Per- and polyfluoroalkyl substances in food systems: occurrence, analytical methods, toxicity, and risk assessment

Abstract Per- and polyfluoroalkyl substances (PFAS) are a structurally diverse class of synthetic organofluoride compounds characterized by exceptional chemical stability, environmental mobility, and resistance to degradation. This review synthesizes current knowledge on PFAS toxicology, analytical determination, occurrence in food systems, and implications for human health risk assessment. Experimental and epidemiological evidence demonstrates that PFAS exposure is associated with a broad spectrum of adverse effects, including immune suppression, endocrine disruption, hepatotoxicity, reproductive and developmental toxicity, neurotoxicity, and carcinogenic potential. In addition to legacy PFAS, increasing attention has focused on emerging replacement compounds, including short-chain PFAS and fluorinated alternatives such as HFPO-DA (GenX), ADONA, 6:2 Cl-PFESA, and 6:2 FTAB, which are increasingly detected in environmental and food matrices and show growing evidence of persistence and potential toxicity. Their occurrence at trace levels in complex matrices necessitates advanced analytical approaches, with liquid chromatography coupled to tandem or high-resolution mass spectrometry, supported by solid-phase extraction and QuEChERS-based workflows, forming the core of contemporary PFAS determination. PFAS are widely detected across food categories, including fish, meat, dairy products, cereals, and vegetables, reflecting environmental contamination, bioaccumulation, and migration from food contact materials, with dietary intake remaining the predominant exposure pathway for the general population. Despite regulatory progress, substantial uncertainties remain regarding mixture toxicity, the long-term health effects of emerging PFAS, and the assessment of structurally diverse PFAS. Addressing these gaps will require standardized analytical methods, expanded surveillance programs, and more comprehensive risk assessment frameworks.