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

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those in the control group that had access to food ad libitum. There were no histopathological lesions
observed in the thyroid gland of rats at the highest dose.
The results indicated that atrazine delays puberty and the development of the reproductive tract
in the male rat. The mode of action appears to be in altering the secretion of steroids, probably due to
disruption of control of pituitary function by the central nervous sysytem.
The NOAEL was 6.25 mg/kg bw per day on the basis of delayed preputial separation at
12.5 mg/kg bw per day and greater (Stoker et al., 2000).
In a subsequent study on the effects of atrazine metabolites on pubertal development and
thyroid function in male rats, groups of 8−18 (dose groups) or 38 (control group) male Wistar rats
were given DEA at a dose of 10.8, 21.7, 43,4, 86.8 or 173.9 mg/kg bw per day, or DIA at a dose of
10.4, 20.8, 40.1, 80.3 or 160.9 mg/kg bw per day, or DACT (purity, 97–98%) at a dose of 4.4, 8.4,
16.9, 33.8, 84.3 or 135.3 mg/kg bw per day by gavage on postnatal days 23–53. These doses were
equivalent to atrazine equimolar doses of 0, 6.25 (DACT only), 12.5, 25, 50, 100 and 200 mg/kg
bw per day.
Preputial separation was significantly delayed by treatment with DEA (atrazine equimolar
dose, 25, 100 and 200 mg/kg bw per day), DIA (atrazine equimolar dose, 25, 100 and 200 mg/kg
bw per day) and DACT (atrazine equimolar dose, 12.5–200 mg/kg bw per day). When the rats were
killed on postnatal day 53, treatment with DEA (atrazine equimolar dose, 100 and 200 mg/kg bw per
day), DIA (atrazine equimolar dose, 50–200 mg/kg bw per day) or DACT (atrazine equimolar dose,
200 mg/kg bw per day) caused a significant reduction in ventral protate weight, while only the highest
doses of DEA and DIA resulted in a significant decrease in the lateral prostate weight. Seminal vesicle
weight was reduced by DEA (atrazine equimolar dose, 25, 100 and 200 mg/kg bw per day), DIA
(atrazine equimolar dose, 100 and 200 mg/kg bw per day) and DACT (atrazine equimolar dose, 100
and 200 mg/kg bw per day). Epididymal weights were reduced in the groups receiving DEA (atrazine
equimolar dose, 200 mg/kg bw per day), DIA (atrazine equimolar dose, 200 mg/kg bw per day) and
DACT (atrazine equimolar dose, 100 and 200 mg/kg bw per day). Serum testosterone concentration
was reduced only in rats receiving DIA at the two higher doses. Serum estrone concentration was
increased in the groups receiving DACT at the two higher doses, while serum E2 concentration was
not changed relative to controls in any group. No differences were observed in any of the measures
of thyroid activity.
The results indicated that the three chlorinated metabolites of atrazine delay puberty in a manner
similar to atrazine, by affecting the control of the pituitary/gonadal axis by the central nervous system
and subsequent development of the reproductive tract. The NOAELs for DEA, DIA, and DACT
(expressed in atrazine equimolar doses) were 12.5, 12.5 and 6.25 mg/kg bw per day, respectively, on
the basis of delayed preputial separation (Stoker et al., 2002).
(g)
Studies on development of the mammary gland
In a study on the effects on development of the mammary gland in rats exposed in utero to atrazine,
groups of 20 timed-pregnant LE rats were given atrazine (purity, 97.1%) at a dose of 0 (vehicle
control) or 100 mg/kg bw per day by gavage on days 15–19 of gestation. On postnatal day 1, half
of all litters were cross-fostered, creating four treatment groups: control–control, atrazine–control,
control–atrazine, and atrazine–atrazine (dam–milk source, respectively). A significant delay in vaginal
opening and increase in body weight at vaginal opening was seen only in the litters receiving
milk from dams exposed to atrazine. However, mammary glands of female offspring (two per dam)
in all groups exposed to atrazine (atrazine–control, control–atrazine, and atrazine–atrazine) displayed
significant delays in epithelial development. These changes were detected as early as postnatal day
4 and stunted development was evident until postnatal day 40. Further, at all developmental stages
ATRAZINE 37–138 JMPR 2007