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

    EVALUATION OF THE TOXICITY OF PESTICIDE RESIDUES IN FOOD

    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
    1965

                
    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

    DEMETON-S-METHYL SULFOXIDE

    Chemical name

         S dimethyl-[2-(ethylthionyl)ethyl]-phosphorothiolate;
    O,O-dimethyl-S [2(ethyl-sulfinyl)ethyl]phosphorothioate.

    Synonyms

         Isomethylsystox-sulfoxide; metasystox R; oxydemeton-methyl;
    meta-isosystox sulfoxide.

    Empirical formula

         C6H15O4PS2

    Structural formula

    

    BIOLOGICAL DATA

    Biochemical aspects

         Demeton-S-methyl sulfoxide is produced in plants from the
    metabolism of demeton-S-methyl. The sulfoxide is further broken down
    by plants and animals. After injection into mice, 97-98% is rapidly
    eliminated (Niessen et al., 1963).

         In vitro: Molar concentrations necessary to produce 50%
    inhibition of sheep erythrocyte cholinesterase expressed as; I50 in
    30 minutes at 37°C are as follows (Heath & Vandekar, 1957):

    demeton-S-methyl P=O isomer 6.5 × 10-5

    demeton-S-methyl sulfoxide 4.1 × 10-5

    demeton-S-methyl sulfone 2.3 × 10-5

    Acute toxicity

                                                                        
    Animal             Route        LD50 mg/kg    References
                                    body-weight
                                                                        

    Mouse              Oral             30        DuBois & Plzak, 1962

    Mouse         Intraperitoneal      8-12       DuBois & Plzak, 1962
                                                  DuBois & Plzak, 1962

    Rat                Oral            30-75      Mühlmann & Tietz, 1956
                                                  Schrader, 1963

    Rat           Intraperitoneal       20        DuBois & Plzak, 1962

    Rat             Intravenous         47        Heath & Vandekar, 1957

    Guinea-pig         Oral             120       DuBois & Plzak, 1962

    Guinea-pig    Intraperitoneal       30        DuBois & Plzak, 1962
                                                                        

         Rat. In groups of 20 rats, administration of the sulfoxide by
    mouth in doses of 5 mg/kg body-weight daily for 3 months caused no
    signs of intoxication or pathological changes, and 10 mg/kg
    body-weight for 21 days caused an inhibition of cholinesterase
    activity after 4.6 days (Wirth, 1958).

         Groups of 6 males and 6 female rats received concentrations of 20
    ppm or less in the diet for a period of 16 weeks: no significant
    influence on growth-rate or food consumption was observed. Ten ppm or
    less caused no significant depression of erythrocyte cholinesterase
    activity. Gross and microscopic examination of the tissues of rats
    revealed no indication of toxic effects except for fatty changes in
    the livers of some of the rats fed 10 ppm and 20 ppm (Bär, 1963). 50
    ppm for 6 months had no effect on weight gains in a group of 6 rats
    and showed no pathological changes attributable to the action of the
    compound. The brain and blood cholinesterase activity was strongly
    inhibited (Vandekar, 1958). Concentrations of 100 and 200 ppm produced
    signs of intoxication in the first 3 weeks of the experiment.

         Dog. Diets containing 5, 10 and 20 ppm have been fed to male
    and female beagle dogs for periods of 12 weeks. None of these dose
    levels produced significant changes in food consumption or body-weight
    or gave rise to cholinergic symptoms. Levels of 10 ppm or less did not
    cause significant inhibition of serum or erythrocyte cholinesterase
    activity (Root et al., 1963).

    Long-term studies

    No data available.

    Comments on experimental studies reported

         When compared with highly purified demeton-S-methyl,
    demeton-S-methyl sulfoxide is about 30% more toxic than
    demeton-S-methyl. The inhibition of cholinesterase activity is
    greater. Long-term toxicity tests on rats have not been carried out.

    EVALUATION

    Level causing no significant toxicological effect

         Rat. 10 ppm, equivalent to 1 mg/kg body-weight, causes no
    significant inhibition of cholinesterase.

         Dog. 10 ppm - equivalent to 0.25 mg/kg body-weight per day did
    not show an effect.

    Estimate of acceptable daily intake for man

         0-0.0025 mg/kg body-weight per day.

    Further work desirable

         Chemical composition and toxicity of the residues. Observations
    on the effect in man. Reproduction studies in the rat.

    REFERENCES

    Bär, F. (1963) Personal communication

    DuBois, K. & Plzak, G. J. (1962) Toxicol. Appl. Pharmacol., 4, 621

    Heath, D. F. & Vandekar, M. (1957) Biochem. J., 67, 187

    Mühlmann, R. & Tietz, H. (1956) Höfchen-Briefe, 9, 116

    Niessen, H., Tietz, H., Hecht, J. & Kimmerli, G. (1963)
    Arch. Toxikol., 20. 44

    Root, M., Gowan, J. & Doull, J. (1963) Confidential report.

    Schrader, G. (1963) Die Entwicklung neuer insectizider
    Phosphorsäure-Ester, Verlag Chemie GMBH, Weinheim

    Vandekar, M. (1958) Brit. J. industr. Med., 15, 158

    Wirth, W. (1958) Arch. exp. Path. Phamacol., 234, 352
    

    See Also:
       Toxicological Abbreviations
       Demeton-S-methyl sulfoxide (Pesticide residues in food: 1984 evaluations)