PESTICIDE RESIDUES IN FOOD - 1979
Sponsored jointly by FAO and WHO
Joint meeting of the
FAO Panel of Experts on Pesticide Residues
in Food and the Environment
WHO Expert Group on Pesticide Residues
Geneva, 3-12 December 1979
Omethoate was evaluated in 1971 and reviewed in 1975 and 1978. The
ADI established in 1971 was a temporary basis because no long-term
studies were available. Data on subacute dermal toxicity, acute and
subacute inhalation toxicity and on pharmacokinetics were received and
are reviewed, and summarized in this monograph addendum.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
Absorption, Distribution and Elimination
The distribution and elimination of 14C-omethoate was investigated in
the rat. After oral administration of 0, 3, 5 or 10 mg/kg omethoate,
96-97% of the radioactivity was eliminated within 48 hours in urine
and 1-2% in faeces. Over this period, about 1% of the radioactive
dose was exhaled as 14CO2. Intravenous injection of 0.3 mg/kg
resulted in a similar rapid elimination pattern. Maximal tissue
residues were reached one hour after administration. After the first
eight hours, about 18% of the residual radioactivity was observed in
the body. After 2 days, less than 0.55% of the administered dose was
observed. From quantitative data and whole body autoradiography, a
relatively homogeneous distribution of 14C-activity was observed,
with the exception of the thyroid, in which a 10-20 fold higher
concentration was found (Weber, et al., 1978).
Acute Inhalation Toxicity
Groups of 10 Wistar rats of each sex were exposed by inhalation to
aerosols of omethoate and observed for 14 days. Estimates of the
LC50 are summarized in Table 1.
Table 1. Exposure by inhalation of rats to aerosols of omethoate
Exposure time LC50 (mg/m3) Lowest concentration causing
clinical signs of poisoning
1 hour 1000 338
4 hours 300 (male) <60
220 (female) 60
5 × 4 hours <49 13
Clinical signs of poisoning were observed for up to 10 days after
exposure. Acetylcholinesterase depression in plasma and erythrocytes,
measures in the multiple-exposure experiment, was found to be
dose-related. Cholinesterase activity was depressed at all dose
levels tested. Three days after the last exposure, no enzyme
inhibition was noted in plasma. This recovery was not noted with
erythrocyte cholinesterase. No treatment-related pathological effects
were observed in the lungs (Thyssen, 1978).
Subacute Dermal Toxicity
Groups of rabbits (3 male and 3 female rabbits per group) were
dermally administered 0, 2.5 or 20 mg/kg body weight omethoate in
aqueous solutions for three weeks (7 hours/day, 5 days/week) to the
intact or abraded skin. No dose-related effects were observed on body
weight or a variety of clinical chemistry, hematological, or
urological parameters. The gross weight of tissues and organs (heart,
lungs, liver, spleen, kidneys, adrenals, thyroid, testes and ovaries)
did not deviate from control values. Pathological examination of
these organs, as well as of the uterus, epididymis, and skin showed no
changes attributable to dermal omethoate treatment.
Inhibition of acetylcholinesterase activity in plasma, erythrocytes,
and brain was observed in those rabbits receiving 20 mg/kg. After 1-3
days of treatment, the enzyme depression was accompanied by clinical
signs of poisoning in animals with abraded skin. In the lower dose
group, only females with abraded skins showed an inhibition of brain
cholinesterase activity (Flucke and Luckhaus, 1979).
Additional information was reviewed confirming that omethoate-induced
inhibition of cholinesterase is the most predominant toxicological
parameter as was previously noted in acute and subacute experiments.
Omethoate is rapidly absorbed following oral administration, and
elimination is complete within a few days. The residual
concentrations found in specific organs of the body decreased very
rapidly after administration, with the exception of the thyroid gland,
in which elimination was relatively slow.
The meeting was informed that the previously required long-term study
was complete, and the report was to be made available shortly. The
existing temporary ADI was therefore extended.
Level Causing No Toxicological Effect
Rat: 1.0 ppm in the diet, equivalent to 0.05 mg/kg body weight
Dog: 1.6 ppm in the diet, equivalent to 0.12 mg/kg body weight
ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR MAN
0-0.0005 mg/kg body weight
FURTHER WORK OR INFORMATION
Required by June 30, 1980:
Report of the long-term study.
Information on the possible accumulation of omethoate in the thyroid.
Flucke, W. and Luckhaus, G. Folimat-Wirkstoff (S 6876, Omethoat).
Subkuter kutaner Toxizitätsversuch an Kanichen. (1979) Unpublished
report submitted by Bayer AG.
Thyssen, J. S 6876 (Folimat-Wirkstoff). Akute Inhalationstoxizität.
(1978) Unpublished report submitted by Bayer AG.
Weber H., Patzschke, K., and Wegner, L.A. Omethoat-14C
(Folimat(R)-Wirkstoff). Biokinetische Untersuchungen an Ratten.
(1978) Unpublished report submitted by Bayer AG.