Chronic effects of atrazine on estrus and mammary tumor formation in female Sprague-Dawley and Fischer 344 rats.

ABSTRACT

The chronic effects of dietary administration of atrazine at levels as high as 400 ppm on selected endocrine and tumor profiles were evaluated in Fischer 344 and Sprague-Dawley female rats. The study showed that lifetime dietary administration of atrazine at a maximum tolerated dose (MTD) to Sprague-Dawley female rats caused (1) lengthening of the estrous cycle, (2) increased number of days in estrus or under the influence of exposure to estrogen, (3) earlier onset of galactocele formation, and (4) earlier onset of mammary and pituitary tumor formation but not an increased incidence of mammary and pituitary tumors when compared to concurrent control rats. Fischer 344 female rats fed atrazine at an MTD exhibited slightly lengthened estrous cycles, but no effects were observed on estradiol or progesterone levels, or on the onset or incidence of mammary tumors. These results support a hypothesis that high-dose atrazine administration in Sprague-Dawley females is related to an acceleration of age-related endocrine changes leading to an earlier onset and/or increased incidence of mammary tumors. This endocrine-mediated response, which appears to be unique to the Sprague-Dawley female rat, occurs only at or above a threshold dose (the MTD) that interferes with normal estrous cycling, promoting prolonged exposure to endogenous estrogen.