Profiling biotoxicities of hexafluoropropylene oxide trimer acid with human embryonic stem cell-based assays

Hexafluoropropylene oxide trimer acid (HFPO-TA), an emerging replacement of perfluorooctanoic acid (PFOA), has recently been reported to be a potential environmental contaminant. Due to the similar structure to PFOA, HFPO-TA may cause comparable adverse effects on human health. Therefore, evaluating the toxic profiles of HFPO-TA has become an urgent task. In this study, we investigated the cytotoxicity and hepatoxicity of HFPO-TA using human embryonic stem cell (hESC)-based assays. Results showed that HFPO-TA reduced hESCs' viability in a dose dependent manner, and the calculated IC50 for 24, 48 and 72 hr were 222.8, 167.4, and 80.6 μmol/L, respectively. Significant intracellular ROS accumulation and mitochondrion membrane potential reduction were detected with HFPO-TA exposure, and increased apoptotic/necrotic cells were also observed in high dose of HFPO-TA treated group. Moreover, HFPO-TA at noncytotoxic concentrations also significantly impaired the functions of induced hepatocytes by diminishing cell glycogen storage ability and deregulating specific functional genes. Transcriptome sequencing analysis identified a set of hepatic associated biological processes responding to HFPO-TA exposure. PPAR was the most significantly enriched pathway. Genes including FGA, FGB, FGG, AHSG, HRG, ITIH2, ALB were characterized as hub genes by cytoHubba plug-in. These data indicated that HFPO-TA is a potential hepatotoxicant, and may not be a safe replacement for PFOA.