Integrated Model for PFAS Environmental and Public Health Risk Assessment (IMPERA): A framework for multidimensional evidence integration

Background Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants of growing public health concern because of their widespread occurrence, environmental persistence, complex environmental behavior, and evolving toxicological understanding. Although advances in analytical chemistry, environmental monitoring, toxicology, and regulatory guidance have strengthened PFAS assessment, interpretation remains limited because concentration- and toxicity-based metrics alone do not capture analytical completeness, PFAS composition, environmental transport, exposure context, or scientific uncertainty. Objectives This review critically evaluates current PFAS interpretation approaches and presents the Integrated Model for PFAS Environmental and Public Health Risk Assessment (IMPERA), a multidimensional evidence-integration framework designed to complement existing PFAS risk-assessment methods. Methods IMPERA was developed through a critical synthesis of evidence from PFAS analytical chemistry, environmental fate and transport, exposure science, toxicology, regulatory guidance, and decision science. Evidence was organized into five complementary domains and integrated using structured Weight-of-Evidence (WoE) principles. Results IMPERA is founded on the premise that equivalent concentration- or toxicity-based indicators do not necessarily imply equivalent environmental or public health significance. The framework integrates Analytical Coverage, PFAS Composition, Environmental Transport, System-Level Exposure, and Toxicological Interpretation through the proposed Analytical–Chemical–Environmental Coupling (ACEC) concept to generate an Integrated Evidence Profile. Multi-Criteria Decision Analysis (MCDA) may be applied after evidence integration when comparison among management alternatives is required. An illustrative comparison of two hypothetical drinking-water systems demonstrates how similar toxicity metrics can produce different Integrated Evidence Profiles because of differences in evidence completeness, environmental context, and uncertainty. The framework is further contextualized within a One Health perspective linking environmental, animal, and human health. Conclusions IMPERA complements existing regulatory and health-based risk-assessment approaches by providing a transparent framework for multidimensional PFAS interpretation. Although the illustrative application demonstrates its operational logic, empirical validation through case studies and reproducibility testing is required before broader implementation.