Comparison of four PFAS mixtures assessment approaches based on extensive tap water and groundwater data

Per- and polyfluoroalkyl substances (PFAS) are persistent and toxic contaminants widely detected in drinking water systems. Regulatory responses have varied globally, with a growing need for science-based approaches to assess the health risks posed by PFAS mixtures. However, existing studies have mainly relied on isolated theoretical examples or small datasets, leaving the real-world implications of these approaches poorly understood. This study addresses this gap by applying to two high-quality datasets from large-scale PFAS monitoring campaigns conducted by the USGS four leading PFAS mixtures assessment approaches: (i) the EU approach based on thresholds for total PFAS and the sum of 20 specific PFAS; (ii) Maximum Contaminant Levels established by the US EPA; (iii) the Relative Potency Factor method under evaluation in the EU; and (iv) the Risk Assessment (US EPA RAGS) approach. These datasets cover more than 1700 groundwater and tap water samples, providing a robust basis to investigate the practical differences and consequences of each method. Results reveal significant discrepancies across methods. The EU approach, although applicable to all samples, does not consider toxicological differences among individual compounds, often underestimating health impacts. The Maximum Contaminant Levels approach offers a more health-based evaluation, though it applies to only a subset of compounds. In contrast, the Relative Potency Factor and Risk Assessment (US EPA RAGS) methods provide toxicity-weighted evaluations, offering a more robust and consistent characterization of health risks. Notably, only the Risk Assessment (US EPA RAGS) evaluates carcinogenicity effects in the PFOA and PFOS assessment, though its estimates rely on evolving and debated toxicological assumptions, requiring cautious interpretation. These findings underscore how methodological choices influence PFAS risk evaluation, offering useful insights for future environmental policy and risk assessment practices.