Sponsored jointly by FAO and WHO


    Food and Agriculture Organization of the United Nations


    pesticide residues in food:
    1981 evaluations

     the monographs

    data and recommendations
    of the joint meeting
    of the
    FAO panel of experts on pesticide residues
    in food and the environment
    and the
    WHO expert group on pesticide residues

    Geneva, 23 November-2 December 1981

    Rome 1982



         Omethoate was evaluated in 1971 and reviewed in 1975, 1978 and
    1979 (FAO/WHO 1972b, 1976b, 1979b and 1980b).* A temporary ADI was
    established in 1971 and the submission of a long-term study required.
    In addition to the report of the long-term study in rats, the results
    of a multi-generation study in rats, of an acute oral study, of a
    mutagenicity study, degradation in soil and data on residues from
    supervised trials have been received and are included in this
    monograph addendum.



    Acute toxicity

         LD50 of omethoate metabolite in male rats, dosed orally with
    aqueous solution, was 908 mg/kg (Flucke 1978).

    Long-term studies


         Four groups of 50 male and 50 female Wistar rats were maintained
    for 24 months on a diet containing omethoate at concentrations of 0.3,
    1, 0, 3 and 10 mg/kg. The control group consisted of 100 males and 100

         Omethoate did not clearly affect behaviour, body weight, survival
    rate, food intake, haematological parameters, clinical chemistry and

         Plasma and erythrocyte cholinesterase activities, measured in 5
    males and 5 females of each group at 1, 2, 4, 8, 13, 26, 52 and 78
    weeks and at the end of the study, were statistically significantly
    depressed in both sexes at 10 mg/kg diet. Erythrocyte cholinesterase
    activity was also inhibited in both sexes in the 3 mg/kg diet group.
    The suppression of brain cholinesterase, as measured in 10 males and
    10 females per group, was dose-related in the 3 and 10 mg/kg diet
    group in both sexes. In addition, brain cholinesterase was also
    significantly affected in females in the 1 mg/kg group, which can be
    considered as a marginal no-effect level.


    *  See Annex II for FAO and WHO documentation.

         Gross and microscopic examination revealed no indication of a
    diverse effect of omethoate. The tumour incidence was not clearly
    affected by treatment (Bomhard  et al 1979).

    Special studies on reproduction

         Groups of FB30 Long Evans rats (10 males and 20 females per
    group) were fed omethoate (94%) in the diet at concentrations of 0, 1,
    3 and 10 ppm for about 10 weeks, after which they were mated to
    initiate a standard 3-generation, 2-litter-per-generation,
    reproduction study. Four days after birth, the litters were reduced to
    10. Immediately after birth, litters were examined for malformations.
    At the age of 8 weeks, the offspring were sacrificed and subjected to
    gross examination. Ten males and 10 female rats of the F3b generation
    of all dose groups were examined histopathologically 4 weeks after

         There were no clear effects either on mating performance and
    pregnancy rate, mortality, or type and distribution of abnormalities.
    In the second generation the litter size was reduced in the 3 and
    10 ppm groups.

         In the F2b litters, litter size was reduced at both 3 and 10 ppm
    after 4 days and at 10 ppm only after 28 days. Since this effect was
    observed only in a single progeny generation, 3 ppm could be
    considered as a no-effect level with regard to reproduction (Löser

    Special studies on mutagenicity

         In a micronucleus test, male and female mice were given
    2 × 6 mg/kg bw or 2 × 12 mg/ kg bw at 30 and 6h before necropsy.
    Omethoate did not increase the frequency of micro-nucleated
    erythrocytes in the bone marrow. The animals, especially those in the
    high-dose group, showed clear clinical symptoms (Herbold 1981).

         Omethoate was examined for mutagenic activity in a series of
     in vitro microbiological assays, using the  Salmonella typhimurium 
    strains TA 1535, TA 100, TA 1537 and TA 98. Each plate was run with
    and without liver homogenate (S-9 mixture). Omethoate was mutagenic
    in strain TA 1535 (2 experiments), TA 100 (2 experiments) and TA 98 (1
    experiment). No mutagenic activity could be observed in strain TA 1537
    (Herbold 1980).



         Some information was provided (Bayer 1981) on residues of
    omethoate occurring on potatoes and sugarbeet following repeated (3 or
    4) treatments at recommended levels. In all cases, residues at harvest
    (about 35 and 80 days after last treatment respectively) were below
    the level of determination of 0.01 mg/kg. Steadily declining residues
    were found on sugarbeet leaves (3, 0.9, 0.4, 0.2 and 0.1 mg/kg at 0,
    14, 28 and 35 days respectively); at harvest (85 days) no detectable
    residue remained.


    In soil

         Omethoate is rapidly degraded in soil. By 16 days after
    application of 14C-labelled omethoate to a standard soil, 48% of the
    14C activity had been eliminated as 14CO2 (Wagner  et al 1978). As
    intermediates in this degradation, the following conversion products,
    shown in Figure 1, were isolated and identified by NMR and MS:

    I    Omethoate

    II   (Phosphonothio)acetic acid

    III  O-Methyl S-methylcarbamoylmethyl hydrogen phosphorothioate

    IV   2-Mercapto-N-methylacetamide

    V    N, N'-Dimethyl-2,2'-dithiodi(acetamide)

    VI   2-(Methylcarbamoylmethyldithio)acetic acid

    VII  N-Methyl-2-methylsulphinylacetamide

    VIII N-Methyl-2-methylsulphonylacetamide

    IX   N,N' -Dimethyl(thio-oxamide)

    X    N,N'Dimethyloxamide

    XI   N-Methyloxamic acid

    XII  Dimethyl hydrogen phosphate

    FIGURE 1

         Of the compounds identified, amounts of I, II, III, V, VI and
    VIII were measured over a period of 112 days as shown in Table 1. The
    other materials listed were shown to be labile intermediates in the
    degradation of omethoate in soil. Similar information is being
    obtained on the degradation of omethoate in plant tissue.

    TABLE 1.  Degradation pattern of 14C-omethoate in soil

                              % of 14C applied

    Days    I          II      III+ VI1     V       VIII    Total

    9       37         3.4       4.2       2.6      <0.1      49

    21      29         5.2       4.0       2.3       0.8      45

    49      17         6.3       4.9       1.3       1.8      32

    85       2.4       0.7       3.9       0.2       2.4      11

    112     <1        <0.3       3.5      <0.1       2.7       7

    1  III and VI were not separated in these determinations.



         In a long-term study in rats, at levels of 3 and 10 ppm in the
    diet, a clear indication of cholinesterase inhibition was evident in
    brain, plasma and red blood cell cholinesterase. At the 1 ppm level,
    no clear effect was observed on cholinesterase activity in plasma
    or red cells in either sex. However, in females receiving 1 ppm
    omethoate in the diet a slight depression (ca. 12%) of brain
    acetylcholinesterase was observed. A no-effect level of 3 ppm in the
    diet could be estimated from a rat 3-generation reproduction study.

         Omethoate was mutagenic in strains TA 1535, 100 and 98 of
     Salmonella typhimurium used in the Ames test. However, no activity
    was observed in TA 1537. No mutagenic activity was detected in a
    micronucleus test and a dominant lethal test previously evaluated. A
    long-term rat study did not indicate carcinogenic potential. In this
    study, the highest dose level (10 ppm) failed to elicit any effect
    other than cholinesterase depression. The relatively low dose levels
    used in this study preclude adequate carcinogenicity evaluation.

    Therefore, the temporary ADI has been extended. Submission of results
    of carcinogenicity studies at higher levels in a rodent species is
    required by 1985.

         Information regarding the degradation of omethoate in soil was
    reviewed, together with a limited amount of additional data on
    residues from supervised trials on potatoes and sugarbeet.

    Levels causing no toxicological effect

         Rat: 1 ppm in the diet equivalent to 0.05 mg/kg bw/day

         Dog: 1.6 ppm in the moist diet equivalent to 0.12 mg/kg bw/day.

    Estimate of temporary acceptable daily intake for man

         0 - 0.0005 mg/kg bw.


         No change is suggested in the maximum residue limits previously


    Required (by 1985)

         Carcinogenicity studies in a rodent species at higher dose


         Clarification of the mutagenic potential in micro-organisms, in
    respect to the "marginal effect" of omethoate in some strains of


    Bayer Reports on omethoate residue trials. Data from Bayer AG,
    1981      Leverkusen. (Unpublished)

    Bomhard, E. S-6876 - Chronische Toxizität an Ratten 22 Oktober,
    1980      Stellungnahme zu Bericht Nr. 8607. Report of the Bayer AG
              Institut für Toxikologie, submitted to WHO by Bayer AG.

    Bomhard, E., Löser, E. and Kaliner, G. S-6876 - chronic toxicity study
    1979      on rats (two-year feeding experiment). Report of the Bayer
              AG Institut f. Toxikologie, submitted to WHO by Bayer AG.

    Flucke, W. Akute orale Toxizität "Omethoat-Metabolit" 23 Oktober.
    1978      Report of the Bayer AG Institut für Toxikologie, submitted
              to WHO by Bayer AG; (Unpublished)

    Herbold, B. S-6876-Salmonella/Mikrosomen-Test zur Untersuchung auf
    1980      punktmutagene Wirking. Report of the Bayer AG Institut für
              Toxikologie, submitted to WHO by Bayer AG. (Unpublished)

    Löser, E. S-6876-Folimat-Wirkstoff Multigenerationeversuche an Ratten
    1981      21 Januar, Bericht Nr. 9731. Report of the Bayer AG Institut
              für Toxikologie, submitted to WHO by Bayer AG. (Unpublished)
              Addendum: Histopathology - Consultox Laboratories Ltd.,

    Wagner, K., Neitzel, H. and Oehlmann, L. Metabolismus von Omethoat im
    1978      Boden. Report submitted by Bayer AG, Leverkusen.

    See Also:
       Toxicological Abbreviations
       Omethoate (WHO Pesticide Residues Series 1)
       Omethoate (WHO Pesticide Residues Series 5)
       Omethoate (Pesticide residues in food: 1978 evaluations)
       Omethoate (Pesticide residues in food: 1979 evaluations)
       Omethoate (Pesticide residues in food: 1980 evaluations)
       Omethoate (Pesticide residues in food: 1984 evaluations)
       Omethoate (Pesticide residues in food: 1985 evaluations Part II Toxicology)