sweet        Canada           25% EC           35       5         1 1/2-4 wks       1         0.02        ICI 1981c
                        (Emerald                                                                            4         0.02
                        Giant)                                                                              7         0.03
                                                                                                           14         0.02
                                                                                                           22        <0.01
                                                                                                                                              

    TABLE 2.  (con't)
                                                                                                                                              

                                                                      Application         Time                                    References
                                                                     Rate                 Between         PHI        Residues
    Crop                Variety      Country          Formulation    (g/ha)     No.       treatment       (Days)     (mg/kg)
                                                                                                                                              

    Pepper              Sweet        Canada           25% EC           50       5         1 1/2-4 wks.      1         0.01        ICI 1981c
                        (Emerald                                                                            4         0.02
                        Giant)                                                                              7         0.02
                                                                                                           14         0.01
                                                                                                           22         0.01

                        Sweet        Canada           25% EC           50       1         -                 1         0.09        ibid
                        (Emerald                                                                            3         0.08
                        Giant)                                                                              7         0.11

                        Chilli       India            10% EC           50       1         -                 7         0.50        Shell Chimie
                                                                                                           14         0.23        S.A. 1980c

                                                                       75       1         -                 7         0.76        ibid
                                                                                                           14         0.54

                                                                      100       1         -                 7         1.00        ibid
                                                                                                           14         0.59

    Eggplant            Long         France           40% EC          112       1         -                 2         0.10        ibid 1976a
                        Black                                                                               7         0.04
                                                                                                           15         0.01
                                                                                                                                              

    TABLE 3.  Residues of cypermethrin in coffee
                                                                                                                                     
                                                                      Application
                                                                     Rate                    PHI          Residues      References
    Crop                Part         Country          Formulation    (g/ha)      No.         (Days)       (mg/kg)
                                                                                                                                     

    Coffee              Dried        Brazil           40% EC            5        1           4 weeks       <0.01        Shell Chimie
                        beans                                                                16 weeks      <0.01        S.A. 1980d
                                                                       10        1           4 weeks       <0.01
                                                                                             16 weeks      <0.01

                        Dried        Brazil           40% EC           10        1           1 month       <0.01        ibid 1981a
                        beans

                        Beans ex     Brazil           25% EC           10        1           1 day         <0.01
                        dried                                                                3 days        <0.01        ICI 1981c
                        cherries                                                             6 days        <0.01
                                                                                             17 days       <0.01
                                                                                             31 days       <0.01

                        Beans ex     Brazil           25% EC           10        1           1 day         <0.01        ibid
                        green                                                                3 days        <0.01
                        cherries                                                             6 days        <0.01
                                                                                             17 days       <0.01
                                                                                             31 days       <0.01

                                     Brazil           25% EC           20        l           1 day         <0.01        ibid
                                                                                             3 days        <0.01
                                                                                             6 days        <0.01
                                                                                             17 days       <0.01
                                                                                             31 days       <0.01

                                     Brazil           25% EC           40        1           1 day         <0.01        ibid
                                                                                             3 days        <0.01
                                                                                             6 days        <0.01
                                                                                             17 days       <0.01
                                                                                             31 days       <0.01
                                                                                                                                     

    TABLE 4.  Additional residue data for cypermethrin in peaches
                                                                                                                                   

                                                Application       Time                                            References
                                               Rate               Between      PHI         Residues
    Variety        Country     Formulation     (g/ha)     No.     treatment    (Days)      (mg/kg)
                                                                                                                                   

    Redhaven       Canada      20% WP           140       4       2-4            0         0.34, 0.38, 0.38       Shell Chimie S.A.
                                                                                           0.51, 0.60             1980e

                                                                                 3         0.31, 0.36, 0.36
                                                                                           0.38, 0.48

                                                                                 7         0.21, 0.23, 0.24
                                                                                           0.25, 0.38

    Loring         Canada      20% WP           140       5       2              0         0.42, 0.52, 0.52       ibid 1981b
                                                                                 7         0.35, 0.26

                                                140       4       2             14         0.17, 0.25, 0.19
                                                                                 7         0.34, 0.20
                                                                                21         0.04, 0.15

    Loring         Canada      12.5%             60       4       3-31/2         1         0.25                   ICI 1981c
                                                                                 3         0.15
                                                                                 8         0.06
                                                                                14         0.09

                                                100       4       3-31/2         1         0.32
                                                                                 3         0.23
                                                                                 8         0.15
                                                                                14         0.15

                                                120       4       3-3 1/2        1         0.72
                                                                                 3         0.38
                                                                                 8         0.44
                                                                                14         0.21
                                                                                                                                   

    TABLE 4.  (con't)
                                                                                                                                   

                                                Application       Time                                            References
                                               Rate               Between      PHI         Residues
    Variety        Country     Formulation     (g/ha)     No.     treatment    (Days)      (mg/kg)
                                                                                                                                   

    Dixired        France      5% EC             30       1       -              1         0.04                   Shell Chimie
                                                                                 7         0.03                   S.A. 1980f
                                                                                14         0.02
                                                                                                                                   
        Additional data on certain crops already reviewed

         The following residue data complement data already considered by
    the 1979 JMPR.

    Cherry and plum

         A summary of recent data on cherries is given in Table 5. As
    cherries were considered together with plums by the 1979 JMPR, new
    data on plums are also presented (Table 6). These new data are
    compatible with those available in 1979.

    Wheat

         New residue information on wheat grain has been obtained from
    trials in Europe and Canada and is summarized in Table 7. It can be
    seen that several figures are near to 0.1 mg/kg. As these data were
    derived from experiments with rather low treatment rates (use against
    aphids rather than the less sensitive pests) it is not, therefore,
    possible to be reasonably assured that maximum levels arising from
    current recommendations will fall below 0.1 mg/kg.

    Cottonseed

         In addition to the extensive data considered in 1979, further
    information has been provided from more recent supervised trials in
    the USA. Multiple applications of cypermethrin were made in 1979 and
    in 1980 with commercial type spray equipment at a total of twelve
    cotton fields. The sites were distributed among nine States coast to
    coast California, Arizona, Texas, Louisiana, Arkansas, Mississippi,
    Alabama, Georgia and North Carolina - and at six of the sites
    cypermethrin was applied by air. Some trial programmes included 24%
    and 36% EC formulations. Up to 16 applications were made at rates up
    to 0.13 kg a.i./ha/application. Higher application rates were also
    used in some of the trials (Table 8). Cotton was harvested 13 to 74
    days after the last application (Ussary 1980, 1981).

         Residue samples normally consisted of approximately 1 kg of
    mature crop. Samples of bolls, separated from burrs in the field,
    were shipped frozen to the analytical laboratory, where they were
    transferred immediately on arrival to a freezer maintained at -18°C.
    Samples were ginned, milled and analysed by gas-chromatography using
    an electron capture detector (as reviewed at the 1979 Meeting).

         The US label involves spraying at 0.07-0.13 kg a.i./ha, with up
    to sixteen applications per season and with a minimum pre-harvest
    withholding interval of 14 days. The results of this residue trial
    programme are shown in Table 8. There was no obvious difference in
    residue levels yielded by 24% and 36% EC formulations under similar
    circumstances (Table 8) (Ussary 1980, 1981).

        TABLE 5.  Residues of cypermethrin in cherries
                                                                                                                                            

                                                  Application             Time                                            References
                                               Rate                       Between             PHI         Residues
    Variety        Country     Formulation     (g/ha)          No.        treatment           (Days)      (mg/kg)
                                                                                                                                            

    Rubin          Germany     10% EC          0.01%           3          2 weeks               0         1.3             Shell Chimie, S.A.
                                               (150 g/ha)                                       4         0.80            1980h
                                                                                                7         0.40
                                                                                               10         0.29
                                                                                               14         0.17

                   Germany     8% WP           0.008%          3          2 and 1 week          0         1.3             ibid 1981 c
                                               (120 g/ha)                                       4         0.6
                                                                                                7         0.54
                                                                                               10         0.27
                                                                                               14         0.22

    Schatten       Germany     8% WP           0.008%          3          2 and 1 week          0         0.47
    Morelle                                    (120 g/ha)                                       4         0.39
                                                                                                7         0.25
                                                                                               10         0.18
                                                                                               14         0.08

    Rubin          Germany     8% WP           0.008%          3          2 and 1 week          0         2.0
                                               (120 g/ha)                                       4         0.70
                                                                                                7         0.35
                                                                                               10         0.25
                                                                                               14         0.11
                                                                                                                                            

    TABLE 6.  Residues of cypermethrin in plums, Fed. Rep. of Germany1
                                                                                                           

                                            Application              Time                          Residues
                                          Rate                       between        PHI
    Variety             Formulation2      (g/ha)        No.          treatments     (days)         (mg/kg)
                                                                                                           

    Auerbacker          8% WP             120           5            2-3 weeks        0             0.08
                                                                                      7             0.07
                                                                                     14             0.06
                                                                                     21             0.05

    Ortenberg           8% WP             120           5            2-3 weeks        0             0.04
                                                                                      7             0.02
                                                                                     14            <0.01
                                                                                     21            <0.01

    Hauszwetsche        8% WP             120           5            2-3 weeks        0             0.1
                                                                                      7             0.09
                                                                                     14             0.08
                                                                                     21             0.06
                                                                                                           

    1  Reference-Shell Chimie S.A. 1981d;
    2  Cypermethrin was applied in admixture with fenbutatin oxide in all these experiments.

    TABLE 7.  Residues of cypermethrin in wheat grain
                                                                                                                                               

                                                    Application           Time (days)                      Residues
                                                   Rate                   between           PHI
    Country        Variety        Formulation      (g/ha)     No.         treatments        (days)         (mg/kg)               Reference
                                                                                                                                               

    Canada         Neepawa        40% EC             28       1           -                  10           0.04,0.05              Shell Research
                                                                                             24           0.04,0.03,0.03         Ltd. 1981e
                                                                                             49           0.02,0.08,<0.01
                                                              3           24 and 14          10           0.05,0.07,0.01
                                                     28       1           -                  20           0.03,0.03,0.02,0.02
                                                                                             32           0.03,0.02,0.01,0.02
                                                                                             57           0.03,<0.01,0.01,0.01
                                                              3           24 and 12          20           0.07,0.08
                                                     28       1           -                  20           0.02,0.02,0.03
                                                                                             32           0.02,0.03,0.03,0.03
                                                                                             57          <0.01,<0.01,<0.01,<0-01
                                                              3           24 and 12          20           0.03,0.03,0.04,0.04
                                                     28       1           -                  32           0.05,0.05,0.06,0.05
                                                                                             40           0.03,0.02,0.03,0.03
                                                                                             62           0.02,0.01,0.02,0.02
                                                              3           22 and 9           32           0.08,0.09,0.07,0.12

    Denmark                       10% EC             50       1           -                  42          <0.01                   Shell Chimie
                                  10% EC             50       1           -                  42          <0.01                   S.A. 1981d
    UK                            25% EC             30       1           -                  18          <0.01
                                                                                             32          <0.01                   ICI 1981c
                                                     60       1           -                  18          <0.01
                                                                                             32          <0.01
                                                                                                                                               

    TABLE 8.  Residues of cypermethrin on cottonseed, 1979 and 1980 USA field trials1
                                                                                                                                           

                                                                                                  Cypermethrin (mg/kg)3
    Trial No.           Formulation      Application        Days after                                                                     
                                               Rate         last application            0.07     0.09     0.11     0.13     0.26     0.53
    and location        Type           No.     (gal/acre)   to harvest         Check    kg/ha    kg/ha    kg/ha    kg/ha    kg/ha    kg/ha
                                                                                                                                           

    38AZ 79-006         24% EC         10         26             14            <0.05                      <0.05
    Yuma, AZ

    38AZ79-005          24% EC         11          5             14            <0.05    <0.05
    Yuma, AZ            36% EC         11          5             14                     <0.05
    (aerial)            24% EC         11          5             74            <0.05    <0.05
                        36% EC         11          5             74                      0.07

    28GA79-003          24% EC         11         13.5           66            <0.05                       0.05
    Smithville,GA

    28GA79-004          24% EC         12          5             61            <0.05     0.05
    Smithville,GA       24% EC         12          5             61                     <0.05
    (aerial)

    29MS79-014          24% EC          6         12.9           72            <0.05                      <0.05
    Greenwood, MS

    06AR79-008          24% EC          5          8             40                                       <0.05
    Scott, AR

    20TX79-009          24% EC          7          7.3           55            <0.05                      <0.05
    Still Store, TX

    EU1-79-03           24% EC          5         19.6           64            <0.05             <0.05
    Goldsboro, NC       36% EC          5         19.6           64                              <0.05
                        24% EC          5         19.6           64                              <0.05
                                                                                                                                           

    TABLE 8.  (con't)
                                                                                                                                           

                                                                                                  Cypermethrin (mg/kg)3
    Trial No.           Formulation      Application        Days after                                                                     
                                               Rate         last application            0.07     0.09     0.11     0.13     0.26     0.53
    and location        Type           No.     (gal/acre)   to harvest         Check    kg/ha    kg/ha    kg/ha    kg/ha    kg/ha    kg/ha
                                                                                                                                           

    EU1-70-04           24% EC          5         19.6           64                                       <0.05
    Goldsboro, NC

    45AL80-008          36% EC         16         10.2           14            <0.01                                0.05     0.01
    Shorter, AL         24% EC         16         10.2           14                                                <0.01

    42AZ80-004          36% EC         16         32             14                                                 0.08     0.13     0.11
    Peoria, AZ          24% EC         16         32             14                                                 0.02

    38AZ80-011          36% EC         16          5             14                                                 0.02
    Yuma, AZ (air)

    41CA80-007          36% EC         16         20             13                                                 0.31              0.52
    Visalia, CA         24% EC         16         20             13            <0.01                                0.13

    28GA80-021          36% EC         16         10             14            <0.01                                0.02
    Athens, GA

    28GA80-023          36% EC         16          4             14                                                 0.01
    Cochran, GA (air)

    36LA80-010          36% EC         16          5             14                                                 0.01
    Jonesville, LA
    (air)

    29MS80-002          36% EC         16          6             16                                                 0.07     0.16
    Glen Allan, MS
                                                                                                                                           

    TABLE 8.  (con't)
                                                                                                                                           

                                                                                                  Cypermethrin (mg/kg)3
    Trial No.           Formulation      Application        Days after                                                                     
                                               Rate         last application            0.07     0.09     0.11     0.13     0.26     0.53
    and location        Type           No.     (gal/acre)   to harvest         Check    kg/ha    kg/ha    kg/ha    kg/ha    kg/ha    kg/ha
                                                                                                                                           

    29MS80-003          36% EC         16          2             16            <0.01                                0.01
    Glen Allan, MS
    (air)

    43MS80-023          36% EC         16          8.2           31            <0.01                                0.03              0.13
    Rocky Mounts, NC

    33TX80-002          36% EC         16          3             14            <0.01                                0.05
    Wilson, TX (air)

    33TX80-009          36% EC         16         41             14            <0.01                                         0.05     0.16
    Lorenzo, TX
                                                                                                                                           

    1  Reference - Ussay 1980, 1981
    2  US gallons/acre = 9.3 litres/hectare
    3  values corrected for analytical recovery.
        Data relating to the use of cypermethrin-treated crops as animal
    feed

         The crop commodities likely to be the main source of cypermethrin
    residues in animal feed are fodder crops and legume crops. Although
    other components of animal feed, such as cottonseed cake or dried
    fruit pomace, may contain residues of cypermethrin, these will be
    either at low levels, or the product will form only a relatively small
    proportion of the total daily ration, so that residues in feeds from
    these sources will not be the determining factor in considering
    maximum residue limits.

         Residue data for fodder crops including straw are given in Table
    9 (recommendations for the use of cypermethrin and data on residues in
    grain components of the crops have previously been examined by the
    JMPR in 1979). Data for legume crops (alfalfa) are given in Table 10.

         The data cover a wide range of levels, depending on crops and
    conditions. However, as cattle may be given feed prepared shortly
    after treatment, it would seem that estimates of maximum levels that
    could occur in feed should be estimated from the higher residues
    arising from short pre-harvest intervals.

         From the information available, therefore, it is considered that
    residues in animal feed components are unlikely to exceed 10 mg/kg in
    total diet but will, in most instances, be considerably below this
    level.

    FATE OF RESIDUES

    In animals

    Cow

         Studies have been undertaken to investigate the fate of
    cypermethrin in cattle and to establish at what level of residues in
    meat or milk could arise as a result of feeding crop products treated
    with cypermethrin as cattle feed. Separate experiments have been
    carried out using both radio-labelled material and technical
    (unlabelled) cypermethrin. In these experiments feeding levels
    corresponding to between 0.2 and 50 mg/kg of the total daily ration
    have been used to investigate the fate and magnitude of residues which
    could occur following the use of feed components containing residues
    at various levels.

         Trials carried out in Australia (Australia 1981) with
    cypermethrin emulsion designed for spraying cattle as protection
    against buffalo fly involved the application of 200 ml of spray
    containing 1 g/l cypermethrin (i.e. 200 mg/animal), the recommended

        TABLE 9.  Residues of cypermethrin in fodder crops
                                                                                                                                           

                                                                       Application       Time
                                                                       Rate              between        PHI      Residues   Reference
    Crop        Crop part              Country        Formulation      (g/ha)   No.      treatments     (days)   (mg/kg)
                                                                                                                                           

    Maize       Stems                  USA            EC                 30      1       -                4        2.6      ICI 1981c
                                                                                                          7        0.92
                                                                                                         14        0.89

                                                                         60      1       -                4        6.9
                                                                                                          7        2.0
                                                                                                         14        2.6

                Husks                                                    30      1       -                4        0.54
                                                                                                          7        0.37
                                                                                                         14        0.23

                                                                         60      1       -                4        1.1
                                                                                                          7        0.54
                                                                                                         14        0.62

                Whole plant            S. Africa      20% EC             15      1       -                1        0.11     ibid
                                                                                                          2        0.06
                                                                                                          4        0.07
                                                                                                         16       <0.05
                                                                                                         32        0.20

                                                                         30      1       -                1        0.12
                                                                                                          2        0.06
                                                                                                          4        0.13
                                                                                                          8        0.08
                                                                                                         16        0.13
                                                                                                         32        0.07
                                                                                                                                           

    TABLE 9.  (con't)
                                                                                                                                           

                                                                       Application       Time
                                                                       Rate              between        PHI      Residues   Reference
    Crop        Crop part              Country        Formulation      (g/ha)   No.      treatments     (days)   (mg/kg)
                                                                                                                                           

                Stalks and leaves      Canada         40% EC             50      5       4-7 days         9        0.83     Shell Chimie
                (at maturity)                                            70      5       4-7 days         9        1.80     S.A. 1980g

                Stems and leaves       Canada         40% EC             50      5       5 days           1        1.7      Shell Research
                (at maturity)                                                                             3        1.4      Ltd. 1981a
                                                                                                         14        0.7

                Husks                  Canada         40% EC             50      5       5 days           1        0.92     ibid
                                                                                                          3        0.65
                                                                                                         14        0.25

                Green maize            Fed. Rep. of   10% EC            100      1       -                0        2.9      Shell Chimie
                                       Germany                                                            7        1.1      S.A. 1979a
                                                                                                         14        0.15

                                                      10% EC            100      1       -                0        1.9      ibid
                                                                                                          7        0.5
                                                                                                         14        0.12

                Green maize            Fed.Rep. of    10% EC            100      1       -                0        2.7      ibid
                                       Germany                                                            7        2.2
                                                                                                         14        0.51

                Green maize            S. Africa      -                 120      1       -               14        0.8      Shell Research
                                                                                                                            Ltd.1977a

                                                                        240      1       -               14        2.0
                                                                                                                                           

    TABLE 9.  (con't)
                                                                                                                                           

                                                                       Application       Time
                                                                       Rate              between        PHI      Residues   Reference
    Crop        Crop part              Country        Formulation      (g/ha)   No.      treatments     (days)   (mg/kg)
                                                                                                                                           

    Wheat       Straw                  Canada         40% EC            140      1       -               13        8.5      Shell Chimie
                                                                                                         20        5.4      S.A.1977a
                                                                                                         27        1.9

                Green plant            Canada         40% EC            140                               0        6.5      ibid 1977b
                                                                                                          6        4.3

                                                                                                          0        7.3
                                                                                                          6        4.3
                                                                                                         13        3.8

                                                                                                          0        8.1
                                                                                                          6        4.5
                                                                                                         13        2.8
                                                                                                         20        1.9

                Green plant            UK             25% EC             30      1       -               18        0.67     ICI 1981c
                                                                                                         32        0.58

                                                                         60      1       -               18        1.3      ibid
                                                                                                         32        0.64

                Straw                  UK             25% EC             30      1       -               18        1.5
                                                                                                         32        1.2

                                                                         60      1       -               18        1.8
                                                                                                         32        1.7
                                                                                                                                           

    TABLE 9.  (con't)
                                                                                                                                           

                                                                       Application       Time
                                                                       Rate              between        PHI      Residues   Reference
    Crop        Crop part              Country        Formulation      (g/ha)   No.      treatments     (days)   (mg/kg)
                                                                                                                                           

    Sorghum     Whole plant            S. Africa      20% EC             15      1       -                1        0.88     ibid
                                                                                                          4        0.67

                                                                         30      1       -                1        3.1
                                                                                                          2        2.2
                                                                                                          4        2.4
                                                                                                          8        2.1
                                                                                                         16        1.8
                                                                                                         32        1.5

    Sorghum     Heads                  S. Africa      20% EC             40      1       -                0        0.76     Shell Research
                                                                                                          1        0.78     Ltd. 1980a
                                                                                                          2        0.61
                                                                                                          4        0.60
                                                                                                          8        0.37

                                                                         70      1       -                0        1.2      ibid
                                                                                                          1        0.82
                                                                                                          2        0.55
                                                                                                          4        0.74
                                                                                                          8        0.79

                                                                        140      1       -                0        1.5      ibid
                                                                                                          1        1.4
                                                                                                          2        1.2
                                                                                                          4        1.2
                                                                                                          8        1.4
                                                                                                                                           

    TABLE 9.  (con't)
                                                                                                                                           

                                                                       Application       Time
                                                                       Rate              between        PHI      Residues   Reference
    Crop        Crop part              Country        Formulation      (g/ha)   No.      treatments     (days)   (mg/kg)
                                                                                                                                           

                                       Australia      20% EC             80      1       -                0        1.7      ibid 1980b
                                                                                                          3        1.3
                                                                                                          7        1.7
                                                                                                         14        1.2

                                                                        160      1       -                0        2.3      ibid
                                                                                                          3        2.7
                                                                                                          7        2.3
                                                                                                         14        2.2

                                       S. Africa      20% EC             30      1       -                1        0.47     ICI 1981c
                                                                                                          2        0.58
                                                                                                          4        0.49
                                                                                                          8        0.82
                                                                                                         16        0.44
                                                                                                         32        0.70
                                                                                                                                           

    TABLE 10.  Residues of cypermethrin in legume animal feeds
                                                                                                                                           

                                                      Application         Time
                                                      Rate                between        PHI            Residues            Reference
    Crop           Country        Formulation         (g/ha)    No.       Treatments     (Days)         (mg/kg)
                                                                                                                                           

    Alfalfa        Canada         4% EC                 28      1         -                 1           2.00,2.50           Shell Research
    Green                                                                                   2           0.12,0.19           Ltd.1981b
                                                                                            8           0.4

    Hay            USA            24% EC                25      2         26 days           41          0.73                ICI 1981c
                                                                                            61          0.64
                                                                                           101          0.8

                                                        50      2         26 days           41          1.6
                                                                                            61          1.8
                                                                                           101          1.8

    Green          USA            24% EC                70      1         -                23           0.51,0.55,0.45      ibid
                                                                                           36           0.82,0.10

                                                       140      1         -                23           0.21,1.4
                                                                                           36           0.30,1.8,1.0        ibid

    Green          USA            24% EC                25      2         26 days           12          0.68                ibid
                                                                                            72          0.37

                                                        50      2         26 days           12          0.95
                                                                                            72          0.74
                                                                                                                                           

    1  includes 3 days drying time, dry matter content 65.7%
    2  Dry matter content 33.3%.
        rate, or various higher rates up to 500 ml of a 1.5 g/l emulsion
    (i.e. 750 mg/animal) to dairy cows from which milk was collected 7 and
    24 h later.

         The only residues detected were in 2 of 6 milk samples taken 7 h
    after spraying the cows with 750 mg cypermethrin, i.e. 3.75 times the
    recommended rate of application. No residues were found in samples
    from cows treated at the recommended rate or at 2.5 times the
    recommended rate of application or in any samples collected 24 h after
    spraying.

         Trials were carried out with cypermethrin prepared as a dip
    against cattle tick and buffalo fly and containing 75 mg/l of dip wash
    (Australia 1981). Six dairy cows were dipped, and milk collected 1, 3
    and 7 days later was analysed for cypermethrin. Low concentrations of
    cypermethrin, 0.002 to 0.010 mg/l were found in milk taken up to 3
    days after treatment, with a mean value of 0.003 mg/l. By the end
    of the 7 days, the residues had declined to below the limit of
    determination (0.002 mg/l). A second dipping 8 days after the first
    did not produce any evidence of accumulation of cypermethrin from the
    cow in the milk.

         In a third study (Australia 1981), in which a cypermethrin spray
    designed to control buffalo fly was applied to dairy cows at the rate
    of 100 mg/l and 200 mg/l (200 ml/animal), cypermethrin residues were
    found to range up to 0.035 mg/kg one day after treatment in butterfat.
    They then decreased slowly over a period of 10 to 13 days. The details
    are given in Tables 11 and 12.

         Fifteen cattle were treated by dipping in cypermethrin at the
    recommended concentration of 75 mg/l (Australia 1981). Three of the
    animals were subjected to a second dipping 8 days later. Three animals
    were slaughtered on each of days 1, 3, 4, 7 and 14 following dipping.
    Those on day 14 were the 3 that had been dipped a second time on day
    8.

         A commercial dairy herd was treated with an overall spray at the
    rate of 200 ml/animal. The solution had a concentration of 1 g/l. One
    litre samples were taken from the bulk milk vat at 1, 3, 7, 10 and 13
    days post-treatment. The samples were kept frozen until analysed. The
    results are given in Table 12.

         Samples of omental fat, perirenal fat, muscle, liver and kidney
    were taken from each animal and analysed for cypermethrin by a
    method sensitive to 0.01 mg/kg. The highest residue detected was
    0.02 mg/kg in omental fat from two animals 3 and 4 days after dipping,
    respectively. There was no evidence that the first dipping caused any
    build-up of cypermethrin in cattle tissues. Liver, kidney and muscle
    contained no detectable residues.

        TABLE 11.  Mean cypermethrin residues in butterfat samples
                                                                                                    

                                                    Residue (mg/kg)
                                                                                                    
    Animal
    number                Day 0                 Day 1           Day 3     Day 7     Day 10    Day 13
                      am           pm        am      pm          am        am         pm        pm
                                                                                                    

    14             ) treatment   0.013      0.018   0.035       0.022     0.024     0.019     <0.01
    118            ) 0.1% a.m.   0.024      0.026   0.028       0.025     0.032     -         <0.01
    267            )            <0.01       0.026   0.024       0.022     0.022     0.035     <0.01
                                                                                                    

    Bulk vat         0.01        as pre-treatment sample



    TABLE 12.  Cypermethrin residues in butterfat samples taken from bulk milk vat
                                                                                                    

                                                      Residue (mg/kg)
                                                                                                    

                         Day 0                 Day 1            Day 3     Day 7     Day 10    Day 13
                     am             pm       am      pm          am        am         pm        pm
                                                                                                    

    Bulk           ) <0.011       0.028     0.046   0.032       0.021     0.019     0.024     <0.01
    Vat            )
    Samples        )
                                                                                                    

    1  Pre-treatment.
    
         Twenty four cattle were sprayed with 200 ml cypermethrin emulsion
    containing 100 mg/l and 200 mg/l cypermethrin (12 with each rate -
    recommended rate and 2 × recommended rate). Three animals from each
    group were slaughtered on days 1, 3, 7, 10 and 13 after spraying.
    Those slaughtered on day 13 were first sprayed a second time on day 8.
    Samples of omental fat, perirenal fat, liver, kidney and muscle were
    analysed for cypermethrin by methods sensitive to 0.005 mg/kg in
    liver, kidney and muscle and 0.01 in fat. The only residues detected
    were in omental fat and perirenal fat from animals sprayed twice at
    the double rate and slaughtered 7 days following the second treatment.
    The residue level in these samples ranged up to 0.036 mg/kg (4 times
    the limit of sensitivity) (Australia 1981).

         Experiments using radio-labelled cypermethrin were carried out
    on separate occasions in which cattle were given feed concentrate
    containing cypermethrin equivalent to 0.2, 5.0 and 10.0 mg/kg in
    the total daily feed (Shell Research Ltd. 1978a, 1979a, 1980c).
    Measurement of radioactivity in urine and faeces showed that the major
    excretory route was into the urine and only small amounts were
    excreted in the milk. A small proportion of the ingested cypermethrin
    remained in the body at the end of the feeding period. Details of the
    studies on milk and tissues are described.

         At the 0.2 mg/kg feeding level, two lactating cows were given
    treated feed concentrate (containing cypermethrin, 14 C-benzyl
    labelled) twice daily over a 3-week period. The radioactivity present
    in whole milk over this time ranged from 0.0003 mg/l to 0.0012 mg/l
    cypermethrin equivalents. 60-70% of this radioactivity was present in
    the cream and totalled about 0.5% of the cypermethrin fed to the
    animals.

         At the end of the 3-week feeding period, the animals were
    slaughtered and samples of tissue examined. Levels were below
    0.001 mg/kg cypermethrin equivalents in blood, muscle and brain. In
    subcutaneous fat, renal fat, liver and kidney, residues were present
    in small amounts up to 0.012 mg/kg cypermethrin equivalents.

         In order to complement information from the 0.2 mg/kg experiment,
    5 mg/kg radio-labelled cypermethrin (labelled in either the benzyl or
    cyclopropyl ring) was fed daily to cows over a 7-day period. Rates of
    intake and excretion of radioactivity were similar after 3 to 4 days,
    after which levels in whole milk ranged between 0.009 mg/l and
    0.013 mg/l radioactivity, in terms of cypermethrin equivalents.

         At the end of the test feeding period the animals were
    slaughtered and the tissues examined. The following results were
    obtained (expressed as cypermethrin equivalents). These were similar
    for either labelled position.

    Muscle                 < 0.04 mg/kg
    Fat                      0.01-0.10 mg/kg
    Liver and kidney         0.05-0.13 mg/kg

         An experiment using a single animal given 10 mg/kg 14C-benzyl-
    labelled cypermethrin in feed, also over a 7-day period, was carried
    out with the objective of developing further information on the nature
    of some of the major components of residues in fat, liver and kidney.
    Total residues in tissues were as anticipated from the previous
    experiments (muscle 0.01 mg/kg, fat 0.08 to 0.10 mg/kg, liver and
    kidney 0.21 and 0.11 mg/kg and milk levels 0.01 to 0.03 mg/kg).

         Further studies on the nature of the compounds present showed
    that residues in tissue fat and in milk consisted almost entirely of
    cypermethrin, whereas in liver and kidney they were largely of
    3-phenoxybenzoic acid conjugated with glutamic acid. In these latter
    tissues, there were also indications of the presence of small amounts
    of unchanged cypermethrin and 4-hydroxy-3-phenoxybenzoic acid.

         Experiments with non-labelled material were carried out using
    three feeding levels 0.2, 5.0 and 50 mg/kg in the daily diet over a
    4-week period. Analyses of tissues and milk for cypermethrin were made
    and gave the results shown in Tables 13 and 14 (ICI 1981a, b).

         These data show that residues of cypermethrin in muscle were
    at or below the limit of determination of 0.01 mg/kg at a feeding
    level of 5 mg/kg or less and that similar levels were present in
    liver and kidney. Following feeding at the higher level of 50 mg/kg,
    cypermethrin residues in these tissues varied between 0.02 mg/kg and
    0.45 mg/kg, but were mostly below 0.2 mg/kg, apart from kidney.
    Residues of cypermethrin in fat were, as expected, higher than in
    other tissues and were roughly in proportion to the feeding rate with
    cypermethrin. Levels ranged from at or near the limit of determination
    at a feeding level of 0.2 mg/kg to 0.10 to 0.34 mg/kg at 5 mg/kg and
    2.3 to 5.3 mg/kg at a feeding rate of 50 mg/kg.

         Comparison of the levels present in feed with those in fat
    shows that even at the high rate of feeding (50 mg/kg) the level of
    cypermethrin in fat was seldom more than one tenth of the level in the
    feed.

         In milk, residues were below the limit of determination of
    0.005 mg/kg in whole milk at the lowest feeding rate, but at the two
    higher levels ranged as follows:

    Feeding level            Range of data
                                                 

    5 mg/kg                  0.008 - 0.037 mg/kg
    50 mg/kg                 0.15 - 0.49 mg/kg

        TABLE 13.  Cypermethrin residues in cow tissues
                                                                                                                                              

                                                   Cypermethrin residue (mg/kg)-duplicate analysis
    Feeding rate   Cow                                                                                                                        
    (mg/kg)        No.                      Muscle                                        Fat                     Liver             Kidney
                           adductor         pectoral        cardiac           subcutaneous      peritoneal
                                                                                                                                              

    0.2            4      <0.01, 0.01      <0.01, 0.01     <0.01, 0.01       <0.01, 0.01        0.01, 0.01       <0.01,<0.01       <0.01, 0.02
    0.2            5      <0.01,<0.01      <0.01,<0.01     <0.01,<0.01        0.01, 0.01        0.02, 0.02       <0.01,<0.01        0.01,<0.01
    0.2            61     <0.01,<0.01      <0.01,<0.01     <0.01,<0.01        0.01,0.01         0.01, 0.01       <0.01, 0.01       <0.01,<0.01
                                                                                                                                              

    5.0            7      <0.01, 0.01      <0.01,<0.01      0.01, 0.01        0.16, 0.17        0.34, 0.32       <0.01,<0.01        0.01, 0.03
    5.0            8      <0.01,<0.01       0.01,<0.01      0.01, 0.01        0.09, 0.10        0.20, 0.17       <0.01, 0.01        0.03, 0.01
    5.0            91     <0.01,<0.01       0.02, 0.01      0.02, 0.01        0.16, 0.15        0.25, 0.21       <0.01,<0.01        0.02, 0.01
                                                                                                                                              

    50             10      0.07, 0.08       0.09, 0.09      0.13, 0.11        2.3 ± 0.242       2.7, 2.8          0.05, 0.04        0.27, 0.25
    50             11      0.16, 0.16       0.47±0.052      0.11, 0.11        4.1   3.3         5.3, 5.2          0.02, 0.02        0.45, 0.43
    50             121     0.06, 0.05       0.09, 0.09      0.09, 0.08        2.1, 1.9          1.6, 1.5         <0.01, <0.01       0.07, 0.08
                                                                                                                                              

    Control        3      <0.01,<0.01      <0.01,<0.01     <0.01             <0.01             <0.01             <0.01             <0.01
                                                                                                                                              

    1  Animal was allowed a seven-day recovery period;  2  mean and standard deviation obtained from seven independent analyses.

    TABLE 14.  Cypermethrin residues in milk
                                                                                                                                                

                                               Cypermethrin residues (mg/kg) in bulked am and pm samples
    Feeding                                                                                                                                     
    Rate      Cow       Pre-
    (mg/kg)   Number    treatment
                        Day - 1    Day 1     Day 3   Day 5   Day 10  Day 15   Day 21   Day 25  Day 28   Day 29   Day 30  Day 32  Day 34   Day 36
                                                                                                                                                

              4                                                                       <0.005
              5                                                                       <0.005
    0.2       6                                                                       <0.005                     <0.005  <0.005  <0.005   <0.005
                                                                                                                                                

              Group B  <0.005      <0.005   <0.005   <0.005  <0.005  <0.005  <0.005            <0.005   <0.005
                                                                                                                                                

              7                                                                        0.022
              8                                                                        0.025
    5.0       9                                                                        0.034                      0.010  <0.005  <0.005   <0.005
                                                                                                                                                

              Group C  <0.005      <0.005    0.021    0.037   0.016   0.021   0.016    0.015    0.015    0.008
                                                                                                                                                

              10                                                                       0.177
              11                                                                       0.3921
                                                                                     ± 0.06
    50        12                                                                       0.492                      0.142   0.017   0.016    0.012
                                                                                                                                                

              Group D  <0.005      <0.005    0.231    0.152   0.223   0.207   0.202             0.211    0.204
                                                                                                                                                

    TABLE 14.  (con't)
                                                                                                                                                

                                               Cypermethrin residues (mg/kg) in bulked am and pm samples
    Feeding                                                                                                                                     
    Rate      Cow       Pre-
    (mg/kg)   Number    treatment
                        Day - 1    Day 1     Day 3   Day 5   Day 10  Day 15   Day 21   Day 25  Day 28   Day 29   Day 30  Day 32  Day 34   Day 36
                                                                                                                                                

              1
    Control   2
              3                                                                                                  <0.005  <0.005
                                                                                                                                                

              Group A  <0.005      <0.005   <0.005   <0.005  <0.005  <0.005  <0.005   <0.005   <0.005   <0.005
                                                                                                                                                

    1  Mean and standard deviation obtained from six replicate analyses.
             At the conclusion of the 4-week feeding period one animal in each
    group was retained on a cypermethrin-free diet for a further 7 days.
    The results of the analysis of the milk and tissues from these animals
    showed that cypermethrin excretion in milk fell rapidly during this
    extra period without cypermethrin. There was also a fall in tissue
    residue levels, particularly in liver and kidney, which fell below the
    limit of determination in liver, even in the case of the animal fed at
    50 mg/kg.

         Samples from animals fed at 50 mg/kg were also analysed for
    DCVA, 3-(2,2-dichlorovinyl) -2,2-dimethylcyclopropane carboxylic acid,
    and 3-phenoxybenzoic acid. These data are summarized in Table 15.
    The levels of 3-phenoxybenzoic acid were low (below 0.05 mg/kg) in
    muscle and fat, but were higher in liver and kidney ranging up to
    0.26 mg/kg. Residues of DCVA were higher in most tissues than those of
    3-phenoxybenzoic acid, generally by a factor of 3 to 4, but were
    similar in the case of liver.

         In milk, residues of both metabolites were at or below the limits
    of determination of 0.01 to 0.02 mg/l. As expected, levels of the
    metabolites, as in the case of the parent compound, fell during the
    subsequent feeding period of 7 days on a cypermethrin-free diet. These
    data are compatible with the results of the experiments using radio-
    labelled material, bearing in mind that analyses were carried out for
    specific products and that feeding was for more extended periods.

         The crop data reviewed indicate that residue levels in cattle
    feed components may occasionally approach 10 mg/kg, although in most
    cases they would be considerably below this level. In general,
    therefore, it is felt that residue levels averaged over the whole diet
    would seldom be above 5 mg/kg.

         From the information cited on cattle feeding experiments it may,
    therefore, be concluded that residues of cypermethrin in products of
    animal origin from stock given feed prepared from cypermethrin-treated
    crops are not likely to exceed the following:

         Carcass fat         0.2 mg/kg
         Muscle              0.05 mg/kg
         Liver and kidney    0.2 mg/kg
         Whole milk          0.05 mg/kg

    Sheep

         Six sheep were dipped in a cypermethrin dip containing 25 mg/l
    cypermthrin (1.5 × recommended rate) and samples were collected
    from 3 sheep following slaughter the next day and from the other
    3 slaughtered 7 days after dipping. Residues were detected only in
    sheep slaughtered one day after treatment. The highest residue level

        TABLE 15.  Levels of cypermethrin, DCVA and 3-phenoxybenzoic acid in milk and tissues of cows receiving
               55:45 cis: trans cypermethrin at 50 ppm in the diet for 28-29 days
                                                                                                                                              

                                                    Levels (µg/g)
    Treatment                                                                                                                                 
    Regime         Residue                                        Muscle                              Fat
                                                                                                                    
                                       Milk         adductor     pectoral      cardiac      subcutaneous  peritoneal   Kidney        Liver
                                                                                                                                              

    50 ppm in      Cypermethrin        0.15-0.231   0.07-0.16    0.09-0.49     0.11-0.13     2.3 -4.1     2.7 -5.3     0.25-0.45     0.02-0.05
    diet for       DCVA               <0.011        0.04-0.07    0.05-0.016    0.19-0.21     0.03-0.05    0.04-0.06    0.42-0.44     0.13-0.22
    28-29 days     3-phenoxybenzoic
                   acid               <0.02         0.01-0.02    0.02          0.05          0.02         0.03-0.04    0.12-0.15     0.13-0.26
                                                                                                                                              

    As above,      Cypemethrin         0.01         0.05-0.06    0.09          0.08-0.09     1.9 -2.1     1.5 -1.6     0.07-0.08    <0.01
    then a         DCVA               <0.01         0.02         0.03          0.04         <0.01        <0.01         0.06          0.04
    further        3-phemoxybenzoic
    7 days on      acid               <0.01         0.01         0.03          0.03          0.02         0.01         0.02          0.07
    untreated
    diet
                                                                                                                                              

    1  Plateau levels.
        was 0.51 mg/kg in liver. Residues in muscle and fat from the same
    animals were 0.18 mg/kg. The limit of determination in liver and
    muscle was 0.005 mg/kg and in fat 0.01 mg/kg (Australia 1981).

    In plants

         In 1979 the Meeting considered the degradation of cypermethrin in
    plants, especially cotton, lettuce and apples. Most of these studies
    involved radio-labelled compound. Since then the results of studies on
    apples, pears, maize and potatoes have become available.

         Trials were carried out in Canada during 1978 (Shell Research
    Ltd. 1979 b,c,d,e) in which an EC formulation of cypermethrin was
    applied to apple trees, pear trees, maize and potatoes and residue
    levels in the crops were measured at harvest (Table 16).

    TABLE 16.  Cypermethrin found in various crops at harvest
                                                              

                        Application         Interval after last
    Crop                                    treatment at which
                        No.     Rate        samples were taken
                                                              

    Apple               1        70             12 weeks
                        7       150              8 weeks
    Pear                2        70             12 weeks
                        4        30              5 weeks
    Maize               3        75              3 days
                        5        70              7 days
    Potato              4       150              7 days
                                                              

         Samples from each crop were analysed for three plant metabolites:
    3-phenoxybenzoic acid (free and conjugated); 2,2-dimethyl-3-
    (2,2-dichlorovinyl)cyclopropane-carboxylic acid (free and conjugated);
    and alpha-amino-3-phenoxybenzyl-2, 2-dimethyl-3-(2,2-dichlorovinyl)
    cyclopropanecarboxylate, either by high performance liquid
    chromatography (HPLC) with UV detection, gas chromatography/mass
    spectography or gas chromatography with electron capture detection. No
    detectable residues of any of the metabolites were found in the
    samples when analysed by a method with a limit of determination of
    0.05 mg/kg.

    NATIONAL MAXIMUM RESIDUE LIMITS

         National maximum residue limits reported to the Meeting are shown
    in Table 17.

        TABLE 17.  National maximum residue limits reported to the Meeting
                                                                                          

    Country                  Commodity                               MRL            PHI
                                                                     (mg/kg)        (days)
                                                                                          

    Australia                fat of meat of cattle                   0.1              3
                             fat of meat of sheep and goats          0.02             3
                             milk and milk products (fat basis)      0.1              -
                             cottonseed                              0.2             14
                             cottonseed oil                          0.02             -
                             soybean                                 0.05            14
                             soybean oil                             0.1              -
                             stone fruit (except cherries)           1.0             14
                             navy beans                              0.05             7
                             mung beans                              0.05             7

    S. Africa                cottonseed                              0.05            28
                             maize                                   1.5             28

    Yugoslavia               grape                                   0.5             28
                             pear                                    0.5

    Fed. Rep.of Germany      maize                                   5               49
                                                                                          
    
    EVALUATION

    COMMENTS AND APPRAISAL

         Cypermethrin, although not well absorbed from the gastro-
    intestinal tract, appears generally to be rapidly metabolized and
    excreted from the body with little potential for accumulation in
    tissues.

         Data were available on exposure of spray applicators, which
    were considered to satisfy the requirements of the previous JMPR.
    The exposure was monitored by measurements of the metabolite
    3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid in the
    urine.

         A two-year feeding study in beagle dogs was also evaluated and a
    no-effect level of 300 ppm in the diet was determined.

         Since cypermethrin was first evaluated in 1979 a considerable
    amount of additional data have been made available to the Meeting.
    This includes information on new and extended uses on a variety of

    crops and on livestock. Residue data from many supervised residue
    trials on peaches, cherries, plums and wheat grain (pre-harvest) have
    confirmed the MRLs recommended in 1979.

         Residue data on cucumbers, sweet peppers, chilli peppers,
    eggplants, coffee, alfalfa and other animal feeds have enabled the
    Meeting to recommend additional MRLs. The Meeting proposes that the
    MRL for nectarines should be the same as for peaches and that the
    limit for cypermethrin residues in cottonseed should be increased.

         The recommendation concerning wheat, questioned at the 13th
    Session of the CCPR, has been confirmed. The Meeting considers that,
    in view of the evidence of residues regularly approaching 0.1 mg/kg
    (0.08 etc.) and the problems known to occur in sampling and analysing
    cereal grains for residues such as cypermethrin, it would be prudent
    not to reduce the limit to 0.1 mg/kg but to retain the previous
    recommendation of 0.2 mg/kg knowing that most of this residue will be
    removed with the bran in the processing of the cereal grain for
    consumption.

         The new evident available to the Meeting enables it to better
    define the residue in alfalfa and to recommend a new limit based in
    the dry (12% moisture) commodity.

         Extensive studies on the spraying, dipping and feeding livestock
    with cypermethrin have provided a new basis for recommending MRLs in
    foods of animal origin. Cypermethrin is virtually insoluble in water
    and it partitions preferentially into animal fats. The Meeting
    therefore proposed MRLs based on the concentration likely to be found
    in the fat of meat and milk.

    Level causing no toxicological effect

         Rat: 100 ppm in the diet, equivalent to 5.0 mg/kg bw/day
         Dog: 300 ppm in the diet, equivalent to 7.5 mg/kg bw/day

    Estimate of acceptable daily intake for man

         0 - 0.05 mg/kg bw

    RECOMMENDATIONS OF RESIDUE LIMITS

         The following new and amended maximum residue limits are
    recommended based on the pre-harvest intervals indicated below. The
    limits refer to the sum of the isomers of the parent compound in the
    portion of the sample to be analysed as described by CCPR.

    3.   Results of ongoing studies on residues in soybeans.

                                                       Pre-harvest
                                                       interval on which
    Commodity                  MRL (mg/kg)            recommendation
                                                       was based
                                                                        

    Cucumber                    0.2                           1
    Sweet pepper                0.5                           1
    Chilli pepper               0.5                           1
    Eggplant                    0.2                           1
    Coffee (dried beans)        0.05                          -
    Nectarine                   2                             7
    Cottonseed                  0.21                         14
    Carcass meat                0.22                        nil
    Meat by-products            0.2                         nil
    Milk                        0.01                        nil
    Milk products (fat basis)   0.2                         nil
    Alfalfa                     5 (dry weight basis)         14
    Maize fodder                5 (dry weight basis)         14
    Wheat straw                 5 (dry weight basis)         14
    Sorghum fodder              5 (dry weight basis)         14
                                                                        

    1  Increase from recommendation made in 1979;
    2  the figure applies to carcass fat.

    FURTHER WORK OR INFORMATION

    Desirable

    1.   Mutagenicity studies on the metabolite 3-(2,2-dichlorovinyl)-
    2,2-dimethyl-cyclopropane-carboxylic acid.

    2.   Results of ongoing studies on the level and fate of cypermethrin
    in poultry and eggs following feeding at levels representing possible
    residues in poultry feed.

    REFERENCES

    Australia. Reports of a series of trials with cypermethrin as a plung
    1981      ans shower dip for sheet; buffalo fly spray for cattle and
              cattle dip in conjunction with chlorfenviphos. Department of
              Primary Industry - Canberra, Australia. Information supplied
              to FAO. (Unpublished)

    Barlow, F., Hadaway, A.B., Flower, L.S., Grose, J.E.H. and Turner,
    1977      C.R. Some laboratory investigations relevant to the possible
              use of new pyrethroids in control of mosquitoes and tsetse
              flies. Pesticide Science 8: 291-300.

    Casida, J.E, and Ruzo, L.O. Metabolic chemistry of pyrethroid
    1980      insecticides. Pesticide Science 11: 257-269.

    Climie, I.J.G. Cypermethrin: the kinetics of cypermethrin in the blood
    1980      of rats following a single oral dose. Research Report TLER.
              80.073 submitted by Imperial Chemicals Industries to WHO.
              (Unpublished)

    Crawford, M.J. Shell toxicology group research report TLGR.0004.77.
    1977      (Unpublished)

    Crawford, M.J. and Hutson, D.H. Shell toxicology group research report
    1977      TLGR. 0131.77. (Unpublished)

    Crawford, M.J. and Croucher, A. The metabolism of cypermethrin
    1979      (WL43467) in mammals. Metabolites derived from a single oral
              dose of [14C-cyclopropyl]-cypermethrin in the dog. Group
              research report TLGR. 79.096, submitted by Shell Research
              Ltd. to WHO. (Unpublished)

    Crawford, M.J., Croucher, A. and Hutson, D.H. Metabolism and cis- and
    1981      trans-cypermethrin in rats. Balance and tissue retention
              study. Journal of Agricultural and Food Chemistry 29:130-
              135.

    Gaughan, L.C., Ackerman, M.E., Unai, T. and Casida, J.E. Distribution
    1978      and metabolism of trans- and cis-permethrin in lactating
              Jersey cows. Journal of Agricultural and Food Chemistry 25:
              613-618.

    Hall, B.E., Vickers, J.A. and Hopkins J.A. 14C-cypermethrin: A study
    1980      to determine the bio-accumulation of radioactivity in the
              rat following repeated oral administration. Report No. 2487-
              72/20, submitted by Imperial Chemical Industries to WHO.
              (Unpublished)

    Hutson, H. The metabolic fate of cypermethrin in the cow: elimination
    1989      and residues derived from 14C-benzyl label. Group research
              report TLGR.80.121, submitted by Shell Research Ltd. to WHO.
              (Unpublished)

    ICI - Imperial Chemical Industries Ltd., Plant Protection Division
    1981a     report no. RJ 0198B. (Unpublished)

    1981b     Report no. RJ 0186B. (Unpublished)

    1981c     Report no. RJ 0189A. (Unpublished)

    Jones, B.K. Cypermethrin: bioaccumulation in the rat. Report no.
    1981      CTL/P/599, submitted by Imperial Chemical Industries to WHO.
              (Unpublished)

    LeQuesne, P.M., Maxwell, I.C, and Butterworth, S.T.G. Transient facial
    1980      sensory symptoms following exposure to synthetic
              pyrethroids: a clinical and electrophysiological assessment.
              Neurotoxicology 2:11

    Logan, C.J. Cypermethrin: excretion and retention of cypermethrin and
    1980      its metabolites in rats following a single oral dose
              (ca 200 mg/kg). Report TLER 80.083, submitted by Imperial
              Chemical Industries to WHO. (Unpublished)

    Prinsen, G.H. and Van Sittert, N.J. Exposure and medical monitoring
    1979      study of the pyrethroid Ripcord after one season of spraying
              on cotton in Ivory Coast. Report series Tox 79.001,
              submitted by Shell International Research to WHO.
              (Unpublished)

    Shell Chimie S.A. Residue of WL 43,467 in aubergines from France -
    1976      1976 trials. Report no. BESR. 0011.76. (Unpublished)

    Shell Chimie S.A. Residues of WL 43,467 in wheat from Canada-1976
    1977a     trials, Part 2: grain and straw. Report no. BESR. 0040.77
              (Unpublished)

    1977b     Residues of WL 43,467 in wheat from Canada-1976 trials-Part
              l:green wheat. Report no. BESR.0039.77 (Unpublished)

    Shell Chimie S.A., report no. BESR,0029.78. (Unpublished)
    1978

    Shell Chimie S.A. Residues of Ripcord in maize from Germany-1978
    1979      trials. Report no. BEGR. 79.082. (Unpublished)

    Shell Chimie S.A. Residues of ripcord in cucumbers from Denmark. 1979
    1980a     trials. Report no. BEGR.80.155. (Unpublished)

    1980b     Residues of Ripcord in cucumbers from Germany-1979 trials.
              Report no. BESR.80.043. (Unpublished)

    1989c     Residues of Ripcord in chillies from India-1980 trials.
              Report no. BEGR. 80.159.(Unpublished)

    Shell Chimie S.A. Residues of Ripcord in coffee from Brazil - 1978
    1980d     trials,  report no. BEGR. 80.006. (Unpublished)

    1980e     Residues of Ripcord in peaches from Canada - 1979 trials. 
              Report no. BEGR. 80.009. (Unpublished)

    1980f     Residues of Ripcord in peaches from France - 1979 trials.   
              Report no. BEGR. 80.123. (Unpublished)

    1980g     Residues of Ripcord in sweet corn from Canada. 1979 trials.  
              Report no. BEGR. 80.151. (Unpublished)

    1980h     Residues of Ripcord in cherries from Germany - 1979 trials, 
              Report no. BEGR.80.042. (Unpublished)

    Shell Chimie S.A. Report no. BEGR.81.124 (Unpublished)
    1981a

    1981b     Report no. BEGR. 81.097. (Unpublished)

    1981c     Residue of Ripcord and Torgue in cherries from Germany-1980
              trials. Report no. BEGR.81.033. (Unpublished)

    1981d     Report no. BEGR.81.037. (Unpublished)

    1981e     Report no. BEGR.81.126. (Unpublished)

    Shell Research Ltd., Residues of 43467 in maize from South Africa.
    1977      Report no. BLGR.0126.77. (Unpublished)

    Shell Research Ltd. The excretion and residues of radioactivity in
    1978      cows treated orally with 14C-labelled WL 43467. Report no.
              TLGR.0029.78. (Unpublished)

    Shell Research Ltd. The excretion of radioactivity from cows fed with
    1979a     radioactivity labelled WL 43467. Report no. TLGR.0075.76
              (Unpublished)

    1979b     Analysis of apples from Canada for residues of Ripcord
              metabolites-WL 44607 and WL 44776 in their free and
              conjugated forms and WL 47133. Group Research Report BLGR.
              79.120. (Unpublished)

    1979c     Analysis of pears from Canada for residues of Ripcord
              metabolites-WL 44607 and WL 44776 in their free and
              conjugated forms and WL 47133. Group Research Report BLGR.
              79.122. (Unpublished)

    1979d     Analysis of maize grain from Canada for residues of Ripcord
              metabolites-WL 44607 and WL 44776 in their free and
              conjugated forms and WL 47133. Group Research Report BLGR.
              79.123. (Unpublished)

    1979e     Analysis of potatoes from Canada for residues of Ripcord
              metabolites-WL 44607 and WL 44776 in their free and
              conjugated forms and WL 47133. Group Research Report BLGR.
              79.121. (Unpublished)

    Shell Research Ltd. Residues of Ripcord in Sorghum from South Africa. 
    1980a     Report no. BLGR.80.010. (Unpublished)

    1980b     Residues of Ripcord in sorghum from Australia. Report no.
              BLGT.80.096. (Unpublished)

    1980c     The metabolic fate of cypermethrin in the cow: elimination
              and residues derived from 14C-benzyl label. Report no.
              TLGR.80.121.(Unpublished)

    Shell Research Ltd. A 2-year feeding study in dogs on WL 43467. Group
    1980d     Research report SBGR.81.126 submitted by Shell Research Ltd.
              to WHO. (Unpublished)

    Shell Research Ltd. Residues of Ripcord in maize from Canada. Report
    1981a     no. SBGR. 81.042. (Unpublished)

    1981b     Residues of Ripcord in alfalfa from Canada. Report no.
              SBGR.81.036. (Unpublished)

    1981c     Residues of Ripcord in wheat grain from Canada. Report no.
              SBGR.81.072. (Unpublished)

    Swaine, H. and Sapiets, A. Residue transfer study with dairy cows fed
    1980a     on a diet containing the insecticide. Report no. RJ 0186B,
              submitted by Imperial Chemical Industries to WHO.
              (Unpublished)

    1980b     Residue levels of the major metabolites of the insecticide
              in the milk and tissues of dairy cows fed on a diet
              containing cypermethrin at 50 mg/kg. Report no. RJ 0198B,
              submitted by Imperial Chemical Industries to WHO.
              (Unpublished)

    Ussary, J.P. Cypermethrin residues in cottonseed: ICI Americas Inc.,
    1980      Agricultural Chemicals Division report no. TMU0567/B.
              (Unpublished)

    Ussary, J.P. Cypermethrin residues on cottonseed. ICI Americas Inc.
    1981      Agricultural Chemicals Division report no. TMU0662.
              (Unpublished)

    van den Bercken, J. Personal communication to Shell International
    1980      Research, submitted to WHO.

    Wouters, W. and van den Bercken, J. Action of pyrethroids (Review).
    1978      Gen. Pharmacol. 9:387-398.


    See Also:
       Toxicological Abbreviations
       Cypermethrin (EHC 82, 1989)
       Cypermethrin (HSG 22, 1989)
       Cypermethrin (ICSC)
       CYPERMETHRIN (JECFA Evaluation)
       Cypermethrin (PIM 163)
       Cypermethrin (Pesticide residues in food: 1982 evaluations)
       Cypermethrin (Pesticide residues in food: 1983 evaluations)
       Cypermethrin (Pesticide residues in food: 1984 evaluations)