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A novel constrained drop surfactometer demonstrates inhibition of lung surfactant function by PFAS aerosols in vitro

Year: 2025
Type: article
Abstract: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in both indoor and outdoor air, and there is an increasing need to effectively screen this diverse class of chemicals for inhalation toxicity potential. Because PFAS have strong surface-active properties, we hypothesized they may interfere with lung surfactant (LS) activity. We investigated the ability of 17 PFAS delivered as liquid aerosols to inhibit LS function in a newly developed constrained drop surfactometer. Using both fluorescent tracers and mass spectrometry techniques, deposition of PFAS aerosols onto exposed LS was determined. Nine of the 17 PFAS increased surface tension (ST) above the inhibition threshold, defined as mean minimum post-exposure ST above 10 mN/m. Inhibitory compounds included legacy PFAS (perfluorooctanoic acid [PFOA], perfluorooctane sulfonic acid [PFOS]), emerging compounds (hexafluoropropylene oxide dimer acid, perfluoro-2-methoxyacetic acid), perfluorooctyltriethoxysilane, and perfluorooctane-sulfonamides and -sulfonamidoethanols. These compounds represent a wide range of molecular weights and functional head groups (carboxylic and sulfonic acids, sulfonamides, and siloxane). Among these compounds, the lowest modeled inhibitory doses were for N-methyl-perfluorooctane-sulfonamidoethanol (0.34 ppm) and N-ethyl-perfluorooctane-sulfonamidoethanol (0.14 ppm). Concentrations of PFOA and PFOS required to inhibit LS were significantly lower when aerosolized than when directly mixed with LS, demonstrating the importance of interactions with surfactant at the air-liquid interface. Our results show that a combination of size, functional groups, and hydrophobicity influence the ability of PFAS to inhibit LS function. Under high exposure conditions, inhaled PFAS may initiate an adverse outcome pathway through surfactant inhibition, which may ultimately produce a reduction of lung function.
Language: English
Open Access status: green
OpenAlex ID: W4416656717
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Cites: 47
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