Sponsored jointly by FAO and WHO


    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



         Captan has been evaluated by the Joint Meetings on Pesticide
    Residues in 1969, 1973, 1974, 1977, 1978 and 1982 (FAO/WHO, 1965b,
    1970, 1974, 1975, 1979, and 1983). In view of the concerns with
    respect to carcinogenicity in mice, the inability to demonstrate a
    no-effect level in the 3-generation reproduction study in rats and the
    finding of the long-term/carcinogenicity studies in both mice and rats
    conducted by IBT being invalid, the 1982 Joint Meeting decided that
    the full ADI be modified to a temporary ADI at 0 - 0.01 mg/kg bw.
    Further work required by 1984 included the complete report of the new
    two-year study in rats and mice, and a two-generation reproduction
    study. New studies were made available to the meeting and are reviewed
    in this monograph addendum.



    Special Study on Reproduction


         Groups of Charles River CD rats (15 males and 30 females per
    group) were fed Captan in the diet at dosages of 0, 6, 12.5 and 25
    mg/kg/day in a one-generation, one-litter reproduction study. After
    102 days of treatment the animals were mated. The F0 adults were
    necropsied after weaning of the F1 pups. The parental rats and the
    pups were observed for signs of toxicity, changes in general
    behaviour, appearance and survival. There were no compound-related
    effects on survival, appearance, behaviour, body weight or food
    consumption among the parental animals. Fertility index, length of
    gestation, and pup viability and weight at birth in all treated groups
    were comparable to controls. Pup survival during lactation was
    comparable to controls. There was slight reduction in mean pup body
    weight and litter weight on lactation days 4, 7 and 14 at the 25 mg/kg
    level. No other compound-related effects on reproduction were reported
    (Aldrige, Shardein & Blair, 1982).

    Special Study on Teratology


         The Joint Meeting in 1982 reviewed a teratology study in Golden
    hamsters in which "non-specified" rat anomalies were reported in
    treated pups. Additional detail was requested and has been provided.
    The rib anomalies were primarily bent ribs, confined to the high-dose
    group and occurred in only one litter. The results of this study
    indicated that Captan produced maternal deaths and weight loss at
    doses of 200 and 400 mg/kg and was also foetotoxic at the 400 mg/kg

    dose. Therefore, these bent rib anomalies may be accounted for by a
    maternal stress effect upon the foetus rather than a teratogenic
    effect (Shardein, 1983).

    Special Studies on Carcinogenicity


         Groups of CD-1 (ICR derived) mice (80 males and 80 females per
    group) were fed Captan (purity 90.7 percent) in their diet at dose
    levels of 0, 2 000, 6 000 and 10 000 ppm for four weeks, after which
    these levels were increased to 0, 6 000, 10 000 and 16 000 ppm,
    respectively, for the remaining 105 weeks of the study. In males there
    was a statistically significant dose-related trend in mortality. The
    survival pattern of females is less clear, but still statistically
    significant, due to higher mortality of the high-dose group. In all
    treatment groups, average body weights were significantly lower than
    the controls throughout the study. No significant haematological
    effects were noted.

         Gross pathological examination demonstrated the presence of
    duodenal lesions and gastrointestinal tract abnormalities. There were
    statistically significant increases in duodenal adenomas and
    adenocarcinomas in both sexes. The incidence of adenoma and carcinoma
    in the stomach, duodenum and jejunum-ileum for males was 3.7 percent
    (control), 23.7 percent (low-dose), 28 percent (mid-dose) and 48.7
    percent (high-dose); for females, 3.7 percent (control), 32 percent
    (low-dose), 26 percent (mid-dose) and 36 percent (high-dose). The
    high-dose males generally showed proliferative changes of the duodenum
    earlier than the other groups. The results demonstrate that captan, at
    dietary concentrations of 6 000, 10 000 and 16 000 ppm induced both
    benign and malignant duodenal tumours in CD-1 mice (Bradfield, Wong &
    MacGregor, 1981).

         Groups of 42-day-old CD-1 mice (100 males and 100 females per
    group) were administered Captan (purity 89 percent in the diet at dose
    levels of 0, 100, 400, 800 and 6 000 ppm continuously for 22 months.
    Cage-side observations for signs of toxic or pharmacologic effects
    were conducted daily and palpations for tissue masses were performed
    weekly. Body weight and food consumption were measured regularly
    throughout the study. Complete gross postmortem examinations were
    conducted on all animals and microscopic examinations were performed
    on selected tissues from all animals.

         The high-dose males exhibited a higher incidence of mortality
    than controls during the first 14 months of the study. Mortality data
    in the other treated groups were comparable to controls. The mean body
    weights of the high-dose males and females were reduced throughout the
    study and were statistically significant in high-dose males during the
    first year, and in high-dose females for the first 18 months. Food
    consumption was variable in control and treated groups.

         Gross postmortem examinations revealed an increased incidence of
    lesions of the small intestine (masses, nodules, raised areas) in
    female mice fed 800 and 6 000 ppm of Captan. Microscopic examination
    demonstrated an increased incidence of duodenal hyperplastic lesions
    in high-dose male and female mice. The number of benign and malignant
    duodenal neoplasias were significantly increased in high-dose females
    only. Although the incidence in low- and high-dose males was
    increased, it was not statistically significant. The incidence of
    adenoma and carcinoma in the stomach, duodenum, and jejunum-ileum for
    males was 0/100, 6/100, 1/100, 1/100 and 5/100; for females 0/100,
    1/100, 3/100, 3/100 and 7/100 for 0, 100, 400, 800 and 6 000 ppm
    groups, respectively. Historic control data derived from concurrent
    studies in CD-1 mice indicate that 1/718 males developed a duodenal
    carcinoma, with 0/737 incidence in females (Daly & Knezevick, 1983).


         Groups of 30-day-old Charles River CD rats (70 males and 70
    females per group) were administered Captan (89 percent purity) in the
    diet at dose levels of 0, 25, 100 and 250 mg/kg bw/day for two years.
    Animals were observed twice daily for signs of acute toxicity,
    moribundity and mortality. Individual body weights were regularly
    determined and food and compound consumption were measured.
    Ophthalmoscopic, haematologic and clinical biochemical measurements
    and urinalysis were performed periodically throughout the study. There
    were no compound-related effects on any of these parameters. The mean
    body weights for males and females given 100 and 250 mg/kg/day were
    significantly lower than controls throughout the study.

         Macroscopic examination at necropsy did not indicate any
    significant differences between treated and control animals.
    Microscopically, hepatocellular hypertrophy was significantly
    increased in high-dose animals only, compared to controls. Male rats
    demonstrated a statistically significant trend for kidney adenomas
    (Krus-Kall Wallis test for adjusted trend, p<0.05; Armitage trend
    test p<0.05). The incidence of kidney adenomas in males was 1/70,
    1/70, 3/70 and 4/70 for control, 25, 100 and 250 mg/kg groups,
    respectively. Although a significant trend is established, the
    occurrence in the mid- and high-dose groups were not biologically
    significant in light of the finding of this rare tumour in a control

         Captan was without demonstrated adverse effects in CD rats when
    administered in the diet for two years at 25 mg/kg bw/day (Goldenthal,


         Captan was last considered by the 1982 JMPR.

         An additional study has confirmed the lack of oncogenicity of
    Captan in the CD rat. The ability of relatively high doses of Captan
    to cause duodenal adenocarcinoma in CD-1 mice has also been confirmed.
    However, duodenal neoplasia occurs in some controls.

         Data from an additional single generation reproduction study
    complemented and extended earlier data, establishing that Captan does
    not adversely affect reproduction of CD rats at 12.5 mg/kg bw/day. The
    meeting determined that there was no further concern with IBT studies,
    as these had not been replaced with validated studies. An ADI was
    therefore estimated.

    Level Causing no Toxicological Effect

         Monkey (rhesus, based on reproduction studies):
         12.5 mg/kg bw/day.

         Rat (based on reproduction studies):
         250 ppm in the diet equal to 12.5 mg/kg bw.

         Mouse:    800 ppm in the diet, equivalent to 120 mg/kg bw.

         Dog:      100 mg/kg bw/day.

    Estimate of Acceptable Daily Intake for Humans

         0 - 0.1 mg/kg bw.



         Comparative study of the metabolic fate of Captan in rats and

         Study of the pathogenesis of gastrointestinal lesions produced by
    Captan in mice (known to be in progress).

         Further observations in humans.


    Aldrige, D., Shardein, J.L. & Blair, M. One-generation reproduction
    1982      study in rats with Captan. International Research and
              Development Corporation, USA. Submitted by Stauffer Chemical
              Company, USA, to WHO. (Unpublished)

    Bradfield, L.C., Wong, T.A. & MacGregor, J.A. Lifetime oncogenic
    1981      feeding study of Captan Technical in CD-1 mice (ICR
              derived). Chevron Environmental Health Center, Environmental
              Health and Toxicology. Submitted by Chevron Chemical
              Company, Richmond, CA, to WHO. (Unpublished)

    Daly, I.W. & Knezevick, A.L. A lifetime oral oncogenicity study of
    1983      Captan in mice. Bio/dynamics Inc. Submitted by Chevron
              Chemical Company to WHO. (Unpublished)

    Goldenthal, E. Two-year oral toxicity/carcinogenicity study of Captan
    1982      in rats. International Research and Development Corporation.
              Submitted by Stauffer Chemical Company, USA, to WHO.

    Shardein, J.L. Teratology studying hamsters; amended final report.
    1983      International Research and Development Corporation, USA.
              Submitted by Chevron Chemical Company, Richmond, CA, to WHO.

    See Also:
       Toxicological Abbreviations
       Captan (HSG 50, 1990)
       Captan (ICSC)
       Captan (PIM 098)
       Captan (FAO/PL:1969/M/17/1)
       Captan (WHO Pesticide Residues Series 3)
       Captan (WHO Pesticide Residues Series 4)
       Captan (Pesticide residues in food: 1977 evaluations)
       Captan (Pesticide residues in food: 1978 evaluations)
       Captan (Pesticide residues in food: 1980 evaluations)
       Captan (Pesticide residues in food: 1982 evaluations)
       Captan (Pesticide residues in food: 1984 evaluations)
       Captan (Pesticide residues in food: 1990 evaluations Toxicology)
       Captan (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Captan (IARC Summary & Evaluation, Volume 30, 1983)