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 names

           S-methylcarbamoyl-methyl-O,O-dimethyl phosphorodithioate;
    O,O-dimethyl-S-(N-methylcarbamoylmethyl) phosphorodithioate;
    methylamide of O,O-dimethyl-dithiophosphorylacetic acid, methyl
    dimethyldithiophosphoryl acetamide.


         "Rogor", "Fortion MM"

    Empirical formula


    Structural formula



    Biochemical aspects

         Dimethoate is a cholinesterase inhibitor. The molar concentration
    of the pure compound necessary to produce 50% cholinesterase
    inhibition in the rat brain in vitro (I50) is 8.5 × 10-3. It
    decomposes to give products which are more toxic than the original
    substance (Casida & Sanderson, 1962, Casida & Sanderson, 1963).

         Various studies (O'Brien, 1959; O'Brien, 1961; Sanderson & Edson,
    1964) carried out with dimethoate labelled with 32P have shown that
    there is rapid absorption from the digestive tract. The radioactivity
    is concentrated in the liver, bile, kidneys and urine. There is no
    accumulation in the fat depots. Elimination is rapid in the rat and in
    man, 76-90% of the radioactivity being found in the urine after 24
    hours. In the guinea-pig, 25-40% of the radioactivity is recovered in
    the faeces. Four dimethoate metabolites with anticholinesterase
    activity (molar I50) s in 30 minutes at 37° in rat brain: 4.7 × 10-6;
    1.1 × 10-5; approximately 0.2 × 10-5 and approximately 0.1 × 10-5)
    have been identified in the rat and in man. One of them seems to be a
    product resulting from thiono-oxidation, leading to the formation of
    the oxygen homologue of dimethoate and followed by hydrolysis with
    production of a thiocarboxyl derivative which constitutes the chief
    metabolite of dimethoate in mammals. Although this thiocarboxyl
    derivative has not been found in treated plants, the oxygen analogue

    of dimethoate has been found in crops (Santi & de Pietri Sonelli,
    1959). Similarly, various short-lived intermediate products have been
    reported, but have not yet been accurately evaluated from the
    toxicological viewpoint (Chilwell & Beechman, 1960; Dauterman et al.,
    1960; Sampaolo, 1961; Santi & de Pietri Sonelli, 1959; Santi &
    Giacomelli, 1962).

         In vitro studies on human liver enzymes indicated that
    dimethoate could inhibit the non-specific esterases to a greater
    degree than acetylesterase (Ecobichon & Kalow, 1963).

    Acute toxicity
                                             LD50 mg/kg body-weight
    Animal                Route                    Laboratory                  References
                                        Pure          grade      Technical

    Rat, male             Oral         500-600       280-350      180-325      Sanderson &
                                                                               Edson, 1964

    Rat, female           Oral         570-680       300-356      240-336           "

    Rat, male        Intraperitoneal      -          175-325         -              "

    Rat, female      Intraperitoneal      -            350           -              "

    Rat, male          Intravenous        -            450           -              "

    Mouse, female         Oral            60            -           60              "

    Hamster, male         Oral            -            200           -              "

    Guinea-pig            Oral           550           600        350-400           "

    Rabbit                Oral           500           450      approx. 300         "

    Hen                   Oral            50            40      approx. 30          "
         Acute oral toxicity was not potentiated by any of 17 other
    insecticides (Sanderson & Edson, 1964).

    Short-term studies

         Rat. Groups of 10 male rats were fed diets containing 1, 5, 25
    and 125 ppm of dimethoate for 15 weeks. The animals were killed in
    order to determine the cholinesterase activity of the erythrocytes,
    plasma and brain as well as to examine and weigh the main organs. At
    the highest concentration, i.e., 125 ppm, a slight fall in the rate of
    gain of weight was observed as well as mild symptoms of poisoning

    (slight muscular fibrillation). In the group fed 25 ppm and higher
    concentrations, a significant fall in the cholinesterase activity of
    the plasma and erythrocytes was observed, while in the animals fed 5
    ppm a fall of 20% in cholinesterase activity was found. At 1 ppm there
    was no effect on the cholinesterase activity of the plasma,
    erythrocytes or brain (Edson & Noakes, 1960).

         Young rats in groups of 20 fed diets containing 2, 8 and 32 ppm
    of dimethoate for 90 days and other groups of 20 rats fed 50, 100 and
    200 ppm for 35 days showed no haematological abnormalities, nor any
    significant histopathological changes. Regarding the cholinesterase
    activity of the plasma and the erythrocytes the highest dose which did
    not give a significant inhibition was 32 ppm of dimethoate (West et
    al., 1961).

         Guinea-pig. Groups of guinea-pigs were fed for 3 weeks on
    lettuce and brassica leaves that had been treated with dimethoate and
    contained residues of up to 189 ppm. No toxic effects were seen and
    the cholinesterase inhibition observed was in agreement with that in
    parallel groups given daily oral doses of the same quantity of
    laboratory grade dimethoate (Sanderson & Edson, 1964).

         Chicken. In laying hens dimethoate given over a period of 59
    weeks at a concentration of 30 ppm daily in the drinking-water caused
    inhibition of plasm cholinesterase and some reduction in appetite, but
    no egg abnormalities (Sherman, et al., 1963).

         Dog. Three groups each of 4 dogs, 2 males and 2 females, were
    fed diets containing 2, 10 and 50 ppm for 13 weeks. No significant
    harmful effect was noted. The cholinesterase activity of the
    erythrocytes was only slightly decreased at the highest concentration
    of 50 ppm while that of the plasma was unaffected at any of the
    concentrations employed (West et al., 1961).

         Man. Twenty subjects ingested daily for 4 weeks 2.5 mg of
    dimethoate in aqueous solution, corresponding to about 0.04 mg/kg
    body-weight. No toxic effect was observed nor any significant change
    in the blood cholinesterase activity. The same results were found in 2
    subjects who ingested daily during 21 days, 9 mg (0.13 mg/kg) and 18
    mg (0.26 mg/kg body-weight) dimethoate respectively (Sanderson &
    Edson, 1964).

    Long-term studies

         Rat. Groups of 20 male rats were maintained for 6-12 months on
    diets containing various concentrations of laboratory grade
    dimethoate. At 800 ppm severe toxic effects developed within a few
    days; the chemical was withdrawn after a week and complete recovery
    occurred in 10-14 days. No toxic effects were seen at 50 ppm or below.
    Marked inhibition of erythrocyte cholinesterase activity occurred at
    50 ppm but at 10 ppm and below neither erythrocyte nor plasma
    cholinesterase showed significant inhibition throughout the test. At

    the end of the experiment there were no macroscopical or microscopical
    changes in any group attributable to dimethoate. The maximum no-effect
    level in these experiments corresponded to 0.5-0.8 mg/kg body-weight
    per day.

           In the same experiment further groups of 20 weanling male rats
    were treated for 5-1/2 months at dose levels of 5, 10 and 20 ppm of
    dimethoate. The maximum no-effect level in these experiments was 5 ppm
    corresponding to 0.3-0.6 mg/kg body-weight per day.

           A further test with the commercial liquid formulation of
    dimethoate on similar groups of male and female rats lasted 12 weeks.
    The maximum no-effect level was again 5 ppm corresponding to 0.4-0.6
    mg/kg body-weight per day (Sanderson & Edson, 1964).

    Comments on the experimental studies reported

           Short-term studies have been made on a number of species, in the
    rat for as long as one year. Some observations have also been made in
    man, and if adequate studies were carried out to establish a level
    causing minimal blood cholinesterase inhibition it might be possible
    to increase the acceptable daily intake.

           It was noted that in the experiment on guinea-pigs fed with
    treated vegetation the inhibition of cholinesterase activity produced
    by the residue in the plant was equivalent to that produced by
    laboratory grade dimethoate.


    Level causing no significant toxicological effect

           Rat. 5 ppm in the diet according to the weight of the animals
    used in the experiment is approximately equivalent to 0.4 mg/kg

           Man. 0.04 mg/kg body-weight per day.

    Estimate of acceptable daily intake for man

           0-0.004 mg/kg body-weight.

    Further work desirable

           Chemical composition and toxicity of the residues. Reproduction
    studies in the rat.


    Casida, J. E. & Sanderson, D. M. (1962) Nature, 189, 507

    Casida, J. E. & Sanderson, D. M. (1963) J. Agr. Food Chem., 2, 91

    Chilwell, E. D. & Beechman, P. T. (1960) J. Sci. Food Agric., 2,

    Dauterman, W. C. et al. (1960) J. Agr. Food Chem., 8, 115

    Ecobichon, D. J. & Kalow, W. (1963) Canad. J. Biochem., 41, 1537

    Edson, E. F. & Noakes, D. N. (1960) Toxicol. Appl. Pharmacol., 2,

    O'Brien, R. D. (1959) Nature, 183, 121

    O'Brien, R. D. (1961) Biochem. J., 79, 229

    Sampaolo, A. (1961) C.R. Ist Super. Sanità, 24, 936

    Sanderson, D. M. & Edson, E. F. (1964) Brit. J. industr. Med., 21,

    Santi, R. & de Pietri Sonelli, P. (1959) Nature, 183, 398

    Santi, R. & Giacomelli, R. (1962) J. Agr. Food Chem., 10, 3

    Sherman, M., Ross, E., Sanchet, F. F. & Chang, M. T. Y. (1963)
    J. econ. Ent., 56, 10

    West, B., Vidone. L. B. & Shaffer, C. B. (1961) Toxicol. Appl.
    Pharmacol., 3, 210

    See Also:
       Toxicological Abbreviations
       Dimethoate (EHC 90, 1989)
       Dimethoate (HSG 20, 1988)
       Dimethoate (ICSC)
       Dimethoate (FAO/PL:CP/15)
       Dimethoate (FAO/PL:1967/M/11/1)
       Dimethoate (JMPR Evaluations 2003 Part II Toxicological)
       Dimethoate (AGP:1970/M/12/1)
       Dimethoate (Pesticide residues in food: 1983 evaluations)
       Dimethoate (Pesticide residues in food: 1984 evaluations)
       Dimethoate (Pesticide residues in food: 1984 evaluations)
       Dimethoate (Pesticide residues in food: 1987 evaluations Part II Toxicology)
       Dimethoate (Pesticide residues in food: 1996 evaluations Part II Toxicological)