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Glycerin (VG) and propylene glycol (PG) are the most common nicotine solvents used in e-cigarettes (ECs). It has been shown that at high temperatures both VG and PG undergo decomposition to low molecular carbonyl compounds, including the carcinogens formaldehyde and acetaldehyde. The aim of this study was to evaluate how various product characteristics, including nicotine solvent and battery output voltage, affect the levels of carbonyls in EC vapor. Twelve carbonyl compounds were measured in vapors from 10 commercially available nicotine solutions and from 3 control solutions composed of pure glycerin, pure propylene glycol, or a mixture of both solvents (50:50). EC battery output voltage was gradually modified from 3.2 to 4.8V. Carbonyl compounds were determined using the HPLC/DAD method. Formaldehyde and acetaldehyde were found in 8 of 13 samples. The amounts of formaldehyde and acetaldehyde in vapors from lower voltage EC were on average 13- and 807-fold lower than in tobacco smoke, respectively. The highest levels of carbonyls were observed in vapors generated from PG-based solutions. Increasing voltage from 3.2 to 4.8V resulted in a 4 to more than 200 times increase in formaldehyde, acetaldehyde, and acetone levels. The levels of formaldehyde in vapors from high-voltage device were in the range of levels reported in tobacco smoke. Vapors from EC contain toxic and carcinogenic carbonyl compounds. Both solvent and battery output voltage significantly affect levels of carbonyl compounds in EC vapors. High-voltage EC may expose users to high levels of carbonyl compounds.

Significance Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. They are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapour generated from e–cigarettes. The aim of this study was to screen e-cigarette vapours for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines and heavy metals. Materials and methods Vapours were generated from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapours into a solid or liquid phase and analysed with chromatographic and spectroscopy methods. Results We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9–450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product. Conclusions Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study. (To view this abstract in Polish and German, please see the supplementary files online.)

Electronic cigarettes (e-cigarettes) are an alternate nicotine delivery system that generate a condensation aerosol to be inhaled by the user. The size of the droplets formed in the aerosol can vary and contributes to drug deposition and ultimate bioavailability in the lung. The growing popularity of e-cigarette products has caused an increase in internet sources promoting the use of drugs other than nicotine (DOTNs) in e-cigarettes. The purpose of this study was to determine the effect of various e-cigarette and e-liquid modifications, such as coil resistance, battery voltage, and glycol and drug formulation, on the aerosol particle size. E-liquids containing 12 mg/mL nicotine prepared in glycol compositions of 100% propylene glycol (PG), 100% vegetable glycerin (VG), or 50:50 PG:VG were aerosolized at three voltages and three coil resistances. Methamphetamine and methadone e-liquids were prepared at 60 mg/mL in 50:50 PG:VG and all e-liquids were aerosolized onto a 10 stage Micro-Orifice Uniform Deposit Impactor. Glycol deposition correlated with drug deposition, and the majority of particles centered between 0.172–0.5 μm in diameter, representing pulmonary deposition. The 100% PG e-liquid produced the largest aerosol particles and the 100% VG and 50:50 PG:VG e-liquids produced ultra-fine particles <0.3 μm. The presence of ultrafine particles indicates that drugs can be aerosolized and reach the pulmonary alveolar regions, highlighting a potential for abuse and risk of overdose with DOTNs aerosolized in an e-cigarette system.

Recent evidence suggests that e-cigarette users tend to change their puffing behaviors when using e-liquids with reduced nicotine concentrations by taking longer and more frequent puffs. Using puffing regimens modelled on puffing topography data from 19 experienced e-cigarette users who switched between 18 and 6 mg/mL e-liquids with and without power adjustments, differences in daily exposure to carbonyl compounds and estimated changes in cancer risk were assessed by production of aerosols generated using a smoking machine and analyzed using gas and liquid chromatography. Significant differences across conditions were found for formaldehyde and acetaldehyde (p < 0.01). Switching from a higher to a lower nicotine concentration was associated with greater exposure regardless of whether power settings were fixed or adjustable which is likely due to increased liquid consumption under lower nicotine concentration settings. Daily exposure for formaldehyde and acetaldehyde was higher for 17/19 participants when using low (6 mg/mL) compared with high (18 mg/mL) nicotine e-liquid concentration when power was fixed. When power adjustments were permitted, formaldehyde and acetaldehyde levels were higher respectively for 16/19 and 14/19 participants with the use of 6 compared with 18 mg/mL nicotine e-liquid.

The use of electronic cigarettes (e-cigarettes) is a growing trend in population. E-cigarettes are evolving at a rapid rate with variety of battery powered devices and combustible nicotine refills such as e-liquids. In contrast to conventional cigarettes which are studied well for their toxicity and health effects, long-term clinical data on e-cigarettes are not available yet. Therefore, safety of e-cigarettes is still a major concern. Although the Food and Drug Administration (FDA) has recently started regulating e-cigarette products, no limits on nicotine and other ingredients in such products have been proposed. Considering the regulatory requirements, it is critical that reliable and standardized analytical methods for analyzing nicotine and other ingredients in e-cigarette products such as e-liquids are available. Here, we are reporting a fully validated high-performance liquid chromatography (HPLC) method based on nicotine peak purity for accurately quantifying nicotine in various e-liquids. The method has been validated as per ICH Q2(R1) and USP guidelines. The method is specific, precise, accurate, and linear to analyze nicotine in e-liquids with 1 to >50 mg/mL of nicotine. Additionally, the method has been proven robust and flexible for parameters such as change in flow rate, column oven temperature, and organic phase composition, which proves applicability of the method over wide variety of e-liquids in market.

In electronic cigarette users, nicotine delivery to lungs depends on various factors. One of the important factors is e-liquid nicotine concentration. Nicotine concentration in e-liquids ranges from 0 to >50 mg/mL. Furthermore, nicotine exists in protonated and unprotonated (“free base”) forms. The two forms are believed to affect the nicotine absorption in body. Therefore, in addition to total nicotine concentration, e-liquids should be characterized for their free base nicotine yield. Two approaches are being used for the determination of free base nicotine in e-liquids. The first is applying a dilution to e-liquids followed by two methods: Henderson–Hasselbalch theory application or a Liquid-Liquid Extraction. The second is the without-dilution approach followed by 1H NMR method. Here, we carried out controlled experiments using five e-liquids of different flavors using these two approaches. In the dilution approach, the Henderson–Hasselbalch method was tested using potentiometric titration. The accuracy was found to be >98% for all five e-liquid samples (n = 3). A Liquid-Liquid Extraction was carried out using toluene or hexane as extraction solvent. The Liquid-Liquid Extraction technique was found to be limited by solvent interactions with flavors. Solvent extractions resulted in flavor dependent inaccuracies in free base nicotine determination (5 to 277% of calculated values). The without-dilution approach was carried out using 1H NMR as described by Duell et al. This approach is proposed to offer an independent and alternative scale. None of the methods have established a strong correlation between pre- and postvaporization free base nicotine yield. Here we present comparative results of two approaches using analytical techniques. Such a comparison would be helpful in establishing a standardized method for free base nicotine determination of e-liquids.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

According to the World Health Organization, cardiovascular diseases are responsible for 31% of global deaths. A reduction in mortality can be achieved by promoting a healthy lifestyle, developing prevention strategies, and developing new therapies. Polyphenols are present in food and drinks such as tea, cocoa, fruits, berries, and vegetables. These compounds have strong antioxidative properties, which might have a cardioprotective effect. The aim of this paper is to examine the potential of polyphenols in cardioprotective use based on in vitro human and rat cardiomyocytes as well as fibroblast research. Based on the papers discussed in this review, polyphenols have the potential for cardioprotective use due to their multilevel points of action which include, among others, anti-inflammatory, antioxidant, antithrombotic, and vasodilatory. Polyphenols may have potential use in new and effective preventions or therapies for cardiovascular diseases, yet more clinical studies are needed.

Electronic cigarettes (ECs) seem to be a less harmful alternative for conventional cigarettes. This study aimed to assess whether the generated aerosols from ECs contain lower amount of cadmium (Cd) and lead (Pb) than cigarette smoke and to detect any changes in exposure to Cd and Pb among cigarette smokers who switched completely or partially to EC. EC aerosols and cigarette smoke were generated, and the determination of Cd and Pb in trapped samples and e-liquids was performed by the electrothermal atomic absorption spectrometry method. A cross-sectional, group-based survey was carried out using 156 volunteers classified into groups of nonsmokers, EC-only users, dual EC users-cigarette smokers, and cigarette-only smokers. Using electrothermal atomic absorption spectrometry, blood Cd and Pb levels were measured, and the results were compared by analysis of covariance. Transfer of Cd and Pb to EC aerosol was found to be minimal, although the metals were present in the remaining e-liquid from tanks used for vapor generation. The geometric mean blood Cd concentration adjusted for age and sex was 0.44 (95% confidence interval = 0.37 to 0.52) µg/L in the EC-only users, which was significantly lower than those in the smokers of 1.44 (1.16 to 1.78) and dual users of 1.38 (1.11 to 1.72). The blood Pb geometric mean differed significantly only between nonsmokers of 11.9 (10.6 to 13.3) and smokers of 15.9 (13.6 to 18.6). The study revealed that smokers who completely switched to ECs and quit smoking conventional cigarettes may significantly reduce their exposure to Cd and probably Pb. Switching to EC use is associated with a rapid and substantial decrease in the exposure to carcinogenic Cd. Exposure to Pb is probably also decreased but may be overshadowed by other factors. The study provides empirical data based not only on the analysis of generated aerosol but also on biological indicators of recent exposure-that is, the concentrations of Cd and Pb in blood, indicating EC as a potential harm-reduction device, especially regarding Cd exposure. However, in this case, dual EC use-cigarette smoking provides doubtful benefits.

Abstract Introduction Article 20 of the European Tobacco Products Directive (EU-TPD) specifies that e-liquids should not contain nicotine in excess of 20 mg/mL, thus many vapers may be compelled to switch to lower concentrations and in so doing, may engage in more intensive puffing. This study aimed to establish whether more intensive puffing produces higher levels of carbonyl compounds in e-cigarette aerosols. Methods Using the HPLC-UV diode array method, four carbonyl compounds (formaldehyde, acetaldehyde, acetone, and acrolein) were measured in liquids and aerosols from nicotine solutions of 24 and 6 mg/mL. Aerosols were generated using a smoking machine configured to replicate puffing topography data previously obtained from 12 experienced e-cigarette users. Results Carbonyl levels in aerosols from the puffing regimen of 6 mg/mL were significantly higher (p < .05 using independent samples t tests) compared with those of 24 mg/mL nicotine. For the 6 and 24 mg/mL nicotine aerosols respectively, means ± SD for formaldehyde levels were 3.41 ± 0.94, and 1.49 ± 0.30 µg per hour (µg/h) of e-cigarette use. Means ± SD for acetaldehyde levels were 2.17 ± 0.36 and 1.04 ± 0.13 µg/h. Means ± SD for acetone levels were 0.73 ± 0.20 and 0.28 ± 0.14 µg/h. Acrolein was not detected. Conclusions Higher levels of carbonyls associated with more intensive puffing suggest that vapers switching to lower nicotine concentrations (either due to the EU-TPD implementation or personal choice), may increase their exposure to these compounds. Based on real human puffing topography data, this study suggests that limiting nicotine concentrations to 20 mg/mL may not result in the desired harm minimalization effect. Implications More intensive puffing regimens associated with the use of low nicotine concentration e-liquids can lead to higher levels of carbonyl generation in the aerosol. Although in need of replication in a larger sample outside a laboratory, this study provides pragmatic empirical data on the potential risks of compensatory puffing behaviors in vapers, and can help to inform future regulatory decisions on nicotine e-liquid concentrations. The cap on nicotine concentration at 20 mg/mL set by the EU-TPD may therefore have the unintended consequence of encouraging use of lower nicotine concentration e-liquid, in turn increasing exposure to carbonyl compounds through compensatory puffing.