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

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In a two-generation study of reproductive toxicity, groups of 30 male and 30 female CD
Sprague-Dawley rats were given diets containing thiacloprid (purity, 96.7–97.5%) at a concentration
of 0, 50, 300 or 600 ppm. Animals were mated after 10 weeks to produce F 1
pups. After weaning,
selected F 1
pups were given diets containing thiacloprid for 10 weeks before mating and production
of the F 2
generation. The study complied with test guideline OECD 416. Determinations of body
weights, feed consumption, clinical signs, estrous cycling, mating, fertility, duration of gestation
and litter size were performed during the study. Offspring were examined for treatment-related
effects on sex ratio, pup viability, body-weight gain and clinical signs. Gross necropsy evaluations
were performed on all adults and pups. Histopathological examination of reproductive organs, liver,
pituitary, thyroids and all gross lesions was performed on all F 0
and F 1
adults. Dietary analyses
revealed satisfactory test substance stability and concentration. The mean daily intakes at 0, 50, 300
and 600 ppm in the period before mating were equal to 0, 3.5, 20.9 and 40.9 mg/kg bw per day in
F 0
males and 0, 4.2, 26,0 and 50.8 mg/kg bw per day in F 0
-females, respectively, and 0, 3.5, 21,7
and 43.9 mg/kg bw per day in F 1
males and 0, 4.1, 25.5 and 51.0 mg/kg bw per day in F 1
females,
respectively.
Four F 0
females at 300 ppm and three females at 600 ppm were sacrificed or found dead on
days 23–24 of gestation due to dystocia. These animals also exhibited pallor, perineal and vaginal
staining. Small numbers of deaths in other groups are not attributable to the effects of treatment. No
clinical signs of toxicity were noted in surviving animals.
In parental animals, body-weight gains were decreased at 600 ppm for F 0
and F 1
females
during the phase before mating and for F 1
males. During the gestation phase lower body weights
with normal weight gains were measured in the F 0
and F 1
groups at the highest dose. Also
during the lactation phase lower body weights were observed in the parental and F 1
groups at the
highest dose (Table 30). No consistent effect on feed consumption was seen in F 0
animals. Feed
consumption was significantly increased in F 1
animals of both sexes at 600 ppm during the period
before mating. No effects on feed consumption were seen during gestation in dams of either
generation.
No effects were seen on fertility or reproductive performance. Gestation duration was increased
in some F 0
animals at 300 and 600 ppm due to dystocia, however no significant effect was seen on the
mean duration of gestation for these groups (Table 31).
There was a possible treatment-related decrease in the live birth index at 600 ppm for the
F 1
and F 2
generations when compared with the concurrent controls and also with the historical
controls (97–100%; data from 10 two-generation studies). The viability index was statistically
non-significantly but markedly lower in the F 1
animals at 600 ppm (97 and 83 for the control
group and the group at the highest dose, respectively). However, the low viability index at 600 ppm was
due to the cannibalization of pups. The viability index for the control group and the group at
the highest dose was 99 and 91, respectively, when the index was calculated without including
the cannibalized pups as part of the litter on lactation day 0. The viability index of 91 was
not considered a compound-related reduction in pup viability as the viability index for the
F 2
generation control group was 94 and the historical-control range for the viability index
was 91–100. There were a markedly higher number of cannibalized pups at 600 ppm when
compared with the control group; however, when the litter was used as the experimental unit,
no statistically significant difference was found for the number of dams with cannibalized
pups.
The pup weights were decreased in the F 1
and F 2
groups at the intermediate and highest doses
on days 14–21, and days 7–21, respectively.
THIACLOPRID X-X JMPR 2006