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Evaluation of Per- and Poly fluoroalkyl Substances (PFAS) in vitro toxicity testing for developmental neurotoxicity (SOT 2023)
Citation:
Carstens, K., T. Freudenrich, K. Wallace, S. Choo, A. Carpenter, A. Richard, G. Patlewicz, B. Wetmore, K. Friedman, AND T. Shafer. Evaluation of Per- and Poly fluoroalkyl Substances (PFAS) in vitro toxicity testing for developmental neurotoxicity (SOT 2023). Presented at Society of Toxicology 62nd Annual Meeting and ToxExpo 2023, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.22714213
Impact/Purpose:
Poster presented at the Society of Toxicology (SOT) meeting in March 2023. The purpose of this poster presentation is to share and receive feedback on work evlauting a set of 160 PFAS screened across mutliple new approach methods (NAMs) for developmental neurotoxicity (DNT). The abstract and the proposal will be reviewed by the meeting planning committee.
Description:
Per- and poly fluoroalkyl substances (PFAS) are a diverse set of commercial chemicals widely detected in humans and the environment. However, only a limited number of PFAS are associated with epidemiological or experimental data for hazard identification. To provide developmental neurotoxicity (DNT) hazard information, the work herein employed DNT new approach methods (NAMs) to generate in vitro screening data for a set of 160 PFAS. The DNT NAM battery was comprised of the microelectrode array neuronal network formation assay and high-content imaging assays (proliferation, apoptosis, and neurite outgrowth). The majority of PFAS (116/160) were inactive in the DNT NAMs, leaving 44 active PFAS that decreased neural network connectivity and neurite length. Analytical quality control indicated 43/116 inactive samples and 10/44 active samples were degraded; as such, careful interpretation is required as some negatives may have been due to loss of the parent PFAS, and some actives may have resulted from a mixture of parent and/or degradants. PFAS containing a perfluorinated carbon (C) chain length ≥8, a high C:fluorine ratio, or a carboxylic acid moiety were more likely to be bioactive in the DNT NAMs. Of the PFAS positives in DNT NAMs, 85% were also active in other EPA ToxCast assays, whereas 79% of PFAS inactives in the DNT NAMs were active in other assays. These data demonstrate that a subset of PFAS perturb neurodevelopmental processes in vitro and suggest focusing future DNT studies on PFAS containing certain structural feature descriptors. (This abstract does not reflect U.S. EPA Policy).
URLs/Downloads:
DOI: Evaluation of Per- and Poly fluoroalkyl Substances (PFAS) in vitro toxicity testing for developmental neurotoxicity (SOT 2023)
CARSTENS_SOT23_PFAS_V2.PDF (PDF, NA pp, 1051.839 KB, about PDF)