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/m 3 . For tank device 2, at 6W and 25W, the formed concentrations were ND and 1.8 μg/m 3 . With benzoic acid and benzaldehyde at ~10 mg/mL, for tank device 1, values at 13W were as high as 5000 μg/m 3 . For tank device 2 at 25W, all values were ≤~100 μg/m 3 . These values may be compared with what can be expected in a conventional (tobacco) cigarette, namely 200,000 μg/m 3 . 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/m 3 , 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/m 3 will not be of negligible risk.

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.

Funding: NIH and FDA supported this work via award R01ES025257. In particular, the work reported in this publication was supported by NIEHS and the FDA Center for Tobacco Products (CTP) ( https://www.nih.gov/ ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2017 Pankow et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Introduction

Electronic cigarettes (“e-cigarettes”) use an electrical resistance coil to vaporize mixtures of propylene glycol (PG), glycerol (GL), nicotine, and flavor chemicals. Vaporization of an e-liquid containing mostly PG and/or GL requires a temperature of ~190 to 290°C: when the ambient pressure is 1 atm, PG boils at ~190°C, GL boils at ~290°C, and PG+GL mixtures will boil between ~190 and ~290°C; the presence of other constituents besides PG and GL (such as water and flavor chemicals) will affect the boiling point. (The presence of significant percentages of other constituents (e.g., water and flavor chemicals) will affect the boiling point.) Temperatures higher than the boiling point of an e-liquid are possible in the coil zone if the rate of e-liquid delivery to the coil does not keep pace with the heat delivery rate: the vicinity of the coil becomes “dry”, and the heat delivery rate surpasses the rate at which heat is carried away by evaporated liquid as “latent heat”.

In general, e-cigarette aerosols tend to be simpler in composition than cigarette aerosols: “e-liquids” are a simpler starting matrix as compared to cigarette filler, and burning cigarettes have been reported to reach 900°C,[1]. Neverthless, multiple toxicants can form upon heating PG and GL.[2–6] Thermal dehydration of PG with loss of one water molecule gives acetaldehyde, and thermal dehydration of GL with loss of two water molecules gives acrolein [2, 6]. Significant amounts of formaldehyde are also possible.[3,4] Kim and Kim [7], using a PG+GL refill fluid (zero nicotine), an unnamed refillable tank device operated, and unspecified settings, reported finding benzene (a known human carcinogen [8,9]) in e-cigarette aerosols at 87.5 μg/m3. McAuley et al.[10], however, using a simple draw-activated device, reported that benzene was mostly “not found”.

Dehydration of GL to benzene has been observed [11], and in e-cigarettes a simple dehydration stoichiometry could be PG + GL = benzene + 5 H 2 O (Fig 1A). A second route to benzene in e-cigarettes is decarboxylation of benzoic acid (Fig 1B), and benzene has been known to form when benzoic acid is used as a preservative in beverages.[12] (Benzoic acid has been found by our laboratory in 14 out of 150 e-liquid refill products at levels estimated to be in the range 0.02 to 2 mg/mL, and benzoic acid is an acknowledged ingredient in e-liquids in the JUUL product line.[13]) For a third route to benzene, many aromatic aldehydes are major e-liquid flavor additives, including benzaldehyde (for “cherry”), vanillin, and ethyl vanillin: aldehyde levels as high as several percent (by mass) have been found.[14] Every aldehyde can be oxidized to its corresponding carboxylic acid, which may then undergo decarboxlation. Thus, oxidation of benzaldehyde can give benzoic acid, and therefore, benzene (Fig 1C). For a fourth route to benzene, in what amounts to abiotic fermentation, an aldehyde can undergo redox disproportionation to form a mix of the corresponding alcohol and the acid, and the latter may then undergo decarboxylation. (The acid is more oxidized then the aldehyde, and the alcohol is less oxidized than the aldehyde.) With benzaldehyde, a mix of benzoic acid and benzyl alcohol can then be formed (Fig 1D). (The disproportionation of an aldehyde lacking an “alpha-position” hydrogen atom is the Cannizzaro reaction, which is base-catalyzed (possibly then, by nicotine).)

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larger image TIFF original image Download: Fig 1. Formation of benzene by four mechanisms: a. dehydration according to GL + PG– 5 H 2 O, with cyclization (note: individually, propylene glycol alone and glycerol follow different stoichiometries); b. decarboxylation of benzoic acid; c. oxidation of benzaldehyde to benzoic acid, followed by decarboxylation (dashed arrow—-> indicates that the exact reaction stoichiometry is not provided); and d. disproportionation (Cannizzaro reaction) of benzaldehyde to form benzoic acid + benzyl alcohol. https://doi.org/10.1371/journal.pone.0173055.g001

Herein we describe measurements of gas-phase benzene in e-cigarette aerosols from three types of e-cigarette: a non-refillable e-cigarette (JUULTM), and two variable-power, tank-type devices. For experiments with the tank devices, the fluids used were prepared in the laboratory from PG, GL, benzoic acid, benzaldehyde, and/or nicotine (see Table 1 for compositions). The power settings used for the tank units ranged from “recommended” to beyond. The higher settings were used because they: 1) were accessible by normal use of the devices; 2) may not be “distasteful” to absolutely every user in every use circumstance; 3) will certainly be encountered by users experimenting with settings (as innumerable postings on social media attest); and 4) provide useful information regarding the potential for toxicant formation in e-cigarettes.