Insights into toxicological mechanisms of per-/polyfluoroalkyl substances by using omics-centered approaches

The extensive presence of per-/polyfluoroalkyl substances (PFASs) in the environment and their adverse effects on organisms have garnered increasing concern. With the shift of industrial development from legacy to emerging PFASs, expanding the understanding of molecular responses to legacy and emerging PFASs is essential to accurately assess their risks to organisms. Compared with traditional toxicological approaches, omics technologies including transcriptomics, proteomics, metabolomics/lipidomics, and microbiomics allow comprehensive analysis of the molecular changes that occur in organisms after PFAS exposure. This paper comprehensively reviews the insights of omics approaches, especially the multi-omics approach, on the toxic mechanisms of both legacy and emerging PFASs in recent five years, focusing on hepatotoxicity, developmental toxicity, immunotoxicity, reproductive toxicity, neurotoxicity, and the endocrine-disrupting effect. PFASs exert various toxic effects via lipid and amino acid metabolism disruption, perturbations in several cell signal pathways, and binding to nuclear receptors. Notably, integrating multi-omics offers a thorough insight into the mechanisms of toxicity associated with PFASs. The gut microbiota plays an essential regulatory role in the toxic mechanisms of PFAS-induced hepatotoxicity. Finally, further research directions for PFAS toxicology based on omics technologies are prospected.