Stability of Flavoring Chemicals in e-Cigarette Liquids: A Naturalistic Product Aging Study over 24 months.

Flavoring chemicals commonly used in many consumer products, including pharmaceuticals, foods, and beverages, deteriorate over time. Flavoring chemicals are also common additives in e-cigarette liquid formulations, but their stability in vaping products has not been evaluated. Since e-cigarette liquids are exposed to varying environmental conditions during storage and use, we assessed the stabilities of 20 flavoring chemicals commonly used in vaping products, including benzaldehyde (cherry flavor), menthol (cooling flavor), and vanillin (vanilla flavor). We prepared reference e-cigarette liquids (reference solutions) containing individual flavorings and a mixed liquid with combined flavorings in a 55:45 (v/v) propylene glycol to vegetable glycerin solution. We also purchased 14 commercial e-cigarette liquids. Liquids were stored over 24 months in different temperatures (room and cold) and light exposure conditions (ambient light and dark). Gas chromatography/mass spectrometry techniques were used to measure the concentration of each flavoring chemical at the baseline and after 1, 3, 6, 12, and 24 months. We used a nontargeted approach to identify potential degradation byproducts. Using an air-liquid interface with bronchial epithelial cells and the Neutral Red assay, we also compared the cytotoxicity of selected reference solutions vaped at the baseline and after storage over 24 months. The flavorings in reference solutions stored at ambient temperature and exposed to light were the least stable. Reducing exposure to light and storing reference solutions in cold temperatures delayed the degradation of some flavorings. Tentatively identified byproducts of flavoring degradation found in unstable reference solutions suggested oxidation, hydrolysis, and condensation reactions with solvents. Despite substantial changes in the chemical composition, no significant cytotoxicity differences were detected between fresh and aged reference solutions. Our findings suggest that storing vaping products in dark places and at cold temperatures improves the stability of flavorings in e-cigarette liquids.