Confronting Novel Alternatives of Per- and Polyfluoroalkyl Substances: From the Exposure Pathway to the Health Risk Estimation

Per- and polyfluoroalkyl substances (PFAS) are characterized by their ability to repel both grease and water, properties that led to their initial development as surfactants and surface protectors. As novel PFAS alternatives emerge and are detected in the environment, these substances present significant challenges related to environmental media, human exposure, and health risk assessments. This article reviews current knowledge on the origins of PFAS and their pathways from production facilities and PFAS-containing products to environmental organisms and humans and summarizes existing data on toxicity and toxicological mechanisms in laboratory animals and examines associated adverse health outcomes in humans through various epidemiological studies. Although risk assessments of PFAS alternatives are complicated by unclear chemical structures and complex effects, quantitative structure–activity relationship (QSAR) models and prioritization approaches offer potential strategies for PFAS management. A comprehensive understanding of the environmental behavior and toxicology of novel PFAS will enhance their management and improve human health risk assessments.