Science Inventory

PFAS Toxprints: A Hierarchical Structure-Based Categorization Method for Characterization of Per- and Polyfluoroalkyl Substances


Lougee, R., G. Patlewicz, Chris Grulke, A. Williams, C. Yany, J. Rathman, T. Magdziarz, AND A. Richard. PFAS Toxprints: A Hierarchical Structure-Based Categorization Method for Characterization of Per- and Polyfluoroalkyl Substances. American Chemical Society Fall 2020 Meeting (Virtual), San Francisco, California, August 16 - 20, 2020.


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.


Per- and polyfluoroalkyl substances (PFAS) are of high public interest due to widespread production, environmental persistence, and adverse ecological and health impacts. Recently, both the OECD and the EPA’s Comptox Chemicals Dashboard have published extensive lists of over 4500 and 6000 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, the unique PFAS structural space is ill-suited for publicly available molecular fingerprinting methods. Furthermore, 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 more than 130 fingerprints to capture 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 used 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.

Record Details:

Product Published Date:08/20/2020
Record Last Revised:09/16/2020
OMB Category:Other
Record ID: 349706