Formation of Tobacco-Specific Nitrosamines from the Atmospheric Aging of Nicotine in E-Cigarette Aerosols

Abstract The atmospheric aging of nicotine-containing e-cigarette aerosols in the presence of nitrogen dioxide (NO2) and ozone (O3) may significantly alter their chemical composition and toxicological properties. However, the chemical transformation of nicotine within the complex e-cigarette aerosol matrix and its interaction with atmospheric oxidants remain largely uncharacterized. This study investigated the formation of tobacco-specific nitrosamines (TSNAs) from the aging of nicotine in e-cigarette aerosols exposed to NO2 and O3. We observed that NO2 facilitates the formation of N′-nitrosonornicotine (NNN) through direct nitrosation pathways, whereas O3 alone does not significantly contribute to TSNA production. In contrast, the presence of both oxidants enhanced the formation of nicotine-derived nitrosamine ketone (NNK), suggesting that oxidative transformation of nicotine plays an important role in its formation. FIGAERO-ToF-CIMS measurements identified several nicotine transformation products in aged e-cigarette aerosols that are not present in the fresh emissions, indicating chemical transformation during aging. Furthermore, long-amplicon qPCR analysis revealed that BEAS-2B cells exposed to aged aerosols experienced increased DNA damage, demonstrating enhanced genotoxic potential relative to their fresh counterparts. These findings indicate that atmospheric aging can convert nicotine into carcinogenic TSNAs and other reactive intermediates, increasing the potential health risks associated with secondhand and thirdhand vaping exposure. This work highlights the importance of considering chemically aged aerosols when evaluating the toxicity of e-cigarette emissions.