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

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slight (3 out of 30) hepatocellular hypertrophy in male P 2
rats compared with 0 out of 30 concurrent
controls. No clinical chemistry assays were performed in this study. Slight, bilateral inflammation
of the epididymis was increased at 100 mg/kg bw per day in parental males of both generations,
relative to concurrent controls, but was within the range for historical controls; epididymides were
not investigated histopathologically at 20 or 5 mg/kg bw per day.
Table 11. Findings in a two-generation study of reproductive toxicity in rats given diets
c ontaining quinoxyfen
Finding
Nominal dose (mg/kg bw per day)
0 5 20 100
F 1a
/F 1b
Litter size day 1 15 / 14 14 / 16 14 / 16 15 / 17
Litter size day 21 14 / 14 13 / 15 14 / 14 14 / 15
Pup weight day 0 (g) 6.7 / 6.9 7.1 / 6.9 6.7 / 6.9 6.6 / 6.7
Pup weight day 21 (g) 43 / 41 47* / 40 42 / 41 39* / 37
F 1a
–P 2
bw, day 83, M/F (g) 553 / 311 561 / 341* 581 / 338* 547 / 315
F 2
Litter size day 1 14 15 14 13
Litter size day 21 13 15 13 12
Pup weight day 0 (g) 6.7 6.9 6.7 6.6
Pup weight day 21 (g) 42 43 41 40
From Liberacki et al. (1995)
* p < 0.05
The NOAEL for general toxicity and pup development was 20 mg/kg bw per day on the
basis of slight but consistent reduction in body-weight gain in pups during lactation and hepatocyte
hypertrophy in the liver of parental males, without investigations on serum enzyme activity. The
NOAEL for reproductive performance was 100 mg/kg bw per day as there were no adverse effects on
reproductive performance at the highest test dose (Liberacki et al., 1995).
(b)
Developmental toxicity
Rats
In a GLP-compliant study, groups of 30 mated specific pathogen free (SPF) female
Crl:CD(SD)BR rats (body weight, 202–239 g) were given quinoxyfen (purity, 97.4%) at a dose
of 0 (control), 100, 300 or 1000 mg/kg bw per day suspended in 1% methyl cellulose by gavage
from day 6 to 15 of presumed gestation. Dams were killed on day 20 and the pups were delivered
by caesarean section. The liver, kidneys, gravid uterine weights, and the number of corpora lutea,
implantations, resorptions and dead and live fetuses were recorded. Fetuses were weighed, sexed
and examined for external, visceral and skeletal abnormalities.
There was a single mortality at 1000 mg/kg bw per day that was the result of an intubation
error. The number of pregnant dams was 24, 27, 28 and 28 at doses of 0 (control), 100, 300 and
1000 mg/kg bw per day. No signs of toxicity or changes in animal behaviour were observed
during the dosing period. Food consumption and body-weight gain were not affected by the
treatment. At termination, no gross abnormalities were observed in dams. There were no
significant treatment-related effects on the number of litters with external, visceral or skeletal
effects. A raised incidence of pups with extra ribs was seen at the highest dose (13% vs 8–9%
in other groups) but was within the range for historical controls (7–22%) and was not clearly
treatment related.
QUINOXYFEN X-X JMPR 2006