Carbon Monoxide and Small Hydrocarbon Emissions from Sub-ohm

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Carbon Monoxide and Small Hydrocarbon Emissions from Sub-ohm Electronic Cigarettes Ahmad El Hellani, Samira Al Moussawi, Rachel El-Hage, Soha Talih, Rola Salman, Alan Shihadeh, and Najat Aoun Saliba Chem. Res. Toxicol., Just Accepted Manuscript • DOI: 10.1021/acs.chemrestox.8b00324 • Publication Date (Web): 18 Jan 2019 Downloaded from http://pubs.acs.org on January 19, 2019

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Carbon Monoxide and Small Hydrocarbon Emissions from Sub-ohm Electronic Cigarettes Ahmad El-Hellani, Ph.D.,†,§ Samira Al-Moussawi, BE,¥ Rachel El-Hage, MS,†,§ Soha Talih, Ph.D., Rola Salman, BS,‡,§ Alan Shihadeh, ScD,‡,§ and Najat Aoun Saliba, Ph.D.†,§,*

‡,§

† Chemistry Department, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon ¥ Chemical Engineering Department, Maroun Semaan Faculty of Engineering and Architecture American University of Beirut, Beirut, Lebanon ‡ Mechanical Engineering Department, Maroun Semaan Faculty of Engineering and Architecture American University of Beirut, Beirut, Lebanon § Center for the Study of Tobacco Products, Virginia Commonwealth University, Richmond, Virginia, USA. * Corresponding Author: Najat A. Saliba, Tel: +961 1 350000/3992. E-mail: [email protected].

KEYWORDS Electronic cigarette, carbon monoxide, sub-ohm device, small hydrocarbon gas, infrared spectroscopy.

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ABSTRACT Electronic cigarettes (ECIGs) are routinely advertised as a safer alternative to combustible cigarettes. ECIGs have been shown to emit less toxicants than conventional cigarettes. This study presents for the first time the mouthpiece emissions of carbon monoxide (CO) and small hydrocarbon gases, in addition to carbonyls, from a re-buildable atomizer sub-ohm device (SOD). Because ECIGs do not involve combustion, CO emissions are commonly thought to be a negligible component of ECIG aerosols. CO exposure is a major causative agent of heart disease among smokers. Aerosol generated by vaping a solution of propylene glycol and glycerol were collected in a small chamber. The gas phase was then directed for analysis to a long-path gas cell of a Fourier transform infrared instrument under reduced pressure. The effects of power, ECIG heating coil material, and coil geometry on the generation of small gases were assessed. Results showed that small gases, including CO, carbon dioxide, methane, ethylene, and acetylene, were detected in SOD-emitted gases. Electrical power and material of construction significantly affected the concentrations of the emitted gases. Nickel metal wire was more reactive than kanthal, nichrome, and stainless steel. Depending on use patterns and device operation, users of SOD devices may be exposed daily to similar levels of CO as are cigarette smokers. This finding casts doubt on the validity of CO as a biomarker to distinguish ECIG from tobacco cigarette use, and suggests that some subset of ECIG users may be at risk from CO-related heart disease.

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INTRODUCTION Tobacco smoking is the leading preventable cause of death worldwide.1 This epidemic contributes to almost 18% of the annual death toll in the United States.2,3 Nowadays, it is generally accepted that people smoke for nicotine but die from the accompanying toxicant emissions.4,5 Therefore, most harm reduction strategies have relied on products that deliver nicotine with significantly lower levels of toxicants, such as light cigarettes, smokeless tobacco products, and nebulizers, among others.4,6,7 However, these products have shown low efficiency in reducing smoking, as they were either mere industry maneuvers (light cigarettes)8 or non-satisfying to users (smokeless tobacco and nebulizers).9 In contrast, electronic cigarettes (ECIGs), recently introduced as “safe” nicotine delivery systems, have been promoted as the healthier alternative to tobacco cigarettes and considered a potent solution for smoking reduction or cessation.10,11 However, the literature still lacks evidence from long-term epidemiological studies to support these claims.12,13 Moreover, the safety of ECIGs was recently questioned with substantial claims that their use could increase the risk of cancer and cardiovascular and pulmonary diseases.14-17 In 2016, the Food and Drug Administration extended its regulatory authority to include ECIGs, among others, as a tobacco product.18 A recent development of ECIGs is sub-ohm devices (SODs), which have coils of total resistance < 1 Ω that enable users to reach high powers, generating larger clouds of vapor.19 High powers are expected to yield high temperatures on the coil surface, and this action can lead to the thermal degradation of the ECIG liquids.20,21 Therefore, several families of toxicants, namely, carbonyls, reactive oxygen species, and volatile organic compounds, are generated.22-25 These toxicants, which are common among ECIG and tobacco cigarette emissions, are emitted at lower quantities in the case of the former.26,27 Other families of toxicants such as small gases (C1-C2), including 4 ACS Paragon Plus Environment

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carbon dioxide (CO2), carbon monoxide (CO), and ethylene, in addition to polycyclic aromatic hydrocarbons, have been considered to be mainly restricted to cigarette smoke because no combustion takes place during ECIG activation.28 However, a recent study reported the detection of CO2 in ECIG, with CO2 emissions being attributed to combustion.29 The effect of the heating temperature and the coil material on the degradation of propylene glycol (PG) and on the formation of carbonyls was recently examined by our group using a tubular flow reactor.30 At temperatures higher than 256 °C, carbonyls were observed to decompose because of extensive oxidation leading either to acids or to cracking into small hydrocarbon gases and CO2. In this study, we report for the first time the detection of CO and CO2 as well as small hydrocarbon gases, including methane, ethylene, and acetylene, emitted from vaping a 30/70 solution of PG/vegetable glycerin (VG) in a re-buildable drip atomizer SOD.

MATERIALS AND METHODS Materials PG (99.5%) (CAS No 57-55-6) and VG (99%–101%) (CAS No 56-81-5) were procured from Sigma-Aldrich. Glass fiber filters (ADVENTEC, QR-100.47 mm) were procured from Pall Corporation. A VGOD ProDrip dual-coil sub-ohm ECIG was used to heat a 30/70 PG/VG solution. Different metal wires, including kanthal A1, nichrome, and stainless steel, were purchased from RBA Depot (24 gauge), and nickel wire was purchased from Vapowire (26 gauge). The coil head was powered with a Lavabox battery, and the coils were manually built using a Coil Master builder. Japanese cotton wicks were used to deliver the liquid to the heated coil. Spectra were recorded on an Avatar 360 Fourier transform infrared (FTIR) machine equipped with a long path gas cell (LPGC) (A cylinder of 60 cm length and 12.5 cm inner diameter that accounts for a total of 33 m 5 ACS Paragon Plus Environment

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optical path). A zero air tank was used for gas supply. The Zero air contained 19.9-20.9% O2, total hydrocarbon (THC), CO + CO2, and H2O < 0.2, 1 and 3 ppm, respectively. All FTIR spectra were collected in a single beam transmittance mode and were subtracted from the background (Figure S1) and presented as absorbance versus wavenumber (cm-1). Study Design Figure 1 illustrates the setup used to generate puffs and trap the effluent gas in the LPGC. Gas from a zero air tank was continuously fed into the small chamber built around the coil head to ensure an atmosphere free of CO2 and H2O. A filter pad was used to intercept the particle phase, and only gases were analyzed with an FTIR spectrophotometer. A mass flow regulator was used to control the flow rate at 1 LPM. To make a puff, the LPGC was first cleaned and emptied using a linear gas pump, the branch going to the pump was then closed, and the cell under reduced pressure was used to suck the generated gases. The valve to the LPGC was simultaneously opened with the activation of the SOD. A vaping session constituted three puffs of a 3 s puff duration and 10 s inter-puff interval. The liquid in the ECIG was replenished after each puffing session to avoid any “dry puff” phenomenon. A pressure gauge connected to the LPGC was used to ensure that the same amount of gas (P ~ 100 Torr) was introduced into the cell in every experiment. To quantify CO, a calibration curve was built using a standard pure CO gas tank. The area under the curve of the CO peak at 2150 cm-1 was plotted against the CO concentrations. The calibration curve is a fifth order polynomial fit, as shown in Figure S2.31 The effect of power increase from 50 to 200 W (increments of 25 W) on the degradation of 30/70 PG/VG mixture was assessed. In addition, four different coil material (kanthal, nichrome, nickel and stainless steel) were tested under the same conditions and compared at a given power. When

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varying the power and the coil metal, the standard geometry of the coils was set to 10 wraps with a 3 mm coil diameter (A) (Table 1), thus fixing the surface area that was estimated using an online calculator (www.steam-engine.org). However, in the case of the thinner nickel wire (26 gauge), the same surface area of the coil was maintained by increasing the number of wraps to 13 (A’). Moreover, two variations in coil geometry, fewer wraps (5 (B)) or a smaller coil diameter (2 mm (C)), of kanthal wire were studied (Figure 1).

RESULTS A puffing session was performed on the inactivated ECIG to account for the interferences from the zero air tank and the surrounding atmosphere of the experimental setup. Only CO2 and H2O were detected in the FTIR spectrum (Figure S2). This spectrum was considered an experimental background, and subtracted from the spectra that were collected for SOD vaping under different conditions. Figure 2 shows the FTIR spectrum of the emitted gases from 30/70 PG/VG mixture vaped at 150 W. Gases such as methane (C-H at 3010 cm-1), CO2 (C-O at 2350 cm-1), CO (C-O at 2150 cm-1), carbonyls (C-O at 1700-1780 cm-1), ethylene (C-H at 950 cm-1), and acetylene (C-H at 730 cm-1) were detected. Note that the same degradation products but with different concentrations were obtained upon varying the operating conditions of the SOD (power, coil material, and geometry) as identified by FTIR. These products were the result of cracking and not oxidation reactions, as similar spectra were obtained under zero air and N2 atmosphere (Figure S3). The effect of different design parameters on the gas emissions was evaluated by taking CO as a tracer. Effect of Power

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No PG/VG degradation products were detected when SOD was operated at P < 100 W (Figure 3). At higher powers, CO concentrations increased linearly (R2 = 0.97) from 42 mg/m3 at 125 W to 2060 mg/m3 at 200 W. The triplicate of each CO measurement exhibited high standard deviations at higher powers (150–200 W). Effect of Coil Material Table 1 summarizes the results that were obtained when different metals of constant coil diameter and surface area (A) were used in the SOD at 125 W. The nickel wire revealed the highest reactivity as deduced from the CO levels. The CO concentrations of the six replicates for nickel were significantly different from those of nichrome and kanthal (P < 0.05) and marginally different from those of stainless steel (P < 0.1; Table S1). Effect of Coil Geometry The coil geometry defined by the number of wraps and the coil diameter also showed an effect on PG/VG degradation. Two dual coils of the same metal and diameter (3 mm each) wrapped in 5 and 10 folds resulted in coils with 225 and 417 mm2 total surface area (B versus A) and led to the formation of 2153.7 ± 1487.3 and 77.7 ± 145.4 mg/m3 of CO, respectively (Table 1). When varying the diameters while keeping the surface area constant (C versus A), a higher CO concentration was observed with the smaller coil volume. No significant difference was found among these variations using the t-test mainly because of the high standard deviations.

DISCUSSION The detection of CO and small hydrocarbon gases in SOD vapor is reported for the first time, up to our knowledge. So far, the major PG/VG degradation products in ECIGs are carbonyls.30,32-34 8 ACS Paragon Plus Environment

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A study dated back to 1983 on VG gas-phase pyrolysis reported the detection of CO, ethylene, methane and hydrogen.35 Thus, detecting CO and small hydrocarbon gases emitted from SOD could be mainly attributed to the decomposition of PG and VG under pyrolysis-like conditions in the coil head.36 The results reported herein also emphasize the role of the different SOD design parameters in gas emission. Power input, which is directly linked to coil temperature, was found to be proportional to the PG/VG degradation, with higher power inputs producing higher concentrations of the cracking products.20,37 The assessment of the effect of coil material showed that nickel was the most active in enhancing the degradation of the PG/VG mixture. The observed significant difference between nickel and other metals should alert users of temperature-controlled SODs that rely on this metal. In addition, coil geometry (surface area and/or volume) was found to play an important role in the emission of small gases from the SOD. In fact, the PG/VG degradation was initiated at higher powers in the case of a larger surface area (100 W for 10 wraps compared with 50 W for 5 wraps). This result is consistent with the notion that larger surface areas can dissipate more heat and thus lower the coil temperature.38 When holding the surface area constant, a smaller coil volume resulted in a higher coil temperature due to lower thermal inertia.39 Note that during the experiment, the wick and the adjacent wells were kept soaked with the ECIG liquid before each puffing session to avoid the occurrence of the “dry puff” phenomenon. From a health perspective, the detection of CO in the SOD is the most remarkable. Combustionrelated harmful or potential harmful compounds, including CO, were considered to be either absent in ECIGs or present at levels far less than conventional cigarette smoke.40-42 ECIGs are perceived as less harmful than conventional tobacco cigarettes because they do not emit “tar”, ash, or CO.43,44 Expired CO is often used as an indicator of the use of combustible tobacco cigarettes.45 Figure 4 9 ACS Paragon Plus Environment

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shows the comparison between the range of CO in the SOD at three different powers using a kanthal 5 wraps coil and the levels detected in cigarette smoke.46 Assuming a typical SOD ECIG liquid nicotine concentration of 3 mg/mL, a user of this device would be exposed to 1/10 and 2/5 times the mass of CO emitted by a combustible cigarette to obtain the same daily nicotine dose, when the device is operated at 75 and 200 Watts, respectively (Figure 4). While commonly thought to emit negligible amounts of CO, this study alludes to the possible risk that high power ECIGs, when operated at high power as recommended by the manufacturer for cloud chasing, can emit cigarette-like levels of carbon monoxide. CO exposure potentially accounts for recently observed tissue hypoxia in intensive high-wattage ECIG users.47 Added to this finding is the potential harm caused by the other small hydrocarbon gases, especially ethylene and acetylene, which can have significant health implications.48

CONCLUSIONS This study showed that the activation of SOD at moderate powers can lead to the degradation of PG/VG to produce CO, CO2, and small hydrocarbon gases, such as methane, ethylene, and acetylene. CO was highly correlated with power, and its concentration was a function of the coil material and geometry. CO emissions from the SOD (150 puffs/day) ranged from levels comparable to several cigarettes to those corresponding with a waterpipe session (0.58–127.29 mg). This finding highlights the importance of regulating these devices, including the coil material and geometry.

FUNDING This work was supported by the National Institute on Drug Abuse of the National Institutes of Health (grant number P50DA036105) and the Center for Tobacco Products of the U.S. Food and 10 ACS Paragon Plus Environment

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Drug Administration. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.

DECLARATION OF INTERESTS The authors declare no conflict of interest.

SUPPORTING INFORMATION Supporting Information includes the following figures and tables: Background spectrum; calibration curve of CO; a spectrum showing the comparison between N2 and air atmospheric conditions; statistical analysis of the difference between metal wire materials.

ABBREVIATIONS LIST ECIGs, electronic cigarette; SOD, sub-ohm device; PG, propylene glycol; VG, vegetable glycerin; FTIR, Fourier transform infrared; LPGC, long path gas cell; LPM, liter per minute.

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Table 1. Data showing the effect of the different metal types and coil configurations on CO emissions in aerosols that were generated at a constant power output of 125 W using the sub-ohm device Geometry Surface Number of Diameter CO Metal Type annotation Area wraps (mm) (mg/m3) (mm2) Nichrome A 417 10 3 76.7 ± 64.1 Stainless A 417 10 3 429.7 ± 376.2 Steel Nickel A’ 417 13* 3 943.7 ± 459.6 Kanthal A 417 10 3 77.7 ± 145.4 B 2153.7 ± Kanthal 225 5 3 1487.3 Kanthal C 417 13 2 2386.9 ± 795.6 *A 26-gauge nickel wire was used. N = 6 replicates for each metal type.

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Chemical Research in Toxicology 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 1. A schematic diagram showing how the aerosols generated from the sub-ohm device were trapped on a filter and the gases directed into the longpath gas cell for infrared analysis Figure 2. A representative infrared spectrum (IR) of the gases emitted from the sub-ohm device vaped using a 3 mm diameter kanthal wire coiled in 10 wraps and operated at 150 W. Labeled are the hydrocarbon and CO gases that were identified and inserted is an expanded view of the CO IR peak. Figure 3. Using a sub-ohm device equipped with a 3 mm diameter kanthal wire that was coiled in 10 wraps (geometry A) and operated at different powers, the FTIR spectra illustrate the increase in the concentrations of the hydrocarbon and CO gases as the operating power increases Figure 4. Comparison of daily CO intake between a sub-ohm device user operated at different powers and a one pack cigarette smoker. The underlying assumption considers that a smoker of one pack of cigarettes inhales 0.77 x 20 = 15.4 mg of nicotine, and 12.6 x 20 = 252 mg of CO49 and that a typical sub-ohm ECIG user takes the same dose of nicotine when vaping the device using a kanthal coil with 5 wraps and a liquid nicotine concentration of 3 mg/mL at powers of 75, 125 and 200 W

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Chemical Research in Toxicology

Figure 1. A schematic diagram showing how the aerosols generated from the sub-ohm device were trapped on a filter and the gases directed into the longpath gas cell for infrared analysis

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Chemical Research in Toxicology

CO Carbonyls

Intensity (a.u.)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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2300

2200

2100

2000 Ethylene-C2H4

Methane-CH4 CO

Acetylene-C2H2

CO2

4000

3000

2000

1000 -1

Wavenumber (cm ) Figure 2. A representative infrared spectrum (IR) of the gases emitted from the sub-ohm device vaped using a 3 mm diameter kanthal wire coiled in 10 wraps and operated at 150 W. Labeled are the hydrocarbon and CO gases that were identified and inserted is an expanded view of the CO IR peak.

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Ethylene Acetylene

Methane CO

Intensity (a. u.)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chemical Research in Toxicology

175 W 150 W 125 W 100 W 75 W 25 W

4000

3000

2000

Wavenumber (cm

1000 -1

)

Figure 3. Using a sub-ohm device equipped with a 3 mm diameter kanthal wire that was coiled in 10 wraps (geometry A) and operated at different powers, the FTIR spectra illustrate the increase in the concentrations of the hydrocarbon and CO gases as the operating power increases

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Chemical Research in Toxicology 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 4. Comparison of daily CO intake between a sub-ohm device user operated at different powers and a one pack cigarette smoker. The underlying assumption considers that a smoker of one pack of cigarettes inhales 0.77 x 20 = 15.4 mg of nicotine, and 12.6 x 20 = 252 mg of CO49 and that a typical sub-ohm ECIG user takes the same dose of nicotine when vaping the device using a kanthal coil with 5 wraps and a liquid nicotine concentration of 3 mg/mL at powers of 75, 125 and 200 W

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