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

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In a study on the effects of atrazine on the sexual maturation of female rats, groups of 8−10
female Wistar and Sprague-Dawley rats were given atrazine (purity, 98.2%) at a dose of 0, 10, 30 or
100 mg/kg bw per day by gavage from postnatal day 21 until postnatal day 43 (Wistar rats) or postnatal
day 46 (Sprague-Dawley rats). A separate group of Wistar rats was given the GnRH agonist,
antarelix (ANT), which is known to block the release of LH from the pituitary and delay vaginal
opening. Uterine weights were determined at postnatal days 30, 33, 43 (Wistar rats) and 46 (Sprague-
Dawley rats), and the time of vaginal opening was assessed.
In rats exposed to ANT, uterine growth and vaginal opening were completely prevented. In
Wistar rats exposed to atrazine at 100 mg/kg bw per day, vaginal opening was significantly delayed
(by 3 days), while uterine growth was delayed at postnatal days 30 and 33, but this growth inhibition
had been overcome by postnatal day 43. In Sprague-Dawley rats exposed to atrazine at 30 and
100 mg/kg bw per day, vaginal opening was significantly delayed (by 2.5 and 3 days, respectively),
while uterine weights were unaffected at postnatal day 46.
The NOAEL was 10 mg/kg bw per day in Sprague-Dawley rats and 30 mg/kg bw per day
in Wistar rats on the basis of delayed vaginal opening at 30 or 100 mg/kg bw per day, respectively
(Ashby et al., 2002).
In a study on the effects of atrazine metabolites on pubertal development and thyroid function
in female rats, groups of 15 female Wistar rats were given DACT (purity, 96.8%) at a dose of 0, 16.7,
33.8, 67.5 or 135 mg/kg bw per day or hydroxyatrazine (purity, 97.1%) at a dose of 0, 22.8, 45.7, 91.5
or 183 mg/kg bw per day by gavage on postnatal days 22–41. These doses were equivalent to atrazine
equimolar doses of 0, 25, 50, 100 and 200 mg/kg bw per day.
The females were monitored daily for vaginal opening and killed on postnatal day 41. DACT
significantly delayed vaginal opening by 3.2, 4.8, and 7.6 days at doses of 33.8, 67.5, and 135 mg/
kg bw per day, respectively. The NOAEL for DACT of 16.7 mg/kg bw per day was identical to the
equimolar NOAEL of 25 mg/kg bw per day for atrazine. For hydroxyatrazine, no significant delays
in pubertal development were observed in two separate studies with doses ranging up to 183 mg/kg
bw per day, identical to the equimolar NOAEL for atrazine of 200 mg/kg bw per day. No significant
or dose-related effects were observed on serum thyroid hormone concentrations (T3, T4 and TSH)
or thyroid histopathology (Laws et al., 2003).
(f)
Studies on male pubertal development
In two separate studies, the effects of atrazine on pubertal development in male rats were
investigated. In the first study, groups of 9−12 male Sprague-Dawley rats were given atrazine (purity,
96.1%) at a dose of 0, 1, 2.5, 5, 10, 25, 50, 100 or 200 mg/kg bw per day on postnatal days 22–47.
Since the first study showed that atrazine significantly suppressed body-weight gain at doses of
100 mg/kg bw per day and greater, a second study was performed. One group received atrazine at a
dose of 100 mg/kg bw per day, another group received the vehicle (0.5% carboxymethylcellulose)
and was fed the mean daily intake of food consumed by the atrazine-treated group on the previous
day, and a further group received the vehicle and was fed ad libitum.
There was no effect on any of the measured variables (body weight, food consumption, day
of preputial separation, serum testosterone, serum LH, intratesticular testosterone, ventral prostate
weight, and seminal vesicle weight) at doses of up to 50 mg/kg bw per day, while doses of
100 mg/kg bw per day or more significantly reduced body-weight development (−9% and −21% at
100 and 200 mg/kg bw per day, respectively). In the second study in the additional pair-fed control
group, body-weight was 10% lower than that of the control group fed ad libitum and was comparable
to that of the group at 100 mg/kg bw per day. Lower values for serum and intratesticular testosterone
concentrations were seen at doses of 100 mg/kg bw per day and greater; similar changes were also
ATRAZINE 37–138 JMPR 2007