A risk characterization for atrazine: oncogenicity profile.
An extensive safety database has been developed for the chlorotriazine herbicide, atrazine. The results from five oncogenicity studies conducted in the Sprague-Dawley rat, two studies in the Fischer 344 rat, and two studies in the CD-1 mouse were reviewed. No increase in the incidence of tumors of any 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 level in their diet for 24 mo. Female Sprague-Dawley rats fed atrazine at levels of 400, 500, and 1000 ppm developed mammary tumors earlier than did the control group. The incidence of female Sprague-Dawley rats with mammary tumors after 24 mo of treatment was statistically increased at feeding levels of > or = 70 ppm in 1 study and at 400 ppm in a second study, whereas there were no significant differences between the treated and the control group in 3 other studies. No increase in tumors of any type was observed in ovariectomized female Sprague-Dawley rats after 24 mo of atrazine 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 normal reproductive aging process resulting in increased exposure to endogenous estrogen and prolactin. The Sprague-Dawley rat differs from the Fischer 344 rat, the CD-1 mouse, and humans in the endocrine control mechanisms affecting reproductive senescence and the development of the mammary tumors during aging. These data indicate that the carcinogenic effect of high doses of atrazine observed in the female Sprague-Dawley is a strain-, sex-, and tissue-specific response that does not have biological relevance to humans.
Stevens
J T
JT
Toxicology, Novartis Crop Protection, Inc., Greensboro, North Carolina 27419, USA. james.stevens@cp.novartis.com.
Breckenridge
C B
CB
Wetzel
L
L
D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D015197:Carcinogenicity Tests; D004305:Dose-Response Relationship, Drug; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced*; D051379:Mice; D008815:Mice, Inbred Strains; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012737:Sex Factors