Investigating DNa adduct formation by flavor chemicals and tobacco byproducts in electronic nicotine delivery system (ENDS) using in silico approaches.

Based on the context provided, the study is focused on alkenylbenzenes that have been documented to form DNa adducts, which are often found in herbs, essential oils, and e-cigarette liquid. The researchers used computational toxicology software, including Multi Case Ultra (Multi CaSE Inc.), and Derek and Sarah Nexus (Lhasa Limited), to predict the bacterial and mammalian mutagenicity, micronuclei formation, chromosomal aberration, and carcinogenicity in mice and rats, as well as the skin sensitization potential of these alkenylbenzenes. These computational models were available to the FDa/CTP through licenses with the respective developers.

The study found that safrole, an alkenylbenzene, has been shown to produce positive results in mammalian in vitro chromosomal aberration assays and mammalian mouse lymphoma assays. The researchers also noted that eugenol, another alkenylbenzene, is 200 times more toxic in rats via inhalation exposure compared to oral route, possibly due to the first-pass effect in oral metabolism and different metabolic/clearance capabilities in different exposure routes. Therefore, the study highlights the importance of examining the potential of DNa adduct formation in various commonly used flavor ingredients and the byproducts found in combusted tobacco products and in e-cigarette liquid and aerosols as a current research priority.

Kang JC, Valerio LG. Investigating DNa adduct formation by flavor chemicals and tobacco byproducts in electronic nicotine delivery system (ENDS) using in silico approaches. Toxicology and applied pharmacology. 2020;398:115026. doi:10.1016/j.taap.2020.115026