The use of the study EVPs, cartridge- and tank-based, did not generate chemicals at levels that could likely pose health concerns for non-users under the study conditions. Given that nicotine, PG and glycerol are the major constituents in the product, it is not surprising that measurable levels are found in a room where EVPs are used. However the cumulative measurement of levels of these constituents over four hours in the room were relatively small and several-fold below the current published limits for workplace exposure to airborne contaminants [53
]. Room air formaldehyde levels from EVPs were not detectable above the background and/or baseline levels. These results corroborate our analytical chemistry study of aerosol generated from the MarkTen®
prototype e-cigarette [7
] and previous report from two studies where indoor vaping of MarkTen®
prototype e-cigarette did not produce chemicals above quantifiable levels or different from background levels using standard industrial hygiene collection techniques and analytical methods [31
4.1. Room Air Levels from Use of Different Tobacco Products
In Group I, during MarkTen®
use, the mean differences between baseline and product use were statistically significant under pre-specified and/or ad libitum conditions for 7 out of 34 chemicals (nicotine, PG, glycerol, hexaldehyde, benzene, isoprene and toluene). The baseline room air levels of benzene, without any product use, were highly variable, the average levels ranging from 0.5843 μg/m3
(Group I) to 2.2685 μg/m3
(Group IV) (see Supplementary Table S1
). During EVP use, the room air levels of benzene were higher than baseline only for Group 1, however the differences were small and in previous studies this chemical was not detected in aerosol from similar devices [7
]. Furthermore, the average room air levels of benzene were higher under pre-specified use conditions (0.8338 μg/m3
) than under ad lib use (0.540 μg/m3
) compared to the baseline levels of 0.5483 μg/m3
). These values are not bioplausible given that the number of puffs taken during the pre-specified (n
= 720) were far fewer than under ad lib use conditions (n
= 1224). Therefore the apparent higher room air levels of benzene from half as many puffs is likely due to inherent background variability from other sources. Similarly only four out of 34 constituents (nicotine, PG, glycerol and isoprene, and only under pre-specified use conditions) were statistically significantly higher than baseline with the cartridge-based prototype EVP use in Group II. The levels of isoprene during EVP use were within the range of baseline levels across the groups from 6.4588 to 7.8865 μg/m3
. No detectable isoprene has been detected in machine generated aerosols from similar products [7
], suggesting that the isoprene levels observed during EVP use could potentially be an artifact.
The room air levels for five out of 34 constituents in Group II were lower under EVP use conditions compared to baseline, confirming the inherent variability in these measurements. The higher baseline levels explain the apparent negative values for the mean change from baseline for benzene and toluene during the EVP use. These observations suggests that while a sensitive analytical method may be able to detect very low levels of constituents, the room air levels should be interpreted with caution due to the changes in background levels of the target analytes.
In Group III, the mean change from baseline for room air levels, from tank-based EVP use, were statistically significant for 6 out of 34 constituents (nicotine, PG, glycerol, acetaldehyde, benzene and isoprene). The average value for one of the constituents in Group III, benzene, during ad libitum product use was higher than baseline.
On the other hand for CC use in Group IV, 17 out of 34 constituents were statistically significantly higher, confirming the sensitivity of the sample collection and analytical methodology.
4.2. Levels of Different Groups of Chemicals
The cumulative four hour room air levels of the chemicals measured above the LOQ were relatively small. For example, the levels of formaldehyde were highly variable and during EVP use were lower than the background or baseline levels. Although comparison to occupational exposure values has been challenged [56
], a simple comparison provides a perspective. The cumulative four hour room air levels of formaldehyde measured during different EVP product use were several-fold below the maximum occupational exposure limit of 370 μg/m3
set by Federal Republic of Germany (DFG) [57
] and the ACGIH TLV of 120 μg/m3
as well as the limit of 980 μg/m3
set by the Occupational Safety and Health Administration (OSHA) [54
]. Occupational exposure values represent the upper limit values that are not expected to adversely affect workers’ health over their working lives (8 h per day, 5 days per week) and do not specifically include any susceptible sub-groups or populations [56
]. It should also be recognized that various guidelines exist for chemical constituents in indoor air including levels of formaldehyde [58
]. The recommended indoor levels of formaldehyde range from 100 μg/m3
] to 9 μg/m3
] depending on the length of exposure and there has been considerable debate regarding the appropriateness of these levels [60
]. For example, Salthammer et al. [60
] concluded that “Moreover, it seems questionable whether formaldehyde concentrations lower than 20 μg/m3
can be permanently achieved under normal living conditions in urban and rural environments.” Our study demonstrated that the EVP products tested resulted in no increase in background levels of formaldehyde compared to an order of magnitude increase in formaldehyde levels when CC were used. Even if we used the most conservative estimate of OEHHA from the California Environmental Protection Agency of 9 μg/m3
the comparisons should be made in the context that the formaldehyde room air levels from EVP use were all below background.
We performed the study in a specialized chamber that has been previously validated and designed as a stand-alone unit for controlled air exchange rates. We also had established several sampling stations within the room to obtain an accurate assessment of various chemicals in the room air after use of EVPs and CCs. Closer review of the individual sampling stations (see Supplementary Table S2
) indicated that there were no patterns for differences in room air levels in different locations in the room. The sampling ports within the breathing sphere of the participants were not directionally different from the sampling ports farthest in the EC. These observations suggest that other than the three major constituents of EVPs (nicotine, PG and glycerol), minimal if any levels of other chemicals should be expected in a room where EVPs are used.
We used experienced EVP users, rather than smoking machines to generate secondhand aerosol, to best represent real-life conditions. We also measured all chemicals in the chamber RAS with (baseline) and without (background) study participants present in the room, in order to account for other potential human and non-human sources of room air toxicants.
Nicotine was not detected in room air at baseline, even when smokers of CCs were present in the EC. However, when the tested EVPs were used, the level of nicotine in room air was quantified at 0.38 to 2.83 μg/m3
, and was significantly higher than at baseline for each test condition. This is in broad agreement with findings from Czogala et al. [13
] and Schober et al. [35
], who found nicotine levels ranging from 0.6 to 6.23 μg/m3
when study participants used different nicotine-containing EVPs. This is also consistent with the work of St. Helen et al. [18
], who found that EVP users exhale, on average, only 6% of the inhaled nicotine. As can be seen in Figure 3
A, a simple comparison of the 4-h cumulative observed in our study provides some context when compared to the 8-h time weighted average (TWA) exposure limits set by OSHA. The assumptions e.g., cumulative value vs. 8-h TWA and purpose of the OSHA limits should be borne in mind when making the comparisons. The relatively low levels of nicotine observed in the room despite consumption of an estimated 54 to 221 mg of nicotine (based on the amount of e-liquid consumed) suggests that a significant fraction of the nicotine is absorbed by users and very little is exhaled out in the environment. The use of CCs produced much higher levels of nicotine in room air than EVPs, with mean nicotine levels of 40.65 μg/m3
in our study that were comparable to that observed by Schober et al.’s study (31.6 μg/m3
]. Our study presents data collected during pre-specified and ad libitum use of various types of EVPs and cigarettes reflecting a spectrum of use conditions. These observations may be considered more relevant than machine-generated aerosols which significantly overestimates the room levels of nicotine and should be interpreted with extreme caution.
Regarding carrier constituents, both PG and glycerol were also significantly higher than at baseline when all EVPs were used. Significant levels of PG were detected in the room during the baseline period, without product use, demonstrating the ubiquitous nature of PG [62
]. Higher levels of PG and glycerol (317 and 242 μg/m3
respectively) were observed during use of tank-based EVPs. These levels were generally similar in range as reported in another study when study participants used a tank device ad libitum (PG ~ 395 μg/m3
and glycerol ~ 81 μg/m3
]. However, PG was BLOQ in another study where a study participant used a tank device in a test chamber [16
]. These differences could be due to differences in delivery of the tanks used in each study, the differing PG:glycerol ratio in the tank devices, or the sensitivity of the analytical methodologies used. A simple comparison of our four hour cumulative measurements of PG and glycerol with the AIHA Workplace Environmental Exposure Level for PG and OEHHA 2016 indoor air guidelines (Figure 3
B) and OSHA Permissible Exposure Limit for glycerol (Figure 3
C) demonstrate that our four hour cumulative measurements of PG and glycerol are orders of magnitude lower [53
]. In our study, the use of CCs did not produce detectable levels of glycerol, but produced levels of PG that were in the range of the EVP. The CCs tested in the study were commercial products and levels of glycerol and PG were not measured. Acrolein has been reported as a thermal degradation by-product of glycerol [64
]. The lack of detectable acrolein suggests that even if glycerol were pyrolyzed, insufficient amount is exhaled in the air to be of any potential consequence.
Generally greater chemicals levels were measured in room air after use of the tank devices than the cartridge-based products. The greater measured levels may be due to the ~3–5-fold higher amount of e-liquid consumed by the tank users. The change from baseline was negative for some of the chemicals (e.g., formaldehyde and acetaldehyde) suggesting that the room air levels were higher at baseline and/or background. These observations are consistent with other reports of significant background levels present from other sources, including our own study [31
]. For example, formaldehyde exposure can occur from environmental sources (combustion processes, building materials, and tobacco smoke) or in occupational settings (furniture, textile, and construction industries) [65
]. Formaldehyde is also formed endogenously in the cellular metabolic pathways [66
] and has been detected in exhaled breath air samples [67
]. Our results clearly demonstrate that the levels of formaldehyde produced under regular EVP use are below the normal background levels. Under the conditions of the study and with the types of EVPs used, little if any toxicity may be anticipated from exposure to the exhaled chemicals measured.
It is worth noting that none of the four heavy metals were detected significantly above the baseline levels during EVP use. These observations suggest that metals from some of EVP design components, as reviewed in a recent publication [69
], are not released in the room, at least for the types of products tested in this study. Out of all the other tested constituents, acetaldehyde, acetone, hexaldehyde, methyl ethyl ketone, benzene, isoprene and toluene could be quantified at some instances when EVPs were used. The levels of these constituents were either above or below the baseline levels, suggesting intrinsic variability either from analytical measurements or background environmental variability. The latter is not uncommon given that VOCs and aldehydes have often been detected in commercial and residential buildings [70
4.3. Potential Limitations
The results of this study should be interpreted relative to some of the limitations. First, given that EVPs are rapidly evolving and the most recent generation such as “direct drip atomizers” [73
] may have differential aerosol characteristics and room air level results from the use of such products may need to be investigated. However, the results from this study are at least applicable to the cartridge-based and tank-based categories of EVPs tested.
Second, the study was conducted under a single condition of room size and air handling, and does not provide information for different conditions e.g., potential exposure in a closed car. The air exchange rate used in this study was based on typical conditions for office buildings and the data should be interpreted with caution since the room air levels of the chemicals could potentially be higher under a scenario of lower exchange rates of a residential environment. We believe that rather than conducting multiple studies under different conditions, the observations from this study will provide parameters for a computational model [74
] that should readily allow changes of the exposure conditions (multiple people present in the room, different size room, and different air exchange rates etc.).
Third, the relatively small magnitude of the reported values for some chemicals should be interpreted with caution due to inherent variability in the background/baseline values, particularly airborne chemicals due to multiple other confounding sources. The design of this study of including background and baseline measurements may help minimize the possibility of reporting artifactual data for these select chemicals.
Finally, some researchers report measurable surface levels of nicotine from tank-based EVPs when machine-generated aerosol was released in the air [40
]. Observations from machine-generated aerosols are a gross overestimation since nicotine uptake by the user is not taken into consideration. We report that surface nicotine levels in our study during EVP use were not statistically significantly higher compared to baseline. However these results should be interpreted with caution since the limited duration of product use may not reflect the potential accumulation over time. Additionally the petri-dish collection method may have limited utility since actual indoor environments contain many more types of surfaces and materials, which are much more porous and may serve as a reservoir for semi-volatile compounds. However, the measurement of the residue deposited on the petri-dish does provide information regarding likelihood of thirdhand exposure as it reflects the cumulative amount deposited over time. Perhaps the report by Bush et al. might be more realistic since the authors measured surface wipe samples from homes of EVP users [39
]. They report that nicotine levels were not significantly different in homes of EVP users compared to homes of non-tobacco users.