Citation:

Tapper, M., J. Denny, B. Sheedy, B. Johnson, AND R. Kolanczyk. Estrogenic Activity of Perfluoro Carboxylic and Sulfonic Acids in Rainbow Trout Estrogen Receptor Binding and Liver Slice Vtg mRNA Expression Assays. Applied In Vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, 9(1):13-22, (2023). https://doi.org/10.1089/aivt.2022.0013

Impact/Purpose:

This study addresses the environmental and health problem of the defining the estrogenic potential of perfluoroalkylated substances (PFAS). The current work used an in vitro rainbow trout estrogen receptor (rtER) binding assay and an ex vivo rtER dependent vitellogenin (Vtg) expression rainbow trout liver slice assay to study the estrogenic potential of a series of perfluoro carboxylic acids and select perfluoro sulfonic acids. The results from this study found the estrogenic potential of these chemicals appears to be low or even nonexistent, as in the case of the smaller perfluoro carboxylic acids, chain length less than six, which had no estrogenic effect in the binding and slice assay results. Furthermore, even with the seven carbon and greater in length perfluoro carboxylic acids and sulfonic acids capable of binding to the rtER and inducing ER dependent gene expression in rainbow trout liver slices, toxicity seems to be having a greater effect than any adverse endocrine effect. This was evident by the low levels of Vtg expression and high levels of toxicity observed in the trout liver slices with exposure to these chemicals. Therefore, the results from these rainbow trout liver assays indicate the estrogenic potential of these PFAS was relatively low or nonexistent. Information generated by such results would be of value to inform toxicological risk assessors about the potential for these chemicals to be endocrine disruptors.

Description:

Introduction: Perfluoroalkylated substances (PFAS) such as carboxylic acids, and sulfonic acids were manufactured in high quantities and are ubiquitous environmental contaminants. These chemicals persist in the environment and tend to bioaccumulate. Materials and Methods: In the current study, the estrogenic potential of a series of perfluoro carboxylic acids and select perfluoro sulfonic acids were assessed in an in vitro rainbow trout estrogen receptor (rtER) binding assay and an ex vivo rtER dependent vitellogenin (Vtg) expression rainbow trout liver slice assay. Results and Discussion: Perfluoro carboxylic acids with perfluoroalkyl chain lengths of four to six did not significantly bind to the rtER or induce Vtg expression in liver slices. Perfluoro carboxylic acids with chain lengths of seven to ten, and sulfonic acids with seven and eight carbon chains bound to the rtER, but with low relative binding affinities. While affinity for the rtER increased with increasing chain length the highest affinity measured was only 0.0025% relative to the endogenous hormone 17β-estradiol at 100%. Both the eight-carbon carboxylic acid and eight-carbon sulfonic acid induced Vtg expression in ex vivo liver slices. However, toxicity did not allow expression to achieve maximum efficacy relative to estradiol. Conclusion: Seven carbon and longer perfluoro carboxylic acids and sulfonic acids are capable of binding to the rtER and inducing ER dependent gene expression in rainbow trout liver slices, but toxicity seems have a greater effect than any adverse endocrine effect.  

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