A Novel Constrained Drop Surfactometer Demonstrates Inhibition of Lung Surfactant Function by PFAS Aerosols In Vitro

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in both indoor and outdoor air, and there is increasing need to effectively screen this diverse class of chemicals for inhalation toxicity potential. Since 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 (CDS). Using both fluorescent tracers and mass spectrometry techniques, deposition of PFAS aerosols onto exposed LS was determined. Nine of the 17 PFAS compounds 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), perfluorooctanesulfonic 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 primary functional group classes (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 compounds to inhibit lung surfactant 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.

Impact/Purpose

Exposure to PFAS by inhalation may be underappreciated given that volatile PFAS (such as fluorotelomer alcohols) can be measured at relatively high levels in the indoor environment, and significant levels of PFAS are also measured after aerosolization of fire-fighting foams and other PFAS-containing products. The integrity and function of pulmonary surfactant, a mixture of phospholipids and proteins in the lung lining fluid, may be disrupted by PFAS deposited in the respiratory tract, potentially causing severe respiratory dysfunction. A new AOP for lung surfactant function inhibition leading to decreased lung function proposes these key events: alveolar collapse, loss of alveolar-capillary membrane integrity, reduced tidal volume, and decreased lung function (https://aopwiki.org/aops/302, Da Silva 2021). The research presented in this paper indicates that a combination of size, functional groups, and hydrophobicity influence the ability of PFAS compounds to inhibit lung surfactant 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.

Citation

Klein, L., J. Heyman, J. Murray, J. Sorli, M. Smeltz, M. Monsees, T. Krantz, E. Puckett, AND S. Gavett. A Novel Constrained Drop Surfactometer Demonstrates Inhibition of Lung Surfactant Function by PFAS Aerosols In Vitro. Society of Toxicology, RESTON, VA, 209(2):kfaf156, (2026). [DOI: 10.1093/toxsci/kfaf156]

DOI: A Novel Constrained Drop Surfactometer Demonstrates Inhibition of Lung Surfactant Function by PFAS Aerosols In Vitro