Abstract
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.
Highlights
Per- and polyfluoroalkyl substances (PFASs) have diverse technical applications due to their superior surface-active properties
The lowest observed adverse effect concentration (LOAEC) was defined as the lowest concentration of a given PFAS producing a minimum surface tension at the 10th round of compression/expansion that was significantly different from the minimum surface tension of the control lung surfactant (LS) in the absence of the compound (Table 2)
LS was diluted with water, except for 8:2 fluorotelomer alcohols (FTOHs), where the control was diluted in phosphate buffered saline (PBS)
Summary
Per- and polyfluoroalkyl substances (PFASs) have diverse technical applications due to their superior surface-active properties. Emerging evidence shows a link between exposure to indoor air pollutants, like PFASs, and lung diseases (Qin et al, 2017; Impinen et al, 2018). Epidemiological studies indicate an association between prenatal PFAS exposure and increased number of infections in children (Granum et al, 2013; Dalsager et al, 2016;Impinen et al, 2018; Impinen et al, 2019) and lower vaccination response (Granum et al., 2013; Grandjean et al, 2017), suggesting that PFASs have an immunosuppressive effect. PFAS exposure and the risk of developing asthma has been studied, the relation is not clear (Humblet et al, 2014; Impinen et al, 2018; Impinen et al, 2019). Consumer products containing PFASs such as fluorinated ski wax, cosmetic sprays or impregnation products may lead to inhalation exposure and add to the total PFAS
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