Per- and polyfluoroalkyl substances (PFASs) modify lung surfactant function and pro-inflammatory responses in human bronchial epithelial cells

• Published in: Toxicology in vitro Vol. 62; p. 104656
• Main Authors: Sørli, Jorid B., Låg, Marit, Ekeren, Leni, Perez-Gil, Jesus, Haug, Line S., Da Silva, Emilie, Matrod, Muhammad N., Gützkow, Kristine B., Lindeman, Birgitte
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2020; Elsevier Science Ltd
• Subjects: Acute inhalation toxicity; Alkanesulfonic Acids - toxicity; Alternative methods; Bronchi - cytology; Bronchial epithelial cells; Caprylates - toxicity; Cell Line; Cell Survival - drug effects; Chemokines; Constrained drop surfactometer; CXCL10 protein; Cytokines - metabolism; Epithelial cells; Fluorocarbons - toxicity; Human behavior; Humans; IL-1β; Inflammation; Inflammatory response; Inhalation; Lung surfactant; Lungs; Perfluoro compounds; Perfluorohexane; Perfluorooctanoic acid; Pro-inflammatory responses; Pulmonary Surfactants - metabolism; Regulators; Respiration; Respiratory system; Salts; Surfactants; Toxicity; Toxicity testing; DMSO; LS; PFAS; LPS; NOAEC; EFSA; Constrained drop surfactometer; CDS; PFDA; CMC; DPPC; PBS; PFBS; Alternative methods; PFHxS; Pro-inflammatory responses; Poly I:C; PFOA; LOAEC; LOQ; POP; REACH; Bronchial epithelial cells; Acute inhalation toxicity; 8:2 FTOH; POSF; Lung surfactant; TLR3; ELISA; PFOS
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2019.104656

The toxicity of some per- and polyfluoroalkyl substances (PFASs), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) has been studied thoroughly, showing that systemic PFASs targets the lungs. However, regulators lack data to assess the impact of other PFASs on the lungs and alternative methods to test substances for lung toxicity are needed. We combined two in vitro models to assess toxicity to the respiratory system; i) a lung surfactant (LS) function assay to assess the acute inhalation toxicity potential, and ii) a cell model with human bronchial epithelial cells to study pro-inflammatory potential and modulation of inflammatory responses. We tested salts of four PFASs: perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), PFOS, and PFOA as well as the fluorotelomer 8:2 FTOH. The results show that PFHxS, PFOA and PFOS can inhibit LS function. High PFOS concentrations induced a pro-inflammatory response, measured as increased IL-1α/β release. Moderate concentrations of PFOS suppressed release of the chemokines CXCL8 and CXCL10, whereas both PFOS and PFOA stimulated the release of the pro-inflammatory cytokine IL-1β in immune stimulated human bronchial epithelial cells. These findings support the concern that some PFASs may increase the risk of acute lung toxicity and of airway infections. •Inhibition of lung surfactant function and modulation of immune response contribute to define acute lung toxicity of PFASs•PFHxS, PFOS and PFOA inhibited lung surfactant function, PFBS or 8:2 FTOH did not at the concentrations tested•PFOS suppressed the release of CXCL8 and CXCL10 from immune stimulated human bronchial epithelial (HBEC3-KT) cells•PFOS and PFOA enhanced the release of IL-1α/β from immune stimulated HBEC3-KT cells•Both in vitro assays point to PFOS and PFOA as the most potent of the tested PFASs