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Evaluation of Per- and Poly fluoroalkyl Substances (PFAS) in vitro toxicity testing for developmental neurotoxicity
Citation:
Carstens, K., T. Freudenrich, K. Wallace, S. Choo, A. Carpenter, A. Richard, G. Patlewicz, B. Wetmore, K. Paul-Friedman, AND T. Shafer. Evaluation of Per- and Poly fluoroalkyl Substances (PFAS) in vitro toxicity testing for developmental neurotoxicity. American Society for Cellular and Computational Toxicology (ASCCT) Conference, Durham, NC, October 19 - 21, 2022. https://doi.org/10.23645/epacomptox.21859527
Impact/Purpose:
Poster presented to the American Society for Cellular and Computational Toxicology (ASCCT) meeting in October 2022. 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 animal 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 (NFA) and high-content imaging (HCI) assays to evaluate proliferation, apoptosis, and neurite outgrowth. The majority of PFAS (116/160) were inactive in the DNT NAMs, leaving 44 active PFAS that decreased measures of neural network connectivity and neurite length. Analytical quality control indicated 35/116 inactive PFAS samples and 10/44 active PFAS 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 of PFAS. 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 studies of DNT on PFAS with certain structural feature descriptors. (This abstract does not reflect Agency Policy).
URLs/Downloads:
DOI: Evaluation of Per- and Poly fluoroalkyl Substances (PFAS) in vitro toxicity testing for developmental neurotoxicity
CARSTENS_ASCCT22_PFAS_CLEARANCE.PDF (PDF, NA pp, 2302.634 KB, about PDF)