Comparative toxicometabolomics of perfluorooctanoic acid (PFOA) and next-generation perfluoroalkyl substances

) was significantly correlated with alkyl chain-length, and toxic concentrations were quantitatively similar to those reported previously for PFAS. Metabolic profiling of zebrafish embryos exposed to selected PFAS, specifically including PFOA and two representative PFECA (i.e., GenX and PFO3TDA), enabled elaboration of an integrated model of the metabolic pathways associated with toxicity of these representative PFAS. Alterations of metabolic profiles suggested targeting of hepatocytes (i.e., hepatotoxicity), as well as apparent modulation of neural metabolites, and moreover, were consistent with a previously proposed role of mitochondrial disruption and peroxisome proliferator-activated receptor (PPAR) activation as reflected by dysfunctions of carbohydrate, lipid and amino acid metabolism, and consistent with a previously proposed contribution of PFAS to metabolic syndrome. Taken together, it was generally concluded that toxicity of PFECA is quantitatively and qualitatively similar to PFOA, and these analogs, likewise, represent potential concerns as environmental toxicants.