Background: Concerns over the presence of the diketones 2,4 butanedione (DA) and 2,3 pentanedione (AP) in e-cigarettes arise from their potential to cause respiratory diseases. Their presence in e-liquids is a primary source, but they may potentially be generated by glycerol (VG) and propylene glycol (PG) when heated to produce aerosols. Factors leading to the presence of AP, DA and acetoin (AC) in e-cigarette aerosols were investigated. We quantified direct transfer from e-liquids, examined thermal degradation of major e-liquid constituents VG, PG and 1,3 propanediol (1,3 PD) and the potential for AC, AP and DA production from sugars and flavor additives when heated in e-cigarettes.Method: Transfers of AC, AP and DA from e-liquids to e-cigarette aerosols were quantified by comparing aerosol concentrations to e-liquid concentrations. Thermal generation from VG, PG or 1,3 PD e-liquids was investigated by measuring AC, AP and DA emissions as a function of temperature in an e-cigarette. Thermal generation of AC, AP and DA from sugars was examined by aerosolising e-liquids containing sucrose, fructose or glucose in an e-cigarette. Pyrolytic formation of AP and DA from a range of common flavors was assessed using flash pyrolysis techniques.Results: AC transfer efficiency was >90%, while AP and DA were transferred less efficiently (65%) indicating losses during aerosolisation. Quantifiable levels of DA were generated from VG and PG, and to a lesser extent 1,3 PD at coil temperatures >300°C. Above 350°C AP was generated from VG and 1,3 PD but not PG. AC was not generated from major constituents, although low levels were generated by thermal reduction of DA. Aerosols from e-liquids containing sucrose contained quantifiable (>6 ng/puff) levels of DA at all sucrose concentrations tested, with DA emissions increasing with increasing device power and concentration. 1% glucose, fructose or sucrose e-liquids gave comparable DA emissions. Furanose ring compounds also generate DA and AP when heated to 250°C.Conclusions: In addition to less than quantitative direct transfer from the e-liquid, DA and AP can be present in the e-cigarette aerosol due to thermal decomposition reactions of glycols, sugars and furanonse ring flavors under e-cigarette operating conditions.

Background: E-cigarette designs, materials, and ingredients are continually evolving, with cotton wicks and diverse coil materials emerging as the popular components of atomisers. Another recent development is the use of nicotine salts in e-liquids to replicate the form of nicotine found in cigarette smoke, which may help cigarette smokers to transition to e-cigarettes. However, scientific understanding of the impact of such innovations on e-cigarette aerosol chemistry is limited. Methods: To address these knowledge gaps, we have conducted a comparative study analyzing relevant toxicant emissions from five e-cigarettes varying in wick, atomiser coil, and benzoic acid content and two tobacco cigarettes, quantifying 97 aerosol constituents and 84 smoke compounds, respectively. Our focus was the potential for benzoic acid in e-liquids and cotton wicks to form aerosol toxicants through thermal degradation reactions, and the potential for nickel-iron alloy coils to catalyze degradation of aerosol formers. In addition, we analyzed e-cigarette emissions for 19 flavor compounds, thermal decomposition products, and e-liquid contaminants that the FDA has recently proposed adding to the established list of Harmful and Potentially Harmful Constituents (HPHCs) in tobacco products. Results: Analyses for benzene and phenol showed no evidence of the thermal decomposition of benzoic acid in the e-cigarettes tested. Measurements of cotton decomposition products, such as carbonyls, hydrocarbons, aromatics, and PAHs, further indicated that cotton wicks can be used without thermal degradation in suitable e-cigarette designs. No evidence was found for enhanced thermal decomposition of propylene glycol or glycerol by the nickel-iron coil. Sixteen of the 19 FDA-proposed compounds were not detected in the e-cigarettes. Comparing toxicant emissions from e-cigarettes and tobacco cigarettes showed that levels of the nine WHO TobReg priority cigarette smoke toxicants were more than 99% lower in the aerosols from each of five e-cigarettes as compared with the commercial and reference cigarettes. Conclusions: Despite continuing evolution in design, components and ingredients, e-cigarettes continue to offer significantly lower toxicant exposure alternatives to cigarette smoking.

A four-arm study was undertaken in Japan to determine the puffing topography, mouth level exposure and average daily consumption by consumers of the tobacco heating products (THPs): the non-mentholated THP1.0(T), the mentholated THP1.0(M) and a tobacco heating system (THS). The extent of lip blocking of air inlet holes while using THP1.0(T) was also assessed. Groups 1, 2, and 4 included smokers, and group 3 included regular THP users. Smokers of 7-8 mg ISO nicotine free dry particulate matter (NFDPM) non-mentholated cigarettes took on average larger mean puff volumes from THPs than from conventional cigarettes, but puff numbers and durations were similar. Mouth level exposure to NFDPM and nicotine levels were significantly lower when using THPs than conventional cigarettes. Similar trends were observed among smokers of 7-8 mg ISO NFDPM mentholated cigarettes who used mentholated cigarettes and THP1.0(M). Regular users of commercial THS had similar puffing behaviours irrespective of whether they were using THS or THP1.0(T), except for mean puff volume which was lower with THP1.0(T). No smokers blocked the air inlet holes when using THP1.0(T). The puffing topography results support the machine puffing regime used to generate toxicant emissions data and in vitro toxicology testing.

BACKGROUND:Modified-risk tobacco products (MRTPs) are being developed that may contribute to tobacco harm reduction. To support reduced exposure or risk claims, a scientific framework needs to be developed to assess the validity of claims and monitor consumers after product launch. We calculated reference change values (RCVs) for biomarker of exposure (BoE): salivary cotinine and hydroxycotinine; and urinary total nicotine equivalents, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and creatinine. Mouth-level exposure (MLE) to nicotine and tar were also recorded in an ambulatory setting to characterise variation among smokers in their everyday environment.METHODS:This non-residential, observational study was conducted over 3.5 years across 10 sites in Germany. Smokers of the same commercial 10 mg ISO tar product were included in the study (N=1011). Urine samples, questionnaires and cigarette filters were collected every 6 months for a total of seven timepoints.RESULTS:Greater variability in BoEs was observed compared with confined clinical studies. Gaussian distributed data showed 2-sided values over 100%, which are uninformative for decreases. The proportion of significant changes increased slightly among switchers, probably as a result of additional variability due to the range of products used post-switching. Overall proportions of changes remained small, consistent with literature reporting that when switching to a different tar yield cigarette, smokers partially compensate by changing their smoking behaviour.CONCLUSION:Variability estimates and RCVs can be useful for monitoring subjects' BoE and MLE endpoints in longitudinal smoking studies where subjects are followed in their own environment and to aid sample size calculation of studies involving these endpoints.

With the rapidly rising popularity and substantial evolution of electronic cigarettes (e-cigarettes) in the past 5–6 years, how these devices are used by vapers and consumers’ exposure to aerosol emissions need to be understood. We used puffing topography to measure directly product use. We adapted a cigarette puffing topography device for use with e-cigarettes. We performed validation using air and e-cigarette aerosol under multiple regimes. Consumer puffing topography was measured for 60 vapers provided with rechargeable “cig-a-like” or larger button-activated e-cigarettes, to use ad-libitum in two sessions. Under all regimes, air puff volumes were within 1 mL of the target and aerosol volumes within 5 mL for all device types, serving to validate the device. Vapers’ mean puff durations (2.0 s and 2.2 s) were similar with both types of e-cigarette, but mean puff volumes (52.2 mL and 83.0 mL) and mean inter-puff intervals (23.2 s and 29.3 s) differed significantly. The differing data show that product characteristics influence puffing topography and, therefore, the results obtained from a given e-cigarette might not read across to other products. Understanding the factors that affect puffing topography will be important for standardising testing protocols for e-cigarette emissions.

A challenge in investigating the effect of public health policies on cigarette consumption and exposure arises from variation in a smoker's exposure from cigarette to cigarette and the considerable differences between smokers. In addition, limited data are available on the effects of spontaneous product switching on a smoker's cigarette consumption and exposure to smoke constituents. Over 1000 adult smokers of the same commercial 10mg International Organization for Standardization (ISO) tar yield cigarette were recruited into the non-residential, longitudinal study across 10 cities in Germany. Cigarette consumption, mouth level exposure to tar and nicotine and biomarkers of exposure to nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone were measured every 6months over a 3 and a half year period. Cigarette consumption remained stable through the study period and did not vary significantly when smokers spontaneously switched products. Mouth level exposure decreased for smokers (n=111) who switched to cigarettes of 7mg ISO tar yield or lower. In addition, downward trends in mouth level exposure estimates were observed for smokers who did not switch cigarettes. Data from this study illustrate some of the challenges in measuring smokers' long-term exposure to smoke constituents in their everyday environment.

Long-term studies of smokers who switch to lower nicotine yield cigarettes have been identified by the World Health Organization Study Group TobReg and the US Food and Drug Administration as one key area where new knowledge is required to guide science based regulation. The limited number of long-term switching studies have concluded that smokers who switch to lower nicotine yield cigarettes show evidence of partial compensation. Since the European Union tobacco product directive of 2001 introduced tar and nicotine yield ceilings, there has been no long-term observational switching study. To address the limitations of previous studies where smokers were forced switched for relatively short durations, we plan to undertake a long-term study of spontaneous switching which is appropriately powered and includes non-switchers as a control group.