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


    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

    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


    Chemical name

           1,1,1-trichloro-2,2-di-(p-methoxyphenyl) ethane;
    2,2-di-4-anisyl, 1,1,1,trichloroethane,
    di-(p-methoxyphenyl)-trichloromethyl methane;


           DMDT; dimethoxy-DT; marlate.

    Empirical formula


    Structural formula



    Biochemical aspects

           Methoxychlor is not excreted intact, and appears to undergo
    metabolize yielding hydroxyphenyl derivatives (von Oettingen &
    Sharpless, 1946).

           Methoxychlor is very rapidly detoxicated in the liver, yielding
    a metabolite which is excreted into the intestine and removed from the
    body in the faeces. This rapid detoxication, together with fairly slow
    gastro-intestinal absorption, explains the low mammalian oral toxicity
    and low tissue storage of methoxychlor (Weikel, 1957).

           Some tissue and fat storage takes place and reaches a maximum 
    in 4 weeks; the stored material is mobilized in 2-4 weeks after 
    exposure ceases (Kunze et al., 1950; Metcalf, 1955).

           Methoxychlor showed very little tendency to be excreted in the
    milk even when dietary concentrations up to 7000 ppm were given to

    dairy cows. At 800 ppm and 7000 ppm the amounts found in the milk were
    0.13 ppm and 2.14 ppm respectively at 16 weeks (Gannon et al., 1959).
    The rate and completeness of methoxychlor metabolism may account for
    the low storage and accumulation.

    Acute toxicity

    Animal     Route    LD50 mg/kg     References

    Mouse      Oral        1850        Domenjoz, 1946

    Rat        Oral      5000-7000     Hodge et al., 1950
                                       Lehman, 1951
                                       Smith et al., 1946

    Sheep      Oral        >2000       Negherbon, 1959
                                       Welch, 1948

    Steer      Oral        >500        Negherbon, 1959
                                       Welch, 1948

    Short-term studies

           Rat. Groups of weaned rats, each of 10 males and 10 females per
    group, were fed for 45 days on a ration containing 100, 1000 and 30
    000 ppm methoxychlor. At 100 ppm there was no effect on growth; at
    1000 ppm growth was slightly retarded; at 30 000 ppm very little
    growth occurred. At 10 000 ppm, rats in paired-feeding tests over 30
    days showed marked growth reduction attributed to a reduced food

           There were no deaths in the 100 ppm and 1000 ppm groups; 8 of 10
    rats died in each of the male and female groups receiving 30 000 ppm.
    The blood picture was normal. At autopsy there was no significant
    difference in the organ-weights of the rats on 100 ppm and 1000 ppm.
    The 30 000 ppm group showed uniformly smaller organ-weights than the
    controls. In the case of the testes, the decrease in weight was very
    marked. There was no evidence of histopathological change in the
    organs examined, except in the testes, which showed apparent
    suppression of spermatogenesis beyond the spermatogonial phase; the
    spermatogonia and Sertoli cells were relatively normal; the primary
    spermatocytes were variable in number, usually with evidence of
    necrosis. The more mature germ cells were absent (Hodge et al., 1950).

           In paired-feeding experiments in which 10 000 ppm of 
    methoxychlor were added to the diet of weanling male rats, a marked 
    reduction in the weight of the testes, seminal vesicles and prostate 
    was found. These effects could be mediated through an oestrogenic 
    action inhibiting the production of anterior pituitary gonadotrophins 

    with consequent deficiencies in the development of the male 
    reproductive system. Cystic tubular nephropathy was also observed 
    (Tullner & Edgcomb, 1962).

           Rabbit. Daily oral doses of 200 mg/kg body-weight killed the
    rabbits after 4 to 15 days. The only symptoms noted were diarrhoea and
    anorexia (Smith et al., 1946; Von Oettingen, 1955). Dermal application
    of 2 or 3 ml of a 30% solution (in dimethyl phthalate) 5 days a week
    for 13 weeks was toxic; growth was depressed and paralysis of the
    forelegs occurred in some cases. Histopathological examination showed
    some fatty degeneration of the liver and lesions of the central
    nervous system. Applications of 1 ml or less had no effect (Haag et
    al., 1950).

           Dog. Groups, each of 2 dogs, were maintained for one year on
    doses of 20, 100 and 300 mg/kg body-weight per day. There were no
    deaths; the blood picture and organ-weights were normal; there were no
    histopathological changes (Hodge et al., 1952).

    Long-term studies

           Rat. Groups each of 25 male and 25 female rats were fed for 2
    years on diets containing 25, 200 and 1600 ppm of methoxychlor. There
    was no effect on growth at doses of 25 ppm and 200 ppm in the diet,
    but there was moderate reduction in growth at 1600 ppm. There was no
    decrease in life-span; organ-weights and blood picture were
    essentially normal and histopathological examination revealed no
    significant changes (Hodge et al., 1952).

    Comments on the experimental studies reported

           From the studies reported the rat appears more sensitive than 
    the dog. Experiments with the rat covered the life-span and may be 
    used to estimate the acceptable daily intake for man.


    Level causing no toxicological effect in the rat

           The maximum no-effect level in rat was 200 ppm in the diet,
    equivalent to 10 mg/kg body-weight per day.

    Estimate of acceptable daily intakes for man

           0-0.10 mg/kg body-weight

    Further work desirable

           Additional biochemical studies. Long-term toxicity studies in
    another species than the rat. Reproduction studies.


    Domenjoz, R. (1946) Arch. int. Pharmacodyn., 73, 128

    Gannon, N., Link, R. P. & Decker, G. C. (1959) J. Agric. Food Chem.,
    7, 829

    Haag, H. B., Finnegan, J. K., Larson, P. S., Riese, W. & Dreyfuss, M.
    L. (1950) Arch. int. Pharmacodyn, 83 (4), 491

    Hodge, H. C., Elliott, A. M., Thomas, J. F., Blanchet, H. J., Wilt, W.
    G. & Mason, K. E. (1950) J. Phamacol. exp. Ther., 99, 140

    Hodge, H. C., Maynard, E. A. & Blanchet, H. J. jr (1952) J.
    Pharmacol. exp. Ther., 104, 60

    Kunze, F. M., Laug, E. P. & Prickett, C. S. (1950) Proc Soc. exp.
    Biol. (N.Y.), 75, 415

    Lehman, A. J. (1951) Quart. Bull. Assoc. Food and Drug Officials
    U.S., 15, 122

    Metcalf, R. L. (1955) Organic insecticides, Interscience, New York

    Negherbon, W. O. (1959) Handbook of Toxicology, vol. 3., Saunders,

    Smith, M. I., Bauer, H., Stohlman, E. F. & Lillie, R. D. (1946) J.
    Pharmacol, exp. Ther., 88, 359

    Tullner, W. W. & Edgcomb, J. H. (1962) J. Pharmacol. exp. Ther.,
    138 (1), 126

    Von Oettingen, W. F. & Sharpless, N. (1946) J. Pharmacol. exp.
    Ther., 88, 400

    Von Oettingen, W. F. (1955) The halogenated hydrocarbons, toxicity
    and potential dangers, United States Department of Health.
    Education and Welfare. Public Health Service Bull. No. 414

    Weikel, J. H. (1957) Arch. int. Pharmacodyn., 110 (4), 423

    Welch, H. L. (1948) J. econ. Ent., 41, 36

    See Also:
       Toxicological Abbreviations
       Methoxychlor (ICSC)
       Methoxychlor (Pesticide residues in food: 1977 evaluations)
       Methoxychlor (IARC Summary & Evaluation, Volume 5, 1974)
       Methoxychlor (IARC Summary & Evaluation, Volume 20, 1979)