Structure-Dependent Toxicological Profiles of PFAS: Mechanistic Determinants, Predictive Models, and Organ-Specific Biomarkers

Per- and polyfluoroalkyl substances (PFAS) comprise a structurally diverse class of thousands of compounds, sharing a persistent carbon-fluorine backbone but displaying strikingly different behavior in the body. Individual PFAS congeners vary widely in how long they persist, how they distribute across organs, and which tissues they affect most — differences that remain poorly explained at the mechanistic level. This gap limits our ability to extrapolate toxicity findings from one PFAS compound to another, and constrains the development of reliable, structure-based models for human health risk assessment.This Research Topic focuses on why structurally different PFAS produce such different toxicological profiles, and on translating that understanding into tools that can predict human toxicity directly from chemical structure. By bringing together researchers working across mechanistic toxicology, computational modeling, and biomarker development, this collection aims to advance a more predictive, structure-informed approach to evaluating PFAS safety.We welcome contributions addressing, but not limited to, the following themes:• Structure-toxicity relationships across PFAS congeners, including how chain length, functional head group, and degree of fluorination shape toxicokinetic behavior (e.g., protein binding, transporter-mediated disposition, tissue half-life)• Mechanistic drivers of organ-specific toxicodynamic effects across different PFAS structures (e.g., hepatic, renal, endocrine, or immune pathways)• Computational and machine learning-based models (QSAR, read-across, adverse outcome pathway frameworks) for predicting PFAS toxicity from structural or physicochemical descriptors• Non-animal and in vitro-to-in vivo extrapolation approaches for assessing toxicity across structurally diverse PFAS• Biomarkers of exposure and early biological effect that can distinguish toxicological risk between different PFAS structural classesWe encourage submissions of Original Research, Reviews, Mini Reviews, Systematic Reviews, and Perspectives that advance the mechanistic and predictive understanding of structure-dependent PFAS toxicity, supporting more accurate, structure-informed human health risk assessment. Topic editors: Hengyi Xu, John Erik Mylroie Source: https://www.frontiersin.org/research-topics/85098/structure-dependent-toxicological-profiles-of-pfas-mechanistic-determinants-predictive-models-and-organ-specific-biomarkers