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

    CAPTAN

    Chemical names

         N-(trichloromethylthio)cyclohex-4-ene-1,2 dicarboxyimide;
    N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide;
    N-(trichloromethylthio)-3a,4,7,7a-tetra-hydrophthalimide.

    Empirical formula

         C9H8O2NCl3S

    Structural formula

    

    BIOLOGICAL DATA

    Biochemical aspects

         In yeast, it seems that the active principle of captan is the
    thiophosgene formed from the trichloromethylthio group. Thiophosgene
    will probably combine with active groups as - OH, -SH2 and NH2
    within the cell (Lukens & Sisler, 1958). In a fungus, captan gave a
    marked depression of the activity of the enzyme glutamine
    dehydrogenase and a stimulation of diphosphopyridine nucleotide
    oxydase (Byrde et al., 1956).

    Acute toxicity

                                                                  
    Animal       Route           LD50 mg/kg       References
                                 body-weight
                                                                  

    Rat          Oral           9 000-15 000      Link et al., 1956
                                 (given as        Spector, 1956
                              wettable powder)

    Rat     Intraperitoneal        50-100         Link et al., 1956
                                                                  

    Short-term studies

         Dog. Groups of 4 dogs, 2 males and 2 females, were fed 400,
    4000 and 12 000 ppm of technical captan for 66 weeks. The animals on
    the highest level, 12 000 ppm, showed slightly enlarged kidneys and
    livers. No histological changes occurred at any dose level (Fitzhugh,
    1963).

         Pig. Seven pigs fed 480 ppm captan in their diet for 14 weeks
    showed good weight gains. Haematological examination did not show any
    abnormalities. Gross and histopathological study of the liver and
    kidney revealed no abnormalities. No residual captan (i.e., <0.1 ppm)
    was found in the tissues (Link et al., 1956).

         Pigs fed 4000 ppm of captan in the diet for 25 weeks showed no
    symptoms, but no further observations were made (Johnson, 1954).

         Chick. Chicks received 320 ppm captan in their food for 74
    days. No abnormalities were found (Link et al., 1956).

    Long-term studies

         Rat. Groups each of 20 rats, 10 males and 10 females, were fed
    1000 and 5000 ppm of captan in their diet for 2 years. Another group
    of 20 rats received 10 000 ppm of captan partly technical and partly
    recrystallized for one year. In the group receiving 1000 ppm in the
    diet a reduction in weight occurred for the last 16 weeks of the
    experiment. Female rats receiving 5000 ppm and both sexes on diets
    containing 10 000 ppm of captan showed growth depression and higher
    mortality. At autopsy atrophied testes were found in the animals on
    the highest dose level. Organ weights, blood picture, tumour frequency
    and histological studies were not significantly different from those
    in controls (Weir, 1956).

         In another experiment 30 rats of each sex were fed 1000 ppm of
    technical captan for 17 months and compared to two untreated control
    groups. Body-weight gains, food consumption, survival rate and tumour
    incidence were comparable in treated and untreated animals (Industrial
    Bio-Test Laboratories, Inc., 1961).

    Comments on the experimental studies reports

         Long-term experiments in rats and short-term experiments in rats,
    dogs and pigs have been carried out. There is no information about the
    metabolism of the compound.

    Level causing no significant effect in animals

         Rat: 1000 ppm equivalent with  50 mg/kg body-weight per day

         Dog: 4000 ppm     "        "  100 mg/kg   "    "     "   "

         Pig:  480 ppm     "        "   19 mg/kg   "    "     "   "

    Estimate of acceptable daily intake for man

         0-0.1 mg/kg body-weight per day.

    Further work desirable

         Determination and evaluation of toxicity of the residues
    occurring in the plant. Studies on the metabolism in animals.
    Extension of the long-term studies in rats and long-term studies in
    other species at dosages designed to find maximum no-effect levels.

    REFERENCES

    Byrde, R. J. W. et al. (1956) Nature, 178, 638

    Fitzhugh, O. G. (1963) Personal communication

    Industrial Bio-Test Laboratories, Inc. (1961) Unpublished report
    submitted to California Chemical Company

    Johnson, D. F. (1954) Southwestern Veterinarian, 8 (1), 30

    Link, R. P., Smith, J. C. & Morrill, C. C. (1956) J. Amer. vet. med.
    Ass., 128, 614

    Lukens, R. J. & Sisler, H. D. (1958) Phytopathology, 48, 235

    Spector, W. S., ed. (1956) Handbook of Toxicology, Philadelphia &
    London, Saunders, vol. I

    Weir, R. J. (1956) Unpublished report of Hazleton Laboratories
    

    See Also:
       Toxicological Abbreviations