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

         2,4-dimethylbenzyl ester of chrysanthemumic acid.

    Empirical formula


    Structural formula



    Biochemical aspects

         Preliminary studies in rabbits suggested that dimethrin is
    excreted as chrysanthemumic acid and the glucuronide of
    2,4-dimethylbenzoic acid (Ambrose, 1964). Later, the two acids were
    isolated and positively identified (Masri et al., 1964a). Urine from
    rabbits and rats gave positive reduction tests with Benedict's
    reagent, which became negative when dimethrin was removed from the
    diet (Ambrose, 1964).

    Acute toxicity

         Large doses produce lassitude, anorexia, weight loss, stupor, and
    death. Hyperactivity and convulsions such as occur in poisoning by
    pyrethrins are not seen.

         Rats tolerated 14 800 mg/kg and guinea-pigs tolerated 9860 mg/kg
    given by stomach-tube (Ambrose, 1964). Mice tolerated doses as high as
    20 000 mg/kg but some were killed by 40 000 mg/kg (Preri, 1959).

    Short-term studies

         Rat. Fifteen oral doses at the rate of 9860 mg/kg caused no
    abnormality of body-weight or general appearance, or gross
    pathological findings (Ambrose, 1964).

         However, Cox (1962a) and later Masri et al. (1964b) reported
    microscopic changes in many liver cells of all rats fed 15 000 or 
    30 000 ppm for three months and in a smaller proportion of the cells 
    of some rats maintained at a dietary level of 6000 ppm. The presence
    of changes in the liver of rats fed 3000 ppm was questionable. Cox
    considered the changes similar to those produced by DDT. This
    possibility was investigated by Kimbrough, Gaines & Ortega (1964) who
    found that a dietary level of 20 000 ppm for 100 days did, in fact,
    produce an increase of liver weight and liver cell changes
    indistinguishable by light microscopy from those produced by DDT and
    described earlier by Ortega et al. (1956). Furthermore, the
    morphological details as revealed by electron microscopy are entirely
    similar to those already described for DDT (Ortega, personal
    communication 1964; Ortega, 1962).

         The morphological changes produced by high dietary levels of
    dimethrin are confined to the liver; other organs studied were: heart,
    lung, spleen, kidney, adrenal, bladder, thyroid, pancreas, intestine,
    stomach, ovary, and testis (Cox, 1962; Masri et al., 1964a).
    Furthermore, the liver cell changes produced by feeding dimethrin at a
    concentration of 20 000 ppm for three months were completely reversed
    within three months. Shorter recovery periods were not investigated
    (Cox, 1962b; Masri et al., 1964a).

         Rabbit. Four animals received technical dimethrin by
    stomach-tube at a rate of 500 mg/kg/day six days per week for a total
    of 80 to 90 doses; three of them showed more than the normal amount of
    fibrous tissue around the bile ducts, and one showed a slight
    accumulation of fat in the parenchymal cells of the liver. Rabbits
    that received both technical dimethrin and piperonyl butoxide each at
    a dosage of 125 mg/kg/day six days per week for 89 doses also showed
    an accumulation of fat in the parenchymal cells (Kimbrough, 1965).

         Dog. Two dogs given technical dimethrin by capsule at the rate
    of 125 mg/kg/day for 105 doses showed moderate accumulation of fat in
    the parenchymal cells of the liver (Kimbrough, 1965).

         Sheep. A concentration of 100 ppm in drinking-water given for 2
    days may produce diarrhoea in sheep, but the effect has not been
    observed in horses, rats, mice, rabbits, or hens (Barnes, 1963).

    Long-term studies

         Rat. According to Ambrose, 1964, dietary levels as high as 20
    000 ppm for 52 weeks caused no change in growth rate, survival, food
    consumption, haemoglobin, red and white cell counts or blood sugar.
    Dietary levels of 10 000 and 20 000 ppm produced increased

    liver-to-body-weight ratios which, however, returned to normal within
    six weeks after feeding was stopped. Liver pathology was specifically
    denied (Ambrose, 1964). However, this conclusion is contradicted by
    the results of short-term tests.

    Comments on the experimental studies reported and evaluation

         Rats tolerate a dietary level of 3000 ppm (equivalent to 150
    mg/kg/day) without any significant differences in the microscopic
    morphology of the liver or in any other parameter between the treated
    and control animals. An acceptable daily intake for man cannot be
    established until the nature and significance of the liver changes
    reported in rats at higher doses have been determined.

    Further work required

         Studies should be made of the long-term effects of dimethrin on
    the liver of at least 1 species and an effort should be made to
    evaluate the liver changes in the rat. This study should involve the
    compound alone and in combination with major synergists. A method
    should be developed to analyse a metabolite of dimethrin in human
    urine so that absorption of the compound by men with prolonged and
    intensive exposure to it may be measured.


    Ambrose, A. M. (1964) Toxicol. Appl. Pharmacol., 6, 112

    Barnes, J. M. (1963) Letter to WHO dated 21 June 1963

    Cox, A. J. jr (1962a) Unpublished report May 18

    Cox, A. J. jr (1962b) Unpublished report August 13

    Kimbrough, R. D., Gaines, T. B. & Ortega, P. (1964) Unpublished report

    Kimbrough, R. D. (1965) Unpublished report February 16

    Masri, M. S., Jones, F. T., Lundin, R. E., Bailey, G. F. & DeEds, F.
    (1964a) Toxicol. Appl. Pharmacol., 6, 711

    Masri, M. S., Hendrickson, A. P., Cox, A. J. jr & DeEds, F. (1964b)
    Toxicol. Appl. Pharmacol., 6, 716

    Ortega, P., Hayes, W. J., jr, Durham, W. F. & Mattson, A. M. (1956)
    Publ. Health Monogr. Nr. 43, PHS Pub. No. 484

    Ortega, P. (1962) Fed. Proc., 21, 306

    Preri, R. J. (1959) Assay Report from Wisconsin Alumni Research
    Foundation, W. A. R. F. No. 9110894-9110895

    See Also:
       Toxicological Abbreviations