Human Exposure to Per- and Polyfluoroalkyl Substances (PFAS): Toxicological Mechanisms, Exposure Pathways, Biomonitoring, and Health Risk Assessment

Per- and polyfluoroalkyl substances (PFAS) are a large class of persistent synthetic chemicals of global concern because of their widespread environmental occurrence, bioaccumulation potential, and adverse human health effects. Although numerous reviews have addressed individual aspects of PFAS chemistry, toxicity, exposure, or regulation, integrated evaluations encompassing exposure pathways, toxicological mechanisms, biomonitoring, epidemiology, and health-risk assessment remain limited. This structured narrative review critically synthesises peer-reviewed literature and authoritative reports from international regulatory organisations to provide a comprehensive assessment of legacy and emerging PFAS. The review examines major exposure pathways, toxicokinetics, molecular mechanisms of toxicity, biomonitoring approaches, epidemiological evidence, and advances in human health-risk assessment. Particular emphasis is placed on well-characterised legacy PFAS, especially perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA), while recognising the limited evidence available for many emerging alternatives. Current evidence identifies drinking water and dietary intake as the dominant exposure pathways and consistently associates PFOS, PFOA, perfluorohexane sulphonate, and related compounds with endocrine, immune, metabolic, developmental, and cardiovascular effects. These findings support a shift from single-compound assessments towards cumulative risk assessment frameworks encompassing both legacy and emerging PFAS. Important uncertainties remain regarding chronic low-dose exposure, mixture toxicity, replacement PFAS, and long-term health outcomes, highlighting the need for longitudinal biomonitoring, advanced exposure assessment, and internationally harmonised regulatory strategies to strengthen evidence-based public health protection.