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

    PHENTHOATE

    EXPLANATION

         Phenthoate was evaluated by the Joint Meeting on Pesticide
    Residues in 1980 (FAO/WHO 1981) at which time only a temporary ADI was
    allocated on the basis that a chronic toxicity in a rodent was needed.
    The required chronic toxicity/carcinogenicity study has been submitted
    and is summarized in this monograph addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    TOXICOLOGICAL STUDIES

    Special Studies on Carcinogenicity

    (see under long-term studies)

    Long-Term Studies

    Rat

         Groups of Sprague-Dawley rats (60 males and 60 females per group)
    were fed diets containing Phenthoate (technical grade, 93.9 percent
    purity at levels of 0, 20, 100 or 500 ppm for 116 weeks.

         Animals were observed three times a day for morbidity and
    mortality. Food and water consumption, body weights and adverse
    clinical (including neurological, ocular and behavioural) signs were
    recorded weekly for the first 13 weeks and bi-weekly thereafter. At
    periodical intervals haematology, clinical chemistry (including
    cholinesterase activity) and urine analyses were performed on ten
    animals/group/sex.  Gross pathology and histopathology examinations
    were performed on all animals.

         No clinically detectable pathological signs were observed. There
    were no significant differences between control and treated groups
    with respect to mortality, growth, food and water consumption,
    haematology, clinical chemistry (except cholinesterase activity) and
    urine analyses. Plasma cholinesterase activity was significantly
    depressed in males and females of the 500 ppm group from week 26 to
    termination and in females at 100 ppm from week 78. Erythrocyte
    cholinesterase depression from 22-25 percent for females and 12-19
    percent for males, in the 20 ppm group as compared to the control and
    is considered the marginal effect level. Brain cholinesterase activity
    was depressed about 20 percent in the high-dose group only.

         Absolute and relative organ weights were not significantly
    different between control and treated groups. No specific gross
    pathological changes attributable to the treatment were noted.
    Histopathologically, nodular hyperplasia of hepatic cells was
    significantly increased, although not dose-related, in treated groups
    when compared to the controls.

         There were no statistically significant differences between
    control and treated groups with respect to type, incidence,
    distribution or latency time of observed tumours. Under the conditions
    of the test, phenthoate did not display any carcinogenic potential.
    Detailed histopathological examinations performed to assess the
    potential neurotoxic effects of phenthoate did not reveal any lesions.
    (Maltoni, 1984).

    COMMENTS

         Phenthoate was evaluated in 1980 when a temporary ADI was
    allocated.

         In the rat long-term toxicity/carcinogenicity study submitted,
    phenthoate did not show oncogenic potential. No changes in
    haematology, clinical chemistry or urine analyses, nor any lesions in
    nervous tissues examined, were observed. The 20 ppm dose level was
    identified as producing a marginal effect on erythrocyte cholinestase
    in this study. The meeting allocated a full ADI.

    Level causing no toxicological effect

         Dog:  10 ppm in the diet, equal to 0.29 mg/kg b.w.

         Rat:  10 ppm in the diet, equal to 1.0 mg/kg b.w.

         Mouse: 30 ppm in the diet, equivalent to 4.5 mg/kg b.w.

    Estimate of acceptable daily intake for humans

         0 - 0.003 mg/kg b.w.

    Further work or information

    Desirable:

         Observation in humans.

         Further information on impurities in the technical products in
    order to evaluate the degree to which these impurities affect the
    acute toxicity of phenthoate.

    REFERENCES

    Maltoni, C. Long-term carcinogenicity and chronic toxicity of
    1984      phenthoate (CAS No.2597-03-7) on Sprague-Dawley rats (oral
              dosing study) Bologna, Italy. Inst. Oncology. Report No. BT
              5005. Submitted by Farmoplant, Italy, to WHO.

    See Also:
       Toxicological Abbreviations
       Phenthoate (Pesticide residues in food: 1980 evaluations)
       Phenthoate (Pesticide residues in food: 1981 evaluations)