Atrazine and breast cancer: A framework assessment of the toxicological and epidemiological evidence.

Publication Type:

Journal Article

Source:

Toxicological sciences : an official journal of the Society of Toxicology, Volume 123, Issue 2, p.441-59 (2011)

Keywords:

2011, ADENOCARCINOMA, Animals, Atrazine, Breast Neoplasms, Carcinogens, Center-Authored Paper, Estrus, Female, Fibroadenoma, Herbicides, Humans, Infertility, Public Health Sciences Division, Rats, Rats, Inbred F344, Rats, Sprague-Dawley, Risk Assessment, September 2011, Species Specificity, Time Factors

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 LH 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, up-regulation 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 IARC's classification of atrazine as "unclassifiable as to carcinogenicity" and the USEPA's classification of atrazine as "not likely to be carcinogenic."