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

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Table 6. Cholinesterase activity in rats fed diets containing azinphos-methyl for 2 years
Tissue
Cholinesterase activity (% of values for controls)
Dietary concentration (ppm)
5 15 45
Males Females Males Females Males Females
Plasma
1 month 93 88 95 88 62** 44**
3 months 91 88 102 65** 60** 35**
6 months 88 92 95 71* 57** 34**
1 year 84 90 87 65** 54** 33**
1.5 years 87 100 90 74* 55** 46**
2 years 113 102 88 81 51** 38**
Erythrocytes
1 month 97 105 84** 87 76** 74*
3 months 101 110** 88** 88** 77** 72**
6 months 97 109* 90 86** 80** 77**
1 year 102 101 82* 81** 73** 69**
1.5 years 96 94 83** 80** 73** 73**
2 years 88** 98 78** 84** 63** 71**
Brain
1 year 130** 112 137** 90 109 50**
2 years 117 102 112 79** 68** 45**
From Schmidt (1987); Annex 1, reference 64, modified with reference to the original data.
* p < 0.05; ** p < 0.01.
there was a decrease in fertility of F 0
and F 1b
dams and the total number of delivered pups (Table 8).
The viability index was significantly reduced in F 1a
, F 1b
and F 2a
litters at 45 ppm, while the effect was
equivocal at 15 ppm (Table 9). At 45 ppm, there was an increased mortality of dams in the F 0
generation
and reduced mean pup viability from days 5 to day 28 of lactation in the F 1a
and F 1b
litters. As a
consequence of these effects, at 45 ppm only five females were available for mating in the F 1b
generation.
During mating of the F 1b
generation, fertility was again slightly reduced at 45 ppm but not to as
great an extent as it was for the F 0
generation.
At all stages of the study, there was no evidence of treatment-induced malformations and food
intake remained unaffected. Clinical signs of reaction to treatment, including cholinergic signs, and
reduced body-weight gain were observed at the highest dose tested (45 ppm). The NOAEL was 15
ppm, equal to 1.5 mg/kg bw per day, on the basis of reduced body-weight gain in F 0
and F 1b
parental
animals and decreased pup body weight and viability at 45 ppm (Eiben & Janda, 1987; Annex 1,
reference 64, modified by reference to original data).
Another study was conducted to investigate the effects on reproductive performance noted in
the study described above. The objectives of this additional, one-generation study were to investigate
whether the slight effect on fertility and pup viability observed at 15 ppm could be confirmed, and, if
reproducible, to determine whether the effect was attributable to treatment of the male or the female
and to determine whether reproductive effects were associated with treatment-induced inhibition of
cholinesterase activity. Groups of 18 male and 46 female Wistar rats were given diets containing azinphos-methyl
(purity, 92.0%) at a concentration of 0 (control), 5, 15, or 45 ppm (equal to 0, 0.43, 1.30,
AZINPHOS-METHYL 139–172 JMPR 2007