HYPOTHESIS FOR MAMMARY TUMORIGENESIS IN SPRAGUE-DAWLEY RATS EXPOSED TO CERTAIN TRIAZINE HERBICIDES

The symmetrical triazine herbicides have been used for the preemergenc e control of broadleaf weeds for nearly three decades. Recently, certa in members of this class, primarily the chlorotriazines (substituted i n the 2 position), have been shown to evoke an increased incidence of mammary tumors in female Sprague-Dawley rats. This response was noted when these chemicals were administered in the diet for 2 yr, and most often at dietary feeding levels at or above the maximum tolerated dose (MTD). At levels exceeding the MTD the health of these animals was co mpromised, as manifested by toxicity-related reduced survival that was not associated with the occurrence of mammary tumors. Mammary tumors in rats frequently occur as a result of the influence of endogenous es tradiol and prolactin. Those hormones, as well as progesterone, growth -stimulating, luteinizing, and follicle-stimulating hormones, were mea sured after 24 mo of dietary administration of the chlorotriazine, sim azine. The plasma hormone pattern seen in aged female Sprague-Dawley r ats administered 1000 ppm simazine in the diet for 24 mo resembled tha t noted for aged female controls, except that the difference was more pronounced in the simazine-treated group. These results suggest that p rolonged exposure of Sprague-Dawley females to excessive levels of tri azines affects the neuroendocrine system, which in turn alters the pat hology of the mammary gland. These changes are comparable to those tha t occur naturally as the rat ages. Changes in neuroendocrine control c ould result in the expression of an earlier onset and/or an increased incidence of mammary tumors, which already occur at a high spontaneous rate in aging Sprague-Dawley female rats.