Pesticide residues in food — 2006: Toxicological ... - ipcs inchem

520
at 2500 ppm. The administration of mecamylamine did not abolish the effect of thiacloprid at
2500 ppm on the estradiol/progesterone ratio. This demonstrates that the thiacloprid-mediated effects
on the adrenal X-zone and hormone changes were not caused by central nervous events, which can
be counteracted by the nicotine-like agent mecamylamine.
Table 43. Selected findings in a study of aromatase induction in mice fed diets containing
t hiacloprid for 13 weeks
Finding
Dietary concentration (ppm)
0 10 30 250 2500 2500 a
Interim sacrifi ce
Body weight (g) 22 22 21 21 21 21++
Liver weight (g) 1.10 1.09 1.06 1.17 1.43** 1.31**
Relative liver weight (%) 5.04 5.00 4.97 5.44* 6.67** 6.31**
Terminal sacrifi ce
Body weight (g) 24 26** 24 24 25 24
Liver weight (g) 1.20 1.20 1.14 1.17 1.51** 1.41**
Relative liver weight (%) 4.97 4.69 4.69 4.81 6.14** 5.94**
Estradiol (pg/ml), week 13 35.2 37.8 37.5 32.3 31.5 28.3
Progesterone (ng/ml), week 13 1.48 1.57 1.43 1.45 2.02 2.10
Estradiol/progesterone ratio, week 13 26.1 28.8 28.0 32.0 17.4 15.5
Aromatase (pmol/g per min) 11.9 – 14.5 19.6** 56.2** –
Adrenal X zone vacuolation, No. examined 15 14 15 15 15 15
Grade 1 9 9 10 1 0 1
Grade 2 3 5 4 7 1 1
Grade 3 0 0 0 7 2 5
Grade 4 0 0 0 0 10 7
Grade 5 0 0 0 0 2 1
Total 12 14 14 15 15 15
Average grade 1.0 1.3 1.2 2.4 3.9 3.4
From Andrews et al. (1998)
a
Plus drinking-water containing mecamylamine.
* p < 0.05; ** p < 0.01.
Continuous stimulation of the ovarian tissue could explain the increased incidence of ovarian
luteomas observed in the study of carcinogenicity. The ovarian and adrenal effects in mice were
interpreted as secondary to the hormonal imbalance induced by the liver enzyme/aromatase
induction.
The NOAEL for female mice was 30 ppm, equal to 18 mg/kg bw per day, on the basis of
clinical signs, enzyme induction and adrenal effects at 250 ppm (Andrews et al., 1998).
Two serial studies had been conducted to investigate the effect of administration of dietary
thiacloprid (purity, 96.2–97.2%) on the activity of aromatase in male and female rats and to provide
additional toxicokinetic data. The studies complied with test guideline OECD 407. In the first study,
groups of 15 male and 15 female Wistar (Hsd Cpb:WU) rats were given diets containing thiacloprid at
a concentration of 0, 100, or 1000 ppm for 4 weeks. In the second study, groups of 10 female Wistar
(Hsd Cpb:WU) rats were given diets containing thiacloprid at a concentration of 0, 200 or 500 ppm for
4 weeks. Clinical observations, body weight and feed intakes were recorded at appropriate time-points.
THIACLOPRID X-X JMPR 2006