Influence of E-Liquid Humectants, Nicotine, and Flavorings on Aerosol Particle Size Distribution and Implications for Modeling Respiratory Deposition

Abstract

Electronic cigarette, or vaping, products are used to heat an e-liquid to form an aerosol (liquid droplets suspended in gas) that the user inhales; a portion of this aerosol deposits in their respiratory tract and the remainder is exhaled, thereby potentially creating opportunity for secondhand exposure to bystanders (e.g., in homes, automobiles, and workplaces). Particle size, a critical factor in respiratory deposition (and therefore potential for secondhand exposure), could be influenced by e-liquid composition. Hence, the purposes of this study were to (1) test the influence of laboratory-prepared e-liquid composition [ratio of propylene glycol (PG) to vegetable glycerin (VG) humectants, nicotine, and flavorings] on particle size distribution and (2) model respiratory dosimetry. All e-liquids were aerosolized using a second-generation reference e-cigarette. We measured particle size distribution based on mass using a low-flow cascade impactor (LFCI) and size distribution based on number using real-time mobility sizers. Mass median aerodynamic diameters (MMADs) of aerosol from e-liquids that contained only humectants were significantly larger compared with e-liquids that contained flavorings or nicotine (p = 0.005). Humectant ratio significantly influenced MMADs; all aerosols from e-liquids prepared with 70:30 PG:VG were significantly larger compared with e-liquids prepared with 30:70 PG:VG (p = 0.017). In contrast to the LFCI approach, the high dilution and sampling flow rate of a fast mobility particle sizer strongly influenced particle size measurements (i.e., all calculated MMAD values were < 75 nm). Dosimetry modeling using LFCI data indicated that a portion of inhaled particles will deposit throughout the respiratory tract, though statistical differences in aerosol MMADs among e-liquid formulations did not translate into large differences in deposition estimates. A portion of inhaled aerosol will be exhaled and could be a source for secondhand exposure. Use of laboratory-prepared e-liquids and a reference e-cigarette to standardize aerosol generation and a LFCI to measure particle size distribution without dilution represents an improved method to characterize physical properties of volatile aerosol particles and permitted determination of MMAD values more representative of e-cigarette aerosol in situ, which in turn, can help to improve dose modeling for users and bystanders.

Oxidative stress and inflammation: elucidating mechanisms of smoking-attributable pathology for therapeutic targeting

“…In the lungs, oxidative stress and inflammation from smoking play central roles in COPD pathogenesis (Sun et al 2023). Smoking-induced oxidative DNA damage, chronic inflammation, and impaired immunity combine to promote lung carcinogenesis (Stefaniak et al 2022). For cardiovascular disease, smoking triggers endothelial dysfunction, platelet activation, and atherogenesis through oxidized LDL and effects on nitric oxide and adhesion molecules (Hameed and Malik 2024).…”

Toxicological Assessment of Particulate and Metal Hazards Associated with Vaping Frequency and Device Age

“…While assessing relevant human exposure levels is critically important in determining the safety of ENDS, understanding various particle reaction dynamics that may occur within biological systems is essential for a holistic appraisal of potential cellular outcomes [ 53 ]. One of the reactions that occurs during complex particle-cell interactions is the Fenton reaction, which involves the generation of oxidizing agents such as hydroxyl radicals through the decomposition of hydrogen peroxide in the presence of ferrous cations or other transition metals [ 54 , 55 ].…”

Carbonyl Profiles of Electronic Nicotine Delivery System (ENDS) Aerosols Reflect Both the Chemical Composition and the Numbers of E-Liquid Ingredients–Focus on the In Vitro Toxicity of Strawberry and Vanilla Flavors

“…This suggests that the operational settings, including wattage, resistance and voltage, applied to these devices from the same fourth generation may be different and that the chemical profiles of those closed ENDS aerosols may be notably distinctive. Overall, while open (third generation devices) versus closed (fourth generation devices) ENDS have distinct operational settings, which influence the chemical profile of the aerosols generated [ 9 ], the presence of harmful and potentially harmful chemicals as well as the form of nicotine (freebase versus salt) in the ENDS aerosols may be key factors to consider when evaluating ENDS toxicity.…”

“…(3) The e-liquid humectant composition. The various ratios of PG/G have a direct impact on the physicochemical characteristics of the aerosols produced [ 9 ]. PG and G are “generally regarded as safe” (GRAS) ingredients in food; however, their pulmonary safety following long-term inhalation exposures has not been thoroughly evaluated.…”