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

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In a study on the effect of atrazine on LH secretion in the intact proestrus female rat, LE rats
displaying regular 4-day estrous cycles reveived atrazine (purity, not reported) at a dose of 0, 6.25,
12.5 or 25 mg/kg bw per day by gavage through a full ovarian cycle, beginning at vaginal estrus.
The rats were maintained on a 14-h light : 10-h dark schedule (lights on at 05:00) and dosing was
done at 12:00. The last dose was administered on the day of vaginal proestrus and groups were
killed at 2-h intervals until lights out (12:00, 14:00, 16:00, 18:00 and 20:00). Atrazine, at all doses
administered, resulted in a significant decrease in peak LH concentration when determined at 18:00.
However, the effect was of a similar extent at all doses tested, and the study authors believed that
the flat dose–response relationship reflected the effect of atrazine on LH within this range of dosing
(Cooper et al., 2007).
Monkeys
In a study on the effect of atrazine on pituitary hormone secretion in a non-human primate
model, groups of six female ovariectomized Rhesus monkeys received atrazine (purity, 97.2%; in
0.5% carboxymethyl cellulose) at a dose of 0 or 25 mg/kg bw per day by oral gavage for 30 days, and
were then kept an additional 60 days for recovery. All monkeys received a subcutaneous injection of
estradiol benzoate (330 µg) on day 5 before treatment, on days 5 and 26 of treatment and on day 26 of
recovery. Blood samples for hormone analysis (LH, FSH, prolactin, progesterone, E2, cortisol) were
collected from each monkey approximately 12 h after administration of E2 (as estradiol benzoate),
and then at 6-h intervals (up to 102 h after administration of E2).
No treatment-related clinical signs were observed. Body weight was not affected by treatment
except in one monkey treated with atrazine that lost 1 kg (19%) of its initial body weight over the
course of the study. This monkey displayed a marked suppression of LH and FSH surges after 5 or
26 days of treatment, which was confounded with the effects of other non-specific stressors. In the
remaining monkeys, no treatment-related effects on concentrations of LH, FSH, E2, progesterone or
prolactin were observed. However, a non-specific stress response in treated monkeys appeared to be
associated with intolerance to high doses of atrazine. This resulted in the inability to acclimatize to
experimental conditions as demonstrated by smaller reductions in cortisol in monkeys treated with
atrazine when compared with controls. In conclusion, the primate model for assessing effects on LH
secretion is limited by intra- and inter-animal variability in the normal response to estrogen-induced
LH secretion, which is confounded by apparent stress effects related to the required experimental
design (Osterburg & Breckenridge, 2004; Simpkins & Eldridge, 2004).
(d)
Studies on reproductive and developmental effects
In a study designed to examine the effects of atrazine on suckling-induced prolactin release
in Wistar rats, dams were given atrazine (purity, 98%) at a dose of 0, 6.25, 12.5, 25, or 50 mg/kg bw
twice per day by gavage on postnatal days 1–4, or the DA-receptor agonist bromocriptine (BROM,
which is known to suppress the release of prolactin) twice per day by subcutaneous injection at a
dose of 0.052, 0.104, 0.208, or 0.417 mg/kg bw. Serum prolactin concentrations were measured
on postnatal day 3 using a serial sampling technique and in-dwelling cardiac catheters. The study
hypothesis was that early lactational exposure to agents that suppress the suckling-induced release
of prolactin would lead to a disruption in the development of the tuberoinfundibular neurons in the
pups (presumably due to the lack of prolactin derived from the dam’s milk), with the consequence of
impaired regulation of prolactin secretion, hyperprolactinaemia before puberty and prostatitis in the
adult male offspring.
A significant rise in the release of prolactin in serum was noted in all females in the control
group within 10 min of the initiation of suckling. At 50 mg/kg bw, atrazine inhibited the sucklinginduced
release of prolactin in all females, while atrazine at a dose of 25 and 12.5 mg/kg bw inhibited
this release in some dams but had no discernible effect in others. Give twice per day at a at
ATRAZINE 37–138 JMPR 2007