In vitro toxicological evaluation of nicotine concentration and flavor variants of Vuse Alto ENDS

In vitro toxicological evaluations are recommended for determination of the appropriateness for the protection of public health (APPH) of tobacco products seeking marketing authorization in USA. In this manuscript, we assessed mutagenicity, genotoxicity, and cytotoxicity by Ames, in vitro micronucleus, and neutral red assays, respectively of 13 Vuse Alto electronic nicotine delivery system (ENDS) products that differed in nicotine concentration and flavor, using established regulatory toxicological assays. Market comparator products for cigarettes and ENDS were also included in these evaluations. The Vuse Alto ENDS test products were non-genotoxic and non-mutagenic in the in vitro micronucleus and Ames assays, respectively, while the cigarettes elicited positive responses in both the assays. Whole smoke generated from cigarettes and whole aerosol from the Vuse Alto ENDS test products was used to test for potential cytotoxicity. While most Vuse Alto ENDS were non-cytotoxic, 3 test products were determined to be cytotoxic, with a markedly (>200 fold) higher IC₅₀ values compared to cigarettes. Overall, our results show that the Vuse Alto ENDS evaluated in this study are non-genotoxic and non-mutagenic, and either non-cytotoxic or exhibit minimal cytotoxicity, compared to cigarettes.