Toxicological risk assessment of VEEV NOW ULTRA e-vapor products shows reduced toxicity compared to cigarette smoke

The toxicological assessment of e-vapor products is crucial for understanding their potential health impacts. In this study, we aim to apply a comprehensive toxicological risk assessment framework to a new e-vapor product (VEEV NOW ULTRA™, Philip Morris Products S.A.) to ensure a high standard of safety. Flavor and e-liquid base ingredients were selected to comply with food and pharmaceutical standards. Their inclusion levels were determined based on regulatory requirements and a rigorous toxicological risk assessment, following the four-step human-health risk assessment process. Contaminants or chemicals of concern potentially leaching from device materials in contact with the e-liquid and/or aerosol were assessed under extreme temperature and pH conditions through extractable analysis. Mass spectrometry (MS) coupled with gas chromatography (GC-MS) was used to detect semi-volatile compounds, liquid chromatography-coupled MS (LC-MS) for non-volatile compounds, and headspace GC-MS for volatile compounds. Aerosol chemistry was characterized, with a focus on typical compounds reported in vaping product aerosols, such as but not limited to carbonyls and metals. The cytotoxicity and genotoxicity of the aerosols produced by the new e-vapor product were assessed in vitro, compared to reference cigarette smoke, using the WST-8 assay, Ames test, and micronucleus assay, according to internationally recognized guidelines. Our findings indicate that the e-liquid ingredients do not pose a toxicological concern at the levels used in the formulations of the new e-vapor product. The device materials were found not to release harmful chemicals under exaggerated usage conditions or over time. Moreover, in vitro studies show that the e-vapor aerosols are not mutagenic, genotoxic, or cytotoxic. In conclusion, the proposed toxicological risk assessment framework has been instrumental in substantiating the toxicological profile of the e-liquids and materials of a new e-vapor product. This framework has also helped elucidate the reduced biological effects of the product in comparison with cigarette smoke.