An unrecognized hazard of inhaled 6:2 FTOH: Pulmonary transformation and interfacial toxicity in the lung

• Surface-active fluorotelomer alcohols (FTOHs) impair pulmonary surfactant function. • FTOHs incorporate into pulmonary surfactant, exhibit microphase segregation. • FTOHs cause lipoprotein impairment accompanied by reactive species generation. • FTOHs undergo transformation in pulmonary fluid, yielding novel fluorinated products. Evidence for the transformation of volatile fluorotelomer alcohols (FTOHs) after respiratory uptake remains elusive, and the role of their surface activity in health risk has been overlooked. Herein, the 6:2 FTOH interaction with the pulmonary barrier formed by pulmonary surfactant (PS) and the potential for undergo transformation was investigated. It turns out that 6:2 FTOH with surface-active properties can altered the ability of PS to reduce surface tension and its compressibility modulus, decreased its phase transition enthalpy (|Δ H |, from 323.5 to 1.5 J/g). Microscopic observations showed that 6:2 FTOH incorporated into intermolecular spaces of PS and exhibited microphase segregation via fluorocarbon–hydrocarbon repulsion. Additionally, 6:2 FTOH interacted with the hydrophobic domains of PS, resulting in a decrease in lipid-protein components, accompanied by lipid peroxidation and protein carbonylation. Furthermore, in PS-containing simulated pulmonary fluid, 6:2 FTOH exhibited time-dependent reactive oxygen species accumulation, while radical content decreased with increasing concentration. 19 F NMR in conjunction with GC–MS confirmed that 6:2 FTOH undergoes transformation. Based on the identification of transformation product, potential transformation pathways of 6: 2 FTOH in pulmonary system were proposed. These findings reveal the impact of FTOH on pulmonary function and provide the first insights into its transformation in the lung, broadening the risk assessment perspective for inhaled surface-active pollutants and diverse per- and polyfluoroalkyl substances.