Citation:

Villeneuve, D. Assessing ecological effects and relevance of estrogenic per- and polyfluoroalkyl substances (PFAS). US EPA Great Lakes Toxicology and Ecology Division Seminar, Duluth, MN, April 05, 2023. https://doi.org/10.23645/epacomptox.22577623

Impact/Purpose:

Results of this research help to develop confidence in the use of this NAMs-based screening approach for identifying PFAS with potential ecological hazards, specifically estrogenic hazards. PFAS that elicited estrogen-receptor mediated bioactivity in human cells in vitro, were shown to be able to elicit changes in estrogen-regulated gene expression in vivo.  Effects on estrogen regulated gene expression were confirmed with two orthogonal methods, both targeted quantitative real-time PCR and with the use of a custom qPCR array (EcoToxChip).  Finally, a selected PFAS (FC10-diol) was evaluated in a 21 d reproduction study and results verified that the chemical was able to cause an adverse effect consistent with an adverse outcome pathway (AOP) linking estrogen receptor activation to reproductive impairment in fish. Evaluation of the in vivo effect concentrations indicates that although certain PFAS can cause estrogenic effects, those effects are likely to occur only in surface waters most heavily contaminated PFAS globally.  Results contribute to the evaluation of hazard and risk associated with PFAS in the environment and help to build confidence in the use of new approach methodologies, AOPs, and tiered testing strategies for the same.     

Description:

Per- and polyfluoroalkyl substances (PFAS) are a large group of chemicals of concern due to their widespread use, accumulation in humans and wildlife, and potential for toxicity. Based on bioactivity screening, over 25% of PFAS evaluated showed some degree of estrogenic activity. This seminar provides an overview of recent and on-going research aimed to evaluating whether PFAS identified as estrogenic in vitro can elicit estrogenic effects in vivo. The potential ecological relevance of the estrogenic activity of PFAS is discussed in the context of the observed effect concentrations in adult fathead minnows exposed to the test compounds.

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