Characterizing the Genotoxic Potential of E-Cigarette Components In Vitro

E-cigarettes are being developed as potentially reduced-risk alternatives to continued smoking. Among the different endpoints of toxicity under investigation, the induction of DNA damage by the chemical constituents present in the aerosols generated from e-cigarettes is an active field of research. The genotoxic potential of one principal aerosol component, nicotine, has been extensively studied for over four decades. However, characterization of its effects in modern-day in vitro genotoxicity methods is scarce. While e-liquids—the matrices aerosolized by e-cigarette devices—are a relatively recent innovation and, as such, have only been the subject of testing for less than ten years. E-liquids are highly diverse and can contain varying proportions of nicotine, flavoring agents, and humectants such as propylene glycol and vegetable glycerin. In our research, contemporary in vitro genetic toxicology approaches have been deployed to characterize the genotoxic potential of nicotine and e-liquids, with a particular focus on its biological relevance. Our results—generated from state-of-the-art regulatory tests, quantitative concentration–response analyses, mode-of-action assessments, and a novel integrated genotoxicity assay in human cells—reveal a likely minimal level of biological and physiological relevance for the effects observed. In addition, the findings of a literature survey unveil a number of opportunities for improving the study of e-cigarette-derived aerosols in submerged cell culture-based assays.