Multiple endpoint in vitro toxicity assessment of a prototype heated tobacco product indicates substantially reduced effects compared to those of combustible cigarette

Twenty-eight day repeated exposure of human 3D bronchial epithelial model to heated tobacco aerosols indicates decreased toxicological responses compared to cigarette smoke

“…IL-6 secretion was generally supressed compared to Sham following exposures to all three test articles, however, this effect was generally not significant for the p-HTPs (with the exception of 16 puffs on day 6 and 16 and 48 puffs on day 28). Pathways involving c-jun and NFκB have an association with IL-6 suppression (Tanaka et al, 2014), and in the previous study by Chapman et al (2023) , both the p-HTP Regular product and 1R6F induced significant (dose dependent) increases in c-jun and NFκB activity, albeit to different degrees (and in a single human bronchial cell type model and measured at two timepoints only). Iskandar et al (2018) also observed decreases in IL-6 upon single exposure of tissues to 1R6F, however, not following exposure to HTP aerosol.…”

“…A number of studies have demonstrated, however, that aerosols generated from HTPs are less complex and contain fewer and substantially lower levels of toxicants compared to combustible cigarette smoke, attributed to the heating, as opposed to burning of tobacco ( Jaccard et al, 2017 ; Forster et al, 2018 ; Malt et al, 2022 ). A recent study by Chapman et al (2023) characterised the aerosols generated by two p-HTPs, one of which was used in this study (p-HTP Regular) and reported substantial reductions in the levels and numbers of toxicants present in the aerosol compared to 1R6F smoke. On a per puff basis, nicotine delivery was around half that for the p-HTPs compared to 1R6F, however, on a nicotine equivalent basis, substantial reductions in vitro toxicological outcomes were observed upon exposure of cells to the p-HTP aerosols.…”

“…NGPs which deliver nicotine via the inhalation route and do not involve tobacco combustion include e-cigarettes and heated tobacco products (HTPs). By eliminating burning, these products do not produce smoke but an inhalable aerosol which contains fewer and lower levels of potentially harmful chemicals ( Forster et al, 2018 ; Bentley et al, 2020 ; Rudd et al, 2020 ; Chapman et al, 2023 ).…”

“…Increasing evidence in the scientific literature suggests that the reduction in levels and number of toxicants within the aerosols of NGPs, including e-cigarettes and heated tobacco, correlates with reductions in vitro toxicological responses compared to combustible cigarette smoke (Schaller et al, 2016; Jaunky et al, 2018 ; Hattori et al, 2020 ; Rudd et al, 2020 ; Simms et al, 2020 ; Simms et al, 2021 ; Chapman et al, 2023 ). Furthermore, the substantially reduced toxicological responses of NGPs compared to combustible cigarette has been demonstrated in a number of in vitro studies, in both 2D and 3D cell models ( Iskandar et al, 2018 ; Czekala et al, 2019 ; Czekala et al, 2020; Haswell et al, 2021 ; Simms et al, 2021 ; Simms et al, 2022 ).…”

“…These models offer a human-relevant cellular system, grown and/or stimulated under air-liquid interface (ALI) conditions, and can include a variety of relevant cell types (e.g., basal, goblet and ciliated cells); this is more closely representative of an in vivo scenario than using single cell-type 2D cultures, for example ( Huang et al, 2013 ; Cervena et al, 2019 ). This, coupled with the application of whole aerosol/smoke exposures at the ALI can model exposure of cells to as representative a chemical mixture to that which the consumer would be exposed to as possible ( Chapman et al, 2023 ). In vitro 3D models exposed to whole NGP aerosol or combustible cigarette smoke have been used to assess a number of endpoints associated with the development and progression of respiratory diseases, including functional and morphological changes like cilia activity and ratios of cell types (e.g., goblet cells, ciliated cells), inflammatory readouts and genomic level changes ( Czekala et al, 2019 ; Rayner et al, 2019 ; Ghosh et al, 2020 ; Haswell et al, 2021 ; Bedford et al, 2022 ).…”