Toxicokinetic Models and Biomonitoring for PFAS Risk Assessment

Dear Colleagues,

Per- and polyfluoroalkyl substances (PFASs) are increasingly contaminating environments worldwide and have become a major global public health concern. Because PFAS exhibit long biological half-lives in humans, blood concentrations are widely used not only as indicators of exposure but also as key metrics in health risk assessment. Estimation of expo-sure levels has often relied on relatively simple compartment models. However, for assessing toxicological effects, inter-species differences, and organ-specific risks, physiologically based pharmacokinetic (PBPK) modeling provides a more scientifically robust framework.

A major challenge in PBPK modeling of PFASs is that their uptake and distribution from blood into tissues are mediated by active transport mechanisms. Moreover, the transporters involved differ across organs, making it difficult to predict tissue-specific accumulation and toxicity. This biological heterogeneity complicates the extrapolation of findings across species and populations.

Additional challenges arise from the global nature of PFAS contamination. Sources of exposure vary considerably across regions, including industrial emissions, military bases, contaminated drinking water, consumer products, and waste disposal sites. Consequently, populations are exposed to diverse mixtures of PFAS compounds. Furthermore, thousands of PFAS chemicals have been identified, including numerous structural isomers with distinct physicochemical and tox-icological properties. Such diversity creates substantial uncertainty in both exposure assessment and risk characteriza-tion.

Given these scientific challenges, uncertainty is an unavoidable component of PFAS risk assessment. Nevertheless, ad-vances in analytical chemistry, toxicology, epidemiology, biomonitoring, and computational modeling are steadily im-proving our understanding of PFAS behavior and health effects. This Special Issue aims to highlight cutting-edge evi-dence from researchers worldwide to develop more rigorous, evidence-based approaches to PFAS risk assessment through biomonitoring.

Prof. Dr. Akio Koizumi
Prof. Dr. Tetsuo Nomiyama
Guest Editors

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• toxicokinetic modeling
• exposure assessment
• biomonitoring
• risk assessment
• PBBK modeling
• PFASs isomers