UC Riverside

This research sought to understand health effects associated with electronic cigarettes (ECs) by: (1) analyzing EC-induced symptoms reported online and in case reports, (2) examining exposure, retention, environmental accumulation, and the relationship between symptoms and dose in JUUL Menthol users, (3) assessing the cytotoxicity of popular ECs, (4) identifying reaction products generated from aerosols of refill fluids reported to induce sickness, and (5) characterizing the toxicity of the dominant reaction product, hydroxyacetone. Using automated computer mining, self-reported symptoms and disorders were captured from a major online EC forum from 2009 to 2015. EC use was associated with respiratory, neurological, and other symptoms. Popular EC refill fluids were identified using by interviewing local store clerks. Dominant flavor chemicals (e.g., maltol, ethyl maltol) were cytotoxic to human bronchial epithelial cells (BEAS-2B) in the MTT assay. To examine the link between EC exposure and symptoms, the puffing topography, exhale, percent transfer of chemicals from pod fluid to aerosol (transfer efficiency), and commonly reported symptoms were then assessed in 11 male JUUL Menthol EC users. The dominant chemicals (nicotine, menthol, propylene glycol, and glycerol), transferred well to aerosols with high retention within participants. A dose-response was observed between the total dominant chemical mass retained and symptoms. To understand the health effects of ECs, a “sickness inducing library” (SIL) of refill fluids was purchased based on online posts linking symptoms to specific products. Reaction products were identified in aerosolized SIL fluids. Hydroxyacetone, the dominant reaction product, affected BEAS-2B cell survival, growth, metabolic activity, F-actin integrity, and oxidative stress. Air-liquid interface (ALI) exposure of 3D EpiAirway tissue to hydroxyacetone followed by proteomics analysis supported the BEAS-2B cell responses and showed effects on xenobiotic metabolism, fatty acid metabolism, and NFkB oxidative stress pathways. These novel studies are significant because they demonstrate the health effects associated with EC use; evaluate the cytotoxicity of popular EC products; measure the retention of dominant JUUL Menthol chemicals and their association to common symptoms; and use an innovative strategy to create a SIL enabling the identification of hydroxyacetone as a major reaction product with toxicological effects in both submerged and ALI exposures.