Firsthand and Secondhand Exposure Levels of Maltol-Flavored Electronic Nicotine Delivery System Vapors Disrupt Amino Acid Metabolism.

Electronic nicotine delivery system (ENDS) use has become a popular, generally regarded as safe, alternative to tobacco use. The e-liquids used for ENDS vapor generation commonly contain flavoring agents, such as maltol, which have been subjected to little investigation of their effects on lung health from ENDS usage. In the present study, we examined the impacts of firsthand (3.9 mM) and secondhand (3.9 µM) exposure levels to maltol-flavored ENDS vapors on lung metabolism. Human lung bronchial epithelial cells were exposed to ENDS vapors using a robotic system for controlled generation and delivery of exposures, and the effects on metabolism were evaluated using high-resolution metabolomics. The results show that maltol in e-liquids impacts lung airway epithelial cell metabolism at both firsthand and secondhand exposure levels. The effects of maltol were most notably seen in amino acid metabolism while oxidative stress was observed with exposure to all ENDS vapors including e-liquids alone and maltol-contained e-liquids. Many effects of firsthand exposure were also observed with secondhand exposure, suggesting need for systematic investigation of both firsthand and secondhand effects of flavored ENDS vapors on lung metabolism and risk of lung disease.