Exposure to fresh whole smoke and aerosols: standard and novel (3D) in vitro models
New Approach Methods (NAMs) describe non-animal- based methodologies that enable more human relevant toxicological risk assessments. In this talk, regulatory in vitro toxicology assays (CORESTA battery) are refined for NGP (Next Generation Product) testing of fresh aerosols to assess the Tobacco Harm Reduction (THR) potential of Electronic Vapour Products (EVP) and Heated Tobacco Products (HTP) compared to a reference cigarette (1R6F). Imperial’s SAEIVS (Smoke and Aerosol Exposure In Vitro System) was used to expose cells to fresh aerosol/smoke for cytotoxicity and genotoxicity (NRU, IVM) assessment. Mutagenicity testing (Ames) was performed via bubbling of a bacterial suspension with the Vitrocell VC10 smoking robot. Using these in vitro systems, fresh aerosol generated by EVP and HTP were markedly less toxic than combustible cigarette smoke.
Building on these findings, in vitro 3D tissue models of the human upper respiratory tract (MucilAir™, Epithelix) were repeatedly exposed to whole smoke/aerosol at the air-liquid Interface (ALI) for 4 weeks, using SAEIVS. Although the EVP and HTP delivered up to 25 times more nicotine compared to the diluted cigarette smoke, minimal effects were observed for the assessed endpoints (Cytotoxicity, cilia function, barrier integrity, histology, and pro-inflammatory markers). In contrast, smoke from the reference cigarette caused significant changes across all the endpoints in a puff dependent manner. These results align with the cytotoxic and genotoxic results from the regulatory toxicology assays described above.
These results demonstrate that NAMs such as those described above can be used to provide a deeper understanding of the potentially reduced biological effects of NGP compared to cigarettes.