FAO Meeting Report No. PL/1965/10/1
    WHO/Food Add./27.65

    EVALUATION OF THE TOXICITY OF PESTICIDE RESIDUES IN FOOD

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Committee on Pesticides in Agriculture and
    the WHO Expert Committee on Pesticide Residues, which met in Rome,
    15-22 March 19651

    Food and Agriculture Organization of the United Nations
    World Health Organization
    1965

                
    1 Report of the second joint meeting of the FAO Committee on
    Pesticides in Agriculture and the WHO Expert Committee on Pesticide
    Residues, FAO Meeting Report No. PL/1965/10; WHO/Food Add./26.65

    CHLOROBENZILATE

    Chemical name

         ethyl-2-hydroxy-2,2-di(p-chlorophenyl) acetate; ethyl
    4,4'-dichlorobenzilate; ethyl 4,4'-dichlorodiphenylglycollate.

    Empirical formula

         C16H14O3Cl2

    Structural formula

    

    BIOLOGICAL DATA

    Biochemical aspects

         Chlorobenzilate appears to undergo extensive hydrolysis in the
    body to the acid form which is the main excretion product.

    Acute toxicity

                                                                
    Animal     Route        LD50 mg/kg          References
                            body-weight
                                                                

    Mouse      Oral             729             Horn et al., 1955
                        (Technical product)

    Mouse      Oral            4 850            Gasser, 1952a;
                                                Gasser, 1952b

    Rat        Oral             702             Horn et al., 1955
                        (Technical product)

    Rat        Oral            3 100            Gasser, 1952a;
                                                Gasser, 1952b

    Rat        Oral             735             Horn et al., 1955
                       (25% xylene emulsion)
                                                                

    Short-term studies

         Rat. Groups of rats, each of 20 males, were fed 40 and 800 ppm
    of technical chlorobenzilate in the diet for 44 or 48 weeks (Geigy,
    1953-55).

         The rats receiving 40 ppm grew at about the same rate as the
    controls, but those receiving 800 ppm were markedly retarded as to
    growth. Several animals receiving 800 ppm exhibited red or swollen
    eyelids and soft faeces, and one developed diarrhoea. During the test,
    2 control rats and 5 rats receiving 800 ppm died, there were no deaths
    among those receiving 40 ppm.

         Gross autopsy of all survivors showed no characteristic changes
    attributable to feeding of the compound. The weights of the liver,
    kidneys, and testes of rats receiving 40 ppm, when expressed as
    percentages of body-weight, were significantly greater than those of
    the controls. The organ weights of rats receiving 800 ppm were not
    evaluated statistically, though the absolute weights were less than at
    40 ppm.

         Microscopic examination of the main organs revealed no
    significant histological changes attributable to the administration of
    the compound, but non-specific histological changes were noted in the
    pancreas and adrenals of some rats receiving 40 ppm and in the spleen,
    pancreas and adrenals of the rats receiving 800 ppm (Geigy, 1953-55).

         Dog. Groups of 2 dogs, one male and one female in each group,
    were given 12.8 mg and 64.1 mg/kg body-weight per day for 35 weeks.

         All dogs either maintained their body-weight or made slight
    weight gains; they showed normal behaviour, had good appetite, and
    showed no gross signs of toxicity throughout the entire study.

         Biochemical and haematological results were within normal limits.
    Gross and microscopic examination of the main organs revealed no
    significant pathological changes at the end of the 35-week period
    (Horn et al., 1955).

    Long-term studies

         Rat. Groups each of 40 rats (20 males and 20 females) were fed
    500 ppm of technical chlorobenzilate for 2 years, and one group of 20
    males was fed 50 ppm of the compound for 2 years (Horn et al., 1955).

         Only the males receiving 500 ppm showed a significantly lower
    weight gain as compared to the controls. Tissues from the main organs
    were examined. The histopathological findings could not be attributed
    to the feeding of chlorobenzilate for 2 years. The organ weights of
    liver, kidneys and spleen were not significantly different from those
    of the controls. In the males receiving 50 and 500 ppm there was an
    increase in the frequency of atrophied testes (Horn et al., 1955).

    Comments on experimental studies reported and evaluation

         The maximum no-effect level in the rat appears to be about 50
    ppm, but further animal studies are required to confirm this before an
    evaluation can be made.

    Further work required

         Metabolic studies in animals. Additional long-term studies in
    rats at lower dose-levels and long-term studies in other species.

    REFERENCES

    Gasser, R. (1952a) Compte Rendues, IIIe Congrès international de
    phytopharmacie, Paris, p. 357

    Gasser, R. (1952b) Experienta, 8, 65

    Geigy Chemical Corp., Yonkers, New York, 1953-55, Unpublished data

    Horn, J. J., Bruce, R. B. & Paynter, O. E. (1955) J. Agric. Food
    Chem., 3, 752
    

    See Also:
       Toxicological Abbreviations
       Chlorobenzilate (ICSC)
       Chlorobenzilate (FAO/PL:1968/M/9/1)
       Chlorobenzilate (WHO Pesticide Residues Series 2)
       Chlorobenzilate (WHO Pesticide Residues Series 5)
       Chlorobenzilate (Pesticide residues in food: 1977 evaluations)
       Chlorobenzilate (Pesticide residues in food: 1980 evaluations)
       Chlorobenzilate (IARC Summary & Evaluation, Volume 5, 1974)
       Chlorobenzilate (IARC Summary & Evaluation, Volume 30, 1983)