A risk characterization for atrazine: Oncogenicity profile

An extensive safety database has been developed for the chlorotriazine herb icide, atrazine. The results from five oncogenicity studies conducted in th e Sprague-Dawley rat, two studies in the Fischer 344 rat, and two studies i n the CD-l mouse were reviewed. No increase in the incidence of tumors of a ny type was observed in male or female Fischer 344 rats, male or female CD- 1 mice, or male Sprague-Dawley rats fed atrazine at a maximum tolerated lev el in their diet For 24 mo. Female Sprague-Dawley rats fed atrazine at leve ls of 400, 500, and 1000 ppm developed mammary tumors ear lier than did the control group. The incidence of female Sprague-Dawley rats with mammary tu mors after 24 mo of treatment was statistically increased at feeding levels of greater than or equal to 70 ppm in 1 study and at 400 ppm in a second s tudy, whereas there were no significant differences between the treated and the control group in 3 other studies. No increase in tumors of any type wa s observed in ovariectomized female Sprague-Dawley rats after 24 mo of atra zine treatment at the highest level tested, 400 ppm. Therefore, the mammary tumor response in female Sprague-Dawley rats following the administration of high levels of atrazine appears to be due to an acceleration of the norm al reproductive aging process resulting in increased exposure to endogenous estrogen and prolactin. The Sprague-Dawley rat differs from the Fischer 34 4 rat, the CD-1 mouse, and humans in the endocrine control mechanisms affec ting reproductive senescence and the development of the mammary tumors duri ng aging. These data indicate that the carcinogenic effect of high doses of atrazine observed in the female Sprague-Dawley is a strain-, sex-, and tis sue-specific response that does not have biological relevance to humans.