This pesticide was evaluated for acceptable daily intake by the Joint
    Meeting in 1965 (FAO/WHO 1965 ). Additional studies on biochemistry,
    long term studies in animal species other than the rat and
    reproduction studies were required.

    Since the previous evaluation new data on acute toxicity and
    teratogenicity, have been presented and are summarized in the
    following monograph addendum.



    In mice, labelled methoxychlor given orally was eliminated to the
    extent of 98.3% within 24 hours.
    and 2,2 bis(p-hydroxyphenyl)-1,1,1-trichloroethane were, identified
    (Metcalf et al., 1970).


    Special study on teratogenicity

    Groups of pregnant rats received oral closes of methoxychlor at dose
    levels of 0, 34.6, 138, 242 and 346 mg/kg from gestation day 6 through
    15. The number of resorptions in animals at 242 and 346 mg/kg, was
    increased in comparison with the control. With the exception of the
    242 mg/kg group foetal weight was decreased. No abnormalities by
    external, visceral and skeletal examination wore observed (Ravert and
    Parke, 1976).

    Special studies on carcinogenicity

    In their evaluation of 4 oral feeding studies in rats and of 2 studies
    in mice with skin painting and with subcutaneous application a group
    of experts convened by IARC, concluded.

    Methoxychlor was tested by the oral route only in the rat. Three
    experiments, including one employing dietary levels of up to 1600 ppm
    (equivalent to about 80 mg/kg bw/day), provided no evidence of
    carcinogenicity. Because of inadequate reporting, conclusions cannot
    be drawn from the results of a fourth experiment in which some liver
    tumours were observed in rats fed up to 2000 ppm in the diet
    (equivalent to about 100 mg/kg bw/day). Data from these four
    experiments do not allow an evaluation of the carcinogenicity of
    methoxychlor to be made at the present time.

    No tumours were reported in limited skin application and subcutaneous
    injection (simple-dose) studies (IARC, 1974).

    Since then further studies have become available:

    2 groups of 50 male B6C3F1 mice were administered in the diet 1750 and
    3500 ppm methoxychlor while 2 groups of 50 female mice received 1000
    and 2000 ppm for 78 weeks. The animals were then kept on basal diet
    for another 15 weeks. 2000 ppm was the maximum tolerated dose. 20
    animals of each sex served as controls. A close-related body weight
    depression of 15-20% was observed only in females, however no effect
    on survival was detected.

    For males the actual survival was adequate, as 69 percent of the high
    dose, 58 percent of the low dose, and 45 percent of the control mice
    survived over 81 weeks. For females the actual survival was high, as
    98 percent of the high dose, 90 percent of the low dose, and 85
    percent of the control mice survived until the end of the test.

    No treatment-related organ lesions occurred. The tumour incidence was
    similar in all groups. In males, hepatocellular carcinomas were found
    in 23% of the controls, 8% of the low and 19% of the high dose group.
    In females no liver carcinomas were found in the control and high dose
    group, whereas the incidence in the low dose group was 6%. Thus, the
    study did not provide any evidence of the carcinogenicity of
    methoxychlor in B6C3P1 mice (NCI, 1977).

    2 groups of 50 male Osborne-Mendel rats were administered in the diet
    360 -500 and 720 -1000 ppm methoxychlor for 78 weeks. This was
    followed by a period of 33 weeks on the basal diet. 2 groups of 50
    female rats received 750, and 1500 ppm for 78 weeks. 20 rats of each
    sex served as controls.

    Weight gain was reduced in both groups by 5 -25%. No effect on
    survival was recorded: 86% of the high dose males, 74% of the low dose
    and 85% of the controls lived at least 100 weeks. In all female groups
    more than 90% survived 100 weeks.

    Inflammatory, degenerative and proliferative lesions as seen in the
    control and treated animals were similar in number and kind to
    spontaneous lesions occurring in aged Osborne-Mendel rats. In regard
    to neoplasms, hemangiosarcomas were the only tumours observed at
    unusually high incidences.

    The hemangiosarcomas occurred in the spleen of 1/20 control males,
    6/44 low dose males, 2/42 high dose males, and 1/20 control females.
    Hemangiosarcomas also occurred as subcutaneous masses in 2/50 low dose
    males and as an abdominal tissue mass in 1/50 low dose male rats.
    Thus, there was an increased incidence of hemangiosarcomas at all
    sites in male rats receiving methoxychlor (9 low dose and 2 high dose)
    as compared to a single control male and a single control female with
    these tumours.

    With the exception of a hemangiosarcoma in the spleen of one control
    female there were no unusual tumours or any unusual incidences of

    spontaneous tumours in the female rats. The occurrence of these
    tumours was not statistically significant.

    Acute Toxicity

              Species   Sex  Route     LD50      References

              Rat       F    Oral      3460      Terrell & Parke, 1976


    Several new studies were examined by the Meeting.

    Methoxychlor is mainly degraded by hydrolysis of the methyl ether
    leading to a polar phenol which is rapidly excreted.

    Methoxychlor does not exhibit a teratogenic potential in rats.

    Several carcinogenicity studies in rats and mice at dose levels up to
    3500 ppm were negative. Therefore the ADI for humans established in
    1965 remains unchanged.


    Level causing no toxicological effect

        Rat: 200 mg/kg in the diet, equivalent to 10 mg/kg bw


    0-0.1 mg/kg bw


    FAO/WHO. (1965) Evaluation de la toxicité de résidues pesticides dans
    les denrées alimentaires. WHO/Food. Add./27.65.

    IARC. (1974) Monographs on the evaluation of carcinogenic risks of
    chemicals to man. Vol. 5, 193. International Agency for Research on

    Metcalf, R.L., Kapoor, I.P., Nystrom, R.F. and Sangha, G.K. (1970)
    Comparative metabolism of methoxychlor, methioclor and DDT in mouse,
    insects and in a model ecosystem. J. agric. Ed Chem. 18, 1145.

    NCI. (1977) Bioassay of Methoxychlor for Possible Carcinogenicity,
    Carcinogenesis Testing Program, Division of Cancer Cause and
    Prevention. National Cancer Institute, National Institutes of Health.
    (Unpublished Report).

    Ravert, J. and Parke, G.S.E. (1976) Investigation of teratogenic and
    toxic potential of methoxychlor in rats. Unpublished report from
    Cannon Laboratories Inc.

    Terrell, Y. and Parke, G.S.E (1976) Acute oral toxicity in rats of
    technical methoxychlor. Unpublished report from Cannon Laboratories,

    See Also:
       Toxicological Abbreviations
       Methoxychlor (ICSC)
       Methoxychlor (FAO Meeting Report PL/1965/10/1)
       Methoxychlor (IARC Summary & Evaluation, Volume 5, 1974)
       Methoxychlor (IARC Summary & Evaluation, Volume 20, 1979)