Toxicity of humectants propylene glycol and vegetable glycerin in electronic nicotine delivery systems.
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BACKGROUND: E-cigarettes and other electronic nicotine delivery systems (ENDs) remain a significant public health risk. Although deployed as tobacco smoking cessation tools, e-cigarettes have gained greater popularity among non-smokers, specifically adolescents and young adults. Previous research has focused primarily on the toxicities associated with nicotine, flavorings, and other chemicals generated from e-cigarette liquid aerosolization; however, little attention has been given to the two primary and most abundant chemicals found in most e-cigarette liquids - propylene glycol (PG) and vegetable glycerin (VG). PURPOSE: The purpose of this review is to assess the toxicity associated with PG/VG in e-cigarettes to inform future ENDS regulations. METHODS: Database searches were performed using PubMed for relevant literature published from 1/1/2014-9/1/2025. Cited articles about the prevalence, toxicities, and public perceptions of PG/VG. RESULTS: Toxicity associated with PG/VG inhalation is primarily due to thermal degradation byproducts (TDBs) generated by PG/VG-containing e-liquids. More specifically, high-power ENDS devices with sub-ohm power capabilities generate aerosols with larger mass and higher concentrations of TDBs. The most common TDBs identified in e-cigarette aerosols include formaldehyde, acetaldehyde, acrolein, acetone, acetoin/diacetyl, as well as benzene. These TDBs, along with other chemical adducts, contribute significantly to the e-cigarette aerosols' potential to cause oxidative stress, airway inflammation, and increase risks for cancer. Mechanistically, the toxicity associated with e-cigarette aerosols is mediated through the activation of the NF-κB and MAPK pathways, as well as the dysfunction of ion channels responsible for mucus hydration. These effects of e-cigarette aerosol exposures, whether induced by TDBs or other chemicals, can be affected by factors involved in the aerosolization process, including the ratio of PG/VG, the device power, and the resistance of the coil. CONCLUSIONS: E-cigarettes are often considered a harm-reduction alternative to combustible cigarettes due to PG and VG's FDA designation as "Generally Recognized as Safe" (GRAS) for consumption. However, when heated and inhaled, mixtures of PG/VG in e-cigarette liquids have their toxicities independent of the other constituents of e-liquids. Future regulations that focus on the PG/VG ratios, set limits on thermal degradation byproducts, and establish exposure thresholds for e-cigarette aerosols will help reduce toxic exposures associated with PG/VG inhalation. As such, further research is needed on PG/VG alone to understand its long-term health effects better and to inform evidence-based public health policies.