Mk. Tennant et al., POSSIBLE ANTIESTROGENIC PROPERTIES OF CHLORO-S-TRIAZINES IN RAT UTERUS, Journal of toxicology and environmental health, 43(2), 1994, pp. 183-196
Several published reports have indicated that certain chloro-s-triazin
e herbicides may alter endocrine function in rats, possibly by androge
n receptor binding. In direct tests of estrogenic bioactivity, oral do
ses of up to 300 mg/kg/d of atrazine, simazine, or the common metaboli
te diaminochlorotriazine (DACT) did not significantly increase uterine
weight of ovariectomized Sprague-Dawley female rats. The highest dose
, which was approximately 10% of the LD50 for these compounds, did cau
se body weight loss. When administered concomitantly with sc injection
s of estradiol (2 mu g/kg), 300 mg/kg of orally administered chlorotri
azines significantly reduced uterine weight in comparison to animals g
iven estrogen alone. Neither atrazine, simazine, nor DACT, at oral dos
es up to 300 mg/kg/d, stimulated incorporation of [H-3]thymidine into
uterine DNA of immature Sprague-Dawley female rats. However, oral trea
tment at doses of 50 mg/kg and higher significantly reduced thymidine
incorporation into uterine DNA extracted from immature rats given a si
ngle injection of 0.15 mu g estradiol. Oral doses of 300 mg/kg of atra
zine, simazine, or DACT significantly reduced expression of progestero
ne receptor binding in cytosol fractions prepared from uteri of ovarie
ctomized rats injected sc with 1 mu g estradiol; 50 mg/kg triazine was
not effective in this case. Uterine progesterone receptor levels were
not stimulated in rats given oral doses up to 300 mg/kg of these tria
zines without estradiol injections. These results suggest that atrazin
e, simazine, and DACT possess no intrinsic estrogenic activity bur tha
t they are capable of weak inhibition of estrogen-stimulated responses
in the rat uterus. This inhibition may play a role in the previously
observed disruptive actions of chlorotriazines on reproductive endocri
ne function of female rats.