POSSIBLE ANTIESTROGENIC PROPERTIES OF CHLORO-S-TRIAZINES IN RAT UTERUS

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.