40 Utilising advanced <i>in vitro</i> lung models to determine the potential toxicological impacts of indoor pollutant component exposure scenarios

Abstract Indoor air pollution (IAP) consists of particulate matter (PM), volatile organic compounds (VOCs), and biological materials. The literature has previously focussed upon components individually, yet this is not realistic of human exposure. Therefore, the aim of this project was to compare different exposure scenarios; individual, sequential and combined; of a range of common IAP components. Using a well characterised in vitro model of the alveolar region (ATI, ATII (epithelial cells) and macrophages), the impact of multi-pollutant exposures (24 h) on the toxicological and immunological responses were assessed as regards IAP components of indoor PM (SRM2583) (232 to 3,100 ng/cm2) alone, before, after, or in combination with house dust mite (HDM) (30 μg/ml), endotoxin (lipopolysaccharide (LPS)) (175 μg/ml) and a common IAP VOC (ethanol) (1,000 μg/m3) via aerosol exposure (VITROCELL® Cloud12). SRM2583 alone decreased (P &amp;gt; 0.05) viability, though was ameliorated by post-exposure with LPS (1.5-fold increase). Interestingly, increases in viability were observed following LPS or HDM exposure before SRM2583 (P &amp;gt; 0.05). HDM exposure before SRM2583 also caused IL-1β, IL-6 and IL-8 to be increased (P &amp;lt; 0.05) compared to all other exposure scenarios. In contrast, IL-1β and IL-8 were decreased (P &amp;lt; 0.05) when LPS was exposed before SRM2583, compared to baseline. Combined VOC exposures (ethanol + SRM2583 + LPS) also induced a significant increase in IL-1β, IL-6, and TNF-α compared to sequential (ethanol-&amp;gt;SRM2583 + LPS) exposures. Thus, in summary, the combination exposure of IAP components compared to sequential exposures shows heightened pro-inflammatory effects, depending upon the IAP component. These findings indicate that the exposure sequence of IAPs, and the specific IAP components themselves influences the biological response in vitro.