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

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Delayed parturition was seen at a dose of 100 mg/kg bw per day and greater in F344 and Sprague-
Dawley rats.
In F344 rats given atrazine at at a dose of 200 mg/kg bw per day on days 11 to 15 of gestation
(after the LH-dependent period of pregnancy), no full-litter resorptions were seen. These findings
suggest that the induction of full-litter resorption by atrazine is maternally mediated, and consistent
with loss of LH support of the corpora lutea (Narotsky et al., 2001).
(e)
Studies on female pubertal development
In a study on the effects of atrazine on pubertal development and thyroid function in rats,
groups of 15 female Wistar rats were given atrazine (purity, 97.1%) at a dose of 0, 12.5, 25, 50, 100
or 200 mg/kg bw per day by gavage on postnatal days 22 to 41. An additional control group was
included that was pair-fed with the group at 200 mg/kg bw per day in order to detect any effects
caused by the reduced food consumption observed at this dose.
Body weight on postnatal day 41 was reduced by 11.6% at 200 mg/kg bw per day, but at 50 and
100 mg/kg bw per day was not different from that of the controls. Adrenal, kidney, pituitary, ovary,
and uterine weights were also reduced at 200 mg/kg bw per day. The day of vaginal opening was
significantly delayed by 3.4, 4.5 or more than 6.8 days at 50, 100, and 200 mg/kg bw per day, respectively.
Although body weight in the pair-fed controls was reduced to the same extent as at 200 mg/kg
bw per day, vaginal opening was not significantly delayed. Serum triiodothyronine (T3), thyroxine
(T4), and TSH concentrations were unaltered by atrazine, which was consistent with the fact that no
histological changes were observed in the thyroid.
Estrous cyclicity was monitored in a second group of females from the day of vaginal opening
to postnatal day 49. The number of females displaying regular 4- or 5-day estrous cycles during the
first 15-day interval after vaginal opening was decreased at 100 and 200 mg/kg bw per day and in the
pair-fed controls. Irregular cycles were characterized by extended periods of diestrus. By the end of
the second 15-day interval (postnatal days 57–71), no effects on estrous cyclicity were observed.
The data indicated that atrazine can delay the onset of puberty and alter estrous cyclicity in
the female Wistar rat. Reduced food consumption and body weight did not account for the delay in
vaginal opening, because this effect was not observed in the pair-fed controls. In addition, no effect
on estrous cyclicity was observed at 100 mg/kg bw per day where no significant reduction in body
weight was observed.
The NOAEL was 25 mg/kg bw per day, on the basis of delayed vaginal opening at 50 mg/kg
bw per day and greater (Laws et al., 2000).
Table 22. Summary of ED 10
estimates and benchmark doses for full-litter resorption in rats given
atrazine by gavage
Strain
NOAEL (mg/kg
bw per day)
LOAEL (mg/kg
bw per day)
Dams with
full-litter resorption
at LOAEL (%)
ED 10
(mg/kg bw
per day)
Benchmark dose
(mg/kg bw per day)
Fischer 344 25 50 36 15.1 11.7
Sprague-Dawley 100 200 67 170.3 97.9
Long-Evans 100 200 67 170.6 103.0
From Narotsky et al. (2001)
ED10, estimated dose that causes full litter resorption in 10% of the dams; LOAEL, lowest-observed-adverse-effect level;
NOAEL, no-observed-adverse-effect level.
ATRAZINE 37–138 JMPR 2007