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Studies on estrogenic and anti-estrogenic potential
In tests for estrogenic bioactivity, groups of five or six ovariectomized adult female Sprague-
Dawley rats were given atrazine (purity, 97.7%) or its metabolite DACT (purity, 98.2%) at an oral
dose of 20, 100 or 300 mg/kg bw per day for three consecutive days. Uterine weight did not increase
statistically significantly. At the highest dose of atrazine or or DACT, loss of body weight was seen.
When the test substances were administered concomitantly with subcutaneous injections of E2 at a
dose of 2 µg per rat, statistically significant decreases in uterine weight were seen with both atrazine
and DACT at doses of 100 mg/kg bw per day and greater.
In further tests by the same research group, immature female Sprague-Dawley rats (age
23 days) were given atrazine or DACT at a dose of 1, 10, 50, 100 or 300 mg/kg bw per day by gavage
for two consecutive days, and received E2 at a dose of 0.15 µg per rat by subcutaneous injection
on the second day. Thymidine incorporation into uterine DNA was significantly reduced at doses of
50 mg/kg bw per day and greater.
Again, in further tests by the same research group, ovariectomized adult female Sprague-
Dawley rats were given atrazine or DACT at a dose of 50 or 300 mg/kg bw per day by gavage for
two consecutive days, and received E2 at a dose of 1 µg per rat by subcutaneous injection each day.
Progesterone receptor-binding capacity in cytosol fractions from uteri was significantly reduced at
300 mg/kg bw per day. Uterine progesterone receptor levels were not stimulated in rats that received
atrazine or DACT at doses of up to 300 mg/kg bw per day without E2 injections.
The results indicated that atrazine and DACT possess no intrinsic estrogenic activity, but that
they are capable of weak inhibition of estrogen-stimulated responses in the rat uterus (Eldridge et al.,
1994; Tennant et al., 1994a).
In a study on the interaction with ER binding, competitive co-incubation of atrazine (purity,
96.9%) or DACT (purity, 98.2%) and radiolabeled estrogen with rat uterine cytosol containing ER
failed to demonstrate significant displacement of estrogen binding by atrazine. However, when cytosols
were pre-incubated with atrazine, and tracer was added to the chilled incubation medium, there
was a significant reduction of [ 3 H]E2 binding. Competition was very weak, with IC 50
estimates of
20 µmol/l for atrazine and 100 µmol/l for DACT, which were four to five orders of magnitude greater
than the approximate IC 50
of E2.
Ex-vivo results in the same report indicated that the uterine ER-binding capacity was reduced
by approximately 30% when ovariectomized adult female Sprague-Dawley rats were given atrazine
or DACT at a dose of 300 mg/kg bw per day by gavage for two consecutive days; a dose of
50 mg/kg bw per day had no effect.
The result confirmed that atrazine and DACT may be capable of a very weak interaction with
estrogen receptors, but only at extremely high concentrations (Tennant et al., 1994b).
The potential estrogenic activities of atrazine were investigated in vivo using the immature
female Sprague-Dawley rat uterus and in vitro using the estrogen-responsive MCF7 human breast
cancer cell line and the estrogen-dependent recombinant yeast strain PL3. Rats that were dosed with
atrazine only at 50, 150, or 300 mg/kg bw per day for three consecutive days did not exhibit any
significant increases in uterine wet weight, although decreases in cytosolic progesterone-receptor
binding levels and uterine peroxidase activity were observed. 17β-estradiol (E2)-induced increases in
uterine wet weight were not (statistically) significantly affected by co-treatment with atrazine; however,
some dose-independent decreases in E2-induced cytosolic progesterone-receptor binding and
uterine peroxidase activity were observed. In vitro, atrazine did not affect basal or E2-induced MCF7
cell proliferation or the formation of nuclear progesterone receptor–DNA complexes as determined
by gel electrophoretic mobility shift assays. In addition, atrazine did not display agonist activity or
ATRAZINE 37–138 JMPR 2007