Electronic cigarette

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An electronic cigarette with a USB-powered charger and wall changer.
The battery portion of the e-cigarette is disconnected and charged, as here through a USB-powered charger.
Displaying a variety of e-cigarettes standing next to each other.
Various types of e-cigarettes.

An electronic cigarette or e-cigarette[note 1] is a handheld electronic device that vaporizes a flavored liquid. The user inhales the vapor,[2] which is called vaping.[4] The fluid in the e-cigarette, called e-liquid,[5] is usually made of nicotine, propylene glycol, glycerine, and flavorings.[2][6][7]

The benefits and the health risks of e-cigarettes are uncertain[8][9][10] and the long-term health effects are unknown.[11][12][13] There is general agreement that they are likely less hazardous than tobacco cigarettes.[6][14][15]:234 There is tentative evidence they can help people quit smoking[6] although they have not been proven to work better than regulated nicotine replacement products,[10] and the regulated medications are safer.[16] Their usefulness in tobacco harm reduction is unclear[16] but they could form part of future strategies to decrease tobacco-related death and disease.[17][18] Overall their safety risk to users is like that of smokeless tobacco.[18] No serious adverse effects from e-cigarettes have been reported in trials.[6] Less serious adverse effects include throat and mouth inflammation, vomiting, nausea, and coughing.[19][20] Non-smokers who use e-cigarettes risk addiction to nicotine,[21] a harmful substance.[22]

E-cigarettes create a vapor[19][23] primarily consisting of flavours, aroma transporters, glycerol and propylene glycol,[24] whose composition varies across and within manufacturers.[23] The vapor can contain a small level of toxins and traces of heavy metals detected at levels permissible in inhalation medicines,[24] and some potentially harmful chemicals not found in tobacco smoke at levels permissible by workplace safety standards.[25] However, chemicals may exceed the more stringent safety limits that apply to the public.[19] High aldehyde levels, which have been generated in laboratory settings by researchers overheating e-liquid, cause a highly aversive acrid taste that users would not subject themselves to.[26]

The modern e-cigarette arose from a 2003 invention by Chinese pharmacist Hon Lik,[27] and as of 2015 most e-cigarettes were made in China.[28] Since their introduction to the market in 2004, global use has risen exponentially.[29] For instance, in the UK user numbers have increased from 700,000 in 2012 to 2.6 million in 2015,[30] In the United States e-cigarettes are used by a significant percentage of young people[31] and adults.[32] Most people's reason for using e-cigarettes involves trying to quit smoking, though many people use them recreationally.[12] A majority of e-cigarette users still smoke tobacco, leading to concerns that dual use can "delay or deter quitting".[19] About 60% of UK users are smokers and about 40% are ex-smokers, while use among never-smokers remains "negligible".[30] Because of the potential relationship with tobacco laws and medical drug policies, e-cigarette legislation is being debated in many countries.[33][34] The European Parliament passed regulations in February 2014, to come into effect by 2016, standardizing liquids and personal vaporizers, listing ingredients, and child-proofing liquid containers.[35] The US FDA published proposed regulations in April 2014 with some similar measures.[36] As of 2014, there were 466 brands of e-cigarette with sales of around $7 billion.[37][38]

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Terminology

Electronic cigarettes are also known as e-cigarettes, e-cigs, EC,[1] electronic nicotine delivery systems (ENDS) or electronic non-nicotine delivery systems (ENNDS),[2] personal vaporizer, or PV.[3] They are handheld devices, often made to look like conventional cigarettes, and used in a similar way.[2][39] E-liquid[5] or juice are names for the flavored solution that goes inside the e-cigarette.[40] An aerosol, or vapor, is produced when the e-liquid is brought to boiling point by pushing a button to activate the battery-powered heating device inside the e-cigarette.[41] Inhaling this vapor is known as vaping.[41][42]

Use

Frequency

Aerosol (vapor) exhaled by an e-cigarette user using a nicotine-free e-cigarette.
Aerosol (vapor) exhaled by an e-cigarette user using a nicotine free e-cigarette.

Since their introduction to the market in 2004, global usage of e-cigarettes has risen exponentially.[29] By 2013, there were several million users globally.[43] Awareness and use of e-cigarettes greatly increased in a relatively short period of time.[44] However, growth in the US and UK had reportedly slowed in 2015, lowering market forecasts for 2016.[45][46]

2010 and 2011 surveys suggested that adults with higher incomes may have been more likely to have heard of e-cigarettes, but those with lower incomes may have been more likely to try them.[47] In addition, most users had a history of smoking regular cigarettes, while results by race were mixed.[47] At least 52% of current or former smokers have used an e-cigarette.[28] Of smokers who have, less than 15% became everyday e-cigarette users.[6] Though e-cigarette use among those who have never smoked is very low, it continues to rise.[48] A survey of e-cigarette users conducted from 2011-2012 found that only 1% of respondents used liquid without nicotine.[49]

Everyday use is common among e-cigarette users.[50] E-cigarette users mostly keep smoking traditional cigarettes.[19] Many say e-cigarettes help them cut down or quit smoking.[24] Adults often vape to replace tobacco, but not always to quit.[47] Most e-cigarette users are middle-aged men who also smoke traditional cigarettes, either to help them quit or for recreational use.[12] E-cigarette use was also rising among women as of 2014.[51] Dual use of e-cigarettes and traditional tobacco is still a definite concern.[8] There is wide concern that vaping may be a "gateway" to smoking.[52] Some young people who have tried an e-cigarette have never smoked tobacco, so ECs can be a starting point for nicotine use.[19] On the other hand, Public Health England found no evidence e-cigarettes increase teen tobacco smoking. They noted tentative evidence that e-cigarettes divert youth away from cigarettes.[26] A 2014 review raised ethical concerns about minors' e-cigarette use and the potential to weaken cigarette smoking reduction efforts.[52]

In the US, as of 2014, 12.6% of adults had used an e-cigarette at least once and approximately 3.7% were still using them.[53] 1.1% of adults were daily users.[54] Non-smokers and former smokers who had quit more than four years earlier were extremely unlikely to be current users.[54] Former smokers who had recently quit were more than four times as likely to be daily users as current smokers.[54] Experimentation was more common among younger adults, but daily users were more likely to be older adults.[54]

National Institute on Drug Abuse director Nora Volkow discussing a study that shows teens using e-cigarettes are more likely to start smoking tobacco.[55]

The recent decline in smoking has accompanied a rapid growth in the use of alternative nicotine products among young people and young adults.[56] In the US, vaping among young people exceeded smoking in 2014.[57] As of 2014, up to 13% of American high school students have used them.[31] Between 2013 and 2014, vaping among students tripled.[58] In 2013 the Centers for Disease Control and Prevention (CDC) estimated that around 160,000 students between 2011 and 2012 who had tried vaping had never smoked.[56] E-cigarette use among never-smoking youth in the US correlates with elevated desires to use traditional cigarettes.[8] Teenagers who had used an e-cigarette were more inclined to become smokers than those who had not.[59] In the 2015 Monitoring the Future survey, a majority of students who used electronic cigarettes reported using liquid without nicotine the last time they vaped.[60] The majority of young people who vape also smoke.[61] A 2010-2011 survey of students at two US high schools found that vapers were more likely to use hookah and blunts than smokers.[62] Among grade 6 to 12 students in the US, the proportion who have tried them rose from 3.3% in 2011 to 6.8% in 2012.[47] Those still vaping over the last month rose from 1.1% to 2.1% and dual use rose from 0.8% to 1.6%.[47] Over the same period, the proportion of grade-6-to-12 students who regularly smoke tobacco fell from 7.5% to 6.7%.[63]

In the UK, user numbers have increased from 700,000 in 2012 to 2.6 million in 2015, but use by current smokers remained flat at 17.6% from 2014 into 2015 (in 2010, it was 2.7%).[30] About one in 20 adults in the UK uses e-cigarettes.[64] In the UK in 2015, 18% of regular smokers said they used e-cigarettes and 59% said they had used them in the past.[30] Among those who had never smoked, 1.1% said they had tried them and 0.2% still use them.[65] In 2013, among those under 18, 7% have used e-cigarettes at least once.[65] Among non-smokers' children, 1% reported having tried e-cigarettes "once or twice", and there was no evidence of continued use.[65] About 60% of all users are smokers and most of the rest are ex-smokers, with "negligible" numbers of never-smokers.[66] In 2015 figures showed around 2% monthly EC-usage among under-18s, and 0.5% weekly, and despite experimentation, "nearly all those using EC regularly were cigarette smokers".[67] 10-11-year-old Welsh never-smokers are more likely to use e-cigarettes if a parent used e-cigarettes.[68]

In France, a 2014 survey estimated between 7.7 and 9.2 million people had tried e-cigarettes and 1.1 to 1.9 million use them on a daily basis.[69] The same survey also found 67% of smokers used e-cigarettes to reduce or quit smoking. Of respondents who indicated they tried e-cigarettes, 9% said they had never smoked tobacco.[69] Of the 1.2% who had recently stopped tobacco smoking at the time of the survey, 84% (or 1% of the population surveyed) credited e-cigarettes as essential in quitting.[69]

Motivation

There are concerns that colorful electronic cigarettes may appeal especially to younger users.[70]
Candy, fruit and coffee flavored e-liquid may appeal to younger users of electronic cigarettes.[71]

Reasons for e-cigarette usage often relate to quitting smoking and recreation.[12][50][72] While many vapers believe usage is healthier than smoking for themselves and bystanders, some are concerned about the possible adverse health effects.[50] Others use them to circumvent smoke-free laws and policies, or to cut back on cigarette smoking.[19] 56% of respondents in a US 2013 survey reported having used e-cigarettes to quit or reduce their smoking.[9] In the same survey, 26% of respondents would use them in areas where smoking was banned.[9] Not having odor from smoke on clothes on some occasions prompted interest in or use of e-cigarettes.[50] Many e-cigarette users use them because they believe they are safer than conventional cigarettes.[72]

Non-smoking adults tried e-cigarettes due to curiosity, because a relative was using them, or because they were given an e-cigarette.[62] College students often vape for experimentation.[11] Expensive marketing aimed at smokers suggests e-cigarettes are "newer, healthier, cheaper and easier to use in smoke-free situations, all reasons that e-cigarette users claim motivate their use".[73] Exposure to e-cigarette advertising influenced people to try them.[59]

The belief that e-cigarettes are safer than traditional cigarettes could widen their use among pregnant women.[8][74] E-cigarettes feel or taste similar to traditional cigarettes, and vapers disagreed about whether this was a benefit or a drawback.[50] The majority of committed e-cigarette users interviewed at an e-cigarette convention found them cheaper than traditional cigarettes.[50]

Some users stopped vaping due to issues with the devices.[50] Dissatisfaction and concerns over safety can discourage ongoing e-cigarette use.[64] E-cigarette users have contradictory views about using them to get around smoking bans.[50] Some surveys found that a small percentage of users' motives were to avoid smoking bans, but other surveys found that over 40% of users said they used the device for this reason.[50] The extent to which traditional cigarette users vape to avoid smoking bans is unclear.[50]

The health and lifestyle appeal may also encourage young non-smokers to use e-cigarettes, as they may perceive that trying e-cigarettes is less risky and more socially appealing. This may decrease negative beliefs or concerns about nicotine addiction.[71] Marketing might appeal to young people as well as adults.[75] Adolescent experimenting with e-cigarettes may be sensation seeking behavior, and is not likely to be associated with tobacco reduction or quitting smoking.[8] Young people may view e-cigarettes as a symbol of rebellion.[48] The main reasons young people experimented with e-cigarettes were due to curiosity, flavors, and peer influences.[76] Some advocates say there is concern that e-cigarettes could be appealing to youth because of their high-tech design, assortment of flavors, and accessibility online.[70] At least one advocacy group claims that candy and fruit flavors e-cigarettes are designed to appeal to young people.[77] Infants and toddlers could ingest the e-liquid from an e-cigarette device out of curiosity.[78]

Users may begin by using a disposable e-cigarette,[7] and e-cigarette users often start with e-cigarettes resembling normal cigarettes, eventually moving to a later-generation device.[79] Most later-generation e-cigarette users shifted to their present device to get a "more satisfying hit",[79] and users may adjust their devices to provide more vapor for better "throat hits".[80]

Other uses

Special e-liquid mixes with THC or other cannabinoids are available for purchase.[81]

Electronic cigarettes may be used with other substances and cartridges can potentially be filled with e-liquid containing substances other than nicotine, thus serving as a new and potentially dangerous way to deliver other drugs,[82] for example psychoactive or psychotropic drugs such as THC.[81]

The emergence of e-cigs has given cannabis smokers a new method of inhaling cannabinoids.[81] E-cigs differ from traditional marijuana cigarettes in several respects.[81] It is assumed that vaporizing cannabinoids at lower temperatures is safer because it produces smaller amounts of toxic substances than the hot combustion of a marijuana cigarette.[81] Recreational cannabis users can discreetly "vape" deodorized cannabis extracts with minimal annoyance to the people around them and less chance of detection, known as "stealth vaping".[81] While cannabis is not readily soluble in the liquid used for e-cigs; recipes containing synthetic cannabinoids which are soluble may be found on the Internet.[81]

Cannabinoid-enriched e-liquids require lengthy, complex processing, some being readily present on the Internet despite lack of quality control, expiry date, conditions of preservation, or any toxicological and clinical assessment.[81]

The health consequences specific to vaping these cannabis preparations remain largely unknown.[81]

Construction

Exploded view of electronic cigarette with transparent clearomizer and changable dual-coil head. This model allows for a wide range of settings.[83]
Electronic cigarettes can come in very different forms—such as this hand-grenade-shaped variant.

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The primary parts that make up an e-cigarette are a mouthpiece, a cartridge (tank), a heating element/atomizer, a microprocessor, a battery, and possibly a LED light on the end.[84] The only exception to this are mechanical e-cigarettes (mods) which contain no electronics and the circuit is closed by using a mechanical action switch.[85] An atomizer comprises a small heating element, or coil, that vaporizes e-liquid and wicking material that draws liquid onto the coil.[86] When the user pushes a button,[11] or (in some variations) activates a pressure sensor by inhaling, the heating element that atomizes the liquid solution;[12] The e-liquid reaches a temperature of roughly 100-250 °C within a chamber to create an aerosolized vapor.[87] The user inhales the aerosol, commonly called vapor, rather than cigarette smoke.[23] The aerosol provides a flavor and feel similar to tobacco smoking.[88]

There are three main types of e-cigarettes: cigalikes, looking like cigarettes; eGos, bigger than cigalikes with refillable liquid tanks; and mods, assembled from basic parts or by altering existing products.[8] As the e-cigarette industry continues to evolve, new products are quickly developed and brought to market.[89] First generation e-cigarettes tend to look like tobacco cigarettes and so are called "cigalikes".[90] Most cigalikes look like cigarettes but there is some variation in size.[91] A traditional cigarette is smooth and light while a cigalike is rigid and slightly heavier.[88] Second generation devices are larger overall and look less like tobacco cigarettes.[92] Third generation devices include mechanical mods and variable voltage devices.[90] The fourth generation includes Sub ohm tanks and temperature control devices.[93] The power source is the biggest component of an e-cigarette,[29] which is frequently a rechargeable lithium-ion battery.[94]

Health effects

Positions of medical organizations

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In 2013, at least a quarter million middle school and high school students who never smoked tobacco cigarettes had used e-cigarettes. This was three times as many as in 2011.
2014 Centers for Disease Control (CDC) press release concerning e-cigarettes.[95]

Medical organizations differ regarding the health implications of e-cigarette use.[96] Many medical organizations have made statements about their health and safety. All agree that more research is needed.[6] There is general agreement that e-cigarettes likely expose users to fewer toxicants than tobacco.[6][97] International organizations such as the WHO and those from the US have hesitated to recommend e-cigarettes for quitting smoking, because of limited evidence of effectiveness and safety,.[21][44][98] Some from the UK have recommended their use by smokers unwilling or unable to quit.[99][100]

In July 2014, a report produced by the World Health Organization (WHO) reported limited evidence that e-cigarettes may help some smokers quit, but did not reach conclusions.[21] It suggested that smokers should be encouraged to use approved methods for help with quitting.[21] The same report also notes expert opinion that suggests e-cigarettes have a role in helping those who have failed to quit by other means.[21] Smokers will get the maximum health benefit if they completely quit all nicotine use.[21] A policy briefing by the Framework Convention Alliance notes widespread agreement that e-cigarettes are "almost certainly considerably less hazardous for individuals than cigarettes", but also notes widespread disagreement on the likelihood and impact of dual use, uptake by never-smokers, and re-normalisation of smoking.[101] The World Lung Foundation has applauded the WHO report's recommendation of tighter regulation due to safety concerns and the risk of increased nicotine addiction or tobacco use among young people.[102]

In a 2015 joint statement, Public Health England and twelve other UK medical bodies concluded "e-cigarettes are significantly less harmful than smoking."[103] PHE also stated that e-cigarettes are estimated to be 95% less harmful than smoking,[104] and that "...[it] looks forward to the arrival on the market of a choice of medicinally regulated products that can be made available to smokers by the NHS on prescription."[105] The UK National Health Service followed with the statement that e-cigarettes have approximately 5% of the risk of tobacco cigarettes,[106] while also concluding that there won't be a complete understanding of their safety for many years.[106] As of 2014, there are clinical trials in progress to test the quality, safety and effectiveness of e-cigarettes, but until these are complete the NHS maintains that the government could not give any advice on them or to recommend their use.[107]

The United States Centers for Disease Control and Prevention released a 2016 report titled E-cigarette Ads and Youth which concerned marketing towards adolescents.[108]

In 2016, the FDA stated its position that e-cigarettes are "likely less hazardous for an individual user than continued smoking of traditional cigarettes", but that the net population effect is unknown.[15]:234 In 2015, the United States Preventive Services Task Force concluded there is insufficient evidence to recommend e-cigarettes for smoking cessation, and recommended clinicians instead recommend more proven smoking cessation aids.[109] The National Institute on Drug Abuse raises concern over the possibility that they could perpetuate nicotine addiction and thus interfere with quitting.[110] In 2015, the American Academy of Pediatrics strongly recommended against using e-cigarettes to quit smoking, stating that for adolescents e-cigarettes are not effective in treating tobacco dependence.[111] In August 2014, the American Heart Association released a policy statement concluding that while e-cigarette aerosol is much less toxic then cigarette smoke, there is insufficient evidence for clinicians to counsel smokers to use them as a primary cessation aid. If a patient failed initial treatment or refuses to use cessation medication, and wishes to use e-cigarettes to quit, it is reasonable to support the attempt after informing about the uncertainties.[112] In 2014, the US FDA said "E-cigarettes have not been fully studied, so consumers currently don't know: the potential risks of e-cigarettes when used as intended, how much nicotine or other potentially harmful chemicals are being inhaled during use, or whether there are any benefits associated with using these products. Additionally, it is not known whether e-cigarettes may lead young people to try other tobacco products, including conventional cigarettes, which are known to cause disease and lead to premature death."[98]

Smoking cessation

File:CDC launches new ads in “Tips From Former Smokers” campaign.ogv
CDC launches "Tips From Former Smokers" ad campaign in 2015. The main information on e-cigarettes begins at 24:45.[113]

The available research on the safety and efficacy of e-cigarette use for smoking cessation is limited. Some consider the evidence contradictory,[9][112] while others attribute negative outcomes to inappropriate study design.[6][99] Some medical authorities recommend that e-cigarettes have a role in smoking cessation, and others disagree. Views of e-cigarettes' role range from on the one hand Public Health England, who recommend that stop-smoking practitioners should:- (1) advise people who want to quit to try e-cigarettes if they are not succeeding with conventional nicotine replacement therapy (NRT); and (2) advise people who cannot or do not want to quit to switch to e-cigarettes to reduce smoking-related disease[103] to, on the other hand, the United States Preventive Services Task Force that advised only use of conventional NRT products in smoking cessation and found insufficient evidence to recommend e-cigarettes for this purpose.[9]

There is tentative evidence that they can help people quit smoking.[6] However a 2016 meta-analysis based on 20 different studies found that smokers who used electronic cigarettes were 28% less likely to quit than those who had not tried electronic cigarettes.[114] This finding persisted whether the smokers were initially interested in quitting or not.[114] A 2015 meta-analysis on clinical trials of e-cigarettes for smoking cessation found that e-cigarettes containing nicotine are more effective than those that do not. They compared their finding that nicotine-containing e-cigarettes helped 20% of people quit with the results from other studies that found conventional NRT helps 10% of people quit.[115] There has only been one study directly comparing first generation e-cigarettes to conventional NRT as smoking cessation tools, so the comparative effectiveness is not known.[115] Two 2016 reviews found a trend towards benefit of e-cigarettes with nicotine for smoking cessation, but that the evidence was of low-quality.[116][117]

However, e-cigarettes have not been subject to the same efficacy testing as nicotine replacement products. Several authorities, including the World Health Organisation, take the view that there is not enough evidence to recommend e-cigarettes for quitting smoking in adults,[9] and there are studies showing a decline in smoking cessation among dual users.[114] A 2014 review found that e-cigarettes do not seem to improve cessation rates compared to regulated nicotine replacement products, and a trial found 29% of e-cigarette users were still vaping at 6 months, but only 8% of patch users still wore patches at 6 months.[47]

Harm reduction

Tobacco harm reduction (THR) is the replacement of tobacco cigarettes with lower risk products to reduce tobacco related death and disease.[118] THR has been controversial out of fear that tobacco companies cannot be trusted to produce and market products that will reduce the risks associated with tobacco use.[119] E-cigarettes can reduce smokers' exposure to carcinogens and other toxic substances found in tobacco.[119][120] Tobacco smoke contains 100 known carcinogens, and 900 potentially cancer causing chemicals,[17] none of which has been found in more than trace quantities in the cartridges or aerosol of e-cigarettes.[119] According to a 2011 review, while e-cigarettes cannot be considered "safe" because there is no safe level for carcinogens, they are doubtless safer than tobacco cigarettes.[119]

However, some reviews have concluded that the benefits and the health risks of e-cigarettes are uncertain,[8][9][10] and the long-term health effects are unknown.[11][12]

A core concern is that smokers who could have quit completely will develop an alternative nicotine addiction instead.[119] A 2014 review stated that promotion of vaping as a harm reduction aid is premature,[16] but in an effort to decrease tobacco related death and disease, e-cigarettes have a potential to be part of the harm reduction strategy.[17][18] Another review found that compared with cigarettes, e-cigarettes are likely to be much less, if at all, harmful to users or bystanders.[24] The authors warned against the potential harm of excessive regulation and advised health professionals to consider advising smokers who are reluctant to quit by other methods to switch to e-cigarettes as a safer alternative to smoking.[24] A 2015 Public Health England report concluded that e-cigarette use "releases negligible levels of nicotine into ambient air with no identified health risks to bystanders".[121] A 2014 review recommended that regulations for e-cigarettes could be similar to those for dietary supplements or cosmetic products to not limit their potential for harm reduction.[33] A 2012 review found e-cigarettes could considerably reduce traditional cigarettes use and they likely could be used as a lower risk replacement for traditional cigarettes, but there is not enough data on their safety and efficacy to draw definite conclusions.[88] E-cigarette use for risk reduction in high-risk groups such as people with mental disorders is unavailable.[122]

A 2014 Public Health England report concluded that hazards associated with products currently on the market are likely to be extremely low, and certainly much lower than smoking. However, harms could be reduced further through appropriate product standards.[123] They found that a considerable number of smokers want to reduce harm from smoking by using these products.[123] The British Medical Association encourages health professionals to recommend conventional nicotine replacement therapies, but for patients unwilling to use or continue using such methods, health professionals may present e-cigarettes as a lower-risk option than tobacco smoking.[124] The American Association of Public Health Physicians (AAPHP) suggests those who are unwilling to quit tobacco smoking or unable to quit with medical advice and pharmaceutical methods should consider other nicotine containing products such as electronic cigarettes and smokeless tobacco for long term use instead of smoking.[125] In an interview, the director of the Office on Smoking and Health for the U.S. federal agency Centers for Disease Control and Prevention (CDC) believes that there is enough evidence to say that using e-cigarettes is likely less harmful than smoking a pack of conventional cigarettes.[126] However, due to the lack of regulation of the contents of e-cigarettes and the presence of nicotine, the CDC has issued warnings.[126] A 2014 WHO report concluded that some smokers will switch completely to e-cigarettes from traditional tobacco but a "sizeable" number will use both.[21] This report found that such "dual use" of e-cigarettes and tobacco "will have much smaller beneficial effects on overall survival compared with quitting smoking completely."[21]

Safety

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Adverse effects of vaping include throat irritation, cough, increased airway resistance, nausea, vomiting, chest pain, increased blood pressure, and increased heart rate.
Claimed adverse effects of vaping.[127]

The safety of electronic cigarettes is uncertain.[8][9][10] However, they are likely much safer than tobacco cigarettes.[6][112][128] There is considerable variability between vaporizers and in quality of their liquid ingredients and thus the contents of the aerosol delivered to the user.[19][129][130] Reviews on the safety of electronic cigarettes, analyzing almost the same studies, resulted in substantially different conclusions.[131] In July 2014 the World Health Organization (WHO) report cautioned about potential risks of using e-cigarettes.[21] Regulated US Food and Drug Administration (FDA) products such as nicotine inhalers are probably safer than e-cigarettes.[16] In 2015, Public Health England stated that e-cigarettes are estimated to be 95% less harmful than smoking,[104] A 2014 systematic review concluded that the risks of e-cigarettes have been exaggerated by health authorities and stated that while there may be some remaining risk, the risk of e-cigarette use is likely small compared to smoking tobacco.[132]

The long-term effects of e-cigarette use are unknown.[11][12] However, improvements in lung function and pulmonary health have been demonstrated among smokers who have switched to e-cigarettes.[133][134] A 2014 Cochrane review found no serious adverse effects reported in trials.[6] Less serious adverse effects from e-cigarette use include throat and mouth inflammation, vomiting, nausea, and cough.[19] The evidence suggests they produce less harmful effects than tobacco.[135] A 2014 WHO report said, "ENDS use poses serious threats to adolescents and fetuses."[21] Aside from toxicity, there are also risks from misuse or accidents[132] such as contact with liquid nicotine,[136] fires caused by vaporizer malfunction,[19] and explosions as result from extended charging, unsuitable chargers, or design flaws.[132] Battery explosions are caused by an increase in internal battery temperature and some have resulted in severe skin burns.[8] There is a small risk of battery explosion in devices modified to increase battery power.[87]

The e-liquid has a low level of toxicity, and contamination with various chemicals has been identified in the product.[137] The majority of toxic chemicals found in tobacco smoke are absent in e-cigarette vapor.[132][123] Those which are present, are mostly below 1% the corresponding levels in tobacco smoke, and far below safety limits for occupational exposure.[25][138] Metal parts of e-cigarettes in contact with the e-liquid can contaminate it with metals.[132] Normal usage of e-cigarettes generates very low levels of formaldehyde.[139] A 2015 review found that later-generation e-cigarettes set at higher power may generate equal or higher levels of formaldehyde compared to smoking.[140][141] A 2015 review found that these levels were the result of overheating under test conditions that bear little resemblance to common usage.[139] The 2015 Public Health England report looking at the research concluded that by applying maximum power and increasing the time the device is used on a puffing machine, e-liquids can thermally degrade and produce high levels of formaldehyde.[26] Users detect the "dry puff" and avoid it, and the report concluded that "There is no indication that EC users are exposed to dangerous levels of aldehydes."[26] E-cigarette users are exposed to potentially harmful nicotine.[23] Nicotine is associated with cardiovascular disease, potential birth defects, and poisoning.[22] In vitro studies of nicotine have associated it with cancer, but carcinogenicity has not been demonstrated in vivo.[22] There is inadequate research to demonstrate that nicotine is associated with cancer in humans.[142] The risk is probably low from the inhalation of propylene glycol and glycerin.[24] No information is available on the long-term effects of the inhalation of flavors.[137]

E-cigarettes create vapor that consists of ultrafine particles, with the majority of particles in the ultrafine range.[19] The vapor has been found to contain flavors, propylene glycol, glycerin, nicotine, tiny amounts of toxicants, carcinogens, heavy metals, and metal nanoparticles, and other chemicals.[19][24] Exactly what comprises the vapor varies in composition and concentration across and within manufacturers.[23] However, e-cigarettes cannot be regarded as simply harmless.[143] There is a concern that some of the mainstream vapor exhaled by e-cigarette users can be inhaled by bystanders, particularly indoors.[29] E-cigarette use by a parent might lead to inadvertent health risks to offspring.[74] A 2014 review recommended that e-cigarettes should be regulated for consumer safety.[33] There is limited information available on the environmental issues around production, use, and disposal of e-cigarettes that use cartridges.[144] A 2014 review found "disposable e-cigarettes might cause an electrical waste problem."[122]

E-liquid

E-liquid is the mixture used in vapor products such as e-cigarettes[17] and generally consists of propylene glycol, glycerin, water, nicotine, and flavorings.[18] While the ingredients vary[6][7][17] the liquid typically contains 95% propylene glycol and glycerin.[145] There are many e-liquids manufacturers in the USA and worldwide,[146] and upwards of 8,000 flavors.[38] While there are currently no US Food and Drug Administration (FDA) manufacturing standards for e-liquid, the FDA has proposed regulations that are expected to be finalized in late 2015.[146] Industry standards have been created and published by the American E-liquid Manufacturing Standards Association (AEMSA).[147]

Addiction

Nicotine, a key ingredient in e-liquids, is a highly addictive substance, on a level comparable to heroin and cocaine.[148] Nicotine induces strong effects on the brain, which lead to considerable changes in the brain's physiology such as stimulation in regions of the cortex associated with reward, pleasure and reducing anxiety.[87] When nicotine intake stops, withdrawal symptoms include cravings for nicotine, anger/irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger or weight gain, and difficulty concentrating.[48][149] It is not clear whether e-cigarette use will decrease or increase overall nicotine addiction,[150] but the nicotine content in e-cigarettes is adequate to sustain nicotine dependence.[151]

The World Health Organization has raised concern about addiction for non-smokers,[21] and the National Institute on Drug Abuse said e-cigarettes could maintain nicotine addiction in those who are attempting to quit.[152] The limited available data suggests that the likelihood of abuse from e-cigarettes is smaller than traditional cigarettes.[153] A 2014 systematic review found that the concerns that e-cigarettes could lead non-smokers to start smoking are unsubstantiated.[132] No long-term studies have been done on the effectiveness of e-cigarettes in treating tobacco addiction,[16] but some evidence suggests that dual use of e-cigarettes and traditional cigarettes may be associated with greater nicotine dependence.[11]

Many studies have focused on young people in particular, since youthful experimentation with e-cigarettes could lead to lifelong addiction.[59] Various organizations, including the UATLD, the AAP and the FDA, have expressed concern that e-cigarette use could increase nicotine addiction in youth.[126][152][154][155][156][157][158] Although regular use of e-cigarettes is generally very low by people who have never smoked,[24] significant numbers of teenagers who have never smoked tobacco have experimented with e-cigarettes.[19] The degree to which teens are using e-cigarettes in ways the manufacturers did not intend, such as increasing the nicotine delivery, is unknown,[136] as is the extent to which e-cigarette use will lead to addiction or substance dependence in youth.[136]

Nicotine yield

Smoking a traditional cigarette yields between 0.5 and 1.5 mg of nicotine,[151] but the nicotine content of the cigarette is only weakly correlated with the levels of nicotine in the smoker's bloodstream.[159] The amount of nicotine in the e-cigarette aerosol varies widely either from puff-to-puff or among products of the same company.[23] In practice e-cigarette users tend to reach lower blood nicotine concentrations than smokers, particularly when the users are inexperienced or using earlier-generation devices.[90] Nicotine in tobacco smoke is absorbed into the bloodstream rapidly, and e-cigarette vapor is relatively slow in this regard.[90] The concentration of nicotine in e-liquid ranges up to 36 mg/mL.[123] New EU regulations cap this at a maximum of 2% (20 mg/mL), but this is an arbitrary ceiling based on limited data.[8] In practice the nicotine concentration in an e-liquid is not a reliable guide to the amount of nicotine that reaches the bloodstream.[123]

History

The earliest e-cigarette can be traced to American Herbert A. Gilbert,[160] who in 1963 patented "a smokeless non-tobacco cigarette" that involved "replacing burning tobacco and paper with heated, moist, flavored air".[161][162] This device produced flavored steam without nicotine.[162] The patent was granted in 1965.[163] Gilbert's invention was ahead of its time.[164] There were prototypes, but it received little attention[165] and was never commercialized[162] because smoking was still fashionable at that time.[166] Gilbert said in 2013 that today's electric cigarettes follow the basic design set forth in his original patent.[163]

Hon Lik, a Chinese pharmacist and inventor who worked as a research pharmacist for a company producing ginseng products, is credited with the invention of the modern e-cigarette.[27] Lik quit smoking after his father, also a heavy smoker, died of lung cancer.[27] In 2001, he thought of using a high frequency, piezoelectric ultrasound-emitting element to vaporize a pressurized jet of liquid containing nicotine.[167] This design creates a smoke-like vapor.[27] Lik said that using resistance heating obtained better results and the difficulty was to scale down the device to a small enough size.[167] Lik's invention was intended to be an alternative to smoking.[167]

Ruyan electronic cigar first generation.
The Ruyan e-cigar was first launched in China in 2004.

Hon Lik registered a patent for the modern e-cigarette design in 2003.[167] The e-cigarette was first introduced to the Chinese domestic market in 2004.[27] Many versions made their way to the U.S., sold mostly over the Internet by small marketing firms.[27] E-cigarettes entered the European market and the US market in 2006 and 2007.[50] The company that Lik worked for, Golden Dragon Holdings, registered an international patent in November 2007.[168] The company changed its name to Ruyan (如烟, literally "Resembling smoking") later the same month[169] and started exporting its products.[27] Many US and Chinese e-cig makers copied his designs illegally, so Lik has not received much financial reward for his invention (although some US manufacturers have compensated him through out of court settlements).[170] Ruyan later changed its company name to Dragonite International Limited.[169] Most e-cigarettes today use a battery-powered heating element rather than the earlier ultrasonic technology design.[112]

When e-cigarettes entered the international market, some users were dissatisfied with their performance,[171][172] and the e-cigarette continued to evolve from the first generation three-part device.[91] In 2007 British entrepreneurs Umer and Tariq Sheikh invented the cartomizer.[173] This is a mechanism that integrates the heating coil into the liquid chamber.[173] They launched this new device in the UK in 2008 under their Gamucci brand,[172] and the design is now widely adopted by most "cigalike" brands.[91] Other users tinkered with various parts to produce more satisfactory homemade devices, and the hobby of "modding" was born.[171] The first mod to replace the e-cigarette's case to accommodate a longer-lasting battery, dubbed the "screwdriver", was developed by Ted and Matt Rogers[171] in 2008.[94] Other enthusiasts built their own mods to improve functionality or aesthetics.[171] When pictures of mods appeared at online vaping forums many people wanted them, so some mod makers produced more for sale.[171]

The demand for customizable e-cigarettes prompted some manufacturers to produce devices with interchangeable components that could be selected by the user.[94] In 2009, Joyetech developed the eGo series[173] which offered the power of the screwdriver model and a user-activated switch to a wide market.[94] The clearomizer was invented in 2009.[173] Originating from the cartomizer design, it contained the wicking material, an e-liquid chamber, and an atomizer coil within a single clear component.[173] The clearomizer allows the user to monitor the liquid level in the device.[173] Soon after the clearomizer reached the market, replaceable atomizer coils and variable voltage batteries were introduced.[173] Clearomizers and eGo batteries became the best-selling customizable e-cigarette components in early 2012.[94]

International tobacco companies dismissed e-cigarettes as a fad at first.[174] However, recognizing the development of a potential new market sector that could render traditional tobacco products obsolete,[175] they began to produce and market their own brands of e-cigarettes and acquire existing e-cigarette companies.[176] blu eCigs, a prominent US e-cigarette manufacturer, was acquired by Lorillard Inc. in 2012.[177] British American Tobacco was the first tobacco business to sell e-cigarettes in the UK.[178] They launched Vype in 2013, while Imperial Tobacco's Fontem Ventures acquired the intellectual property owned by Hon Lik through Dragonite International Limited for $US 75 million in 2013 and launched Puritane in partnership with Boots UK.[179] On 1 October 2013 Lorillard Inc. acquired another e-cigarette company, this time the UK based company SKYCIG.[180] SKY was rebranded as blu.[181] On 3 February 2014, Altria Group, Inc. acquired popular electronic cigarette brand Green Smoke for $110 million.[182] The deal was finalized in April 2014 for $110 million with $20 million in incentive payments.[182] Altria also markets its own e-cigarette, the MarkTen, while Reynolds American has entered the sector with its Vuse product.[176] Philip Morris, the world's largest tobacco firm, purchased UK's Nicocigs in June 2014.[183] On 30 April 2015, Japan Tobacco bought the US Logic e-cigarette brand.[184] Japan Tobacco also bought the UK E-Lites brand in June 2014.[184] On 15 July 2014, Lorillard sold blu to Imperial Tobacco as part of a deal for $7.1 billion.[185]

In 2014, dollar sales of customizable e-cigarettes and e-liquid surpassed sales of cigalikes in the US, despite the fact that customizables are less expensive.[186]

Society and culture

Consumers of e-cigarettes, sometimes called "vapers", have shown passionate support for the device that other nicotine replacement therapy did not receive.[123][187] This suggests e-cigarettes have potential mass appeal that could challenge combustible tobacco's market position.[123]

A subculture has emerged which calls itself "the vaping community".[187][188] Members of this emerging subculture often see e-cigarettes as a safer alternative to smoking[24] and some view it as a hobby.[189] The online forum E-Cig-Reviews.com was one of the first major communities.[171] It and other online forums, such as UKVaper.org, were the origins of the hobby of modding.[171] There are also groups on Facebook and Reddit.[190] Online forums based around modding have grown in the vaping community.[191] Vapers energetically embrace activities associated with e-cigarettes and sometimes act as unpaid evangelicals according to a 2014 review.[80] A 2014 Postgraduate Medical Journal editorial stated that e-cigarette companies have a substantial online presence, as well as many individual vapers who blog and tweet about e-cigarette related products.[192] The editorial stated that vapers "also engage in grossly offensive online attacks on anyone who has the temerity to suggest that ENDS are anything other than an innovation that can save thousands of lives with no risks".[192] A 2014 review stated that tobacco and e-cigarette companies interact with consumers for their policy agenda.[19] The companies use websites, social media, and marketing to get consumers involved in opposing bills that include e-cigarettes in smoke-free laws.[19] The same review said this is similar to tobacco industry activity going back to the 1980s.[19] These approaches were used in Europe to minimize the EU Tobacco Product Directive in October 2013.[19] True grassroots lobbying also influenced the TPD decision.[193] Rebecca Taylor, a member of the European Parliament, stated, "to say it's an orchestrated campaign is absolute rubbish."[193] Contempt for "big tobacco" is part of vaping culture.[194][195]

E-cigarette user blowing a large cloud of aerosol (vapor). This activity is known as cloud-chasing.
E-cigarette user blowing a cloud of aerosol (vapor). The activity is known as cloud-chasing.[196]

Large gatherings of vapers, called vape meets, take place around the US.[187] They focus on e-cig devices, accessories, and the lifestyle that accompanies them.[187] Vapefest, which started in 2010, is an annual show hosted by different cities.[190] People attending these meetings are usually enthusiasts that use specialized, community-made products not found in convenience stores or gas stations.[187] These products are mostly available online or in dedicated "vape" storefronts where mainstream e-cigarettes brands from the tobacco industry and larger e-cig manufacturers are not as popular.[197] Some vape shops have a vape bar where patrons can test out different e-liquids and socialize.[198] The Electronic Cigarette Convention in North America which started in 2013, is an annual show where companies and consumers meet up.[199]

A subclass of vapers configure their atomizers to produce large amounts of vapor by using low-resistance heating coils.[200] This practice is called "cloud-chasing"[201][202] By using a coil with very low resistance, the batteries are stressed to a potentially unsafe extent.[201] This could present a risk of dangerous battery failures.[201] As vaping comes under increased scrutiny, some members of the vaping community have voiced their concerns about cloud-chasing, claiming the practice gives vapers a bad reputation when doing it in public.[203] The Oxford Dictionaries' word of the year for 2014 was "vape".[204]

Regulation

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A no smoking or vaping sign from the US
A no smoking or vaping sign from the US.

Regulation of e-cigarettes varies across countries and states, ranging from no regulation to banning them entirely.[34] As of 2015, around two thirds of major nations have regulated e-cigarettes in some way.[205] Because of the potential relationship with tobacco laws and medical drug policies, e-cigarette legislation is being debated in many countries.[33] in 2016 the US Department of Transportation banned the use of e-cigs on commercial flights.[206] This regulation applies to all flights to and from the United States.[206]

The legal status of e-cigarettes is currently pending in many countries.[19] Some countries such Brazil, Singapore, the Seychelles, and Uruguay have banned e-cigarettes.[19] In Canada, they are technically illegal to sell, as no nicotine-containing e-fluid is approved by Health Canada, but this is generally unenforced and they are commonly available for sale Canada-wide.[207] In the US and the UK, the use and sale of e-cigarettes are legal.[208][209] In May 2016 the FDA used its authority under the Family Smoking Prevention and Tobacco Control Act to deem e-cigarette devices and e-liquids to be tobacco products, which meant it intended to regulate the marketing, labelling, and manufacture of devices and liquids; vape shops that mix e-liquids or make or modify devices were considered manufacturing sites that needed to register with FDA and comply with good manufacturing practice regulation.[15]:12, 265ff

In February 2014 the European Parliament passed regulations requiring standardization and quality control for liquids and vaporizers, disclosure of ingredients in liquids, and child-proofing and tamper-proofing for liquid packaging.[35][210] In April 2014 the US FDA published proposed regulations for e-cigarettes along similar lines.[211][212] In the US some states tax e-cigarettes as tobacco products, and some state and regional governments have broadened their indoor smoking bans to include e-cigarettes.[73] As of 9 October 2015, at least 48 states and 2 territories banned e-cigarette sales to minors.[213]

E-cigarettes have been listed as drug delivery devices in several countries because they contain nicotine, and their advertising has been restricted until safety and efficacy clinical trials are conclusive.[214] Since they do not contain tobacco, television advertising in the US is not restricted.[215] Some countries have regulated e-cigarettes as a medical product even though they have not approved them as a smoking cessation aid.[216] A 2014 review stated the emerging phenomenon of e-cigarettes has raised concerns in the health community, governments, and the general public and recommended that e-cigarettes should be regulated to protect consumers.[33] It added, "heavy regulation by restricting access to e-cigarettes would just encourage continuing use of much unhealthier tobacco smoking." [33] A 2014 review said these products should be considered for regulation in view of the "reported adverse health effects".[216]

Marketing

Adolescents are exposed to electronic cigarette marketing in a number of ways, many of which are not available to traditional cigarettes.[108]

A 2014 review said, "the e-cigarette companies have been rapidly expanding using aggressive marketing messages similar to those used to promote cigarettes in the 1950s and 1960s."[19] E-cigarettes and nicotine are regularly promoted as safe and beneficial in the media and on brand websites.[74] While advertising of tobacco products is banned in most countries, television and radio e-cigarette advertising in some countries may be indirectly encouraging traditional cigarette smoking.[19] There is no evidence that the cigarette brands are selling e-cigarettes as part of a plan to phase out traditional cigarettes, despite some claiming to want to cooperate in "harm reduction".[19] In the US, six large e-cigarette businesses spent $59.3 million on promoting e-cigarettes in 2013.[217] Easily circumvented age verification at company websites enables young people to access and be exposed to marketing for e-cigarettes.[71]

A national US television advertising campaign starred Steven Dorff exhaling a "thick flume" of what the ad describes as "vapor, not tobacco smoke", exhorting smokers with the message "We are all adults here, it's time to take our freedom back."[218] The ads, in a context of longstanding prohibition of tobacco advertising on TV, were criticized by organizations such as Campaign for Tobacco-Free Kids as undermining anti-tobacco efforts.[218] Cynthia Hallett of Americans for Non-Smokers' Rights described the US advertising campaign as attempting to "re-establish a norm that smoking is okay, that smoking is glamorous and acceptable".[218] University of Pennsylvania communications professor Joseph Cappella stated that the setting of the ad near an ocean was meant to suggest an association of clean air with the nicotine product.[218] In 2012 and 2013, e-cigarette companies advertised to a large television audience in the US which included 24 million youth.[219] The channels on which e-cigarette advertising reached the largest numbers of youth (ages 12–17) were AMC, Country Music Television, Comedy Central, WGN America, TV Land, and VH1.[219]

A 2014 review said e-cigarettes are aggressively promoted, mostly via the internet, as a healthy alternative to smoking in the US.[29] Celebrity endorsements are used to encourage e-cigarette use.[75] "Big tobacco" markets e-cigarettes to young people,[220] with industry strategies including cartoon characters and candy flavors to sell e-cigarettes.[221] E-cigarette companies commonly promote that their products contain only water, nicotine, glycerin, propylene glycol, and flavoring but this assertion is misleading as scientists have found differing amounts of heavy metals in the vapor, including chromium, nickel, tin, silver, cadmium, mercury, and aluminum.[57] The assertion that e-cigarette emit "only water vapor" is false because the evidence indicates e-cigarette vapor contains possibly harmful chemicals such as nicotine, carbonyls, metals, and organic volatile compounds, in addition to particulates.[222]

Economics

Vaping stand, London shopping centre.

The number of e-cigarettes sold has increased every year[112] until 2015, when a slowdown in the growth in usage occurred in both the US and the UK.[45][46] As of 2014 there were at least 466 e-cigarette brands.[49] Worldwide e-cigarette sales in 2014 were around US$7 billion.[37] Approximately 30–50% of total e-cigarettes sales are handled on the internet.[29]

As of 2015 most e-cigarette devices were made in China,[28] mainly in Shenzhen.[223][224] Chinese companies' market share of e-liquid is low.[225] In China, where combustible cigarettes are relatively inexpensive.[226]

In the US, tobacco producers have a significant share of the e-cigarette market.[59][227] As of 2015, 80% of all e-cigarette sales in convenience stores in the U.S. were products made by tobacco companies.[228] According to Nielsen Holdings, convenience store e-cigarette sales in the US went down for the first time during the four-week period ending on 10 May 2014.[229] Wells Fargo analyst Bonnie Herzog attributes this decline to a shift in consumers' behavior, buying more specialized devices or what she calls "vapor/tank/mods (VTMs)" that are not tracked by Nielsen.[229] Wells Fargo estimated that VTMs accounted for 57% of the 3.5 billion dollar market in the US for vapor products in 2015.[230] In 2014, the Smoke-Free Alternatives Trade Association estimated that there were 35,000 vape shops in the US, more than triple the number a year earlier.[231] However the 2015 slowdown in market growth affected VTMs as well.[45]

In Canada, e-cigarettes had an estimated value of 140 million CAD in 2015.[232] There are numerous e-cigarette retail shops in Canada.[233] A 2014 audit of retailers in four Canadian cities found that 94% of grocery stores, convenience stores, and tobacconist shops which sold e-cigarettes sold nicotine-free varieties only, while all vape shops stocked at least one nicotine-containing product.[234]

In the UK in 2015 the "most prominent brands of cigalikes" were owned by tobacco companies, but except for one model all the tank types came from "non-tobacco industry companies".[99] However some tobacco industry products, while using prefilled cartridges, resemble tank models.[99]

France's electronic cigarette market was estimated by Groupe Xerfi to be 130 million in 2015. Additionally, France's e-liquid market was estimated at €265 million.[235] In December 2015, there were 2,400 vape shops in France, 400 fewer than in March of the same year.[235] Industry organization Fivape said the reduction was due to consolidation, not to reduced demand.[235]

Related technologies

Other devices to deliver inhaled nicotine have been developed.[236] They aim to mimic the ritual and behavioral aspects of traditional cigarettes.[236]

British American Tobacco, through their subsidiary Nicoventures Limited, licensed a nicotine delivery system based on existing asthma inhaler technology from UK-based healthcare company Kind Consumer Limited.[237] In September 2014 a product based on this named Voke obtained approval from the United Kingdom's Medicines and Healthcare Products Regulatory Agency.[238]

Philip Morris International (PMI) bought the rights to a nicotine pyruvate technology developed by Jed Rose at Duke University.[239] The technology is based on the chemical reaction between pyruvic acid and nicotine, which produces an inhalable nicotine pyruvate vapor.[240]

PAX Labs has developed vaporizers that heats the leaves of tobacco to deliver nicotine in a vapor.[241][242] On 1 June 2015, they introduced Juul a different type of e-cigarette which delivers 10 times as much nicotine as other e-cigarettes, equivalent to an actual cigarette puff.[243]

BLOW started selling e-hookahs, an electronic version of the hookah, in 2014.[244]

Several companies including Canada's Eagle Energy Vapor are selling caffeine-based e-cigarettes instead of nicotine.[245]

Notes

  1. Electronic cigarettes are variously known as e-cigarettes, e-cigs, EC,[1] electronic nicotine delivery systems (ENDS) or electronic non-nicotine delivery system (ENNDS),[2] personal vaporizer, or PV.[3]

References

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  92. Lua error in package.lua at line 80: module 'strict' not found.
  93. Lua error in package.lua at line 80: module 'strict' not found.
  94. 94.0 94.1 94.2 94.3 94.4 Lua error in package.lua at line 80: module 'strict' not found.
  95. Lua error in package.lua at line 80: module 'strict' not found.
  96. Lua error in package.lua at line 80: module 'strict' not found.
  97. Lua error in package.lua at line 80: module 'strict' not found.
  98. 98.0 98.1 Lua error in package.lua at line 80: module 'strict' not found.
  99. 99.0 99.1 99.2 99.3 Lua error in package.lua at line 80: module 'strict' not found.
  100. Lua error in package.lua at line 80: module 'strict' not found.
  101. Lua error in package.lua at line 80: module 'strict' not found.
  102. Lua error in package.lua at line 80: module 'strict' not found.
  103. 103.0 103.1 Lua error in package.lua at line 80: module 'strict' not found.
  104. 104.0 104.1 Lua error in package.lua at line 80: module 'strict' not found.
  105. Lua error in package.lua at line 80: module 'strict' not found.
  106. 106.0 106.1 Lua error in package.lua at line 80: module 'strict' not found.
  107. Lua error in package.lua at line 80: module 'strict' not found.
  108. 108.0 108.1 Lua error in package.lua at line 80: module 'strict' not found.
  109. Lua error in package.lua at line 80: module 'strict' not found.
  110. Lua error in package.lua at line 80: module 'strict' not found.
  111. Lua error in package.lua at line 80: module 'strict' not found.
  112. 112.0 112.1 112.2 112.3 112.4 Lua error in package.lua at line 80: module 'strict' not found.
  113. Lua error in package.lua at line 80: module 'strict' not found.
  114. 114.0 114.1 114.2 Lua error in package.lua at line 80: module 'strict' not found.
  115. 115.0 115.1 Lua error in package.lua at line 80: module 'strict' not found.
  116. Lua error in package.lua at line 80: module 'strict' not found.
  117. Lua error in package.lua at line 80: module 'strict' not found.
  118. Lua error in package.lua at line 80: module 'strict' not found.
  119. 119.0 119.1 119.2 119.3 119.4 Lua error in package.lua at line 80: module 'strict' not found.
  120. Lua error in package.lua at line 80: module 'strict' not found.
  121. Lua error in package.lua at line 80: module 'strict' not found.
  122. 122.0 122.1 Lua error in package.lua at line 80: module 'strict' not found.
  123. 123.0 123.1 123.2 123.3 123.4 123.5 123.6 Lua error in package.lua at line 80: module 'strict' not found.
  124. Lua error in package.lua at line 80: module 'strict' not found.
  125. Lua error in package.lua at line 80: module 'strict' not found.
  126. 126.0 126.1 126.2 Lua error in package.lua at line 80: module 'strict' not found.
  127. Detailed reference list is located on a separate image page.
  128. Lua error in package.lua at line 80: module 'strict' not found.
  129. Lua error in package.lua at line 80: module 'strict' not found.
  130. Lua error in package.lua at line 80: module 'strict' not found.
  131. Lua error in package.lua at line 80: module 'strict' not found.
  132. 132.0 132.1 132.2 132.3 132.4 132.5 Lua error in package.lua at line 80: module 'strict' not found.
  133. Lua error in package.lua at line 80: module 'strict' not found.
  134. Lua error in package.lua at line 80: module 'strict' not found.
  135. Lua error in package.lua at line 80: module 'strict' not found.
  136. 136.0 136.1 136.2 Lua error in package.lua at line 80: module 'strict' not found.
  137. 137.0 137.1 Lua error in package.lua at line 80: module 'strict' not found.
  138. Lua error in package.lua at line 80: module 'strict' not found.
  139. 139.0 139.1 Lua error in package.lua at line 80: module 'strict' not found.
  140. Lua error in package.lua at line 80: module 'strict' not found.
  141. Lua error in package.lua at line 80: module 'strict' not found.
  142. Lua error in package.lua at line 80: module 'strict' not found.
  143. Lua error in package.lua at line 80: module 'strict' not found.
  144. Lua error in package.lua at line 80: module 'strict' not found.
  145. Lua error in package.lua at line 80: module 'strict' not found.
  146. 146.0 146.1 Lua error in package.lua at line 80: module 'strict' not found.
  147. Lua error in package.lua at line 80: module 'strict' not found.
  148. Lua error in package.lua at line 80: module 'strict' not found.
  149. Lua error in package.lua at line 80: module 'strict' not found.
  150. Lua error in package.lua at line 80: module 'strict' not found.
  151. 151.0 151.1 Lua error in package.lua at line 80: module 'strict' not found.
  152. 152.0 152.1 Lua error in package.lua at line 80: module 'strict' not found.
  153. Lua error in package.lua at line 80: module 'strict' not found.
  154. Lua error in package.lua at line 80: module 'strict' not found.
  155. Lua error in package.lua at line 80: module 'strict' not found.
  156. Lua error in package.lua at line 80: module 'strict' not found.
  157. Lua error in package.lua at line 80: module 'strict' not found.
  158. Lua error in package.lua at line 80: module 'strict' not found.
  159. Lua error in package.lua at line 80: module 'strict' not found.
  160. Lua error in package.lua at line 80: module 'strict' not found.
  161. Lua error in package.lua at line 80: module 'strict' not found.
  162. 162.0 162.1 162.2 Lua error in package.lua at line 80: module 'strict' not found.
  163. 163.0 163.1 Lua error in package.lua at line 80: module 'strict' not found.
  164. Lua error in package.lua at line 80: module 'strict' not found.
  165. Lua error in package.lua at line 80: module 'strict' not found.
  166. Lua error in package.lua at line 80: module 'strict' not found.
  167. 167.0 167.1 167.2 167.3 Lua error in package.lua at line 80: module 'strict' not found.
  168. Lua error in package.lua at line 80: module 'strict' not found.
  169. 169.0 169.1 Lua error in package.lua at line 80: module 'strict' not found.
  170. Lua error in package.lua at line 80: module 'strict' not found.
  171. 171.0 171.1 171.2 171.3 171.4 171.5 171.6 Lua error in package.lua at line 80: module 'strict' not found.
  172. 172.0 172.1 Lua error in package.lua at line 80: module 'strict' not found.
  173. 173.0 173.1 173.2 173.3 173.4 173.5 173.6 Lua error in package.lua at line 80: module 'strict' not found.
  174. Lua error in package.lua at line 80: module 'strict' not found.
  175. Lua error in package.lua at line 80: module 'strict' not found.
  176. 176.0 176.1 Lua error in package.lua at line 80: module 'strict' not found.
  177. Lua error in package.lua at line 80: module 'strict' not found.
  178. Lua error in package.lua at line 80: module 'strict' not found.
  179. Lua error in package.lua at line 80: module 'strict' not found.
  180. Lua error in package.lua at line 80: module 'strict' not found.
  181. Lua error in package.lua at line 80: module 'strict' not found.
  182. 182.0 182.1 Lua error in package.lua at line 80: module 'strict' not found.
  183. Lua error in package.lua at line 80: module 'strict' not found.
  184. 184.0 184.1 Lua error in package.lua at line 80: module 'strict' not found.
  185. Lua error in package.lua at line 80: module 'strict' not found.
  186. Lua error in package.lua at line 80: module 'strict' not found.
  187. 187.0 187.1 187.2 187.3 187.4 Lua error in package.lua at line 80: module 'strict' not found.
  188. Lua error in package.lua at line 80: module 'strict' not found.
  189. Lua error in package.lua at line 80: module 'strict' not found.
  190. 190.0 190.1 Lua error in package.lua at line 80: module 'strict' not found.
  191. Lua error in package.lua at line 80: module 'strict' not found.
  192. 192.0 192.1 Lua error in package.lua at line 80: module 'strict' not found.
  193. 193.0 193.1 Lua error in package.lua at line 80: module 'strict' not found.
  194. Lua error in package.lua at line 80: module 'strict' not found.
  195. Lua error in package.lua at line 80: module 'strict' not found.
  196. Lua error in package.lua at line 80: module 'strict' not found.
  197. Lua error in package.lua at line 80: module 'strict' not found.
  198. Lua error in package.lua at line 80: module 'strict' not found.
  199. Lua error in package.lua at line 80: module 'strict' not found.
  200. Lua error in package.lua at line 80: module 'strict' not found.
  201. 201.0 201.1 201.2 Lua error in package.lua at line 80: module 'strict' not found.
  202. Lua error in package.lua at line 80: module 'strict' not found.
  203. Lua error in package.lua at line 80: module 'strict' not found.
  204. Lua error in package.lua at line 80: module 'strict' not found.
  205. Lua error in package.lua at line 80: module 'strict' not found.
  206. 206.0 206.1 Lua error in package.lua at line 80: module 'strict' not found.
  207. Lua error in package.lua at line 80: module 'strict' not found.
  208. Lua error in package.lua at line 80: module 'strict' not found.
  209. Lua error in package.lua at line 80: module 'strict' not found.
  210. Lua error in package.lua at line 80: module 'strict' not found.
  211. Lua error in package.lua at line 80: module 'strict' not found.
  212. Lua error in package.lua at line 80: module 'strict' not found.
  213. Lua error in package.lua at line 80: module 'strict' not found.
  214. Lua error in package.lua at line 80: module 'strict' not found.
  215. Lua error in package.lua at line 80: module 'strict' not found.
  216. 216.0 216.1 Lua error in package.lua at line 80: module 'strict' not found.
  217. Lua error in package.lua at line 80: module 'strict' not found.
  218. 218.0 218.1 218.2 218.3 Lua error in package.lua at line 80: module 'strict' not found.
  219. 219.0 219.1 Lua error in package.lua at line 80: module 'strict' not found.
  220. Lua error in package.lua at line 80: module 'strict' not found.
  221. Lua error in package.lua at line 80: module 'strict' not found.
  222. Lua error in package.lua at line 80: module 'strict' not found.
  223. Lua error in package.lua at line 80: module 'strict' not found.
  224. Lua error in package.lua at line 80: module 'strict' not found.
  225. Lua error in package.lua at line 80: module 'strict' not found.
  226. Lua error in package.lua at line 80: module 'strict' not found.
  227. Lua error in package.lua at line 80: module 'strict' not found.
  228. Lua error in package.lua at line 80: module 'strict' not found.
  229. 229.0 229.1 Lua error in package.lua at line 80: module 'strict' not found.
  230. Lua error in package.lua at line 80: module 'strict' not found.
  231. Lua error in package.lua at line 80: module 'strict' not found.
  232. Lua error in package.lua at line 80: module 'strict' not found.
  233. Lua error in package.lua at line 80: module 'strict' not found.
  234. Lua error in package.lua at line 80: module 'strict' not found.
  235. 235.0 235.1 235.2 Lua error in package.lua at line 80: module 'strict' not found.
  236. 236.0 236.1 Lua error in package.lua at line 80: module 'strict' not found.
  237. Lua error in package.lua at line 80: module 'strict' not found.
  238. Lua error in package.lua at line 80: module 'strict' not found.
  239. Lua error in package.lua at line 80: module 'strict' not found.
  240. Lua error in package.lua at line 80: module 'strict' not found.
  241. Lua error in package.lua at line 80: module 'strict' not found.
  242. Lua error in package.lua at line 80: module 'strict' not found.
  243. Lua error in package.lua at line 80: module 'strict' not found.
  244. Lua error in package.lua at line 80: module 'strict' not found.
  245. Lua error in package.lua at line 80: module 'strict' not found.

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