Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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methylation and oxidation of mercaptomethyl-benzazimide forms benzazimide, methylthiomethylbenzazimide
and its corresponding oxidized metabolites. Hydrolysis of glutathionyl methylbenzazimide
may result in the formation of cysteinylmethyl-benzazimide. Subsequent oxidation of
cysteinyl-methylbenzazimide forms its corresponding sulfoxide and sulfone (Kao, 1988; Annex 1,
r eference 64).
The rate of disappearance of azinphos-methyl via a hepatic oxidative desulfurating system and
a demethylating system was investigated in liver homogenates from four different species (rat, guinea-pig,
chicken and monkey). Azinphos-methyl was metabolized by both systems and homogenates
from all species were uniformly active (Rao & McKinley, 1969; Annex 1, reference 64).
1.3 Effect on enzymes and other biochemical parameters
The acute oral toxicity of azinphos-methyl, dissolved in propylene glycol, was investigated
in groups of female mice and the effect of the oxime antidote, toxogonin (80 mg/kg bw intraperitoneally,
15 min before oral dosing), was determined. Antidote treatment reduced the toxicity of
azinphos-methyl by increasing the median lethal dose (LD 50
) by a factor of 2 (Sterri et al., 1979;
Annex 1, reference 64).
2. Toxicological studies
2.1 Acute oral toxicity
The results of studies to establish the acute toxicity of azinphos-methyl are summarized in
Table 1.
The acute oral toxicity of azinphos-methyl technical in mammals was high. Consistent with the
cholinergic effects observed with other organophosphorus compounds, signs of acute intoxication
with azinphos-methyl included diarrhoea, salivation, lacrimation and vomiting (muscarinic effects),
muscular tremors and paralysis (nicotinic effects), and restlessness, ataxia and convulsions (central
nervous system effects).
2.2 Short-term studies of toxicity
Rats
In a dose-range finding study with emphasis on the most sensitive end-point, namely inhibition
of cholinesterase activity, groups of five male and five female SPF BOR:WISW (SPF/Cpb) rats were
fed diets containing azinphos-methyl (purity, 93.3%) at a concentration of 0, 5, 20, or 50 ppm for 28
days. The average doses ingested at 5, 20, or 50 ppm were 0.35, 1.30, and 3.37 mg/kg bw per day
for males and 0.46, 1.54, and 3.96 mg/kg bw per day for females, respectively. There were no effects
on appearance, behaviour, mortality, body-weight gain, food consumption, and gross pathology. A
statistically significant reduction in plasma cholinesterase activity of 44–66%, relative to the control
group, was seen in females at 50 ppm. Appreciably less inhibition of plasma cholinesterase activity
was observed in males and this was consistent across the entire sampling period. Erythrocyte acetylcholinesterase
activity was unaffected in males at 20 ppm, but was significantly reduced (17–22%) in
females. Brain cholinesterase activity was significantly in females at 50 ppm (Table 2).
The NOAEL was 20 ppm, equal to 1.30 mg/kg bw per day in males and 1.54 mg/kg bw per day
in females, on the basis of inhibition of cholinesterase activity in the brain at 50 ppm (Eiben et al.,
1983).
AZINPHOS-METHYL 139–172 JMPR 2007