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This study suggests that grouping and categorizing PFAS using fundamental classification criteria based on composition and structure can be used to identify appropriate groups of PFAS substances for risk assessment, thereby dispelling assertions that there are too many PFAS chemistries to conduct proper regulatory risk assessments for the commercially relevant substances. Integr Environ Assess Manag 2021;001-11. © 2021 The Chemours Company, Beach Edge Consulting, LLC, AGC Chemicals Americas Inc., Daikin America Inc. Integrated Environmental Assessm