Toxicological risk assessment framework for e-vapor products: From product ideation to product commercialization

The safety assessment of e-vapor products, commonly known as electronic cigarettes, requires a comprehensive approach involving multidisciplinary scientific evaluations. These evaluations must address critical aspects of e-vapor product safety, including the chemical and toxicological profiles of their aerosols. The aerosol produced by an e-vapor product results from the complex interactions between e-liquid components, device settings, and puffing topography. Understanding the aerosolization process and maintaining strict control over product characteristics are essential to ensure a consistent and predictable aerosol composition. Here, we aim to propose a framework for the safety profile assessment of e-vapor products, from e-liquid characterization to material and toxicological assessment. Key considerations include the careful selection and sourcing of e-liquid ingredients, which must undergo rigorous quantitative toxicological risk assessments. Flavor and e-liquid base ingredients must comply with food and pharmaceutical standards and be evaluated for their toxicological risk when inhaled. In addition, assessing the fate of aerosolized ingredients is crucial to minimize the presence of toxic thermal degradation by-products. Materials in direct contact with the e-liquid, aerosol, and the consumer's mouth, such as metal coils, wicks, and pod containers, are assessed for their potential to leach harmful substances. The cytotoxicity and genotoxicity of aerosols are evaluated in vitro using assays, such as cell viability, Ames, and micronucleus tests, as recommended by internationally recognized guidelines. Adhering to the 3R principles, in vivo studies are minimized but may be conducted for specific needs to further mitigate risks. In conclusion, the safety assessment of e-vapor products requires a comprehensive approach that includes stringent controls over ingredients, flavors, material selection, and system operating characteristics. By understanding and mitigating risks associated with each component, it is possible to develop vaping products with even better risk profiles. This framework ensures that e-vapor products adhere to the highest safety standards.