Towards a Better Understanding of the Human Health Risk of Per- and Polyfluoroalkyl Substances Using Organoid Models.

The ubiquitous presence of per- and polyfluoroalkyl substances (PFAS) in the environment has garnered global public concern. Epidemiological studies have proved that exposure to PFAS is associated with human health risks. Although evidence demonstrated the toxic mechanisms of PFAS based on animal models and traditional cell cultures, their limitations in inter-species differences and lack of human-relevant microenvironments hinder the understanding of health risks from PFAS exposure. There is an increasing necessity to explore alternative methodologies that can effectively evaluate human health risks. Human organoids derived from stem cells accurately mimic the sophisticated and multicellular structures of native human organs, providing promising models for toxicology research. Advanced organoids combined with innovative technologies are expected to improve understanding of the breadth and depth of PFAS toxicity.