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.

Periodic surveying of characteristics of ECIG products available in the marketplace is valuable for understanding population-wide changes in ECIG use patterns over time.

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.

Introduction Reliable characterization of the nicotine content and emissions from electronic cigarettes (ECIGs) is crucial for product regulation. Understanding nicotine delivery, and therefore efficacy and abuse potential, from ECIG products requires quantifying the total nicotine contained or emitted, as well as the partitioning between its free-base and protonated forms. To date, studies reporting nicotine content and emissions of ECIGs have not addressed whether the reported values correspond to the total nicotine or only one of its forms, making the reported results difficult to compare across studies, or to correlate against blood exposure measurements. In this study we investigate whether nicotine in ECIGs is indeed present in more than one form, whether measurements are affected by sampling media, and report a validated method for determining total, free-base (Nic) and protonated nicotine (NicH+) in ECIG liquids and aerosol emissions. Methods We developed an analytical method based on liquid-liquid extraction coupled with GC analysis to assess the respective amounts of Nic and NicH+. The method was first verified on pH-controlled solutions (5 < pH < 10) and then was applied to several ECIG liquids and aerosols generated using a smoking machine. Results The method showed high repeatability and efficiency, and the results were in agreement with theoretical predictions based on measured pH of the standard nicotine solutions. ECIG liquids and aerosols contained both Nic and NicH+, and their relative proportions varied widely. Free-base nicotine was found to account for 18-95% of the total nicotine depending on the product in question. Conclusions The wide variation in nicotine partitioning across products suggests that studies of nicotine delivery from ECIGs should account for this factor. A convenient method for analyzing nicotine fractions in electronic cigarettes has been demonstrated.

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<.0001). As predicted, device power, nicotine concentration, PG/VG ratio, and puff duration influenced nicotine flux (p<.05), while water content and puff velocity did not. Additional empirical investigation revealed that PG/VG liquids act as ideal solutions, that liquid vaporization accounts for more than 95% of ECIG aerosol mass emissions, and that as device power increases the aerosol composition shifts towards the less volatile components of the parent liquid. To the extent that ECIG regulations focus on nicotine emissions, mathematical models like this one can be used to predict ECIG nicotine emissions and to test the effects of proposed regulation of factors that influence nicotine flux.

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.

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.

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.