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5918817 
Journal Article 
Per- and polyfluoroalkyl substances (PFASs) modify lung surfactant function and pro-inflammatory responses in human bronchial epithelial cells 
Sørli, JB; Låg, M; Ekeren, L; Perez-Gil, J; Haug, LS; Da Silva, E; Matrod, MN; Gützkow, KB; Lindeman, B 
2020 
Toxicology In Vitro
ISSN: 0887-2333
EISSN: 1879-3177 
62 
104656 
English 
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. 
Acute inhalation toxicity; Lung surfactant; Constrained drop surfactometer; Pro-inflammatory responses; Bronchial epithelial cells; Alternative methods 
• Additional PFAS (formerly XAgency)
• Expanded PFAS SEM (formerly PFAS 430)
     Litsearch: September 2019
          PubMed
     Not prioritized for screening
     Perfluorooctane
• PFAS 150
     Literature Search Update December 2021
          PubMed
          WOS
     Missing 2021 searches
     Literature Search Update December 2020
          PubMed
          WOS
     Literature Search August 2019
          PubMed
          Web of Science
     Screened Studies
          Supplemental
     Perfluorinated compounds
     Perfluorobutanesulfonate
     Perfluorobutanesulfonyl fluoride
     Perfluorohexanesulfonic acid
     Perfluorooctane
     (Perfluorooctyl)ethanol
• PFBS
     Search
          PubMed
          WOS
     Lit Search Update: May 2019 - May 2020
          WoS
          PubMed
     Scopus: April 2021
• PFHxS
     Database searches
          Pubmed
          WOS
          Scopus
          Pelch PFAS SEM
     Supplemental
          TiAb
          In vitro or in silico studies (non-genotoxicity)
          In vivo mechanistic or MOA studies, including non-PECO routes of exposure and populations
     Literature Search Update April 2023
          Supplemental
               In vivo mechanistic or MOA studies, including non-PECO routes of exposure (e.g., nonmammalian)
               In vitro in silico (non-genotoxicity)
• PFOA (335-67-1) and PFOS (1763-23-1)
     LitSearch: Feb 2019 - May 2020
          PubMed
          WoS
     Literature Search Update (Apr 2019 - Sep 2020)
          PubMed
          WOS