Assessment of the Tobacco Heating System 2.2, a candidate Reduced Risk Product, on human organotypic nasal and bronchial epithelial tissue culture using systems toxicology approach

Abstract

New tobacco products with the potential to reduce individual risk and population harm in comparison to smoking cigarettes are under development and require a careful safety assessment strategy. In line with the 21st century toxicology paradigm and with the use of human in vitro organotypic models as substitute of animal testing, we exposed human nasal and bronchial epithelial tissue culture to an aerosol generated by a candidate Reduced Risk Product (RRP), Tobacco Heating System (THS) 2.2, versus air (sham control) or cigarette smoke (CS) with the same nicotine content as THS2.2. Different endpoints (cytotoxicity, cilia beating frequency, CYP1A1/1B1 enzyme activity, inflammatory markers release, morphological and transcriptomic changes) were analyzed at 4, 24, 48 and 72h after exposure to identify and compare the dose- and time-dependent effect of the different test item used.
By using systems toxicology-based risk assessment approaches combining computable biological network models and gene expression changes, we compared the molecular perturbations in both conventional cigarette and THS2.2 exposure conditions. A significant impact was quantified over different CS post-exposure time points in the networks representing cell death, inflammation, proliferation and cellular stress; instead, the impact of THS2.2 was closer to sham controls and detectable only shortly after exposure (4h). These results indicate a reduced toxicity of THS2.2 acute exposure on both nasal and bronchial epithelial tissue culture when compared to CS.

Reduced Risk Products (“RRPs”) is the term we use to refer to products with the potential to reduce individual risk and population harm in comparison to smoking cigarettes.