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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 safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapor generated from e-cigarettes. The aim of this study was to screen e-cigarette vapors for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines, and heavy metals. Materials and methods Vapors 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 vapors into a solid or liquid phase and analyzed with chromatographic and spectroscopy methods. Results We found that the e-cigarette vapors contained some toxic substances. The levels of the toxicants were 9 to 450 times lower than in cigarette smoke and were, in many cases, comparable to trace amounts found in the reference product. Conclusions Our findings are consistent with the idea that substituting tobacco cigarettes with electronic 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.

Nicotine underlies tobacco addiction, influences tobacco use patterns, and is used as a pharmacological aid to smoking cessation. The absorption, distribution and disposition characteristics of nicotine from tobacco and medicinal products are reviewed. Nicotine is metabolized primarily by the liver enzymes CYP2A6, UDP-glucuronosyltransfease (UGT), and flavin-containing monooxygenase (FMO). In addition to genetic factors, nicotine metabolism is influenced by diet and meals, age, sex, use of estrogen-containing hormone preparations, pregnancy and kidney disease, other medications, and smoking itself. Substantial racial/ethnic differences are observed in nicotine metabolism, which are likely influenced by both genetic and environmental factors. The most widely used biomarker of nicotine intake is cotinine, which may be measured in blood, urine, saliva, hair, or nails. The current optimal plasma cotinine cut-point to distinguish smokers from non-smokers in the general US population is 3 ng ml −1 . This cut-point is much lower than that established 20 years ago, reflecting less secondhand smoke exposure due to clear air policies and more light or occasional smoking.

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Pfizer and GlaxoSmithKline.

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The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose-response relationships based on the precise parameters and conditions inherent to a specific hypothesis. This review provides a new, experimentally based compilation of species-specific dose selection for studies on the in vivo effects of nicotine.

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