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    FENPROPATHRIN

    First draft prepared by
    E. Bosshard
    Federal Office of Public Health
    Schwerzenbach, Switzerland

    EXPLANATION

         Fenpropathrin is an ingestion and contact synthetic pyrethroid
    insecticide and acaricide used against various pests in cotton,
    grapes, ornamentals, fruits and vegetables and other field crops. 
    The compound was considered for the first time by the present
    Meeting.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOLOGICAL DATA

    Biochemical aspects

    Absorption, distribution, and excretion

         Biokinetics and biotransformation of fenpropathrin was studied
    in rats, goats, cows and chickens.  In all the species investigated
    the compound was efficiently absorbed and excreted in urine and
    faeces.  The biotransformation pattern was similar in the various
    species (Crawford, 1975; Crawford & Hutson, 1976, 1977; Kaneko  et
     al., 1981; Ku & Doran, 1990a,b).

    Rats

         After oral application of single doses of 2.4-26.8 mg/kg bw
    14C-acid and 14C-alcohol-labelled fenpropathrin, 25%-60% of the
    radiocarbon was eliminated in urine and 40%-70% in faeces (Crawford,
    1975; Kaneko  et al., 1987).  Excretion was rapid and amounted to
    95% of the dose within 48 hours.  Residues in tissues were low.

         After a single oral dose of 1.5 mg/kg bw of 14C-benzyl-
    labelled fenpropathrin, 42-70% of the administered radioactivity was
    excreted in urine and 25-63% in faeces.  Highest residues of 0.6 ppm
    were measured in fat tissue and liver one day after treatment. 
    Residues in all other tissues were less than 0.1 ppm (Crawford,
    1975).

         The lipophilic nature of the compound together with its very
    rapid elimination indicated that metabolism to polar products must
    be very effective.

    Cows

         Two lactating cows were fed twice daily for 21 days a diet
    containing 0.2 ppm 14C-labelled fenpropathrin.  Fenpropathrin was
    rapidly absorbed and eliminated and an equilibrium established
    within five days.  Total urinary and faecal excretion amounted to
    48% and 39%, respectively.  Residue levels in milk and tissues were
    below the limits of detection of 0.001-0.008 ppm (Crayford, 1975).

    Hens

         Hens fed with 14C-cyclo- or 14C-benzyl-fenpropathrin at doses
    of 0.5 or 5 mg/kg bw for 10 days showed rapid excretion and
    biotransformation.  14C-levels were low in eggs (< 0.5 ppm) and
    meat (< 0.6 ppm).  Metabolites were identical to those found in
    rats (Ku & Doran, 1990b).

    Biotransformation

    Rats

         On the basis of the identified metabolites, the major
    biotransformation reactions of fenpropathrin in rats consisted of
    oxidation at the methyl groups of the acid moiety and at the 2'-and
    4'-positions of the alcohol moiety, cleavage of the ester linkage
    and the conjugation of the resultant carboxylic acids, alcohols and
    phenols with glucuronic acid, sulfuric acid and glycine.  Most of
    the urinary metabolites were ester-cleaved ones. The predominant
    urinary metabolites derived from the acid moiety were identified as
    TMPA1-glucuronide and TMPA-CH2OH (trans). Other metabolites
    identified were TMPA-COOH (trans), TMPA-CH2OH-lactone in free form
    or as glucuronide. The major urinary metabolites derived from the
    alcohol moiety were PB2 acid in free form and as glycine
    conjugate, 4'-OH-PB acid-sulfate and 2'-OH-PB acid-sulfate.  The
    urinary metabolites from the alcohol moiety were similar to those
    from other pyrethroids (e.g., fenvalerate, deltamethrin,
    cypermethrin).  Almost all faecal metabolites retained the ester
    linkage.  The major faecal metabolite was identified as CH2OH
    (trans)-fenpropathrin, followed by COOH (trans)-fenpropathrin, 4'-
    OH-fenpropathrin and 4'-OH-, CH2OH(trans)-fenpropathrin.  Depending
    on the dose administered, 30-50% of the applied radioactivity was
    excreted in faeces as parent compound.  A maximum of 0.3% of the
    applied radiocarbon was exhaled as 14CO2 after administration of
    14C-acid or 14C-alcohol fenpropathrin.  Fenpropathrin and TMPA were
    the major components of 14C in tissues.  No sex difference was
    apparent (Ruzo  et al., 1978; Ohkawa  et al., 1979; Kaneko  et al.,
    1987).

         An aryl-hydroxylated ester (alpha-cyano-3-(4-
    hydroxyphenoxy)benzyl ester) was identified in bile.  The ester was
    eliminated in the bile presumably conjugated (Crawford & Hutson,
    1977).

    Goats

         14C-benzyl- and 14C-cyclo-fenpropathrin were orally
    administered to lactating goats at 50 ppm for five days.  As in the
    other species the majority of the radiolabel was excreted rapidly
    and 14C levels were low in milk and tissues.  The parent 

                      

    1TMPA: 2,2,3,3-Tetramethylcyclopropane carboxylic acid.

    2PB acid: 3-Phenoxybenzoic acid.

    fenpropathrin was the major component of residues in milk, meat, fat
    and heart.  In kidney and liver, the major metabolites resulting
    from hydrolysis and oxidation reactions of the benzyl ring moiety
    were identified as PB acid and its glycine derivative as well as 4'-
    OH-PB acid.  Other metabolites found in milk and tissue samples were
    TMPA and its oxidative derivatives including TMPA-CH2OH, TMPA-COOH
    and TMPA-CH2OH-lactone (Ku & Doran, 1990a).

         The proposed metabolic pathway for fenpropathrin in mammals is
    given in Figure 1.

    Toxicological studies

    Acute toxicity studies

         Signs of acute toxicity of fenpropathrin were typical of
    pyrethroid intoxication and included decreased motor activity,
    hyperexcitability, tremors, diarrhoea and salivation.  Survivors
    recovered from the clinical signs within a few days (Hiromori  et
     al., 1982a).  The results of the studies on the acute toxicity of
    fenpropathrin are summarized in Table 1.  Fenpropathrin has been
    classified as moderately hazardous by WHO (WHO, 1992).

         The acute oral toxicity of the following impurities were tested
    in mice: alpha-cyano-4-phenoxybenzyl 2,2,3,3-tetramethyl-1-
    cyclopropane carboxylate and alpha-(3-phenoxybenzoyl)-3-
    phenoxybenzyl 2,2,3,3-tetramethyl-1-cyclopropane carboxylate, both
    showing an oral LD50 of > 5000 mg/kg bw in both sexes (Misaki &
    Kohda, 1981a).

         Another impurity tested was 2,2,3,3-tetramethylcyclopropane
    carboxylic anhydride, showing an oral LD50 in mice of 1450 mg/kg bw
    in males and 1880 mg/kg bw in females (Misaki & Kohda, 1981b).

    Short-term toxicity studies

    Mice

         Groups of mice (CD-1; 8/sex/group) were fed diets containing 0,
    100, 200 or 300 ppm fenpropathrin for 4 weeks.  No adverse reactions
    were observed in any of the treated animals (Colley  et al., 
    1981a).  A second study was performed at dietary concentrations of
    0, 500, 1000 or 1500 ppm for 4 weeks.  At 1000 ppm reduced body-
    weight gain and higher liver weights were observed.  At 1500 ppm
    mortalities occurred at the very beginning of the study (Colley  et
     al., 1981b).

    FIGURE 01


        Table 1.  Acute toxicity of fenpropathrin (technical material)
                                                                                                                
    Species        Sex       Route                               LD50          Purity    References
                                                              (mg/kg bw)        (%)
                                                                                                                

    Rat            M         oral                                 54           97        Kohda, 1975
                   F         oral                                 49           97        Kohda, 1975
                   M         oral                                 71           91.8      Hiromori et al., 1983b
                                                                                         Misaki et al., 1983
                   F         oral                                 67           91.8      Hiromori et al., 1983b
                                                                                         Misaki et al., 1983
                   M         oral                                 77           97.3      Hiromori et al., 1983a
                                                                                         Misaki et al., 1983
                   F         oral                                 67           97.3      Hiromori et al., 1983a
                                                                                         Misaki et al., 1983
                   M         oral                                 164          97.3      Hiromori et al., 1983b
                   F         oral                                 107          97.3      Hiromori et al., 1983b
                   M&F       oral                                 60           93.8      Omodaka et al., 1986a
                   F         oral                                 70           93.8      Omodaka et al., 1986a
                   M&F       inhalative (vapour)             > 0.009 g/l*     94.5      Bruce et al., 1986
                   M&F       inhalative (Xylene EC mist)      > 96 g/l*       97        Kohda et al., 1976
                   M         dermal (sol. in corn oil)           1600          97        Kohda, 1976
                   F         dermal (sol. in corn oil)            870          97        Kohda, 1976
                   M&F       dermal (viscous liquid)            > 5000         93.8      Omodaka et al., 1986b
                   M         sc                                  1410          97        Kohda & Kadota, 1976b
                   F         sc                                   900          97        Kohda & Kadota, 1976b
                   M         ip                                   225          97        Kohda & Kadota, 1976b
                   F         ip                                   180          97        Kohda & Kadota, 1976b

    Mouse          M         oral                                 67           97        Kohda & Kadota, 1975
                   F         oral                                 58           97        Kohda & Kadota, 1975
                   M         oral                                 135          93.8      Suzuki et al., 1986
                   F         oral                                 154          93.8      Suzuki et al., 1986
                   M         inhalative (Xylene EC mist)       100 g/l*       97        Kohda et al., 1976
                   F         inhalative (Xylene EC mist)       43 g/l*        97        Kohda et al., 1976

                                                                                                                

    Table 1 (contd)
                                                                                                                
    Species        Sex       Route                               LD50          Purity    References
                                                              (mg/kg bw)        (%)
                                                                                                                

    Mouse          M         dermal                               740          97        Kohda & Kadota, 1976a
                   F         dermal                               920          97        Kohda & Kadota, 1976a
                   M         sc                                  1350          97        Kohda & Kadota, 1976b
                   F         sc                                   900          97        Kohda & Kadota, 1976b
                   M         ip                                   230          97        Kohda & Kadota, 1976b
                   F         ip                                   210          97        Kohda & Kadota, 1976b
                   M         iv                                   4.5          ?         Summitt & Albert, 1976

    Rabbit         M         oral                                 675          96.2      Hara & Suzuki, 1980
                   F         oral                                 510          96.2      Hara & Suzuki, 1980
                   M&F       dermal                             > 2000         ?         Marroquin et al., 1981

    Dog            M&F       oral                               > 1000         96.2      Pence et al., 1978

                                                                                                                

    *    LC50
    

    Rats

         Fenpropathrin (purity 96%) was fed to groups of Carworth Farm E
    rats (12/sex/dose; control 24/sex) at dietary concentrations of 0,
    2, 10, 50 or 250 ppm over 13 weeks.  The treatment did not influence
    the general health and behaviour, haematology, clinical chemistry or
    pathology of treated animals.  Body-weight gain was slightly
    increased at all dose levels.  A slight increase in spleen weight in
    male rats at 250 ppm was the only change concerning organ weights
    and may present a borderline effect.  The NOAEL was > 250 ppm,
    equal to 18 mg/kg/day (males) and 21 mg/kg bw/day females) (Hend &
    Butterworth, 1975).

         In a similar study, rats (12/sex/group; control 24/sex) were
    fed diets containing fenpropathrin (purity 97%) at concentrations of
    0, 3, 30, 100, 300 or 600 ppm over 13 weeks. After 5 weeks of
    exposure, most females and one male showed tremors and reduced body-
    weight gain at 600 ppm.  The tremors disappeared towards the end of
    the study.  Changes in a few haematological parameters were marginal
    and were - though statistically significant - not considered
    biologically significant.  Slight increases in plasma ALP were
    observed at 600 ppm.  Organ weights were not influenced by treatment
    and no abnormal histopathological findings were observed.  The NOAEL
    was 300 ppm, equal to 17 mg/kg bw/day (males) and 24 mg/kg bw/day
    (females) based on the appearance of clinical signs and reduced
    body-weight gain at 600 ppm (Hend & Butterworth, 1976a).

         In a third study, groups of rats (SPF SD(Crj:CD); 12/sex/dose)
    were fed concentrations of 0, 15, 50, 150, 450 or 600 ppm
    fenpropathrin (purity 93.1%) over a period of 13 weeks.  One female
    died at 600 ppm.  A dose-dependent depression of body-weight gain
    was observed at 600 ppm and 450 ppm in female rats, and at 600 ppm
    in male rats.  Food consumption was reduced at the beginning of the
    study at 600 ppm in males and at 450 ppm and above in females; food
    efficiency was reduced in females treated with 600 ppm.  An increase
    in urinary protein and specific gravity was observed in males at 450
    ppm and above.  Haematological and ophthalmological parameters as
    well as organ weights were not influenced by the treatment.  A
    slightly elevated alkaline phosphatase activity was noted in females
    of the 600 ppm group.  There was no evidence of treatment-related
    histopathological changes in any organ.  The NOAEL was 150 ppm,
    equal to 8 mg/kg bw/day, based on depression of body-weight gain and
    urinalysis at higher dose levels (Yoshida  et al., 1986).

    Rabbits

         In a 21-day dermal toxicity study with fenpropathrin (purity
    91.4%), groups of New Zeeland white rabbits (10/sex/dose) received
    dermal applications on either intact or abraded skin at dose levels
    of 0, 500, 1200 or 3000 mg/kg bw.  The treatment did not influence
    survival, body weight, food consumption, haematology, clinical

    chemistry, organ weights, or macroscopic or microscopic findings. 
    Single instances of slight skin reactions were observed at the
    application sites of animals treated with 500 and 1200 mg/kg bw and
    in most animals at 3000 mg/kg bw.  The NOAEL was > 3000 mg/kg bw
    based on systemic toxicity (Riley  et al., 1982).

    Dogs

         Fenpropathrin (purity 96.2%) was administered in the diet to
    groups of beagle dogs (6/sex/dose) at concentrations of 0, 250, 500
    or 1000/750 ppm over 13 weeks (1000 ppm for 3 weeks, 750 ppm for the
    rest of the study because of the appearance of severe tremors and
    ataxia).  The doses were adjusted for purity.  Treatment did not
    affect survival, food consumption, ophthalmoscopy, clinical
    chemistry, urinalysis, organ weights, gross or microscopic
    pathology.  Treatment-related clinical signs consisted of emesis,
    tremors, ataxia, diarrhoea, lethargic appearance and salivation. 
    Some effects were observed in all treatment groups.  The frequency
    of the observed clinical signs in all of the compound-treated groups
    decreased after week 5. One high-dose male dog was sacrificed
    moribund. Reduced body-weight gain was observed at concentrations of
    500 and 1000/750 ppm.  Haematocrit and haemoglobin values and the
    erythrocyte count in females at 1000/750 ppm were decreased.  The
    NOAEL was < 250 ppm, equal to 7 mg/kg bw/day in males and 10 mg/kg
    bw/day in females, based on the occurrence of emesis at 250 ppm
    (Pence  et al., 1980a,b).

         Fenpropathrin (purity 92.5%) was fed to groups of beagle dogs
    (4/sex/dose) at dietary concentrations of 0, 100, 250 or 750 ppm
    (adjusted to 100% active ingredient) over a period of 52 weeks.  One
    high-dose male died in the middle of the study after exhibiting
    tremor and ataxia.  Emesis occurred at an increased incidence in the
    mid-dose and high-dose females but without a clear dose-response
    relationship.  The incidence of tremors however showed a clear dose-
    related increase at 250 and 750 ppm (males: 0, 0, 49, 181; females:
    0, 1, 42, 168 observations at 0, 100, 250 and 750 ppm,
    respectively).  Ataxia occurred at 750 ppm.  Reduced body-weight
    gain was observed at 750 ppm and at 250 ppm in females. The
    treatment did not influence ophthalmoscopy, haematology, clinical
    chemistry, urinalyses, gross or microscopic pathology.  The only
    significant difference concerning organ weight was an increase in
    the relative kidney weight in females at 750 ppm.  The NOAEL was 100
    ppm, equal to 3 mg/kg bw/day, based on reduced body-weight gain and
    occurrence of clinical signs at 250 ppm and higher (Pence  et al.,
    1984).

    Long-term toxicity/carcinogenicity studies

    Mice

         In a 104-week feeding study, groups of mice (Charles River (UK)
    CD-1; 52/sex/group in main study; 40/sex/group in satellite groups
    for interim sacrifice) were fed fenpropathrin (purity 91.4%-92.5%)
    at concentrations of 0, 40, 150 or 600 ppm.  These concentration
    levels were based on two range-finding studies (Colley  et al.,
    1981a,b).  Treatment did not affect the general behaviour, with the
    exception of a marginal increase in the number of females at 600 ppm
    showing hyperactivity at week 78.  No effects on survival rate, body
    weight, food consumption, food efficiency, urinalysis, macroscopic
    pathology or organ weights were reported.  Changes in haematological
    parameters at 600 ppm included slight decreases in Hb and MCHC in
    males and an increase in MCHC in females at week 25. Because these
    changes were small, occurring only on some occasions and only in one
    sex, they are not considered to be toxicologically significant. 
    Sporadic changes in some clinical chemical parameters were not
    considered to be of toxicological significance (e.g., decrease in
    urea nitrogen in males at 600 ppm, increase in GOT and GPT levels at
    all dose levels without clear dose-response relationship).  An
    increased incidence in lung tumours (adenoma and adenocarcinoma) was
    observed in males and females of treated groups.  The incidences in
    the satellite groups (spontaneous deaths and interim sacrifice after
    26, 52 and 78 weeks) were 10, 12.5, 18 and 2.5% for males and 7.5,
    12.5, 7.5 and 7.5% for females at 0, 40, 150 and 600 ppm,
    respectively.  The incidences in the main study were 12, 23, 35 and
    31% for males and 10, 29, 19 and 13% females at 0, 40, 150 and 600
    ppm, respectively.  The incidences did not show a clear dose-
    response relationship.  The absence of any statistical significance
    or significant trend supports the interpretation that the increased
    incidences in the treatment groups were not due to a tumorigenic
    activity of fenpropathrin.  Moreover, data on the incidence of lung
    tumours in historical controls showed that incidences of pulmonary
    adenoma and adenocarcinoma in untreated animals may vary between 7
    and 36%.  There was no sex difference concerning lung tumours in
    these controls.  Therefore the results of this study gave no
    evidence of fenpropathrin-induced carcinogenic potential. The NOAEL
    was the highest dose tested, 600 ppm, equal to 56 mg/kg bw/day
    (males) and 65 mg/kg bw/day (females) (Colley  et al., 1985, 1987).

    Rats

         Groups of rats (COBS) were fed diets containing 0, 1, 5, 25,
    125 or 500 ppm fenpropathrin (purity 97%) for two years.  The group
    sizes were 12/sex and 48/sex for the satellite and main study
    controls, respectively; while the treatment groups included 6/sex
    and 24/sex for the satellite and main study, respectively.  The
    treatment did not affect the survival, general health, behaviour of

    the animals, clinical chemical or haematological parameters.  The
    depression in body-weight gain observed at 500 ppm was statistically
    significant in females only.  Food consumption of treated animals
    was comparable with control animals at most observation times. 
    Absolute spleen weight increased at 500 ppm in females of the 6-
    month satellite group and kidney weights decreased in females of all
    treatment groups in the 12-month satellite groups without showing a
    clear dose-response relationship.  In the 2-year main study groups,
    no treatment-related alterations in organ weights were observed. 
    Gross pathological examination showed a higher incidence of
    white/grey foci or plaques in the lungs at 125 and 500 ppm in
    females at 6 and 24 months.  In the 2-year main groups, the number
    of deaths attributable to renal failure in males at 500 ppm was
    greater than in the other groups, but no increase was observed when
    animals from satellite and main study groups were combined.

         The histopathological neoplastic and non-neoplastic changes
    found were consistent with the range and severity of changes usually
    observed in this rat strain and did not give any evidence of
    carcinogenicity. The NOAEL was 125 ppm, equal to 5 mg/kg bw/day
    based on depression in body-weight gain at higher dose levels (Hend
    & Gellatly, 1979; Okuno, 1981; Aitken & Rushton, 1981).

         Single animals of a satellite group fed the above-mentioned
    concentrations for 18 months were used for functional and
    neurochemical investigations.  For results see "Special Studies on
    Neurotoxicity" (Hend & Gellatly, 1980).

         Fenpropathrin (purity 91.4-92.5%) was fed to groups of rats
    (Charles River CD; 50/sex/dose in main study and 15/sex/dose in
    satellite groups for interim sacrifice) at dietary concentrations of
    0, 50, 150, 450 or 600 ppm for 104 weeks.  The dose levels were
    selected based on the results of range-finding studies (Colley  et
     al., 1982a,b; Heywood, 1982).  Clinical signs were restricted to
    body tremors, most prevalent in females receiving 600 ppm, but were
    also observed in males at the highest dose levels in the first few
    weeks of the study and in females at 450 ppm.

         Mortality increased in males and females receiving 600 ppm and
    in females receiving 450 ppm during the first 26 weeks of treatment;
    subsequently, mortality was less than that of control animals
    resulting in highest survival rates in males at 600 ppm and in
    females at 450 ppm.  Exposure of main group females receiving 600
    ppm was terminated after 52 weeks.  A slightly higher food
    consumption was reported for the high-dose females during the first
    3 months of treatment, most probably resulting in the mortalities
    observed.  Body-weight gain was reduced in females at 600 ppm and
    food utilization efficiency was marginally impaired. 
    Ophthalmological examination did not reveal treatment-related ocular
    lesions.  No abnormal haematological findings were reported. 

    Changes in clinical chemistry parameters at 450 and 600 ppm included
    slightly reduced creatinine levels and reduced total protein levels
    in males.  The differences were minimal however and - though
    statistically significant - most probably of no biological
    significance.  Urinalysis did not indicate any kidney lesions.

         Macroscopic examination revealed no findings which were
    treatment-related with the exception of an increased incidence of
    alopecia in females at 600 ppm at 52 weeks.  Changes in organ
    weights were observed on some occasions but did not show a
    treatment-related pattern and histopathological examination did not
    reveal changes attributable to treatment.  A few lymphoreticular
    tumours were seen in treated groups of male rats, but none in
    control group.  The increases observed were not dose-related and
    were within the incidence range of the historical controls for this
    rat strain.  There was no indication of a treatment-related increase
    in tumour incidence or non-neoplastic organ changes.  The electron
    microscopic examination of tibial nerve did not reveal treatment-
    related effects.  The NOAEL was 150 ppm, equal to 7 mg/kg bw/day,
    based on the appearance of clinical signs at higher doses (Warren
     et al., 1986; Fish  et al., 1986; Dean  et al., 1987).

    Reproduction studies

    Rats

         In a 3-generation reproduction study, fenpropathrin (purity
    97%) was fed to rats (COBS; 30/sex/group) at dietary concentrations
    of 0, 5, 25 or 250 ppm.  Treatment did not influence the general
    health condition or mortality, body-weight gain, food consumption,
    pregnancy rates, litter size or litter weight.  However, pup weights
    in the F3a generation were reduced at 250 ppm.  No macroscopic or
    microscopic lesions were attributable to treatment.  A very small
    number of cases of locomotor incoordination occurred in pups fed 5
    and 250 ppm.  Most pups in the 5 ppm group showing these signs were
    from one litter in the F1b generation.  No similar lesions were
    observed in the second litter of that pair nor in the following
    generation and no macroscopic lesions were identified in these
    animals.  Histopathological examination (F2 parents, F3b pups) did
    not reveal treatment-related tissue lesions.  The NOAEL was 25 ppm,
    equal to 1.6 mg/kg bw/day, based on decreased pup weights in the
    F3a generation at 250 ppm (Fleming, 1979; Hend  et al., 1979; Else
    & Rushton, 1981).

         In a second 3-generation study, groups of rats (CrL: COBS CD
    (SD)BR; 11-28/sex/dose) were fed diets containing 0, 40, 120 or 360
    ppm fenpropathrin (purity 92.5%).  Animals of the last generation
    (F2) were reared to maturity.  At 360 ppm, most females that
    littered showed body tremors associated with muscle twitches and
    increased sensitivity.  These signs were generally observed during

    the lactation period.  Increased mortality occurred at 360 ppm in
    females only; 18/28 females at this dose died, most during the
    lactation period of the F1b females.  At 120 ppm, 2/24 F1b females
    died during lactation.  Mean body-weight gain of males in the F1
    and F2 generations were reduced at 360 ppm.  F1b females at 120
    ppm showed also some indication of retarded weight gain.  Treatment
    had no influence on mating performance and no macroscopic or
    microscopic abnormalities were observed at terminal autopsy that
    were considered to be associated with treatment.  At 360 ppm, F0
    females showed a slight increase in liver weights.  A few F2b pups
    at 120 ppm showed body tremors prior to weaning and 2/3 of these
    pups died subsequently.  A slight reduction in litter size was
    observed at 360 ppm in F0 animals (second mating) and in both
    matings of F1b animals from days 4 to 21.  At 360 ppm, pup weights
    were lower in all generations.  The NOAEL was 40 ppm, equal to 3
    mg/kg bw/day, based on depression of body-weight gain, increased
    mortality in females and the occurrence of tremors in pups at 120
    ppm and above (Cozens  et al., 1986).

    Special studies on embryotoxicity/teratogenicity

    Rats

         Fenpropathrin (purity 96.2%) was fed by intubation to groups of
    rats (Fischer 344 CDF; 27/28 females/dose) from days 6 through 15 of
    gestation at dose levels of 0, 0.4, 2 or 10 mg/kg bw/day.  One mid-
    dose and 9 high-dose females were found dead during the study. 
    Clinical signs noted at a somewhat greater incidence in the treated
    animals included soft faeces, red or lacrimating eyes, alopecia or
    hunched appearance.  Post-dose tremors occurred on a few occasions
    in some high-dose females.  Body-weight gain was reduced in high-
    dose females during the treatment period, and increased slightly
    afterwards, resulting in an overall change comparable to the control
    group.  Food consumption was also reduced at the highest dose level. 
    Various gross lesions were found in animals that died during the
    study.  The findings included discolorations of organs, but no
    specific target organ was identified.  The pregnancy rate was lower
    in the high-dose group compared to the other dose groups but other
    reproduction parameters (e.g., number of corpora lutea, resorptions,
    fetal viability) were not impaired by treatment.  No visceral or
    skeletal anomalies were noted in the pups.  Visceral or skeletal
    variants did not show dose-related increases.  No teratogenic
    effects were observed. The NOAEL for maternal toxicity was 2 mg/kg
    bw/day. The NOAEL for embryotoxicity and teratogenicity was 10 mg/kg
    bw/day (Pence  et al., 1980c; Cox, 1986, 1987).

         Groups of rats (Fischer-344; 30 females/dose group) were orally
    treated with fenpropathrin (purity 91.9%) at dose levels of 0, 0.44,
    1.6, 2.2, 3.3, 6.5 or 11 mg/kg bw/day (corresponding to 0, 0.4, 1.5,
    2, 3, 6 or 10 mg/kg bw/day active ingredient) from day 6 to day 15

    of gestation.  Seven animals died in the highest dose group.  Signs
    of toxicity included ataxia, sensitivity to external stimuli,
    tremors, prostration and convulsions.  At 6 and 10 mg/kg bw/day,
    mean maternal body-weight gains and food consumption were lower
    during the dosing period.  Pregnancy rate of high-dose females was
    slightly lower (90%) compared to the other treatment groups (93%-
    97%).  Treatment had no influence on reproduction parameters such as
    resorptions, fetal viability or fetal body weight.  No visceral or
    skeletal anomalies were observed that were considered treatment-
    related.  Skeletal variations were noted in all groups and included
    variations in the stage of ossification and rib counts, but not in a
    dose-dependent pattern.  A higher incidence of incomplete
    ossification of the sternebrae was observed in all treatment groups
    but without a clear dose-response relationship.  The highest
    incidences with respect to some differences in ossification (e.g.,
    5th/6th sternebrae incomplete ossification, asymmetric ossification
    of sternebrae) were noted at 10 mg/kg bw.  Statistical analysis
    revealed no significant trend for the overall incidence of delayed
    ossification of the 5th/6th sternebrae. The NOAEL for maternal
    toxicity was 3 mg/kg bw/day. The NOAEL for embryotoxicity and
    teratogenicity was 10 mg/kg bw/day (Morseth, 1990).

    Rabbits

         Groups of rabbits (banded Dutch; 20-30 females/group) were fed
    fenpropathrin (purity 97%) at dose levels of 0, 1.5, 3 or 6 mg/kg
    bw/day from day 6 to day 18 of gestation.  No clinical signs of
    intoxication were observed.  A lower number of rabbits survived to
    term at 3 mg/kg bw/day but this was unrelated to treatment. 
    Treatment had no effect on body weight of the dams.  No adverse
    effects were observed with respect to pre-implantation loss, number
    of resorptions, fetal deaths, litter size, or pup weight.  Increased
    incidence in minor skeletal and visceral abnormalities (e.g.,
    enlarged fontanelles, interparietal bones, fused sternebrae, extra
    centres of ossification) were noted at 3 mg/kg bw but not at the
    higher dose.  Therefore these changes were not considered treatment-
    related.  The NOAEL for maternotoxicity, embryotoxicity and
    teratogenicity was 6 mg/kg bw/day (van der Pauw  et al., 1975; Dix,
    1975).

         Groups of rabbits (New Zeeland white; 17-19 females/dose) were
    treated with oral doses of 0, 4, 12 or 36 mg/kg bw/day fenpropathrin
    (purity 92.5%) from days 7 to 19 of gestation.  A dose-related
    increase in the incidence of grooming was observed in all dose
    groups.  At 12 and 36 mg/kg bw/day, flicking of forepaws was also
    observed, with a few animals at 36 mg/kg bw/day showing shaky
    movements and tremor.  Slight reduction in body-weight gain and
    reduced food consumption were noted at 36 mg/kg bw/day.  One dam at
    12 and two at 36 mg/kg bw failed to maintain their pregnancies.  One
    dam at each dosage (including control) was sacrificed in poor

    condition.  Treatment did not adversely affect litter parameters
    (e.g., litter size, fetal weight).  There was no dose-related
    increase in the incidence of malformations.  The NOAEL was 4 mg/kg
    bw/day with respect to maternotoxicity and 36 mg/kg bw/day for
    fetotoxicity and teratogenicity (Cozens  et al., 1985).

    Special studies on genotoxicity

         Fenpropathrin has been adequately tested in a series of  in
     vitro and  in vivo genotoxicity assays.  The results are
    summarized in Table 2.

    Special studies on neurotoxicity

    Hens

         Six laying hens were treated with daily oral doses of 1 g/kg
    bw/day for five days.  Dosing was repeated after three weeks and the
    birds sacrificed three weeks later.  A positive control group was
    treated with tri-ortho-tolyl phosphate (TOTP).  No signs of
    intoxication were noted.  Histological examination of nervous
    tissues revealed no lesions (Milner & Butterworth, 1977).

    Rats

         Groups of rats (6/sex/group) were fed diets containing 0 or 900
    ppm fenpropathrin (purity not specified) for up to 25 days.  Tremors
    and high mortality were noted.  On histological examination of the
    sciatic nerve, swelling and disintegration of nerve axons were
    observed whereas no myelin lesions were noted (Hend & Butterworth,
    1976b).

         The neurotoxic effect of fenpropathrin in rats was assessed by
    means of the slip angle test.  Oral doses of 0, 10, 25, 50, 75 or
    100 mg/kg bw were administered to male rats (10/dose) and the angle
    at which the treated animals slipped from the board determined. The
    mean slip angle (MSA) decreased dose-dependently at 50 mg/kg bw and
    higher.  Clinical signs observed in animals treated with doses of 25
    mg/kg bw and above consisted of slight to severe tremor, ataxia and
    limb paralysis appearing at 3-7 hours after administration.  The
    effects on MSA and toxic signs almost disappeared after 24 hours. 
    Dose-related mortalities were observed at 50 mg/kg bw and above
    (Hiromori  et al., 1986b).


        Table 2.  Mutagenicity of fenpropathrin
                                                                                                                                            
    Test system         Test object            Concentration             Purity %               Results             Reference
                                                                                     non-activated    activated
                                                                                                                                            

    In vitro

    Ames test           S. typhimurium         50-5000 g/plate          92.5        negative         negative      Izumozaki et al., 1984
                        (various strains)                                                                           Yoshitake et al., 1987

    Ames test           S. typhimurium         10-1000 g/plate          97.0        negative1        negative      Suzuki, 1977
                        (various strains)

    Reverse mutation    Saccharomyces                                    92.5        negative         negative      Hara et al., 1984
    mitotic crossing    cerevisiae D7
    over and mitiotic
    gene convn. assay

    Mammalian cell      Mouse lymphoma         50-400 g/ml (-activ).    91.4        negative         negative      Richold et al., 1982b
    mutation assay      L5178Y cells           30-300 g/ml (+activ).

    Gene mutation       V79 Chinese            50-500 g/ml              92.4        negative         negative      Yoshitake et al., 1988
    assay               hamster cells

    DNA repair assay    HeLa S3 cells          0.16-2.5 g/ml            ?           negative         negative      Richold et al., 1982a

    Rec-assay           Bacillus subtilis      10-5000 g/disc           97.0        negative         negative      Kishida et al., 1980
                        M45 rec and H17

    DNA repair assay    Bacillus subtilis      100-10 000 g/disc        92.5        negative         negative      Yoshitake et al., 1986

    Chromosome damage   Chinese hamster        10 or 20 mg/kg bw         97.0        negative         negative      Dean, 1975
                        bone marrow cells      orally on two 
                                               succcessive days

                                                                                                                                            

    Table 2 (contd)
                                                                                                                                            
    Test system         Test object            Concentration             Purity %               Results             Reference
                                                                                     non-activated    activated
                                                                                                                                            

    Chromosome          Chinese hamster        50-500 g/ml (-activ).    92.5        negative         negative      McSheehy & Nunziata, 
    aberration assay    ovary cells (CHO)      500-5000 g/ml (+activ).                                             1984

    Chromosome          CHO-K1 cells           10-30 g/ml (-activ).     92.4        negative         negative      Yoshitake et al., 1989
    aberration assay                           250-1000 g/ml (+activ).

    Chromosome          Chiense hamster        0.003-0.1 mmol/l          92.5        negative         negative      Yoshitake et al., 1989b
    aberration assay    ovarian cells 
                        (CHO-K1)

    Sister chromatid    Chinese hamster        0.003-0.1 mmol/l          92.5        negative         negative      Hara & Suzuki, 1984b
    exchange            ovarian cells 
                        (CHO-K1)

    In vivo

    Micronucleus test   Mouse femur cells      50-200 mg/kg              92.5        negative         negative      Hara & Suzuki, 1984a,c 
                                               intraperitoneally

    Host mediated       S. cerevisiae JD1      10-20 mg/kg bw orally     97.0        negative         negative      Brooks et al., 1976
    assay               (in male mice)

                                                                                                                                            

    1    +activation by hepatic S-9 fractions obtained from 6 different mouse strains
    

         Functional testing was performed on 2 animals/sex at 0, 125 or
    500 ppm (satellite group of long-term study in rats, Hend &
    Gellatly, 1979) using the "inclined plane test".  Preliminary
    results revealed an impaired performance in animals fed 500 ppm. 
    Measurements of -glucuronidase activity (parameter indicative of
    Wallerian degeneration in nerves) did not reveal a clear increase as
    would be expected as a result of toxic neuropathy.  Macroscopy and
    histopathology of sciatic and tibial nerves did not show treatment-
    related changes (Hend & Gellatly, 1980).

    Special study on effects on enzymes

         A preliminary investigation was performed to study the possible
    effect of fenpropathrin on the induction of hepatic microsomal
    enzymes.  Four Charles River CD rats were fed dietary concentrations
    of 1, 10, 100 or 1000 ppm over two weeks.  No significant difference
    was observed between the activities of control and test livers in
    the  in vitro O-dealkylation of 14C-chlorfenvinphos and no dose-
    related increase in liver weights was induced.  Therefore, the
    results of this study do not provide any evidence for an inducing
    effect of fenpropathrin on liver microsomal enzymes (Creedy &
    Potter, 1976).

    Special study on antidotes

         The therapeutic potency of intraperitoneally administered
    methocarbamol [3-(o-methoxyphenoxy)-1,2-propanediol 1-carbamate] was
    examined against acute oral intoxication of rats after treatment
    with lethal doses of fenpropathrin (100 mg/kg bw) and some other
    pyrethroids.  Methocarbamol was initially administered
    intraperitoneally at a dose of 400 mg/kg bw followed by repeated
    doses of 200 mg/kg bw.  Treatment with methocarbamol reduced the
    mortality from 60% to 0% and depressed tremors (Hiromori  et al.,
    1986a).

    Special study on paresthesia

    Rabbits

         Facial paresthesia activities following exposure to
    fenpropathrin and other pyrethroids were estimated using a rabbit
    model.  To determine the intensity of facial paresthesia changes in
    behaviour after dermal application of the pyrethroids were recorded. 
    Doses applied ranged from 0.0001-10 mg/animal.  The frequency of
    licking and/or biting after application showed a clear dose-response
    relationship with all pyrethroids tested.  Post-treatment with
    vaseline-based 5% benzocaine ointment (local anaesthetic) was
    effective in reducing the intensity of animal response.  Post-
    treatment by application of undiluted vitamin E was also effective
    for treatment of facial paresthesia (Hiromori & Takemura, 1983).

    Special studies on irritation and sensitization

         The test material (purity 90.2%) caused no skin irritation and
    only very slight eye irritation in rabbits (Matsubara  et al.,
    1978).

         Two skin sensitization studies were conducted with guinea-pigs. 
    No sensitization reactions occurred (Okuno  et al., 1975; Suzuki &
    Miyamoto, 1981).

    Observations in humans

         In a field study in Japan, six workers participated in two
    tests using a 5% emulsifiable concentrate.  The spray concentrations
    were 25-50 ppm (a.i.), the spraying time 2 hours.  A motor mounted
    sprayer was used.  The workers wore protective clothing.  No effects
    were reported (e.g., headache, nasal discharge, itching, burning,
    pain in face or limbs) (Fujita, 1980).

         Some workers exposed to pyrethroids in the laboratory during
    formulation processes or in field trials in England reported
    transient abnormal facial sensations.  A clinical and
    electrophysiological study using an electromyograph was carried out
    on 23 workers.  Electrophysiological studies were also carried out
    on an equal number of age and sex-matched control subjects who had
    no contact with pyrethroids.  Nineteen had experienced at least one
    episode of abnormal facial sensations and 13/23 had experienced
    several such episodes. Permethrin, cypermethrin, fenpropathrin and
    fenvalerate were most frequently used. Symptoms were limited to the
    face. Characteristically, the symptoms appeared 30 minutes to eight
    hours after exposure.  Since exposure to the different pyrethroids
    varied, it was not possible to determine which compounds were more
    likely to produce symptoms.  Electrophysiological investigation
    showed statistically significant increase in maximal nerve
    conduction velocity in exposed workers compared to controls, which
    is contrary to what is expected in subclinical neuropathy.  The
    increase must therefore be fortuitous.  This conclusion is supported
    by the observation that no difference in nerve conduction velocity
    was noted in workers more exposed than others (Le Quesne  et al.,
    1980; Matsumoto  et al., no date).

         In a survey of 18 operators using a 10% fenpropathrin product,
    no adverse effects were reported, with the exception of slight nasal
    irritation. All operators wore protective clothing (Shell Chemical
    Ltd., 1978).

    COMMENTS

         After oral administration of fenpropathrin to rats, the
    compound was almost completely absorbed and eliminated in urine and
    in faeces.  The major biotransformation reactions consisted of
    oxidation at the methyl groups of the acid moiety and at the 2'-and
    4'-positions of the alcohol moiety, cleavage of the ester linkage
    followed by glucuronide, sulfate or glycine conjugation.

         Fenpropathrin has been tested for acute toxicity and it has
    been classified as moderately hazardous by WHO.

         In a short-term feeding study in rats conducted at dietary
    concentrations of 0, 3, 30, 100, 300 or 600 ppm over thirteen weeks,
    the NOAEL was 300 ppm, equal to 17 mg/kg bw/day, based on reduced
    body-weight gain and the appearance of clinical signs at higher dose
    levels.  In a second 13-week study in rats, the NOAEL was 150 ppm,
    equal to 8 mg/kg bw/day, based on depression of body-weight gain at
    higher dose levels.

         A one-year study in dogs conducted at dose levels of 0, 100,
    250 or 750 ppm revealed a NOAEL of 100 ppm equal to 3 mg/kg bw/day,
    based upon reduced body-weight gain and clinical signs (emesis,
    tremors) at 250 ppm.

         A long-term toxicity/carcinogenicity study was performed in
    mice over 2 years at 0, 40, 150 and 600 ppm. The NOAEL was the
    highest dose tested, 600 ppm, equal to 56 mg/kg bw/day.  There was
    no evidence of carcinogenicity.

         In a long-term toxicity/carcinogenicity study in rats conducted
    at dietary concentrations of 0, 1, 5, 25, 125 or 500 ppm over two
    years, the NOAEL was 125 ppm, equal to 5 mg/kg bw/day, based on
    depression in body-weight gain at 500 ppm.  There was no evidence of
    carcinogenicity.

         A second long-term toxicity/carcinogenicity study in rats
    performed at dietary concentrations of 0, 50, 150, 450 or 600 ppm
    over two years revealed a NOAEL of 150 ppm, equal to 7 mg/kg bw/day,
    based on the appearance of clinical signs at higher doses.  There
    was no evidence of carcinogenicity.

         In a multigeneration reproduction study in rats, fenpropathrin
    was administered at dietary levels of 0, 5, 25 or 250 ppm.  The
    NOAEL was 25 ppm, equal to 1.6 mg/kg bw/day, based on decreased pup
    weights in the F3a generation at 250 ppm.

         In a second multigeneration reproduction study conducted at
    dose levels of 0, 40, 120 or 360 ppm, the NOAEL was 40 ppm, equal to

    3 mg/kg bw/day, based on depression of body weight gain, increased
    mortality in females and the occurrence of tremors in pups at 120
    ppm and above.

         Two oral teratogenicity studies in rats were performed at dose
    levels of 0, 0.4, 2 or 10 mg/kg bw/day and 0, 0.4, 1.5, 2, 3, 6 or
    10 mg/kg bw/day.  The NOAELs were 2 and 3 mg/kg bw/day in the two
    studies, respectively, with respect to maternotoxic effects and a
    NOAEL of 10 mg/kg bw/day in both for embryotoxicity and
    teratogenicity.

         In an oral teratogenicity study in rabbits at dose levels of 0,
    1.5, 3 or 6 mg/kg bw/day, the NOAEL was 6 mg/kg bw/day.  In a second
    study with oral doses of 0, 4, 12 or 36 mg/kg bw/day the NOAEL was 4
    mg/kg bw/day with respect to maternotoxicity.

         Fenpropathrin has been adequately tested in a series of  in
     vitro and  in vivo genotoxicity assays.  The Meeting concluded
    that fenpropathrin was not genotoxic.

         Based upon studies in hens and rats, fenpropathrin exhibited no
    potential for delayed neurotoxicity.

         Data on observations in humans were not suitable for the
    estimation of an acceptable daily intake.

         An ADI of 0-0.03 mg/kg bw was established based on a NOAEL of 3
    mg/kg bw/day in the multigeneration reproduction study in rats, the
    teratogenicity studies in rats and the one-year feeding study in
    dogs, using a safety factor of 100.

    TOXICOLOGICAL EVALUATION

    Levels causing no toxicological effect

         Mouse:    600 ppm, equal to 56 mg/kg bw/day (two-year study)

         Rat:      150 ppm, equal to 7 mg/kg bw/day (two-year study)
                   40 ppm, equal to 3 mg/kg bw/day (reproduction study)
                   3 mg/kg bw/day (maternotoxicity in teratogenicity
                   study)

         Rabbit:   4 mg/kg bw/day (maternotoxicity in teratogenicity
                   study)

         Dog:      100 ppm, equal to 3 mg/kg bw/day (one-year study)

    Estimate of acceptable daily intake for humans

                   0-0.03 mg/kg bw

    Studies which will provide information valuable in the continued
    evaluation of the compound

         Further observations in humans.

    REFERENCES

    Aitken, R. & Rushton, B. (1981) Histopathology report for compound
    WL41706. 26, 53 and 104 week study in rats. Inveresk report project
    415386. Unpublished study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-11-0046.

    Brooks, T.M., Dean, B.J. & Thorpe, E. (1976) Toxicity studies with
    WL 41706 in the host mediated assay. Shell research report TLGR 0003
    76. Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-61-0007.

    Bruce, E.D., Griffis, L.C. & Wong, Z.A. (1986) The acute vapor
    inhalation toxicity of Danitol technical (SX-1713) in mice and rats.
    Chevron Study CEHC 2545. Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-61-
    0170.

    Colley, J., Gopinath, C. & Offer, J.M. (1987) S-3206: Two-year
    feeding study in mice (Addendum to final report). Huntingdon report
    SMO 149 861391 (Addendum to SMO 149 8640 (FT-51-0135)). Unpublished
    study submitted to WHO by Sumitomo Chemical Company Limited under
    the reference number FT-71-0180.

    Colley, J., Heywood, R., Street, A.E., Gopinath, C., Offer, J.M.,
    Gibson, W.A., & Almond, R.H. (1985) S-3206: Two year feeding study
    in mice. Huntingdon report SMO 14984607. Unpublished study submitted
    to WHO by Sumitomo Chemical Company Limited under the reference
    number FT-51-0135.

    Colley, J., Welch, P.J., Heywood,R., Prentice, D.E. & Gibson, W.A.
    (1981a) S-3206 Preliminary assessment of toxicity to mice by dietary
    administration for four weeks. Huntingdon report SMO 121 81289.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-11-0047.

    Colley, J., Welch, P.J., Heywood, R., Prentice,D.E. & Gibson, W.A.
    (1981b) S-3206 Second preliminary assessment of toxicity to mice by
    dietary administration for four weeks. Huntingdon report SMO 139
    81574. Unpublished study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-11-0049.

    Colley, J., Welch, P.J., Heywood, R., Prentice, D.E., Cherry, C.P.,
    Isaacs, K.R., Gibson, W.A. & Almond, R.H. (1982a) S-3206 Toxicity to
    rats by dietary administration for four weeks. Huntingdon report SMO
    146 8210. Unpublished study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-21-0064.

    Colley, J., Welch, P.J., Heywood, R., Prentice, D.E., Gibson, W.A. &
    Almond, R.H. (1982b) S-3206 Toxicity to rats by dietary
    administration for four weeks. Huntingdon report SMO 158 82335.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-21-0074.

    Cox, R.H. (1986) Teratology study in rats S-3206. Addendum I to
    final report. Hazleton report project 343 122 (Addendum to FT-01-
    0031). Unpublished study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-61-0176.

    Cox, R.H. (1987) S-3206: Amendment II to final report teratology
    study in rats. Hazleton report project 343 122 (Addendum to FT-01-
    0031). Unpublished study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-71-0188.

    Cozens, D.D., Barton, S.J., Offer, J.M., Gibson, W.A. & Anderson, A.
    (1986) Effect of S-3206 on multiple generations of the rat.
    Huntingdon report SMO 164 85707. Unpublished study submitted to WHO
    by Sumitomo Chemical Company Limited under the reference number FT-
    61-0159.

    Cozens, D.D., Hughes, E.W., Masters, R.E. & Anderson, A. (1985) The
    effect of S-3206 on pregnancy of the New Zealand white rabbit.
    Huntingdon report SMO 181 84667. Unpublished study submitted to WHO
    by Sumitomo Chemical Company Limited under the reference number FT-
    51-0134.

    Crawford, M.J. (1975) The metabolism of WL 41706 in mammals. The
    fate of a single oral dose of (14C) WL 41706 in the rat. Shell
    Research TLGR 0071 75. Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FM-51-
    0002.

    Crawford, M.J. & Hutson, D.H. (1976) Metabolic fate of (14C) WL
    41706 in rats. Shell Research TLGR. 0034 76. Unpublished study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FM-61-0001.

    Crawford, M.J. & Hutson, D.H. (1977) The metabolism of the
    pyrethroid insecticide (+)-alpha-cyano-3-phenoxybenzyl 2,2,3,3-
    tetramethyl-cyclopropanecarboxylate, WL 41706, in the rat.  Pestic.
     Sci., 8: 579-599. Submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FM-71-0050.

    Crayford, J.V. (1975) The excretion and residues of radioactivity in
    cows fed (14C) WL 41706 in their diet. Shell Research TLGR 0096 75.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FR-51-0015.

    Creedy, C.L. & Potter, D. (1976) The effect of feeding WL 41706 on
    the microsomal mono-oxygenase system of rat liver. Shell Research
    report TLGR 0043 76. Unpublished study submitted to WHO by Sumitomo
    Chemical Company Limited under the reference number FT-61-0009.

    Dean, B.J. (1975) Toxicity studies with WL 41706 (S-3206).
    Chromosome studies on bone marrow cells of Chinese Hamsters after
    two daily oral doses of WL 41706 (S-3206). Shell Research report
    TLGR 0104 75. Unpublished study submitted to WHO by Sumitomo
    Chemical Company Limited under the reference number FT-51-0003.

    Dean, G.A., Gopinath, C. & Fish, L.E. (1987) Potential tumorigenic
    and toxic effects in prolonged dietary administration to rats
    (Addendum to final report). Huntingdon report SMO 167 87185
    (Addendum to SMO 167 851348). Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-71-
    0181.

    Dix, K.M. (1975) Toxicity studies of WL 41706: Teratological studies
    in rabbits given WL 41706 orally. Shell Research report TLGR 0103 75
    (Addendum to FT-51-0006). Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-51-
    0133.

    Else, R. & Rushton, B. (1981) Histopathology report for compound WL
    41706 3-generation study in rats. Inveresk report project 415370.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-21-0069.

    Fish, C.J., Lewis, D.J. & Gopinath, C. (1986) Electron micrograph
    Addendum to histopathology report No SMO/167 S-3206 potential
    tumorigenic and toxic effects in prolonged dietary administration to
    rats. Huntingdon report SMO 167 86602 (Addendum to SMO 167 851348
    (FT-61-0161)). Unpublished study submitted to WHO by Sumitomo
    Chemical Company Limited under the reference number FT-61-0162.

    Fleming, D.J. (1979) Toxicity studies on the insecticide WL 41706: A
    three generation reproduction study (minus histopathology) in rats -
    Corrigendum to FT-91-0027. Shell Research report TLGR 79 0071.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-01-0028.

    Fujita, Y. (1980) Interview survey concerning complaints connected
    with use of S3206 in the field. Unpublished Sumitomo study submitted
    to WHO by Sumitomo Chemical Company Limited under the reference
    number FT-00-0040.

    Hara, S. & Suzuki, T. (1980) Acute oral toxicity of S-3206 in
    rabbits. Unpublished Sumitomo study submitted to WHO by Sumitomo
    Chemical Company Limited under the reference number FT-00-0039.

    Hara, M. & Suzuki, T. (1984a) Micronucleus test of S-3206.
    Unpublished Sumitomo study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-40-0106.

    Hara, M. & Suzuki, T. (1984b)  In vitro sister chromatid exchanges
    test of S-3206 in CHO-K1 cells. Unpublished Sumitomo study submitted
    to WHO by Sumitomo Chemical Company Limited under the reference
    number FT-40-0108.

    Hara, M. & Suzuki, T. (1984c) Addendum: Micronucleus test of S-3206.
    Unpublished Sumitomo study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-40-0114.

    Hara, M., Yamada, F., Kogiso, S., Yoshitake, A., Matsuo, M. &
    Miyamoto, J. (1984) Mutagenicity test of S-3206 in  Saccharomyces
     cerevisiae D7. Unpublished Sumitomo study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-40-
    0121.

    Hend, R.W. & Butterworth, S.T.G (1975) Toxicity studies on the
    insecticide WL 41706: A three month feeding study in rats. Shell
    Research report TLGR 0031 75. Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-71-
    0001.

    Hend, R.W. & Butterworth, S.T.G (1976a) Toxicity studies on the
    insecticide WL 41706: A three month feeding study in rats. Shell
    Research report TLGR 0020 76. Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-61-
    0013.

    Hend, R.W. & Butterworth, S.T.G. (1976b) Toxicity studies on the
    insecticide WL 41706: A short-term feeding study in rats. Shell
    Research report TLGR 0041 76. Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-61-
    0011.

    Hend, R.W. & Gellatly, J.B.M. (1979) Toxicity studies on the
    insecticide WL 41706: Results of physical appearance, survival,
    bodyweight, food intake, organ weights, clinical chemistry,
    hematology and gross pathological observations of rats exposed to WL
    41706 for up to two years. Shell Research report TLGR 79 062.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-91-0026.

    Hend, R.W. & Gellatly, J.B.M. (1980) Toxicity studies on the
    insecticide WL 41706: Results of physical appearance, survival, body
    weight, food intake, organ weights, clinical chemistry, hematology
    and gross pathological observations of rats exposed to WL 41706 for
    up to two years, Results of studies after 18 months. Shell Research
    report TLGR 79 062 (Addendum to FT-91-0026). Unpublished study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FT-01-0032.

    Hend, R.W., Gellatly, J.B.M. & Fleming, D.J. (1979) Toxicity studies
    on the insecticide WL 41706: A three generation reproduction study
    (minus histopathology) in rats. Shell Research report TLGR 79 071.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-91-0027.

    Heywood, R. (1982) An appraisal of the toxicological findings on
    rats receiving a synthetic pyrethroid S-3206 (fenpropathrin) by
    dietary administration for 4 weeks. Huntingdon report (unnumbered,
    1982). Unpublished study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-21-0075.

    Hiromori, T. Hosokawa, S. & Miyamoto, J. 1982a: Fenpropathrin
    toxicology overview - Acute toxicity and safety in use. Unpublished
    Sumitomo study submitted to WHO by Sumitomo Chemical Company Limited
    under the reference number FT-20-0079.

    Hiromori, T., Misaki, Y., Ito, S., Hosokawa, S. & Miyamoto, J.
    (1982b) Acute oral toxicity in rats. Unpublished Sumitomo study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FT-20-0076.

    Hiromori, T., Misaki, Y., Ito, S., Hosokawa, S. & Miyamoto, J.
    (1983a) Acute oral toxicity of S-3206 (97.3%) in rats. Unpublished
    Sumitomo study submitted to WHO by Sumitomo Chemical Company Limited
    under the reference number FT-30-0082.

    Hiromori, T., Misaki, Y., Seki, T., Hosokawa, S. & Miyamoto, J.
    (1983b) Acute oral toxicity of S-3206 (91.8%) in rats. Unpublished
    Sumitomo study submitted to WHO by Sumitomo Chemical Company Limited
    under the reference number FT-30-0081.

    Hiromori, T., Nakanishi, T., Kawaguchi, S., Sako, H., Suzuki, T. &
    Miyamoto, J. (1986a) Therapeutic effects of methocarbamol on acute
    intoxication by pyrethroids in rats.  J. Pestic. Sci. 11: 9-14.

    Hiromori, T., Nakanishi, T., Suzuki, T., Kato, T. & Miyamoto, J.
    (1986b) The mean slip angle test of S-3206 in rats. Unpublished
    Sumitomo study submitted to WHO by Sumitomo Chemical Company Limited
    under the reference number FT-60-0153.

    Hiromori, T. & Takemura, T. (1983) Short report on facial
    paresthesia following exposure to fenpropathrin, cypermethrin,
    fenvalerate or permethrin in rabbits. Unpublished Sumitomo study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FT-30-0087.

    Izumozaki, H., Hara, M. & Suzuki, T. (1984) Gene mutation test of S-
    3206 in bacterial system. Unpublished Sumitomo study submitted to
    WHO by Sumitomo Chemical Company Limited under the reference number
    FT-40-0107.

    Kaneko, H., Ohkawa, H. & Miyamoto, J. (1981) Comparative metabolism
    of fenvalerate and the (2S, alphaS)-isomer in rats and mice.  J.
     Pestic. Sci. 6: 317-326.

    Kaneko, H., Shiba, K., Yoshitake, A. & Miyamoto, J. (1987)
    Metabolism of fenpropathrin (S-3206) in rats.  J. Pestic. Sci. 12:
    385-395. 

    Kishida, F., Suzuki, H., Miyamoto, J. (1980) Studies on DNA damaging
    capacity of S-3206 with  Bacillus subtilis. Unpublished Sumitomo
    study submitted to WHO by Sumitomo Chemical Company Limited under
    the reference number FT-00-0038.

    Kohda, H. (1975) Acute oral toxicity of S-3206 in rats. Unpublished
    Sumitomo study submitted to WHO by Sumitomo Chemical Company Limited
    under the reference number FT-50-0018.

    Kohda, H. (1976) Acute dermal toxicity of S-3206 in rats.
    Unpublished Sumitomo study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-60-0019.

    Kohda, H. & Kadota, T. (1975) Acute oral toxicity of S-3206
    technical in mice. Unpublished Sumitomo study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-50-
    0035.

    Kohda, H. & Kadota, T. (1976a) Acute dermal toxicity of S-3206
    technical in mice. Unpublished Sumitomo study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-60-
    0036.

    Kohda, H. & Kadota, T. (1976b) Acute subcutaneous and
    intraperitoneal toxicity of S-3206 technical in rats and mice.
    Unpublished Sumitomo study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-60-0037.

    Kohda, H., Kadota, T. & Miyamoto, J. (1976) Acute inhalation
    toxicity of S-3206 and S-5602 in mice an rats. Unpublished Sumitomo
    study submitted to WHO by Sumitomo Chemical Company Limited under
    the reference number AT-50-0043.

    Ku, H.S. & Doran, T.J. (1990a) A study to determine the nature of
    the residue in milk, meat and tissue from lactating goats dosed with
    14C fenpropathrin. Ricerca Inc report project 89 0109. Unpublished
    study submitted to WHO by Sumitomo Chemical Company Limited under
    the reference number FM-01-0041.

    Ku, H.S. & Doran, T.J. (1990b) A study to determine the nature of
    the residue in poultry end eggs from chickens dosed with 14C
    fenpropathrin. Ricerca Inc., report project 89 0084. Unpublished
    study submitted to WHO by Sumitomo Chemical Company Limited under
    the reference number FM-01-0042.

    Le Quesne, P.M., Maxwell, I.C. & Butterworth, S.T.G. (1980)
    Transient facial sensory symptoms following exposure to synthetic
    pyrethroids: a clinical and electrophysiological assessment.
     Neurotoxicology, 2: 1-11. 

    Marroquin, F., Richter, W.R., Myer, J.R. & Johnson, D.E. (1981) S-
    3206 technical grade: Acute dermal toxicity (LD50) study in rabbits
    (TSCA 7/79) (EPA 8/78) (OSHA). IRDC report project 491 002.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-11-0051.

    Matsubara, T., Hara, S. & Kadota, T. (1978) Primary eye and skin
    irritation tests of S-3206 in rabbits. Unpublished Sumitomo study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FT-80-0023.

    Matsumoto,S., Suzuki, T., Kato, T. & Yamada, H. (no date) Comments
    on the facial sensation-inducing potential of fenpropathrin.
    Unpublished Sumitomo study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number FT-80-0195.

    McSheehy, T. & Nunziata, A. (1984) Chromosome aberrations in Chinese
    hamster ovary (CHO) cells  in vitro. Test substance: S-3206 Final
    report 113-005. Life Science Research Roma report project 113 005.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-41-0104.

    Milner, C.K. & Butterworth, S.T.G. (1977) Toxicity of pyrethroid
    insecticides: investigation of the neurotoxic potential of WL 41706
    to adult hens. Shell Research report TLGR 0068 77. Unpublished study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FW-81-0006.

    Misaki, Y., Hiromori, T., Hosokawa, S. & Miyamoto, J. (1983)
    Comments on acute oral toxicity of fenpropathrin technicals with
    high purity and lower purity in rats. Unpublished Sumitomo study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FT-30-0083.

    Misaki, Y. & Kohda, H. (1981a) Acute oral toxicity of two impurities
    of S-3206 (technical) in mice. Unpublished Sumitomo study submitted
    to WHO by Sumitomo Chemical Company Limited under the reference
    number FT-00-0044.

    Misaki, Y. & Kohda, H. (1981b) Acute oral toxicity of 2,2,3,3-
    tetramethylcyclopropane carboxylic anhydride in mice. Unpublished
    Sumitomo study submitted to WHO by Sumitomo Chemical Company Limited
    under the reference number FT-90-0045.

    Morseth, S.L. (1990) Rat teratology study with S-3206. Hazleton
    report project 343 216. Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-01-
    0216.

    Ohkawa, H., Kaneko, H., Tsuji, H. & Miyamoto, J. (1979) Metabolism
    of fenvalerate (Sumicidin) in rats.  J. Pestic. Sci., 4: 143-155.

    Okuno, Y. (1981) Comment on possible weight changes of kidney and no
    effect levels in a 2-year chronic toxicity study on WL 41706
    (fenpropathrin). Comments 0n FT-91-0026 and FT-11-9946. Unpublished
    Sumitomo study submitted to WHO by Sumitomo Chemical Company Limited
    under the reference number FT-10-0048.

    Okuno, Y., Kadota, T. & Miyamoto, J. (1975) Skin sensitization study
    of S-3206 in guinea-pigs. Unpublished Sumitomo study submitted to
    WHO by Sumitomo Chemical Company Limited under the reference number
    FT-50-0024.

    Omodaka, H., Misaki, Y. & Okuno, Y. (1986a) Acute oral toxicity of
    S-3206 in rats. Unpublished Sumitomo study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-60-
    0138.

    Omodaka, H., Suzuki, T. & Kato, T. (1986b) Acute dermal toxicity
    study of S-3206 in rats. Unpublished Sumitomo study submitted to WHO
    by Sumitomo Chemical Company Limited under the reference number FT-
    60-0139.

    Pauw van der, C.L., Dix, K.M., Blanchard, P.M., McCarthy, W.V. &
    Stevenson, D.E. 1975: Teratological studies in rabbits given WL
    41706 orally. Shell Research report TLGR 0103 75. Unpublished study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FT-51-0006.

    Pence, D.H., Alsaker, R.D., Hepner, K.E., Dawkins, B.G., Vargus,
    K.J., Hagen, W.H. & Hitzelberg, D.A. (1984) Chronic study in dogs S-
    3206 T.G. Final report. Hazleton report project 343 153. Unpublished
    study submitted to WHO by Sumitomo Chemical Company Limited under
    the reference number FT-41-0122.

    Pence, D.H., Dawkins, B.G., Alsaker, R.D., Weatherholtz, W.M. &
    Marshall, P.M. (1980a) Subchronic toxicity study in dogs S-3206.
    Final report. Hazleton report project 343 125. Unpublished study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FT-01-0034.

    Pence, D.H., Dawkins, B.G., Alsaker, R.D., Weatherholtz, W.M. &
    Marshall, P.M. (1980b) Subchronic toxicity study in dogs S-3206.
    Addendum to final report. Hazleton report project 343 125. Addendum
    to FT-01-0034. Unpublished study submitted to WHO by Sumitomo
    Chemical Company Limited under the reference number FT-01-0041.

    Pence, D.H., Pence, L.A., Durloo, R. and Cameron, J. (1980c)
    Teratology study in rats S-3206. Final report. Hazleton report
    project 343 122. Unpublished study submitted to WHO by Sumitomo
    Chemical Company Limited under the reference number FT-010031.

    Pence, D.H., Weatherholtz, W.M. & Cameron, J.T. (1978) Oral dose
    range finding study in dogs, S-3206. Final report. Hazleton report
    project 343 123. Unpublished study submitted to WHO by Sumitomo
    Chemical Company Limited under the reference number FT-91-0025.

    Richold, M., Allen, J.A. & Proudlock, R.J. (1982a) Autoradiographic
    assessment of DNA repair in mammalian cells after exposure to S-3206
    (fenpropathrin). Huntingdon report SMO 143 81881. Unpublished study
    submitted to WHO by Sumitomo Chemical Company Limited under the
    reference number FT-21-0068.

    Richold, M., Grantham, C.J. & Basham, K.J. (1982b) An assessment of
    the mutagenic potential of S-3206 using an  in vitro mammalian cell
    test system (with comment by J. Miyamoto). Huntingdon report SMO 144
    8252. Unpublished study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference numberFT-21-0060.

    Riley, J.H., Nair, K.P.C., Kopplin, J.R., Johnson, D.E., Ott, S.S.,
    Meyer, J.R. & Spicer, E.J.F. (1982) S-3206 (technical grade) 21-day
    dermal study in rabbits (EPA) (technical product). IRDC report
    project 491 010. Unpublished study submitted to WHO by Sumitomo
    Chemical Company Limited under the reference number FT-21-0058.

    Ruzo, L.O., Unai, T. & Casida, J.E. 1978: Decamethrin metabolism in
    rats.  J. Agric. Food Chem. 26: 918-925. 

    Shell Chemical (UK) Limited (1978) A survey of operator experience
    with fenpropathrin 10% EC - A pyrethroid insecticide/acaricide for
    use in fruit and ornamental crops in 1986. Shell UK report 16th
    January 1987. Unpublished study submitted to WHO by Sumitomo
    Chemical Company Limited under the reference number FT-71-0179.

    Summitt, L.M. & Albert, J.R. (1976) Intravenous toxicity of SD 41706
    (1-24-0-0) in the mouse. Shell Development Co report TIR 74 110 76.
    Unpublished study submitted to WHO by Sumitomo Chemical Company
    Limited under the reference number FT-61-0010.

    Suzuki, H. (1977) Studies on mutagenicity of some pyrethroids on
     Salmonella strains in the presence of mouse hepathic S9 fractions.
    Unpublished Sumitomo study submitted to WHO by Sumitomo Chemical
    Company Limited under the reference number AT-70-0157.

    Suzuki, T. & Miyamoto, J. (1981) Skin sensitization test of S-3206
    in guinea-pigs. Unpublished Sumitomo study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-10-
    0078.

    Suzuki, T., Sako, H. & Okuno, Y. (1986) Acute oral toxicity study of
    S-3206 in mice. Unpublished Sumitomo study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-60-
    0175.

    Warren, S., Heywood, R., Street, A.E., Gopinath, C., Browne, J.G.,
    Gibson, W.A., Reed, L.E. & Anderson, A. (1986) S-3206: Potential
    tumorigenic and toxic effects in prolonged dietary administration to
    rats (Final report. Huntingdon report SMO 167 851348. Unpublished
    study submitted to WHO by Sumitomo Chemical Company Limited under
    the reference number FT-61-0161.

    WHO (1992). The WHO recommended classification of pesticides by
    hazard and guidelines to classification 1992-1993 (WHO/PCS/92.14).
    Available from the International Programme on Chemical Safety, World
    Health Organization, Geneva, Switzerland.

    Yoshida, A., Kosaka, T., Miyaoka, T., Maita, K. & Goto, S. (1986) S-
    3206: 13-week oral subchronic toxicity study in rats. Inst. Environ.
    Toxicol. Tokyo report 17th, July 1986. Unpublished study submitted
    to WHO by Sumitomo Chemical Company Limited under the reference
    number FT-61-0166.

    Yoshitake, A., Kogiso, S. & Hara, M. (1990)  In vitro chromosomal
    aberration test of S-3206 in Chinese Hamster ovary cells (CHO-K1).
    Sumitomo study M83-54. Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-00-
    0215.

    Yoshitake, A., Kogiso, S., Kato, H. & Hara, M. (1988)  In vitro 
    gene mutation test of S-3206 in V79 Chinese Hamster cells in
    culture. Sumitomo study 1174. Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-80-
    0209.

    Yoshitake, A. Kogiso, S. & Yamada, F. (1986) Bacterial DNA repair
    test of S-3206. Sumitomo study MUT86020. Unpublished study submitted
    to WHO by Sumitomo Chemical Company Limited under the reference
    number FT-60-0165.

    Yoshitake, A., Kogiso, S & Yamada, F. (1987) Reverse mutation test
    of S-3206 in bacterial systems. Sumitomo study 704. Unpublished
    study submitted to WHO by Sumitomo Chemical Company Limited under
    the reference number FT-70-0182.

    Yoshitake, A., Kogiso, S., Yamamoto, K. & Hara, M. (1989)  In vitro
    chromosomal aberration test of S-3206 in Chinese Hamster ovary cells
    (CHO-K1). Sumitomo study 1730. Unpublished study submitted to WHO by
    Sumitomo Chemical Company Limited under the reference number FT-90-
    0200.


    See Also:
       Toxicological Abbreviations
       Fenpropathrin (UKPID)