E-cigarette liquids are typically solutions of propylene glycol, glycerol, or both, plus nicotine and flavorant chemicals. We have observed that formaldehyde-containing hemiacetals, shown by others to be entities that are detectable by means of nuclear magnetic resonance (NMR) spectroscopy,¹ can be formed during the e-cigarette “vaping” process. Formaldehyde is a known degradation product of propylene glycol that reacts with propylene glycol and glycerol during vaporization to produce hemiacetals ( Figure 1 ). These molecules are known formaldehyde-releasing agents that are used as industrial biocides.⁵ In many samples of the particulate matter (i.e., the aerosol) in “vaped” e-cigarettes, more than 2% of the total solvent molecules have converted to formaldehyde-releasing agents, reaching concentrations higher than concentrations of nicotine. This happens when propylene glycol and glycerol are heated in the presence of oxygen to temperatures reached by commercially available e-cigarettes operating at high voltage. How formaldehyde-releasing agents behave in the respiratory tract is unknown, but formaldehyde is an International Agency for Research on Cancer group 1 carcinogen.⁴

The heating of the fluids used in electronic cigarettes (“e-cigarettes”) used to create “vaping” aerosols is capable of causing a wide range of degradation reaction products. We investigated formation of benzene (an important human carcinogen) from e-cigarette fluids containing propylene glycol (PG), glycerol (GL), benzoic acid, the flavor chemical benzaldehyde, and nicotine. Three e-cigarette devices were used: the JUUL^TM “pod” system (provides no user accessible settings other than flavor cartridge choice), and two refill tank systems that allowed a range of user accessible power settings. Benzene in the e-cigarette aerosols was determined by gas chromatography/mass spectrometry. Benzene formation was ND (not detected) in the JUUL system. In the two tank systems benzene was found to form from propylene glycol (PG) and glycerol (GL), and from the additives benzoic acid and benzaldehyde, especially at high power settings. With 50:50 PG+GL, for tank device 1 at 6W and 13W, the formed benzene concentrations were 1.9 and 750 μg/m³. For tank device 2, at 6W and 25W, the formed concentrations were ND and 1.8 μg/m³. With benzoic acid and benzaldehyde at ~10 mg/mL, for tank device 1, values at 13W were as high as 5000 μg/m³. For tank device 2 at 25W, all values were ≤~100 μg/m³. These values may be compared with what can be expected in a conventional (tobacco) cigarette, namely 200,000 μg/m³. Thus, the risks from benzene will be lower from e-cigarettes than from conventional cigarettes. However, ambient benzene air concentrations in the U.S. have typically been 1 μg/m³, so that benzene has been named the largest single known cancer-risk air toxic in the U.S. For non-smokers, chronically repeated exposure to benzene from e-cigarettes at levels such as 100 or higher μg/m³ will not be of negligible risk.

Knowledge of the mechanism of formation, levels and toxicological profiles of the chemical products in the aerosols (i.e., vapor plus particulate phases) of e-cigarettes is needed in order to better inform basic research as well as the general public, regulators, and industry. To date, studies of e-cigarette emissions have mainly focused on chromatographic techniques for quantifying and comparing the levels of selected e-cigarette aerosol components to those found in traditional cigarettes. E-cigarettes heat and aerosolize the solvents propylene glycol (PG) and glycerol (GLY), thereby affording unique product profiles as compared to traditional cigarettes. The chemical literature strongly suggests that there should be more compounds produced by PG and GLY than have been reported in e-cigarette aerosols to date. Herein we report an extensive investigation of the products derived from vaporizing PG and GLY under mild, single puff conditions. This has led to the discovery of several new compounds produced under vaping conditions. Prior reports on e-cigarette toxin production have emphasized temperature as the primary variable in solvent degradation. In the current study, the molecular pathways leading to enhanced PG/GLY reactivity are described, along with the most impactful chemical conditions promoting byproduct production.