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New public CSRML-based structure-fingerprint method for profiling and categorizing PFAS structures for modeling and read-across
Citation:
Richard, A., R. Lougee, G. Patlewicz, Chris Grulke, A. Williams, C. Yang, J. Rathman, AND T. Magdziarz. New public CSRML-based structure-fingerprint method for profiling and categorizing PFAS structures for modeling and read-across. Society of Toxicology 2021 Virtual Annual meeting, Virtual, NC, March 12 - 26, 2021. https://doi.org/10.23645/epacomptox.14470782
Impact/Purpose:
Poster presented to the Society of Toxicology 2021 Virtual Annual meeting March 2021. Studies under this output will be designed to address data gaps associated with PFAS and to investigate whether the structural categories that had been defined to select the ~150 PFAS are supported by the NAM data being generated by HTT. The insights gained will be used to refine a harmonized scheme of categorizing PFAS. For PFAS with legacy in vivo data, the concordance of the NAM data relative to the in vivo data will also be evaluated in order to anchor what in vivo toxicity predictions can be made within the PFAS categories and with what level of scientific confidence. The results of these efforts will be of direct benefit to program and regional offices as well as the greater scientific community.
Description:
Per- and polyfluoroalkyl substances (PFAS) are of high public interest due to widespread production, environmental persistence, and adverse ecological and health impacts. EPA’s Comptox Chemicals Dashboard has published an extensive list of over 8000 curated PFAS structures. Whereas most studies to-date have focused on the health effects of a small number of PFAS compounds, such as PFOA and PFOS, relatively little is known about the health effects of the vast majority of PFAS and their byproducts. Methods for profiling the PFAS chemical structure space are needed to support modeling and structure-based categorization efforts. However, naming conventions and publicly available molecular fingerprinting methods are ill-suited to capturing the wide range of potentially relevant PFAS structural patterns. Expert-defined PFAS chemical category terms are limited to simpler categories (e.g., perfluorocarboxylic acids) and often lack clear structure definition. With the publicly available CSRML (Chemical Subgraphs and Reactions Markup Language), we developed a set of 130 TxP_PFAS fingerprints, including an expanded set of ToxPrint functional groups, augmented by over 80 new fingerprints capturing higher level categories, as well as unique aspects of PFAS structures, including perfluoro chains, polyfluoro substructures, fluorinated rings, and various perfluoro branching patterns. These CSRML PFAS categories and features can be processed with the public Chemotyper, provide comprehensive coverage of available PFAS lists, and are being used to profile and describe PFAS chemical lists currently undergoing testing within EPA. Abstract does not reflect EPA policy.
URLs/Downloads:
DOI: New public CSRML-based structure-fingerprint method for profiling and categorizing PFAS structures for modeling and read-across
RICHARD_SOT2021_PFAS_TXPS_POSTER_20210224.PDF (PDF, NA pp, 1716.353 KB, about PDF)