Metabolomics of per- and polyfluoroalkyl substances (PFAS) exposure: Advances in LC-MS technology and applications

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals known for their high stability and bioaccumulation potential, leading to their widespread presence in the environment and human tissues. Exposure to PFAS has been associated with significant health concerns, including neurotoxicity, hepatotoxicity, and metabolic disturbances. Liquid chromatography-mass spectrometry (LC-MS) based metabolomics has emerged as a powerful and central tool for PFAS research, enabling the comprehensive analysis of metabolic changes induced by exposure. This review provides a critical summary of the applications of LC-MS metabolomics in both clinical studies and various experimental models, including in vivo models (mice) and in vitro systems (cell cultures and zebrafish embryos). We highlight key findings from these studies, specifically focusing on the identification of altered metabolic pathways (e.g., lipid, amino acid, and purine metabolism) and the discovery of specific metabolic biomarkers. Furthermore, we explore the intricate interconnections among these metabolic perturbations, which collectively provide a clearer picture of PFAS toxicological effects. By integrating systematic experimental design with advanced LC-MS techniques, PFAS metabolomics offers invaluable insights into the molecular-level responses to exposure, helping to elucidate toxicological mechanisms and identify specific metabolic biomarkers. The findings synthesized in this review are crucial for supporting a more standardized approach to risk assessment and for informing evidence-based public health policies related to PFAS monitoring and regulation.