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

James W. Simpkins, James A. Swenberg, Noel Weiss, David Brusick, J. Charles Eldridge, James T. Stevens, Robert J Handa, Russell C. Hovey, Tony M. Plant, Timothy P. Pastoor, Charles B. Breckenridge

Research output: Contribution to journalArticle

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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."

Original languageEnglish (US)
Pages (from-to)441-459
Number of pages19
JournalToxicological Sciences
Volume123
Issue number2
DOIs
StatePublished - Oct 2011

Fingerprint

Atrazine
Toxicology
Breast Neoplasms
Rats
Tumors
Sprague Dawley Rats
Inbred F344 Rats
Prolactin
Neoplasms
Estrogens
International Agencies
Fibroadenoma
United States Environmental Protection Agency
Aromatase
Environmental Protection Agency
Estrus
Human Mammary Glands
Luteinizing Hormone
Gene expression
Epidemiologic Studies

Keywords

  • Atrazine
  • Breast cancer
  • Endocrine
  • Framework
  • Mode of action
  • Weight-of-the-evidence

ASJC Scopus subject areas

  • Toxicology

Cite this

Simpkins, J. W., Swenberg, J. A., Weiss, N., Brusick, D., Eldridge, J. C., Stevens, J. T., ... Breckenridge, C. B. (2011). Atrazine and breast cancer: A framework assessment of the toxicological and epidemiological evidence. Toxicological Sciences, 123(2), 441-459. https://doi.org/10.1093/toxsci/kfr176

Atrazine and breast cancer : A framework assessment of the toxicological and epidemiological evidence. / Simpkins, James W.; Swenberg, James A.; Weiss, Noel; Brusick, David; Eldridge, J. Charles; Stevens, James T.; Handa, Robert J; Hovey, Russell C.; Plant, Tony M.; Pastoor, Timothy P.; Breckenridge, Charles B.

In: Toxicological Sciences, Vol. 123, No. 2, 10.2011, p. 441-459.

Research output: Contribution to journalArticle

Simpkins, JW, Swenberg, JA, Weiss, N, Brusick, D, Eldridge, JC, Stevens, JT, Handa, RJ, Hovey, RC, Plant, TM, Pastoor, TP & Breckenridge, CB 2011, 'Atrazine and breast cancer: A framework assessment of the toxicological and epidemiological evidence', Toxicological Sciences, vol. 123, no. 2, pp. 441-459. https://doi.org/10.1093/toxsci/kfr176
Simpkins JW, Swenberg JA, Weiss N, Brusick D, Eldridge JC, Stevens JT et al. Atrazine and breast cancer: A framework assessment of the toxicological and epidemiological evidence. Toxicological Sciences. 2011 Oct;123(2):441-459. https://doi.org/10.1093/toxsci/kfr176
Simpkins, James W. ; Swenberg, James A. ; Weiss, Noel ; Brusick, David ; Eldridge, J. Charles ; Stevens, James T. ; Handa, Robert J ; Hovey, Russell C. ; Plant, Tony M. ; Pastoor, Timothy P. ; Breckenridge, Charles B. / Atrazine and breast cancer : A framework assessment of the toxicological and epidemiological evidence. In: Toxicological Sciences. 2011 ; Vol. 123, No. 2. pp. 441-459.
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