Current Status of Per- and Poly-Fluoroalkyl Substances (PFAS) Exposure on Lung Cell Biology and Pulmonary Outcomes along Human Health Risk Assessment Steps

This review aims to summarize the effects of per- and poly-fluoroalkyl substances (PFAS) exposures on the lung, emphasizing data coverage across steps of human health risk assessments. There is expansive literature characterizing PFAS contamination in water, but recent studies have identified PFAS as a component of air pollution, thus impacts on the lung have been an increasing point of inquiry. Mounting evidence from human clinical/epidemiological, animal, and in vitro investigations supports relationships between PFAS exposures and adverse pulmonary outcomes including asthma, allergies, infections, and cancer. Focusing on toxicology studies using animal and in vitro lung cell models, exposures to PFAS modulated inflammation/immune responses, oxidative stress, mucus production, surfactant properties, and epithelial barrier integrity, representing important mechanisms impacting pulmonary health. There are expanding datasets linking PFAS exposures to adverse pulmonary outcomes; however, these data originated from mostly oral/ingestion exposure and not from volatilized or aerosolized PFAS exposure designs. Furthermore, there is a general lack of data informing dose-response modeling and risk characterization, representing gaps needed to characterize pulmonary health risks.