Journal Article 1)
Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation. Surveys document that most smokers would like to quit, and many have made repeated efforts to do so. However, conventional smoking cessation approaches require nicotine addicted smokers to abstain from tobacco and nicotine entirely. Many smokers are unable– or at least unwilling– to achieve this goal, and so they continue smoking in the face of impending adverse health consequences. In effect, the status quo in smoking cessation presents smokers with just two unpleasant alternatives: quit or suffer the harmful effects of continuing smoking. But, there is a third choice for smokers: tobacco harm reduction. It involves the use of alternative sources of nicotine, including modern smokeless tobacco products like snus and the electronic cigarette (E-cig), or even pharmaceutical nicotine products, as a replacement for smoking. E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking’s damaging effect, they also replace some of the rituals associated with smoking behaviour.
Thus it is likely that smokers who switch to E-cigs will achieve large health gains. The focus of this article is on the health effects of using an E-cig, with consideration given to the acceptability, safety and effectiveness of this product as a long-term substitute for smoking.
Are there important associated adverse health consequences of nicotine intake?
The landmark work, Nicotine Safety and Toxicity, edited by Neal Benowitz, considered the potentially harmful effects of nicotine as well as its benefits . After reviewing the evidence, the authors concluded that nicotine presents little if any cardiovascular risk, and that nicotine has not been shown to be carcinogenic. It is has been reported that nicotine may be potentially harmful during pregnancy, but probably less harmful than continued smoking [27-29]. There are data suggesting that nicotine may be beneficial in treating ulcerative colitis  and Tourette syndrome . Other conditions for which nicotine is being considered as treatment include memory impairment, attention deficit disorder, depression, and Parkinson’s disease .
Regarding long-term use, even though nicotine is a potential toxin, it appears to be well-tolerated during weeks and months of nicotine medication therapy without evidence of serious adverse health effects . Using the multi-criteria decision analysis method previously used by the Independent Scientific Committee on Drugs (ISCD) to rank the harms of drugs used in the UK, a working group of international nicotine experts convened by the ISCD considered the potential harms of a wide range of nicotine containing products based on sixteen parameters of harm to individuals and harm to others. Not only conventional cigarettes were judged to be by far the most harmful form of nicotine containing product, but e-cigarettes were ranked as similar in harm to nicotine patches . By and large, nicotine perse does not cause much risk when separated from inhaling smoke.
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Toxicological characterization of e-cigarettes
The available evidence indicates that e-cigarettes do not raise serious health concerns and can be considered a much safer alternative to conventional smoking [63-66].
Detailed toxicology characterization of e-cigarette liquid and vapour using gas chromatography mass spectrometry (GC-MS) demonstrates that their primary components are water, propylene glycol (PG), glycerin, and nicotine .
In an independent study, Laugesen tested E-cig mist for over 50 priority-listed cigarette smoke toxicants and found none . This report only revealed traces (8.2 ng/g) of TSNAs in the “high” nicotine cartridge of a Ruyan brand E-cig. However, it must be noted that this amount is equal to the quantity reported to be present in a nicotine medicinal patch  (Table 1).
FDA-commissioned testing of e-cigarette cartridge fluids found diethylene glycol in one of the 18 e-cigarette cartridges tested . Formaldehyde, acetaldehyde, and acroleine (potentially toxic carbonyl compounds) have been detected in e-cigarette vapour in 12 brands of e-cigarettes but at levels substantially lower than in cigarette smoke. These compounds may be formed by the oxidation of propylene glycol or glycerol when in contact with the heating coil.
Cahn and Siegel  reviewed the results of 16 laboratory analyses of E-cig liquid, including the FDA’s Report noted above . TSNAs were reported in two studies, but at trace levels, which are similar to those found in a nicotine patch, and, most importantly, about 500-fold to 1400-fold lower than TSNA levels measured in regular cigarettes (E-cigs containing only 0.07–0.2% of the TSNAs present in cigarettes) (Table 1).
It must be however noted that the e-cigarette industry is now adopting improved manufacturing standards. According to American e-liquid Manufacturing Standards Association (AESMA), liquids produced before 2013 were largely inaccurate, whereas newest products have substantially improved in term of purity, consistency and accuracy of nicotine content.
For example,  in a recent analysis of 20 refill liquids of 10 of the most popular brands have shown that the nicotine content in the bottles corresponded closely to the labels on the bottles with levels of nicotine degradation products being 1–2% for most samples. Also, this analysis did not detect ethylene glycol nor diethylene glycol; for several brands the levels of impurities were above the level set for nicotine products in the European Pharmacopoeia, but below the level likely to cause harm.
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E-cigarette vapour contains a number of potentially toxic compounds. Testing on some devices has found tobacco-specific nitrosamines (TSNAs) ) and polycyclic aromatic hydrocarbons present in cartridge fluid, but generally in very low levels, similar to those in nicotine replacement therapy [64,68,71].
Cadmium, lead and nickel have also been detected in vapour but in trace levels only, comparable with levels found in Nicorette inhaler . Metal and silicate particles were detected in fluid and vapour from e-cigarette cartomisers obtained from one manufacturer over several years, leading to exposure to amounts of these particles equal to or higher than users of tobacco cigarettes might typically experience .
In essence, these products appear to be much safer than tobacco cigarettes and comparable in toxicity to conventional nicotine replacement products. Of note, retailers have already sold hundreds of thousands of E-cigs with no evidence that these products have endangered anyone when used as directed. Although there is no indication that E-cigs are any more an immediate threat to public health and safety than traditional cigarettes, which are readily available to the public, the current data is insufficient to conclude that E-cigs are safe in absolute terms, and further studies are needed to comprehensively assess their safety, particularly in the long term.
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