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

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a dose of 6.25 mg/kg bw (i.e. 12.5 mg/kg bw per day), atrazine was without effect. BROM, used
as a positive control, also inhibited the suckling-induced release of prolactin at doses of 0.104 to
0.417 mg/kg bw, with no effect at 0.052 mg/kg bw. To examine the effect of postnatal exposure
to atrazine and BROM on the incidence and severity of inflammation of the lateral prostate of the
offspring, adult males were examined at 90 and 120 days. While no effect was noted at age 90 days,
by 120 days, the incidence and severity of prostate inflammation were both increased in offspring of
dams treated with atrazine at 25 and 50 mg/kg bw. Atrazine at a dose of 12.5 mg/kg bw and BROM
at a dose of 0.208, or 0.417 mg/kg bw increased the incidence, but not the severity, of prostatitis.
Combined treatment with ovine prolactin and atrazine at 25 or 50 mg/kg bw on postnatal day 1–4
reduced the incidence of inflammation observed at 120 days, indicating that this increase in inflammation,
seen after atrazine alone, resulted from the suppression of prolactin in the dam.
To determine whether there was a critical period for these effects, dams were given atrazine at
a dose of 25 or 50 mg/kg bw twice per day on postnatal days 6–9 and postnatal days 11–14. Inflammation
was increased in offspring from dams treated on postnatal days 6–9, but this increase was not
statistically significant. Dosing on postnatal day 11–14 was without effect. These data demonstrated
that atrazine suppresses the suckling-induced release of prolactin and that this suppression results in
lateral prostate inflammation in the offspring. The critical period for this effect is postnatal days 1–9
(Stoker et al., 1999).
In a study on the effects of atrazine on implantation and embryo viability during early gestation
in rats, groups of rats of one of four strains (Holtzman; Sprague-Dawley; LE; Fischer 344,
F344) were given atrazine (purity, 97.1%) at a dose of 0, 50, 100 or 200 mg/kg bw per day by gavage
during days 1–8 of gestation during either the light or dark period of a 14 : 10 light : dark cycle.
All rats were necropsied on day 8 or 9 of pregnancy. At a dose of 200 mg/kg bw per day, atrazine
reduced body-weight gain in all except one group (F344 diurnal dosing), and nocturnal dosing
resulted in significant effects on body-weight gain at lower doses than did diurnal dosing. F344 rats
showed a significant increase in pre-implantation loss after nocturnal dosing at 100 and 200 mg/
kg bw per day, with no effect in other strains, while Holtzman rats showed a significant increase in
postimplantation loss after diurnal and nocturnal dosing at 100 and 200 mg/kg bw per day, with no
effect in other strains. Only in Holtzman rats was there a significant decrease in serum progesterone
concentrations at 100 and/or 200 mg/kg bw per day in both intervals of dosing, while serum E2
concentration was significantly increased only in Sprague-Dawley rats at 200 mg/kg bw per day and
by diurnal dosing. A significant reduction in serum LH concentration was seen in several groups,
but there was no effect in Sprague-Dawley rats. In conclusion, F344 rats were most susceptible to
the pre-implantation effects of atrazine, while Holtzman rats appeared to be most sensitive to the
postimplantation effects. LE and Sprague-Dawley rats were least sensitive to the effects of atrazine
during very early pregnancy (Cummings et al., 2000).
In a study on the effects of atrazine on the early postimplantation phase of pregnancy, F344,
Sprague-Dawley and LE rats were given atrazine (purity, 97.1%) at a dose of 0, 25, 50, 100 or
200 mg/kg bw per day by gavage on days 6 to 10 of gestation. The dams were allowed to deliver and
litters were examined postnatally.
Significant maternal body-weight losses on days 6–7 of gestation were seen in F344 rats at a
dose of 50 mg/kg bw per day and greater, in Sprague-Dawley rats at a dose of 25 mg/kg bw per day
and greater and in LE rats at a dose of 100 mg/kg bw per day and greater. The F344 strain was the
most sensitive to effects on pregnancy, showing full-litter resorption at a dose of 50 mg/kg bw per
day and greater. In surviving F344 litters, prenatal loss was increased at 200 mg/kg bw per day. In
Sprague-Dawley and LE rats, full-litter resorption occurred only at 200 mg/kg bw per day (Table 22).
ATRAZINE 37–138 JMPR 2007