The health and safety of using e-cigarette products (vaping) have been challenging to assess and further regulate due to their complexity. Inhaled e-cigarette aerosols contain chemicals with under-recognized toxicological profiles, which could influence endogenous processes once inhaled. We urgently need more understanding on the metabolic effects of e-cigarette exposure and how they compare to combustible cigarettes. To date, the metabolic landscape of inhaled e-cigarette aerosols, including chemicals originated from vaping and perturbed endogenous metabolites in vapers, is poorly characterized. To better understand the metabolic landscape and potential health consequences of vaping, we applied liquid chromatography-mass spectrometry (LC-MS) based nontargeted metabolomics to analyze compounds in the urine of vapers, cigarette smokers, and nonusers. Urine from vapers (n = 34), smokers (n = 38), and nonusers (n = 45) was collected for verified LC-HRMS nontargeted chemical analysis. The altered features (839, 396, and 426 when compared smoker and control, vaper and control, and smoker and vaper, respectively) among exposure groups were deciphered for their structural identities, chemical similarities, and biochemical relationships. Chemicals originating from e-cigarettes and altered endogenous metabolites were characterized. There were similar levels of nicotine biomarkers of exposure among vapers and smokers. Vapers had higher urinary levels of diethyl phthalate and flavoring agents (e.g., delta-decalactone). The metabolic profiles featured clusters of acylcarnitines and fatty acid derivatives. More consistent trends of elevated acylcarnitines and acylglycines in vapers were observed, which may suggest higher lipid peroxidation. Our approach in monitoring shifts of the urinary chemical landscape captured distinctive alterations resulting from vaping. Our results suggest similar nicotine metabolites in vapers and cigarette smokers. Acylcarnitines are biomarkers of inflammatory status and fatty acid oxidation, which were dysregulated in vapers. With higher lipid peroxidation, radical-forming flavoring, and higher level of specific nitrosamine, we observed a trend of elevated cancer-related biomarkers in vapers as well. Together, these data present a comprehensive profiling of urinary biochemicals that were dysregulated due to vaping.
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