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

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Table 2. Cholinesterase activity in rats fed diets containing azinphos-methyl for 28 days
Time-point
Cholinesterase activity (% inhibition relative to control values)
Dietary concentration (ppm)
5 20 50
Males Females Males Females Males Females
Plasma
Day 1 0 0 8 0 10 15
4 0 0 21/0 0 25 44*
14 0 0 21 0 33* 53**
28 0 0 26* 0 26* 61**
Erythrocytes
Day 1 0 0 0 0 0 0
4 0 0 0 +15 0 0
14 0 0 0 17* 22** 34**
28 0 0 0 22** 14** 35**
Brain
Day 28 0 0 0 0 9 53**
From Eiben et al. (1983)
* p < 0.05; ** p < 0.01.
There were no treatment-related effects on absolute organ weights or histopathological abnormalities.
The NOAEL was 0.86 mg/kg bw per day on the basis of salivation in male rats and
significant inhibition of brain cholinesterase activity at 3.44 mg/kg bw per day (Broadmeadow et al.,
1987).
Dogs
In a 52-week study of toxicity, groups of four male and four female beagle dogs were given
diets containing azinphos-methyl (purity, 91.9%) at a concentration of 0 (control), 5, 25 or 125 ppm
(equal to 0.16, 0.74, or 4.09 mg/kg bw per day). Clinical signs of reaction to treatment were confined
to a higher incidence of diarrhoea in dogs at 125 ppm. Two males at 125 ppm failed to gain weight
during the course of the study, but food intake remained unaffected by treatment. Haematology and
urine analysis revealed no indication of any reaction to treatment. Clinical biochemistry tests revealed
a depression of cholinesterase activity in plasma and erythrocytes in dogs at 25 and 125 ppm
and in brain at termination of dogs at 125 ppm (Table 4).
There was also a very slight increase, compared with controls, in liver cytochrome P450 and
N-demethylase activity at the highest dose and a reduction in albumin levels. Pathological investigations
(macroscopic examination, organ weight analysis and histopathology) revealed no evidence of
any reaction to treatment with azinphos-methyl. The NOAEL was 25 ppm (0.74 mg/kg bw per day)
on the basis of reduced body-weight gain and inhibition of cholinesterase activity in brain (modified
with reference to the original data, Allen, et al., 1990; Annex 1, reference 64).
2.3 Long-term studies of toxicity and carcinogenicity
Mice
A bioassay of azinphos-methyl (purity, 90%; from manufacturing specification) for possible
carcinogenicity was conducted by the National Cancer Institute (NCI). Osborne-Mendel rats and
AZINPHOS-METHYL 139–172 JMPR 2007