US EPA's regulatory pesticide evaluations need clearer guidelines for considering mammary gland tumors and other mammary gland effects

Mol Cell Endocrinol. 2020 Dec 1:518:110927. doi: 10.1016/j.mce.2020.110927. Epub 2020 Jul 7.

Abstract

Breast cancer risk from pesticides may be missed if effects on mammary gland are not assessed in toxicology studies required for registration. Using US EPA's registration documents, we identified pesticides that cause mammary tumors or alter development, and evaluated how those findings were considered in risk assessment. Of 28 pesticides that produced mammary tumors, EPA's risk assessment acknowledges those tumors for nine and dismisses the remaining cases. For five pesticides that alter mammary gland development, the implications for lactation and cancer risk are not assessed. Many of the mammary-active pesticides activate pathways related to endocrine disruption: altering steroid synthesis in H295R cells, activating nuclear receptors, or affecting xenobiotic metabolizing enzymes. Clearer guidelines based on breast cancer biology would strengthen assessment of mammary gland effects, including sensitive histology and hormone measures. Potential cancer risks from several common pesticides should be re-evaluated, including: malathion, triclopyr, atrazine, propylene oxide, and 3-iodo-2-propynyl butylcarbamate (IPBC).

Keywords: Breast cancer; Endocrine disrupting chemicals; Estradiol synthesis; Malathion; Progesterone; Triazines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / chemically induced
  • Breast Neoplasms / pathology
  • Endocrine Disruptors / pharmacology
  • Female
  • Government Regulation
  • Humans
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Human / drug effects*
  • Pesticides / toxicity*
  • Practice Guidelines as Topic / standards*
  • Risk Assessment
  • Toxicity Tests / methods
  • Toxicity Tests / standards*
  • United States
  • United States Environmental Protection Agency / legislation & jurisprudence
  • United States Environmental Protection Agency / standards

Substances

  • Endocrine Disruptors
  • Pesticides