Multi-endpoint in vitro toxicity profiling of heated tobacco products versus e-cigarettes under air-liquid interface exposure.

Heated tobacco products (HTPs) and electronic cigarettes (E-cigs) are prominent next-generation tobacco products; However, a toxicological comparison using physiologically relevant air-liquid interface (ALI) models is lacking. We evaluated three HTPs and three E-cigs using human bronchial epithelial cells (NCI-H292) at ALI. The IC50 values for HTPs ranged from 302.8 to 577.6 puffs, suggesting a significantly higher cytotoxicity than E-cigs (IC50: 1065-1277 puffs). All three HTPs induced dose-dependent increases in ROS and decreases in GSH. In contrast, among the E-cigs, only E-cig-1 produced similar dose-dependent responses for ROS and GSH, while the others showed minimal effects. A modest, dose-dependent increase in γ-H2AX expression was observed for HTPs, whereas only one E-cig induced a comparable increase. Overall, under ALI conditions, the examined HTPs exhibited substantially higher toxicological potential than the E-cigs, highlighting differences in their relative health risks.