PESTICIDE RESIDUES IN FOOD - 1984


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1984




    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
    Rome, 24 September - 3 October 1984

    Food and Agriculture Organization of the United Nations
    Rome 1985

    PHOXIM

    Explanation

         Phoxim was evaluated by the Joint Meeting in 1982 1/ and a
    temporary ADI was allocated. An appropriate neurotoxicity study in
    hens was required and has now been submitted, together with an
    additional embryotoxicity teratogenicity study in rabbits. These data
    are reviewed in this monograph addendum.

         Corrigenda: The 1982 Evaluations, page 380, misreported the
    temporary ADI of 0-0.05 mg/kg bw. The 1982 Report correctly stated the
    temporary ADI as 0-0.0005 mg/kg bw.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    TOXICOLOGICAL STUDIES

    Special Study on Embryotoxicity and Teratogenicity

    Rabbit

         Groups of 20 mated female chinchilla rabbits received, by gavage,
    daily doses of Phoxim (technical grade, 83.8 percent pure) at levels
    of 0, 12, 36 or 72 mg/kg bw/day, from day 6 through day 18 of
    pregnancy. On day 28 of pregnancy, dams were killed and foetuses
    removed by caesarean section for external, visceral and skeletal
    examination. No dose-related mortality was observed. Compound-related
    symptoms were observed in the high dose group only. In the dams,
    Phoxim caused a reduction of food consumption and mean body weight
    gain which were slight at 36 mg/kg and marked at 72 mg/kg. The number
    of pregnant females, pre-implantation losses, implantations per dam,
    live foetuses and sex ratio of live foetuses were comparable among all
    groups. An increased ratio of embryonic resorption and decreased mean
    body weight of foetuses were observed in the high dose group compared
    to the control and other treated groups. The no-effect level for
    embryotoxicity is 36 mg/kg bw. No malformations or anomalies
    attributable to the treatment were observed (Becker, 1982).

    Special Study on Delayed Neurotoxicity

         Thirty white Leghorn hens, 10-15 months old, received, by gavage,
    Phoxim at a dose level of 50 mg/kg bw, protected with atropine
    (50 mg/kg bw). After an interval of 21 days, the same procedure was
    repeated. The dose of 50 mg/kg bw of Phoxim administered in a pilot
    study produced 80 percent mortality when given without atropine
    protection. A negative control group of six hens received the same
    quantity of vehicle solution and atropine. A positive control group of
    five hens received a single dose of 375 mg/kg bw of 
    triorthocresyl-phosphate (TOCP).

              
    1/  See Annex 2 for FAO and WHO documentation.

         At the end of the observation period (42 days after the first
    administration for compound and solvent-treated hens, 24 days for
    TOCP-treated hens), the animals were sacrificed and sciatic nerve
    tissue was removed for histopathological examination.

         In the compound-treated group, after the end of the acute phase
    of poisoning, the hens were free of effects up to the time of the
    repeated administration. Signs similar to paralysis, disturbance of
    coordination of movement and protracted effects were not observed at
    any time during the observation period. The histopathological
    examinations also showed that no treatment-induced peripheral
    neuropathy or demyelinization had been induced. All hens in the
    positive control (TOCP) group showed progressive disturbance of
    coordination of movement with severe paralysis in the final stage;
    histopathological examination revealed varying degrees of nerve fibre
    degeneration in the peripheral nerve (demyelinization, lysis of axon,
    ballooned fibre segments, activated Schwan cells). Phoxim did not
    produce neurotoxic effect, as determined in this study. (Pauluhn &
    Kaliner, 1984).

         The acute oral LD50 to hens (15-20 months old) was determined to
    be 40 mg/kg bw (Pauluhn, 1983).

    COMMENTS

         Phoxim was evaluated in 1982, when a temporary ADI was allocated
    and an appropriate neurotoxicity study in hens was required. Phoxim
    did not display delayed neurotoxicity effects in a double-dose test in
    hens. No teratogenic effects were observed in rabbits. The temporary
    ADI was changed to a full ADI.

    TOXICOLOGICAL EVALUATION

    Level Causing no Toxicological Effect

         Rat: 5 ppm in the diet, equal to 0.56 mg/kg bw

         Dog: 2 ppm in the diet, equivalent to 0.05 mg/kg bw

    Estimate of Acceptable Daily Intake in Man

         0 - 0.001 mg/kg bw

    FURTHER WORK OR INFORMATION

    Desirable

    1.   Observations in humans (particularly effects on cholinesterase).

    2.   Type and content of impurities in the technical products.

    REFERENCES

    Becker, H. Embryotoxicity and teratogenicity study on SRA 7502 in
    1982      Rabbits. Report No. R 2354 from Research & Consulting
              Company Ltd., Switzerland, submitted by Bayer AG to WHO.
              (Unpublished)

    Pauluhn, J. SRA 7502 (Active ingredient of Baythion and Volaton) -
    1983      Acute oral toxicity study on hens. Report No. 11978 from
              Institute of Toxicology, Bayer, submitted by Bayer AG to
              WHO. (Unpublished)

    Paulunh, J. & Kaliner, G. SRA 7502 (c.n.: phoxim) - Study of acute
    1984      neurotoxicity in hens. Report No. 12632 from Institute of
              Toxicology, Bayer, submitted by Bayer AG to WHO.
              (Unpublished)

    See Also:
       Toxicological Abbreviations
       PHOXIM (JECFA Evaluation)
       Phoxim (Pesticide residues in food: 1982 evaluations)
       Phoxim (Pesticide residues in food: 1983 evaluations)
       Phoxim (Pesticide residues in food: 1984 evaluations)