title: Atrazine and breast cancer: a framework assessment of the toxicological and epidemiological evidence.
abstract: The causal relationship between atrazine exposure and the occurrence of breast cancer in women was evaluated using the framework developed by Adami et al. (2011) wherein biological plausibility and epidemiological evidence were combined to conclude that a causal relationship between atrazine exposure and breast cancer is "unlikely". Carcinogenicity studies in female Sprague-Dawley (SD) but not Fischer-344 rats indicate that high doses of atrazine caused a decreased latency and an increased incidence of combined adenocarcinoma and fibroadenoma mammary tumors. There were no effects of atrazine on any other tumor type in male or female SD or Fischer-344 rats or in three strains of mice. Seven key events that precede tumor expression in female SD rats were identified. Atrazine induces mammary tumors in aging female SD rats by suppressing the luteinizing hormone surge, thereby supporting a state of persistent estrus and prolonged exposure to endogenous estrogen and prolactin. This endocrine mode of action has low biological plausibility for women because women who undergo reproductive senescence have low rather than elevated levels of estrogen and prolactin. Four alternative modes of action (genotoxicity, estrogenicity, upregulation of aromatase gene expression or delayed mammary gland development) were considered and none could account for the tumor response in SD rats. Epidemiological studies provide no support for a causal relationship between atrazine exposure and breast cancer. This conclusion is consistent with International Agency for Research on Cancer's classification of atrazine as "unclassifiable as to carcinogenicity" and the United States Environmental Protection Agency's classification of atrazine as "not likely to be carcinogenic."
authors.affiliation: Department of Pharmacology and Neurosciences, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
authors.forename: James A
authors.initials: JA
authors.lastname: Swenberg
authors.forename: Noel
authors.initials: N
authors.lastname: Weiss
authors.forename: David
authors.initials: D
authors.lastname: Brusick
authors.forename: J Charles
authors.initials: JC
authors.lastname: Eldridge
authors.forename: James T
authors.initials: JT
authors.lastname: Stevens
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Handa
authors.forename: Russell C
authors.initials: RC
authors.lastname: Hovey
authors.forename: Tony M
authors.initials: TM
authors.lastname: Plant
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Pastoor
authors.forename: Charles B
authors.initials: CB
authors.lastname: Breckenridge
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D004971:Estrus / Q000187:drug effects / Q000502:physiology; D005260:Female; D018226:Fibroadenoma / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D007246:Infertility / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D013045:Species Specificity; D013997:Time Factors
chemical_list: D002273:Carcinogens; D006540:Herbicides; D001280:Atrazine