Electronic (e-)cigarettes have emerged in recent years as putative alternative to conventional tobacco cigarettes. These products do not contain typical carcinogens that are present in tobacco smoke, due to the lack of combustion. However, besides nicotine, hazards can also arise from other constituents of liquids, such as solvents, flavors, additives and contaminants. In this study, we have analyzed 28 liquids of seven manufacturers purchased in Germany. We confirm the presence of a wide range of flavors to enhance palatability. Although glycerol and propylene glycol were detected in all samples, these solvents had been replaced by ethylene glycol as dominant compound in five products. Ethylene glycol is associated with markedly enhanced toxicological hazards when compared to conventionally used glycerol and propylene glycol. Additional additives, such as coumarin and acetamide, that raise concerns for human health were detected in certain samples. Ten out of 28 products had been declared "free-of-nicotine" by the manufacturer. Among these ten, seven liquids were identified containing nicotine in the range of 0.1-15 µg/ml. This suggests that "carry over" of ingredients may occur during the production of cartridges. We have further analyzed the formation of carbonylic compounds in one widely distributed nicotine-free brand. Significant amounts of formaldehyde, acetaldehyde and propionaldehyde were only found at 150 °C by headspace GC-MS analysis. In addition, an enhanced formation of aldehydes was found in defined puff fractions, using an adopted machine smoking protocol. However, this effect was delayed and only observed during the last third of the smoking procedure. In the emissions of these fractions, which represent up to 40 % of total vapor volume, similar levels of formaldehyde were detected when compared to conventional tobacco cigarettes. By contrast, carbonylic compounds were hardly detectable in earlier collected fractions. Our data demonstrate the necessity of standardized machine smoking protocols to reliably address putative risks of e-cigarettes for consumers.

Consumers of combustible cigarettes are exposed to many different toxicologically relevant substances associated with negative health effects. Newly developed “heat not burn” (HNB) devices are able to contain lower levels of Harmful and Potentially Harmful Constituents (HPHCs) in their emissions compared to tobacco cigarettes. However, to develop toxicological risk assessment strategies, further independent and standardized investigations addressing HPHC reduction need to be done. Therefore, we generated emissions of a commercially available HNB product following the Health Canada Intense smoking regimen and analyzed total particulate matter (TPM), nicotine, water, aldehydes, and other volatile organic compounds (VOCs) that are major contributors to health risk. We show that nicotine yield is comparable to typical combustible cigarettes, and observe substantially reduced levels of aldehydes (approximately 80–95%) and VOCs (approximately 97–99%). Emissions of TPM and nicotine were found to be inconsistent during the smoking procedure. Our study confirms that levels of major carcinogens are markedly reduced in the emissions of the analyzed HNB product in relation to the conventional tobacco cigarettes and that monitoring these emissions using standardized machine smoking procedures generates reliable and reproducible data which provide a useful basis to assess exposure and human health risks.Electronic supplementary materialThe online version of this article (10.1007/s00204-018-2215-y) contains supplementary material, which is available to authorized users.

BackgroundElectronic cigarettes (e-cigarettes) are advertised to tobacco users as a tool to decrease cigarette consumption and to reduce toxic exposure associated with conventional tobacco smoking. Little is known about the compounds contained in such products, their exposure and long-term health effects.MethodsNMR spectroscopy was used to ascertain the content of several constituents of e-cigarette liquids including nicotine, solvents and some bioactive flavour compounds. Risk assessment was based on probabilistic exposure estimation and comparison with toxicological thresholds using the margin of exposure (MOE) approach.ResultsIn 54 samples of e-cigarette liquids, the average nicotine content was 11 mg/ml. Only 18 from 23 samples were confirmed as nicotine-free samples and in one e-cigarette liquid nicotine was not detected while being declared on the labelling. Major compounds of e-cigarette liquids include glycerol (average 37 g/100 g), propylene glycol (average 57 g/100 g) and ethylene glycol (average 10 g/100 g). Furthermore, 1,3-propanediol, thujone and ethyl vanillin were detected in some samples. The average exposure for daily users was estimated as 0.38 mg/kg bw/day for nicotine, 8.9 mg/kg bw/day for glycerol, 14.5 mg/kg bw/day for 1,2-propanediol, 2.1 mg/kg bw/day for ethylene glycol, and below 0.2 mg/kg bw/day for the other compounds. The MOE was below 0.1 for nicotine, but all other compounds did not reach MOE values below 100 except ethylene glycol and 1,2-propanediol.ConclusionsNMR spectroscopy is a useful and rapid method to simultaneously detect several ingredients in e-cigarette liquids. From all compounds tested, only nicotine may reach exposures that fall into a high risk category with MOE <1. Therefore, e-cigarette liquid products should be subjected to regulatory control to ensure consistent nicotine delivery. Solvents with more favourable toxicological profiles should be used instead of ethylene glycol and 1,2-propanediol, which may fall into a risk category with MOE < 100.

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The popularity and the high nicotine content of the American pod e-cigarette JUUL have raised many concerns. To comply with European law, the nicotine concentration in the liquids of the European version, which has been recently released on the market, is limited to below 20 mg/mL. This limit can possibly be circumvented by technological adjustments that increase vaporization and consequently, elevate nicotine delivery. In this study, we compare vapor generation and nicotine delivery of the initial European version, a modified European version, and the original American high-nicotine variant using a machine vaping setup. Additionally, benzoic acid and carbonyl compounds are quantified in the aerosol. Further, concentrations of nicotine, benzoic acid, propylene glycol, and glycerol, along with the density and pH value of JUUL e-liquids have been assessed. Whereas the initial European version did not compensate for the low nicotine content in the liquid, we provide evidence for an increased vaporization by the modified European version. As a consequence, nicotine delivery per puff approximates the American original. Notably, this is not associated with an increased generation of carbonyl compounds. Our data suggest a similar addictiveness of the enhanced European version and the original American product.