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BackgroundIn response to the popularity of JUUL and other flavored ENDS products among youth, the US Food and Drug Administration issued in February 2020 an enforcement policy to remove all flavoured cartridge/pod-based e-cigarettes from the market except for tobacco and menthol. Subsequent studies found that some former users of the now-removed flavoured JUUL pods (especially cool mint) switched to menthol-flavoured JUUL pods with similar satisfaction.MethodsWe quantified menthol, nicotine, propylene glycol (PG) and vegetable glycerol (VG) in JUUL pod samples (Menthol, Classic Menthol and Cool Mint) that were purchased in 2017, 2018 and 2020 (only Menthol) to evaluate composition differences before and after the enforcement policy. We also analysed the samples to detect other cooling agents using a screening gas chromatography-mass spectrometry headspace method that we developed for this purpose.ResultsNicotine and menthol concentrations were significantly higher in 2020 products than in products from prior years. Moreover, other cooling agents varied across pods. The PG/VG volume ratio was 27/63 in all pods examined.ConclusionThis study shows that concentrations of nicotine and menthol in JUUL products procured over a three year period decreased over time. The findings highlight the challenges of reconstructing product characteristics at the time of manufacture and time of consumption, and suggests the utility of an ENDS product bank that could preserve samples for retrospective studies. They also underscore that manufacturers should be required to release to the public and the scientific community what they know about time- and temperature-dependent degradation of their products.

SignificanceIQOS is a heated tobacco product that has been widely advertised by Philip Morris International (PMI) as a reduced-exposure product compared with cigarettes. Reduced exposure results from reduced emission of toxicants which could be influenced by product constituents and user behaviour. This study aims to assess the influence of user behaviour, including device cleaning and puffing parameters, on toxicant emissions from IQOS.MethodsIQOS aerosols were generated by a smoking machine using the combination of two cleaning protocols (after 1 stick vs 20 sticks) and five puffing regimes (including standard cigarette puffing regimes and IQOS-tailored regimes). The generated aerosols were analysed by targeted methods for phenol and carbonyl quantification, and by chemical screening for the identification of unknown compounds.ResultsPuffing parameters significantly affected phenol and carbonyl emissions while device cleaning had no effect. Harsher puffing conditions like more, longer, and larger puffs yielded higher levels for most toxicant emissions. Comparing the obtained data with data reported by PMI on 50 cigarette brands smoked under different puffing regimes showed various trends for phenol and carbonyl emissions, with IQOS emissions sometimes higher than cigarettes. Also, the chemical screening resulted in the tentative identification of ~100 compounds in the IQOS aerosols (most of limited toxicity data).ConclusionThis study showed that puffing parameters, but not device cleaning, have significant effects on carbonyl, phenol and other emissions. Data analysis highlighted the importance of comparing IQOS emissions with an array of commercial cigarettes tested under different puffing regimes before accepting reduced exposure claims.

IntroductionUse of flavoured pod-mod-like disposable electronic cigarettes (e-cigarettes) has grown rapidly, particularly among cost-sensitive youth and young adults. To date, little is known about their design characteristics and toxicant emissions. In this study, we analysed the electrical and chemical characteristics and nicotine and pulmonary toxicant emission profiles of five commonly available flavoured disposable e-cigarettes and compared these data with those of a JUUL, a cartridge-based e-cigarette device that pod-mod-like disposables emulate in size and shape.MethodsDevice construction, electrical power and liquid composition were determined. Machine-generated aerosol emissions including particulate matter, nicotine, carbonyl compounds and heavy metals were also measured. Liquid and aerosol composition were measured by high-performance liquid chromatography, gas chromatography-mass spectrometry/flame ionisation detection, and inductively coupled plasma mass spectrometry.ResultsWe found that unlike JUUL, disposable devices did not incorporate a microcontroller to regulate electrical power to the heating coil. Quality of construction varied widely. Disposable e-cigarette power ranged between 5 and 9 W and liquid nicotine concentration ranged between 53 and 85 mg/mL (~95% in the protonated form). In 15 puffs, total nicotine yield for the disposables ranged between 1.6 and 6.7 mg, total carbonyls ranged between 28 and 138 µg, and total metals ranged between 1084 and 5804 ng. JUUL emissions were near the floors of all of these ranges.ConclusionsDisposable e-cigarettes are designed with high nicotine concentration liquids and are capable of emitting much higher nicotine and carbonyl species relative to rechargeable look-alike e-cigarettes. These differences are likely due to the lower quality in construction, unreliable labelling and lack of temperature control regulation that limits the power during operation. From a public health perspective, regulating these devices is important to limit user exposure to carbonyls and nicotine, particularly because these devices are popular with youth and young adults.

In 2019, JUUL Labs began marketing in the European Union ‘new technology’ pods that incorporated a new wick that it claimed provided ‘more satisfaction’. In this study, we compared design and materials of construction, electrical characteristics, liquid composition and nicotine and carbonyl emissions of new technology JUUL pods to their predecessors. Consistent with manufacturer’s claims, we found that the new pods incorporated a different wicking material. However, we also found that the new pod design resulted in 50% greater nicotine emissions per puff than its predecessor, despite exhibiting unchanged liquid composition, device geometry and heating coil resistance. We found that when connected to the new technology pods, the JUUL power unit delivered a more consistent voltage to the heating coil. This behaviour suggests that the new coil-wick system resulted in better surface contact between the liquid and the temperature-regulated heating coil. Total carbonyl emissions did not differ across pod generations. That nicotine yields can be greatly altered with a simple substitution of wick material underscores the fragility of regulatory approaches that centre on product design rather than product performance specifications.

SignificanceElectronic cigarettes (e-cigarettes) aerosolise liquids that contain nicotine, propylene glycol, glycerol and appealing flavours. In the USA, regulations have limited the availability of flavoured e-cigarettes in pod-based systems, and further tightening is expected. In response, some e-cigarette users may attempt to make their e-liquids (do-it-yourself, DIY). This study examined toxicant emissions from several aerosolised DIY e-liquids.MethodsDIY additives were identified by reviewing users’ responses to a hypothetical flavour ban, e-cigarette internet forums and DIY mixing internet websites. They include essential oils, cannabidiol, sucralose and ethyl maltol. E-liquids with varying concentrations and combinations of additives and tobacco and menthol flavours were prepared and were used to assess reactive oxygen species (ROS), carbonyl and phenol emissions in machine-generated aerosols.ResultsData showed that adding DIY additives to unflavoured, menthol-flavoured or tobacco-flavoured e-liquids increases toxicant emissions to levels comparable with those from commercial flavoured e-liquids. Varying additive concentrations in e-liquids did not have a consistently significant effect on the tested emissions, yet increasing power yielded significantly higher ROS, carbonyl and phenol emissions for the same additive concentration. Adding nicotine to DIY e-liquids with sucralose yielded increase in some emissions and decrease in others, with freebase nicotine-containing e-liquid giving higher ROS emissions than that with nicotine salt.ConclusionThis study showed that DIY additives can impact aerosol toxicant emissions from e-cigarettes and should be considered by policymakers when restricting commercially available flavoured e-liquids.

The JUUL electronic cigarette (e-cigarette) remains popular in the USA and has a big prevalence among youth. In response to the popularity of JUUL and similar devices among youth, the US Food and Drug Administration issued in February 2020 an enforcement policy to remove all flavoured cartridge/pod-based e-cigarettes from the market except for tobacco and menthol. Subsequent studies showed that some users of the now-removed flavoured JUUL pods (especially cool mint) switched to menthol-flavoured JUUL pods with similar satisfaction.We quantified menthol, nicotine, propylene glycol (PG) and vegetable glycerol (VG) in JUUL pod samples (Menthol, Classic Menthol and Cool Mint) that were purchased in 2017, 2018 and 2020 (only Menthol) to evaluate composition differences before and after the enforcement policy. We also analysed the samples to detect other cooling agents using a screening gas chromatography-mass spectrometry headspace method that we developed for this purpose.Menthol concentration was significantly higher in 2020 products than in products from prior years. Moreover, other cooling agents varied across pods. The PG/VG volume ratio was 27/63 in all pods examined.This study highlights how regulations intended to reduce e-cigarette prevalence among youth may influence changes in tobacco product characteristics in ways that regulators may not have foreseen.

Flavors in electronic cigarette (ECIG) liquids may increase ECIG aerosol toxicity via intact distillation or chemical transformation. For this report, we performed a meta-analysis of the literature to categorize the compounds found in flavored ECIG liquids into a few chemical classes and to predict their possible chemical transformations upon ECIG liquid aerosolization. This analysis allowed us to propose specific correlations between flavoring chemicals and aerosol toxicants. A literature search was conducted in November 2019 using PubMed. Keywords included terms related to ECIGs and flavors. Studies were included if they reported chemical ingredients of flavored liquids and clearly stated the commercial names of these liquids. The obtained data were visualized on a network diagram to show the common chemical compounds identified in flavored ECIG liquids and categorize them into different chemical classes. The systematic literature review included a total of 11 articles. Analysis of the data reported gave a total of 189 flavored liquids and 173 distinct chemical compounds that were categorized into 22 chemical classes according to their functional groups. The subsequent prediction of chemical transformations of these functional groups highlighted the possible correlation of flavor compounds to aerosol toxicants.

Nicotine in electronic cigarette (ECIG) liquids can exist in a free-base or protonated (or “salt”) form. Protonated nicotine is less aversive upon inhalation than free-base nicotine, and many ECIG manufacturers have begun marketing protonated nicotine products, often with high nicotine concentrations. Regulations intended to control ECIG nicotine delivery limit nicotine concentration but do not consider nicotine form. In this study, we systematically examined the effect of nicotine form on nicotine yield for varying powers and liquid vehicles. A Kanger Subox Mini-C tank ECIG (0.5 Ω) was used to generate aerosols at varying powers (5–45 W) from liquid solutions that contained either free-base or protonated nicotine at 15 mg/g concentration, with a liquid vehicle consisting of either propylene glycol (PG) or vegetable glycerin (VG), resulting in four different solutions (free-base/PG, free-base/VG, protonated/PG, and protonated/VG). Nicotine yield was quantified using gas chromatography-mass spectrometry. Nicotine yields were not influenced by nicotine form under any condition investigated. At each power level, PG-based liquids resulted in approximately double the nicotine yield of VG-based liquids. Nicotine concentrations in the aerosols matched those of the parent liquids for both the PG and VG conditions. Increasing power led to greater nicotine yield across all conditions. The amount of nicotine emitted by an ECIG is independent of whether the nicotine is free-base or protonated, however the liquid vehicle has a strong effect on yield. Regulations intended to limit nicotine emissions must consider not only nicotine concentration, but also liquid vehicle and device power.

Electronic cigarettes (ECIGs) have always been promoted as safer alternatives to combustible cigarettes. However, a growing amount of literature shows that while ECIGs do not involve combustion-derived toxicants, thermal degradation of the main constituents of ECIG liquid produces toxicants such as carbonyls. In this study, we report the detection of phenolic compounds in ECIG aerosols using a novel analytical method. The introduced method relies on liquid-liquid extraction to separate phenols from the major constituents of ECIG aerosol: propylene glycol (PG) and vegetable glycerol (VG). Phenol emissions from ECIGs were tested at different powers, puff durations, PG/VG ratios, nicotine benzoate concentrations, and flow rates to assess the influence of these operating parameters on phenol formation. The performance metrics showed that the analytical method has high specificity and reliability to separate and quantify phenolic compounds in ECIG aerosols. Increasing power and puff duration significantly increased all phenol emissions, while flow rate had no significant effects. The phenol profile in the ECIG aerosol was dominated by the unsubstituted phenol that reached comparable levels to those of IQOS, combustible cigarettes, and waterpipe. In contrast, low levels of the more toxic phenolic compounds, like catechol and hydroxyquinone, were quantified in ECIG aerosols. Emission of toxicants is presented, for the first time in this study, as the yield per unit of time, or flux (μg/s), which is more suitable for interstudy and interproduct comparison. This work demonstrates a robust analytical method for isolating and quantifying phenol emissions in ECIG aerosols. Using this method, the study shows that phenols, which are not present in the simple solution of nicotine benzoate dissolved in mixtures of PG/VG, are formed upon vaping. Phenol emissions are independent of the nicotine benzoate concentration but significantly correlated with the PG/VG ratio. Emissions increased with power and puff duration, consistent with conditions that lead to a higher temperature and greater thermal degradation.

Electronic nicotine delivery systems (ENDS) continue to rapidly evolve. Current products pose unique challenges and opportunities for researchers and regulators. This commentary aims to highlight research gaps, particularly in toxicity research, and provide guidance on priority research questions for the tobacco regulatory community. Disposable flavoured ENDS have become the most popular device class among youth and may contain higher nicotine levels than JUUL devices. They also exhibit enhanced harmful and potentially harmful constituents production, contain elevated levels of synthetic coolants and pose environmental concerns. Synthetic nicotine and flavour capsules are innovations that have recently enabled the circumvention of Food and Drug Administration oversight. Coil-less ENDS offer the promise of delivering fewer toxicants due to the absence of heating coils, but initial studies show that these products exhibit similar toxicological profiles compared with JUULs. Each of these topic areas requires further research to understand and mitigate their impact on human health, especially their risks to young users.

Some jurisdictions have instituted limits on electronic cigarette (ECIG) liquid nicotine concentration, in an effort to control ECIG nicotine yield, and others are considering following suit. Because ECIG nicotine yield is proportional to the product of liquid nicotine concentration (milligram per millilitre) and device power (watts) regulations that limit liquid nicotine concentration may drive users to adopt higher wattage devices to obtain a desired nicotine yield. In this study we investigated, under various hypothetical regulatory limits on ECIG liquid nicotine concentration, a scenario in which a user of a common ECIG device (SMOK TF-N2) seeks to obtain in 15 puffs the nicotine emissions equivalent to one combustible cigarette (ie, 1.8 mg). We measured total aerosol and carbonyl compound (CC) yields in 15 puffs as a function of power (15–80 W) while all else was held constant. The estimated nicotine concentration needed to achieve combustible cigarette-like nicotine yield at each power level was then computed based on the measured liquid consumption. We found that for a constant nicotine yield of 1.8 mg, reducing the liquid nicotine concentration resulted in greater amount of liquid aerosolised (p

Electronic cigarettes (ECIGs) are appealing in part because of the many flavors of the liquids used in them. Concerns have been raised that some ECIG liquid flavors, especially those that are sweet, are attracting otherwise nicotine-naïve youth to ECIGs. Sucralose is an artificial, non-caloric sweetener that is added to some ECIG liquids. In this study, we evaluated the toxicants, namely isomers of chloropropanols that can be produced when sucralose-containing ECIG liquid is aerosolized. An analytical separation method relying on solid-phase extraction (SPE) to isolate chloropropanols from the propylene glycol/glycerol matrix was developed. Chloropropanols were then derivatized by silylation before they were analyzed on GC-MS. The influence of different ECIG operating conditions on the generation of chloropropanols was studied by varying ECIG device design and power output and also the sucralose concentration of the liquid. Heated sucralose-containing ECIG liquids produce two toxic compounds that can be found in the resulting aerosols. The two chloropropanols, 3-monochloro-1,2-propanediol (3-MCPD), and 1,3-dichloropropanol (1,3-DCP) that were detected under all conditions were found to be correlated significantly with liquid sucralose content. Effective regulation of ECIGs will minimize user and bystander exposure to these and other ECIG toxicants. Copyright © 2019 American Association for Aerosol Research

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

ObjectiveTo highlight the general features of IQOS literature focusing on the chemical analysis of IQOS emissions.Data sourcesPubMed, Web of Science and Scopus databases were searched on 8 November 2021 using the terms ‘heated tobacco product’, ‘heat-not-burn’, ‘IQOS’ and ‘tobacco heating system’ with time restriction (2010–2021). The search yielded 5480 records.Study selectionRelevant publications on topics related to IQOS assessment were retrieved (n=341). Two reviewers worked separately and reached agreement by consensus.Data extractionData on author affiliation and funding, article type and date of publication were extracted. Publications were categorised depending on their focus and outcomes. Data on IQOS emissions from the chemical analysis category were extracted.Data synthesisOf the included publications, 25% were published by Philip Morris International (PMI) affiliates or PMI-funded studies. PMI-sponsored publications on emissions, toxicology assessments and health effects were comparable in number to those reported by independent research, in contrast to publications on IQOS use, market trends and regulation. Data on nicotine yield, carbonyl emissions, other mainstream emissions, secondhand emissions and IQOS waste were compared between data sources to highlight agreement or disagreement between PMI-sponsored and independent research.ConclusionsOur analysis showed agreement between the data sources on nicotine yield from IQOS under the same puffing conditions. Also, both sources agreed that IQOS emits significantly reduced levels of some emissions compared with combustible cigarettes. However, independent studies and examination of PMI’s data showed significant increases in other emissions from and beyond the Food and Drug Administration’s harmful and potentially harmful constituents list.

Electronic cigarettes (ECIGs) are a class of tobacco products that emit a nicotine-containing aerosol by heating and vaporizing a liquid. Apart from initiating nicotine addiction in nonsmokers, a persistent concern about these products is that their emissions often include high levels of carbonyl species, toxicants thought to cause most noncancer pulmonary diseases in smokers. This study examined whether the phenomenon of film boiling can account for observations of high carbonyl emissions under certain operating conditions and, if so, whether film boiling theory can be invoked to predict conditions where high carbonyl emissions are likely. We measured the critical heat flux for several common heating materials and liquids and carbonyl emissions for several ECIG types while varying the power. We found that emissions rise drastically whenever the power exceeds the value corresponding to the critical heat flux. While limiting the heat flux to below this threshold can greatly reduce carbonyl exposure, ECIG manufacturer operating instructions often exceed it. Product regulations that limit heat flux may reduce the public health burden of electronic cigarette use.

Introduction IQOS is an emerging heated tobacco product marketed by Philip Morris International (PMI). Because the tobacco in IQOS is electrically heated and not combusted, PMI claims that it generates significantly lower toxicant levels than combustible cigarettes. To date, a few independent studies have addressed IQOS toxicant emissions, and none have reported reactive oxygen species (ROS), and the form of the nicotine emitted by the device. Methods In this study, IQOS aerosol was generated using a custom-made puffing machine. Two puffing regimens were used: Health Canada Intense and ISO. ROS, carbonyl compounds (CCs), and total nicotine and its partitioning between free-base and protonated forms were quantified in the IQOS aerosol by fluorescence, high-performance liquid chromatography, and gas chromatography, respectively. The same toxicants were also quantified in combustible cigarette aerosols for comparison. In addition, propylene glycol and vegetable glycerin were also measured in the IQOS tobacco and aerosol. Results IQOS and combustible cigarettes were found to emit similar quantities of total and free-base nicotine. IQOS total ROS (6.26 ± 2.72 nmol H2O2/session) and CC emissions (472 ± 19 µg/session) were significant, but 85% and 77% lower than levels emitted by combustible cigarettes. Conclusions IQOS emits harmful constituents that are linked to cancer, pulmonary disease, and addiction in cigarette smokers. For a given nicotine intake, inhalation exposure to ROS and CCs from IQOS is likely to be significantly less than that for combustible cigarettes. Implications IQOS is PMI’s new heated tobacco product. PMI claims that because IQOS heats and does not burn tobacco it generates low toxicant yields. We found that one IQOS stick can emit similar free-base and total nicotine yields as a combustible cigarette. A pack-a-day equivalent user of IQOS may experience significant inhalation exposure of ROS and CCs compared to background air. However, substituting IQOS for combustible cigarettes will likely result in far lower ROS and carbonyl inhalation exposure for a given daily nicotine intake.

Electronic cigarettes (ECIGs) are battery-powered devices that heat and vaporize solutions containing propylene glycol (PG) and/or vegetable glycerin (VG), nicotine and possible trace flavorants to produce an inhalable aerosol. The heating process can lead to the formation of reactive oxygen species (ROS), which are linked to various oxidative damage-initiated diseases. Several studies in the literature have addressed ROS emissions in ECIG aerosols, but the effects of power, ECIG device design and liquid composition on ROS are relatively unknown. In addition, ROS emissions have not been examined in the emerging high power, sub-Ohm device (SOD) category. In this study, an acellular 2',7'-dichlorofluorescin (DCFH) probe technique was optimized to measure ROS in ECIG aerosols. The technique was deployed to measure ROS emissions in SOD and supra-Ohm ECIGs while varying power, heater coil head design and liquid composition (PG/VG ratio and nicotine concentration). Liquids were made from analytical standards of PG, VG and nicotine and contained no flavorants. At high powers, ROS emissions in ECIGs and combustible cigarettes were similar. Across device designs, ROS emissions were uncorrelated with power (R(2) = 0.261) but were highly correlated with power per unit area (R(2) = 0.78). It was noticed that an increase in the VG percentage in the liquid yielded higher ROS flux, and nicotine did not affect ROS emissions. ROS emissions are a function of device design and liquid composition at a given power. For a given liquid composition, a promising metric for predicting ROS emissions across device designs and operating conditions is power per unit area of the heating coil. Importantly, ROS formation is significant even when the ECIG liquid consists of pure analytical solutions of PG and VG; it can therefore be viewed as intrinsic to ECIG operation and not solely a by-product of particular flavorants, contaminants or additives.

IntroductionJUUL is an electronic cigarette (ECIG) with a compact form factor. It is prefilled with a liquid that is advertised to contain a high concentration of nicotine salt. JUUL commands 50% of the US ECIG market share, and its wide popularity with underage users has triggered unprecedented actions by the US FDA. Apart from its nicotine salt-containing liquid and compact form, a salient advertised design feature is a control circuit that limits the heating coil temperature, presumably reducing unwanted toxicants. In this study, several tobacco-flavoured JUUL devices were reverse engineered, and their aerosol emissions were studied.MethodsTotal nicotine and its partitioning (freebase and protonated), propylene glycol/vegetable glycerin (PG/VG) ratio, and carbonyls were quantified by gas chromatography (GC) and high performance liquid chromatography (HPLC). The temperature control functionality of JUUL was investigated using a temperature-controlled bath in which the coil was submerged.ResultsThe liquid nicotine concentration was found to be 69 mg/mL, and the liquid and aerosol PG/VG ratio was found to be 30/70. In 15 puffs, JUUL emitted 2.05 (0.08) mg of nicotine, overwhelmingly in the protonated form. Carbonyl yields were significantly lower than those reported for combustible cigarettes, but similar to other closed-system ECIG devices. The heating coil resistance was 1.6 (0.66) Ohm, while the maximum power delivered by the JUUL device was 8.1 W. The control circuit limited the peak operating temperature to approximately 215C.ConclusionsJUUL emits a high-nicotine concentration aerosol predominantly in the protonated form. JUUL’s nicotine-normalised formaldehyde and total aldehyde yields are lower than other previously studied ECIGs and combustible cigarettes.

In 2018, JUUL entered the UK market, where EU regulations limit liquid nicotine concentration to 20 mg/mL, approximately one-third the level of JUUL products sold in the USA. We hypothesized that JUUL’s UK product was engineered to deliver greater electrical power and boost liquid vaporization such that the net nicotine delivery rate was similar to the US version. We compared electrical characteristics, liquid composition, and aerosol emissions of JUUL devices procured in the USA and the UK. Study outcomes included electrical power, total and freebase nicotine, propylene glycol/vegetable glycerin ratio, carbonyls, and reactive oxygen species. Liquids and aerosols were analyzed by GCMS, HPLC, and fluorescence. Compared to the US version, JUUL UK had approximately one-third the liquid nicotine concentration in the liquid (5.4 vs. 1.6 wt.%) and aerosol (4.7 and 1.3 wt.%). Other than nicotine concentration and yield, we found no differences in any other study outcome, including electrical power. Currently, JUUL UK emits nicotine at a far lower rate than the US product, offering an opportunity to study how this factor impacts user behavior, JUUL uptake, and other population-level outcomes across the two markets.

Introduction Carbonyls, a class of compounds strongly linked to pulmonary disease in smokers, are probably the most reported non-nicotine toxicants found in electronic cigarette (ECIG) aerosols. Reported emissions vary from negligible quantities to those far exceeding combustible cigarettes. Observations of high emissions are commonly attributed to “dry puffing”, whereby the ECIG heating filament runs dry of liquid and reaches temperatures that induce thermal degradation of the ECIG vapor components at the filament’s metal surface. Using a pyrolysis flow reactor, in this study we examined the potential role of surface chemistry in the formation of carbonyl compounds in ECIGs, and whether the different commercially available filament materials could potentially impact their toxicant emissions through catalysis. This information could inform nascent efforts to regulate the design of ECIGs for public health ends. Methods Nitrogen or air saturated with propylene glycol vapor was drawn through a temperature and residence-time controlled tubular quartz pyrolysis flow reactor in which nichrome, Kanthal, or stainless steel ECIG heating filament wires were inserted. A control condition with no inserted wire was also included. Concentrations of carbonyl products at the reactor outlet were measured as a function of temperature, heating filament wire material, and carrier gas composition (N2 vs air). Carbonyls were sampled using DNPH cartridges and analyzed by HPLC. Results ECIG heating filament wires were found to have a strong catalytic effect. Carbonyl formation initiated at temperatures lower than 250 °C in the presence of the metallic wires, compared to 460 °C without them. Carbonyl formation was found to be a function of the material of construction, and whether the wire was new or aged. New nichrome wires were the least reactive, but when aged they exhibited the highest reactivity. Carbonyls were formed via dehydration or oxidation reactions of PG. Conclusions Carbonyl formation chemistry is catalyzed by commonly used ECIG heating filament materials, at temperatures that are well below those expected during “dry puffing”. The variability in the distribution and yield of carbonyl compounds across ECIG filament materials suggests that this heretofore unaccounted variable may partially explain the wide ranges reported in the literature to date. More importantly, it suggests that ECIG construction materials may be an important variable for regulations designed to protect public health.

Electronic cigarettes (ECIGs) electrically heat and aerosolize a liquid containing propylene glycol (PG), vegetable glycerin (VG), flavorants, water, and nicotine. ECIG effects and proposed methods to regulate them are controversial. One regulatory focal point involves nicotine emissions. We describe a mathematical model that predicts ECIG nicotine emissions. The model computes the vaporization rate of individual species by numerically solving the unsteady species and energy conservation equations. To validate model predictions, yields of nicotine, total particulate matter, PG, and VG were measured while manipulating puff topography, electrical power, and liquid composition across 100 conditions. Nicotine flux, the rate at which nicotine is emitted per unit time, was the primary outcome. Across conditions, the measured and computed nicotine flux were highly correlated (r = 0.85, p

Electronic cigarettes (ECIGs) use electricity to power a heating element that aerosolizes a liquid containing solvents, flavorants, and the dependence-producing drug nicotine for user inhalation. ECIGs have evolved rapidly in the past 8 years, and the changes in product design and liquid constituents affect the resulting toxicant yield in the aerosol and delivery to the user. This rapid evolution has been accompanied by dramatic increases in ECIG use prevalence in many countries among adults and, especially, adolescents in the United States. The increased prevalence of ECIGs that deliver nicotine and other toxicants to users' lungs drives a rapidly growing research effort. This review highlights the most recent information regarding the design of ECIGs and their liquid and aerosol constituents, the epidemiology of ECIG use among adolescents and adults (including correlates of ECIG use), and preclinical and clinical research regarding ECIG effects. The current literature suggests a strong rationale for an empirical regulatory approach toward ECIGs that balances any potential ECIG-mediated decreases in health risks for smokers who use them as substitutes for tobacco cigarettes against any increased risks for nonsmokers who may be attracted to them.

Popularity of electronic cigarettes (ECIGs) has increased tremendously among young people, in part due to flavoring additives in ECIG liquids. Pyrazines are an important class of these additives, and their presence in tobacco cigarettes has been correlated with increased acceptability of smoking among smokers and bystanders. Pyrazine use by the tobacco industry is therefore thought to encourage smoking. However, the extent of transfer of pyrazines present in the liquid to aerosols upon vaping remains unclear. We present a simple analytical method to quantify six pyrazine derivatives in liquids and aerosols of ECIGs that allows the isolation of pyrazines from interfering compounds, like nicotine. Standard pyrazine solutions and commercial ECIG samples of different brands and flavors were tested for their pyrazine content in the liquids and in the generated aerosols from these solutions. Testing on ECIG commercial liquids revealed a heterogeneous distribution in the levels and types of pyrazines, with acetyl and alkyl pyrazines present in more than 70% of the samples. This method confirmed that pyrazine additives are common in ECIG and that labels do not usually reflect the type and quantity of pyrazines in the liquid. Pyrazines were not correlated with the nicotine content or the brand of the liquid. The aerosols showed similar pyrazine profiles to their corresponding liquids. The efficiency of transfer of pyrazines into the particle phase was approximately 46%. Therefore, addition of pyrazines to ECIGs should be regulated, because they act synergistically with nicotine to increase product appeal, ease smoking initiation, and discourage cessation. Copyright © 2018 American Association for Aerosol Research

Here, we report a study of two isoelectronic Ir(I) complexes supported by different carboranyl phosphines, bearing either o-carborane or carba-closo-dodecaborate ligand substituents. The neutral Ir(I) complex containing the o-carboranyl phosphine ligand is not isolable and undergoes spontaneous B–H cyclometalation to afford an Ir(III) hydride. In contrast, the anionic Ir(I) complex supported by a phosphine with a carba-closo-dodecaborate ligand R-group is stable towards B–H activation. This divergent reactivity has important implications for the design of carborane containing ligands for catalysis. Both compounds are fully characterized by multinuclear NMR spectroscopy, HRMS spectrometry, and single crystal x-ray diffraction studies.

As with other tobacco aerosols, nicotine delivery from e-cigarettes (ECIG) depends on the total nicotine and its partitioning between free-base (Nic) and protonated (NicH+) forms. Previous studies ...

An emerging category of electronic cigarettes (ECIGs) is sub-Ohm devices (SODs) that operate at ten or more times the power of conventional ECIGs. Because carcinogenic volatile aldehyde (VA) emissions increase sharply with power, SODs may expose users to greater VAs. In this study, we compared VA emissions from several SODs and found that across device, VAs and power were uncorrelated unless power was normalized by coil surface area. VA emissions and liquid consumed were correlated highly. Analyzed in light of EU regulations limiting ECIG liquid nicotine concentration, these findings suggest potential regulatory levers and pitfalls for protecting public health.

The wide pH range reported for electronic cigarette (ECIG) liquids indicates that nicotine may be present in one or more chemical forms. The nicotine form affects the bioavailability and delivery of nicotine from inhaled products. Protonated nicotine is normally associated with counteranions in tobacco products. The chemical and physical properties of counteranions may differently influence the nicotine form and emissions in ECIG aerosols. In this study, we examined how these anions influence nicotine emissions and their evaporation behavior and potential decomposition during ECIG operation. ECIG liquid solutions with equal nicotine concentration and pH but different counteranions (formate, acetate, and citrate) were prepared from analytical standards to assess the effect of the counteranion on nicotine partitioning. High performance liquid and gas chromatography methods were developed to determine the counteranions and the two protonated (NicH+) and free base (Nic) forms of nicotine in commercially avail...

Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products. Here, we review current methods for measuring exposure to new and emerging tobacco products, such as electronic cigarettes, little cigars, water pipes, and cigarillos. Rigorously validated biomarkers specific to these new products have not yet been identified. Here, we discuss the strengths and limitations of current approaches, including whether they provide reliable exposure estimates for new and emerging products. We provide specific guidance for choosing practical and economical biomarkers for different study designs and experimental conditions. Our goal is to help both new and experienced investigators measure exposure to tobacco products accurately and avoid common experimental errors. With the identification of the capacity gaps in biomarker research on new and emerging tobacco products, we hope to provide researchers, policymakers, and funding agencies with a clear action plan for conducting and promoting research on the patterns of use and health effects of these products.

Introduction: Some electronic cigarette (ECIG) users attain tobacco cigarette-like plasma nicotine concentrations, while others do not. Understanding the factors that influence ECIG aerosol nico- tine delivery is relevant to regulation, including product labeling and abuse liability. These factors may include user puff topography, ECIG liquid composition, and ECIG design features. This study addresses how these factors can influence ECIG nicotine yield. Methods: Aerosols were machine generated with 1 type of ECIG cartridge (V4L CoolCart) using 5 distinct puff profiles representing a tobacco cigarette smoker (2-s puff duration, 33-ml/s puff velocity), a slow average ECIG user (4 s, 17 ml/s), a fast average user (4 s, 33 ml/s), a slow extreme user (8 s, 17 ml/s), and a fast extreme user (8 s, 33 ml/s). Output voltage (3.3-5.2 V or 3.0-7.5 W) and e-liquid nicotine concentration (18-36 mg/ml labeled concentration) were varied. A theoretical model was also developed to simulate the ECIG aerosol production process and provide insight into the empirical observations. Results: Nicotine yields from 15 puffs varied by more than 50-fold across conditions. Experienced ECIG user profiles (longer puffs) resulted in higher nicotine yields relative to the tobacco smoker (shorter puffs). Puff velocity had no effect on nicotine yield. Higher nicotine concentration and higher voltages resulted in higher nicotine yields. These results were predicted well by the theoretical model (R 2 = 0.99). Conclusions: Depending on puff conditions and product features, 15 puffs from an ECIG can provide far less or far more nicotine than a single tobacco cigarette. ECIG emissions can be predicted using physical principles, with knowledge of puff topography and a few ECIG device design parameters.

A zwitterionic iridium complex of a phosphine, bearing the carba-closo-dodecaborate anion as a ligand substituent, is reported. When tethered directly to a phosphine ligand, the CB11H11– R group engages in agostic-like bonding, utilizing the B–H bonds adjacent to the carbon atom in the cluster. Evidence for the interactions is observed in solution by variable-temperature NMR and also in the solid state by a single-crystal X-ray diffraction study. The bonding between the cluster and the iridium center has also been analyzed computationally and can be described as a double agostic bonding augmented by an overlap of the skeletal electrons of the cluster with the dz2 orbital of the metal. A significant lengthening of a trans-olefin C–C bond suggests that this ligand substituent has a pronounced trans influence, which is in contrast to the unfunctionalized weakly coordinating HCB11H11– anion.

Significance The wide availability of sweet flavours has been hypothesised as a factor in the popularity of electronic cigarette (ECIG), especially among youth. Saccharides, which are commonly used to impart a sweet flavour to ECIG liquids, thermally degrade to produce toxic compounds, like aldehydes and furans. This study investigates the formation of furanic compounds in aerosols when ECIG liquid solutions of varying sweetener concentrations are vaped under different power and puff duration. Methods Liquids are prepared by mixing aqueous sucrose, glucose or sorbitol solutions to a 70/30 propylene glycol/glycerin solution. Aerosols are generated and trapped on filter pads using a commercially available ECIG operating at 4.3 and 10.8 W and 4 and 8 s puff duration. Extraction, elimination of matrix interference and quantification are achieved using novel solid phase extraction and gas chromatography tandem mass spectrometry methods (GC-MS). Results Well-resolved GC peaks of 5-hydroxymethylfurfural (HMF) and furfural (FA) are detected. Both HMF and FA are quantified in the aerosols of sweet-flavoured e-liquids under various vaping conditions. Levels of furan emissions are significantly correlated with electric power and sweetener concentration and not with puff duration. Unlike saccharides, the formation of HMF and FA from a sugar alcohol is negligible. Conclusions The addition of sweeteners to ECIG liquids exposes ECIG user to furans, a toxic class of compounds. Under certain conditions, the per-puff yield of HMF and FA in ECIG emissions is comparable to values reported for combustible cigarettes.

The syntheses of the first carboranyl N-heterocyclic carbene complexes with transition metals are reported. Both unsymmetrical mono-anionic and symmetrical dianionic NHCs readily react with ClAuSMe2 to afford unusual zwitterionic and anionic Au(I) dimethyl sulfide adducts. The compounds are characterized by NMR, mass spectrometry, and single crystal X-ray diffraction studies. Percent buried volume (%Vbur) calculations indicate that replacement of an adamantyl group by a hydride substituted icosahedral carborane anion results in a 3.7% increase in %Vbur.

Electronic cigarettes (ECIGs) use electricity to power a heating element that aerosolizes a liquid that often contains solvents, flavorants, and the dependence-producing drug nicotine for user inhalation. ECIGs have evolved rapidly in the past 8 years, and the changes in product design and liquid constituents affect the resulting toxicant yield in the aerosol and delivery to the user. This rapid evolution has been accompanied by dramatic increases in ECIG use prevalence in many countries, including among adults and especially adolescents in the United States. This increased prevalence of a novel product that has the potential to deliver nicotine and other toxicants to users’ lungs drives a rapidly growing research effort. This review highlights the most recent information regarding the design of ECIGs and liquid and aerosol constituents, the epidemiology of ECIG use among adolescents and adults (including correlates of ECIG use), and preclinical and clinical research regarding ECIG effects. The current literature suggests a strong rationale for an empirical regulatory approach toward ECIGs that balances any potential ECIG-mediated decreases in health risks for smokers who use them as substitutes for tobacco cigarettes and against any increased risks for nonsmokers who may be attracted to them.

A molecular donor-acceptor adduct has been isolated by the reaction of the N-heterocyclic carbene 1,3-dimethyl imidazol-2-ylidene (diMe-IMD) with GaCl(3). In contrast, the structurally related, yet much more nucleophilic, 1,3-dimethyl-2-methylene-2,3-dihydro-1H-imidazole (diMe-MDI) gave rise to ion pairs of type [L(2)GaX(2)][GaX(4)], where X = Cl, Br, or I. With IBioxMe(4), a N-heterocyclic carbene that is more nucleophilic than diMe-IMD, the outcome of the reaction was dependent on the nature of the halide. Ionic 1:1 adducts between monodentate ligands and GaX(3) salts have only one precedent in the literature. The peculiar behavior of carbon-based ligands was explained on the basis of their electronic properties and reaction kinetics.

Carbodiphosphoranes [C(PR3)2] are divalent carbon(0) derivatives which can be used as ligands to form either MC(PR3)2 or (M)2 C(PR3)2 species. They were computationally predicted to be even stronger electron donors than N-heterocyclic carbenes. We have introduced hexaphenylcarbodiphosphorane [C(PPh3)2] for the first time in gold catalysis in order to validate this prediction by experimentation. Its mono- and digold complexes were compared to tris(2,4-di-tert-butylphenyl) phosphite, triphenylphosphine, and 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene in representative gold(I)-catalyzed transformations. The advantages and limitations of these ligands are discussed.

DFT methods are used to calculate the ionization energy (IE) and electron affinity (EA) trends in a series of pincer ligated d(8)-Ir((tBu4)PXCXP) complexes (1-X), where C is a 2,6-disubstituted phenyl ring with X = O, NH, CH2, BH, S, PH, SiH2, and GeH2. Both C2v and C2 geometries are considered. Two distinct σ-type ((2)A1 or (2)A) and π-type ((2)B1 or (2)B) electronic states are calculated for each of the free radical cation and anion. The results exhibit complex trends, but can be satisfactorily accounted for by invoking a combination of electronegativity and specific π-orbital effects. The calculations are also used to study the effects of varying X on the thermodynamics of oxidative H2 addition to 1-X. Two closed shell singlet states differentiated in the C2 point group by the d(6)-electon configuration are investigated for the five-coordinate Ir(III) dihydride product. One electronic state has a d(6)-(a)(2)(b)(2)(b)(2) configuration and a square pyramidal geometry, the other a d(6)-(a)(2)(b)(2)(a)(2) configuration with a distorted-Y trigonal bipyramidal geometry. No simple correlations are found between the computed reaction energies of H2 addition and either the IEs or EAs. To better understand the origin of the computed trends, the thermodynamics of H2 addition are analyzed using a cycle of hydride and proton addition steps. The analysis highlights the importance of the electron and hydride affinities, which are not commonly used in rationalizing trends of oxidative addition reactions. Thus, different complexes such as 1-O and 1-CH2 can have very similar reaction energies for H2 addition arising from opposing hydride and proton affinity effects. Additional calculations on methane C-H bond addition to 1-X afford reaction and activation energy trends that correlate with the reaction energies of H2 addition leading to the Y-product.

Here we describe the fusion of two families of unusual carbon-containing molecules that readily disregard the tendency of carbon to form four chemical bonds, namely N-heterocyclic carbenes (NHCs) and carborane anions. Deprotonation of an anionic imidazolium salt with lithium diisopropylamide at room temperature leads to a mixture of lithium complexes of C-2 and C-5 dianionic NHC constitutional isomers as well as a trianionic (C-2, C-5) adduct. Judicious choice of the base and reaction conditions allows the selective formation of all three stable polyanionic carbenes. In solution, the so-called abnormal C-5 NHC lithium complex slowly isomerizes to the normal C-2 NHC, and the process can be proton-catalyzed by the addition of the anionic imidazolium salt. These results indicate that the combination of two unusual forms of carbon atoms can lead to unexpected chemical behavior, and that this strategy paves the way for the development of a broad new generation of NHC ligands for catalysis.

International audience; Six new molecular GaCl3 adducts of electron rich compounds of the carbone (carbodiphosphorane, tetraaminoallene) and cyclic alkyl amino carbene (CAAC) families have been synthesized and characterized by X-ray crystallography. The sum of their Cl-Ga-Cl angles has been compared to those of 20 other complexes exhibiting various oxygen-, nitrogen-, phosphorus-, and carbon-donor ligands for which good quality X-ray analyses have been reported. The pyramidalization of the GaCl3 moiety in L*GaCl3 complexes has been checked against the computed antisymmetric stretching of the Ga-Cl bonds. It has also been compared to the symmetric stretching of the C-O bonds of the corresponding L*Ni(CO)3 complexes (Tolman Electronic Parameter). On this basis, a relationship between the pyramidalization observed in the gallium complexes and the electronic ligand properties has been established.

Introduction Available in hundreds of device designs and thousands of flavors, electronic cigarette (ECIG) may have differing toxicant emission characteristics. This study assesses nicotine and carbonyl yields in the most popular brands in the U.S. market. These products included disposable, prefilled cartridge, and tank-based ECIGs. Methods Twenty-seven ECIG products of 10 brands were procured and their power outputs were measured. The e-liquids were characterized for pH, nicotine concentration, propylene glycol/vegetable glycerin (PG/VG) ratio, and water content. Aerosols were generated using a puffing machine and nicotine and carbonyls were, respectively, quantified using gas chromatograph and high-performance liquid chromatography. A multiregression model was used to interpret the data. Results Nicotine yields varied from 0.27 to 2.91 mg/15 puffs, a range corresponding to the nicotine yield of less than 1 to more than 3 combustible cigarettes. Nicotine yield was highly correlated with ECIG type and brand, liquid nicotine concentration, and PG/VG ratio, and to a lower significance with electrical power, but not with pH and water content. Carbonyls, including the carcinogen formaldehyde, were detected in all ECIG aerosols, with total carbonyl concentrations ranging from 3.72 to 48.85 µg/15 puffs. Unlike nicotine, carbonyl concentrations were mainly correlated with power. Conclusion In 15 puffs, some ECIG devices emit nicotine quantities that exceed those of tobacco cigarettes. Nicotine emissions vary widely across products but carbonyl emissions showed little variations. In spite of that ECIG users are exposed to toxicologically significant levels of carbonyl compounds, especially formaldehyde. Regression analysis showed the importance of design and e-liquid characteristics as determinants of nicotine and carbonyl emissions. Implications Periodic surveying of characteristics of ECIG products available in the marketplace is valuable for understanding population-wide changes in ECIG use patterns over time.

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The new complexes are efficient catalysts for the asymmetric aminolysis of heterocyclic epoxides.

A new family of chiral lanthanide complexes derived from (R)-binaphthol has been synthesized by a one-pot procedure using only commercially available substrates. These complexes were evaluated for the aminolysis of meso-epoxides and proved to be efficient enantioselective catalysts. The samarium complex coordinated by two (R)-binaphthoxide ligands was the most enantioselective catalyst of this series. β-Amino alcohols including heterocycles have been isolated with enantiomeric excesses up to 84%.