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

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Table 8. Fertility of F 0
and F 1b
rats fed diets containing azinphos-methyl
Parameter
Dietary concentration (ppm)
0 5 15 45
Mating 1/2 Mating 1/2 Mating 1/2 Mating 1/2
F 0
Mated females (No.) 24/24 24/24 24/23 23/19
Insemination index (%) 100/100 95.8/100 91.6/91.3 95.6/94.7
Fertility index (%) 91.7/91.7 95.7/95.8 90.0/85.7 86.4/83.3
Gestation index (%) 100/100 100/100 100/100 100/93.3
Duration of gestation (days) 22.5/22.3 22.5/22.7 22.5/22.6 22.8/22.8
F 1b
Mated females (No.) 24/24 24/24 24/23 5/5
Insemination index (%) 100/100 100/100 100/100 100/100
Fertility index (%) 91.7/87.5 100/91.7 87.5/95.7 100/80.0
Gestation index (%) 100/95.2 100/100 100/95.5 100/75.0
Duration of gestation (days) 22.1/22.2 22.3/22.6 22.6/22.2 22.4/22.3
From Eiben & Janda (1987); Annex 1, reference 64, modified by reference to original data.
At 45 ppm, two females that were sacrificed in extremis exhibited clinical signs consistent
with cholinergic effects, such as poor general condition, bloody noses, inertia and a stumbling gait.
Males at the same dietary concentration showed no clinical signs. There were no treatment-related
effects on fertility parameters (insemination, fertility and gestation indices, and duration of gestation)
(Table 10). At 15 ppm, when males and females were treated, the viability index was slightly reduced
but it was in the absence of any corresponding reduction in pup body-weight gain. In contrast, dams
at 45 ppm delivered pups that had significantly reduced viability and body-weight gain by postnatal
day 5. After treatment of male parental animals only, reproductive parameters remained unaffected,
even at 45 ppm (Table 11). Investigations of cholinesterase activity in parental animals revealed a
depression in activity in plasma and erythrocytes at all dietary concentrations, and a depression in
activity in brain at 45 ppm in males and at 15 and 45 ppm in females (Table 12).
There were no treatment-related clinical signs observed in F 1
pups at birth or during the 4-week
rearing period. Similarly, no treatment-related pathological changes were observed.
At 45 ppm, brain cholinesterase activity in pups was also depressed. The NOAEL was 5 ppm,
equal to 0.55 mg/kg bw per day, on the basis of depression of brain cholinesterase activity at 15 ppm
(Holzum, 1990; Annex 1, reference 64, modified by reference to original data).
(b)
Developmental toxicity
Mice and rats
The effects of azinphos-methyl (purity, 90.6%) on development in rats and mice were investigated
in a series of experiments. On the basis of preliminary studies of toxicity, doses of 0, 1.25,
2.5 or 5.0 mg/kg bw per day were selected for two-phase studies of developmental toxicity in both
species. During the first phase, pregnant rats and mice were treated for 10 days, starting on day 6
of gestation. During the second phase, pregnant rats were treated from day 6 of gestation to postnatal
day 21. In the first phase, maternal toxicity was seen only in rats receiving the highest dose.
When dams and fetuses were examined (day 18 of gestation for mice, day 20 for rats) there was no
AZINPHOS-METHYL 139–172 JMPR 2007