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Chemical Composition of Aerosol from an E-Cigarette: A Quantitative Comparison with Cigarette Smoke

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Research and Development, British American Tobacco Investments Ltd., Regents Park Road, Southampton, Hampshire SO15 8TL, U.K.
*E-mail: [email protected]
Cite this: Chem. Res. Toxicol. 2016, 29, 10, 1662–1678
Publication Date (Web):September 18, 2016
https://doi.org/10.1021/acs.chemrestox.6b00188

Copyright © 2016 American Chemical Society. This publication is licensed under these Terms of Use.

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Abstract

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There is interest in the relative toxicities of emissions from electronic cigarettes and tobacco cigarettes. Lists of cigarette smoke priority toxicants have been developed to focus regulatory initiatives. However, a comprehensive assessment of e-cigarette chemical emissions including all tobacco smoke Harmful and Potentially Harmful Constituents, and additional toxic species reportedly present in e-cigarette emissions, is lacking. We examined 150 chemical emissions from an e-cigarette (Vype ePen), a reference tobacco cigarette (Ky3R4F), and laboratory air/method blanks. All measurements were conducted by a contract research laboratory using ISO 17025 accredited methods. The data show that it is essential to conduct laboratory air/method measurements when measuring e-cigarette emissions, owing to the combination of low emissions and the associated impact of laboratory background that can lead to false-positive results and overestimates. Of the 150 measurands examined in the e-cigarette aerosol, 104 were not detected and 21 were present due to laboratory background. Of the 25 detected aerosol constituents, 9 were present at levels too low to be quantified and 16 were generated in whole or in part by the e-cigarette. These comprised major e-liquid constituents (nicotine, propylene glycol, and glycerol), recognized impurities in Pharmacopoeia-quality nicotine, and eight thermal decomposition products of propylene glycol or glycerol. By contrast, approximately 100 measurands were detected in mainstream cigarette smoke. Depending on the regulatory list considered and the puffing regime used, the emissions of toxicants identified for regulation were from 82 to >99% lower on a per-puff basis from the e-cigarette compared with those from Ky3R4F. Thus, the aerosol from the e-cigarette is compositionally less complex than cigarette smoke and contains significantly lower levels of toxicants. These data demonstrate that e-cigarettes can be developed that offer the potential for substantially reduced exposure to cigarette toxicants. Further studies are required to establish whether the potential lower consumer exposure to these toxicants will result in tangible public health benefits.

1 Introduction

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The past decade has seen the rapid emergence and increasingly widespread use of electronic nicotine delivery systems (ENDS), and electronic cigarettes (e-cigarettes) in particular, as alternatives to conventional tobacco cigarettes. (1) The first modern e-cigarette design has been widely attributed to Hon Lik in the early 2000s. (2) As a result of rapid product innovation and changes in design since then, and in the past 5 years in particular, a wide range of e-cigarette designs has emerged around the world. (3) Nonetheless, most e-cigarettes comprise a battery unit providing energy to a heating coil or atomizer that generates an aerosol from a liquid (“e-liquid”). Most e-liquids tend to comprise excipients such as propylene glycol (PG), vegetable glycerol (VG), and water, as well as nicotine and flavors. Currently, e-cigarette designs can be grouped into four basic categories: small cigarette-like disposable and rechargeable designs; closed-system modular designs, comprising separate battery units and e-liquid cartridges; open-system modular designs, wherein the user adds a separately sold e-liquid to a refillable atomizer unit; and tank or box-mod systems, where the user can customize both individual components of the device and their operating conditions as well as add a choice of e-liquids.
The increasing popularity of e-cigarettes has been described as a largely consumer-led development, (4) with many tobacco cigarette users electing to trial and switch partially or totally from smoking to use of e-cigarettes. There are currently more than 10 million e-cigarette users across the world, particularly in the United States, United Kingdom, France, and wider European countries. (5-7) The predominant population of e-cigarette users comprises either ex-smokers or dual users, with relatively few never-smokers. (7, 8) E-cigarettes have been recognized by some scientists as being as effective as, or more effective than, smoking-cessation treatments including traditional nicotine-administration cigarette surrogates such as nicotine patches and chewing gums; (8) consequently, the use of e-cigarettes among smokers is increasing.
Tobacco cigarette users face significant health risks associated with smoking: lung cancer, chronic obstructive pulmonary disorders, and heart disease are the major causes of mortality and morbidity among smokers. (9) For over 50 years, scientists have worked to establish disease mechanisms and their sources in cigarette smoke, with efforts focusing on a number of toxic chemicals in cigarette smoke. (10) The presence of over 100 harmful and potentially harmful constituents (HPHCs) of tobacco and cigarette smoke has been recognized by various scientific bodies, (11, 12) and several regulatory authorities have mandated the reporting of different toxicant suites in smoke emissions from cigarettes. (10, 13-16) Recently, an advisory body on Tobacco Product Regulation (TobReg) to the World Health Organisation (WHO) has proposed mandated lowering of the emission levels from cigarettes of nine toxicants: carbon monoxide, formaldehyde, acetaldehyde, acrolein, 1,3-butadiene, benzene, benzo[a]pyrene, N′-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). (17)
E-cigarette use is regarded by many (but not all) scientists as being likely to have substantially lower levels of risk than smoking tobacco cigarettes. (18, 19) Support for this position comes from in vitro biological studies (20, 21) and the relatively simple composition of e-cigarette aerosols (22) in comparison to cigarette smoke with its thousands of constituents. (23) A growing number of studies have also investigated the emissions of some cigarette smoke toxicants from e-cigarettes, such as tobacco-specific nitrosamines, (24-27) tobacco alkaloids and nicotine decomposition products, (24, 28, 29) volatile organic compounds, (22, 26, 30-33) aromatic amines, (26) CO, (26) polycyclic aromatic hydrocarbons (PAHs), (26, 32, 34) phenolics, (26, 27) metals, (26, 30, 35, 36) and carbonyls. (27, 30, 31, 37-47) Most of these studies report aerosol emission levels of toxicants that are either undetectable or a few percent of those found in cigarette smoke, and comparisons have also been made to room air. (26) However, the presence of toxicants in e-cigarette aerosols, even at comparatively low levels, suggests that e-cigarette use is not risk-free.
Although the levels of toxicants in e-cigarette aerosols have commonly been reported to be a fraction of those found from tobacco cigarettes, the carbonyls formaldehyde, acetaldehyde, and acrolein are an exception to this general trend. Levels of these carbonyls can approach those from traditional tobacco cigarettes, particularly under dry-puff conditions when e-liquid transport to the atomizer is insufficient for the applied electrical power setting. Two studies that used very high e-cigarette power settings reported carbonyl emission levels higher than those found in cigarette smoke, owing to overheating of the e-liquid in the atomizer. (41, 48) While the use of these high e-cigarette power settings has been criticized on the basis that they are unrepresentative of human exposure, and the attendant unpleasant off-tastes and odors generated by overheating in such dry-puff situations would restrict or prevent consumer exposure to high carbonyl emissions, the presence of carbonyls in e-cigarette emissions remains a concern. (42, 43, 49)
Additional compounds have been identified in the emissions of e-cigarettes that have historically received little focus in cigarette smoke toxicant prioritization exercises, such as ethylene glycol and diethylene glycol, glyoxal, methylglyoxal, (39) diacetyl and acetyl propionyl, (50, 51) acetoin, (51) copper, (36) and zinc. (35)
There is emerging regulatory focus on toxicant emissions from e-cigarettes. For example, a recent data dictionary, (52) issued by the European Commission during the development and National Implementation of the 2014 EU Tobacco Products Directive, suggested the following list of emissions for product notification purposes in the EU: nicotine, ethylene glycol and diethylene glycol, formaldehyde, acetaldehyde, acrolein, crotonaldehyde, NNN, NNK, cadmium, chromium, copper, lead, nickel and arsenic, toluene, benzene, 1,3-butadiene, isoprene, diacetyl, and acetyl propionyl. In contrast, the recent FDA final deeming of regulations covering e-cigarettes did not identify any specific compounds of interest at this time. (53)
To date, no single study has attempted to comprehensively characterize the chemical composition of e-cigarettes by comparing the emissions of all known e-cigarette and tobacco cigarette priority compounds with those from a tobacco cigarette. This information is an important contribution to current interest in understanding the relative toxicities of e-cigarettes and tobacco cigarettes. To our knowledge, only three groups have examined a reasonably broad range of compounds: Flora et al.; (54) Tayyarah and Long, (26) who measured e-cigarette emissions of 55 HPHCs; and Lauterbach and Laugesen, (55, 56) who examined 62 cigarette smoke emissions from an early e-cigarette design. Even these studies provide an incomplete picture of the potential chemical composition of e-cigarettes in comparison to that of tobacco cigarettes. The absence of a complete data set is an important gap that needs to be resolved. The current work addresses that gap, reporting the emission levels of 142 chemicals and 8 collated measures, covering the widest practicable range of HPHCs of cigarette smoke and key e-cigarette constituents of concern.

2 Experimental Procedures

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2.1 Test Pieces

The tobacco cigarette used in the current work was the Ky3R4F Kentucky Reference Cigarette (Center for Tobacco Reference Products, University of Kentucky, USA), designed to provide a standard test piece for scientific studies. It is a US-blended king-sized product with a cellulose acetate filter and an ISO tar yield of 9.4 mg/cigarette in 9 puffs. The composition, construction, and mainstream smoke HPHC yields from this product have been reported previously. (57, 58)
The e-cigarette used was Vype ePen (Nicoventures Trading Ltd., Blackburn, UK). It is a closed-modular system (Figure 1) consisting of two modules: a rechargeable battery section and a replaceable e-liquid-containing cartridge (“cartomizer”). The device also has a removable mouthpiece and a screw connector for the cartomizer to connect to the battery section.

Figure 1

Figure 1. Vype ePen construction.

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The battery section comprises a USB-rechargeable 650 mAh battery and an integrated circuit power controller with two voltage settings, 4 and 3.6 V, selectable by the consumer via an external twin-setting surface mounted switch. Device operation commences when the user presses either setting of the power switch, usually 1 s in advance of the puff being taken (1 s preheat time), with power operating within the device as long as the button is pressed, usually the length of the puff.
The disposable e-liquid cartomizers comprise a liquid tank and an atomizer. The tank is composed of an inner polypropylene liquid reservoir held within an outer polypropylene aerosol-transport tube. The liquid contained within the inner tank is fed to the atomizer through a sintered porous ceramic disk in contact with a silica transport wick. The atomizer comprises a 2.85 Ω nichrome (80% Ni/20% Cr) wire coil heater wrapped around the wick. The resistance of the nichrome wire generates heat when current is supplied by the battery; the heated wire and wick vaporize the e-liquid carried by the wick. The vapor condenses downstream of the atomizer into aerosol particles that are carried by the outer transport tube to the device user for inhalation.
A number of Vype e-liquid flavors are sold, including the “Blended Tobacco” variant examined in this study, chosen because it is the variant sold in the greatest number (data not shown). The cartomizer contained 1.58 mL of the Blended Tobacco e-liquid composed of 25% (w/w) propylene glycol containing low levels (<1%) of blended tobacco flavor, 48.14% VG, 25% water, and 1.86% nicotine. Vype ePen has an operating life of in excess of 200 puffs, depending on usage patterns, and was operated in these tests at the 3.6 V setting. The e-cigarette was developed in accordance with a detailed duty-of-care protocol, (59) which examines the device materials, liquid composition, device performance, and aerosol content.
Products were sampled from the factory at a single point in time and contained e-liquid prepared in a single batch operation. The samples were quality-control-checked to ensure compliance with product specification prior to dispatch to the testing laboratory.

2.2 Analysis of Emissions from the E-Cigarette Aerosol and Cigarette Smoke

Analyses were conducted by a single laboratory, Labstat International ULC (Labstat; Kitchener, Ontario, Canada), with the exception of polychlorinated dibenzodioxins/dibenzofurans and radioactive isotopes, which were subcontracted by Labstat to external laboratories.
Smoking machine parameters for the measurement of cigarette smoke constituents have been the subject of much debate. (60) The most widely used puffing conditions of a 35 cm3 puff volume, 2 s puff duration, and 58 s interpuff interval, as defined by the International Organization for Standardization (ISO), (61) have been widely criticized for under-representing the yields of emissions in comparison to those taken by smokers while puffing. A second puffing regime has gained prominence and widespread support since 1999, (16, 62) namely, the Health Canada Intense (HCI) smoking regime, (13) with a 55 cm3 puff volume and a 2 s puff duration, with a bell-shaped puff profile, taken twice per minute, with all filter ventilation holes blocked. The increased puff volume, shorter interpuff interval, and blocked ventilation holes lead to higher smoke yields than those under the ISO conditions and, although also unlikely to represent actual human exposure, are considered by many to be more representative than ISO data. In the current study, HCI parameters were used to generate cigarette smoke emissions for subsequent toxicant measurement.
At present, there are no standardized e-cigarette puffing parameters for analytical measurements. Studies have reported the use of a wide range of puffing parameters by e-cigarette consumers, and various values have been used in machine-based aerosol chemistry measurements. (63-68) Overall, a longer puff duration has been commonly observed for e-cigarette users as compared with cigarette smokers. (69, 70) Whether a single puffing regime is appropriate for all e-cigarettes remains to be demonstrated; nevertheless, urgent standardization is required to enable comparisons to be made between studies. With this in mind, the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) has published Recommended Method 81 for machine puffing e-cigarettes and uses a regime with rectangular flow profile puffs, a puff volume of 55 cm3, and a duration of 3 s, taken twice per minute. (71) These puffing parameters were applied to the e-cigarette in the current study.
Cigarettes smoked under HCI parameters often provide between 10 and 15 puffs per cigarette. (72) Vype ePen provides in excess of 200 puffs to the consumer before the e-liquid becomes exhausted. In the measurement phase of this study, emissions data were collected on a per-cigarette basis for Ky3R4F, with the puff number recorded. For the e-cigarette, the analyses were conducted in two blocks, each with a duration of 100 puffs. Data were therefore obtained for blocks of puffs 1–100 and puffs 101–200. The reported data are based on five independent replicates of products sampled at one point in time.

2.3 Measurement Methods

The methods used by the analysis laboratory are summarized in Supporting Information Table S1. In total, 27 different analytical methods were used to quantify the emissions of 150 measurands, including 142 analytes and 8 collated values, in the mainstream emissions from the e-cigarette, Ky3R4F, and air/method blanks. The methods used were largely based on Health Canada methods for cigarette smoke analysis, with additional methods developed by Labstat for the other HPHCs and e-cigarette compounds of interest. The methods were adapted for use with e-cigarettes where necessary. The operation of the methods is accredited to ISO/IEC 17025:2005 (73) for all reported constituents of mainstream tobacco smoke and e-cigarette aerosols, except where noted in Supporting Information Table S1. No analytical methods were identified for the analysis of three HPHCs, NSAR, coumarin, and aflatoxin, in smoke or aerosol. The FDA TPSAC 2010 draft list implies that these substances and N-nitrosomorpholine are not expected to be present in smoke, only in tobacco; (74) therefore, these compounds were not included in the study.

2.4 Data Treatment for Comparison Between Test Pieces

As noted above, tobacco cigarettes are consumed in approximately 10 puffs when machine smoked, whereas e-cigarettes may continue to function for several hundred puffs. Consequently, the current data are presented both “as measured” (i.e., per-stick for Ky3R4F or per-100 puff block for the e-cigarette) and also on a per-puff basis by dividing the reported values by the number of puffs taken during the measurement. The calculated per-puff values allow a direct comparison of emissions between products and facilitate scaling by daily puff consumption values to provide a daily toxicant exposure assessment. Percentage differences between the emissions from the two devices are calculated on a per-puff basis.
This approach seems to be a reasonable basis for comparison because, on average, cigarette smokers smoke between 15 and 20 cigarettes per day, (7) leading to a total cigarette puff count approaching 200 per day. Consumption measurements with e-cigarettes suggest that 150–250 puffs are taken each day by the average vaper. (67, 75) Extending per-puff comparisons to provide daily exposure estimates is challenging because Ky3R4F is a research cigarette rather than a commercial product; in addition, the intake/uptake efficiency of toxicants from either test piece is unclear at present.

2.5 Inclusion of Limit of Detection/Quantification Values

For many measurands, the emissions were below the limit of detection (LOD) and/or limit of quantification (LOQ). To enable the percentage difference between ePen and Ky3R4F to be calculated for as many constituents from each toxicant subset as possible, <LOD and <LOQ values were imputed as follows. For data <LOD, the value was calculated as one-half of the analytical method’s reported LOD:For data <LOQ but >LOD, the value was calculated as the midpoint between the reported LOD and LOQ of the analytical method:In cases where the e-cigarette and Ky3R4F reference cigarette emissions were both <LOD or <LOQ, the measurand was omitted from the percentage difference calculation.

2.6 Estimation of Ky3R4F Smoke Yields under ISO Conditions

Our study focused on measurement of Ky3R4F smoke yields under the HCI regime. When comparing smoke yields from Ky3R4F to the e-cigarette aerosol emissions, it was considered of interest to also conduct comparisons with Ky3R4F mainstream smoke emissions conducted under ISO conditions, as these would provide a lower comparative set of toxicant levels with which to compare the e-cigarette emissions. To achieve this comparison, we used the data of Roemer et al., (58) who reported the emissions of a number of cigarette smoke toxicants from Ky3R4F under both ISO and HCI smoking regimes, and provided ratios for the yields measured under the two regimes. Roemer et al. identified smoke yields that were, on average, approximately 2.75 times higher under HCI smoking conditions than those under the ISO regime. For a small number of toxicants, the ratio was higher or lower than the average ratio. Data from Eldridge et al. were also used to identify a typical puff number of 8 puffs for 3R4F under ISO smoking conditions. (81)
From the data measured in the present study for all 150 measurands, equivalent emissions under the ISO regime were estimated on a per-puff basis for Ky3R4F using our measured HCI values, the HCI/ISO ratio for each compound from Roemer et al. (where no value was available the mean value of 2.75 was used), and the respective puff numbers for Ky3R4F under HCI and ISO.

2.7 Air/Method Blank Measurements

Tayyarah and Long (26) noted that e-cigarette emissions of some HPHCs approach those of background air. Consequently, the 142 target constituents were measured in the laboratory background at the same time as the e-cigarette emissions. This facilitated an assessment of HPHC background contamination within the air, analytical equipment, and reagents used to measure the e-cigarette emissions, thereby distinguishing between potential background contaminants and actual e-cigarette emissions.
Background air/method blank measurements were performed by collecting blocks of 100 puffs of laboratory air without any e-cigarette present on the puffing machine and by analyzing the puffs with the same equipment and reagents used for the e-cigarette emission analysis. An equivalent control step was not practicable for the tobacco cigarette measurements because cigarettes release relatively high emissions of toxicants into the sidestream (room) air while they burn; therefore, obtaining a simultaneous relevant measure of room air/method contamination is not straightforward.
To minimize the potential for the e-cigarette measurements to be contaminated by background from tobacco cigarette smoking, the e-cigarette emissions were generated by using puffing machines in a separate laboratory from that used for smoking tobacco cigarettes, with segregated air-handling systems. Because Ky3R4F and the e-cigarette were puffed in different rooms with different puffing machines, different air/method background levels might be expected. However, laboratory background is less of a concern for tobacco cigarettes than for e-cigarettes because toxicant levels are significantly higher in tobacco smoke, and the 10-fold fewer puffs taken on tobacco cigarettes might reduce contamination commensurately. The use of air/method background values is discussed in detail below.

3 Results

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All of the emissions data for the 150 measurands are presented in Supporting Information Tables S2–S11. The study encompassed all but three HPHCs, as well as compounds previously associated with e-cigarettes. Supporting Information Tables S2–S11 provide separate LODs and LOQs for the analytical methods used for the e-cigarette and air experiments and the LODs and LOQs operating for the cigarette smoke measurement experiments. Different values operate in many cases owing to the substantially different numbers of puffs taken on the different test pieces. In all cases, the data for the e-cigarette are presented as two 100-puff blocks, covering puffs 1–100 and puffs 101–200. Air/method blank data are also presented in Supporting Information Tables S2–S11, also in two separate blocks equivalent to puffs 1–100 and 101–200 taken at exactly the same time as the e-cigarette puffs. Tables 1 and 2 summarize the 25 compounds detected at some level in the emissions from the e-cigarette, Table 3 summarizes the compounds showing no significant difference from the air/method blank values, and Table 4 presents the results of the puff volume experiment. The data are discussed by compound group below.
Table 1. Emissions Measured from ePen at Quantifiable Levelsa
    ePenair/method blankKentucky reference 3R4F smoke measurements
  ePen and air/method blank LOD and LOQ per collectionpuffs 1–100puffs 101–200 puffs 1–100puffs 101–200 LOD and LOQ per collection per cigarette emission 
smoke constituenttoxicant listLODLOQmeanSDmeanSDePen per puffmeanSDmeanSDblank per puffLODLOQnumber of puffsmeanSD3R4F per puff
formaldehyde, μgT, F18, BCV, FEL0.7222.4112.14.812.34.90.1226.590.316.790.40.0670.41.210.894.96.28.79
acetaldehyde, μgT, F18, BCV, FEL1.956.4910.42.710.72.90.106NQNQNQNQ0.0420.973.2410.8173243160.4
acrolein, μgT, F18, BCV, FEL1.434.756.114.947.95.560.070BDLBDLBDLBDL0.0070.712.3810.8172315.94
allyl alcohol, ngECIG67.65226.54641346092825.365BDLBDLBDLBDL0.33867.65226.510.4169786441.63 × 103
glyoxal, μgECIG0.1260.424.8110.16.457.60.056NQNQ0.440.170.0040.632.110.620.442.661.93
methyl glyoxal, μgECIG0.0770.2564.592.74.621.920.0460.290.12NQNQ0.0020.381.2810.618.20.681.72
glycerol, mgECIG0.0720.2415318.3162.7131.579NQNQNQNQ0.0020.020.0810.52.050.121.95 × 10–1
propylene glycol, mgECIG0.0120.0466.78.6175.066.220.709NQNQNQNQ0.00000.0110.50.0302.92 × 10–3
chrysene, ngFEL0.230.780.880.351.230.330.011NQNQBDLBDL0.0030.080.2610.336.793.593.57
nicotine, mgF18, FEL0.0070.0223.571.102.750.9810.032BDLBDLBDLBDL0.000040.0020.00710.81.840.0770.170
myosmine, ngECIG31810602664526281045527.37BDLBDLBDLBDL1.5906421211.19809701883.7
cotinine, ngECIG76.32541123145104414810.835BDLBDLBDLBDL0.382155111.15086119124582
NNN, ngT, F18, BCV0.4921.6415.160.565.611.030.054NQNQ1.830.510.0140.20.6610.6264.6722.224.97
chromium, ngBCV, FEL13.5445.1350.413.9NQNQ0.399NQNQNQNQ0.2931.354.5110.9NQNQ0.27
Compounds Not Higher than Air/Method Blank in Original Study but Measured Higher from ePen than Air/Method Blank during Puff Volume Study (Table 4)
acetone, μgBCV, FEL1.695.645.953.298.562.980.073100.711.10.90.1060.82.810.87261667.21
butyraldehydeBCV1.625.41BDLBDLBDLBDL0.008BDLBDLBDLBDL0.0080.8122.7110.892.54.808.56
a

Abbreviations: NNN, N-nitrosonornicotine; BCV, British Columbia List; ECIG, chemicals reported in e-cigarette emissions; F18, FDA current reporting list; FEL, full FDA established lists of HPHCs; BDL, below detection limit; LOD, limit of detection; LOQ, limit of quantification; NQ, not quantifiable.

Table 2. Emissions Identified from ePen at Levels Too Low to Quantifya
    ePenair/method blankKentucky reference 3R4F smoke measurements
  ePen and method blank LOD and LOQ per collectionpuffs 1–100puffs 101–200 puffs 1–100puffs 101–200 LOD and LOQ per collectionnumber of puffsper cigarette emission 
smoke constituenttoxicant listLODLOQmeanSDmeanSDePen per puffmeanSDmeanSDair blank per puffLODLOQmeanSD3R4F per puff
propionaldehyde, μgBCV, FEL26.67BDLBDLNQNQ2.67 × 10–2BDLBDLBDLBDL1.00 × 10–213.3410.8133512.3
menthol, mgECIG0.0120.041NQNQNQNQ2.65 × 10–4NQNQBDLBDL1.63 × 10–400.0110.5BDLBDL1.94 × 10–4
diacetyl, μgECIG0.0870.29NQNQNQNQ1.89 × 10–3BDLBDLBDLBDL4.35 × 10–40.441.4510.6266.5227.92.51 × 101
anatabine, ngECIG252841NQNQNQNQ5.47BDLBDLBDLBDL1.2650.416811.13007111312709.07
anabasine, ngFEL4311440NQNQNQNQ9.36BDLBDLBDLBDL2.1686.228811.19364450843.56
β-nicotyrine, ngECIG234779NQNQNQNQ5.07BDLBDLBDLBDL1.174715611.19790149882.01
NDMA, ngFEL1.785.93BDLBDLNQNQ2.37 × 10–2BDLBDLBDLBDL8.89 × 10–30.591.9810.58.462.580.81
nickel, ngBCV, FEL28.4894.92NQNQNQNQ6.17 × 10–1NQNQBDLBDL3.80 × 10–12.859.4910.9NQNQ0.57
Compound BDL in Original Study but Measured Higher from ePen than Air/Method Blank in Some Experiments of Puff Volume Study (Table 4)
propylene oxide, ngFEL156520BDLBDLBDLBDL0.78BDLBDLBDLBDL0.7815.65210.51.1 × 10390.7103
a

Abbreviations: NDMA, N-nitrosodimethylamine; BCV, British Columbia List; ECIG, chemicals reported in e-cigarette emissions; F18, FDA current reporting list; FEL, full FDA established lists of HPHCs; BDL, below detection limit; LOD, limit of detection; LOQ, limit of quantification; NQ, not quantifiable.

Table 3. Compounds Showing No Significant Difference between ePen and Air/Method Blank Emissionsa
Table a

Abbreviations:; NAT, N-nitrosoanatabine; NNK, nicotine-derived nitrosamine ketone;.NDBA, N-nitrosodi-n-butylamine; NPYR, N-nitrosopyrrolidine; NDELA, N-nitrosodiethanolamine; BCV, British Columbia List; ECIG, chemicals reported in e-cigarette emissions; F18, FDA current reporting list; FEL, full FDA established lists of HPHCs; BDL, below detection limit; LOD, limit of detection; LOQ, limit of quantification; EDL, estimated detection limit; NQ, not quantifiable.

Table 4. Emissions of Toxicants under Different Machine Puff Volumesa
 Vype ePen blended tobacco regular strength eCaps (100 puffs)air blank (100 puffs)  
 35 mL, 30 s, 3 s80 mL, 30 s, 3 s110 mL, 30 s, 3 s140 mL, 30 s, 3 s35 mL, 30 s, 3 s80 mL, 30 s, 3 s110 mL, 30 s, 3 s140 mL, 30 s, 3 smodified reagent blanks
aerosol constituentmeanSDmeanSDmeanSDmeanSDmeanSDmeanSDmeanSDmeanSDmeanSD
Selected Carbonyls
formaldehyde, μg18.914.417.3214.91.714.61.58.610.2713.11.712.81.312.50.38.20.25
acetaldehyde, μg22.113.314.71.712.60.712.70.810.808.930.188.610.48.810.21110.1
acetone, μg6.951.446.310.226.841.378.011.17NQNQNQNQNQNQNQNQNQNQ
acrolein, μg1513.511.22.76.722.425.862.43BDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
propionaldehyde, μgNQNQNQNQBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
crotonaldehyde, μgNQNQBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
methyl ethyl ketone, μgNQNQNQNQNQNQNQNQNQNQNQNQNQNQNQNQNQNQ
butyraldehyde, μg6.340.737.680.218.51.4310.42.1NQNQBDLBDLBDLBDLBDLBDLBDLBDL
Semivolatiles
pyridine, μgBDLBDLBDLBDLNQNQBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
quinoline, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
styrene, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
nitrobenzene, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
benzo(b)furan, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
Tar, Nicotine, and Carbon Monoxide
CO, mgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLNANA
Volatiles
1,3-butadiene, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
isoprene, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
acrylonitrile, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
benzene, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
toluene, μgNQNQ3.260.094.220.17NQNQNQNQ3.190.063.890.1BDLBDLNQNQ
ethylbenzene, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
ethylene oxide, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
vinyl chloride, ngBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
propylene oxide, ngNQNQNQNQBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
furan, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
vinyl acetate, ngBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
nitromethane, ngBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
Aromatic Amines
1-aminonaphthalene, ngNQNQBDLBDLBDLBDLBDLBDLBDLBDLNQNQBDLBDLNQNQBDLBDL
2-aminonaphthalene, ngNQNQNQNQNQNQNQNQNQNQNQNQNQNQNQNQNQNQ
3-aminobiphenyl, ngNQNQNQNQNQNQNQNQ0.0420.017BDLBDLNQNQNQNQNQNQ
4-aminobiphenyl, ngNQNQNQNQNQNQNQNQNQNQBDLBDLNQNQBDLBDLBDLBDL
2,6-dimethylaniline, ngBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
benzidine, ngBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
o-anisidine, ngBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLNQNQNQNQBDLBDL
o-toluidine, ng0.4570.2250.5470.2830.620.1410.7430.0850.480.050.3610.2420.60.3120.570.114NQNQ
Acrylamide and Acetamide
acetamide, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
acrylamide, μgBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDLBDL
a

Abbreviations: BDL, below detection limit; LOD, limit of detection; LOQ, limit of quantification; NA, not applicable; NQ, not quantifiable.

3.1 Oxygen-Containing Toxicants

3.1.1 Carbon and Nitrogen Oxides (Supporting Information Table S2)

Carbon monoxide was detected in the emissions of ePen (Table 3); this was unexpected because CO is a combustion-generated product and combustion does not occur in e-cigarettes. However, effectively identical levels of CO were detected in the room air/method analyses, indicating that the measured CO is an air/method contaminant rather than an e-cigarette generated emission. The background levels were 98% lower than the levels from Ky3R4F. Other combustion gases, NO and NOx, were not detected in the e-cigarette emissions or room air, but they were present in Ky3R4F mainstream smoke (MSS; ePen levels >99% lower per-puff versus Ky3R4F).

3.1.2 Carbonyl Emissions (Supporting Information Table S3)

All of the measured carbonyl emissions from the e-cigarette were considerably lower (98.6–99.9%) than those from Ky3R4F, whether on a per-collection or per-puff basis. Emissions of butyraldehyde, crotonaldehyde, and, in one puff block, propionaldehyde were not detected from the e-cigarette. In contrast, emissions of acetone, 2-butanone, and, in one puff block, propionaldehyde were detected for the e-cigarette, but they were at lower levels than those measured for the air/method blank, suggesting their presence in the e-cigarette emissions may be artifactual rather than due to the e-cigarette (Table 3); this is discussed further in Section 3.5.
Emissions of formaldehyde, acetaldehyde, and acrolein were also quantified in the e-cigarette (Table 1). For formaldehyde and acetaldehyde, however, the levels measured in the air/method blank were approximately one-half of those measured in the e-cigarette aerosol, demonstrating a significant but not exclusive contribution from room air. Acrolein was not detected in the air/method blank samples; therefore, the measured emissions from ePen, albeit much lower than those from Ky3R4F, were generated by the e-cigarette.

3.1.3 Dicarbonyls (Supporting Information Table S4)

Glyoxal and methyl glyoxal were quantified in both e-cigarette emissions and in Ky3R4F MSS at levels substantially higher than in the corresponding air/method blanks (Table 1). The emissions from the e-cigarette were 97% lower on a per-puff basis as compared with Ky3R4F.
Diacetyl was detected but not quantifiable in the e-cigarette emissions (Table 2) and was not detected in the air/method blank, but it was quantified at substantially higher levels in Ky3R4F MSS. The levels of diacetyl were 99.9% lower on a per-puff basis in the e-cigarette emissions than in Ky3R4F MSS. The homologue acetyl propionyl was not detected in the e-cigarette emissions or in the air/method blanks; however, it was quantified in Ky3R4F MSS at substantially higher levels (Supporting Information Table S4). The levels in the e-cigarette aerosol were estimated to be at least 99.9% lower on a per-puff basis as compared with those in Ky3R4F smoke. Neither diacetyl nor acetyl propionyl is an ingredient included in Vype products; therefore, their presence in these aerosol measurements is unlikely.

3.1.4 Alcohols and Polyalcohols (Supporting Information Table S4)

Menthol was detected at unquantifiable levels in the e-cigarette emissions and in one puff block of the air/method blanks; it was not detected in Ky3R4F emissions (Table 2). Allyl alcohol was quantified at higher levels in emissions from the e-cigarette than in the air/method blank, but its level was >99% lower than Ky3R4F on a per-puff basis (Table 1).
Acetoin was not detected in any of the samples analyzed. Ethylene glycol was detected but not quantifiable in either the e-cigarette emissions or the air/method blank, but it was quantified in Ky3R4F smoke (Table 2). On a per-puff basis, the e-cigarette emissions of ethylene glycol were >98% lower compared with those of Ky3R4F MSS. Diethylene glycol was not detected in ePen emissions or the air/method blank, and it was not quantifiable in Ky3R4F smoke. Both propylene glycol and glycerol were measured at higher per-puff levels in the e-cigarette emissions than in Ky3R4F MSS.

3.1.5 Phenols (Supporting Information Table S3)

None of the measured phenols was detected in the e-cigarette aerosol or air/method blanks. In contrast, Ky3R4F generated measurable levels of all phenols except caffeic acid (which was not detected). Consequently, the levels of phenolics were >99% lower on a per-puff basis from the e-cigarette than from the Ky3R4F tobacco cigarette.

3.1.6 Oxygen Heterocycles (Supporting Information Tables S2 and S5)

Ethylene oxide, propylene oxide, furan, benzo{b}furan, and glycidol were all detected in the MSS from Ky3R4F, but none was detected in the e-cigarette emissions or air/method blanks. Per-puff emissions of these compounds were >99% lower from the e-cigarette than from Ky3R4F.

3.1.7 Polychlorinated Dibenzo-p-dioxins and Dibenzofurans (Supporting Information Table S6)

Seven chlorinated dibenzodioxins and 10 chlorinated dibenzofurans were examined in the emissions from the e-cigarette, air/method blanks, and Ky3R4F. Very few of these compounds were observed in these measurements: most were below the LOD for all three matrices. For the e-cigarette, octa-CDD was detected at an unquantifiable level in one puff block, but because the air/method blank also registered unquantifiable levels in the same puff block, we concluded that this signal was a background measurement rather than an e-cigarette emission (Table 3). The emissions from Ky3R4F showed unquantifiable levels for 1,2,3,4,6,7,8-hepta-CDD and a quantifiable level of octa-CDD.

3.2 Hydrocarbons

3.2.1 Volatile Hydrocarbons (Supporting Information Table S2)

1,3-Butadiene, isoprene, and the aromatic hydrocarbons benzene and ethylbenzene were not detectable in the e-cigarette emissions or room air, but they were detected in Ky3R4F smoke (ePen levels >99% lower versus Ky3R4F).
Styrene and toluene were quantified in Ky3R4F MSS and in one e-cigarette puff block but not in the other; the levels were >99% lower from the e-cigarette than from Ky3R4F. They were also found in the matching air/method blanks at levels effectively identical to those of the e-cigarette (Table 3). On that basis, we conclude that they are present as analytical background and not as ePen-generated toxicants.

3.2.2 Polycyclic Aromatic Hydrocarbons (Supporting Information Table S7)

The e-cigarette aerosol, laboratory air, and Ky3R4F MSS were examined for the possible presence of 16 PAHs. Two PAHs, dibenz[a,h]pyrene and dibenz[a,l]pyrene, were not detected in any sample. Dibenz[a,e]pyrene was not detected in the e-cigarette emissions or the air/method blank, and it was detected but not quantified in Ky3R4F MSS (e-cigarette levels 93% lower versus Ky3R4F). Eleven PAHs were not detected in the e-cigarette or the air/method blanks, but they were detected in Ky3R4F emissions (e-cigarette levels 94–99.9% lower versus Ky3R4F). Naphthalene and chrysene were quantified at low levels in both puff blocks of the e-cigarette aerosol and were also identified in the air/method blank. For naphthalene, the air/method blank value was almost identical to the e-cigarette emissions value (Table 3), suggesting that it was present in ePen aerosol due to contamination. Chrysene also had a measurable level in one block of the air/method blank, but not both, suggesting some formation in the e-cigarette aerosol (Table 1). However, both naphthalene and chrysene were quantified at much higher levels in Ky3R4F emissions than in the e-cigarette aerosol (ePen levels both >99.7% lower versus Ky3R4F).

3.2.3 Substituted Hydrocarbons (Supporting Information Table S2)

Nitromethane, 2-nitropropane, vinyl acetate, and vinyl chloride were detected in Ky3R4F MSS but not in ePen emissions or air/method blanks. Levels from the e-cigarette were >99% lower than those from Ky3R4F. In contrast, nitrobenzene was not detected in any of the samples analyzed.

3.3 Nitrogenous Species

3.3.1 Volatile Nitrogenous Species (Supporting Information Table S2)

NO, NOx, ammonia, and acrylonitrile were quantified in Ky3R4F MSS, but they were not detected in the e-cigarette emissions (>99% lower versus Ky3R4F) or laboratory air. Hydrazine was not detected in the ePen, air/method blank samples, or Ky3R4F MSS.

3.3.2 Amines, Amides, and Azines (Supporting Information Table S5)

Ethyl carbamate was not detected in any of the samples. Acetamide, acrylamide, and quinoline were not detected in the e-cigarette emissions or in the air/method blanks. Pyridine was detected but not quantified in the e-cigarette and laboratory air (Table 3). The comparability of the e-cigarette and air/method blank values indicated that pyridine is a laboratory background contaminant rather than an ePen-generated toxicant. All four compounds were present in the e-cigarette aerosol at levels >99% lower than those from Ky3R4F MSS.

3.3.3 Aromatic and Aliphatic Amines (Supporting Information Table S8)

Three aliphatic amines (Glu-P-1, Glu-P-2, and PhIP) were not detected in any sample. Three aromatic amines (1-aminonaphthalene, o-anisidine, and 2,6-dimenthylaniline) and five aliphatic amines (IQ, Trp-P-2, AaC, Trp-P-1, and MeAac) were not detected in the e-cigarette aerosol or the air/method blank, but they were detected in Ky3R4F MSS (ePen levels >99% lower versus Ky3R4F).
Three aromatic amines (2-aminonaphthalene, 3-aminobiphenyl, and 4-aminobiphenyl) were detected at comparable levels, but not quantified, in the e-cigarette and air/method blank samples (Table 3). One aromatic amine, o-toluidine, had quantifiable levels in the e-cigarette emissions and the air/method blank that were not statistically different. These observations suggest that the source of these compounds in the e-cigarette aerosol is laboratory contamination. The levels observed in ePen aerosol were >99% lower than those in Ky3R4F MSS.

3.3.4 Nicotine and Related Compounds (Supporting Information Table S9)

Nicotine yields were higher from the e-cigarette than from Ky3R4F on a per puff-block basis, but they were significantly lower on a per-puff basis (Table 1). Nicotine-related impurities might be expected at low levels in e-cigarette emissions (76) because they are permitted impurities in European Pharmacopeia standard nicotine. (77) Anabasine, anatabine, β-nicotyrine, cotinine, myosmine, nicotine-N-oxide, and nornicotine are allowed individually at levels up to 0.3%, together with 0.1% of unspecified impurities, as long as the total impurity level does not exceed 0.8%. (28)
Our analysis showed the presence of most of these impurities in the e-cigarette aerosol. The levels of myosmine and cotinine were quantifiable in the e-cigarette emissions but not in the air/method blank samples (Table 1). Anatabine, anabasine, and β-nicotyrine were detected but not quantifiable in the e-cigarette emissions, and they were not found in the air/method blank samples (Table 2). In contrast, nornicotine and nicotine-N-oxide were not detected in either the e-cigarette or air/method blank samples. All of these compounds were quantified at much higher levels in the MSS from Ky3R4F: the per-puff emissions from the e-cigarette were all at least 97% lower than those from Ky3R4F. These observations confirm that some impurities in pharmaceutical-grade nicotine may be present in e-cigarette emissions; nonetheless, the levels of these nicotine-related impurities were significantly lower than those in Ky3R4F cigarette smoke.

3.3.5 Nitrosamines (Supporting Information Table S10)

The IARC Group 1 carcinogen NNN was quantified in the emissions from the e-cigarette and at lower levels in the air/method blank samples (Table 1). Per-puff emissions from the e-cigarette were 99.8% lower than those from Ky3R4F. The likely source of NNN is an impurity in the Pharmacopoeia-standard nicotine used in the e-cigarette. (78)
The other IARC Group 1 carcinogen NNK was either not detected or not quantifiable in the e-cigarette and air/method blank samples (Table 3): the measurements from the first and second puff blocks were equivalent between the e-cigarette and air/method blank samples; consequently, it is not possible to determine conclusively that the e-cigarette contributed to the measured NNK emissions. E-cigarette emissions of N-nitrosoanatabine (NAT) were detected but not quantifiable in one puff block and were not detectable in the second puff block; by contrast, the air/method blanks gave unquantifiable but detectable levels in both puff blocks, suggesting an analytical artifact (Table 3). N-Nitrosoanabasine (NAB) was not detectable in either puff block from the e-cigarette or air/method blank. All four tobacco-specific nitrosamines were quantified in Ky3R4F MSS at substantially higher levels: per-puff emissions of NNK, NAT, and NAB were 99.9% lower in the e-cigarette aerosol than for Ky3R4F.
Measurements of volatile nitrosamines (VNAs) provided a comparatively complex picture. Ten VNAs were measured, six of which were not detected in the e-cigarette aerosol or air/method blanks. Three VNAs, N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), and N-nitrosodiethanolamine (NDELA), were detected and quantified in emissions from Ky3R4F. NDMA was detected but not quantified in one puff block from the e-cigarette but not in the other block or the corresponding air/method blanks, suggesting possible low-level emissions from the e-cigarette (Table 2). NDELA was quantified in all e-cigarette and air/method blank puff blocks, although the measured values for the e-cigarette and the background levels were not statistically different from each other (Table 3). Similarly, N-nitrosodi-n-butylamine (NDBA) and NPYR were detected in both puff blocks, but they were quantifiable in only one puff block for both the e-cigarette aerosol and the air/method blanks. For both of these VNAs, levels from the air/method blanks were not significantly different from those from the e-cigarette, suggesting analytical artifacts may be the source of these compounds. Per-puff emissions from the e-cigarette and air/method blanks were substantially lower in comparison to those from Ky3R4F smoke, other than emissions of NDBA and NDELA, which were higher for the per-puff air/method blank measurements and e-cigarette aerosol.

3.4 Metals and Radionuclides (Supporting Information Table S11)

Mercury, cadmium, lead, selenium, cobalt, beryllium, tin, uranium-235, uranium-238, and polonium-210 were not detectable in either the e-cigarette aerosol or air/method blank samples. Analysis of Ky3R4F MSS showed that cobalt, beryllium, tin, and uranium isotope emissions were undetectable, and chromium, nickel, and selenium emissions were not quantifiable.
Arsenic was detected but not quantifiable in the e-cigarette and air/method blank samples, but it was quantifiable in Ky3R4F MSS (Table 2). Arsenic emissions from the e-cigarette and air/method blanks were estimated to be 78% lower than those from Ky3R4F. Nickel emissions from the e-cigarette and Ky3R4F were detected but not quantifiable, whereas nickel was not detected in one puff block of the air/method blank sample and not quantifiable in the other (Table 2). This suggests the possible presence of nickel in the e-cigarette emissions, albeit at very low levels.
Zinc, iron, and copper were identified and quantified in all three samples (Table 3). Zinc emissions from the e-cigarette were comparable to those from air/blank samples, which were approximately one-half (on a per-puff basis) of those quantified from Ky3R4F MSS. Iron emissions from the e-cigarette and air/method blank were neither significantly different from each other or from Ky3R4F MSS on a per-puff basis. Similarly, although higher mean levels of copper were found in the e-cigarette emissions than in the air/method blank sample, the very high variance between replicates meant that these differences were not significant at the 95% confidence level and were comparable on a per-puff basis to Ky3R4F MSS.
Chromium emissions were quantified only in the emissions from one e-cigarette puff block; the other puff block, both air/method blanks, and Ky3R4F MSS showed detectable but not quantifiable chromium emissions (Table 1). Notably, the level measured for the first e-cigarette puff block was very close to the LOQ (within 5%), and replicates were variable (coefficient of variance, 60%); therefore, it is difficult to establish whether the measured e-cigarette chromium emissions are significantly different from those of the air/method blank. However, it is also worth noting that all air/method blank replicates were below the LOQ, whereas the levels of 2–4 of the five replicates of the two puff blocks of the e-cigarette were above the LOQ. Therefore, it seems possible that the chromium emission from the e-cigarette may be higher than that from the air/method blank and possibly higher than from Ky3R4F MSS on a per-puff basis. If the e-cigarette emission levels are higher than the air/method blank, then the toxicological significance of this is difficult to establish. Chromium may exist in up to three distinct chemical states, elemental Cr(0) or as Cr(III) and Cr(VI) compounds, with exposure to Cr(VI) posing the greatest toxicological concern. Cr(VI) is highly reactive, and although it is stable in oxidizing environments, it is unstable in reducing or redox neutral environments. Recent chromium speciation studies found no evidence for the presence of Cr(VI) in cigarette smoke, (79) but there is no comparable information currently available for e-cigarette aerosols. Consequently, this is an area that requires further investigation to fully understand.

3.5 Contribution and Significance of Air/Method Blank Contaminants to E-Cigarette Emissions

A clear finding emerging from the above data was the importance of conducting air/method blank experiments to understand the presence of some constituents found in e-cigarette emission measurements, reinforcing the conclusions of Tayyarah and Long. (26) To further understand the sources of external contamination in low level e-cigarette constituent measurements, a series of ePen and air/method blank constituent measurements was conducted in which different puff volumes (35, 80, 110, and 140 cm3) were used at a fixed puff duration of 3 s and a puffing frequency of twice per minute. The analytes measured were the carbonyls, semivolatile compounds, CO, volatile constituents, and aromatic amines.
The premise behind these experiments was to distinguish the possible contributions of laboratory air and other sources of contamination to the measured yields of the e-cigarette toxicants; if laboratory air made a significant contribution to the measured e-cigarette yields, then increasing the puff volume would increase the quantity of any contaminants trapped from the air and hence higher emissions would be seen from the air/method blank and e-cigarette experiments. If, however, other aspects of the methodology and reagents were responsible for the observed air/method blank levels, then the levels would not change with the 4-fold range in air volumes. The possibility of reagent contamination has been raised by Flora et al., (54) who reported the presence of formaldehyde in the 2,4-dinitrophenylhydrazine analytical reagent used in e-cigarette carbonyl measurements. Hence, an additional experiment was conducted for each constituent measurement in which the reagents were measured on a blank sample in which no puffs were taken, and the results were compared to the air/method blanks and e-cigarette emissions (Table 4).
The CO yield in all of these experiments was below the LOD, in sharp contrast to the value of 4.74 mg/100 puffs observed for both air/method blanks and e-cigarette emissions in the original measurements (Supporting Information Table S2). However, the observations confirm the hypothesis of air contamination as the source of the ePen CO emissions, given the absence of e-cigarette CO emissions when CO is absent in the laboratory air and the presence at identical levels when it is present. The presence and absence of CO in these measurements is most likely due to transient environmental factors.
Similarly, styrene and pyridine yields were below the LOD in all but one (pyridine, 100 mL puff volume experiment) of these experiments, in contrast to the 0.52 and 1.05 μg/100 puffs of styrene measured for e-cigarette and air/method blanks and the not quantifiable levels of pyridine observed in the original experiments. The reagent blanks were also below the LOD. Overall, these observations are consistent with random and variable levels of air contamination as the source of these volatile organic compounds in our original e-cigarette emissions. Similarly, there was considerable consistency in toluene levels between air blanks and e-cigarette emissions; however, the measured emissions did not increase with increasing air volume, and the reagent blank showed the presence of toluene, albeit not at a quantifiable level, raising the possibility of combined air and reagent contamination. Propylene oxide was observed in two of the low volume experiments, at unquantifiable levels; the other four measurements conducted in this study showed below LOD levels, as were the corresponding air/method blank values. Therefore, there is a possibility of low-level propylene oxide emissions, but the lack of consistency in these observations precludes a firm conclusion at this time.
The aromatic amine measurements also showed evidence of both air and reagent contamination. Both 3- and 4-aminobiphenyl showed unquantifiable levels in most e-cigarette emission and air/method blank measurements. The most insightful observations were those of o-toluidine, which showed an increase in emissions from the e-cigarette with increasing puff volume, although the relationship was less than uniform. The air/method blank samples were not significantly different from the e-cigarette samples at any volume, and the reagent blank had detectable but not quantifiable levels.
The most complex behavior in these experiments was shown by carbonyls. We focus initially on the emissions of formaldehyde, acetaldehyde, and acrolein because these three compounds are known thermal decomposition products of glycerol, (80) and some commonality in drivers of emission levels from the e-cigarette might be expected. Although some contribution of air/method contamination was found for formaldehyde and acetaldehyde (but not acrolein) in our original experiments, the second experiments reflected a major contribution to the overall yields measured in the e-cigarette aerosol.
In these second experiments, both reagent blank and air/method blank levels of acrolein were below the LOD, confirming that observed acrolein levels are generated by the e-cigarette alone. In contrast, comparable levels of acetaldehyde were found in the reagent blank and air/method blank, and the air blank levels of acetaldehyde did not change with increasing air volume, suggesting that the acetaldehyde contamination in these e-cigarette emission measurements is reagent-based. Lastly, the reagent blank levels of formaldehyde were comparable to those of the lowest volume air/method blank, but the air/method blank formaldehyde emissions increased with increasing puff volume, showing a clear contribution of laboratory air to the measured formaldehyde levels.
The emissions of formaldehyde, acetaldehyde, and acrolein were all greater from the e-cigarette than from the air/method blanks, confirming a contribution from the device. Interestingly, the levels of these three species decreased with increasing puff volume. The magnitudes of the reductions were greater for acrolein (3-fold) than for the other two carbonyls. In the case of formaldehyde and acetaldehyde, at the highest puff volumes the contribution of the e-cigarette to the overall emissions was lower than the contributions of laboratory air and reagent blank. Subtraction of the air/method blank values from e-cigarette emissions for all three compounds showed that there was a 3–5-fold reduction in the e-cigarette generated emissions of these three carbonyls for a 4-fold increase in puff volume, implying an inverse quasi-linear correlation. Thermal decomposition of glycerol to form these three carbonyls has been attributed to both the temperature of the coil/wick and the wicking time of the e-liquid prior to aerosol formation. (41) Increasing air flow may serve to reduce coil and wick temperatures through convective cooling. Alternatively, there may be a reduction in aerosol residence time in the higher temperature zones of the e-cigarette. Both mechanisms could, in principle, reduce carbonyl generation; this is an area worthy of further investigation.
Of the remaining carbonyls, propionaldehyde showed detectable levels in the e-cigarette aerosol at low puff volumes only, whereas 2-butanone emissions from the e-cigarette, the air/method blank, and reagent blank were all not quantifiable, suggesting a reagent contaminant. One puff volume experiment gave unquantified levels of crotonaldehyde, whereas the other three measurements in the puff volume experiment and the original two measurements were below the LOD. Butyraldehyde, which was below the LOD in the original measurements, showed measurable levels from the e-cigarette at all puff volumes and was either not quantified or below the LOD for all air/method and reagent blank measurements. Similarly, acetone showed higher levels in the e-cigarette emissions than with the air/method blank and reagent blanks, all of which were not quantifiable. Both of these compounds therefore appear to be released from the e-cigarette.
In summary, these experiments signal the need to conduct background air, reagent, and method blank measurements when attempting to quantify e-cigarette emissions. Failure to do so raises the risk of both inaccuracies in the measured emissions and the reporting of false positives.

4 Discussion

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4.1 Consistency of Measured Emission Levels with Literature Values

To understand the robustness of our data set, we compared our 3R4F emission measurements with those of Roemer et al., (58) who provided 3R4F data measured under HCI and ISO smoking conditions. Our comparison of HCI data showed generally good agreement between our data set and that of Roemer et al. (within 30% for the majority of analytes). A small number of analytes showed more substantial differences, such as toluene, cadmium, and acrylonitrile (40–70% higher from those in Roemer et al.), whereas the present study provided higher values for emissions of formaldehyde (39%) and vinyl chloride (60%). There was no consistent bias between the data sets; our study tended to give higher carbonyl values and TSNAs, and the study of Roemer et al. measured higher levels of gaseous, volatile, semivolatiles, and PAH toxicants. We therefore concluded that the measurements provided by this study are a robust measure of the emissions from 3R4F.
We also sought to compare our e-cigarette emission data with literature values. This is a challenging undertaking, as there is little consistency in the experimental conditions used in historic studies. The wide range of puffing parameters used in previous studies is likely to have a particularly strong influence on the magnitude of published emission values. (68) A range of LOD/LOQ values apply in different studies, which prevents accurate comparison of low-level constituents. In addition, many studies do not disclose whether air/method blank values were measured as part of the experimental design. Hence, it is unlikely that quantitative comparisons of emission values across different studies is meaningful. However, some qualitative comparisons can be made with previous studies. The very low, unquantifiable, or undetectable emissions of TSNAs found from the e-cigarette in this study are consistent with the findings of Goniewicz et al. (30) Similarly, low levels of nicotine-related compounds in e-cigarette aerosols is consistent with the findings of Trehy et al. (76) Williams et al. also quantified chromium in e-cigarette aerosols. (35) Laugesen also presented data for chrysene emissions from an e-cigarette. (34) Hence, a number of the observations from this study are consistent with previous data. There are also some differences with previous studies; for example, the current study did not find toluene emissions to be generated by the e-cigarette, as reported previously. (32) Nevertheless, one of the main conclusions of this study, namely, that emission levels of many toxicants from e-cigarettes are several orders of magnitude lower than those from tobacco cigarettes, is entirely consistent with the collective e-cigarette literature on this topic.

4.2 Complexity of E-Cigarette Aerosol in Comparison to Cigarette Smoke

To compare the complexity of the e-cigarette aerosol to mainstream cigarette smoke, the emissions data in Supporting Information Tables S2–S11 were combined with the findings from the puff volume study (Table 4) to establish how many toxicants were undetectable, how many were present due to air/method blank factors, the number generated at unquantifiable levels, and the number of quantifiable toxicants.
One-hundred four chemical measurands were not detected in ePen emissions, and 21 were present due to laboratory background (Table 3). Among the remaining 25 compounds, 9 were present at levels too low to be quantified (Table 2) and therefore 16 compounds were generated by the e-cigarette at quantifiable levels. (Table 1 and Figure 2). Eight of these compounds are carbonyls or alcohols that have been linked to thermal decomposition of the aerosol carrier (i.e., PG or VG), three are major e-liquid ingredients, and three are impurities present in pharmaceutical-grade nicotine. One is a metallic element used in the e-cigarette coil, and one (chrysene) is of unknown origin. This is in clear contrast to Ky3R4F MSS, which contained approximately 100 compounds at quantifiable levels. These data demonstrate the comparative simplicity of the e-cigarette aerosol in comparison to tobacco cigarette smoke.

Figure 2

Figure 2. Emissions detected from the e-cigarette at quantifiable levels.

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4.3 Comparison of E-Cigarette Emissions in Different Puff Blocks

Some authors have reported higher e-cigarette carbonyl yields from later puff blocks. (40) The current study design examined two separate puff blocks of 100 puffs each in an attempt to provide an overview of the emissions from the e-cigarette aerosol during the normal usage of a cartomizer. In terms of future investigations of this kind, it would be of interest to determine whether this is a necessary step or whether a single puff block can be used.
The e-cigarette emission measurements of puffs 1–100 and 101–200 in Table 1 were compared by t-test to establish whether any of the compounds showed a preferential bias for either puff block, focusing on the 16 compounds that were quantified in the e-cigarette aerosol at higher levels than in the corresponding air/method blank. None of the measurable constituents differed significantly between the puff blocks (t-test, significance criterion of p < 0.05). Consequently, we conclude that it is necessary to measure only one puff block when conducting e-cigarette emission measurements of this kind.

4.4 Comparative Emissions from ePen and Ky3R4F

This study has also shown substantial differences between the magnitudes of e-cigarette and Ky3R4F emissions. To summarize these differences, we grouped together the percentage differences between the e-cigarette and Ky3R4F per-puff emissions, organized by four toxicant lists: the nine WHO TobReg constituents proposed for mandated lowering in cigarette smoke, (17) the 18 constituents on the FDA abbreviated HPHC reporting list, (12) the Health Canada list of 44 tobacco smoke toxicants, (10) and the full FDA list of 96 HPHCs (other than the three species for which no analytical method was available). In conducting our comparison, ePen emissions were used “as-is”, without subtraction of air/method blank values.
Figure 3 shows these comparisons between cigarette smoke and e-cigarette aerosol. In each case, the estimated exposure to the toxicant set was substantially lower for ePen than for Ky3R4F, with the reduction ranging between 92 and >99% depending on the toxicant list chosen.

Figure 3

Figure 3. Comparison of percent reduction in e-cigarette emissions in comparison to those from Ky3R4F under HCI puffing conditions.

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As noted above, use of the HCI smoking regime provides higher emission levels than would occur if the ISO regime were used, and comparisons between Ky3R4F and e-cigarette yields would potentially differ under the different smoking regimes. The ISO regime is regarded by many as an underestimate of human exposure, and the HCI regime as more representative. (60) Nevertheless, to understand the impact on Ky3R4F emission levels, and our comparisons with ePen, of using less intense smoking parameters, we estimated the emissions that would be generated for the 150 measurands under ISO conditions. Our analysis showed that most estimated per-puff emission levels from Ky3R4F under ISO puffing were approximately one-half those measured under HCI. The percent reduction in emissions from the estimated Ky3R4F ISO values to those of the e-cigarette were slightly smaller (but similar overall) than those found using the measured Ky3R4F HCI data; for the WHO 9 and FDA 18 chemicals, e-Pen emissions were 99% lower than from the tobacco cigarette, 90% lower with the Health Canada list toxicants, and 82% lower for the FDA 93 HPHC.
These data demonstrate that, in addition to its simpler composition, the e-cigarette aerosol contains substantially lower levels of regulatory interest toxicants as compared with tobacco cigarette smoke. However, it is important to note that, although significantly lower than those from a tobacco cigarette, e-cigarette emissions may still represent a toxicologically significant dose. Quantitative risk assessment approaches and clinical and population studies may help to better understand this issue.

4.5 Sources of Background Toxicant Levels

Our study has demonstrated the importance of conducting air/method/reagent blank measurements when seeking to either establish the presence of a compound in an e-cigarette aerosol or to quantify it. We have presented evidence for low-level contamination from both laboratory air and analytical reagents. The presence of volatile organic species in occupational and residential room air is a well-recognized phenomenon, with indoor air quality standards established for a number of species. In addition, the presence of an analyte in the laboratory reagent used to analyze for it, such as carbonyls in 2.4-dinitrophenylhydrazine, is a well-recognized phenomenon. (54)
In our study, a number of steps were taken to minimize the potential sources of contamination. For example, separate laboratory rooms were used for the e-cigarettes and tobacco cigarettes when generating and collecting the aerosols. This arrangement was designed to minimize cross-contamination from tobacco cigarettes to e-cigarettes, particularly from the cigarette sidestream plume. The room used to generate e-cigarettes had historically been used for cigarette smoke generation, but it had been thoroughly cleaned and tested prior to use with e-cigarette analysis.
The puffing machines are also a likely source of contamination during metals analysis (data not shown). The puffing machines used in this study for e-cigarette aerosol generation were a mixture of machines that had never been used for cigarette smoking, and machines that had been repurposed from cigarette smoking to e-cigarette puffing. The latter puffing machines were thoroughly cleaned prior to use with e-cigarettes. Both e-cigarette analysis laboratories and puffing engines had been used exclusively for e-cigarettes for an extended period of time prior to this study.
One factor contributing to the measured contamination in e-cigarette aerosols is the number of puffs taken with the e-cigarettes in this study (200 puffs) in comparison to the number taken with tobacco cigarettes (10–11 puffs). With the e-cigarettes, approximately 20 times more laboratory air was drawn through the sampling system, corresponding to 11 L of air in comparison to 0.5 L with the tobacco cigarettes during the main study experiment. This represents a significant potential source of contamination in the e-cigarette aerosol measurement. A second factor is the low level of most e-cigarette emissions, with many compounds present at less than 1% of the levels in a cigarette; in comparison to these low levels, even trace level air contamination may appear significant.
In summary, despite efforts to minimize contamination in our study, we saw significant contributions to our data. We therefore recommend that laboratory background measurements are taken at the same time as e-cigarette aerosol emissions testing to contextualize and account for experimental artifacts.

5 Conclusions

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We have reported an extensive study of toxicant emissions from an e-cigarette. Our data provide the broadest comparison available of e-cigarette and MSS smoke emissions. By covering all of the existing proposed and established tobacco cigarette toxicant lists identified by regulatory authorities and their advisory groups, as well as other compounds reported to be present in e-cigarette aerosols, we provide the most complete comparison of toxicant emissions possible with current scientific capability in this area. The study has demonstrated the relative chemical simplicity of the e-cigarette aerosol in comparison to that from a tobacco cigarette and also shown how levels of cigarette smoke HPHCs are, on average, between 82 and >99% lower per-puff from an e-cigarette than from tobacco cigarette smoke. These findings are an example of what can be achieved in the design of an e-cigarette product if extensive duty-of-care work is conducted to identify and use device parameters and ingredients that offer as little potential for toxicant generation as is possible. On a wider level, these measurements provide additional support to views that e-cigarettes may represent a less harmful alternative to tobacco cigarette smoking, although the presence of toxicants in e-cigarette aerosols means that their use is unlikely to be risk-free. Further studies—in particular, preclinical in vitro studies, clinical biomarker studies, and population studies—are necessary to test this hypothesis. However, the findings of the present study are an encouraging starting point for future research.
The study also provides key insights into how to conduct chemical measurements of this kind. In particular, we have demonstrated the necessity of both conducting air/method blank measurements and managing the chemical background of the testing environment in order to minimize the presence of contaminants and errors in the analytical data. This is a fundamental finding that must be considered by future researchers in this area.

Supporting Information

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.chemrestox.6b00188.

  • Description of Tables S1–S11 (PDF)

  • Methodology and experimental results (XLSX)

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

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  • Corresponding Author
    • Kevin McAdam - Research and Development, British American Tobacco Investments Ltd., Regents Park Road, Southampton, Hampshire SO15 8TL, U.K.;  Email: [email protected]
  • Authors
    • Jennifer Margham - Research and Development, British American Tobacco Investments Ltd., Regents Park Road, Southampton, Hampshire SO15 8TL, U.K.
    • Mark Forster - Research and Development, British American Tobacco Investments Ltd., Regents Park Road, Southampton, Hampshire SO15 8TL, U.K.
    • Chuan Liu - Research and Development, British American Tobacco Investments Ltd., Regents Park Road, Southampton, Hampshire SO15 8TL, U.K.
    • Christopher Wright - Research and Development, British American Tobacco Investments Ltd., Regents Park Road, Southampton, Hampshire SO15 8TL, U.K.
    • Derek Mariner - Research and Development, British American Tobacco Investments Ltd., Regents Park Road, Southampton, Hampshire SO15 8TL, U.K.
    • Christopher Proctor - Research and Development, British American Tobacco Investments Ltd., Regents Park Road, Southampton, Hampshire SO15 8TL, U.K.
  • Funding

    The research described in this article was funded by British American Tobacco Investments Ltd.

  • Notes
    The authors declare the following competing financial interest(s): All authors are employees of British American Tobacco. British American Tobacco is the sole source of funding and sponsor of this project.

Abbreviations

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ISO

International Organization for Standardization

MSS

mainstream smoke

NAB

N-nitrosoanabasine

NAT

N-nitrosoanatabine

NDBA

N-nitrosodi-n-butylamine

NDELA

N-nitrosodiethanolamine

NDMA

N-nitrosodimethylamine

NNK

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

NNN

N-nitrosonornicotine

NPYR

N-nitrosopyrrolidine

PAH

polycyclic aromatic hydrocarbon

VNA

volatile nitrosamine

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    Journal of Chromatography A (2013), 1291 (), 48-55CODEN: JCRAEY; ISSN:0021-9673. (Elsevier B.V.)
    A liq. chromatog.-tandem mass spectrometric method was described to detect tobacco-specific nitrosamines (TSNAs) in replacement liqs. of electronic cigarettes. Solid-phase extn. (SPE) and liq.-liq. extn. (LLE) were compared to each other to select the optimum clean-up method. Under the established condition, the limits of quantification of N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N'-nitrosoanabasine (NAB), and N'-nitrosoanatabine (NAT) were 0.06, 0.07, 0.06, and 0.04 μg/L resp., by using 0.5 mL of replacement liqs., resp., and the relative std. deviation was less than 10% at concns. of 5.0 and 25.0 μg/L. The concns. of TSNAs were measured in concn. ranges of 0.34-60.08 μg/L (64.8% detection frequency) for NNN, 0.22-9.84 μg/L (88.6% detection frequency) for NNK, 0.11-11.11 μg/L (54.3% detection frequency) for NNB, and 0.09-62.19 μg/L (75.2% detection frequency) for NAT in 105 replacement liq. brands from 11 electronic cigarette companies purchased in the Korean market.
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  26. 26
    Tayyarah, R. and Long, G. A. (2014) Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air Regul. Toxicol. Pharmacol. 70, 704– 710 DOI: 10.1016/j.yrtph.2014.10.010
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    26
    Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air
    Tayyarah, Rana; Long, Gerald A.
    Regulatory Toxicology and Pharmacology (2014), 70 (3), 704-710CODEN: RTOPDW; ISSN:0273-2300. (Elsevier Inc.)
    Leading com. electronic cigarettes were tested to det. bulk compn. The e-cigarettes and conventional cigarettes were evaluated using machine-puffing to compare nicotine delivery and relative yields of chem. constituents. The e-liqs. tested were found to contain humectants, glycerin and/or propylene glycol, (≥75% content); water (<20%); nicotine (approx. 2%); and flavor (<10%). The aerosol collected mass (ACM) of the e-cigarette samples was similar in compn. to the e-liqs. Aerosol nicotine for the e-cigarette samples was 85% lower than nicotine yield for the conventional cigarettes. Anal. of the smoke from conventional cigarettes showed that the mainstream cigarette smoke delivered approx. 1500 times more harmful and potentially harmful constituents (HPHCs) tested when compared to e-cigarette aerosol or to puffing room air. The deliveries of HPHCs tested for these e-cigarette products were similar to the study air blanks rather than to deliveries from conventional cigarettes; no significant contribution of cigarette smoke HPHCs from any of the compd. classes tested was found for the e-cigarettes. Thus, the results of this study support previous researchers' discussion of e-cigarette products' potential for reduced exposure compared to cigarette smoke.
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  27. 27
    Farsalinos, K. E., Gillman, I. G., Melvin, M. S., Paolantonio, A. R., Gardow, W. J., Humphries, K. E., Brown, S. E., Poulas, K., and Voudris, V. (2015) Nicotine levels and presence of selected tobacco-derived toxins in tobacco flavoured electronic cigarette refill liquids Int. J. Environ. Res. Public Health 12, 3439– 3452 DOI: 10.3390/ijerph120403439
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    27
    Nicotine levels and presence of selected tobacco-derived toxins in tobacco flavoured electronic cigarette refill liquids
    Farsalinos, Konstantinos E.; Gillman, I. Gene; Melvin, Matt S.; Paolantonio, Amelia R.; Gardow, Wendy J.; Humphries, Kathy E.; Brown, Sherri E.; Poulas, Konstantinos; Voudris, Vassilis
    International Journal of Environmental Research and Public Health (2015), 12 (4), 3439-3452CODEN: IJERGQ; ISSN:1660-4601. (MDPI AG)
    Background. Some electronic cigarette (EC) liqs. of tobacco flavor contain exts. of cured tobacco leaves produced by a process of solvent extn. and steeping. These are commonly called Natural Ext. of Tobacco (NET) liqs. The purpose of the study was to evaluate nicotine levels and the presence of tobacco-derived toxins in tobacco-flavoured conventional and NET liqs. Methods. Twenty-one samples (10 conventional and 11 NET liqs.) were obtained from the US and Greek market. Nicotine levels were measured and compared with labeled values. The levels of tobacco-derived chems. were compared with literature data on tobacco products. Results. Twelve samples had nicotine levels within 10% of the labeled value. Inconsistency ranged from -21% to 22.1%, with no difference obsd. between conventional and NET liqs. Tobacco-specific nitrosamines (TSNAs) were present in all samples at ng/mL levels. Nitrates were present almost exclusively in NET liqs. Acetaldehyde was present predominantly in conventional liqs. while formaldehyde was detected in almost all EC liqs. at trace levels. Phenols were present in trace amts., mostly in NET liqs. Total TSNAs and nitrate, which are derived from the tobacco plant, were present at levels 200-300 times lower in 1 mL of NET liqs. compared to 1 g of tobacco products. Conclusions. NET liqs. contained higher levels of phenols and nitrates, but lower levels of acetaldehyde compared to conventional EC liqs. The lower levels of tobacco-derived toxins found in NET liqs. compared to tobacco products indicate that the extn. process used to make these products did not transfer a significant amt. of toxins to the NET. Overall, all EC liqs. contained far lower (by 2-3 orders of magnitude) levels of the tobacco-derived toxins compared to tobacco products.
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    Etter, J. F., Zäther, E., and Svensson, S. (2013) Analysis of refill liquids for electronic cigarettes Addiction 108, 1671– 1679 DOI: 10.1111/add.12235
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    28
    Analysis of refill liquids for electronic cigarettes
    Etter Jean-Francois; Zather Eva; Svensson Sofie
    Addiction (Abingdon, England) (2013), 108 (9), 1671-9 ISSN:.
    AIMS: To assess levels of nicotine, nicotine degradation products and some specific impurities in commercial refill liquids for electronic cigarettes. DESIGN AND SETTING: We analyzed 20 models of 10 of the most popular brands of refill liquids, using gas and liquid chromatography. MEASUREMENTS: We assessed nicotine content, content of the known nicotine degradation products and impurities, and presence of ethylene glycol and diethylene glycol. FINDINGS: The nicotine content in the bottles corresponded closely to the labels on the bottles. The levels of nicotine degradation products represented 0-4.4% of those for nicotine, but for most samples the level was 1-2%. Cis-N-oxide, trans-N-oxide, myosmine, anatabine and anabasine were the most common additional compounds found. Neither ethylene glycol nor diethylene glycol were detected. CONCLUSION: The nicotine content of electronic cigarette refill bottles is close to what is stated on the label. Impurities are detectable in several brands above the level set for nicotine products in the European Pharmacopoeia, but below the level where they would be likely to cause harm.
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  29. 29
    Lisko, J. G., Tran, H., Stanfill, S. B., Blount, B. C., and Watson, C. H. (2015) Chemical composition and evaluation of nicotine, tobacco alkaloids, pH, and selected flavors in e-cigarette cartridges and refill solutions Nicotine Tob. Res. 17, 1270– 1278 DOI: 10.1093/ntr/ntu279
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    29
    Chemical Composition and Evaluation of Nicotine, Tobacco Alkaloids, pH, and Selected Flavors in E-Cigarette Cartridges and Refill Solutions
    Lisko Joseph G; Tran Hang; Stanfill Stephen B; Blount Benjamin C; Watson Clifford H
    Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco (2015), 17 (10), 1270-8 ISSN:.
    INTRODUCTION: Electronic cigarette (e-cigarette) use is increasing dramatically in developed countries, but little is known about these rapidly evolving products. This study analyzed and evaluated the chemical composition including nicotine, tobacco alkaloids, pH, and flavors in 36 e-liquids brands from 4 manufacturers. METHODS: We determined the concentrations of nicotine, alkaloids, and select flavors and measured pH in solutions used in e-cigarettes. E-cigarette products were chosen based upon favorable consumer approval ratings from online review websites. Quantitative analyses were performed using strict quality assurance/quality control validated methods previously established by our lab for the measurement of nicotine, alkaloids, pH, and flavors. RESULTS: Three-quarters of the products contained lower measured nicotine levels than the stated label values (6%-42% by concentration). The pH for e-liquids ranged from 5.1-9.1. Minor tobacco alkaloids were found in all samples containing nicotine, and their relative concentrations varied widely among manufacturers. A number of common flavor compounds were analyzed in all e-liquids. CONCLUSIONS: Free nicotine levels calculated from the measurement of pH correlated with total nicotine content. The direct correlation between the total nicotine concentration and pH suggests that the alkalinity of nicotine drives the pH of e-cigarette solutions. A higher percentage of nicotine exists in the more absorbable free form as total nicotine concentration increases. A number of products contained tobacco alkaloids at concentrations that exceed U.S. pharmacopeia limits for impurities in nicotine used in pharmaceutical and food products.
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  30. 30
    Goniewicz, M. L., Knysak, J., Gawron, M., Kosmider, L., Sobczak, A., Kurek, J., Prokopowicz, A., Jablonska-Czapla, M., Rosik-Dulewska, C., Havel, C., Jacob, P., and Benowitz, N. (2014) Levels of selected carcinogens and toxicants in vapour from electronic cigarettes Tob. Control 23, 133– 139 DOI: 10.1136/tobaccocontrol-2012-050859
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    Levels of selected carcinogens and toxicants in vapour from electronic cigarettes
    Goniewicz Maciej Lukasz; Knysak Jakub; Gawron Michal; Kosmider Leon; Sobczak Andrzej; Kurek Jolanta; Prokopowicz Adam; Jablonska-Czapla Magdalena; Rosik-Dulewska Czeslawa; Havel Christopher; Jacob Peyton 3rd; Benowitz Neal
    Tobacco control (2014), 23 (2), 133-9 ISSN:.
    SIGNIFICANCE: Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. They are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapour generated from e-cigarettes. The aim of this study was to screen e-cigarette vapours for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines and heavy metals. MATERIALS AND METHODS: Vapours were generated from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapours into a solid or liquid phase and analysed with chromatographic and spectroscopy methods. RESULTS: We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9-450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product. CONCLUSIONS: Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study. (To view this abstract in Polish and German, please see the supplementary files online.).
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    Schripp, T., Markewitz, D., Uhde, E., and Salthammer, T. (2013) Does e-cigarette consumption cause passive vaping? Indoor Air 23, 25– 31 DOI: 10.1111/j.1600-0668.2012.00792.x
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    Does e-cigarette consumption cause passive vaping?
    Schripp, T.; Markewitz, D.; Uhde, E.; Salthammer, T.
    Indoor Air (2013), 23 (1), 25-31CODEN: INAIE5; ISSN:0905-6947. (Wiley-Blackwell)
    Electronic cigarette consumption ('vaping') is marketed as an alternative to conventional tobacco smoking. Tech., a mixt. of chems. contg. carrier liqs., flavors, and optionally nicotine is vaporized and inhaled. The present study aims at the detn. of the release of volatile org. compds. (VOC) and (ultra)fine particles (FP/UFP) from an e-cigarette under near-to-real-use conditions in an 8-m3 emission test chamber. Furthermore, the inhaled mixt. is analyzed in small chambers. An increase in FP/UFP and VOC could be detd. after the use of the e-cigarette. Prominent components in the gas-phase are 1,2-propanediol, 1,2,3-propanetriol, diacetin, flavorings, and traces of nicotine. As a consequence, 'passive vaping' must be expected from the consumption of e-cigarettes. Furthermore, the inhaled aerosol undergoes changes in the human lung that is assumed to be attributed to deposition and evapn.
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  32. 32
    Pellegrino, R. M., Tinghino, B., Mangiaracina, G., Marani, A., Vitali, M., Protano, C., Osborn, J. F., and Cattaruzza, M. S. (2012) Electronic cigarettes: an evaluation of exposure to chemicals and fine particulate matter (PM) Annali di igiene: medicina preventiva e di comunità 24, 279– 288
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    Herrington, J. S. and Hays, M. D. (2012) Concerns regarding 24-h sampling for formaldehyde, acetaldehyde, and acrolein using 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents Atmos. Environ. 55, 179– 184 DOI: 10.1016/j.atmosenv.2012.02.088
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    33
    Concerns regarding 24-h sampling for formaldehyde, acetaldehyde, and acrolein using 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents
    Herrington, Jason S.; Hays, Michael D.
    Atmospheric Environment (2012), 55 (), 179-184CODEN: AENVEQ; ISSN:1352-2310. (Elsevier Ltd.)
    A review. There is high demand for accurate and reliable airborne carbonyl measurement methods due to the human and environmental health impacts of carbonyls and their effects on atm. chem. Standardized 2,4-dinitrophenylhydrazine (DNPH)-based sampling methods are frequently applied for measuring gaseous carbonyls in the atm. environment. However, there are multiple short-comings assocd. with these methods that detract from an accurate understanding of carbonyl-related exposure, health effects, and atm. chem. The purpose of this brief tech. communication is to highlight these method challenges and their influence on national ambient monitoring networks, and to provide a logical path forward for accurate carbonyl measurement. This manuscript focuses on 3 specific carbonyl compds. of high toxicol. interest - formaldehyde, acetaldehyde, and acrolein. Further method testing and development, the revision of standardized methods, and the plausibility of introducing novel technol. for these carbonyls are considered elements of the path forward. The consolidation of this information is important because it seems clear that carbonyl data produced utilizing DNPH-based methods are being reported without acknowledgment of the method short-comings or how to best address them.
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    Laugesen, M. (2009) Ruyan® e-cigarette bench-top tests. Poster presented at Society for Research on Nicotine and Tobacco (SRNT) Meeting, April 30, Dublin, Ireland. http://www.seeht.org/Laugesen_Apr_2009.pdf (accessed December 21, 2015).
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    Williams, M., Villarreal, A., Bozhilov, K., Lin, S., and Talbot, P. (2013) Metal and silicate particles including nanoparticles are present in electronic cigarette cartomizer fluid and aerosol PLoS One 8, e57987 DOI: 10.1371/journal.pone.0057987
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    Metal and silicate particles including nanoparticles are present in electronic cigarette cartomizer fluid and aerosol
    Williams, Monique; Villarreal, Amanda; Bozhilov, Krassimir; Lin, Sabrina; Talbot, Prue
    PLoS One (2013), 8 (3), e57987CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
    Background: Electronic cigarettes (EC) deliver aerosol by heating fluid contg. nicotine. Cartomizer EC combine the fluid chamber and heating element in a single unit. Because EC do not burn tobacco, they may be safer than conventional cigarettes. Their use is rapidly increasing worldwide with little prior testing of their aerosol. Objectives: We tested the hypothesis that EC aerosol contains metals derived from various components in EC. Methods: Cartomizer contents and aerosols were analyzed using light and electron microscopy, cytotoxicity testing, x-ray microanal., particle counting, and inductively coupled plasma optical emission spectrometry. Results: The filament, a nickel-chromium wire, was coupled to a thicker copper wire coated with silver. The silver coating was sometimes missing. Four tin solder joints a ttached the wires to each other and coupled the copper/silver wire to the air tube and mouthpiece. All cartomizers had evidence of use before packaging (burn spots on the fibers and electrophoretic movement of fluid in the fibers). Fibers in two cartomizers had green deposits that contained copper. Centrifugation of the fibers produced large pellets contg. tin. Tin particles and tin whiskers were identified in cartridge fluid and outer fibers. Cartomizer fluid with tin particles was cytotoxic in assays using human pulmonary fibroblasts. The aerosol contained particles >1 μm comprised of tin, silver, iron, nickel, aluminum, and silicate and nanoparticles (<100 nm) of tin, chromium and nickel. The concns. of nine of eleven elements in EC aerosol were higher than or equal to the corresponding concns. in conventional cigarette smoke. Many of the elements identified in EC aerosol are known to cause respiratory distress and disease. Conclusions: The presence of metal and silicate particles in cartomizer aerosol demonstrates the need for improved quality control in EC design and manuf. and studies on how EC aerosol impacts the health of users and bystanders.
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  36. 36
    Lerner, C. A., Sundar, I. K., Watson, R. M., Elder, A., Jones, R., Done, D., Kurtzman, R., Ossip, D. J., Robinson, R., McIntosh, S., and Rahman, I. (2015) Environmental health hazards of e-cigarettes and their components: Oxidants and copper in e-cigarette aerosols Environ. Pollut. 198, 100– 107 DOI: 10.1016/j.envpol.2014.12.033
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    Environmental health hazards of e-cigarettes and their components: Oxidants and copper in e-cigarette aerosols
    Lerner, Chad A.; Sundar, Isaac K.; Watson, Richard M.; Elder, Alison; Jones, Ryan; Done, Douglas; Kurtzman, Rachel; Ossip, Deborah J.; Robinson, Risa; McIntosh, Scott; Rahman, Irfan
    Environmental Pollution (Oxford, United Kingdom) (2015), 198 (), 100-107CODEN: ENPOEK; ISSN:0269-7491. (Elsevier Ltd.)
    To narrow the gap in our understanding of potential oxidative properties assocd. with Electronic Nicotine Delivery Systems (ENDS) i.e. e-cigarettes, we employed semi-quant. methods to detect oxidant reactivity in disposable components of ENDS/e-cigarettes (batteries and cartomizers) using a fluorescein indicator. These components exhibit oxidants/reactive oxygen species reactivity similar to used conventional cigarette filters. Oxidants/reactive oxygen species reactivity in e-cigarette aerosols was also similar to oxidant reactivity in cigarette smoke. A cascade particle impactor allowed sieving of a range of particle size distributions between 0.450 and 2.02 μm in aerosols from an e-cigarette. Copper, being among these particles, is 6.1 times higher per puff than reported previously for conventional cigarette smoke. The detection of a potentially cytotoxic metal as well as oxidants from e-cigarette and its components raises concern regarding the safety of e-cigarettes use and the disposal of e-cigarette waste products into the environment.
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    Ohta, K., Uchiyama, S., Inaba, Y., Nakagome, H., and Kunugita, N. (2011) Determination of carbonyl compounds generated from the electronic cigarette using coupled silica cartridges impregnated with hydroquinone and2,4-dinitrophenylhydrazine Bunseki Kagaku 60, 791– 797 DOI: 10.2116/bunsekikagaku.60.791
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    Theophilus, E. H., Potts, R., Fowler, K., Fields, W., and Bombick, B. (2014) VUSE electronic cigarette aerosol chemistry and cytotoxicity Toxicol. Lett. 229, S211 DOI: 10.1016/j.toxlet.2014.06.710
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    Uchiyama, S., Ohta, K., Inaba, Y., and Kunugita, N. (2013) Determination of carbonyl compounds generated from the E-cigarette using coupled silica cartridges impregnated with hydroquinone and 2,4-dinitrophenylhydrazine, followed by high-performance liquid chromatography Anal. Sci. 29, 1219– 1222 DOI: 10.2116/analsci.29.1219
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    39
    Determination of carbonyl compounds generated from the E-cigarette using coupled silica cartridges impregnated with hydroquinone and 2,4-dinitrophenylhydrazine, followed by high-performance liquid chromatography
    Uchiyama, Shigehisa; Ohta, Kazushi; Inaba, Yohei; Kunugita, Naoki
    Analytical Sciences (2013), 29 (12), 1219-1222CODEN: ANSCEN; ISSN:0910-6340. (Japan Society for Analytical Chemistry)
    Carbonyl compds. in E-cigarette smoke mist were measured using coupled silica cartridges impregnated with hydroquinone and 2,4-dinitrophenylhydrazine, followed by high-performance liq. chromatog. A total of 363 E-cigarettes (13 brands) were examd. Four of the 13 E-cigarette brands did not generate any carbonyl compds., while the other nine E-cigarette brands generated various carbonyl compds. However, the carbonyl concns. of the E-cigarette products did not show typical distributions, and the mean values were largely different from the median values. It was elucidated that E-cigarettes incidentally generate high concns. of carbonyl compds.
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    Hutzler, C., Paschke, M., Kruschinski, S., Henkler, F., Hahn, J., and Luch, A. (2014) Chemical hazards present in liquids and vapors of electronic cigarette Arch. Toxicol. 88, 1295– 1308 DOI: 10.1007/s00204-014-1294-7
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    Chemical hazards present in liquids and vapors of electronic cigarettes
    Hutzler, Christoph; Paschke, Meike; Kruschinski, Svetlana; Henkler, Frank; Hahn, Juergen; Luch, Andreas
    Archives of Toxicology (2014), 88 (7), 1295-1308CODEN: ARTODN; ISSN:0340-5761. (Springer)
    Electronic (e-)cigarettes have emerged in recent years as putative alternative to conventional tobacco cigarettes. These products do not contain typical carcinogens that are present in tobacco smoke, due to the lack of combustion. However, besides nicotine, hazards can also arise from other constituents of liqs., such as solvents, flavors, additives and contaminants. In this study, we have analyzed 28 liqs. of seven manufacturers purchased in Germany. We confirm the presence of a wide range of flavors to enhance palatability. Although glycerol and propylene glycol were detected in all samples, these solvents had been replaced by ethylene glycol as dominant compd. in five products. Ethylene glycol is assocd. with markedly enhanced toxicol. hazards when compared to conventionally used glycerol and propylene glycol. Addnl. additives, such as coumarin and acetamide, that raise concerns for human health were detected in certain samples. Ten out of 28 products had been declared "free-of-nicotine" by the manufacturer. Among these ten, seven liqs. were identified contg. nicotine in the range of 0.1-15 μg/mL. This suggests that "carry over" of ingredients may occur during the prodn. of cartridges. We have further analyzed the formation of carbonylic compds. in one widely distributed nicotine-free brand. Significant amts. of formaldehyde, acetaldehyde and propionaldehyde were only found at 150 °C by headspace GC-MS anal. In addn., an enhanced formation of aldehydes was found in defined puff fractions, using an adopted machine smoking protocol. However, this effect was delayed and only obsd. during the last third of the smoking procedure. In the emissions of these fractions, which represent up to 40 % of total vapor vol., similar levels of formaldehyde were detected when compared to conventional tobacco cigarettes. By contrast, carbonylic compds. were hardly detectable in earlier collected fractions. Our data demonstrate the necessity of standardized machine smoking protocols to reliably address putative risks of e-cigarettes for consumers.
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    Kosmider, L., Sobczak, A., Fik, M., Knysak, J., Zaciera, M., Kurek, J., and Goniewicz, M. L. (2014) Carbonyl compounds in electronic cigarette vapors: effects of nicotine solvent and battery output voltage Nicotine Tob. Res. 16, 1319– 1326 DOI: 10.1093/ntr/ntu078
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    41
    Carbonyl compounds in electronic cigarette vapors: effects of nicotine solvent and battery output voltage
    Kosmider, Leon; Sobczak, Andrzej; Fik, Maciej; Knysak, Jakub; Zaciera, Marzena; Kurek, Jolanta; Goniewicz, Maciej Lukasz
    Nicotine & Tobacco Research (2014), 16 (10), 1319-1326CODEN: NTREF6; ISSN:1462-2203. (Oxford University Press)
    Introduction: Glycerin (VG) and propylene glycol (PG) are the most common nicotine solvents used in e-cigarettes (ECs). It has been shown that at high temps. both VG and PG undergo decompn. to low mol. carbonyl compds., including the carcinogens formaldehyde and acetaldehyde. The aim of this study was to evaluate how various product characteristics, including nicotine solvent and battery output voltage, affect the levels of carbonyls in EC vapor. Methods: Twelve carbonyl compds. were measured in vapors from 10 com. available nicotine solns. and from 3 control solns. composed of pure glycerin, pure propylene glycol, or a mixt. of both solvents (50:50). EC battery output voltage was gradually modified from 3.2 to 4.8 V. Carbonyl compds. were detd. using the HPLC/DAD method. Results: Formaldehyde and acetaldehyde were found in 8 of 13 samples. The amts. of formaldehyde and acetaldehyde in vapors from lower voltage EC were on av. 13- and 807-fold lower than in tobacco smoke, resp. The highest levels of carbonyls were obsd. in vapors generated from PG-based solns. Increasing voltage from 3.2 to 4.8 V resulted in a 4 to more than 200 times increase in formaldehyde, acetaldehyde, and acetone levels. The levels of formaldehyde in vapors from high-voltage device were in the range of levels reported in tobacco smoke. Conclusions: Vapors from EC contain toxic and carcinogenic carbonyl compds. Both solvent and battery output voltage significantly affect levels of carbonyl compds. in EC vapors. High-voltage EC may expose users to high levels of carbonyl compds.
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    Bates, C. D. and Farsalinos, K. E. (2015) E-cigarettes need to be tested for safety under realistic conditions Addiction 110, 1688– 1689 DOI: 10.1111/add.13028
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    Bates, C. D. and Farsalinos, K. E. (2015) Research letter on e-cigarette cancer risk was so misleading it should be retracted Addiction 110, 1686– 1687 DOI: 10.1111/add.13018
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    Gupta, R., Brazier, J., and Moyses, C. (2015) No quantifiable carbonyls, including formaldehyde, detected in Voke® Inhaler J. Liq. Chromatogr. Relat. Technol. 38, 1687– 1690 DOI: 10.1080/10826076.2015.1091978
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    No Quantifiable Carbonyls, Including Formaldehyde, Detected in Voke Inhaler
    Gupta, Ritika; Brazier, Jonathan; Moyses, Chris
    Journal of Liquid Chromatography & Related Technologies (2015), 38 (18), 1687-1690CODEN: JLCTFC; ISSN:1082-6076. (Taylor & Francis, Inc.)
    Carbonyls such as formaldehyde, acetaldehyde, and acrolein have been detected in e-cigarette vapors, with one study (albeit at a higher than the typical voltage) reporting formaldehyde-releasing agents in quantities sufficient to increase the risk of cancer by 5-15 fold when compared with long-term smoking. This study examines the Voke Inhaler for traces of carbonyls and aims to quantify any that are detected in its aerosol. Three batches of five Voke devices each were charged with formulation and allowed to rest for 0, 1, and 24 h resp., before being sampled. Aerosol from each device was extd. using a linear smoking machine and collected by dissoln. into DNPH derivatization soln. Samples of the ext. soln. were analyzed for carbonyls using UHPLC. Results were reported as μg/8 puffs. Samples were analyzed for the presence of formaldehyde, acetaldehyde, acetone, acrolein, propionaldehyde, crotonaldehyde, butan-2-one, and butyraldehyde. At the given LOD, no carbonyls were detected in 13 of the 15 samples tested. Acetaldehyde was detected in two samples, one tested immediately after charging and the other tested 1 h after sampling; however, both samples contained the analyte in quantities below its LOQ (3.18 μg/mL). Among various carbonyls, formaldehyde, in particular, has been identified as a known carcinogen by the IARC and as a probable human carcinogen by the US EPA. The absence of measurable quantities of carbonyls in the Voke Inhaler establishes its clear distinction from e-cigarettes and reflects on a significant advantage of not having a heating element.
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    Guthery, W. (2016) Emissions of toxic carbonyls in an electronic cigarette Beitr. Tabakforsch. Int. 27, 30– 37 DOI: 10.1515/cttr-2016-0005
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    Emissions of Toxic Carbonyls in an Electronic Cigarette
    Guthery, William
    Beitraege zur Tabakforschung International (2016), 27 (1), 30-37CODEN: BTAID3; ISSN:1612-9237. (De Gruyter Open Ltd.)
    Summary : Electronic cigarettes (e-cigs) provide a smoke-free alternative for inhalation of nicotine without the vast array of toxic and carcinogenic combustion products produced by tobacco smoke. Elevated levels of toxic carbonyls may be generated during vaporisation; however, it is unclear whether that is indicative of a fault with the device or is due to the applied conditions of the test. A device, designed and built at this facility, was tested to det. the levels of selected toxic carbonyls. The reservoir was filled with approx. 960 mg of an e-liq. formulation contg. 1.8% (w/v) nicotine. Devices were puffed 200 times in blocks of 40 using a standardised regime consisting of a 55 mL puff vol.; 3 s puff duration; 30 s puff interval; square wave puff profile. Confirmatory testing for nicotine and total aerosol delivery resulted in mean (n = 8) values of 10 mg (RSD 12.3%) and 716 mg (RSD 11.2%), resp. Emissions of toxic carbonyls were highly variable yet were between < 0.1% and 22.9% of expected levels from a Kentucky Ref. Cigarette (K3R4F) puffed 200 times under Health Canada Intense smoking conditions. It has been shown that a device built to a high specification with relatively consistent nicotine and aerosol delivery emits inconsistent levels of carbonyls. The exposure is greatly reduced when compared with lit tobacco products. However, it was obsd. that as the reservoirs neared depletion then emission levels were significantly higher.
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    Geiss, O., Bianchi, I., and Barrero-Moreno, J. (2016) Correlation of volatile carbonyl yields emitted by e-cigarettes with the temperature of the heating coil and the perceived sensorial quality of the generated vapours Int. J. Hyg. Environ. Health 219, 268– 277 DOI: 10.1016/j.ijheh.2016.01.004
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    Correlation of volatile carbonyl yields emitted by e-cigarettes with the temperature of the heating coil and the perceived sensorial quality of the generated vapours
    Geiss, Otmar; Bianchi, Ivana; Barrero-Moreno, Josefa
    International Journal of Hygiene and Environmental Health (2016), 219 (3), 268-277CODEN: IJEHFT; ISSN:1438-4639. (Elsevier GmbH)
    E-liqs. generally contain four main components: nicotine, flavours, water and carrier liqs. The carrier liq. dissolves flavours and nicotine and vaporises at a certain temp. on the atomizer of the e-cigarette. Propylene glycol and glycerol, the principal carriers used in e-liqs., undergo decompn. in contact with the atomizer heating-coil forming volatile carbonyls. Some of these, such as formaldehyde, acetaldehyde and acrolein, are of concern due to their adverse impact on human health when inhaled at sufficient concns. The aim of this study was to correlate the yield of volatile carbonyls emitted by e-cigarettes with the temp. of the heating coil.For this purpose, a popular com. e-liq. was machine-vaped on a third generation e-cigarette which allowed the variation of the output wattage (5-25 W) and therefore the heat generated on the atomizer heating-coil. The temp. of the heating-coil was detd. by IR thermog. and the vapor generated at each temp. underwent subjective sensorial quality evaluation by an experienced vaper.A steep increase in the generated carbonyls was obsd. when applying a battery-output of at least 15 W corresponding to 200-250 °C on the heating coil. However, when considering concns. in each inhaled puff, the short-term indoor air guideline value for formaldehyde was already exceeded at the lowest wattage of 5 W, which is the wattage applied in most 2nd generation e-cigarettes. Concns. of acetaldehyde in each puff were several times below the short-term irritation threshold value for humans. Acrolein was only detected from 20 W upwards. The neg. sensorial quality evaluation by the volunteering vaper of the vapor generated at 20 W demonstrated the unlikelihood that such a wattage would be realistically set by a vaper. This study highlights the importance to develop standardised testing methods for the assessment of carbonyl-emissions and emissions of other potentially harmful compds. from e-cigarettes. The wide variety and variability of products available on the market make the development of such methods and the assocd. standardised testing conditions particularly demanding.
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    Talih, S., Balhas, Z., Salman, R., Karaoghlanian, N., and Shihadeh, A. (2016) Direct dripping”: a high-temperature, high-formaldehyde emission electronic cigarette use method Nicotine Tob. Res. 18, 453– 459 DOI: 10.1093/ntr/ntv080
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    "Direct Dripping": A High-Temperature, High-Formaldehyde Emission Electronic Cigarette Use Method
    Talih Soha; Balhas Zainab; Shihadeh Alan; Salman Rola; Karaoghlanian Nareg
    Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco (2016), 18 (4), 453-9 ISSN:.
    INTRODUCTION: Electronic cigarettes (ECIGs) electrically heat and vaporize a liquid solution to produce an inhalable nicotine-containing aerosol. Normally the electrical heater is fed the liquid via an automatic wick system. Some ECIG users, however, elect to directly drip liquid onto an exposed heater coil, reportedly for greater vapor production and throat hit. Use of such "direct drip atomizers" (DDAs) may involve greater exposure to non-nicotine toxicants due to the potentially higher temperatures reached by the coil. In this study we examined nicotine and volatile aldehyde (VA) emissions from one type of DDA under various use scenarios, and measured heater temperature. METHODS: Aerosols were machine-generated from an NHALER 510 Atomizer powered by an eGo-T battery (Joyetech), using a common PG-based liquid and a fixed puffing regimen. Inter-drip interval, the number of puffs drawn between replenishing the liquid on the coil, was varied from 2-4 puffs/drip. Total particulate matter, nicotine, and VA yields were quantified. Heater temperature was monitored using an infrared camera. RESULTS: Depending on the condition, VA emissions, including formaldehyde, greatly exceeded values previously reported for conventional ECIGs and combustible cigarettes, both per puff and per unit of nicotine yield. Increasing the inter-drip interval resulted in greater VA emissions, and lower total particulate matter and nicotine yields. Maximum heater coil temperature ranged from 130°C to more than 350°C. CONCLUSIONS: Due to the higher temperatures attained, DDAs are inherently likely to produce high toxicant emissions. The diversity of ECIG use methods, including potential off-label methods, should be considered as ECIG regulatory efforts proceed.
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    Hidden formaldehyde in e-cigarette aerosols
    Jensen, R. Paul; Luo, Wentai; Pankow, James F.; Strongin, Robert M.; Peyton, David H.
    New England Journal of Medicine (2015), 372 (4), 392-394CODEN: NEJMAG; ISSN:1533-4406. (Massachusetts Medical Society)
    There is no expanded citation for this reference.
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    Farsalinos, K. E., Voudris, V., and Poulas, K. (2015) E-cigarettes generate high levels of aldehydes only in ‘dry puff’ conditions Addiction 110, 1352– 1356 DOI: 10.1111/add.12942
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    E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions
    Farsalinos Konstantinos E; Voudris Vassilis; Farsalinos Konstantinos E; Poulas Konstantinos
    Addiction (Abingdon, England) (2015), 110 (8), 1352-6 ISSN:.
    BACKGROUND AND AIMS: Aldehydes are emitted by electronic cigarettes due to thermal decomposition of liquid components. Although elevated levels have been reported with new-generation high-power devices, it is unclear whether they are relevant to true exposure of users (vapers) because overheating produces an unpleasant taste, called a dry puff, which vapers learn to avoid. The aim was to evaluate aldehyde emissions at different power levels associated with normal and dry puff conditions. DESIGN: Two customizable atomizers were prepared so that one (A1) had a double wick, resulting in high liquid supply and lower chance of overheating at high power levels, while the other (A2) was a conventional setup (single wick). Experienced vapers took 4-s puffs at 6.5 watts (W), 7.5 W, 9 W and 10 W power levels with both atomizers and were asked to report whether dry puffs were generated. The atomizers were then attached to a smoking machine and aerosol was trapped. SETTING: Clinic office and analytical chemistry laboratory in Greece. PARTICIPANTS: Seven experienced vapers. MEASUREMENTS: Aldehyde levels were measured in the aerosol. FINDINGS: All vapers identified dry puff conditions at 9 W and 10 W with A2. A1 did not lead to dry puffs at any power level. Minimal amounts of aldehydes per 10 puffs were found at all power levels with A1 (up to 11.3 μg for formaldehyde, 4.5 μg for acetaldehyde and 1.0 μg for acrolein) and at 6.5 W and 7.5 W with A2 (up to 3.7 μg for formaldehyde, 0.8 μg for acetaldehyde and 1.3 μg for acrolein). The levels were increased by 30 to 250 times in dry puff conditions (up to 344.6 μg for formaldehyde, 206.3 μg for acetaldehyde and 210.4 μg for acrolein, P < 0.001), while acetone was detected only in dry puff conditions (up to 22.5 μg). CONCLUSIONS: Electronic cigarettes produce high levels of aldehyde only in dry puff conditions, in which the liquid overheats, causing a strong unpleasant taste that e-cigarette users detect and avoid. Under normal vaping conditions aldehyde emissions are minimal, even in new-generation high-power e-cigarettes.
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    Farsalinos, K. E., Kistler, K. A., Gillman, G., and Voudris, V. (2015) Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins Nicotine Tob. Res. 17, 168– 174 DOI: 10.1093/ntr/ntu176
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    Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins
    Farsalinos, Konstantinos E.; Kistler, Kurt A.; Gillman, Gene; Voudris, Vassilis
    Nicotine & Tobacco Research (2015), 17 (2), 168-174CODEN: NTREF6; ISSN:1462-2203. (Oxford University Press)
    Introduction: The purpose of this study was to evaluate sweet-flavored electronic cigarette (EC) liqs. for the presence of diacetyl (DA) and acetyl propionyl (AP), which are chems. approved for food use but are assocd. with respiratory disease when inhaled. Methods: In total, 159 samples were purchased from 36 manufacturers and retailers in 7 countries. Addnl., 3 liqs. were prepd. by dissolving a concd. flavor sample of known DA and AP levels at 5%, 10%, and 20% concn. in a mixt. of propylene glycol and glycerol. Aerosol produced by an EC was analyzed to det. the concn. of DA and AP. Results: DA and AP were found in 74.2% of the samples, with more samples contg. DA. Similar concns. were found in liq. and aerosol for both chems. The median daily exposure levels were 56 μg/day (IQR: 26-278 μg/day) for DA and 91 μg/day (IQR: 20-432 μg/day) for AP. They were slightly lower than the strict NIOSH-defined safety limits for occupational exposure and 100 and 10 times lower compared with smoking resp.; however, 47.3% of DA and 41.5% of AP-contg. samples exposed consumers to levels higher than the safety limits. Conclusions: DA and AP were found in a large proportion of sweet-flavored EC liqs., with many of them exposing users to higher than safety levels. Their presence in EC liqs. represents an avoidable risk. Proper measures should be taken by EC liq. manufacturers and flavoring suppliers to eliminate these hazards from the products without necessarily limiting the availability of sweet flavors.
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    Allen, J. G., Flanigan, S. S., LeBlanc, M., Vallarino, J., MacNaughton, P., Stewart, J. H., and Christiani, D. C. (2016) Flavouring chemicals in e-cigarettes: diacetyl, 2,3-pentanedione, and acetoin in a sample of 51 products, including fruit-, candy-, and cocktail-flavoured e-cigarettes Environ. Health Perspect. 124, 733– 739 DOI: 10.1289/ehp.1510185
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    European Union (2016) TPD Submission Data Dictionary: electronic cigarettes, Data Dictionary Document version: 1.0.2. https://circabc.europa.eu/sd/a/2935ab99-a719-4e4c-8dfa-c9c86751a074/TPD_submission_data_dictionary_electronic_cigarettes%201.0.2.docx (accessed July 15, 2016).
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    Flora, J. W., Meruva, N., Huang, C. B., Wilkinson, C. T., Ballentine, R., Smith, D. C., Werley, M. S., and McKinney, W. J. (2016) Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols Regul. Toxicol. Pharmacol. 74, 1– 11 DOI: 10.1016/j.yrtph.2015.11.009
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    Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols
    Flora, Jason W.; Meruva, Naren; Huang, Chorng B.; Wilkinson, Celeste T.; Ballentine, Regina; Smith, Donna C.; Werley, Michael S.; McKinney, Willie J.
    Regulatory Toxicology and Pharmacology (2016), 74 (), 1-11CODEN: RTOPDW; ISSN:0273-2300. (Elsevier Inc.)
    E-cigarettes are gaining popularity in the U. S. as well as in other global markets. Currently, limited published anal. data characterizing e-cigarette formulations (e-liqs.) and aerosols exist. While FDA has not published a harmful and potentially harmful constituent (HPHC) list for e-cigarettes, the HPHC list for currently regulated tobacco products may be useful to anal. characterize e-cigarette aerosols. For example, most e-cigarette formulations contain propylene glycol and glycerin, which may produce aldehydes when heated. In addn., nicotine-related chems. have been previously reported as potential e-cigarette formulation impurities. This study detd. e-liq. formulation impurities and potentially harmful chems. in aerosols of select com. MarkTen e-cigarettes manufd. by NuMark LLC. The potential hazard of the identified formulation impurities and aerosol chems. was also estd. E-cigarettes were machine puffed (4-s duration, 55-mL vol., 30-s intervals) to battery exhaustion to maximize aerosol collection. Aerosols analyzed for carbonyls were collected in 20-puff increments to account for analyte instability. Tobacco specific nitrosamines were measured at levels obsd. in pharmaceutical grade nicotine. Nicotine-related impurities in the e-cigarette formulations were below the identification and qualification thresholds proposed in ICH Guideline Q3B(R2). Levels of potentially harmful chems. detected in the aerosols were detd. to be below published occupational exposure limits.
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    Lauterbach, J. H., Laugesen, M., and Ross, J. D. (2012) Suggested protocol for estimation of harmful and potentially harmful constituents in mainstream aerosols generated by electronic nicotine delivery systems (ENDS). Poster 1860, Society of Toxicology, San Francisco, March 11–15.
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    Lauterbach, J. H. and Laugesen, M. (2012) Comparison of toxicant levels in mainstream aerosols generated by Ruyan® electronic nicotine delivery systems (ENDS) and conventional cigarette products. Poster 1861, Society of Toxicology, San Francisco, March 11–15.
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    Kentucky Tobacco Research & Development Center (2015) University of Kentucky Reference Cigarette 3R4F Preliminary Analysis. https://ctrp.uky.edu/resources/pdf/webdocs/3R4F%20Preliminary%20Analysis.pdf (accessed October 15, 2015).
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    Roemer, E., Schramke, H., Weiler, H., Buettner, A., Kausche, S., Weber, S., Berges, A., Stueber, M., Muench, M., Trelles-Sticken, E., Pype, J., Kohlgrueber, K., Voelkel, H., and Wittke, S. (2012) Mainstream smoke chemistry and in vitro and in vivo toxicity of the reference cigarettes 3R4F and 2R4F Beitr. Tabakforsch. Int. 25, 316– 335 DOI: 10.2478/cttr-2013-0912
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    Mainstream smoke chemistry and in vitro and in vivo toxicity of the reference cigarettes 3R4F and 2R4F
    Roemer, Ewald; Schramke, Heike; Weiler, Horst; Buettner, Ansgar; Kausche, Sandra; Weber, Susanne; Berges, An; Stueber, Markus; Muench, Monja; Trelles-Sticken, Edgar; Pype, Jan; Kohlgrueber, Karola; Voelkel, Hartmut; Wittke, Sandra
    Beitraege zur Tabakforschung International (2012), 25 (1), 316-335CODEN: BTAID3; ISSN:0173-783X. (BTFI Beitraege zur Tabakforschung GmbH)
    A new ref. cigarette, the 3R4F, has been developed to replace the depleting supply of the 2R4F cigarette. The present study was designed to compare mainstream smoke chem. and toxicity of the two ref. cigarettes under the International Organization for Standardization (ISO) machine smoking conditions, and to further compare mainstream smoke chem. and toxicol. activity of the 3R4F cigarette by two different smoking regimens, i.e., the machine smoking conditions specified by ISO and the Health Canada intensive (HCI) smoking conditions. The in vitro cytotoxicity and mutagenicity was detd. in the neutral red uptake assay, the Salmonella reverse mutation assay, and the mouse lymphoma thymidine kinase assay. Addnl., a 90-day nose-only inhalation study in rats was conducted to assess the in vivo toxicity. The comparison of smoke chem. between the two ref. cigarettes found practically the same yields of total particulate matter (TPM), 'tar', nicotine, carbon monoxide, and most other smoke constituents. For both cigarettes, the in vitro cytotoxicity, mutagenicity, and in vivo toxicity showed the expected smoke-related effects compared to controls without smoke exposure. There were no meaningful differences between the 2R4F and 3R4F regarding these toxicol. endpoints. The assessments for the 3R4F cigarette by smoking regimen found as a trivial effect, due to the higher amt. of smoke generated per cigarette under HCI conditions, an increased yield of toxicant and higher toxicol. activity per cigarette. However, per mg TPM, 'tar', or nicotine, the amts. of toxicants and the in vitro toxicity were generally lower under HCI conditions, but the in vivo activity was not different between the two machine smoking conditions. Overall, as the main result, the present study suggests equiv. smoke chem. and in vitro and in vivo toxicity for the 2R4F and 3R4F ref. cigarettes.
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    Costigan, S. and Meredith, C. (2015) An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids Regul. Toxicol. Pharmacol. 72, 361– 369 DOI: 10.1016/j.yrtph.2015.05.018
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    An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids
    Costigan, S.; Meredith, C.
    Regulatory Toxicology and Pharmacology (2015), 72 (2), 361-369CODEN: RTOPDW; ISSN:0273-2300. (Elsevier Inc.)
    Flavor ingredients are an essential part of e-liqs. Their responsible selection and inclusion levels in e-liqs. must be guided by toxicol. principles. We propose an approach to the screening and toxicol. risk assessment of flavor ingredients for e-liqs. The screening involves purity requirements and avoiding ingredients that are carcinogenic, mutagenic or toxic to reprodn. Addnl., owing to the uncertainties involved in potency detn. and the derivation of a tolerable level for respiratory sensitization, we propose excluding respiratory sensitizers. After screening, toxicol. data on the ingredients should be reviewed. Inhalation-specific toxicol. issues, for which no reliable safe levels can currently be derived, can lead to further ingredient exclusions. We discuss the use of toxicol. thresholds of concern for flavours that lack inhalation data suitable for quant. risk assessment. Higher toxicol. thresholds of concern are suggested for flavor ingredients (170 or 980 μg/day) than for contaminant assessment (1.5 μg/day). Anal. detection limits for measurements of potential reaction and thermal breakdown products in vaping aerosol, should be informed by the contaminant threshold. This principle leads us to recommend 5 ng/puff as an appropriate limit of detection for untargeted aerosol measurements.
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    Norton, K. J., June, K. M., and O’Connor, R. J. (2014) Initial puffing behaviors and subjective responses differ between an electronic nicotine delivery system and traditional cigarettes Tob. Induced Dis. 12, 17 DOI: 10.1186/1617-9625-12-17
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    Initial puffing behaviors and subjective responses differ between an electronic nicotine delivery system and traditional cigarettes
    Norton Kaila J; June Kristie M; O'Connor Richard J
    Tobacco induced diseases (2014), 12 (1), 17 ISSN:2070-7266.
    BACKGROUND: Electronic nicotine delivery systems (ENDS) present an emerging issue for tobacco control and data on product use behaviors are limited. METHODS: Participants (N = 38 enrolled; N = 16 compliant) completed three lab visits over 5 days and were asked to abstain from regular cigarettes for 72 hours in favor of ENDS (Smoke 51 TRIO - 3 piece, First Generation with 11 mg/ml filters). Lab visits included measurement of exhaled carbon monoxide (CO) and salivary cotinine concentration, questionnaire measures of regular cigarette craving after the 72 hour abstinence, and subjective product effects. Participants used a topography device to record puff volume, duration, flow rate, and inter-puff interval. RESULTS: Analyses revealed significant differences across products in puff count, average volume, total volume and inter-puff interval, with ENDS broadly showing a more intensive smoking pattern. Cigarette craving scores dropped significantly after smoking regular cigarettes, but not ENDS (p = .001), and subjective measures showed ENDS rated less favorably. CO boost, after ENDS use, decreased significantly (p < .001), and saliva cotinine significantly dropped between visits 1 and 3 (p < 0.001) after ENDS use relative to after cigarette smoking. For compliant and non-compliant participants, there was an average 82.0% [V1 - 16.1 cpd; V3 - 2.9 cpd] and average 73.9% [V1 - 20.3 cpd; V3 - 5.3 cpd] reduction in regular cigarette use per day during the ENDS trial period, respectively. CONCLUSIONS: The ENDS were smoked more intensively than own brand cigarettes, but delivered significantly less nicotineand were less satisfying. These findings have implications for the viability of certain ENDS as alternatives to cigarettes.
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    Spindle, T. R., Breland, A. B., Karaoghlanian, N. V., Shihadeh, A. L., and Eissenberg, T. (2015) Preliminary results of an examination of electronic cigarette user puff topography: the effect of a mouthpiece-based topography measurement device on plasma nicotine and subjective effects Nicotine Tob. Res. 17, 142– 149 DOI: 10.1093/ntr/ntu186
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    Preliminary results of an examination of electronic cigarette user puff topography: the effect of a mouthpiece-based topography measurement device on plasma nicotine and subjective effects
    Spindle, Tory R.; Breland, Alison B.; Karaoghlanian, Nareg V.; Shihadeh, Alan L.; Eissenberg, Thomas
    Nicotine & Tobacco Research (2015), 17 (2), 142-149CODEN: NTREF6; ISSN:1462-2203. (Oxford University Press)
    Electronic cigarettes (ECIGs) heat a nicotine-contg. soln.; the resulting aerosol is inhaled by the user. Nicotine delivery may be affected by users' puffing behavior (puff topog.), and little is known about the puff topog. of ECIG users. Puff topog. can be measured using mouthpiece-based computerized systems. However, the extent to which a mouthpiece influences nicotine delivery and subjective effects in ECIG users is unknown. Methods: Plasma nicotine concn., heart rate, and subjective effects were measured in 13 experienced ECIG users who used their preferred ECIG and liq. (≥12 mg/mL nicotine) during 2 sessions (with or without a mouthpiece). In both sessions, participants completed an ECIG use session in which they were instructed to take 10 puffs with 30-s inter-puff intervals. Puff topog. was recorded in the mouthpiece condition. Almost all measures of the effects of ECIG use were independent of topog. measurement. Collapsed across session, mean plasma nicotine concn. increased by 16.8 ng/mL, and mean heart rate increased by 8.5 bpm (ps < .05). Withdrawal symptoms decreased significantly after ECIG use. Participants reported that the mouthpiece affected awareness and made ECIG use more difficult. Relative to previously reported data for tobacco cigarette smokers using similar topog. measurement equipment, ECIG-using participants took larger and longer puffs with lower flow rates. In experienced ECIG users, measuring ECIG topog. did not influence ECI Gassocd. nicotine delivery or most measures of withdrawal suppression. Topog. measurement systems will need to account for the low flow rates obsd. for ECIG users.
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    Evaluation of electronic cigarette use (vaping) topography and estimation of liquid consumption: implications for research protocol standards definition and for public health authorities' regulation
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    International journal of environmental research and public health (2013), 10 (6), 2500-14 ISSN:.
    BACKGROUND: Although millions of people are using electronic cigarettes (ECs) and research on this topic has intensified in recent years, the pattern of EC use has not been systematically studied. Additionally, no comparative measure of exposure and nicotine delivery between EC and tobacco cigarette or nicotine replacement therapy (NRTs) has been established. This is important, especially in the context of the proposal for a new Tobacco Product Directive issued by the European Commission. METHODS: A second generation EC device, consisting of a higher capacity battery and tank atomiser design compared to smaller cigarette-like batteries and cartomizers, and a 9 mg/mL nicotine-concentration liquid were used in this study. Eighty subjects were recruited; 45 experienced EC users and 35 smokers. EC users were video-recorded when using the device (ECIG group), while smokers were recorded when smoking (SM-S group) and when using the EC (SM-E group) in a randomized cross-over design. Puff, inhalation and exhalation duration were measured. Additionally, the amount of EC liquid consumed by experienced EC users was measured at 5 min (similar to the time needed to smoke one tobacco cigarette) and at 20 min (similar to the time needed for a nicotine inhaler to deliver 4 mg nicotine). RESULTS: Puff duration was significantly higher in ECIG (4.2 ± 0.7 s) compared to SM-S (2.1 ± 0.4 s) and SM-E (2.3 ± 0.5 s), while inhalation time was lower (1.3 ± 0.4, 2.1 ± 0.4 and 2.1 ± 0.4 respectively). No difference was observed in exhalation duration. EC users took 13 puffs and consumed 62 ± 16 mg liquid in 5 min; they took 43 puffs and consumed 219 ± 56 mg liquid in 20 min. Nicotine delivery was estimated at 0.46 ± 0.12 mg after 5 min and 1.63 ± 0.41 mg after 20 min of use. Therefore, 20.8 mg/mL and 23.8 mg/mL nicotine-containing liquids would deliver 1 mg of nicotine in 5 min and 4 mg nicotine in 20 min, respectively. Since the ISO method significantly underestimates nicotine delivery by tobacco cigarettes, it seems that liquids with even higher than 24 mg/mL nicotine concentration would be comparable to one tobacco cigarette. CONCLUSIONS: EC use topography is significantly different compared to smoking. Four-second puffs with 20-30 s interpuff interval should be used when assessing EC effects in laboratory experiments, provided that the equipment used does not get overheated. Based on the characteristics of the device used in this study, a 20 mg/mL nicotine concentration liquid would be needed in order to deliver nicotine at amounts similar to the maximum allowable content of one tobacco cigarette (as measured by the ISO 3308 method). The results of this study do not support the statement of the European Commission Tobacco Product Directive that liquids with nicotine concentration of 4 mg/mL are comparable to NRTs in the amount of nicotine delivered to the user.
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    A "market map" comparison methodol. for cigarette smoke chem. yields is presented. Federal Trade Commission machine-method smoke chem. was detd. for a range of filtered cigarettes from the US marketplace. These data were used to develop illustrative market maps for each smoke constituent as anal. tools for comparing new or non-conventional cigarettes to a sampling of the broader range of marketplace cigarettes. Each market map contained best-est. "market-means," showing the relationship between com. cigarette constituent and tar yields, and yield "market ranges" defined by prediction intervals. These market map means and ranges are the basis for comparing new cigarette smoke yields to those of conventional cigarettes. The potential utility of market maps for evaluating differences in smoke chem. was demonstrated with 1R4F and 2R4F Kentucky ref. cigarettes, an Accord cigarette, and an Advance cigarette. Conventional cigarette tobacco nicotine, nitrate, sol. ammonia, and tobacco specific nitrosamine levels are reported. Differences among conventional cigarette constituent yields at similar tar levels were explained in part by the chem. compn. range of those cigarette tobaccos. The study also included a comparison of smoke constituent yields and in vitro smoke cytotoxicity and mutagenicity assay results for the 1R4F Kentucky ref. cigarette and its replacement 2R4F. Significant smoke yield differences were noted for lead, NNK, and NNN. The majority of their smoke constituent yields were within the market range developed from the sampled conventional cigarettes. Within the sensitivity and specificity of the in vitro bioassays used, smoke toxic activity differences for the two ref. cigarettes were not statistically significant. These results add to the limited information available for the 2R4F ref. cigarette.
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    Variation in tobacco and mainstream smoke toxicant yields from selected commercial cigarette products
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    Regulatory Toxicology and Pharmacology (2015), 71 (3), 409-427CODEN: RTOPDW; ISSN:0273-2300. (Elsevier Inc.)
    There is a drive toward the mandated lowering and reporting of selected toxicants in tobacco smoke. Several studies have quantified the mainstream cigarette emissions of toxicants, providing benchmark levels. Few, however, have examd. how measured toxicant levels within a single product vary over time due to natural variation in the tobacco, manufg. and measurement. In a single center anal., key toxicants were measured in the tobacco blend and smoke of 3R4F ref. cigarette and three com. products, each sampled monthly for 10 mo. For most analytes, monthly variation was low (coeff. of variation <15%); but higher (≥20%) for some compds. present at low (ppb) levels. Reporting toxicant emissions as a ratio to nicotine increased the monthly variation of the 9 analytes proposed for mandated lowering, by 1-2 percentage points. Variation in toxicant levels was generally 1.5-1.7-fold higher in com. cigarettes compared with 3R4F over the 10-mo period, but increased up to 3.5-fold for analytes measured at ppb level. The potential error (2CV) assocd. with single-point-in-time sampling averaged ∼20%. Together, these data demonstrate that measurement of emissions from com. cigarettes is assocd. with considerable variation for low-level toxicants. This variation would increase if the analyses were conducted in more than one lab.
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  2. Beiran Yang, Sainan Wang, Liming Wang. Rapid Gas-Phase Autoxidation of Nicotine in the Atmosphere. The Journal of Physical Chemistry A 2022, 126 (37) , 6495-6501. https://doi.org/10.1021/acs.jpca.2c04551
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    Figure 1

    Figure 1. Vype ePen construction.

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    Figure 2. Emissions detected from the e-cigarette at quantifiable levels.

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    Figure 3. Comparison of percent reduction in e-cigarette emissions in comparison to those from Ky3R4F under HCI puffing conditions.

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      Electronic nicotine delivery system (electronic cigarette) awareness, use, reactions and beliefs: a systematic review
      Pepper Jessica K; Brewer Noel T
      Tobacco control (2014), 23 (5), 375-84 ISSN:.
      OBJECTIVE: We sought to systematically review the literature on electronic nicotine delivery systems (ENDS, also called electronic cigarettes) awareness, use, reactions and beliefs. DATA SOURCES: We searched five databases for articles published between 2006 and 1 July 2013 that contained variations of the phrases 'electronic cigarette', 'e-cigarette' and 'electronic nicotine delivery'. STUDY SELECTION: Of the 244 abstracts identified, we excluded articles not published in English, articles unrelated to ENDS, dissertation abstracts and articles without original data on prespecified outcomes. DATA EXTRACTION: Two reviewers coded each article for ENDS awareness, use, reactions and beliefs. DATA SYNTHESIS: 49 studies met inclusion criteria. ENDS awareness increased from 16% to 58% from 2009 to 2011, and use increased from 1% to 6%. The majority of users were current or former smokers. Many users found ENDS satisfying, and some engaged in dual use of ENDS and other tobacco. No longitudinal studies examined whether ENDS serve as 'gateways' to future tobacco use. Common reasons for using ENDS were quitting smoking and using a product that is healthier than cigarettes. Self-reported survey data and prospective trials suggest that ENDS might help cigarette smokers quit, but no randomised controlled trials with probability samples compared ENDS with other cessation tools. Some individuals used ENDS to avoid smoking restrictions. CONCLUSIONS: ENDS use is expanding rapidly despite experts' concerns about safety, dual use and possible 'gateway' effects. More research is needed on effective public health messages, perceived health risks, validity of self-reports of smoking cessation and the use of different kinds of ENDS.
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      Application of toxicological risk assessment principles to the chemical constituents of cigarette smoke
      Fowles J; Dybing E
      Tobacco control (2003), 12 (4), 424-30 ISSN:.
      OBJECTIVE: To provide a hazard prioritisation for reported chemical constituents of cigarette smoke using toxicological risk assessment principles and assumptions. The purpose is to inform prevention efforts using harm reduction. DATA SOURCES: International Agency for Research on Cancer Monographs; California and US Environmental Protection Agency cancer potency factors (CPFs) and reference exposure levels; scientific journals and government reports from the USA, Canada, and New Zealand. STUDY SELECTION: This was an inclusive review of studies reporting yields of cigarette smoke constituents using standard ISO methods. DATA EXTRACTION: Where possible, the midpoint of reported ranges of yields was used. DATA SYNTHESIS: Data on 158 compounds in cigarette smoke were found. Of these, 45 were known or suspected human carcinogens. Cancer potency factors were available for 40 of these compounds and reference exposure levels (RELs) for non-cancer effects were found for 17. A cancer risk index (CRI) was calculated by multiplying yield levels with CPFs. A non-cancer risk index (NCRI) was calculated by dividing yield levels with RELs. Gas phase constituents dominate both CRI and NCRI for cigarette smoke. The contribution of 1,3-butadiene (BDE) to CRI was more than twice that of the next highest contributing carcinogen (acrylonitrile) using potencies from the State of California EPA. Using those potencies from the USEPA, BDE ranked third behind arsenic and acetaldehyde. A comparison of CRI estimates with estimates of smoking related cancer deaths in the USA showed that the CRI underestimates the observed cancer rates by about fivefold using ISO yields in the exposure estimate. CONCLUSIONS: The application of toxicological risk assessment methods to cigarette smoke provides a plausible and objective framework for the prioritisation of carcinogens and other toxicant hazards in cigarette smoke. However, this framework does not enable the prediction of actual cancer risk for a number of reasons that are discussed. Further, the lack of toxicology data on cardiovascular end points for specific chemicals makes the use of this framework less useful for cardiovascular toxicity. The bases for these priorities need to be constantly re-evaluated as new toxicology information emerges.
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      Food and Drug Administration (2012) Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Established List, April 2012, http://www.fda.gov/downloads/TobaccoProducts/GuidanceComplianceRegulatoryInformation/UCM297981.pdf (accessed December 21, 2015).
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      (2012) Tobacco Hazards Prevention and Control Act, Bureau of Health Promotion, Department of Health, Taiwan (R.O.C). http://www.hpa.gov.tw/English/ClassShow.aspx?No=200907130001 (accessed July 14, 2016).
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      Burns, D. M., Dybing, E., Gray, N., Hecht, S., Anderson, C., Sanner, T., O’Connor, R., Djordjevic, M., Dresler, C., Hainaut, P., Jarvis, M., Opperhuizen, A., and Straif, K. (2008) Mandated lowering of toxicants in cigarette smoke: a description of the World Health Organization TobReg proposal Tob. Control 17, 132– 141 DOI: 10.1136/tc.2007.024158
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      Mandated lowering of toxicants in cigarette smoke: a description of the World Health Organization TobReg proposal
      Burns D M; Dybing E; Gray N; Hecht S; Anderson C; Sanner T; O'Connor R; Djordjevic M; Dresler C; Hainaut P; Jarvis M; Opperhuizen A; Straif K
      Tobacco control (2008), 17 (2), 132-41 ISSN:.
      There is no expanded citation for this reference.
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      Royal College of Physicians (2016) Nicotine without smoke: Tobacco harm reduction. A report by the Tobacco Advisory Group of the Royal College of Physicians, London, April 28. https://www.rcplondon.ac.uk/projects/outputs/nicotine-without-smoke-tobacco-harm-reduction-0 (accessed May 25, 2016).
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      McNeill, A., Brose, L. S., Calder, R., Hitchman, S. C., Hajek, P., and McRobbie, H. (2015) E-cigarettes: an evidence update. A report commissioned by Public Health England. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/457102/Ecigarettes_an_evidence_update_A_report_commissioned_by_Public_Health_England_FINAL.pdf (accessed December 21, 2015).
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      Scheffler, S., Dieken, H., Krischenowski, O., Förster, C., Branscheid, D., and Aufderheide, M. (2015) Evaluation of e-cigarette liquid vapor and mainstream cigarette smoke after direct exposure of primary human bronchial epithelial cells Int. J. Environ. Res. Public Health 12, 3915– 3925 DOI: 10.3390/ijerph120403915
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      Evaluation of e-cigarette liquid vapor and mainstream cigarette smoke after direct exposure of primary human bronchial epithelial cells
      Scheffler, Stefanie; Dieken, Hauke; Krischenowski, Olaf; Foerster, Christine; Branscheid, Detlev; Aufderheide, Michaela
      International Journal of Environmental Research and Public Health (2015), 12 (4), 3915-3925CODEN: IJERGQ; ISSN:1660-4601. (MDPI AG)
      E-cigarettes are emerging products, often described as "reduced-risk" nicotine products or alternatives to combustible cigarettes. Many smokers switch to e-cigarettes to quit or significantly reduce smoking. However, no regulations for e-cigarettes are currently into force, so that the quality and safety of e-liqs. is not necessarily guaranteed. We exposed primary human bronchial epithelial cells of two different donors to vapor of e-cigarette liq. with or without nicotine, vapor of the carrier substances propylene glycol and glycerol as well as to mainstream smoke of K3R4F research cigarettes. The exposure was done in a CULTEX RFS compact module, allowing the exposure of the cells at the air-liq. interface. 24 h post-exposure, cell viability and oxidative stress levels in the cells were analyzed. We found toxicol. effects of e-cigarette vapor and the pure carrier substances, whereas the nicotine concn. did not have an effect on the cell viability. The viability of mainstream smoke cigarette exposed cells was 4.5-8 times lower and the oxidative stress levels 4.5-5 times higher than those of e-cigarette vapor exposed cells, depending on the donor. Our exptl. setup delivered reproducible data and thus provides the opportunity for routine testing of e-cigarette liqs. to ensure safety and quality for the user.
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      Neilson, L., Mankus, C., Thorne, D., Jackson, G., DeBay, J., and Meredith, C. (2015) Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol Toxicol. In Vitro 29, 1952– 1962 DOI: 10.1016/j.tiv.2015.05.018
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      Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol
      Neilson, Louise; Mankus, Courtney; Thorne, David; Jackson, George; De Bay, Jason; Meredith, Clive
      Toxicology In Vitro (2015), 29 (7), 1952-1962CODEN: TIVIEQ; ISSN:0887-2333. (Elsevier Ltd.)
      Development of physiol. relevant test methods to analyze potential irritant effects to the respiratory tract caused by e-cigarette aerosols is required. This paper reports the method development and optimization of an acute in vitro MTT cytotoxicity assay using human 3D reconstructed airway tissues and an aerosol exposure system. The EpiAirway tissue is a highly differentiated in vitro human airway culture derived from primary human tracheal/bronchial epithelial cells grown at the air-liq. interface, which can be exposed to aerosols generated by the VITROCELL smoking robot. Method development was supported by understanding the compatibility of these tissues within the VITROCELL system, in terms of airflow (L/min), vacuum rate (mL/min) and exposure time. Dosimetry tools (QCM) were used to measure deposited mass, to confirm the provision of e-cigarette aerosol to the tissues. EpiAirway tissues were exposed to cigarette smoke and aerosol generated from two com. e-cigarettes for up to 6 h. Cigarette smoke reduced cell viability in a time dependent manner to 12% at 6 h. E-cigarette aerosol showed no such decrease in cell viability and displayed similar results to that of the untreated air controls. Applicability of the EpiAirway model and exposure system was demonstrated, showing little cytotoxicity from e-cigarette aerosol and different aerosol formulations when compared directly with ref. cigarette smoke, over the same exposure time.
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      Marco, E. and Grimalt, J. O. (2015) A rapid method for the chromatographic analysis of volatile organic compounds in exhaled breath of tobacco cigarette and electronic cigarette smokers J. Chromatogr. A 1410, 51– 59 DOI: 10.1016/j.chroma.2015.07.094
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      Rodgman, A. and Perfetti, T. A. (2013) The Chemical Components of Tobacco and Tobacco Smoke, 2nd ed., CRC Press.
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      Westenberger, B. (2009) Evaluation of e-Cigarettes, US Department of Health and Human Services, Center for Drug Evaluation and Research. http://www.fda.gov/downloads/drugs/scienceresearch/ucm173250.pdf (accessed May 25, 2015).
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      Kim, H. J. and Shin, H. S. (2013) Determination of tobacco-specific nitrosamines in replacement liquids of electronic cigarettes by liquid chromatography-tandem mass spectrometry J. Chromatogr. A 1291, 48– 55 DOI: 10.1016/j.chroma.2013.03.035
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      Determination of tobacco-specific nitrosamines in replacement liquids of electronic cigarettes by liquid chromatography-tandem mass spectrometry
      Kim, Hyun-Ji; Shin, Ho-Sang
      Journal of Chromatography A (2013), 1291 (), 48-55CODEN: JCRAEY; ISSN:0021-9673. (Elsevier B.V.)
      A liq. chromatog.-tandem mass spectrometric method was described to detect tobacco-specific nitrosamines (TSNAs) in replacement liqs. of electronic cigarettes. Solid-phase extn. (SPE) and liq.-liq. extn. (LLE) were compared to each other to select the optimum clean-up method. Under the established condition, the limits of quantification of N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N'-nitrosoanabasine (NAB), and N'-nitrosoanatabine (NAT) were 0.06, 0.07, 0.06, and 0.04 μg/L resp., by using 0.5 mL of replacement liqs., resp., and the relative std. deviation was less than 10% at concns. of 5.0 and 25.0 μg/L. The concns. of TSNAs were measured in concn. ranges of 0.34-60.08 μg/L (64.8% detection frequency) for NNN, 0.22-9.84 μg/L (88.6% detection frequency) for NNK, 0.11-11.11 μg/L (54.3% detection frequency) for NNB, and 0.09-62.19 μg/L (75.2% detection frequency) for NAT in 105 replacement liq. brands from 11 electronic cigarette companies purchased in the Korean market.
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      Tayyarah, R. and Long, G. A. (2014) Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air Regul. Toxicol. Pharmacol. 70, 704– 710 DOI: 10.1016/j.yrtph.2014.10.010
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      Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air
      Tayyarah, Rana; Long, Gerald A.
      Regulatory Toxicology and Pharmacology (2014), 70 (3), 704-710CODEN: RTOPDW; ISSN:0273-2300. (Elsevier Inc.)
      Leading com. electronic cigarettes were tested to det. bulk compn. The e-cigarettes and conventional cigarettes were evaluated using machine-puffing to compare nicotine delivery and relative yields of chem. constituents. The e-liqs. tested were found to contain humectants, glycerin and/or propylene glycol, (≥75% content); water (<20%); nicotine (approx. 2%); and flavor (<10%). The aerosol collected mass (ACM) of the e-cigarette samples was similar in compn. to the e-liqs. Aerosol nicotine for the e-cigarette samples was 85% lower than nicotine yield for the conventional cigarettes. Anal. of the smoke from conventional cigarettes showed that the mainstream cigarette smoke delivered approx. 1500 times more harmful and potentially harmful constituents (HPHCs) tested when compared to e-cigarette aerosol or to puffing room air. The deliveries of HPHCs tested for these e-cigarette products were similar to the study air blanks rather than to deliveries from conventional cigarettes; no significant contribution of cigarette smoke HPHCs from any of the compd. classes tested was found for the e-cigarettes. Thus, the results of this study support previous researchers' discussion of e-cigarette products' potential for reduced exposure compared to cigarette smoke.
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    27. 27
      Farsalinos, K. E., Gillman, I. G., Melvin, M. S., Paolantonio, A. R., Gardow, W. J., Humphries, K. E., Brown, S. E., Poulas, K., and Voudris, V. (2015) Nicotine levels and presence of selected tobacco-derived toxins in tobacco flavoured electronic cigarette refill liquids Int. J. Environ. Res. Public Health 12, 3439– 3452 DOI: 10.3390/ijerph120403439
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      27
      Nicotine levels and presence of selected tobacco-derived toxins in tobacco flavoured electronic cigarette refill liquids
      Farsalinos, Konstantinos E.; Gillman, I. Gene; Melvin, Matt S.; Paolantonio, Amelia R.; Gardow, Wendy J.; Humphries, Kathy E.; Brown, Sherri E.; Poulas, Konstantinos; Voudris, Vassilis
      International Journal of Environmental Research and Public Health (2015), 12 (4), 3439-3452CODEN: IJERGQ; ISSN:1660-4601. (MDPI AG)
      Background. Some electronic cigarette (EC) liqs. of tobacco flavor contain exts. of cured tobacco leaves produced by a process of solvent extn. and steeping. These are commonly called Natural Ext. of Tobacco (NET) liqs. The purpose of the study was to evaluate nicotine levels and the presence of tobacco-derived toxins in tobacco-flavoured conventional and NET liqs. Methods. Twenty-one samples (10 conventional and 11 NET liqs.) were obtained from the US and Greek market. Nicotine levels were measured and compared with labeled values. The levels of tobacco-derived chems. were compared with literature data on tobacco products. Results. Twelve samples had nicotine levels within 10% of the labeled value. Inconsistency ranged from -21% to 22.1%, with no difference obsd. between conventional and NET liqs. Tobacco-specific nitrosamines (TSNAs) were present in all samples at ng/mL levels. Nitrates were present almost exclusively in NET liqs. Acetaldehyde was present predominantly in conventional liqs. while formaldehyde was detected in almost all EC liqs. at trace levels. Phenols were present in trace amts., mostly in NET liqs. Total TSNAs and nitrate, which are derived from the tobacco plant, were present at levels 200-300 times lower in 1 mL of NET liqs. compared to 1 g of tobacco products. Conclusions. NET liqs. contained higher levels of phenols and nitrates, but lower levels of acetaldehyde compared to conventional EC liqs. The lower levels of tobacco-derived toxins found in NET liqs. compared to tobacco products indicate that the extn. process used to make these products did not transfer a significant amt. of toxins to the NET. Overall, all EC liqs. contained far lower (by 2-3 orders of magnitude) levels of the tobacco-derived toxins compared to tobacco products.
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      Etter, J. F., Zäther, E., and Svensson, S. (2013) Analysis of refill liquids for electronic cigarettes Addiction 108, 1671– 1679 DOI: 10.1111/add.12235
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      Analysis of refill liquids for electronic cigarettes
      Etter Jean-Francois; Zather Eva; Svensson Sofie
      Addiction (Abingdon, England) (2013), 108 (9), 1671-9 ISSN:.
      AIMS: To assess levels of nicotine, nicotine degradation products and some specific impurities in commercial refill liquids for electronic cigarettes. DESIGN AND SETTING: We analyzed 20 models of 10 of the most popular brands of refill liquids, using gas and liquid chromatography. MEASUREMENTS: We assessed nicotine content, content of the known nicotine degradation products and impurities, and presence of ethylene glycol and diethylene glycol. FINDINGS: The nicotine content in the bottles corresponded closely to the labels on the bottles. The levels of nicotine degradation products represented 0-4.4% of those for nicotine, but for most samples the level was 1-2%. Cis-N-oxide, trans-N-oxide, myosmine, anatabine and anabasine were the most common additional compounds found. Neither ethylene glycol nor diethylene glycol were detected. CONCLUSION: The nicotine content of electronic cigarette refill bottles is close to what is stated on the label. Impurities are detectable in several brands above the level set for nicotine products in the European Pharmacopoeia, but below the level where they would be likely to cause harm.
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      Lisko, J. G., Tran, H., Stanfill, S. B., Blount, B. C., and Watson, C. H. (2015) Chemical composition and evaluation of nicotine, tobacco alkaloids, pH, and selected flavors in e-cigarette cartridges and refill solutions Nicotine Tob. Res. 17, 1270– 1278 DOI: 10.1093/ntr/ntu279
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      Chemical Composition and Evaluation of Nicotine, Tobacco Alkaloids, pH, and Selected Flavors in E-Cigarette Cartridges and Refill Solutions
      Lisko Joseph G; Tran Hang; Stanfill Stephen B; Blount Benjamin C; Watson Clifford H
      Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco (2015), 17 (10), 1270-8 ISSN:.
      INTRODUCTION: Electronic cigarette (e-cigarette) use is increasing dramatically in developed countries, but little is known about these rapidly evolving products. This study analyzed and evaluated the chemical composition including nicotine, tobacco alkaloids, pH, and flavors in 36 e-liquids brands from 4 manufacturers. METHODS: We determined the concentrations of nicotine, alkaloids, and select flavors and measured pH in solutions used in e-cigarettes. E-cigarette products were chosen based upon favorable consumer approval ratings from online review websites. Quantitative analyses were performed using strict quality assurance/quality control validated methods previously established by our lab for the measurement of nicotine, alkaloids, pH, and flavors. RESULTS: Three-quarters of the products contained lower measured nicotine levels than the stated label values (6%-42% by concentration). The pH for e-liquids ranged from 5.1-9.1. Minor tobacco alkaloids were found in all samples containing nicotine, and their relative concentrations varied widely among manufacturers. A number of common flavor compounds were analyzed in all e-liquids. CONCLUSIONS: Free nicotine levels calculated from the measurement of pH correlated with total nicotine content. The direct correlation between the total nicotine concentration and pH suggests that the alkalinity of nicotine drives the pH of e-cigarette solutions. A higher percentage of nicotine exists in the more absorbable free form as total nicotine concentration increases. A number of products contained tobacco alkaloids at concentrations that exceed U.S. pharmacopeia limits for impurities in nicotine used in pharmaceutical and food products.
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    30. 30
      Goniewicz, M. L., Knysak, J., Gawron, M., Kosmider, L., Sobczak, A., Kurek, J., Prokopowicz, A., Jablonska-Czapla, M., Rosik-Dulewska, C., Havel, C., Jacob, P., and Benowitz, N. (2014) Levels of selected carcinogens and toxicants in vapour from electronic cigarettes Tob. Control 23, 133– 139 DOI: 10.1136/tobaccocontrol-2012-050859
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      Levels of selected carcinogens and toxicants in vapour from electronic cigarettes
      Goniewicz Maciej Lukasz; Knysak Jakub; Gawron Michal; Kosmider Leon; Sobczak Andrzej; Kurek Jolanta; Prokopowicz Adam; Jablonska-Czapla Magdalena; Rosik-Dulewska Czeslawa; Havel Christopher; Jacob Peyton 3rd; Benowitz Neal
      Tobacco control (2014), 23 (2), 133-9 ISSN:.
      SIGNIFICANCE: Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. They are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapour generated from e-cigarettes. The aim of this study was to screen e-cigarette vapours for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines and heavy metals. MATERIALS AND METHODS: Vapours were generated from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapours into a solid or liquid phase and analysed with chromatographic and spectroscopy methods. RESULTS: We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9-450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product. CONCLUSIONS: Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study. (To view this abstract in Polish and German, please see the supplementary files online.).
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      Schripp, T., Markewitz, D., Uhde, E., and Salthammer, T. (2013) Does e-cigarette consumption cause passive vaping? Indoor Air 23, 25– 31 DOI: 10.1111/j.1600-0668.2012.00792.x
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      31
      Does e-cigarette consumption cause passive vaping?
      Schripp, T.; Markewitz, D.; Uhde, E.; Salthammer, T.
      Indoor Air (2013), 23 (1), 25-31CODEN: INAIE5; ISSN:0905-6947. (Wiley-Blackwell)
      Electronic cigarette consumption ('vaping') is marketed as an alternative to conventional tobacco smoking. Tech., a mixt. of chems. contg. carrier liqs., flavors, and optionally nicotine is vaporized and inhaled. The present study aims at the detn. of the release of volatile org. compds. (VOC) and (ultra)fine particles (FP/UFP) from an e-cigarette under near-to-real-use conditions in an 8-m3 emission test chamber. Furthermore, the inhaled mixt. is analyzed in small chambers. An increase in FP/UFP and VOC could be detd. after the use of the e-cigarette. Prominent components in the gas-phase are 1,2-propanediol, 1,2,3-propanetriol, diacetin, flavorings, and traces of nicotine. As a consequence, 'passive vaping' must be expected from the consumption of e-cigarettes. Furthermore, the inhaled aerosol undergoes changes in the human lung that is assumed to be attributed to deposition and evapn.
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    32. 32
      Pellegrino, R. M., Tinghino, B., Mangiaracina, G., Marani, A., Vitali, M., Protano, C., Osborn, J. F., and Cattaruzza, M. S. (2012) Electronic cigarettes: an evaluation of exposure to chemicals and fine particulate matter (PM) Annali di igiene: medicina preventiva e di comunità 24, 279– 288
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      Herrington, J. S. and Hays, M. D. (2012) Concerns regarding 24-h sampling for formaldehyde, acetaldehyde, and acrolein using 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents Atmos. Environ. 55, 179– 184 DOI: 10.1016/j.atmosenv.2012.02.088
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      33
      Concerns regarding 24-h sampling for formaldehyde, acetaldehyde, and acrolein using 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents
      Herrington, Jason S.; Hays, Michael D.
      Atmospheric Environment (2012), 55 (), 179-184CODEN: AENVEQ; ISSN:1352-2310. (Elsevier Ltd.)
      A review. There is high demand for accurate and reliable airborne carbonyl measurement methods due to the human and environmental health impacts of carbonyls and their effects on atm. chem. Standardized 2,4-dinitrophenylhydrazine (DNPH)-based sampling methods are frequently applied for measuring gaseous carbonyls in the atm. environment. However, there are multiple short-comings assocd. with these methods that detract from an accurate understanding of carbonyl-related exposure, health effects, and atm. chem. The purpose of this brief tech. communication is to highlight these method challenges and their influence on national ambient monitoring networks, and to provide a logical path forward for accurate carbonyl measurement. This manuscript focuses on 3 specific carbonyl compds. of high toxicol. interest - formaldehyde, acetaldehyde, and acrolein. Further method testing and development, the revision of standardized methods, and the plausibility of introducing novel technol. for these carbonyls are considered elements of the path forward. The consolidation of this information is important because it seems clear that carbonyl data produced utilizing DNPH-based methods are being reported without acknowledgment of the method short-comings or how to best address them.
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    34. 34
      Laugesen, M. (2009) Ruyan® e-cigarette bench-top tests. Poster presented at Society for Research on Nicotine and Tobacco (SRNT) Meeting, April 30, Dublin, Ireland. http://www.seeht.org/Laugesen_Apr_2009.pdf (accessed December 21, 2015).
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    35. 35
      Williams, M., Villarreal, A., Bozhilov, K., Lin, S., and Talbot, P. (2013) Metal and silicate particles including nanoparticles are present in electronic cigarette cartomizer fluid and aerosol PLoS One 8, e57987 DOI: 10.1371/journal.pone.0057987
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      35
      Metal and silicate particles including nanoparticles are present in electronic cigarette cartomizer fluid and aerosol
      Williams, Monique; Villarreal, Amanda; Bozhilov, Krassimir; Lin, Sabrina; Talbot, Prue
      PLoS One (2013), 8 (3), e57987CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
      Background: Electronic cigarettes (EC) deliver aerosol by heating fluid contg. nicotine. Cartomizer EC combine the fluid chamber and heating element in a single unit. Because EC do not burn tobacco, they may be safer than conventional cigarettes. Their use is rapidly increasing worldwide with little prior testing of their aerosol. Objectives: We tested the hypothesis that EC aerosol contains metals derived from various components in EC. Methods: Cartomizer contents and aerosols were analyzed using light and electron microscopy, cytotoxicity testing, x-ray microanal., particle counting, and inductively coupled plasma optical emission spectrometry. Results: The filament, a nickel-chromium wire, was coupled to a thicker copper wire coated with silver. The silver coating was sometimes missing. Four tin solder joints a ttached the wires to each other and coupled the copper/silver wire to the air tube and mouthpiece. All cartomizers had evidence of use before packaging (burn spots on the fibers and electrophoretic movement of fluid in the fibers). Fibers in two cartomizers had green deposits that contained copper. Centrifugation of the fibers produced large pellets contg. tin. Tin particles and tin whiskers were identified in cartridge fluid and outer fibers. Cartomizer fluid with tin particles was cytotoxic in assays using human pulmonary fibroblasts. The aerosol contained particles >1 μm comprised of tin, silver, iron, nickel, aluminum, and silicate and nanoparticles (<100 nm) of tin, chromium and nickel. The concns. of nine of eleven elements in EC aerosol were higher than or equal to the corresponding concns. in conventional cigarette smoke. Many of the elements identified in EC aerosol are known to cause respiratory distress and disease. Conclusions: The presence of metal and silicate particles in cartomizer aerosol demonstrates the need for improved quality control in EC design and manuf. and studies on how EC aerosol impacts the health of users and bystanders.
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    36. 36
      Lerner, C. A., Sundar, I. K., Watson, R. M., Elder, A., Jones, R., Done, D., Kurtzman, R., Ossip, D. J., Robinson, R., McIntosh, S., and Rahman, I. (2015) Environmental health hazards of e-cigarettes and their components: Oxidants and copper in e-cigarette aerosols Environ. Pollut. 198, 100– 107 DOI: 10.1016/j.envpol.2014.12.033
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      36
      Environmental health hazards of e-cigarettes and their components: Oxidants and copper in e-cigarette aerosols
      Lerner, Chad A.; Sundar, Isaac K.; Watson, Richard M.; Elder, Alison; Jones, Ryan; Done, Douglas; Kurtzman, Rachel; Ossip, Deborah J.; Robinson, Risa; McIntosh, Scott; Rahman, Irfan
      Environmental Pollution (Oxford, United Kingdom) (2015), 198 (), 100-107CODEN: ENPOEK; ISSN:0269-7491. (Elsevier Ltd.)
      To narrow the gap in our understanding of potential oxidative properties assocd. with Electronic Nicotine Delivery Systems (ENDS) i.e. e-cigarettes, we employed semi-quant. methods to detect oxidant reactivity in disposable components of ENDS/e-cigarettes (batteries and cartomizers) using a fluorescein indicator. These components exhibit oxidants/reactive oxygen species reactivity similar to used conventional cigarette filters. Oxidants/reactive oxygen species reactivity in e-cigarette aerosols was also similar to oxidant reactivity in cigarette smoke. A cascade particle impactor allowed sieving of a range of particle size distributions between 0.450 and 2.02 μm in aerosols from an e-cigarette. Copper, being among these particles, is 6.1 times higher per puff than reported previously for conventional cigarette smoke. The detection of a potentially cytotoxic metal as well as oxidants from e-cigarette and its components raises concern regarding the safety of e-cigarettes use and the disposal of e-cigarette waste products into the environment.
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    37. 37
      Ohta, K., Uchiyama, S., Inaba, Y., Nakagome, H., and Kunugita, N. (2011) Determination of carbonyl compounds generated from the electronic cigarette using coupled silica cartridges impregnated with hydroquinone and2,4-dinitrophenylhydrazine Bunseki Kagaku 60, 791– 797 DOI: 10.2116/bunsekikagaku.60.791
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      Theophilus, E. H., Potts, R., Fowler, K., Fields, W., and Bombick, B. (2014) VUSE electronic cigarette aerosol chemistry and cytotoxicity Toxicol. Lett. 229, S211 DOI: 10.1016/j.toxlet.2014.06.710
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      Uchiyama, S., Ohta, K., Inaba, Y., and Kunugita, N. (2013) Determination of carbonyl compounds generated from the E-cigarette using coupled silica cartridges impregnated with hydroquinone and 2,4-dinitrophenylhydrazine, followed by high-performance liquid chromatography Anal. Sci. 29, 1219– 1222 DOI: 10.2116/analsci.29.1219
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      39
      Determination of carbonyl compounds generated from the E-cigarette using coupled silica cartridges impregnated with hydroquinone and 2,4-dinitrophenylhydrazine, followed by high-performance liquid chromatography
      Uchiyama, Shigehisa; Ohta, Kazushi; Inaba, Yohei; Kunugita, Naoki
      Analytical Sciences (2013), 29 (12), 1219-1222CODEN: ANSCEN; ISSN:0910-6340. (Japan Society for Analytical Chemistry)
      Carbonyl compds. in E-cigarette smoke mist were measured using coupled silica cartridges impregnated with hydroquinone and 2,4-dinitrophenylhydrazine, followed by high-performance liq. chromatog. A total of 363 E-cigarettes (13 brands) were examd. Four of the 13 E-cigarette brands did not generate any carbonyl compds., while the other nine E-cigarette brands generated various carbonyl compds. However, the carbonyl concns. of the E-cigarette products did not show typical distributions, and the mean values were largely different from the median values. It was elucidated that E-cigarettes incidentally generate high concns. of carbonyl compds.
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    40. 40
      Hutzler, C., Paschke, M., Kruschinski, S., Henkler, F., Hahn, J., and Luch, A. (2014) Chemical hazards present in liquids and vapors of electronic cigarette Arch. Toxicol. 88, 1295– 1308 DOI: 10.1007/s00204-014-1294-7
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      40
      Chemical hazards present in liquids and vapors of electronic cigarettes
      Hutzler, Christoph; Paschke, Meike; Kruschinski, Svetlana; Henkler, Frank; Hahn, Juergen; Luch, Andreas
      Archives of Toxicology (2014), 88 (7), 1295-1308CODEN: ARTODN; ISSN:0340-5761. (Springer)
      Electronic (e-)cigarettes have emerged in recent years as putative alternative to conventional tobacco cigarettes. These products do not contain typical carcinogens that are present in tobacco smoke, due to the lack of combustion. However, besides nicotine, hazards can also arise from other constituents of liqs., such as solvents, flavors, additives and contaminants. In this study, we have analyzed 28 liqs. of seven manufacturers purchased in Germany. We confirm the presence of a wide range of flavors to enhance palatability. Although glycerol and propylene glycol were detected in all samples, these solvents had been replaced by ethylene glycol as dominant compd. in five products. Ethylene glycol is assocd. with markedly enhanced toxicol. hazards when compared to conventionally used glycerol and propylene glycol. Addnl. additives, such as coumarin and acetamide, that raise concerns for human health were detected in certain samples. Ten out of 28 products had been declared "free-of-nicotine" by the manufacturer. Among these ten, seven liqs. were identified contg. nicotine in the range of 0.1-15 μg/mL. This suggests that "carry over" of ingredients may occur during the prodn. of cartridges. We have further analyzed the formation of carbonylic compds. in one widely distributed nicotine-free brand. Significant amts. of formaldehyde, acetaldehyde and propionaldehyde were only found at 150 °C by headspace GC-MS anal. In addn., an enhanced formation of aldehydes was found in defined puff fractions, using an adopted machine smoking protocol. However, this effect was delayed and only obsd. during the last third of the smoking procedure. In the emissions of these fractions, which represent up to 40 % of total vapor vol., similar levels of formaldehyde were detected when compared to conventional tobacco cigarettes. By contrast, carbonylic compds. were hardly detectable in earlier collected fractions. Our data demonstrate the necessity of standardized machine smoking protocols to reliably address putative risks of e-cigarettes for consumers.
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    41. 41
      Kosmider, L., Sobczak, A., Fik, M., Knysak, J., Zaciera, M., Kurek, J., and Goniewicz, M. L. (2014) Carbonyl compounds in electronic cigarette vapors: effects of nicotine solvent and battery output voltage Nicotine Tob. Res. 16, 1319– 1326 DOI: 10.1093/ntr/ntu078
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      41
      Carbonyl compounds in electronic cigarette vapors: effects of nicotine solvent and battery output voltage
      Kosmider, Leon; Sobczak, Andrzej; Fik, Maciej; Knysak, Jakub; Zaciera, Marzena; Kurek, Jolanta; Goniewicz, Maciej Lukasz
      Nicotine & Tobacco Research (2014), 16 (10), 1319-1326CODEN: NTREF6; ISSN:1462-2203. (Oxford University Press)
      Introduction: Glycerin (VG) and propylene glycol (PG) are the most common nicotine solvents used in e-cigarettes (ECs). It has been shown that at high temps. both VG and PG undergo decompn. to low mol. carbonyl compds., including the carcinogens formaldehyde and acetaldehyde. The aim of this study was to evaluate how various product characteristics, including nicotine solvent and battery output voltage, affect the levels of carbonyls in EC vapor. Methods: Twelve carbonyl compds. were measured in vapors from 10 com. available nicotine solns. and from 3 control solns. composed of pure glycerin, pure propylene glycol, or a mixt. of both solvents (50:50). EC battery output voltage was gradually modified from 3.2 to 4.8 V. Carbonyl compds. were detd. using the HPLC/DAD method. Results: Formaldehyde and acetaldehyde were found in 8 of 13 samples. The amts. of formaldehyde and acetaldehyde in vapors from lower voltage EC were on av. 13- and 807-fold lower than in tobacco smoke, resp. The highest levels of carbonyls were obsd. in vapors generated from PG-based solns. Increasing voltage from 3.2 to 4.8 V resulted in a 4 to more than 200 times increase in formaldehyde, acetaldehyde, and acetone levels. The levels of formaldehyde in vapors from high-voltage device were in the range of levels reported in tobacco smoke. Conclusions: Vapors from EC contain toxic and carcinogenic carbonyl compds. Both solvent and battery output voltage significantly affect levels of carbonyl compds. in EC vapors. High-voltage EC may expose users to high levels of carbonyl compds.
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    42. 42
      Bates, C. D. and Farsalinos, K. E. (2015) E-cigarettes need to be tested for safety under realistic conditions Addiction 110, 1688– 1689 DOI: 10.1111/add.13028
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      Bates, C. D. and Farsalinos, K. E. (2015) Research letter on e-cigarette cancer risk was so misleading it should be retracted Addiction 110, 1686– 1687 DOI: 10.1111/add.13018
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    44. 44
      Gupta, R., Brazier, J., and Moyses, C. (2015) No quantifiable carbonyls, including formaldehyde, detected in Voke® Inhaler J. Liq. Chromatogr. Relat. Technol. 38, 1687– 1690 DOI: 10.1080/10826076.2015.1091978
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      44
      No Quantifiable Carbonyls, Including Formaldehyde, Detected in Voke Inhaler
      Gupta, Ritika; Brazier, Jonathan; Moyses, Chris
      Journal of Liquid Chromatography & Related Technologies (2015), 38 (18), 1687-1690CODEN: JLCTFC; ISSN:1082-6076. (Taylor & Francis, Inc.)
      Carbonyls such as formaldehyde, acetaldehyde, and acrolein have been detected in e-cigarette vapors, with one study (albeit at a higher than the typical voltage) reporting formaldehyde-releasing agents in quantities sufficient to increase the risk of cancer by 5-15 fold when compared with long-term smoking. This study examines the Voke Inhaler for traces of carbonyls and aims to quantify any that are detected in its aerosol. Three batches of five Voke devices each were charged with formulation and allowed to rest for 0, 1, and 24 h resp., before being sampled. Aerosol from each device was extd. using a linear smoking machine and collected by dissoln. into DNPH derivatization soln. Samples of the ext. soln. were analyzed for carbonyls using UHPLC. Results were reported as μg/8 puffs. Samples were analyzed for the presence of formaldehyde, acetaldehyde, acetone, acrolein, propionaldehyde, crotonaldehyde, butan-2-one, and butyraldehyde. At the given LOD, no carbonyls were detected in 13 of the 15 samples tested. Acetaldehyde was detected in two samples, one tested immediately after charging and the other tested 1 h after sampling; however, both samples contained the analyte in quantities below its LOQ (3.18 μg/mL). Among various carbonyls, formaldehyde, in particular, has been identified as a known carcinogen by the IARC and as a probable human carcinogen by the US EPA. The absence of measurable quantities of carbonyls in the Voke Inhaler establishes its clear distinction from e-cigarettes and reflects on a significant advantage of not having a heating element.
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    45. 45
      Guthery, W. (2016) Emissions of toxic carbonyls in an electronic cigarette Beitr. Tabakforsch. Int. 27, 30– 37 DOI: 10.1515/cttr-2016-0005
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      45
      Emissions of Toxic Carbonyls in an Electronic Cigarette
      Guthery, William
      Beitraege zur Tabakforschung International (2016), 27 (1), 30-37CODEN: BTAID3; ISSN:1612-9237. (De Gruyter Open Ltd.)
      Summary : Electronic cigarettes (e-cigs) provide a smoke-free alternative for inhalation of nicotine without the vast array of toxic and carcinogenic combustion products produced by tobacco smoke. Elevated levels of toxic carbonyls may be generated during vaporisation; however, it is unclear whether that is indicative of a fault with the device or is due to the applied conditions of the test. A device, designed and built at this facility, was tested to det. the levels of selected toxic carbonyls. The reservoir was filled with approx. 960 mg of an e-liq. formulation contg. 1.8% (w/v) nicotine. Devices were puffed 200 times in blocks of 40 using a standardised regime consisting of a 55 mL puff vol.; 3 s puff duration; 30 s puff interval; square wave puff profile. Confirmatory testing for nicotine and total aerosol delivery resulted in mean (n = 8) values of 10 mg (RSD 12.3%) and 716 mg (RSD 11.2%), resp. Emissions of toxic carbonyls were highly variable yet were between < 0.1% and 22.9% of expected levels from a Kentucky Ref. Cigarette (K3R4F) puffed 200 times under Health Canada Intense smoking conditions. It has been shown that a device built to a high specification with relatively consistent nicotine and aerosol delivery emits inconsistent levels of carbonyls. The exposure is greatly reduced when compared with lit tobacco products. However, it was obsd. that as the reservoirs neared depletion then emission levels were significantly higher.
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    46. 46
      Geiss, O., Bianchi, I., and Barrero-Moreno, J. (2016) Correlation of volatile carbonyl yields emitted by e-cigarettes with the temperature of the heating coil and the perceived sensorial quality of the generated vapours Int. J. Hyg. Environ. Health 219, 268– 277 DOI: 10.1016/j.ijheh.2016.01.004
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      46
      Correlation of volatile carbonyl yields emitted by e-cigarettes with the temperature of the heating coil and the perceived sensorial quality of the generated vapours
      Geiss, Otmar; Bianchi, Ivana; Barrero-Moreno, Josefa
      International Journal of Hygiene and Environmental Health (2016), 219 (3), 268-277CODEN: IJEHFT; ISSN:1438-4639. (Elsevier GmbH)
      E-liqs. generally contain four main components: nicotine, flavours, water and carrier liqs. The carrier liq. dissolves flavours and nicotine and vaporises at a certain temp. on the atomizer of the e-cigarette. Propylene glycol and glycerol, the principal carriers used in e-liqs., undergo decompn. in contact with the atomizer heating-coil forming volatile carbonyls. Some of these, such as formaldehyde, acetaldehyde and acrolein, are of concern due to their adverse impact on human health when inhaled at sufficient concns. The aim of this study was to correlate the yield of volatile carbonyls emitted by e-cigarettes with the temp. of the heating coil.For this purpose, a popular com. e-liq. was machine-vaped on a third generation e-cigarette which allowed the variation of the output wattage (5-25 W) and therefore the heat generated on the atomizer heating-coil. The temp. of the heating-coil was detd. by IR thermog. and the vapor generated at each temp. underwent subjective sensorial quality evaluation by an experienced vaper.A steep increase in the generated carbonyls was obsd. when applying a battery-output of at least 15 W corresponding to 200-250 °C on the heating coil. However, when considering concns. in each inhaled puff, the short-term indoor air guideline value for formaldehyde was already exceeded at the lowest wattage of 5 W, which is the wattage applied in most 2nd generation e-cigarettes. Concns. of acetaldehyde in each puff were several times below the short-term irritation threshold value for humans. Acrolein was only detected from 20 W upwards. The neg. sensorial quality evaluation by the volunteering vaper of the vapor generated at 20 W demonstrated the unlikelihood that such a wattage would be realistically set by a vaper. This study highlights the importance to develop standardised testing methods for the assessment of carbonyl-emissions and emissions of other potentially harmful compds. from e-cigarettes. The wide variety and variability of products available on the market make the development of such methods and the assocd. standardised testing conditions particularly demanding.
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    47. 47
      Talih, S., Balhas, Z., Salman, R., Karaoghlanian, N., and Shihadeh, A. (2016) Direct dripping”: a high-temperature, high-formaldehyde emission electronic cigarette use method Nicotine Tob. Res. 18, 453– 459 DOI: 10.1093/ntr/ntv080
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      47
      "Direct Dripping": A High-Temperature, High-Formaldehyde Emission Electronic Cigarette Use Method
      Talih Soha; Balhas Zainab; Shihadeh Alan; Salman Rola; Karaoghlanian Nareg
      Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco (2016), 18 (4), 453-9 ISSN:.
      INTRODUCTION: Electronic cigarettes (ECIGs) electrically heat and vaporize a liquid solution to produce an inhalable nicotine-containing aerosol. Normally the electrical heater is fed the liquid via an automatic wick system. Some ECIG users, however, elect to directly drip liquid onto an exposed heater coil, reportedly for greater vapor production and throat hit. Use of such "direct drip atomizers" (DDAs) may involve greater exposure to non-nicotine toxicants due to the potentially higher temperatures reached by the coil. In this study we examined nicotine and volatile aldehyde (VA) emissions from one type of DDA under various use scenarios, and measured heater temperature. METHODS: Aerosols were machine-generated from an NHALER 510 Atomizer powered by an eGo-T battery (Joyetech), using a common PG-based liquid and a fixed puffing regimen. Inter-drip interval, the number of puffs drawn between replenishing the liquid on the coil, was varied from 2-4 puffs/drip. Total particulate matter, nicotine, and VA yields were quantified. Heater temperature was monitored using an infrared camera. RESULTS: Depending on the condition, VA emissions, including formaldehyde, greatly exceeded values previously reported for conventional ECIGs and combustible cigarettes, both per puff and per unit of nicotine yield. Increasing the inter-drip interval resulted in greater VA emissions, and lower total particulate matter and nicotine yields. Maximum heater coil temperature ranged from 130°C to more than 350°C. CONCLUSIONS: Due to the higher temperatures attained, DDAs are inherently likely to produce high toxicant emissions. The diversity of ECIG use methods, including potential off-label methods, should be considered as ECIG regulatory efforts proceed.
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    48. 48
      Jensen, R. P., Luo, W., Pankow, J. F., Strongin, R. M., and Peyton, D. H. (2015) Hidden formaldehyde in e-cigarette aerosols N. Engl. J. Med. 372, 392– 394 DOI: 10.1056/NEJMc1413069
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      Hidden formaldehyde in e-cigarette aerosols
      Jensen, R. Paul; Luo, Wentai; Pankow, James F.; Strongin, Robert M.; Peyton, David H.
      New England Journal of Medicine (2015), 372 (4), 392-394CODEN: NEJMAG; ISSN:1533-4406. (Massachusetts Medical Society)
      There is no expanded citation for this reference.
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    49. 49
      Farsalinos, K. E., Voudris, V., and Poulas, K. (2015) E-cigarettes generate high levels of aldehydes only in ‘dry puff’ conditions Addiction 110, 1352– 1356 DOI: 10.1111/add.12942
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      49
      E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions
      Farsalinos Konstantinos E; Voudris Vassilis; Farsalinos Konstantinos E; Poulas Konstantinos
      Addiction (Abingdon, England) (2015), 110 (8), 1352-6 ISSN:.
      BACKGROUND AND AIMS: Aldehydes are emitted by electronic cigarettes due to thermal decomposition of liquid components. Although elevated levels have been reported with new-generation high-power devices, it is unclear whether they are relevant to true exposure of users (vapers) because overheating produces an unpleasant taste, called a dry puff, which vapers learn to avoid. The aim was to evaluate aldehyde emissions at different power levels associated with normal and dry puff conditions. DESIGN: Two customizable atomizers were prepared so that one (A1) had a double wick, resulting in high liquid supply and lower chance of overheating at high power levels, while the other (A2) was a conventional setup (single wick). Experienced vapers took 4-s puffs at 6.5 watts (W), 7.5 W, 9 W and 10 W power levels with both atomizers and were asked to report whether dry puffs were generated. The atomizers were then attached to a smoking machine and aerosol was trapped. SETTING: Clinic office and analytical chemistry laboratory in Greece. PARTICIPANTS: Seven experienced vapers. MEASUREMENTS: Aldehyde levels were measured in the aerosol. FINDINGS: All vapers identified dry puff conditions at 9 W and 10 W with A2. A1 did not lead to dry puffs at any power level. Minimal amounts of aldehydes per 10 puffs were found at all power levels with A1 (up to 11.3 μg for formaldehyde, 4.5 μg for acetaldehyde and 1.0 μg for acrolein) and at 6.5 W and 7.5 W with A2 (up to 3.7 μg for formaldehyde, 0.8 μg for acetaldehyde and 1.3 μg for acrolein). The levels were increased by 30 to 250 times in dry puff conditions (up to 344.6 μg for formaldehyde, 206.3 μg for acetaldehyde and 210.4 μg for acrolein, P < 0.001), while acetone was detected only in dry puff conditions (up to 22.5 μg). CONCLUSIONS: Electronic cigarettes produce high levels of aldehyde only in dry puff conditions, in which the liquid overheats, causing a strong unpleasant taste that e-cigarette users detect and avoid. Under normal vaping conditions aldehyde emissions are minimal, even in new-generation high-power e-cigarettes.
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      Farsalinos, K. E., Kistler, K. A., Gillman, G., and Voudris, V. (2015) Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins Nicotine Tob. Res. 17, 168– 174 DOI: 10.1093/ntr/ntu176
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      Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins
      Farsalinos, Konstantinos E.; Kistler, Kurt A.; Gillman, Gene; Voudris, Vassilis
      Nicotine & Tobacco Research (2015), 17 (2), 168-174CODEN: NTREF6; ISSN:1462-2203. (Oxford University Press)
      Introduction: The purpose of this study was to evaluate sweet-flavored electronic cigarette (EC) liqs. for the presence of diacetyl (DA) and acetyl propionyl (AP), which are chems. approved for food use but are assocd. with respiratory disease when inhaled. Methods: In total, 159 samples were purchased from 36 manufacturers and retailers in 7 countries. Addnl., 3 liqs. were prepd. by dissolving a concd. flavor sample of known DA and AP levels at 5%, 10%, and 20% concn. in a mixt. of propylene glycol and glycerol. Aerosol produced by an EC was analyzed to det. the concn. of DA and AP. Results: DA and AP were found in 74.2% of the samples, with more samples contg. DA. Similar concns. were found in liq. and aerosol for both chems. The median daily exposure levels were 56 μg/day (IQR: 26-278 μg/day) for DA and 91 μg/day (IQR: 20-432 μg/day) for AP. They were slightly lower than the strict NIOSH-defined safety limits for occupational exposure and 100 and 10 times lower compared with smoking resp.; however, 47.3% of DA and 41.5% of AP-contg. samples exposed consumers to levels higher than the safety limits. Conclusions: DA and AP were found in a large proportion of sweet-flavored EC liqs., with many of them exposing users to higher than safety levels. Their presence in EC liqs. represents an avoidable risk. Proper measures should be taken by EC liq. manufacturers and flavoring suppliers to eliminate these hazards from the products without necessarily limiting the availability of sweet flavors.
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      Allen, J. G., Flanigan, S. S., LeBlanc, M., Vallarino, J., MacNaughton, P., Stewart, J. H., and Christiani, D. C. (2016) Flavouring chemicals in e-cigarettes: diacetyl, 2,3-pentanedione, and acetoin in a sample of 51 products, including fruit-, candy-, and cocktail-flavoured e-cigarettes Environ. Health Perspect. 124, 733– 739 DOI: 10.1289/ehp.1510185
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      European Union (2016) TPD Submission Data Dictionary: electronic cigarettes, Data Dictionary Document version: 1.0.2. https://circabc.europa.eu/sd/a/2935ab99-a719-4e4c-8dfa-c9c86751a074/TPD_submission_data_dictionary_electronic_cigarettes%201.0.2.docx (accessed July 15, 2016).
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      Food and Drug Administration (2016) Extending Authorities to All Tobacco Products, Including E-Cigarettes, Cigars, and Hookah. http://www.fda.gov/TobaccoProducts/Labeling/RulesRegulationsGuidance/ucm388395.htm (accessed May 25, 2016).
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      Flora, J. W., Meruva, N., Huang, C. B., Wilkinson, C. T., Ballentine, R., Smith, D. C., Werley, M. S., and McKinney, W. J. (2016) Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols Regul. Toxicol. Pharmacol. 74, 1– 11 DOI: 10.1016/j.yrtph.2015.11.009
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      Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols
      Flora, Jason W.; Meruva, Naren; Huang, Chorng B.; Wilkinson, Celeste T.; Ballentine, Regina; Smith, Donna C.; Werley, Michael S.; McKinney, Willie J.
      Regulatory Toxicology and Pharmacology (2016), 74 (), 1-11CODEN: RTOPDW; ISSN:0273-2300. (Elsevier Inc.)
      E-cigarettes are gaining popularity in the U. S. as well as in other global markets. Currently, limited published anal. data characterizing e-cigarette formulations (e-liqs.) and aerosols exist. While FDA has not published a harmful and potentially harmful constituent (HPHC) list for e-cigarettes, the HPHC list for currently regulated tobacco products may be useful to anal. characterize e-cigarette aerosols. For example, most e-cigarette formulations contain propylene glycol and glycerin, which may produce aldehydes when heated. In addn., nicotine-related chems. have been previously reported as potential e-cigarette formulation impurities. This study detd. e-liq. formulation impurities and potentially harmful chems. in aerosols of select com. MarkTen e-cigarettes manufd. by NuMark LLC. The potential hazard of the identified formulation impurities and aerosol chems. was also estd. E-cigarettes were machine puffed (4-s duration, 55-mL vol., 30-s intervals) to battery exhaustion to maximize aerosol collection. Aerosols analyzed for carbonyls were collected in 20-puff increments to account for analyte instability. Tobacco specific nitrosamines were measured at levels obsd. in pharmaceutical grade nicotine. Nicotine-related impurities in the e-cigarette formulations were below the identification and qualification thresholds proposed in ICH Guideline Q3B(R2). Levels of potentially harmful chems. detected in the aerosols were detd. to be below published occupational exposure limits.
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      Lauterbach, J. H., Laugesen, M., and Ross, J. D. (2012) Suggested protocol for estimation of harmful and potentially harmful constituents in mainstream aerosols generated by electronic nicotine delivery systems (ENDS). Poster 1860, Society of Toxicology, San Francisco, March 11–15.
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      Lauterbach, J. H. and Laugesen, M. (2012) Comparison of toxicant levels in mainstream aerosols generated by Ruyan® electronic nicotine delivery systems (ENDS) and conventional cigarette products. Poster 1861, Society of Toxicology, San Francisco, March 11–15.
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      Kentucky Tobacco Research & Development Center (2015) University of Kentucky Reference Cigarette 3R4F Preliminary Analysis. https://ctrp.uky.edu/resources/pdf/webdocs/3R4F%20Preliminary%20Analysis.pdf (accessed October 15, 2015).
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      Roemer, E., Schramke, H., Weiler, H., Buettner, A., Kausche, S., Weber, S., Berges, A., Stueber, M., Muench, M., Trelles-Sticken, E., Pype, J., Kohlgrueber, K., Voelkel, H., and Wittke, S. (2012) Mainstream smoke chemistry and in vitro and in vivo toxicity of the reference cigarettes 3R4F and 2R4F Beitr. Tabakforsch. Int. 25, 316– 335 DOI: 10.2478/cttr-2013-0912
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      Mainstream smoke chemistry and in vitro and in vivo toxicity of the reference cigarettes 3R4F and 2R4F
      Roemer, Ewald; Schramke, Heike; Weiler, Horst; Buettner, Ansgar; Kausche, Sandra; Weber, Susanne; Berges, An; Stueber, Markus; Muench, Monja; Trelles-Sticken, Edgar; Pype, Jan; Kohlgrueber, Karola; Voelkel, Hartmut; Wittke, Sandra
      Beitraege zur Tabakforschung International (2012), 25 (1), 316-335CODEN: BTAID3; ISSN:0173-783X. (BTFI Beitraege zur Tabakforschung GmbH)
      A new ref. cigarette, the 3R4F, has been developed to replace the depleting supply of the 2R4F cigarette. The present study was designed to compare mainstream smoke chem. and toxicity of the two ref. cigarettes under the International Organization for Standardization (ISO) machine smoking conditions, and to further compare mainstream smoke chem. and toxicol. activity of the 3R4F cigarette by two different smoking regimens, i.e., the machine smoking conditions specified by ISO and the Health Canada intensive (HCI) smoking conditions. The in vitro cytotoxicity and mutagenicity was detd. in the neutral red uptake assay, the Salmonella reverse mutation assay, and the mouse lymphoma thymidine kinase assay. Addnl., a 90-day nose-only inhalation study in rats was conducted to assess the in vivo toxicity. The comparison of smoke chem. between the two ref. cigarettes found practically the same yields of total particulate matter (TPM), 'tar', nicotine, carbon monoxide, and most other smoke constituents. For both cigarettes, the in vitro cytotoxicity, mutagenicity, and in vivo toxicity showed the expected smoke-related effects compared to controls without smoke exposure. There were no meaningful differences between the 2R4F and 3R4F regarding these toxicol. endpoints. The assessments for the 3R4F cigarette by smoking regimen found as a trivial effect, due to the higher amt. of smoke generated per cigarette under HCI conditions, an increased yield of toxicant and higher toxicol. activity per cigarette. However, per mg TPM, 'tar', or nicotine, the amts. of toxicants and the in vitro toxicity were generally lower under HCI conditions, but the in vivo activity was not different between the two machine smoking conditions. Overall, as the main result, the present study suggests equiv. smoke chem. and in vitro and in vivo toxicity for the 2R4F and 3R4F ref. cigarettes.
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      Costigan, S. and Meredith, C. (2015) An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids Regul. Toxicol. Pharmacol. 72, 361– 369 DOI: 10.1016/j.yrtph.2015.05.018
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      An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids
      Costigan, S.; Meredith, C.
      Regulatory Toxicology and Pharmacology (2015), 72 (2), 361-369CODEN: RTOPDW; ISSN:0273-2300. (Elsevier Inc.)
      Flavor ingredients are an essential part of e-liqs. Their responsible selection and inclusion levels in e-liqs. must be guided by toxicol. principles. We propose an approach to the screening and toxicol. risk assessment of flavor ingredients for e-liqs. The screening involves purity requirements and avoiding ingredients that are carcinogenic, mutagenic or toxic to reprodn. Addnl., owing to the uncertainties involved in potency detn. and the derivation of a tolerable level for respiratory sensitization, we propose excluding respiratory sensitizers. After screening, toxicol. data on the ingredients should be reviewed. Inhalation-specific toxicol. issues, for which no reliable safe levels can currently be derived, can lead to further ingredient exclusions. We discuss the use of toxicol. thresholds of concern for flavours that lack inhalation data suitable for quant. risk assessment. Higher toxicol. thresholds of concern are suggested for flavor ingredients (170 or 980 μg/day) than for contaminant assessment (1.5 μg/day). Anal. detection limits for measurements of potential reaction and thermal breakdown products in vaping aerosol, should be informed by the contaminant threshold. This principle leads us to recommend 5 ng/puff as an appropriate limit of detection for untargeted aerosol measurements.
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      Baker, R. (2002) The development and significance of standards for smoking-machine methodology Beitr. Tabakforsch. Int. 20, 23– 41 DOI: 10.2478/cttr-2013-0728
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      International Organization for Standardization (2012) Routine analytical cigarette-smoking machine – Definitions and standard conditions. ISO 3308:2012, Geneva.
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      WHO Study Group on Tobacco Product Regulation (2008) The Scientific Basis of Tobacco Product Regulation, WHO Technical Report Series 951, ISBN: 978 92 4 120951 9 (accessed May 2016) .
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      Evans, S. E. and Hoffman, A. C. (2014) Electronic cigarettes: abuse liability, topography and subjective effects Tob. Control 23, ii23– ii29 DOI: 10.1136/tobaccocontrol-2013-051489
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      Norton, K. J., June, K. M., and O’Connor, R. J. (2014) Initial puffing behaviors and subjective responses differ between an electronic nicotine delivery system and traditional cigarettes Tob. Induced Dis. 12, 17 DOI: 10.1186/1617-9625-12-17
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      Initial puffing behaviors and subjective responses differ between an electronic nicotine delivery system and traditional cigarettes
      Norton Kaila J; June Kristie M; O'Connor Richard J
      Tobacco induced diseases (2014), 12 (1), 17 ISSN:2070-7266.
      BACKGROUND: Electronic nicotine delivery systems (ENDS) present an emerging issue for tobacco control and data on product use behaviors are limited. METHODS: Participants (N = 38 enrolled; N = 16 compliant) completed three lab visits over 5 days and were asked to abstain from regular cigarettes for 72 hours in favor of ENDS (Smoke 51 TRIO - 3 piece, First Generation with 11 mg/ml filters). Lab visits included measurement of exhaled carbon monoxide (CO) and salivary cotinine concentration, questionnaire measures of regular cigarette craving after the 72 hour abstinence, and subjective product effects. Participants used a topography device to record puff volume, duration, flow rate, and inter-puff interval. RESULTS: Analyses revealed significant differences across products in puff count, average volume, total volume and inter-puff interval, with ENDS broadly showing a more intensive smoking pattern. Cigarette craving scores dropped significantly after smoking regular cigarettes, but not ENDS (p = .001), and subjective measures showed ENDS rated less favorably. CO boost, after ENDS use, decreased significantly (p < .001), and saliva cotinine significantly dropped between visits 1 and 3 (p < 0.001) after ENDS use relative to after cigarette smoking. For compliant and non-compliant participants, there was an average 82.0% [V1 - 16.1 cpd; V3 - 2.9 cpd] and average 73.9% [V1 - 20.3 cpd; V3 - 5.3 cpd] reduction in regular cigarette use per day during the ENDS trial period, respectively. CONCLUSIONS: The ENDS were smoked more intensively than own brand cigarettes, but delivered significantly less nicotineand were less satisfying. These findings have implications for the viability of certain ENDS as alternatives to cigarettes.
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      Behar, R. Z., Hua, M., and Talbot, P. (2015) Puffing topography and nicotine intake of electronic cigarette users PLoS One 10, e0117222 DOI: 10.1371/journal.pone.0117222
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      Spindle, T. R., Breland, A. B., Karaoghlanian, N. V., Shihadeh, A. L., and Eissenberg, T. (2015) Preliminary results of an examination of electronic cigarette user puff topography: the effect of a mouthpiece-based topography measurement device on plasma nicotine and subjective effects Nicotine Tob. Res. 17, 142– 149 DOI: 10.1093/ntr/ntu186
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      Preliminary results of an examination of electronic cigarette user puff topography: the effect of a mouthpiece-based topography measurement device on plasma nicotine and subjective effects
      Spindle, Tory R.; Breland, Alison B.; Karaoghlanian, Nareg V.; Shihadeh, Alan L.; Eissenberg, Thomas
      Nicotine & Tobacco Research (2015), 17 (2), 142-149CODEN: NTREF6; ISSN:1462-2203. (Oxford University Press)
      Electronic cigarettes (ECIGs) heat a nicotine-contg. soln.; the resulting aerosol is inhaled by the user. Nicotine delivery may be affected by users' puffing behavior (puff topog.), and little is known about the puff topog. of ECIG users. Puff topog. can be measured using mouthpiece-based computerized systems. However, the extent to which a mouthpiece influences nicotine delivery and subjective effects in ECIG users is unknown. Methods: Plasma nicotine concn., heart rate, and subjective effects were measured in 13 experienced ECIG users who used their preferred ECIG and liq. (≥12 mg/mL nicotine) during 2 sessions (with or without a mouthpiece). In both sessions, participants completed an ECIG use session in which they were instructed to take 10 puffs with 30-s inter-puff intervals. Puff topog. was recorded in the mouthpiece condition. Almost all measures of the effects of ECIG use were independent of topog. measurement. Collapsed across session, mean plasma nicotine concn. increased by 16.8 ng/mL, and mean heart rate increased by 8.5 bpm (ps < .05). Withdrawal symptoms decreased significantly after ECIG use. Participants reported that the mouthpiece affected awareness and made ECIG use more difficult. Relative to previously reported data for tobacco cigarette smokers using similar topog. measurement equipment, ECIG-using participants took larger and longer puffs with lower flow rates. In experienced ECIG users, measuring ECIG topog. did not influence ECI Gassocd. nicotine delivery or most measures of withdrawal suppression. Topog. measurement systems will need to account for the low flow rates obsd. for ECIG users.
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      Robinson, R. J., Hensel, E. C., Morabito, P. N., and Roundtree, K. A. (2015) Electronic cigarette topography in the natural environment PLoS One 10, e0129296 DOI: 10.1371/journal.pone.0129296
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      Electronic cigarette topography in thec natural environment
      Robinson, R. J.; Hensel, E. C.; Morabito, P. N.; Roundtree, K. A.
      PLoS One (2015), 10 (6), e0129296/1-e0129296/14CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
      This paper presents the results of a clin., observational, descriptive study to quantify the use patterns of electronic cigarette users in their natural environment. Previously published work regarding puff topog. has been widely indirect in nature, and qual. rather than quant., with the exception of three studies conducted in a lab. environment for limited amts. of time. The current study quantifies the variation in puffing behaviors among users as well as the variation for a given user throughout the course of a day. Puff topog. characteristics computed for each puffing session by each subject include the no. of subject puffs per puffing session, the mean puff duration per session, the mean puff flow rate per session, the mean puff vol. per session, and the cumulative puff vol. per session. The same puff topog. characteristics are computed across all puffing sessions by each single subject and across all subjects in the study cohort. Results indicate significant inter-subject variability with regard to puffing topog., suggesting that a range of representative puffing topog. patterns should be used to drive machine-puffed electronic cigarette aerosol evaluation systems.
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      Cheng, T. (2013) Chemical evaluation of electronic cigarettes Tob. Control 23 (Suppl. 2) ii11– ii17 DOI: 10.1136/tobaccocontrol-2013-051482
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      Hua, M., Alfi, M., and Talbot, P. (2013) Health-related effects reported by electronic cigarette users in online forums J. Med. Internet Res. 15, e59 DOI: 10.2196/jmir.2324
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      Farsalinos, K. E., Romagna, G., Tsiapras, D., Kyrzopoulos, S., and Voudris, V. (2013) Evaluation of electronic cigarette use (vaping) topography and estimation of liquid consumption: implications for research protocol standards definition and for public health authorities’ regulation Int. J. Environ. Res. Public Health 10, 2500– 2514 DOI: 10.3390/ijerph10062500
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      70
      Evaluation of electronic cigarette use (vaping) topography and estimation of liquid consumption: implications for research protocol standards definition and for public health authorities' regulation
      Farsalinos Konstantinos E; Romagna Giorgio; Tsiapras Dimitris; Kyrzopoulos Stamatis; Voudris Vassilis
      International journal of environmental research and public health (2013), 10 (6), 2500-14 ISSN:.
      BACKGROUND: Although millions of people are using electronic cigarettes (ECs) and research on this topic has intensified in recent years, the pattern of EC use has not been systematically studied. Additionally, no comparative measure of exposure and nicotine delivery between EC and tobacco cigarette or nicotine replacement therapy (NRTs) has been established. This is important, especially in the context of the proposal for a new Tobacco Product Directive issued by the European Commission. METHODS: A second generation EC device, consisting of a higher capacity battery and tank atomiser design compared to smaller cigarette-like batteries and cartomizers, and a 9 mg/mL nicotine-concentration liquid were used in this study. Eighty subjects were recruited; 45 experienced EC users and 35 smokers. EC users were video-recorded when using the device (ECIG group), while smokers were recorded when smoking (SM-S group) and when using the EC (SM-E group) in a randomized cross-over design. Puff, inhalation and exhalation duration were measured. Additionally, the amount of EC liquid consumed by experienced EC users was measured at 5 min (similar to the time needed to smoke one tobacco cigarette) and at 20 min (similar to the time needed for a nicotine inhaler to deliver 4 mg nicotine). RESULTS: Puff duration was significantly higher in ECIG (4.2 ± 0.7 s) compared to SM-S (2.1 ± 0.4 s) and SM-E (2.3 ± 0.5 s), while inhalation time was lower (1.3 ± 0.4, 2.1 ± 0.4 and 2.1 ± 0.4 respectively). No difference was observed in exhalation duration. EC users took 13 puffs and consumed 62 ± 16 mg liquid in 5 min; they took 43 puffs and consumed 219 ± 56 mg liquid in 20 min. Nicotine delivery was estimated at 0.46 ± 0.12 mg after 5 min and 1.63 ± 0.41 mg after 20 min of use. Therefore, 20.8 mg/mL and 23.8 mg/mL nicotine-containing liquids would deliver 1 mg of nicotine in 5 min and 4 mg nicotine in 20 min, respectively. Since the ISO method significantly underestimates nicotine delivery by tobacco cigarettes, it seems that liquids with even higher than 24 mg/mL nicotine concentration would be comparable to one tobacco cigarette. CONCLUSIONS: EC use topography is significantly different compared to smoking. Four-second puffs with 20-30 s interpuff interval should be used when assessing EC effects in laboratory experiments, provided that the equipment used does not get overheated. Based on the characteristics of the device used in this study, a 20 mg/mL nicotine concentration liquid would be needed in order to deliver nicotine at amounts similar to the maximum allowable content of one tobacco cigarette (as measured by the ISO 3308 method). The results of this study do not support the statement of the European Commission Tobacco Product Directive that liquids with nicotine concentration of 4 mg/mL are comparable to NRTs in the amount of nicotine delivered to the user.
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      CORESTA (2015) 2014 Electronic cigarette aerosol parameters study. https://www.coresta.org/sites/default/files/technical_documents/main/ECIG-CTR_ECigAerosolParameters-2014Study_March2015.pdf (accessed May 17, 2016).
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      Counts, M. E., Hsu, F. S., and Tewes, F. J. (2006) Development of a commercial cigarette “market map” comparison methodology for evaluating new or non-conventional cigarettes Regul. Toxicol. Pharmacol. 46, 225– 224 DOI: 10.1016/j.yrtph.2006.07.002
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      Development of a commercial cigarette "market map" comparison methodology for evaluating new or non-conventional cigarettes
      Counts, M. E.; Hsu, F. S.; Tewes, F. J.
      Regulatory Toxicology and Pharmacology (2006), 46 (3), 225-242CODEN: RTOPDW; ISSN:0273-2300. (Elsevier)
      A "market map" comparison methodol. for cigarette smoke chem. yields is presented. Federal Trade Commission machine-method smoke chem. was detd. for a range of filtered cigarettes from the US marketplace. These data were used to develop illustrative market maps for each smoke constituent as anal. tools for comparing new or non-conventional cigarettes to a sampling of the broader range of marketplace cigarettes. Each market map contained best-est. "market-means," showing the relationship between com. cigarette constituent and tar yields, and yield "market ranges" defined by prediction intervals. These market map means and ranges are the basis for comparing new cigarette smoke yields to those of conventional cigarettes. The potential utility of market maps for evaluating differences in smoke chem. was demonstrated with 1R4F and 2R4F Kentucky ref. cigarettes, an Accord cigarette, and an Advance cigarette. Conventional cigarette tobacco nicotine, nitrate, sol. ammonia, and tobacco specific nitrosamine levels are reported. Differences among conventional cigarette constituent yields at similar tar levels were explained in part by the chem. compn. range of those cigarette tobaccos. The study also included a comparison of smoke constituent yields and in vitro smoke cytotoxicity and mutagenicity assay results for the 1R4F Kentucky ref. cigarette and its replacement 2R4F. Significant smoke yield differences were noted for lead, NNK, and NNN. The majority of their smoke constituent yields were within the market range developed from the sampled conventional cigarettes. Within the sensitivity and specificity of the in vitro bioassays used, smoke toxic activity differences for the two ref. cigarettes were not statistically significant. These results add to the limited information available for the 2R4F ref. cigarette.
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      International Organization for Standardization (2005) General requirements for the competence of testing and calibration laboratories. ISO/IEC 17025:2005, Geneva.
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      Journal of Analytical Atomic Spectrometry (2016), 31 (9), 1818-1829CODEN: JASPE2; ISSN:0267-9477. (Royal Society of Chemistry)
      Speciation data for chromium in tobacco products, as obtained by complementary HPLC-ICP-MS and synchrotron-based X-ray Absorption Near-Edge Structure spectroscopy (XANES), are presented for the first time. Non-denaturing extn. conditions were investigated to avoid Cr species redox inter-conversion before anal. of exts. using HPLC-ICP-MS. Methodol. based on HPLC-ICP-MS, which is compatible with the extn. conditions, was developed for sepn. and detection of inorg. Cr species such as Cr(III) and Cr(VI) in aq. std. solns. The instrumental limits of detection (3σ criterion) obtained for Cr(III) and Cr(VI) were 0.12 and 0.08 ng g-1 Cr, resp. The total Cr extd. from 3R4F cut tobacco with water was around 10% of the total Cr in the solid (1949 ± 171 ng g-1 of Cr on a dry wt. basis), with 75% of the aq. Cr assocd. with species of mol. mass > 3 kDa. Cr(III) was the main identified species in the tobacco exts. using HPLC-ICP-MS, while Cr(VI) could not be detected. In situ XANES anal. revealed that the cut tobacco from 3R4F ref. cigarettes contained only Cr(III). Following leaching with water, leaching with sodium dodecylsulfate (SDS) on the solid residue led to extn. of a further 10% of the Cr contained in the solid tobacco. The total Cr data obtained by ICP-MS for HNO3 and HNO3/HF acid digests of 3R4F cut tobacco suggested that addnl. 12% of the total Cr in the solid appears to be assocd. with silicates, which are known to occur naturally in tobacco products. Although Cr species could not be detected in water leachates from 3R4F smoke condensates using the HPLC-ICP-MS method developed here, XANES measurements identified Cr(III) as the main Cr species present in cigarette smoke condensate, with no detectable Cr(VI). HPLC-ICP-MS data obtained for smoke condensates from cigarettes spiked with Cr(III) before smoke collection revealed that Cr(III) is the main Cr species in present the water sol. fraction of the condensate. Spiking expts. demonstrated that Cr(VI) was highly unstable in trapped smoke condensate. In this work no evidence was obsd. for the presence of Cr(VI) in mainstream smoke generated from 3R4F cigarettes.
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      Dehydration of glycerol soln. and further oxidn. have been investigated with different mixed oxide catalysts. Among them, iron phosphates were found to be highly active and selective toward acrolein. Glycerol conversion was nearly complete and acrolein yields reach 80-90% after 5 h of test. Fresh and used catalysts were also characterized by different techniques (XRD, SEM, BET and TGA-DSC). Pure and well-defined structures were found more stable than relatively poor cryst. phase. Distribution of products changes during the deactivation of the catalyst, leading to byproducts such as acetol, propanal and coke deposit on the surface of the catalyst, indicating a modification of the mechanism. Introducing some oxygen in the feed allowed decreasing the amt. of those byproducts, but oxidn. products appeared such as acetic acid or COx on detriment of the yield in acrolein. Using appropriate mixed oxide catalysts such as molybdenum/tungsten vanadium based catalysts showed interesting performances to obtain acrylic acid directly from glycerol.
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      There is a drive toward the mandated lowering and reporting of selected toxicants in tobacco smoke. Several studies have quantified the mainstream cigarette emissions of toxicants, providing benchmark levels. Few, however, have examd. how measured toxicant levels within a single product vary over time due to natural variation in the tobacco, manufg. and measurement. In a single center anal., key toxicants were measured in the tobacco blend and smoke of 3R4F ref. cigarette and three com. products, each sampled monthly for 10 mo. For most analytes, monthly variation was low (coeff. of variation <15%); but higher (≥20%) for some compds. present at low (ppb) levels. Reporting toxicant emissions as a ratio to nicotine increased the monthly variation of the 9 analytes proposed for mandated lowering, by 1-2 percentage points. Variation in toxicant levels was generally 1.5-1.7-fold higher in com. cigarettes compared with 3R4F over the 10-mo period, but increased up to 3.5-fold for analytes measured at ppb level. The potential error (2CV) assocd. with single-point-in-time sampling averaged ∼20%. Together, these data demonstrate that measurement of emissions from com. cigarettes is assocd. with considerable variation for low-level toxicants. This variation would increase if the analyses were conducted in more than one lab.
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