Health effects of electronic cigarettes: Difference between revisions

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Use of electronic cigarettes raises concerns regarding health effects.^[1] Risks involved in use are deemed uncertain,^[2]^[3] on account of there being little data regarding health effects,^[4] and to the variability of vaporizers and the composition, concentration and quality of their liquid ingredients and thus the contents of the "vapor" delivered to the user.^[5]^[2]^[6] The limited evidence suggests that e-cigarettes are probably safer than traditional cigarettes.^[6]

Safety concerns surrounding e-cigarettes generally fall into two categories: ordinary risks to the user, and risks from misuse or accidents (e.g., accidental fires caused by vaporizer malfunction, other vaporizer design issues, or accidental contact with liquid nicotine).

Electronic cigarette usage appears to be similar in toxicity to the use of other nicotine replacement products, but there is not enough data to draw conclusions.^[7] The evidence suggests that other products accepted by the US Food and Drug Administration (FDA), such as nicotine inhalers may be a safer way to give nicotine than e-cigarettes.^[8] A July 2014 World Health Organization (WHO) report cautioned about potential risks of using electronic cigarettes. The report concluded that "the existing evidence shows that ENDS aerosol is not merely "water vapour" as is often claimed in the marketing for these products. ENDS use poses serious threats to adolescents and fetuses. In addition, it increases exposure of non-smokers and bystanders to nicotine and a number of toxicants."^[9] A 2014 systematic review concluded that the risks of e-cigarettes have been exaggerated by health authorities and stated that it is apparent that there may be some remaining risk accompanied with e-cigarette use, though the risk of e-cigarette use is likely small compared to smoking tobacco.^[10] As of 2014^[update], e-cigarettes cannot be regarded as harmless.^[11] A 2013 review found that until additional data is available, using e-cigarettes cannot be regarded as safe.^[12] No long-term studies have shown that e-cigarettes are a "healthier alternative" to traditional cigarettes.^[8]

The amount of nicotine inhaled by the user is not clear.^[8] The risk is probably low from the inhalation of propylene glycol and glycerol.^[13] When heated at hotter temperatures glycerol may generate harmful acrolein.^[13] Acrolein levels were reduced by 60% in dual users and 80% for those that completely switched to e-cigarettes when compared to traditional cigarettes.^[13] There are no studies of the short- and long-term effects of the inhalation of the various aromatic substances used as flavorings.^[12] The levels of chemical constituents in the vapor were found to be 1 to 2 orders of magnitude smaller than in cigarette smoke but greater compared to a nicotine inhaler.^[5] There is limited information available on the environmental issues around the production, the usage, and the disposal of e-cigarette models that use cartridges.^[14] While no serious adverse effects from e-cigarettes have yet been reported in trials,^[15] the long-term health impacts of e-cigarette use are unknown.^[13]^[16] Less serious adverse effects from e-cigarette use can include throat and mouth inflammation, vomiting, nausea, and cough.^[5]

The aerosol (mist^[12]) emitted from an e-cigarette is commonly but inaccurately called vapor.^[17] The particle size distribution of particles emitted by e-cigarettes is similar to that of traditional cigarettes, with the majority of particles in the ultrafine range (modes, ≈100–200 nm).^[5] The aerosol particle concentration is 5 times lower from an e-cigarette than from a traditional cigarette.^[8] The particle size is larger than in cigarette smoke, with the mean size being 600nm in inhaled aerosol and 300nm in exhaled.^[12] Exhaled vapor consists of nicotine and some other particles, primarily consisting of flavors, aroma transporters, glycerol and propylene glycol.^[13] A 2014 WHO report stated passive exposure was a concern, indicating that current evidence is insufficient to determine whether the levels of exhaled vapor are safe to involuntarily exposed bystanders.^[9] The report stated that "it is unknown if the increased exposure to toxicants and particles in exhaled aerosol will lead to an increased risk of disease and death among bystanders."^[9] E-cigarette vapor has notably fewer toxicants than cigarette smoke and is likely to pose less harm to users or bystanders.^[5] Other studies found insufficient data to determine the impact on public health of e-cigarettes,^[18] and recommended that e-cigarettes should be regulated for consumer safety.^[1]

Health concerns

The emerging phenomenon of e-cigarettes is raising concerns among the health community, pharmaceutical industry, and other groups.^[1] A 2014 review recommended that e-cigarettes should be adequately tested for consumer safety.^[1] Another 2014 review stated that there are "reported" adverse health effects.^[19] For example, they found that "The Food and Drug Administration (FDA) reported that e-cigarettes contain carcinogens and toxic chemicals, such as nitrosamines and diethylene glycol, which have potentially harmful effects on humans."^[19] Additionally, a WHO report in 2009 cautioned that the "safety of e-cigarettes is not confirmed."^[19] "In a nutshell, the WHO report shows that e-cigarettes and similar devices pose threats to public health," said Douglas Bettcher, director of WHO's prevention of noncommunicable diseases.^[20] ^{[unreliable source?]} A 2014 review stated that "The precautionary principle may be invoked when a phenomenon, a product or a process with potentially dangerous effects has not been subjected to full scientific and objective evaluation so that the harm cannot be determined with sufficient certainty.^[1] In several countries advertising for e-cigarettes has been monetarily restricted until safety and efficacy clinical trials are conclusive.^[21] A 2014 systematic review found that "Due to many methodological problems, severe conflicts of interest, the relatively few and often small studies, the inconsistencies and contradictions in results, and the lack of long-term follow-up no firm conclusions can be drawn on the safety of ECs."^[11]

Adverse effects

No serious adverse effects from e-cigarette have been reported in trials.^[15] Less serious adverse effects including throat and mouth inflammation, vomiting, nausea, and cough have resulted from e-cigarette use.^[5] Short-term adverse effects include mouth and throat inflammation, dry cough, and nausea.^[16] Adverse effect are mostly associated with a short term of use, and their frequency was significantly lower after 52 weeks of use.^[16] Long-term studies regarding the effects of e-cigarettes after chronic exposure are unavailable.^[16] Some case reports found harms to health brought about by e-cigarettes in many countries, such as the US and in Europe; the most common effect was dryness of the mouth and throat.^[19] Many of the observed negative effects from e-cigarette use concerning the nervous system and the sensory system are probably related to nicotine overdose or withdrawal.^[22] In youth, e-cigarette use risks involve accidental nicotine exposure.^[23] In pediatric patients, accidental exposures include ingesting of e-liquids and inhaling of e-cigarette vapor; choking on e-cigarette components is also a potential hazard.^[23] In the United States, a child died after ingesting liquid nicotine.^[24]

Poisoning associated with e-cigarettes may happen by ingestion, inhalation, or absorption.^[25] The US Food and Drug Administration Center for Tobacco Products reported between 2008 and the beginning of 2012, 47 cases of adverse effects associated with e-cigarettes, of which eight were considered serious.^[13] A causal relationship between e-cigarettes and the reported adverse effects was not established with the exception of two severe outcomes in the United States: a death when an infant choked on the cartridges and burns when one blew up.^[13] In the United States the number of calls to poison control centers related to electronic cigarettes have increased between 2010 and 2014, such that they now represent 42% of reported cases due to either cigarettes and e-cigarettes up from 0.3%.^[26] These calls were in connection to both adults and children.^[26] E-cigarettes were associated with fewer adverse effects than nicotine patches.^[26] Calls to U.S. poison control centers related to e-cigarette exposures involved inhalations, eye exposures, skin exposures, and ingestion, in both adults and young children.^[27] The California Poison Control System reported 35 cases of e-cigarette contact from 2010 to 2012, 14 were in children and 25 were from accidental contact.^[10] The majority of adverse effects reported were nausea, vomiting, dizziness and oral irritation.^[10]

Toxicology

A preliminary analysis of e-cigarette cartridges by the US Food and Drug Administration (FDA) in 2009 identified that some contain tobacco-specific nitrosamines (TSNAs), known cancer-causing agents.^[29] The tobacco specific impurities suspected of being harmful to humans were anabasine, myosmine, and β-nicotyrine. They were detected in a majority of the samples.^[30] The amounts of TSNAs present were on par with a nicotine inhaler.^[29] The FDA's analysis also detected diethylene glycol, which is poisonous, in a single cartridge manufactured by Smoking Everywhere and nicotine in one cartridge claimed to be nicotine-free.^[29]^[31] This prompted the FDA to warn that e-cigarettes may present a health risk.^[8] While diethylene glycol was found in a cartridge tested in 2009 by the FDA, in 2011 researchers reviewed the data and noted that 15 other studies had failed to find any evidence of this chemical in e-cigarettes.^[32]

The UK National Health Service noted that the toxic chemicals found by the FDA were at levels one-thousandth that of cigarette smoke, and that while there is no certainty that these small traces are harmless, initial test results are reassuring.^[33] Further concerns were raised over inconsistent amounts of nicotine delivered when drawing on the device.^[31] They appear to be similar in toxicity to other nicotine replacement products, but there is not enough data to draw conclusions.^[7] A 2014 review found higher levels of carcinogens and toxins than in an FDA-approved nicotine inhaler, suggesting that FDA-approved devices may deliver nicotine more safely.^[8] The 2015 California Department of Public Health has reported that "Mainstream and secondhand e-cigarette aerosol has been found to contain at least ten chemicals that are on California’s Proposition 65 list of chemicals known to cause cancer, birth defects, or other reproductive harm."^[34]

A policy statement by the American Association for Cancer Research and the American Society of Clinical Oncology has reported that nicotine is regarded as a potentially lethal poison.^[25] Research suggests that experienced e-cigarettes users are able to get as much nicotine from e-cigarettes as traditional cigarettes.^[25] The levels were above that of nicotine replacement product users.^[25] Other research have demonstrated that some e-cigarettes users experience adverse effects like throat irritation which could be the result of exposure to nicotine, nicotine solvents, or toxicants in the aerosol.^[25] However at the low amount of nicotine provided by e-cigarettes fatal overdose from use is unlikely; in contrast, the potent amount of nicotine in e-cigarettes liquids may be toxic if it is accidentally ingested or absorbed via the skin.^[25] The user inhales an aerosol containing chemicals and very addictive nicotine.^[35] The distribution on the amount of nicotine inhaled by the user is not clear^[8] Newer e-cigarettes with more concentrated nicotine liquids may deliver nicotine at levels similar to traditional cigarettes.^[25] Serum nicotine levels identified are inharmonious and rely upon the user and the device.^[8] There was inconsistent labeling of the actual nicotine content on e-liquid cartridges from some brands.^[5] Some nicotine has been found in ‘no nicotine' liquids.^[12] Due to nicotine content inconstancy, it is recommended that e-cigarette companies develop quality standards with respect to nicotine content.^[17] There are safety issues with the nicotine exposure from e-cigarettes, which has the possibility of causing addiction and other adverse effects.^[17] Serum cotinine levels are comparable to that of traditional cigarettes.^[18]

The risk from the inhalation of propylene glycol and glycerol is probably low.^[13] Some research states that propylene glycol emissions may cause respiratory irritation and raise the likelihood to develop asthma.^[36] E-cigarettes companies use purified water and glycerin instead of propylene glycol for aerosol production to lessen the risks.^[36] When heated at hotter temperatures glycerol may generate harmful acrolein.^[13] Some e-cigarette products had acrolein identified in the aerosol.^[13] Acrolein levels were reduced by 60% in dual users and 80% for those that completely switched to e-cigarettes when compared to traditional cigarettes.^[13] If exposure of aerosols to propylene glycol and glycerin rises to levels that one would consider the exposure in association with a workplace setting, it would be sensible to investigate the health of exposed persons.^[37] The essential propylene glycol and/or glycerol mixture may consist of natural or artificial substances to provide it flavor.^[12] Some of these substances are regarded as toxic and a number of them resemble known carcinogens.^[12] Generally, flavoring additives are imprecisely described, using terms such as "vegetable flavoring".^[12] Although they are approved for human consumption there are no studies on the short- or long-term effects of inhaling them.^[12] Some artificial flavors have been demonstrated as being cytotoxic.^[12]

A 2014 review found "Various chemical substances and ultrafine particles known to be toxic, carcinogenic and/or to cause respiratory and heart distress have been identified in e-cigarette aerosols, cartridges, refill liquids and environmental emissions."^[17] Few of the methods in the studies the review looked at were validated.^[17] Many toxic chemical compounds have been produced from e-cigarettes, especially carbonyl compounds like formaldehyde, acetaldehyde, acrolein, and glyoxal, which are frequently identified in e-cigarette aerosols.^[19]^[38] These materials may cause harmful health effects; though, in the majority of cases, the amounts inhaled are less than those in traditional cigarettes.^[19]The toxicity of e-cigarettes and e-liquid can vary greatly, as there is potential differences in construction and materials in the delivery device, kind and origin of ingredients in the e-liquid, and the use or non-use of good manufacturing practices and quality control approaches.^[39] Devices using higher voltages can produce carcinogens including formaldehyde at levels found in cigarette smoke.^[38] While there is variability in the ingredients and concentrations of ingredients in e-cigarette liquids, tobacco smoke contains thousands of chemicals, most of which are not understood and many of which are known to be harmful.^[1] The levels of chemical constituents in the vapor were found to be 1 to 2 orders of magnitude smaller than in cigarette smoke but greater compared to a nicotine inhaler.^[5] The Centers for Disease Control and Prevention (CDC) stated the possible negative impact between nicotine and brain development in youth is a concern.^[40] There is no long-term research concerning the cancer risk related to the small level of exposure to the identified carcinogens.^[8] The short-term toxicity of e-cigarette use appears to be low, with the exception for some people with reactive airways.^[12] The long-term health impacts of e-cigarette use are unknown.^[13] The long-term toxicity is subject to the additives and contaminants in the e-liquid.^[12] There is limited peer-reviewed data about the toxicity of e-cigarettes for a complete toxicological evaluation.^[39]

A 2013 review found an instant increase in airway resistance after using a single e-cigarette, and concluded that they can harm the respiratory system.^[12] The risks, especially to the lungs, are not fully understood and are of concern to public health authorities.^[41]^[42]^[43] The particles are of the ultrafine size which can go deep in the lungs and then into the systemic circulation.^[5] Reports in the literature have shown respiratory and cardiovascular effects by these smaller size particles, suggesting a possible health concern.^[44] A 2014 review found e-cigarettes emissions contain the heavy metals nickel, tin, and chromium.^[5] These nanoparticles can deposit in the lung's alveolar sacs, potentially leading to local respiratory toxicity and entering the bloodstream.^[5] A 2014 review found it can be concluded that there is no evidence of contamination of the aerosol with metals that justifies a health concern.^[37] A 2014 review noted a study had found metal particles in the fluid and aerosol, however that study did not evaluate the relevance of the levels identified.^[13] The same review found that these levels were 10-50 times less than that allowed in medicines that are inhaled.^[13]

Effects on breathing and lung function

A 2014 review found that tests of cardiovascular and respiratory functions after short-term use of e-cigarettes demonstrated some harmful effects of vaping, but these were appreciably milder in comparison to traditional cigarettes.^[10] When used in the short-term, an e-cigarette results in a rise of respiratory resistance comparatively to traditional cigarettes.^[16] The long-term effects regarding respiratory flow resistance are unknown.^[16] E-cigarette use can be associated with a substantial dispersion of nicotine, thus generating a plasma nicotine concentration which can be comparable to that of traditional cigarettes.^[21] This is due to the minute nicotine particles in the vapor, which permit quick delivery into the bloodstream.^[21] This could increase the risk of cardiac arrhythmias and hypertension which may put some users, particularly those with atherosclerosis or other cardiovascular risk factors, at significant risk of acute coronary syndrome.^[21] Some case reports documented the possible cardiovascular adverse effects from using e-cigarettes, the majority associated was with improper use.^[21] Even though e-cigarettes are anticipated to produce fewer dangerous substances than traditional cigarettes, limited evidence supports they comparatively have a lessened raised cardiovascular risk for e-cigarettes users.^[21] The limited evidence suggests that e-cigarettes produce less short-term effects on lung function than traditional cigarettes.^[8] Like cancer risk, there is no literature outlining the long-term lung function or cardiovascular consequences.^[8] A 2014 review found that e-cigarette aerosol contains far fewer carcinogens than tobacco smoke, and concluded that e-cigarettes "impart a lower potential disease burden" than traditional cigarettes.^[36] The effect on population health from e-cigarettes is unknown.^[8]

Ultrafine particles

E-cigarettes produce particles, in the form of an aerosol.^[17]^[45] The aerosol produced by an e-cigarette is commonly but inaccurately called vapor.^[17] In physics, a vapor is a substance in the gas phase whereas an aerosol is a suspension of tiny particles of liquid, solid or both within a gas.^[17] The word "vaping" is not technically accurate when applied to e-cigarettes.^[45] The aerosol is made-up of liquid sub-micron particles of condensed vapor; thus, the users of these devices are rather "aerosolizing."^[45] The aerosol the e-cigarette produces resembles cigarette smoke.^[17] A 2014 review found "Following a puff, the aerosol is delivered into the user's mouth and lungs by inhalation, after which the remaining aerosol is exhaled into the environment."^[17] E-cigarettes provide nicotine by creating liquid particles.^[5] E-cigarette vapor mostly consist of propylene glycol, glycerol, water, flavorings, nicotine, and other chemicals.^[10]

A 2014 review found that fine particles can be chemically intricate and not uniform, and what a particle is made of, the exact harmful elements, and the importance of the size of the particle is mostly unknown. They found that because these things are uncertain, it is not clear whether the ultrafine particles in e-cigarette vapor have health effects similar to those produced by traditional cigarettes.^[5] Emissions from electronic cigarettes are not comparable to environmental pollution or cigarette smoke as their nature and chemical composition are completely different,^[10] although a 2014 review found that the particle size distribution and sum of particles emitted by e-cigarettes are like traditional cigarettes, with the majority of particles in the ultrafine range (modes, ≈100–200).^[5] The particles are larger, with the mean size being 600nm in inhaled aerosol and 300nm in exhaled.^[12] Different devices generate different particle sizes and cause different depositions in the respiratory tract, even from the same nicotine liquid.^[38] A 2014 review found that the aerosol particle concentration is 5 times lower than from a traditional cigarette.^[8] A 2014 WHO report found e-cigarettes release a lower level of particles than traditional cigarettes.^[9] A 2014 review found that the density of particles in the vapor is lower than in cigarette smoke by a factor of between 6 and 880 times lower.^[10]

Effects on bystanders

There is insufficient data to determine the impact on public health from e-cigarettes.^[18] A white paper published in 2014 by the American Industrial Hygiene Association concluded e-cigarettes emit airborne contaminants that may be inhaled by the user and those nearby.^[44] Due to this possible risk, they urged restriction of their use indoors, similar to smoking bans, until research has shown the aerosol does not significantly harm others in the area.^[44] A 2014 review indicated that the levels of inhaled contaminants from the e-cigarette vapor are not of significant health concern for human exposures by the standards used in workplaces to ensure safety.^[37]

Since e-cigarettes do not burn (or contain) tobacco, no side-stream smoke or any cigarette smoke is produced.^[5] Only what is exhaled by electronic cigarettes users enters the surrounding air.^[13] E-cigarettes used in indoor environments can put at risk nonsmokers to elevated levels of nicotine and aerosol emissions.^[8] A 2014 review of limited data concluded this vapor can cause indoor air pollution and is not just "water vapor" as is frequently stated in the advertising of e-cigarettes.^[5] Exhaled vapor consists of nicotine and some other particles, primarily consisting of flavors, aroma transporters, glycerol and propylene glycol.^[13] Bystanders are exposed to these particles from exhaled e-cigarette vapor.^[5] A mixture of harmful substances, particularly nicotine, ultrafine particles, and volatile organic compounds can be exhaled into the air.^[21] The dense vapor consists of liquid sub-micron droplets.^[45] The liquid particles condenses into a viewable fog.^[12] The vapor is in the air for a short time, with a half-life of about 10 seconds; traditional cigarette smoke is in the air 100 times longer.^[12] This is because of fast revaporization at room temperature.^[12] Some of the few studies examining the effects on health shown that being exposed to e-cigarette vapor may produce biological effects. Since e-cigarettes have not been widely used long enough for evaluation, the long-term health effects from the second-hand vapor are not known.^[5]

As of 2013^[update], the only clinical study currently published evaluating the respiratory effects of passive vaping found no adverse effects were detected.^[10] A 2014 review found it is safe to infer that their effects on bystanders are minimal in comparison to traditional cigarettes.^[10] A 2014 WHO report stated passive exposure was as a concern, indicating that current evidence is insufficient to determine whether the levels of exhaled vapor are safe to involuntarily exposed bystanders.^[9] The report stated that "it is unknown if the increased exposure to toxicants and particles in exhaled aerosol will lead to an increased risk of disease and death among bystanders."^[9] E-cigarette vapor has notably fewer toxicants than cigarette smoke and is likely to pose less harm to users or bystanders.^[5]

Nonsmokers exposed to e-cigarette aerosol produced by a machine and pumped into a room were found to have detectable levels of the nicotine metabolite cotinine in their blood. The same study stated that 80% of nicotine is normally absorbed by the user, so these results may be higher than in actual second hand exposure.^[5]

A policy statement by the American Association for Cancer Research and the American Society of Clinical Oncology has reported that "Third-hand exposure occurs when nicotine and other chemicals from second-hand aerosol deposit on surfaces, exposing people through touch, ingestion, and inhalation".^[25] Nicotine is actually hard to get rid of from surfaces.^[25] The statement noted there are no published studies of third hand exposure from e-cigarettes, however initial data suggests that nicotine from e-cigarettes may stick to surfaces.^[25] In January 2014, the International Union Against Tuberculosis and Lung Disease stated "Adverse health effects for exposed third parties (second-hand exposure) cannot be excluded because the use of electronic cigarettes leads to emission of fine and ultrafine inhalable liquid particles, nicotine and cancer-causing substances into indoor air."^[46]

Effects during pregnancy

A 2014 review stated there are concerns about pregnant women exposure to e-cigarette vapor through direct use or via exhaled vapor.^[5] As of 2014^[update], there is no conclusions on the possible hazards of pregnant women using e-cigarettes, and there is a developing research on the negative effects of nicotine on prenatal brain development.^[8] A 2014 review concluded no amount of nicotine is safe for pregnant women.^[47] As of 2014^[update], the long-term issues of e-cigarettes on both mother and unborn baby are unknown.^[47] There are concerns about the health impacts of pediatric exposure to second-hand and third-hand e-cigarette vapor.^[23] The 2014 Surgeon General of the United States report has found "that nicotine adversely affects maternal and fetal health during pregnancy, and that exposure to nicotine during fetal development has lasting adverse consequences for brain development."^[25]

Environmental impact

There is limited information available on any environmental issues connected to the production, usage, and disposal of e-cigarette models that use cartridges.^[14] No formal studies have been done to evaluate the environmental effects of making or disposing of any part of an e-cigarettes including the batteries or nicotine production.^[14] As of 2014^[update], it is uncertain if the nicotine in e-liquid is United States Pharmacopeia-grade nicotine, a tobacco extract, or a synthetic nicotine when questioning the environmental impact of how it is made.^[14] It is not clear which manufacturing methods may be used by the industry to make nicotine that are used in e-cigarettes.^[14] The emissions from making nicotine could be considerable from manufacturing if not appropriately controlled.^[14] Some e-cigarette brands that use cartridges state their products are ‘eco-friendly’ or ‘green’, despite the absence of any supporting studies.^[14] It is unclear how many traditional cigarettes are comparable to using one e-cigarette that uses a cartridge for the average user.^[14] Information is limited on energy and materials used for production of e-cigarettes versus traditional cigarettes, for comparable use.^[14] Although some brands have began recycling services for their e-cigarette cartridges; the prevalence of recycling, as well as the prevalence of recycling information on expandable e-cigarette containers, is unknown.^[14] Some brands have also began recycling services for their e-cigarette batteries.^[14]

Fires, explosions, and other battery-related malfunctions

Most e-cigarettes use lithium batteries, the improper use of which may result in accidents.^[10] Rare major injuries have occurred from battery malfunctions such as explosions and fires.^[5] The United States Fire Administration said that 25 fires and explosions were caused by e-cigarettes between 2009 and 2015.^[48] The explosions resulted either through extended charging and use of unsuitable chargers or as a result of design flaws.^[10]

After a review of fire safety issues, including two incidents in which fires were caused by e-cigarettes packed in checked luggage, the U.S. Federal Aviation Administration issued a safety alert to air carriers in January 2015 saying that e-cigarettes should not be allowed in checked baggage.^[49]^[48] Although they are permitted to be brought on board flights as carry-on belongings, in-flight use of e-cigarettes is prohibited in the U.S.^[49]

The International Civil Aviation Organization, a United Nations agency, also recommends prohibiting e-cigarettes in checked luggage.^[48]

A spokesman for the Tobacco Vapor Electronic Cigarette Association said that e-cigarettes do not pose a problem if they are packed correctly in static-free packaging, but that irresponsible people may sometimes pack them carelessly or tamper with them.^[48]

It has been recommended that manufacturing quality standards be imposed in order to prevent such accidents.^[10] Some of the risks from e-cigarette use could probably be reduced by better product design and standards.^[50]

Risks related to e-liquid

Nicotine overdose from e-liquid is another potential risk. In December 2014, a one-year-old child in Fort Plain, New York died after an accidental ingestion of nicotine liquid.^[51] A man died in 2012 after injecting himself with nicotine liquid.^[51] The American Association of Poison Control Centers recorded 3,638 "exposure" incidents relating to liquid nicotine as of November 30, 2014.^[51]

Use-related concerns with e-liquids also include leaks or spills and contact with contaminants in the e-liquid.^[50]

References

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^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Cheng, T. (2014). "Chemical evaluation of electronic cigarettes". Tobacco Control. 23 (Supplement 2): ii11–ii17. doi:10.1136/tobaccocontrol-2013-051482. ISSN 0964-4563. PMC 3995255. PMID 24732157.
^ ^a ^b ^c Callahan-Lyon, P. (2014). "Electronic cigarettes: human health effects". Tobacco Control. 23 (Supplement 2): ii36–ii40. doi:10.1136/tobaccocontrol-2013-051470. ISSN 0964-4563. PMID 24732161.
^ ^a ^b ^c ^d ^e ^f Bekki, Kanae; Uchiyama, Shigehisa; Ohta, Kazushi; Inaba, Yohei; Nakagome, Hideki; Kunugita, Naoki (2014). "Carbonyl Compounds Generated from Electronic Cigarettes". International Journal of Environmental Research and Public Health. 11 (11): 11192–11200. doi:10.3390/ijerph111111192. ISSN 1660-4601. PMID 25353061.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ "WHO calls for ban on e-cigarette use indoors". Big News Network.com. 26 August 2014. {{cite news}}: Italic or bold markup not allowed in: |publisher= (help)
^ ^a ^b ^c ^d ^e ^f ^g Cervellin, Gianfranco; Borghi, Loris; Mattiuzzi, Camilla; Meschi, Tiziana; Favaloro, Emmanuel; Lippi, Giuseppe (2013). "E-Cigarettes and Cardiovascular Risk: Beyond Science and Mysticism". Seminars in Thrombosis and Hemostasis. 40 (01): 060–065. doi:10.1055/s-0033-1363468. ISSN 0094-6176. PMID 24343348.
^ Lauterstein, Dana; Hoshino, Risa; Gordon, Terry; Watkins, Beverly-Xaviera; Weitzman, Michael; Zelikoff, Judith (2014). "The Changing Face of Tobacco Use Among United States Youth". Current Drug Abuse Reviews. 7 (1): 29–43. doi:10.2174/1874473707666141015220110. ISSN 1874-4737. PMID 25323124.
^ ^a ^b ^c Durmowicz, E. L. (2014). "The impact of electronic cigarettes on the paediatric population". Tobacco Control. 23 (Supplement 2): ii41–ii46. doi:10.1136/tobaccocontrol-2013-051468. ISSN 0964-4563. PMID 24732163.
^ Wise, Lindsay (13 January 2015). "Child's death revives call for federal government to regulate liquid nicotine for e-cigarettes". McClatchyDC. McClatchy. Retrieved 13 January 2014.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Brandon, T. H.; Goniewicz, M. L.; Hanna, N. H.; Hatsukami, D. K.; Herbst, R. S.; Hobin, J. A.; Ostroff, J. S.; Shields, P. G.; Toll, B. A.; Tyne, C. A.; Viswanath, K.; Warren, G. W. (2015). "Electronic Nicotine Delivery Systems: A Policy Statement from the American Association for Cancer Research and the American Society of Clinical Oncology". Clinical Cancer Research. doi:10.1158/1078-0432.CCR-14-2544. ISSN 1078-0432.
^ ^a ^b ^c Orr, KK; Asal, NJ (November 2014). "Efficacy of Electronic Cigarettes for Smoking Cessation". The Annals of pharmacotherapy. 48 (11): 1502–1506. doi:10.1177/1060028014547076. PMID 25136064.
^ Centers for Disease Control and Prevention (CDC) (April 2014). "Notes from the field: calls to poison centers for exposures to electronic cigarettes--United States, September 2010-February 2014". MMWR Morb. Mortal. Wkly. Rep. 63 (13): 292–3. PMID 24699766.
^ Arnold, Carrie (2014). "Vaping and Health: What Do We Know about E-Cigarettes?". Environmental Health Perspectives. 122 (9): A244–A249. doi:10.1289/ehp.122-A244. PMC 4154203. PMID 25181730.
^ ^a ^b ^c "Safety Watch: Electronic Cigarettes". U.S. Food and Drug Administration.
^ FDA (22 July 2009). "Summary of Results: Laboratory Analysis of Electronic Cigarettes Conducted By FDA". Retrieved 22 July 2009.
^ ^a ^b FDA (4 May 2009). "FDA 2009 Study Data: Evaluation of e-cigarettes" (PDF). Food and Drug Administration (US) -center for drug evaluation and research. Retrieved 4 May 2009.
^ Palmer, Roxanne (8 September 2013). "E-Cigarettes As Effective As Nicotine Patches in Helping Smokers Quit: Study". International Business Times. Retrieved 15 December 2013.
^ "E-cigarettes to be regulated as medicines". National Health Service. 12 June 2013. Retrieved August 2013. {{cite web}}: Check date values in: |accessdate= (help)
^ "State Health Officer's Report on E-Cigarettes: A Community Health Threat" (PDF). California Department of Public Health, California Tobacco Control Program. January 2015.
^ "Public Health Focus: Electronic Cigarettes (e-Cigarettes)". FDA. 24 April 2014.
^ ^a ^b ^c Oh, Anne Y.; Kacker, Ashutosh (December 2014). "Do electronic cigarettes impart a lower potential disease burden than conventional tobacco cigarettes?: Review on e-cigarette vapor versus tobacco smoke". The Laryngoscope. 124 (12): 2702–2706. doi:10.1002/lary.24750. PMID 25302452.
^ ^a ^b ^c Burstyn, I (9 January 2014). "Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks". BMC Public Health. 14: 18. doi:10.1186/1471-2458-14-18. PMC 3937158. PMID 24406205.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ ^a ^b ^c Collaco, Joseph M. (2015). "Electronic Use and Exposure in the Pediatric Population". JAMA Pediatrics. 169 (2): 177–182. doi:10.1001/jamapediatrics.2014.2898. PMID 25546699.
^ ^a ^b Orr, M. S. (2014). "Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future". Tobacco Control. 23 (Supplement 2): ii18–ii22. doi:10.1136/tobaccocontrol-2013-051474. ISSN 0964-4563. PMID 24732158.
^ Centers for Disease Control and Prevention, (CDC) (6 September 2013). "Notes from the field: electronic cigarette use among middle and high school students – United States, 2011–2012". MMWR. Morbidity and mortality weekly report. 62 (35): 729–30. PMID 24005229.
^ Britton, John; Bogdanovica, Ilze (15 May 2014), Electronic cigarettes – A report commissioned by Public Health England (PDF), Public Health England
^ "Electronic cigarettes (e-cigarettes) or electronic nicotine delivery systems". World Health Organization. 3 June 2014.
^ "Position Statement on Electronic Cigarettes [ECs] or Electronic Nicotine Delivery Systems [ENDS]" (PDF). The International Union against Tuberculosis and Lung Disease. October 2013.
^ ^a ^b ^c "White Paper: Electronic Cigarettes in the Indoor Environment" (PDF). American Industrial Hygiene Association. October 19, 2014.
^ ^a ^b ^c ^d Offermann, Francis (June 2014). "The Hazards of E-Cigarettes" (PDF). ASHRAE Journal. 56 (6).
^ Bam, T. S.; Bellew, W.; Berezhnova, I.; Jackson-Morris, A.; Jones, A.; Latif, E.; Molinari, M. A.; Quan, G.; Singh, R. J.; Wisotzky, M. (1 January 2014). "Position statement on electronic cigarettes or electronic nicotine delivery systems [Official statement]". The International Journal of Tuberculosis and Lung Disease. 18 (1): 5–7. doi:10.5588/ijtld.13.0815.
^ ^a ^b Suter, Melissa A.; Mastrobattista, Joan; Sachs, Maike; Aagaard, Kjersti (2014). "Is There Evidence for Potential Harm of Electronic Cigarette Use in Pregnancy?". Birth Defects Research Part A: Clinical and Molecular Teratology: n/a–n/a. doi:10.1002/bdra.23333. ISSN 1542-0752. PMID 25366492.
^ ^a ^b ^c ^d Jansen, Bart, "Packing e-Cigarettes in luggage is a fire risk, FAA warns", USA Today, January 23, 2015.
^ ^a ^b Hasley III, Ashley, "The FAA wants you to carry on your e-Cigs", The Washington Post, January 26, 2015.
^ ^a ^b Yang, L.; Rudy, S. F.; Cheng, J. M.; Durmowicz, E. L. (2014). "Electronic cigarettes: incorporating human factors engineering into risk assessments". Tobacco Control. 23 (Supplement 2): ii47–ii53. doi:10.1136/tobaccocontrol-2013-051479. ISSN 0964-4563. PMID 24732164.
^ ^a ^b ^c Mohney, Gillian, "First Child's Death From Liquid Nicotine Reported as 'Vaping' Gains Popularity", ABC News, December 12, 2014.

External links

Media related to Electronic cigarettes at Wikimedia Commons
Legal status of electronic cigarettes
Positions of medical organizations regarding electronic cigarettes

[Saitta2014-1] ^ ^a ^b ^c ^d ^e ^f Saitta, D; Ferro, GA; Polosa, R (Mar 2014). "Achieving appropriate regulations for electronic cigarettes". Therapeutic advances in chronic disease. 5 (2): 50–61. doi:10.1177/2040622314521271. PMC 3926346. PMID 24587890.

[Odum2012-2] Odum, L. E.; O'Dell, K. A.; Schepers, J. S. (December 2012). "Electronic cigarettes: do they have a role in smoking cessation?". Journal of pharmacy practice. 25 (6): 611–4. doi:10.1177/0897190012451909. PMID 22797832.

[Harrell2014-3] Harrell, PT; Simmons, VN; Correa, JB; Padhya, TA; Brandon, TH (4 June 2014). "Electronic Nicotine Delivery Systems ("E-cigarettes"): Review of Safety and Smoking Cessation Efficacy". Otolaryngology—head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. doi:10.1177/0194599814536847. PMID 24898072. These devices are unregulated, of unknown safety, and of uncertain benefit in quitting smoking.

[Palazzolo-4] Palazzolo, Dominic L. (Nov 2013), "Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review.", Frontiers in Public Health, 1 (56), doi:10.3389/fpubh.2013.00056, PMC 3859972, PMID 24350225{{citation}}: CS1 maint: unflagged free DOI (link)

[Grana2014-5] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v Grana, R; Benowitz, N; Glantz, SA (13 May 2014). "E-cigarettes: a scientific review". Circulation. 129 (19): 1972–86. doi:10.1161/circulationaha.114.007667. PMC 4018182. PMID 24821826.

[O2012-6] O'Connor, RJ (March 2012). "Non-cigarette tobacco products: what have we learnt and where are we headed?". Tobacco control. 21 (2): 181–90. doi:10.1136/tobaccocontrol-2011-050281. PMC 3716250. PMID 22345243.

[Caponnetto2013-7] Caponnetto P; Russo C; Bruno CM; Alamo A; Amaradio MD; Polosa R. (Mar 2013). "Electronic cigarette: a possible substitute for cigarette dependence". Monaldi archives for chest disease. 79 (1): 12–19. PMID 23741941.

[Drummond2014-8] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o Drummond, MB; Upson, D (February 2014). "Electronic cigarettes. Potential harms and benefits". Annals of the American Thoracic Society. 11 (2): 236–42. doi:10.1513/annalsats.201311-391fr. PMID 24575993.

[WHOPosition2014-9] ^ ^a ^b ^c ^d ^e ^f WHO. "Electronic nicotine delivery systems" (PDF). Retrieved 28 August 2014.

[FarsalinosPolosa2014-10] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Farsalinos, K. E.; Polosa, R. (2014). "Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review". Therapeutic Advances in Drug Safety. 5 (2): 67–86. doi:10.1177/2042098614524430. ISSN 2042-0986. PMC 4110871. PMID 25083263.

[Pisinger2014-11] Pisinger, Charlotta; Døssing, Martin (December 2014). "A systematic review of health effects of electronic cigarettes". Preventive Medicine. 69: 248–260. doi:10.1016/j.ypmed.2014.10.009. PMID 25456810.

[Bertholon2013-12] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q Bertholon, J.F.; Becquemin, M.H.; Annesi-Maesano, I.; Dautzenberg, B. (2013). "Electronic Cigarettes: A Short Review". Respiration. doi:10.1159/000353253. ISSN 1423-0356. PMID 24080743.

[Hajek2014-13] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p Hajek, P; Etter, JF; Benowitz, N; Eissenberg, T; McRobbie, H (31 July 2014). "Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit" (PDF). Addiction (Abingdon, England). 109 (11): 1801–10. doi:10.1111/add.12659. PMID 25078252.

[Chang2014-14] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Chang, H. (2014). "Research gaps related to the environmental impacts of electronic cigarettes". Tobacco Control. 23 (Supplement 2): ii54–ii58. doi:10.1136/tobaccocontrol-2013-051480. ISSN 0964-4563. PMC 3995274. PMID 24732165.

[Cochrane2014-15] McRobbie, Hayden; Bullen, Chris; Hartmann-Boyce, Jamie; Hajek, Peter; McRobbie, Hayden (2014). "Electronic cigarettes for smoking cessation and reduction". The Cochrane Library. doi:10.1002/14651858.CD010216.pub2. PMID 25515689.

[Gualano2014-16] ^ ^a ^b ^c ^d ^e ^f Gualano, M. R.; Passi, S.; Bert, F.; La Torre, G.; Scaioli, G.; Siliquini, R. (9 August 2014). "Electronic cigarettes: assessing the efficacy and the adverse effects through a systematic review of published studies". Journal of Public Health. doi:10.1093/pubmed/fdu055. PMID 25108741.

[Cheng2014-17] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Cheng, T. (2014). "Chemical evaluation of electronic cigarettes". Tobacco Control. 23 (Supplement 2): ii11–ii17. doi:10.1136/tobaccocontrol-2013-051482. ISSN 0964-4563. PMC 3995255. PMID 24732157.

[Callahan2014-18] Callahan-Lyon, P. (2014). "Electronic cigarettes: human health effects". Tobacco Control. 23 (Supplement 2): ii36–ii40. doi:10.1136/tobaccocontrol-2013-051470. ISSN 0964-4563. PMID 24732161.

[Bekki2014-19] ^ ^a ^b ^c ^d ^e ^f Bekki, Kanae; Uchiyama, Shigehisa; Ohta, Kazushi; Inaba, Yohei; Nakagome, Hideki; Kunugita, Naoki (2014). "Carbonyl Compounds Generated from Electronic Cigarettes". International Journal of Environmental Research and Public Health. 11 (11): 11192–11200. doi:10.3390/ijerph111111192. ISSN 1660-4601. PMID 25353061.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[Bettcher2014-20] "WHO calls for ban on e-cigarette use indoors". Big News Network.com. 26 August 2014. {{cite news}}: Italic or bold markup not allowed in: |publisher= (help)

[Cervellin2013-21] ^ ^a ^b ^c ^d ^e ^f ^g Cervellin, Gianfranco; Borghi, Loris; Mattiuzzi, Camilla; Meschi, Tiziana; Favaloro, Emmanuel; Lippi, Giuseppe (2013). "E-Cigarettes and Cardiovascular Risk: Beyond Science and Mysticism". Seminars in Thrombosis and Hemostasis. 40 (01): 060–065. doi:10.1055/s-0033-1363468. ISSN 0094-6176. PMID 24343348.

[Lauterstein2014-22] Lauterstein, Dana; Hoshino, Risa; Gordon, Terry; Watkins, Beverly-Xaviera; Weitzman, Michael; Zelikoff, Judith (2014). "The Changing Face of Tobacco Use Among United States Youth". Current Drug Abuse Reviews. 7 (1): 29–43. doi:10.2174/1874473707666141015220110. ISSN 1874-4737. PMID 25323124.

[Durmowicz2014-23] Durmowicz, E. L. (2014). "The impact of electronic cigarettes on the paediatric population". Tobacco Control. 23 (Supplement 2): ii41–ii46. doi:10.1136/tobaccocontrol-2013-051468. ISSN 0964-4563. PMID 24732163.

[24] Wise, Lindsay (13 January 2015). "Child's death revives call for federal government to regulate liquid nicotine for e-cigarettes". McClatchyDC. McClatchy. Retrieved 13 January 2014.

[Brandon2015-25] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Brandon, T. H.; Goniewicz, M. L.; Hanna, N. H.; Hatsukami, D. K.; Herbst, R. S.; Hobin, J. A.; Ostroff, J. S.; Shields, P. G.; Toll, B. A.; Tyne, C. A.; Viswanath, K.; Warren, G. W. (2015). "Electronic Nicotine Delivery Systems: A Policy Statement from the American Association for Cancer Research and the American Society of Clinical Oncology". Clinical Cancer Research. doi:10.1158/1078-0432.CCR-14-2544. ISSN 1078-0432.

[OrrAsal2014-26] Orr, KK; Asal, NJ (November 2014). "Efficacy of Electronic Cigarettes for Smoking Cessation". The Annals of pharmacotherapy. 48 (11): 1502–1506. doi:10.1177/1060028014547076. PMID 25136064.

[MMWR2014-27] Centers for Disease Control and Prevention (CDC) (April 2014). "Notes from the field: calls to poison centers for exposures to electronic cigarettes--United States, September 2010-February 2014". MMWR Morb. Mortal. Wkly. Rep. 63 (13): 292–3. PMID 24699766.

[28] Arnold, Carrie (2014). "Vaping and Health: What Do We Know about E-Cigarettes?". Environmental Health Perspectives. 122 (9): A244–A249. doi:10.1289/ehp.122-A244. PMC 4154203. PMID 25181730.

[FDA_nitrosamines-29] "Safety Watch: Electronic Cigarettes". U.S. Food and Drug Administration.

[FDAChemicalAnalysis-30] FDA (22 July 2009). "Summary of Results: Laboratory Analysis of Electronic Cigarettes Conducted By FDA". Retrieved 22 July 2009.

[FDAStudy2009-31] FDA (4 May 2009). "FDA 2009 Study Data: Evaluation of e-cigarettes" (PDF). Food and Drug Administration (US) -center for drug evaluation and research. Retrieved 4 May 2009.

[32] Palmer, Roxanne (8 September 2013). "E-Cigarettes As Effective As Nicotine Patches in Helping Smokers Quit: Study". International Business Times. Retrieved 15 December 2013.

[nhs-33] "E-cigarettes to be regulated as medicines". National Health Service. 12 June 2013. Retrieved August 2013. {{cite web}}: Check date values in: |accessdate= (help)

[34] "State Health Officer's Report on E-Cigarettes: A Community Health Threat" (PDF). California Department of Public Health, California Tobacco Control Program. January 2015.

[FDAPublicHealthFocus-35] "Public Health Focus: Electronic Cigarettes (e-Cigarettes)". FDA. 24 April 2014.

[Kacker2014-36] Oh, Anne Y.; Kacker, Ashutosh (December 2014). "Do electronic cigarettes impart a lower potential disease burden than conventional tobacco cigarettes?: Review on e-cigarette vapor versus tobacco smoke". The Laryngoscope. 124 (12): 2702–2706. doi:10.1002/lary.24750. PMID 25302452.

[Bur2014-37] Burstyn, I (9 January 2014). "Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks". BMC Public Health. 14: 18. doi:10.1186/1471-2458-14-18. PMC 3937158. PMID 24406205.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[Collaco2015-38] Collaco, Joseph M. (2015). "Electronic Use and Exposure in the Pediatric Population". JAMA Pediatrics. 169 (2): 177–182. doi:10.1001/jamapediatrics.2014.2898. PMID 25546699.

[Orr2014-39] Orr, M. S. (2014). "Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future". Tobacco Control. 23 (Supplement 2): ii18–ii22. doi:10.1136/tobaccocontrol-2013-051474. ISSN 0964-4563. PMID 24732158.

[MMWR2013-40] Centers for Disease Control and Prevention, (CDC) (6 September 2013). "Notes from the field: electronic cigarette use among middle and high school students – United States, 2011–2012". MMWR. Morbidity and mortality weekly report. 62 (35): 729–30. PMID 24005229.

[NHE2014-41] Britton, John; Bogdanovica, Ilze (15 May 2014), Electronic cigarettes – A report commissioned by Public Health England (PDF), Public Health England

[WHO2013-42] "Electronic cigarettes (e-cigarettes) or electronic nicotine delivery systems". World Health Organization. 3 June 2014.

[IUATLD-43] "Position Statement on Electronic Cigarettes [ECs] or Electronic Nicotine Delivery Systems [ENDS]" (PDF). The International Union against Tuberculosis and Lung Disease. October 2013.

[AIHA2014-44] "White Paper: Electronic Cigarettes in the Indoor Environment" (PDF). American Industrial Hygiene Association. October 19, 2014.

[Offermann2014-45] Offermann, Francis (June 2014). "The Hazards of E-Cigarettes" (PDF). ASHRAE Journal. 56 (6).

[46] Bam, T. S.; Bellew, W.; Berezhnova, I.; Jackson-Morris, A.; Jones, A.; Latif, E.; Molinari, M. A.; Quan, G.; Singh, R. J.; Wisotzky, M. (1 January 2014). "Position statement on electronic cigarettes or electronic nicotine delivery systems [Official statement]". The International Journal of Tuberculosis and Lung Disease. 18 (1): 5–7. doi:10.5588/ijtld.13.0815.

[Suter2014-47] Suter, Melissa A.; Mastrobattista, Joan; Sachs, Maike; Aagaard, Kjersti (2014). "Is There Evidence for Potential Harm of Electronic Cigarette Use in Pregnancy?". Birth Defects Research Part A: Clinical and Molecular Teratology: n/a–n/a. doi:10.1002/bdra.23333. ISSN 1542-0752. PMID 25366492.

[USAtodayCarry-48] Jansen, Bart, "Packing e-Cigarettes in luggage is a fire risk, FAA warns", USA Today, January 23, 2015.

[WPCarry-49] Hasley III, Ashley, "The FAA wants you to carry on your e-Cigs", The Washington Post, January 26, 2015.

[Yang2014-50] Yang, L.; Rudy, S. F.; Cheng, J. M.; Durmowicz, E. L. (2014). "Electronic cigarettes: incorporating human factors engineering into risk assessments". Tobacco Control. 23 (Supplement 2): ii47–ii53. doi:10.1136/tobaccocontrol-2013-051479. ISSN 0964-4563. PMID 24732164.

[Mohney-51] Mohney, Gillian, "First Child's Death From Liquid Nicotine Reported as 'Vaping' Gains Popularity", ABC News, December 12, 2014.

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@@ Line 1: / Line 1: @@
+{{POV|date=January 2015}}
-Use of '''[[electronic cigarette]]s''' raises concerns regarding [[health effect]]s.<ref name=Saitta2014/> Risks involved in use are deemed uncertain,<ref name=Odum2012>{{cite journal|last1=Odum|first1=L. E.|last2=O'Dell|first2=K. A.|last3=Schepers|first3=J. S.|title=Electronic cigarettes: do they have a role in smoking cessation?|journal=Journal of pharmacy practice|date=December 2012|volume=25|issue=6|pages=611–4|pmid=22797832|doi=10.1177/0897190012451909}}</ref><ref name=Harrell2014>{{cite journal |last1=Harrell |first1=PT|last2=Simmons|first2=VN|last3=Correa|first3=JB|last4=Padhya|first4=TA|last5=Brandon|first5=TH|title=Electronic Nicotine Delivery Systems ("E-cigarettes"): Review of Safety and Smoking Cessation Efficacy.|journal=Otolaryngology—head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery|date= 4 June 2014|pmid=24898072|quote=These devices are unregulated, of unknown safety, and of uncertain benefit in quitting smoking.|doi=10.1177/0194599814536847}}</ref> on account of there being little data regarding health effects,<ref name=Palazzolo>{{Citation | title=Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review. | url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859972/ | author1-first=Dominic L. |author1-last=Palazzolo | journal=Frontiers in Public Health | volume=1 |issue=56 | date=Nov 2013| doi=10.3389/fpubh.2013.00056 | pmid=24350225 | pmc=3859972}}</ref> and to the variability of vaporizers and the composition, concentration and quality of their liquid ingredients and thus the contents of the "vapor" delivered to the user.<ref name=Grana2014>{{cite journal|last=Grana|first=R|author2=Benowitz, N |author3=Glantz, SA |title=E-cigarettes: a scientific review.|journal=Circulation|date=13 May 2014|volume=129|issue=19|pages=1972–86|pmid=24821826|doi=10.1161/circulationaha.114.007667|pmc=4018182}}</ref><ref name=Odum2012/><ref name=O2012>{{cite journal|last=O'Connor|first=RJ|title=Non-cigarette tobacco products: what have we learnt and where are we headed?|journal=Tobacco control|date=March 2012|volume=21|issue=2|pages=181–90|pmid=22345243|doi=10.1136/tobaccocontrol-2011-050281|pmc=3716250}}</ref> The limited evidence suggests that e-cigarettes are probably safer than traditional [[cigarette]]s.<ref name=O2012/> Safety concerns surrounding e-cigarettes generally fall into two categories: ordinary risks to the user, and risks from misuse or accidents (e.g., accidental fires caused by vaporizer malfunction, other vaporizer design issues, or accidental contact with liquid nicotine).<ref name=FarsalinosPolosa2014/><ref name=Grana2014/><ref name=Durmowicz2014/>
+Use of '''[[electronic cigarette]]s''' raises concerns regarding [[health effect]]s.<ref name=Saitta2014/> Risks involved in use are deemed uncertain,<ref name=Odum2012>{{cite journal|last1=Odum|first1=L. E.|last2=O'Dell|first2=K. A.|last3=Schepers|first3=J. S.|title=Electronic cigarettes: do they have a role in smoking cessation?|journal=Journal of pharmacy practice|date=December 2012|volume=25|issue=6|pages=611–4|pmid=22797832|doi=10.1177/0897190012451909}}</ref><ref name=Harrell2014>{{cite journal |last1=Harrell |first1=PT|last2=Simmons|first2=VN|last3=Correa|first3=JB|last4=Padhya|first4=TA|last5=Brandon|first5=TH|title=Electronic Nicotine Delivery Systems ("E-cigarettes"): Review of Safety and Smoking Cessation Efficacy.|journal=Otolaryngology—head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery|date= 4 June 2014|pmid=24898072|quote=These devices are unregulated, of unknown safety, and of uncertain benefit in quitting smoking.|doi=10.1177/0194599814536847}}</ref> on account of there being little data regarding health effects,<ref name=Palazzolo>{{Citation | title=Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review. | url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859972/ | author1-first=Dominic L. |author1-last=Palazzolo | journal=Frontiers in Public Health | volume=1 |issue=56 | date=Nov 2013| doi=10.3389/fpubh.2013.00056 | pmid=24350225 | pmc=3859972}}</ref> and to the variability of vaporizers and the composition, concentration and quality of their liquid ingredients and thus the contents of the "vapor" delivered to the user.<ref name=Grana2014>{{cite journal|last=Grana|first=R|author2=Benowitz, N |author3=Glantz, SA |title=E-cigarettes: a scientific review.|journal=Circulation|date=13 May 2014|volume=129|issue=19|pages=1972–86|pmid=24821826|doi=10.1161/circulationaha.114.007667|pmc=4018182}}</ref><ref name=Odum2012/><ref name=O2012>{{cite journal|last=O'Connor|first=RJ|title=Non-cigarette tobacco products: what have we learnt and where are we headed?|journal=Tobacco control|date=March 2012|volume=21|issue=2|pages=181–90|pmid=22345243|doi=10.1136/tobaccocontrol-2011-050281|pmc=3716250}}</ref> The limited evidence suggests that e-cigarettes are probably safer than traditional [[cigarette]]s.<ref name=O2012/>
+Safety concerns surrounding e-cigarettes generally fall into two categories: ordinary risks to the user, and risks from misuse or accidents (e.g., accidental fires caused by vaporizer malfunction, other vaporizer design issues, or accidental contact with liquid nicotine).
 Electronic cigarette usage appears to be similar in [[toxicity]] to the use of other [[nicotine replacement products]], but there is not enough data to draw conclusions.<ref name=Caponnetto2013/> The evidence suggests that other products accepted by the US [[Food and Drug Administration]] (FDA), such as [[nicotine inhaler]]s may be a safer way to give nicotine than e-cigarettes.<ref name=Drummond2014/> A July 2014 [[World Health Organization]] (WHO) report cautioned about potential risks of using electronic cigarettes.<!-- <ref name=WHOPosition2014/> --> The report concluded that "the existing evidence shows that ENDS aerosol is not merely "water vapour" as is often claimed in the marketing for these products. ENDS use poses serious threats to adolescents and fetuses. In addition, it increases exposure of non-smokers and bystanders to nicotine and a number of toxicants."<ref name=WHOPosition2014>{{cite web|last1=WHO|title=Electronic nicotine delivery systems|url=http://apps.who.int/gb/fctc/PDF/cop6/FCTC_COP6_10-en.pdf|accessdate=28 August 2014}}</ref> A 2014 [[systematic review]] concluded that the risks of e-cigarettes have been exaggerated by health authorities and stated that it is apparent that there may be some remaining risk accompanied with e-cigarette use, though the risk of e-cigarette use is likely small compared to smoking tobacco.<ref name=FarsalinosPolosa2014/> {{Asof|2014}}, e-cigarettes cannot be regarded as harmless.<ref name=Pisinger2014/> A 2013 review found that until additional data is available, using e-cigarettes cannot be regarded as safe.<ref name=Bertholon2013/> No long-term studies have shown that e-cigarettes are a "healthier alternative" to traditional cigarettes.<ref name=Drummond2014>{{cite journal|last1=Drummond|first1=MB|last2=Upson|first2=D|title=Electronic cigarettes. Potential harms and benefits.|journal=Annals of the American Thoracic Society|date=February 2014|volume=11|issue=2|pages=236–42|pmid=24575993|doi=10.1513/annalsats.201311-391fr}}</ref>
@@ Line 5: / Line 8: @@
 The amount of [[nicotine]] inhaled by the user is not clear.<ref name=Drummond2014/> The risk is probably low from the inhalation of [[propylene glycol]] and [[glycerol]].<ref name=Hajek2014/> When heated at hotter temperatures glycerol may generate harmful [[acrolein]].<ref name=Hajek2014/> Acrolein levels were reduced by 60% in dual users and 80% for those that completely switched to e-cigarettes when compared to traditional cigarettes.<ref name=Hajek2014/> There are no studies of  the short- and long-term effects of the inhalation of the various aromatic substances used as flavorings.<ref name=Bertholon2013/> The levels of [[toxicant|chemical constituents]] in the vapor were found to be 1 to 2 [[orders of magnitude]] smaller than in cigarette smoke but greater compared to a nicotine inhaler.<ref name=Grana2014/> There is limited information available on the [[environmental issue]]s around the production, the usage, and the disposal of e-cigarette models that use cartridges.<ref name=Chang2014/> While no serious adverse effects from e-cigarettes have yet been reported in trials,<ref name=Cochrane2014>{{cite journal|last1=McRobbie|first1=Hayden|last2=Bullen|first2=Chris|last3=Hartmann-Boyce|first3=Jamie|last4=Hajek|first4=Peter|last5=McRobbie|first5=Hayden|title=Electronic cigarettes for smoking cessation and reduction|journal=The Cochrane Library|year=2014|doi=10.1002/14651858.CD010216.pub2|pmid=25515689}}</ref> the long-term health impacts of e-cigarette use are unknown.<ref name=Hajek2014/><ref name=Gualano2014/> Less serious [[adverse effect]]s from e-cigarette use can include throat and mouth inflammation, vomiting, nausea, and cough.<ref name=Grana2014/>
-The [[aerosol]] (mist<ref name=Bertholon2013/>) emitted from an e-cigarette is commonly but inaccurately called [[vapor]].<ref name=Cheng2014/> The particle size distribution of particles emitted by e-cigarettes is similar to that of traditional cigarettes, with the majority of [[ultrafine particle|particles in the ultrafine range]] (modes, ≈100–200&nbsp;nm).<ref name=Grana2014/> The aerosol particle concentration is 5 times lower from an e-cigarette than from a traditional cigarette.<ref name=Drummond2014/> The particle size is larger than in cigarette smoke, with the mean size being 600nm in inhaled aerosol and 300nm in exhaled.<ref name=Bertholon2013/> Exhaled vapor consists of nicotine and some other particles, primarily consisting of flavors, aroma transporters, glycerol and propylene glycol.<ref name=Hajek2014/> A 2014 WHO report stated passive exposure was a concern, indicating that current evidence is insufficient to determine whether the levels of exhaled vapor are safe to involuntarily exposed bystanders.<ref name=WHOPosition2014/> The report stated that "it is unknown if the increased exposure to toxicants and particles in exhaled aerosol will lead to an increased risk of disease and death among bystanders."<ref name=WHOPosition2014/> E-cigarette vapor has notably fewer toxicants than cigarette smoke and is likely to pose less harm to users or bystanders.<ref name=Grana2014/> A 2014 found insufficient data to determine the impact on [[public health]] of e-cigarettes.<ref name=Callahan2014/> A 2014 review recommended that e-cigarettes should be regulated for [[consumer safety]].<ref name=Saitta2014/>
+The [[aerosol]] (mist<ref name=Bertholon2013/>) emitted from an e-cigarette is commonly but inaccurately called [[vapor]].<ref name=Cheng2014/> The particle size distribution of particles emitted by e-cigarettes is similar to that of traditional cigarettes, with the majority of [[ultrafine particle|particles in the ultrafine range]] (modes, ≈100–200&nbsp;nm).<ref name=Grana2014/> The aerosol particle concentration is 5 times lower from an e-cigarette than from a traditional cigarette.<ref name=Drummond2014/> The particle size is larger than in cigarette smoke, with the mean size being 600nm in inhaled aerosol and 300nm in exhaled.<ref name=Bertholon2013/> Exhaled vapor consists of nicotine and some other particles, primarily consisting of flavors, aroma transporters, glycerol and propylene glycol.<ref name=Hajek2014/> A 2014 WHO report stated passive exposure was a concern, indicating that current evidence is insufficient to determine whether the levels of exhaled vapor are safe to involuntarily exposed bystanders.<ref name=WHOPosition2014/> The report stated that "it is unknown if the increased exposure to toxicants and particles in exhaled aerosol will lead to an increased risk of disease and death among bystanders."<ref name=WHOPosition2014/> E-cigarette vapor has notably fewer toxicants than cigarette smoke and is likely to pose less harm to users or bystanders.<ref name=Grana2014/> Other studies found insufficient data to determine the impact on [[public health]] of e-cigarettes,<ref name=Callahan2014/> and recommended that e-cigarettes should be regulated for [[consumer safety]].<ref name=Saitta2014/>
 ==Health concerns==
-The emerging phenomenon of e-cigarettes is raising concerns among the health community, pharmaceutical industry, and other groups.<ref name=Saitta2014/> A 2014 review recommended that e-cigarettes should be adequately regulated for [[consumer safety]].<ref name=Saitta2014/> Another 2014 review stated that there are "reported" adverse health effects.<ref name=Bekki2014/> For example, they found that "The Food and Drug Administration (FDA) reported that e-cigarettes contain carcinogens and toxic chemicals, such as nitrosamines and diethylene glycol, which have potentially harmful effects on humans."<ref name=Bekki2014/> Additionally, a WHO report in 2009 cautioned that the "safety of e-cigarettes is not confirmed."<ref name=Bekki2014/> A 2014 review stated that "The precautionary principle may be invoked when a phenomenon, a product or a process with potentially dangerous effects has not been subjected to full scientific and objective evaluation so that the harm cannot be determined with sufficient certainty.<ref name=Saitta2014/> In several countries advertising for e-cigarettes has been monetarily restricted until safety and efficacy [[clinical trial]]s are conclusive.<ref name=Cervellin2013/> A 2014 [[systematic review]] found that "Due to many methodological problems, severe conflicts of interest, the relatively few and often small studies, the inconsistencies and contradictions in results, and the lack of long-term follow-up no firm conclusions can be drawn on the safety of ECs."<ref name=Pisinger2014>{{cite journal|last1=Pisinger|first1=Charlotta|last2=Døssing|first2=Martin|title=A systematic review of health effects of electronic cigarettes|journal=Preventive Medicine|date=December 2014|volume=69|pages=248–260|doi=10.1016/j.ypmed.2014.10.009|pmid=25456810}}</ref> Scientific studies advocate caution before designating e-cigarettes as beneficial but vapers continue to believe they are beneficial.<ref name=Dagaonkar2014/>
+The emerging phenomenon of e-cigarettes is raising concerns among the health community, pharmaceutical industry, and other groups.<ref name=Saitta2014/> A 2014 review recommended that e-cigarettes should be adequately tested for [[consumer safety]].<ref name=Saitta2014/> Another 2014 review stated that there are "reported" adverse health effects.<ref name=Bekki2014/> For example, they found that "The Food and Drug Administration (FDA) reported that e-cigarettes contain carcinogens and toxic chemicals, such as nitrosamines and diethylene glycol, which have potentially harmful effects on humans."<ref name=Bekki2014/> Additionally, a WHO report in 2009 cautioned that the "safety of e-cigarettes is not confirmed."<ref name=Bekki2014/> "In a nutshell, the WHO report shows that e-cigarettes and similar devices pose threats to public health," said Douglas Bettcher, director of WHO's prevention of noncommunicable diseases.<ref name=Bettcher2014>{{cite news|title=WHO calls for ban on e-cigarette use indoors|url=http://www.bignewsnetwork.com/index.php/sid/225119529|date=26 August 2014|publisher=''Big News Network.com''}}</ref> {{unreliable source?|date=February 2015}} A 2014 review stated that "The precautionary principle may be invoked when a phenomenon, a product or a process with potentially dangerous effects has not been subjected to full scientific and objective evaluation so that the harm cannot be determined with sufficient certainty.<ref name=Saitta2014/> In several countries advertising for e-cigarettes has been monetarily restricted until safety and efficacy [[clinical trial]]s are conclusive.<ref name=Cervellin2013/> A 2014 [[systematic review]] found that "Due to many methodological problems, severe conflicts of interest, the relatively few and often small studies, the inconsistencies and contradictions in results, and the lack of long-term follow-up no firm conclusions can be drawn on the safety of ECs."<ref name=Pisinger2014>{{cite journal|last1=Pisinger|first1=Charlotta|last2=Døssing|first2=Martin|title=A systematic review of health effects of electronic cigarettes|journal=Preventive Medicine|date=December 2014|volume=69|pages=248–260|doi=10.1016/j.ypmed.2014.10.009|pmid=25456810}}</ref>
-In August 2014, the [[Forum of International Respiratory Societies]] stated that e-cigarettes have not been demonstrated to be safe.<ref>{{cite journal|last1=&NA;|title=E-Cigarettes|journal=Oncology Times|date=August 2014|volume=36|issue=15|pages=49–50|doi=10.1097/01.COT.0000453432.31465.77}}</ref> A [[National Institute for Health and Care Excellence]] (NICE) guideline did not recommend e-cigarettes as they are questions regarding the safety, efficacy, and quality of these products.<ref>{{cite web|title=Nicotine products can help people to cut down before quitting smoking|url=http://www.nice.org.uk/news/article/nicotine-products-can-help-people-to-cut-down-before-quitting-smoking|publisher=National Institute for Health and Care Excellence}}</ref> In June 2014, the [[Royal College of Physicians]] stated that, "Close monitoring of the use of electronic cigarettes in UK society is essential to ensure trends that are counter to public health are identified and acted upon promptly."<ref>{{cite web | url=https://www.rcplondon.ac.uk/press-releases/rcp-statement-e-cigarettes | title=RCP statement on e-cigarettes | publisher=Royal College of Physicians | date=25 June 2014}}</ref> In 2014, the [[American Medical Association]] "called for reining in the sale and marketing practices of companies that produce electronic nicotine delivery systems" to minors.<ref>{{cite web | url=http://www.ama-assn.org/ama/pub/news/news/2014/2014-06-10-regulating-electronic-cigarettes.page | title=AMA Strengthens Position on Regulation of Electronic Cigarettes | publisher=AMA | date=10 June 2014}}</ref> The [[American Cancer Society]] has stated, "The makers of e-cigarettes say that the ingredients are "safe," but this only means the ingredients have been found to be safe to eat. Inhaling a substance is not the same as swallowing it. There are questions about how safe it is to inhale some substances in the e-cigarette vapor into the lungs."<ref>{{cite web|title=What about electronic cigarettes? Aren’t they safe?|url=http://www.cancer.org/cancer/cancercauses/tobaccocancer/questionsaboutsmokingtobaccoandhealth/questions-about-smoking-tobacco-and-health-e-cigarettes|publisher=American Cancer Society}}</ref> The US [[National Association of County and City Health Officials]] has stated, "Public health experts have expressed concern that e-cigarettes may increase nicotine addiction and tobacco use in young people. E-cigarettes may be particularly appealing to youth due to their high-tech design, wide array of available flavors, including candy-and fruit-flavored cartridges, and easy availability online and in shopping malls. Because in nearly all jurisdictions they are not taxed as tobacco products, e-cigarettes may be more easily obtained by price-sensitive youth."<ref>{{cite web|title=Regulation of Electronic Cigarettes ("E-Cigarettes")|url=http://www.naccho.org/advocacy/positions/upload/12-04-e-Cigarettes.pdf|publisher=National Association of County and City Health Officials}}</ref> The [[American Diabetes Association]] states "There is no evidence that e-cigarettes are a healthier alternative to smoking."<ref>{{cite journal|title=Standards of Medical Care in Diabetes--2015: Summary of Revisions|journal=Diabetes Care|date=2015|volume=54|issue=38|page=S25|doi=10.2337/dc15-S003}}</ref> [[Health Canada]] has stated that, "their safety, quality, and efficacy remain unknown."<ref>{{cite web|title=Nicotine addiction|url=http://healthycanadians.gc.ca/healthy-living-vie-saine/tobacco-tabac/addiction-dependance-eng.php?_ga=1.27186174.259825273.1415301828|publisher=Health Canada}}</ref> The [[Canadian Cancer Society]] has stated that, "A few studies have shown that there may be low levels of harmful substances in some e-cigarettes, even if they don’t have nicotine."<ref>{{cite web|title=Ways to quit|url=http://www.cancer.ca/en/cancer-information/cancer-101/what-is-a-risk-factor/tobacco/ways-to-quit/?region=nu|publisher=Canadian Cancer Society}}</ref> The Canadian [[Heart and Stroke Foundation]] has stated, "Marketing and promotion of e-cigarettes is common. Youth are targeted with the addition of attractive candy or fruit flavours."<ref>{{cite web|title=Heart and Stroke Foundation: E-cigarettes in Canada|url=http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.9207931/k.D09C/Heart_and_Stroke_Foundation_Ecigarettes_in_Canada.htm|publisher=Heart and Stroke Foundation}}</ref> The [[Cancer Council Australia]] and [[Heart Foundation]] released a joint position statement that stated, "The limited evidence available points to a risk that widespread electronic cigarette use could undo the decades of public policy work in Australia that has reduced the appeal of cigarette use in children. Already there are anecdotal reports of electronic cigarettes being confiscated in Australian schools."<ref>{{cite web|title=Position Statement Electronic Cigarettes|url=http://wiki.cancer.org.au/policy/Position_statement_-_Electronic_cigarettes#Key_health_concerns|publisher=Cancer Council Australia, Heart Foundation}}</ref>  The [[Cancer Society of New Zealand]] released a position statement which states, "E-cigarettes are a novelty product, which look like cigarettes. They are also marketed in a similar way, and come in candy-like flavours, such as chocolate and fruit,which may appeal to and encourage young people to try these products."<ref>{{cite web|title=Position Statement on Electronic Cigarettes|url=http://www.cancernz.org.nz/assets/files/info/Position%20Statements/2011/E-cigarette_Position%20statementFINALJul13.pdf|publisher=Cancer Society of New Zealand}}</ref> The [[Spanish Society of Pneumonology and Thoracic Surgery]] (SEPAR) released a position statement which states that "indiscriminate use" of e-cigarettes is a public health risk and they may encourage young people to start smoking.<ref name=JimenezRuiz2014>{{cite journal|last1=Jimenez Ruiz|first1=CA|last2=Solano Reina|first2=S|last3=de Granda Orive|first3=JI|last4=Signes-Costa Minaya|first4=J|last5=de Higes Martinez|first5=E|last6=Riesco Miranda|first6=JA|last7=Altet Gómez|first7=N|last8=Lorza Blasco|first8=JJ|last9=Barrueco Ferrero|first9=M|last10=de Lucas Ramos|first10=P|title=The electronic cigarette. Official statement of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) on the efficacy, safety and regulation of electronic cigarettes.|journal=Archivos de bronconeumologia|date=August 2014|volume=50|issue=8|pages=362–7|pmid=24684764|doi=10.1016/j.arbr.2014.06.007}}</ref>
 ==Adverse effects==
-The UK [[National Health Service]] has stated, "While e-cigarettes may be safer than conventional cigarettes, we don’t yet know the long-term effects of vaping on the body."<ref>{{cite web|title=Stop smoking treatments|url=http://www.nhs.uk/Conditions/Smoking-%28quitting%29/Pages/Treatment.aspx|publisher=UK National Health Service}}</ref> Smokefree.gov, a website run by the Tobacco Control Research Branch of the [[National Cancer Institute]] to provide information to help quit smoking, stated that "Since e-cigs aren’t regulated yet, there’s no way of knowing how much nicotine is in them or what other chemicals they contain. These two things make the safety of e-cigs unclear."<ref name=smokefree2014>{{cite web|title=E-Cigarettes|url=http://smokefree.gov/e-cigarettes|publisher=Tobacco Control Research Branch of the National Cancer Institute}}</ref> No serious adverse effects from e-cigarette have been reported in trials.<ref name=Cochrane2014/> Reports to the [[Food and Drug Administration]] (FDA) for minor adverse effects identified with using e-cigarettes include headache, chest pain, nausea, and cough.<ref name=EbbertAgunwamba2015/> Major adverse effects reported to the FDA included hospitalizations for pneumonia, congestive heart failure, seizure, rapid heart rate, and burns due to regular use.<ref name=EbbertAgunwamba2015/> Less serious [[adverse effect]]s including throat and mouth inflammation, vomiting, nausea, and cough have resulted from e-cigarette use.<ref name=Grana2014/> Short-term adverse effects include mouth and throat inflammation, dry cough, and nausea.<ref name=Gualano2014/> Adverse effect are mostly associated with a short term of use, and their frequency was significantly lower after 52 weeks of use.<ref name=Gualano2014/> Long-term studies regarding the effects of e-cigarettes after chronic exposure are unavailable.<ref name=Gualano2014>{{cite journal|last1=Gualano|first1=M. R.|last2=Passi|first2=S.|last3=Bert|first3=F.|last4=La Torre|first4=G.|last5=Scaioli|first5=G.|last6=Siliquini|first6=R.|title=Electronic cigarettes: assessing the efficacy and the adverse effects through a systematic review of published studies|journal=Journal of Public Health|date=9 August 2014|doi=10.1093/pubmed/fdu055|pmid=25108741}}</ref> Some [[case report]]s found harms to health brought about by e-cigarettes in many countries, such as the US and in Europe; the most common effect was dryness of the mouth and throat.<ref name=Bekki2014/> Many of the observed negative effects from e-cigarette use concerning the [[nervous system]] and the [[sensory system]] are probably related to nicotine overdose or withdrawal.<ref name=Lauterstein2014>{{cite journal|last1=Lauterstein|first1=Dana|last2=Hoshino|first2=Risa|last3=Gordon|first3=Terry|last4=Watkins|first4=Beverly-Xaviera|last5=Weitzman|first5=Michael|last6=Zelikoff|first6=Judith|title=The Changing Face of Tobacco Use Among United States Youth|journal=Current Drug Abuse Reviews|volume=7|issue=1|year=2014|pages=29–43|issn=18744737|doi=10.2174/1874473707666141015220110|pmid=25323124}}</ref> The most frequently reported benefits of e-cigarettes were reduced shortness of breath in comparison to traditional cigarettes, reduced cough, reduced spitting, and reduced sore throat.<ref name=Dagaonkar2014/> In youth, e-cigarette use risks involve accidental nicotine exposure.<ref name=Durmowicz2014/> In [[pediatric]] patients, accidental exposures include ingesting of e-liquids and inhaling of e-cigarette vapor; choking on e-cigarette components is also a potential hazard.<ref name=Durmowicz2014>{{cite journal|last1=Durmowicz|first1=E. L.|title=The impact of electronic cigarettes on the paediatric population|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii41–ii46|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051468|pmid=24732163}}</ref> In the United States, a child died after ingesting liquid nicotine.<ref>{{cite news|last=Wise|first=Lindsay|title=Child’s death revives call for federal government to regulate liquid nicotine for e-cigarettes|url=http://www.mcclatchydc.com/2015/01/13/252945/childs-death-revives-call-for.html|date=13 January 2015|accessdate=13 January 2014|newspaper=McClatchyDC|publisher=[[The McClatchy Company|McClatchy]]}}</ref>
+No serious adverse effects from e-cigarette have been reported in trials.<ref name=Cochrane2014/> Less serious [[adverse effect]]s including throat and mouth inflammation, vomiting, nausea, and cough have resulted from e-cigarette use.<ref name=Grana2014/> Short-term adverse effects include mouth and throat inflammation, dry cough, and nausea.<ref name=Gualano2014/> Adverse effect are mostly associated with a short term of use, and their frequency was significantly lower after 52 weeks of use.<ref name=Gualano2014/> Long-term studies regarding the effects of e-cigarettes after chronic exposure are unavailable.<ref name=Gualano2014>{{cite journal|last1=Gualano|first1=M. R.|last2=Passi|first2=S.|last3=Bert|first3=F.|last4=La Torre|first4=G.|last5=Scaioli|first5=G.|last6=Siliquini|first6=R.|title=Electronic cigarettes: assessing the efficacy and the adverse effects through a systematic review of published studies|journal=Journal of Public Health|date=9 August 2014|doi=10.1093/pubmed/fdu055|pmid=25108741}}</ref> Some [[case report]]s found harms to health brought about by e-cigarettes in many countries, such as the US and in Europe; the most common effect was dryness of the mouth and throat.<ref name=Bekki2014/> Many of the observed negative effects from e-cigarette use concerning the [[nervous system]] and the [[sensory system]] are probably related to nicotine overdose or withdrawal.<ref name=Lauterstein2014>{{cite journal|last1=Lauterstein|first1=Dana|last2=Hoshino|first2=Risa|last3=Gordon|first3=Terry|last4=Watkins|first4=Beverly-Xaviera|last5=Weitzman|first5=Michael|last6=Zelikoff|first6=Judith|title=The Changing Face of Tobacco Use Among United States Youth|journal=Current Drug Abuse Reviews|volume=7|issue=1|year=2014|pages=29–43|issn=18744737|doi=10.2174/1874473707666141015220110|pmid=25323124}}</ref> In youth, e-cigarette use risks involve accidental nicotine exposure.<ref name=Durmowicz2014/> In [[pediatric]] patients, accidental exposures include ingesting of e-liquids and inhaling of e-cigarette vapor; choking on e-cigarette components is also a potential hazard.<ref name=Durmowicz2014>{{cite journal|last1=Durmowicz|first1=E. L.|title=The impact of electronic cigarettes on the paediatric population|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii41–ii46|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051468|pmid=24732163}}</ref> In the United States, a child died after ingesting liquid nicotine.<ref>{{cite news|last=Wise|first=Lindsay|title=Child’s death revives call for federal government to regulate liquid nicotine for e-cigarettes|url=http://www.mcclatchydc.com/2015/01/13/252945/childs-death-revives-call-for.html|date=13 January 2015|accessdate=13 January 2014|newspaper=McClatchyDC|publisher=[[The McClatchy Company|McClatchy]]}}</ref>
 Poisoning associated with e-cigarettes may happen by ingestion, inhalation, or absorption.<ref name=Brandon2015/> The US [[Regulation of tobacco by the U.S. Food and Drug Administration#Center for Tobacco Products|Food and Drug Administration Center for Tobacco Products]] reported between 2008 and the beginning of 2012, 47 cases of adverse effects associated with e-cigarettes, of which eight were considered serious.<ref name=Hajek2014/> A causal relationship between e-cigarettes and the reported adverse effects was not established with the exception of two severe outcomes in the United States: a death when an infant choked on the cartridges and burns when one blew up.<ref name=Hajek2014/> In the United States the number of calls to poison control centers related to electronic cigarettes have increased between 2010 and 2014, such that they now represent 42% of reported cases due to either cigarettes and e-cigarettes up from 0.3%.<ref name=OrrAsal2014/> These calls were in connection to both adults and children.<ref name=OrrAsal2014/> E-cigarettes were associated with fewer adverse effects than nicotine patches.<ref name=OrrAsal2014>{{cite journal|last1=Orr|first1=KK|last2=Asal|first2=NJ|title=Efficacy of Electronic Cigarettes for Smoking Cessation.|journal=The Annals of pharmacotherapy|date=November 2014|volume=48|issue=11|pages=1502–1506|pmid=25136064|doi=10.1177/1060028014547076}}</ref> Calls to U.S. [[poison control center]]s related to e-cigarette exposures involved inhalations, eye exposures, skin exposures, and ingestion, in both adults and young children.<ref name=MMWR2014>{{cite journal |title=Notes from the field: calls to poison centers for exposures to electronic cigarettes--United States, September 2010-February 2014 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=63 |issue=13 |pages=292–3 |date=April 2014 |pmid=24699766 |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6313a4.htm |author1= Centers for Disease Control and Prevention (CDC)}}</ref> The California Poison Control System reported 35 cases of e-cigarette contact from 2010 to 2012, 14 were in children and 25 were from accidental contact.<ref name=FarsalinosPolosa2014/> The majority of adverse effects reported were nausea, vomiting, dizziness and oral irritation.<ref name=FarsalinosPolosa2014>{{cite journal|last1=Farsalinos|first1=K. E.|last2=Polosa|first2=R.|title=Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review|journal=Therapeutic Advances in Drug Safety|volume=5|issue=2|year=2014|pages=67–86|issn=2042-0986|doi=10.1177/2042098614524430|pmc=4110871|pmid=25083263}}</ref>
@@ Line 20: / Line 21: @@
 <!-- Toxicology evidence -->
 [[File:Toxicants emitted by tobacco cigarettes and e-cigarettes ehp.122-A244.t001.png|thumbnail|left|Chart showing various toxicants as measured in cigarette and e-cigarette smoke.<ref>{{cite journal|last1=Arnold|first1=Carrie|title=Vaping and Health: What Do We Know about E-Cigarettes?|journal=Environmental Health Perspectives|volume=122|issue=9|year=2014|pages=A244–A249|doi=10.1289/ehp.122-A244|pmc=4154203|pmid=25181730}}</ref>]]
-A preliminary analysis of e-cigarette cartridges by the US Food and Drug Administration (FDA) in 2009 identified that some contain [[tobacco-specific nitrosamines]] (TSNAs), known cancer-causing agents.<ref name=FDA_nitrosamines>{{cite web|title=Safety Watch: Electronic Cigarettes|url=http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm173327.htm|publisher=U.S. Food and Drug Administration}}</ref> The tobacco specific impurities suspected of being harmful to humans were [[anabasine]], [[myosmine]], and β-nicotyrine. They were detected in a majority of the samples.<ref name=FDAChemicalAnalysis>{{cite web|url=http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm173146.htm|author=FDA|title=Summary of Results: Laboratory Analysis of Electronic Cigarettes Conducted By FDA|date=22 July 2009|accessdate=22 July 2009}}</ref> The amounts of TSNAs present were on par with a nicotine inhaler.<ref name=FDA_nitrosamines/> The FDA's analysis also detected [[diethylene glycol]], which is poisonous, in a single cartridge manufactured by Smoking Everywhere and nicotine in one cartridge claimed to be nicotine-free.<ref name=FDA_nitrosamines/><ref name=FDAStudy2009/> This prompted the FDA to warn that e-cigarettes may present a health risk.<ref name=Drummond2014/> While diethylene glycol was found in a cartridge tested in 2009 by the FDA, in 2011 researchers reviewed the data and noted that 15 other studies had failed to find any evidence of this chemical in e-cigarettes.<ref>{{cite web | url=http://www.ibtimes.com/e-cigarettes-effective-nicotine-patches-helping-smokers-quit-study-1403523 | title=E-Cigarettes As Effective As Nicotine Patches in Helping Smokers Quit: Study | work=[[International Business Times]] | date=8 September 2013 | accessdate=15 December 2013 | author=Palmer, Roxanne}}</ref>
+A preliminary analysis of e-cigarette cartridges by the US [[Food and Drug Administration]] (FDA) in 2009 identified that some contain [[tobacco-specific nitrosamines]] (TSNAs), known cancer-causing agents.<ref name=FDA_nitrosamines>{{cite web|title=Safety Watch: Electronic Cigarettes|url=http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm173327.htm|publisher=U.S. Food and Drug Administration}}</ref> The tobacco specific impurities suspected of being harmful to humans were [[anabasine]], [[myosmine]], and β-nicotyrine. They were detected in a majority of the samples.<ref name=FDAChemicalAnalysis>{{cite web|url=http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm173146.htm|author=FDA|title=Summary of Results: Laboratory Analysis of Electronic Cigarettes Conducted By FDA|date=22 July 2009|accessdate=22 July 2009}}</ref> The amounts of TSNAs present were on par with a nicotine inhaler.<ref name=FDA_nitrosamines/> The FDA's analysis also detected [[diethylene glycol]], which is poisonous, in a single cartridge manufactured by Smoking Everywhere and nicotine in one cartridge claimed to be nicotine-free.<ref name=FDA_nitrosamines/><ref name=FDAStudy2009/> This prompted the FDA to warn that e-cigarettes may present a health risk.<ref name=Drummond2014/> While diethylene glycol was found in a cartridge tested in 2009 by the FDA, in 2011 researchers reviewed the data and noted that 15 other studies had failed to find any evidence of this chemical in e-cigarettes.<ref>{{cite web | url=http://www.ibtimes.com/e-cigarettes-effective-nicotine-patches-helping-smokers-quit-study-1403523 | title=E-Cigarettes As Effective As Nicotine Patches in Helping Smokers Quit: Study | work=[[International Business Times]] | date=8 September 2013 | accessdate=15 December 2013 | author=Palmer, Roxanne}}</ref>
-The UK National Health Service noted that the toxic chemicals found by the FDA were at levels one-thousandth that of cigarette smoke, and that while there is no certainty that these small traces are harmless, initial test results are reassuring.<ref name=nhs>{{cite web|title=E-cigarettes to be regulated as medicines |publisher=[[National Health Service]]|date=12 June 2013|accessdate=August 2013|url=http://www.nhs.uk/news/2013/06June/Pages/e-cigarettes-and-vaping.aspx}}</ref> Further concerns were raised over inconsistent amounts of nicotine delivered when drawing on the device.<ref name=FDAStudy2009>{{cite web|url=http://www.fda.gov/downloads/Drugs/ScienceResearch/UCM173250.pdf|author=FDA|title=FDA 2009 Study Data: Evaluation of e-cigarettes|work=Food and Drug Administration (US) -center for drug evaluation and research|date=4 May 2009|accessdate=4 May 2009}}</ref> They appear to be similar in [[toxicity]] to other [[nicotine replacement products]], but there is not enough data to draw conclusions.<ref name=Caponnetto2013>{{cite journal|title=Electronic cigarette: a possible substitute for cigarette dependence.|journal=Monaldi archives for chest disease|date=Mar 2013|author1=Caponnetto P|author2=Russo C|author3=Bruno CM|author4=Alamo A|author5=Amaradio MD|author6=Polosa R.|volume=79|issue=1|pages=12–19|pmid=23741941}}</ref> A 2014 review found higher levels of carcinogens and toxins than in an FDA-approved nicotine inhaler, suggesting that FDA-approved devices may deliver nicotine more safely.<ref name=Drummond2014/> In 2014, The [[World Lung Foundation]] stated that "Researchers find that many e-cigarettes contain toxins, contaminants and carcinogens that conflict with the industry’s portrayal of its products as purer, healthier alternatives. They also find considerable variations in the amount of nicotine delivered by different brands. None of this information is made available to consumers so they really don’t know what they are ingesting, or how much."<ref name=WorldLungFederation2014>{{cite web|title=WHO Right to Call for E-Cigarette Regulation|url=http://www.worldlungfoundation.org/ht/d/ReleaseDetails/i/32757|publisher=World Lung Federation}}</ref> The [[British Medical Association]] (BMA) reported in 2013 that there are "concerns that the use of e-cigarettes could threaten the norm of not smoking in public places and workplaces."<ref>{{cite web | url=http://bma.org.uk/news-views-analysis/news/2013/january/ecigarettes-not-proven-quitting-aid-says-bma | title=E-cigarettes not proven quitting aid, says BMA | work=British Medical Association | date=30 January 2013}}</ref> In October 2012, the [[World Medical Association]] stated, "Manufacturers and marketers of e-cigarettes often claim that use of their products is a safe alternative to smoking, particularly since they do not produce carcinogenic smoke. However, no studies have been conducted to determine that the vapor is not carcinogenic, and there are other potential risks associated with these devices: Appeal to children, especially when flavors like strawberry or chocolate are added to the cartridges."<ref>{{cite web|title=WMA Statement on Electronic Cigarettes and Other Electronic Nicotine Delivery Systems|url=http://www.wma.net/en/30publications/10policies/e19/|publisher=World Medical Association}}</ref> The 2015 [[California Department of Public Health]] has reported that "Mainstream and secondhand e-cigarette aerosol has been found to contain at least ten chemicals that are on California’s Proposition 65 list of chemicals known to cause cancer, birth defects, or other reproductive harm."<ref name=Chapman2015>{{cite web | url=http://cdph.ca.gov/programs/tobacco/Documents/Media/State%20Health-e-cig%20report.pdf | title=State Health Officer’s Report on E-Cigarettes: A Community Health Threat | publisher = California Department of Public Health, California Tobacco Control Program | date = January 2015}}</ref>
+The UK [[National Health Service]] noted that the toxic chemicals found by the FDA were at levels one-thousandth that of cigarette smoke, and that while there is no certainty that these small traces are harmless, initial test results are reassuring.<ref name=nhs>{{cite web|title=E-cigarettes to be regulated as medicines |publisher=[[National Health Service]]|date=12 June 2013|accessdate=August 2013|url=http://www.nhs.uk/news/2013/06June/Pages/e-cigarettes-and-vaping.aspx}}</ref> Further concerns were raised over inconsistent amounts of nicotine delivered when drawing on the device.<ref name=FDAStudy2009>{{cite web|url=http://www.fda.gov/downloads/Drugs/ScienceResearch/UCM173250.pdf|author=FDA|title=FDA 2009 Study Data: Evaluation of e-cigarettes|work=Food and Drug Administration (US) -center for drug evaluation and research|date=4 May 2009|accessdate=4 May 2009}}</ref> They appear to be similar in [[toxicity]] to other [[nicotine replacement products]], but there is not enough data to draw conclusions.<ref name=Caponnetto2013>{{cite journal|title=Electronic cigarette: a possible substitute for cigarette dependence.|journal=Monaldi archives for chest disease|date=Mar 2013|author1=Caponnetto P|author2=Russo C|author3=Bruno CM|author4=Alamo A|author5=Amaradio MD|author6=Polosa R.|volume=79|issue=1|pages=12–19|pmid=23741941}}</ref> A 2014 review found higher levels of carcinogens and toxins than in an FDA-approved nicotine inhaler, suggesting that FDA-approved devices may deliver nicotine more safely.<ref name=Drummond2014/> The 2015 California Department of Public Health has reported that "Mainstream and secondhand e-cigarette aerosol has been found to contain at least ten chemicals that are on California’s Proposition 65 list of chemicals known to cause cancer, birth defects, or other reproductive harm."<ref>{{cite web | url=http://cdph.ca.gov/programs/tobacco/Documents/Media/State%20Health-e-cig%20report.pdf | title=State Health Officer’s Report on E-Cigarettes: A Community Health Threat | publisher = California Department of Public Health, California Tobacco Control Program | date = January 2015}}</ref>
 [[File:Nicotine-2D-skeletal.png|thumb|The [[nicotine]] [[molecule]].]]
-A policy statement by the [[American Association for Cancer Research]] and the [[American Society of Clinical Oncology]] has reported that nicotine is regarded as a potentially [[potency (pharmacology)|lethal]] poison.<ref name=Brandon2015/> Research suggests that experienced e-cigarettes users are able to get as much nicotine from e-cigarettes as traditional cigarettes.<ref name=Brandon2015/> The levels were above that of nicotine replacement product users.<ref name=Brandon2015/> Other research have demonstrated that some e-cigarettes users experience adverse effects like throat irritation which could be the result of exposure to nicotine, nicotine solvents, or toxicants in the aerosol.<ref name=Brandon2015/> However at the low amount of nicotine provided by e-cigarettes fatal overdose from use is unlikely; in contrast, the potent amount of nicotine in e-cigarettes liquids may be toxic if it is accidentally ingested or absorbed via the skin.<ref name=Brandon2015>{{cite journal|last1=Brandon|first1=T. H.|last2=Goniewicz|first2=M. L.|last3=Hanna|first3=N. H.|last4=Hatsukami|first4=D. K.|last5=Herbst|first5=R. S.|last6=Hobin|first6=J. A.|last7=Ostroff|first7=J. S.|last8=Shields|first8=P. G.|last9=Toll|first9=B. A.|last10=Tyne|first10=C. A.|last11=Viswanath|first11=K.|last12=Warren|first12=G. W.|title=Electronic Nicotine Delivery Systems: A Policy Statement from the American Association for Cancer Research and the American Society of Clinical Oncology|journal=Clinical Cancer Research|url=http://clincancerres.aacrjournals.org/content/early/2015/01/08/1078-0432.CCR-14-2544.full.pdf+html|year=2015|issn=1078-0432|doi=10.1158/1078-0432.CCR-14-2544}}</ref> The user inhales an [[aerosol]] containing chemicals and very addictive nicotine.<ref name=FDAPublicHealthFocus>{{cite web|title=Public Health Focus: Electronic Cigarettes (e-Cigarettes)|url=http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm172906.htm|publisher=FDA|date=24 April 2014}}</ref> The distribution on the amount of nicotine inhaled by the user is not clear.<ref name=Drummond2014/> A 2014 review found that "compared with traditional cigarettes, e-cigarette average puff duration was significantly longer, and e-cigarette use required stronger suction."<ref name=Evans2014>{{cite journal|last1=Evans|first1=S. E.|last2=Hoffman|first2=A. C.|title=Electronic cigarettes: abuse liability, topography and subjective effects|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii23–ii29|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051489|pmid=24732159}}</ref> Studies suggest that inexperienced users obtain moderate amounts of nicotine from e-cigarettes.<ref name=Schroeder2014>{{cite journal|last1=Schroeder|first1=M. J.|last2=Hoffman|first2=A. C.|title=Electronic cigarettes and nicotine clinical pharmacology|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii30–ii35|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051469|pmid=24732160}}</ref> Newer e-cigarettes with more concentrated nicotine liquids may deliver nicotine at levels similar to traditional cigarettes.<ref name=Brandon2015/> Some e-cigarettes have tank systems with stronger batteries that heat solutions to higher temperatures which could result in users with blood nicotine levels similar to those of traditional cigarettes.<ref name=AHA2014/> In May 2014, [[Cancer Research UK]] stated that, "There is some evidence that suggests nicotine may promote tumour growth in animal and human cells. There are also some further very preliminary results that suggest that e-cigarettes promote tumour growth in human cells."<ref name=CancerResearchUK2014>{{cite web | url=http://www.cancerresearchuk.org/sites/default/files/policy_may2014_e-cigarette_briefing.pdf | title=Cancer Research UK Briefing: Electronic Cigarettes | publisher=Cancer Research UK | date=May 2014}}</ref> It is not fully understood the long-term health impacts of the main chemicals nicotine and propylene glycol in the vapor.<ref name=CancerResearchUK2014/> Nicotine can cause high blood pressure and abnormal heart rhythms.<ref name=WorldLungFederation2014/> Nicotine drops estrogen levels and has been associated with early menopause in women.<ref name=WorldLungFederation2014/> There is a greater possibility for a negative effect of nicotine on growing brain development, as well as the chance of nicotine addiction for life.<ref name=WorldLungFederation2014/> [[Serum (blood)|Serum]] nicotine levels identified are inharmonious and rely upon the user and the device.<ref name=Drummond2014/> There was inconsistent labeling of the actual nicotine content on e-liquid cartridges from some brands.<ref name=Grana2014/> Some nicotine has been found in ‘no nicotine' liquids.<ref name=Bertholon2013/> Due to nicotine content inconstancy, it is recommended that e-cigarette companies develop quality standards with respect to nicotine content.<ref name=Cheng2014/> There are safety issues with the nicotine exposure from e-cigarettes, which has the possibility of causing addiction and other adverse effects.<ref name=Cheng2014/> Serum [[cotinine]] levels are comparable to that of traditional cigarettes.<ref name=Callahan2014/> E-cigarettes provide nicotine to the blood quicker than nicotine inhalers.<ref name=Dagaonkar2014>{{cite journal|last1=Dagaonkar RS|first1=R.S.|last2=Udwadi|first2=Z.F.|title=Water pipes and E-cigarettes: new faces of an ancient enemy|journal=Journal of the Association of Physicians of India|volume=62|issue=4|year=2014|pages=324-328|url=http://www.japi.org/april_2014/05_ra_water_pipes.pdf|pmid=25327035}}</ref> In August 2014, the [[American Heart Association]] released a policy statement in which they noted that "Proponents of e-cigarettes maintain that these products emulate smoking behavior without exposing the user to the toxic smoke constituents of conventional cigarettes that are deleterious to health, so there would be a public health benefit if individual smokers completely switched or substantially reduced their cigarette smoking habit. However, the use of e-cigarettes could be a problem at the population level. For instance, e-cigarettes could fuel and promote nicotine addiction, especially in children, and their acceptance has the potential to renormalize smoking behavior. E-cigarette use could also potentially serve as a gateway to other drugs and harmful substances."<ref name=AHA2014>{{cite journal|last1=Bhatnagar|first1=A.|last2=Whitsel|first2=L. P.|last3=Ribisl|first3=K. M.|last4=Bullen|first4=C.|last5=Chaloupka|first5=F.|last6=Piano|first6=M. R.|last7=Robertson|first7=R. M.|last8=McAuley|first8=T.|last9=Goff|first9=D.|last10=Benowitz|first10=N.|title=Electronic Cigarettes: A Policy Statement From the American Heart Association|journal=Circulation|date=24 August 2014|volume=130|issue=16|pages=1418–1436|doi=10.1161/CIR.0000000000000107}}</ref>
+A policy statement by the [[American Association for Cancer Research]] and the [[American Society of Clinical Oncology]] has reported that nicotine is regarded as a potentially [[potency (pharmacology)|lethal]] poison.<ref name=Brandon2015/> Research suggests that experienced e-cigarettes users are able to get as much nicotine from e-cigarettes as traditional cigarettes.<ref name=Brandon2015/> The levels were above that of nicotine replacement product users.<ref name=Brandon2015/> Other research have demonstrated that some e-cigarettes users experience adverse effects like throat irritation which could be the result of exposure to nicotine, nicotine solvents, or toxicants in the aerosol.<ref name=Brandon2015/> However at the low amount of nicotine provided by e-cigarettes fatal overdose from use is unlikely; in contrast, the potent amount of nicotine in e-cigarettes liquids may be toxic if it is accidentally ingested or absorbed via the skin.<ref name=Brandon2015>{{cite journal|last1=Brandon|first1=T. H.|last2=Goniewicz|first2=M. L.|last3=Hanna|first3=N. H.|last4=Hatsukami|first4=D. K.|last5=Herbst|first5=R. S.|last6=Hobin|first6=J. A.|last7=Ostroff|first7=J. S.|last8=Shields|first8=P. G.|last9=Toll|first9=B. A.|last10=Tyne|first10=C. A.|last11=Viswanath|first11=K.|last12=Warren|first12=G. W.|title=Electronic Nicotine Delivery Systems: A Policy Statement from the American Association for Cancer Research and the American Society of Clinical Oncology|journal=Clinical Cancer Research|url=http://clincancerres.aacrjournals.org/content/early/2015/01/08/1078-0432.CCR-14-2544.full.pdf+html|year=2015|issn=1078-0432|doi=10.1158/1078-0432.CCR-14-2544}}</ref> The user inhales an [[aerosol]] containing chemicals and very addictive nicotine.<ref name=FDAPublicHealthFocus>{{cite web|title=Public Health Focus: Electronic Cigarettes (e-Cigarettes)|url=http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm172906.htm|publisher=FDA|date=24 April 2014}}</ref> The distribution on the amount of nicotine inhaled by the user is not clear<ref name=Drummond2014/> Newer e-cigarettes with more concentrated nicotine liquids may deliver nicotine at levels similar to traditional cigarettes.<ref name=Brandon2015/> [[Serum (blood)|Serum]] nicotine levels identified are inharmonious and rely upon the user and the device.<ref name=Drummond2014/> There was inconsistent labeling of the actual nicotine content on e-liquid cartridges from some brands.<ref name=Grana2014/> Some nicotine has been found in ‘no nicotine' liquids.<ref name=Bertholon2013/> Due to nicotine content inconstancy, it is recommended that e-cigarette companies develop quality standards with respect to nicotine content.<ref name=Cheng2014/> There are safety issues with the nicotine exposure from e-cigarettes, which has the possibility of causing addiction and other adverse effects.<ref name=Cheng2014/> Serum [[cotinine]] levels are comparable to that of traditional cigarettes.<ref name=Callahan2014/>
-The risk from the inhalation of [[propylene glycol]] and [[glycerol]] is probably low.<ref name=Hajek2014>{{cite journal|last1=Hajek|first1=P|last2=Etter|first2=JF|last3=Benowitz|first3=N|last4=Eissenberg|first4=T|last5=McRobbie|first5=H|title=Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit.|url=http://tobonline.com/Media/Default/Article/Addiction-%20Hajek%2014.pdf|journal=Addiction (Abingdon, England)|date=31 July 2014|pmid=25078252|doi=10.1111/add.12659|volume=109|issue=11|pages=1801–10}}</ref> Some research states that propylene glycol emissions may cause respiratory irritation and raise the likelihood to develop asthma.<ref name=Kacker2014/> E-cigarettes companies use purified water and glycerin instead of propylene glycol for aerosol production to lessen the risks.<ref name=Kacker2014/> When heated at hotter temperatures glycerol may generate harmful [[acrolein]].<ref name=Hajek2014/> Some e-cigarette products had acrolein identified in the aerosol.<ref name=Hajek2014/> Acrolein levels were reduced by 60% in dual users and 80% for those that completely switched to e-cigarettes when compared to traditional cigarettes.<ref name=Hajek2014/> If exposure of aerosols to propylene glycol and glycerin rises to levels that one would consider the exposure in association with a workplace setting, it would be sensible to investigate the health of exposed persons.<ref name=Bur2014/> The essential propylene glycol and/or glycerol mixture may consist of natural or artificial substances to provide it flavor.<ref name=Bertholon2013/> Some of these substances are regarded as toxic and a number of them resemble known [[carcinogen]]s.<ref name=Bertholon2013/> Generally, flavoring additives are imprecisely described, using terms such as "vegetable flavoring".<ref name=Bertholon2013/> Although they are approved for human consumption there are no studies on the short- or long-term effects of inhaling them.<ref name=Bertholon2013/> Some artificial flavors have been demonstrated as being [[cytotoxic]].<ref name=Bertholon2013/> For example, cinnamaldehyde has been documented as a highly cytotoxic material in cinnamon-flavored refill solutions.<ref name=EbbertAgunwamba2015/>
+The risk from the inhalation of [[propylene glycol]] and [[glycerol]] is probably low.<ref name=Hajek2014>{{cite journal|last1=Hajek|first1=P|last2=Etter|first2=JF|last3=Benowitz|first3=N|last4=Eissenberg|first4=T|last5=McRobbie|first5=H|title=Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit.|url=http://tobonline.com/Media/Default/Article/Addiction-%20Hajek%2014.pdf|journal=Addiction (Abingdon, England)|date=31 July 2014|pmid=25078252|doi=10.1111/add.12659|volume=109|issue=11|pages=1801–10}}</ref> Some research states that propylene glycol emissions may cause respiratory irritation and raise the likelihood to develop asthma.<ref name=Kacker2014/> E-cigarettes companies use purified water and glycerin instead of propylene glycol for aerosol production to lessen the risks.<ref name=Kacker2014/> When heated at hotter temperatures glycerol may generate harmful [[acrolein]].<ref name=Hajek2014/> Some e-cigarette products had acrolein identified in the aerosol.<ref name=Hajek2014/> Acrolein levels were reduced by 60% in dual users and 80% for those that completely switched to e-cigarettes when compared to traditional cigarettes.<ref name=Hajek2014/> If exposure of aerosols to propylene glycol and glycerin rises to levels that one would consider the exposure in association with a workplace setting, it would be sensible to investigate the health of exposed persons.<ref name=Bur2014/> The essential propylene glycol and/or glycerol mixture may consist of natural or artificial substances to provide it flavor.<ref name=Bertholon2013/> Some of these substances are regarded as toxic and a number of them resemble known [[carcinogen]]s.<ref name=Bertholon2013/> Generally, flavoring additives are imprecisely described, using terms such as "vegetable flavoring".<ref name=Bertholon2013/> Although they are approved for human consumption there are no studies on the short- or long-term effects of inhaling them.<ref name=Bertholon2013/> Some artificial flavors have been demonstrated as being [[cytotoxic]].<ref name=Bertholon2013/>
-A 2014 review found "Various chemical substances and ultrafine particles known to be toxic, carcinogenic and/or to cause respiratory and heart distress have been identified in e-cigarette aerosols, cartridges, refill liquids and environmental emissions."<ref name=Cheng2014/> Few of the methods in the studies the review looked at were validated.<ref name=Cheng2014/> Many toxic chemical compounds have been produced from e-cigarettes, especially carbonyl compounds like [[formaldehyde]], [[acetaldehyde]], [[acrolein]], and [[glyoxal]], which are frequently identified in e-cigarette aerosols.<ref name=Bekki2014/> These materials may cause harmful health effects; though, in the majority of cases, the amounts inhaled are less than those in traditional cigarettes.<ref name=Bekki2014>{{cite journal|last1=Bekki|first1=Kanae|last2=Uchiyama|first2=Shigehisa|last3=Ohta|first3=Kazushi|last4=Inaba|first4=Yohei|last5=Nakagome|first5=Hideki|last6=Kunugita|first6=Naoki|title=Carbonyl Compounds Generated from Electronic Cigarettes|journal=International Journal of Environmental Research and Public Health|volume=11|issue=11|year=2014|pages=11192–11200|issn=1660-4601|doi=10.3390/ijerph111111192|pmid=25353061}}</ref> The toxicity of e-cigarettes and e-liquid can vary greatly, as there is potential differences in construction and materials in the delivery device, kind and origin of ingredients in the e-liquid, and the use or non-use of [[good manufacturing practice]]s and [[quality control]] approaches.<ref name=Orr2014/> Devices using higher voltages can produce carcinogens including formaldehyde at levels found in cigarette smoke.<ref name=Collaco2015/> While there is variability in the ingredients and concentrations of ingredients in e-cigarette liquids, tobacco smoke contains thousands of chemicals, most of which are not understood and many of which are known to be harmful.<ref name=Saitta2014>{{cite journal|last=Saitta|first=D|author2=Ferro, GA |author3=Polosa, R |title=Achieving appropriate regulations for electronic cigarettes.|journal=Therapeutic advances in chronic disease|date=Mar 2014|volume=5|issue=2|pages=50–61|pmid=24587890|doi=10.1177/2040622314521271|pmc=3926346}}</ref> The levels of [[toxicant|chemical constituents]] in the vapor were found to be 1 to 2 [[orders of magnitude]] smaller than in cigarette smoke but greater compared to a [[nicotine inhaler]].<ref name=Grana2014/> The [[Centers for Disease Control and Prevention]] (CDC) stated the possible negative impact between nicotine and [[brain development]] in youth is a concern.<ref name=MMWR2013>{{cite journal|last=Centers for Disease Control and Prevention|first=(CDC)|title=Notes from the field: electronic cigarette use among middle and high school students – United States, 2011–2012|url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6235a6.htm |journal=MMWR. Morbidity and mortality weekly report|date=6 September 2013|volume=62|issue=35|pages=729–30|pmid=24005229}}</ref> Nicotine use during adolescence may damage brain development.<ref name=Chapman2015/> There is no long-term research concerning the cancer risk related to the small level of exposure to the identified carcinogens.<ref name=Drummond2014/> The short-term toxicity of e-cigarette use appears to be low, with the exception for some people with reactive airways.<ref name=Bertholon2013>{{cite journal|last1=Bertholon|first1=J.F.|last2=Becquemin|first2=M.H.|last3=Annesi-Maesano|first3=I.|last4=Dautzenberg|first4=B.|title=Electronic Cigarettes: A Short Review|journal=Respiration|year=2013|issn=1423-0356|doi=10.1159/000353253|pmid=24080743}}</ref> The long-term [[health effect|health impacts]] of e-cigarette use are unknown.<ref name=Hajek2014/> The long-term toxicity is subject to the additives and contaminants in the e-liquid.<ref name=Bertholon2013/> There is limited [[peer-review]]ed data about the toxicity of e-cigarettes for a complete toxicological evaluation.<ref name=Orr2014>{{cite journal|last1=Orr|first1=M. S.|title=Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii18–ii22|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051474|pmid=24732158}}</ref>
+A 2014 review found "Various chemical substances and ultrafine particles known to be toxic, carcinogenic and/or to cause respiratory and heart distress have been identified in e-cigarette aerosols, cartridges, refill liquids and environmental emissions."<ref name=Cheng2014/> Few of the methods in the studies the review looked at were validated.<ref name=Cheng2014/> Many toxic chemical compounds have been produced from e-cigarettes, especially carbonyl compounds like [[formaldehyde]], [[acetaldehyde]], [[acrolein]], and [[glyoxal]], which are frequently identified in e-cigarette aerosols.<ref name=Bekki2014/><ref name=Collaco2015/> These materials may cause harmful health effects; though, in the majority of cases, the amounts inhaled are less than those in traditional cigarettes.<ref name=Bekki2014>{{cite journal|last1=Bekki|first1=Kanae|last2=Uchiyama|first2=Shigehisa|last3=Ohta|first3=Kazushi|last4=Inaba|first4=Yohei|last5=Nakagome|first5=Hideki|last6=Kunugita|first6=Naoki|title=Carbonyl Compounds Generated from Electronic Cigarettes|journal=International Journal of Environmental Research and Public Health|volume=11|issue=11|year=2014|pages=11192–11200|issn=1660-4601|doi=10.3390/ijerph111111192|pmid=25353061}}</ref>The toxicity of e-cigarettes and e-liquid can vary greatly, as there is potential differences in construction and materials in the delivery device, kind and origin of ingredients in the e-liquid, and the use or non-use of [[good manufacturing practice]]s and [[quality control]] approaches.<ref name=Orr2014/> Devices using higher voltages can produce carcinogens including formaldehyde at levels found in cigarette smoke.<ref name=Collaco2015/> While there is variability in the ingredients and concentrations of ingredients in e-cigarette liquids, tobacco smoke contains thousands of chemicals, most of which are not understood and many of which are known to be harmful.<ref name=Saitta2014>{{cite journal|last=Saitta|first=D|author2=Ferro, GA |author3=Polosa, R |title=Achieving appropriate regulations for electronic cigarettes.|journal=Therapeutic advances in chronic disease|date=Mar 2014|volume=5|issue=2|pages=50–61|pmid=24587890|doi=10.1177/2040622314521271|pmc=3926346}}</ref> The levels of [[toxicant|chemical constituents]] in the vapor were found to be 1 to 2 [[orders of magnitude]] smaller than in cigarette smoke but greater compared to a [[nicotine inhaler]].<ref name=Grana2014/> The [[Centers for Disease Control and Prevention]] (CDC) stated the possible negative impact between nicotine and [[brain development]] in youth is a concern.<ref name=MMWR2013>{{cite journal|last=Centers for Disease Control and Prevention|first=(CDC)|title=Notes from the field: electronic cigarette use among middle and high school students – United States, 2011–2012|url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6235a6.htm |journal=MMWR. Morbidity and mortality weekly report|date=6 September 2013|volume=62|issue=35|pages=729–30|pmid=24005229}}</ref>  There is no long-term research concerning the cancer risk related to the small level of exposure to the identified carcinogens.<ref name=Drummond2014/> The short-term toxicity of e-cigarette use appears to be low, with the exception for some people with reactive airways.<ref name=Bertholon2013>{{cite journal|last1=Bertholon|first1=J.F.|last2=Becquemin|first2=M.H.|last3=Annesi-Maesano|first3=I.|last4=Dautzenberg|first4=B.|title=Electronic Cigarettes: A Short Review|journal=Respiration|year=2013|issn=1423-0356|doi=10.1159/000353253|pmid=24080743}}</ref> The long-term [[health effect|health impacts]] of e-cigarette use are unknown.<ref name=Hajek2014/> The long-term toxicity is subject to the additives and contaminants in the e-liquid.<ref name=Bertholon2013/> There is limited [[peer-review]]ed data about the toxicity of e-cigarettes for a complete toxicological evaluation.<ref name=Orr2014>{{cite journal|last1=Orr|first1=M. S.|title=Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii18–ii22|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051474|pmid=24732158}}</ref>
 A 2013 review found an instant increase in airway resistance after using a single e-cigarette, and concluded that they can harm the [[respiratory system]].<ref name=Bertholon2013/> The risks, especially to the lungs, are not fully understood and are of concern to public health authorities.<ref name=NHE2014>{{citation|url=https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/311887/Ecigarettes_report.pdf|title=Electronic cigarettes – A report commissioned by Public Health England |publisher=[[Public Health England]]|date=15 May 2014|author1-first=John |author1-last=Britton|author2-first=Ilze|author2-last=Bogdanovica}}</ref><ref name=WHO2013>{{cite web|title=Electronic cigarettes (e-cigarettes) or electronic nicotine delivery systems|url=http://www.who.int/tobacco/communications/statements/eletronic_cigarettes/en/index.html|work=World Health Organization|date=3 June 2014}}</ref><ref name=IUATLD>{{cite web |title=Position Statement on Electronic Cigarettes [ECs] or Electronic Nicotine Delivery Systems [ENDS] |url=http://www.theunion.org/what-we-do/publications/official/body/E-cigarette_statement_FULL.pdf |format=PDF |date=October 2013 |publisher=The International Union against Tuberculosis and Lung Disease}}</ref> The [[ultrafine particle|particles are of the ultrafine size]] which can go deep in the lungs and then into the [[systemic circulation]].<ref name=Grana2014/> Reports in the literature have shown respiratory and cardiovascular effects by these smaller size particles, suggesting a possible health concern.<ref name=AIHA2014/> A 2014 review found e-cigarettes emissions contain the [[heavy metals]] nickel, tin, and chromium.<ref name=Grana2014/> These [[nanoparticle]]s can deposit in the [[pulmonary alveoli|lung's alveolar sacs]], potentially leading to local respiratory toxicity and entering the bloodstream.<ref name=Grana2014/> A 2014 review found it can be concluded that there is no evidence of contamination of the aerosol with metals that justifies a health concern.<ref name=Bur2014/> A 2014 review noted a study had found metal particles in the fluid and aerosol, however that study did not evaluate the relevance of the levels identified.<ref name=Hajek2014/> The same review found that these levels were 10-50 times less than that allowed in [[nebulizer|medicines that are inhaled]].<ref name=Hajek2014/>
 ==Effects on breathing and lung function==
-E-cigarettes companies assert that the particulates produced by an e-cigarette are too tiny to be deposited in the [[alveoli]] but the carcinogens identified in an e-cigarette include nitrosamines, di-ethylene glycol, acetaldehyde, and other toxins such as mercury, anabasine, myosmineand beta-nicotyrine.<ref name=Dagaonkar2014/> Comparable to a traditional cigarette, e-cigarette particles are tiny enough to enter the alveoli, enabling nicotine absorption.<ref name=EbbertAgunwamba2015/> The short-term effects of e-cigarettes on pulmonary function resulted in considerable increases in resistance to lung airflow.<ref name=EbbertAgunwamba2015/> A 2014 review found that tests of cardiovascular and respiratory functions after short-term use of e-cigarettes demonstrated some harmful effects of vaping, but these  were appreciably milder in comparison to traditional cigarettes.<ref name=FarsalinosPolosa2014/> When used in the short-term, an e-cigarette results in a rise of respiratory resistance comparatively to traditional cigarettes.<ref name=Gualano2014/> The long-term effects regarding respiratory flow resistance are unknown.<ref name=Gualano2014/> E-cigarette use can be associated with a substantial dispersion of nicotine, thus generating a plasma nicotine concentration which can be comparable to that of traditional cigarettes.<ref name=Cervellin2013/> This is due to the minute nicotine particles in the vapor, which permit quick delivery into the bloodstream.<ref name=Cervellin2013/> This could increase the risk of [[cardiac arrhythmias]] and [[hypertension]] which may put some users, particularly those with [[atherosclerosis]] or other cardiovascular risk factors, at significant risk of [[acute coronary syndrome]].<ref name=Cervellin2013>{{cite journal|last1=Cervellin|first1=Gianfranco|last2=Borghi|first2=Loris|last3=Mattiuzzi|first3=Camilla|last4=Meschi|first4=Tiziana|last5=Favaloro|first5=Emmanuel|last6=Lippi|first6=Giuseppe|title=E-Cigarettes and Cardiovascular Risk: Beyond Science and Mysticism|journal=Seminars in Thrombosis and Hemostasis|volume=40|issue=01|year=2013|pages=060–065|issn=0094-6176|doi=10.1055/s-0033-1363468|pmid=24343348}}</ref> Some case reports documented the possible cardiovascular adverse effects from using e-cigarettes, the majority associated was with improper use.<ref name=Cervellin2013/> Even though e-cigarettes are anticipated to produce fewer dangerous substances than traditional cigarettes, limited evidence supports they comparatively have a lessened raised cardiovascular risk for e-cigarettes users.<ref name=Cervellin2013/> The limited evidence suggests that e-cigarettes produce less short-term effects on [[lung function]] than traditional cigarettes.<ref name=Drummond2014/> Like cancer risk, there is no literature outlining the long-term lung function or cardiovascular consequences.<ref name=Drummond2014/> A 2014 review found that e-cigarette aerosol contains far fewer carcinogens than tobacco smoke, and concluded that e-cigarettes "impart a lower potential disease burden" than traditional cigarettes.<ref name=Kacker2014>{{cite journal|last1=Oh|first1=Anne Y.|last2=Kacker|first2=Ashutosh|title=Do electronic cigarettes impart a lower potential disease burden than conventional tobacco cigarettes?: Review on e-cigarette vapor versus tobacco smoke|journal=The Laryngoscope|date=December 2014|volume=124|issue=12|pages=2702–2706|doi=10.1002/lary.24750|pmid=25302452}}</ref> The effect on [[population health]] from e-cigarettes is unknown.<ref name=Drummond2014/>
+A 2014 review found that tests of cardiovascular and respiratory functions after short-term use of e-cigarettes demonstrated some harmful effects of vaping, but these  were appreciably milder in comparison to traditional cigarettes.<ref name=FarsalinosPolosa2014/> When used in the short-term, an e-cigarette results in a rise of respiratory resistance comparatively to traditional cigarettes.<ref name=Gualano2014/> The long-term effects regarding respiratory flow resistance are unknown.<ref name=Gualano2014/> E-cigarette use can be associated with a substantial dispersion of nicotine, thus generating a plasma nicotine concentration which can be comparable to that of traditional cigarettes.<ref name=Cervellin2013/> This is due to the minute nicotine particles in the vapor, which permit quick delivery into the bloodstream.<ref name=Cervellin2013/> This could increase the risk of [[cardiac arrhythmias]] and [[hypertension]] which may put some users, particularly those with [[atherosclerosis]] or other cardiovascular risk factors, at significant risk of [[acute coronary syndrome]].<ref name=Cervellin2013>{{cite journal|last1=Cervellin|first1=Gianfranco|last2=Borghi|first2=Loris|last3=Mattiuzzi|first3=Camilla|last4=Meschi|first4=Tiziana|last5=Favaloro|first5=Emmanuel|last6=Lippi|first6=Giuseppe|title=E-Cigarettes and Cardiovascular Risk: Beyond Science and Mysticism|journal=Seminars in Thrombosis and Hemostasis|volume=40|issue=01|year=2013|pages=060–065|issn=0094-6176|doi=10.1055/s-0033-1363468|pmid=24343348}}</ref> Some case reports documented the possible cardiovascular adverse effects from using e-cigarettes, the majority associated was with improper use.<ref name=Cervellin2013/> Even though e-cigarettes are anticipated to produce fewer dangerous substances than traditional cigarettes, limited evidence supports they comparatively have a lessened raised cardiovascular risk for e-cigarettes users.<ref name=Cervellin2013/> The limited evidence suggests that e-cigarettes produce less short-term effects on [[lung function]] than traditional cigarettes.<ref name=Drummond2014/> Like cancer risk, there is no literature outlining the long-term lung function or cardiovascular consequences.<ref name=Drummond2014/> A 2014 review found that e-cigarette aerosol contains far fewer carcinogens than tobacco smoke, and concluded that e-cigarettes "impart a lower potential disease burden" than traditional cigarettes.<ref name=Kacker2014>{{cite journal|last1=Oh|first1=Anne Y.|last2=Kacker|first2=Ashutosh|title=Do electronic cigarettes impart a lower potential disease burden than conventional tobacco cigarettes?: Review on e-cigarette vapor versus tobacco smoke|journal=The Laryngoscope|date=December 2014|volume=124|issue=12|pages=2702–2706|doi=10.1002/lary.24750|pmid=25302452}}</ref> The effect on [[population health]] from e-cigarettes is unknown.<ref name=Drummond2014/>
 == Ultrafine particles ==
@@ Line 41: / Line 42: @@
 <!-- Particle distribution -->
-A 2014 review found that fine particles can be chemically intricate and not uniform, and what a particle is made of, the exact harmful elements, and the importance of the size of the particle is mostly unknown.<!-- <ref name=Grana2014/> --> They found that because these things are uncertain, it is not clear whether the ultrafine particles in e-cigarette vapor have health effects similar to those produced by traditional cigarettes.<ref name=Grana2014/> Emissions from electronic cigarettes are not comparable to environmental pollution or cigarette smoke as their nature and chemical composition are completely different,<ref name=FarsalinosPolosa2014/> although a 2014 review found that the particle size distribution and sum of particles emitted by e-cigarettes are like traditional cigarettes, with the majority of particles in the ultrafine range (modes, ≈100–200).<ref name=Grana2014/> The particles are larger, with the mean size being 600nm in inhaled aerosol and 300nm in exhaled.<ref name=Bertholon2013/> Different devices generate different particle sizes and cause different depositions in the [[respiratory tract]], even from the same nicotine liquid.<ref name=Collaco2015>{{cite journal|last1=Collaco|first1=Joseph M.|title=Electronic Use and Exposure in the Pediatric Population|journal=JAMA Pediatrics|volume=169|issue=2|year=2015|pages=177-182|doi=10.1001/jamapediatrics.2014.2898|pmid=25546699}}</ref> A 2014 review found that the aerosol particle concentration is 5 times lower from an e-cigarette than from a traditional cigarette.<ref name=Drummond2014/> A 2014 WHO report found e-cigarettes release a lower level of particles than traditional cigarettes.<ref name=WHOPosition2014/> A 2014 review found that the density of particles in the vapor is lower than in cigarette smoke by a factor of between 6 and 880 times lower.<ref name=FarsalinosPolosa2014/>
+A 2014 review found that fine particles can be chemically intricate and not uniform, and what a particle is made of, the exact harmful elements, and the importance of the size of the particle is mostly unknown.<!-- <ref name=Grana2014/> --> They found that because these things are uncertain, it is not clear whether the ultrafine particles in e-cigarette vapor have health effects similar to those produced by traditional cigarettes.<ref name=Grana2014/> Emissions from electronic cigarettes are not comparable to environmental pollution or cigarette smoke as their nature and chemical composition are completely different,<ref name=FarsalinosPolosa2014/> although a 2014 review found that the particle size distribution and sum of particles emitted by e-cigarettes are like traditional cigarettes, with the majority of particles in the ultrafine range (modes, ≈100–200).<ref name=Grana2014/> The particles are larger, with the mean size being 600nm in inhaled aerosol and 300nm in exhaled.<ref name=Bertholon2013/>  Different devices generate different particle sizes and cause different depositions in the [[respiratory tract]], even from the same nicotine liquid.<ref name="Collaco2015">{{cite journal|last1=Collaco|first1=Joseph M.|title=Electronic Use and Exposure in the Pediatric Population|journal=JAMA Pediatrics|volume=169|issue=2|year=2015|pages=177-182|doi=10.1001/jamapediatrics.2014.2898|pmid=25546699}}</ref> A 2014 review found that the aerosol particle concentration is 5 times lower than from a traditional cigarette.<ref name=Drummond2014/> A 2014 WHO report found e-cigarettes release a lower level of particles than traditional cigarettes.<ref name=WHOPosition2014/> A 2014 review found that the density of particles in the vapor is lower than in cigarette smoke by a factor of between 6 and 880 times lower.<ref name=FarsalinosPolosa2014/>
 ==Effects on bystanders==
-There is insufficient data to determine the impact on [[public health]] from e-cigarettes.<ref name=Callahan2014>{{cite journal|last1=Callahan-Lyon|first1=P.|title=Electronic cigarettes: human health effects|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii36–ii40|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051470|pmid=24732161}}</ref> The potential harm to bystanders from e-cigarettes is unknown.<ref>{{cite web | url=http://www.lung.org/stop-smoking/tobacco-control-advocacy/federal/e-cigarettes.html | title=American Lung Association Statement on E-Cigarettes | publisher=American Lung Association | date=25 August 2014}}</ref> A [[white paper]] published in 2014 by the [[American Industrial Hygiene Association]] concluded e-cigarettes emit airborne contaminants that may be inhaled by the user and those nearby.<ref name=AIHA2014/> Due to this possible risk, they urged restriction of their use indoors, similar to smoking bans, until research has shown the aerosol does not significantly harm others in the area.<ref name=AIHA2014>{{cite web|title=White Paper: Electronic Cigarettes in the Indoor Environment|url=http://tobacco.ucsf.edu/sites/tobacco.ucsf.edu/files/u9/AIHA-Electronc%20Cig%20Document_Final.pdf|publisher=American Industrial Hygiene Association|date=October 19, 2014}}</ref> A 2014 review indicated that the levels of inhaled contaminants from the e-cigarette vapor are not of significant health concern for human exposures by the standards used in workplaces to ensure safety.<ref name=Bur2014>{{cite journal|last1=Burstyn|first1=I|title=Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks.|journal=BMC Public Health|date=9 January 2014|volume=14|pages=18|pmid=24406205|doi=10.1186/1471-2458-14-18|pmc=3937158}}</ref>
+There is insufficient data to determine the impact on [[public health]] from e-cigarettes.<ref name=Callahan2014>{{cite journal|last1=Callahan-Lyon|first1=P.|title=Electronic cigarettes: human health effects|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii36–ii40|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051470|pmid=24732161}}</ref> A [[white paper]] published in 2014 by the [[American Industrial Hygiene Association]] concluded e-cigarettes emit airborne contaminants that may be inhaled by the user and those nearby.<ref name=AIHA2014/> Due to this possible risk, they urged restriction of their use indoors, similar to smoking bans, until research has shown the aerosol does not significantly harm others in the area.<ref name=AIHA2014>{{cite web|title=White Paper: Electronic Cigarettes in the Indoor Environment|url=http://tobacco.ucsf.edu/sites/tobacco.ucsf.edu/files/u9/AIHA-Electronc%20Cig%20Document_Final.pdf|publisher=American Industrial Hygiene Association|date=October 19, 2014}}</ref> A 2014 review indicated that the levels of inhaled contaminants from the e-cigarette vapor are not of significant health concern for human exposures by the standards used in workplaces to ensure safety.<ref name=Bur2014>{{cite journal|last1=Burstyn|first1=I|title=Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks.|journal=BMC Public Health|date=9 January 2014|volume=14|pages=18|pmid=24406205|doi=10.1186/1471-2458-14-18|pmc=3937158}}</ref>
 [[File:Cigarrillo electronico funcionando.jpg|thumb|[[Aerosol]] (vapor) exhaled by a first generation e-cigarette user.]]
-Since e-cigarettes do not burn (or contain) tobacco, no [[side-stream smoke]] or any [[cigarette smoke]] is produced.<ref name=Grana2014/> The vapor from e-cigarettes appears similar to tobacco smoke.<ref name=smokefree2014/> Only what is exhaled by e-cigarettes users enters the surrounding air.<ref name=Hajek2014/> E-cigarettes may have adverse effects to bystanders.<ref name=EbbertAgunwamba2015>{{cite journal|last1=Ebbert|first1=Jon O.|last2=Agunwamba|first2=Amenah A.|last3=Rutten|first3=Lila J.|title=Counseling Patients on the Use of Electronic Cigarettes|journal=Mayo Clinic Proceedings|volume=90|issue=1|year=2015|pages=128–134|issn=00256196|doi=10.1016/j.mayocp.2014.11.004|pmid=25572196}}</ref> E-cigarettes used in indoor environments can put at risk nonsmokers to elevated levels of nicotine and aerosol emissions.<ref name=Drummond2014/> A 2014 review of limited data concluded this vapor can cause [[indoor air pollution]] and is not just "water vapor" as is frequently stated in the advertising of e-cigarettes.<ref name=Grana2014/> Exhaled vapor consists of nicotine and some other particles, primarily consisting of flavors, aroma transporters, glycerol and propylene glycol.<ref name=Hajek2014/> Bystanders are exposed to these particles from exhaled e-cigarette vapor.<ref name=Grana2014/> A mixture of harmful substances, particularly nicotine, ultrafine particles, and volatile organic compounds can be exhaled into the air.<ref name=Cervellin2013/> The dense vapor consists of liquid sub-micron [[Drop (liquid)|droplets]].<ref name=Offermann2014/> The liquid particles condenses into a viewable fog.<ref name=Bertholon2013/> The vapor is in the air for a short time, with a [[half-life]] of about 10 seconds; traditional cigarette smoke is in the air 100 times longer.<ref name=Bertholon2013/> This is because of fast revaporization at room temperature.<ref name=Bertholon2013/> Some of the few studies examining the effects on health shown that being exposed to e-cigarette vapor may produce biological effects.<!-- <ref name=Grana2014/> --> Since e-cigarettes have not been widely used long enough for evaluation, the long-term health effects from the second-hand vapor are not known.<ref name=Grana2014/>
+Since e-cigarettes do not burn (or contain) tobacco, no [[side-stream smoke]] or any [[cigarette smoke]] is produced.<ref name=Grana2014/> Only what is exhaled by electronic cigarettes users enters the surrounding air.<ref name=Hajek2014/> E-cigarettes used in indoor environments can put at risk nonsmokers to elevated levels of nicotine and aerosol emissions.<ref name=Drummond2014/> A 2014 review of limited data concluded this vapor can cause [[indoor air pollution]] and is not just "water vapor" as is frequently stated in the advertising of e-cigarettes.<ref name=Grana2014/> Exhaled vapor consists of nicotine and some other particles, primarily consisting of flavors, aroma transporters, glycerol and propylene glycol.<ref name=Hajek2014/> Bystanders are exposed to these particles from exhaled e-cigarette vapor.<ref name=Grana2014/> A mixture of harmful substances, particularly nicotine, ultrafine particles, and volatile organic compounds can be exhaled into the air.<ref name=Cervellin2013/> The dense vapor consists of liquid sub-micron [[Drop (liquid)|droplets]].<ref name=Offermann2014/> The liquid particles condenses into a viewable fog.<ref name=Bertholon2013/> The vapor is in the air for a short time, with a [[half-life]] of about 10 seconds; traditional cigarette smoke is in the air 100 times longer.<ref name=Bertholon2013/> This is because of fast revaporization at room temperature.<ref name=Bertholon2013/> Some of the few studies examining the effects on health shown that being exposed to e-cigarette vapor may produce biological effects.<!-- <ref name=Grana2014/> --> Since e-cigarettes have not been widely used long enough for evaluation, the long-term health effects from the second-hand vapor are not known.<ref name=Grana2014/>
-{{Asof|2013}}, the only clinical study currently published evaluating the respiratory effects of passive vaping found no adverse effects were detected.<ref name=FarsalinosPolosa2014/> A 2014 review found it is safe to infer that their effects on bystanders are minimal in comparison to traditional cigarettes.<ref name=FarsalinosPolosa2014/> A 2014 WHO report stated passive exposure was as a concern, indicating that current evidence is insufficient to determine whether the levels of exhaled vapor are safe to involuntarily exposed bystanders.<ref name=WHOPosition2014/> The report stated that "it is unknown if the increased exposure to toxicants and particles in exhaled aerosol will lead to an increased risk of disease and death among bystanders."<ref name=WHOPosition2014/> E-cigarette vapor has notably fewer toxicants than cigarette smoke and is likely to pose less harm to users or bystanders.<ref name=Grana2014/> A 2014 practice guideline by [[NPS MedicineWise]] states, "Although data on health effects of passive vapour are currently lacking, the risks are argued to be small, but claims that e-cigarettes emit only water vapour are nevertheless incorrect. Serum cotinine levels (a metabolite of nicotine) have been found to be similar in bystanders exposed to either e-cigarette vapour or cigarette smoke."<ref>{{cite web|title=e-Cigarettes: a safe way to quit?|url=http://www.nps.org.au/publications/health-professional/health-news-evidence/2014/e-cigarettes|publisher=NPS MedicineWise}}</ref>
+{{Asof|2013}}, the only clinical study currently published evaluating the respiratory effects of passive vaping found no adverse effects were detected.<ref name=FarsalinosPolosa2014/> A 2014 review found it is safe to infer that their effects on bystanders are minimal in comparison to traditional cigarettes.<ref name=FarsalinosPolosa2014/> A 2014 WHO report stated passive exposure was as a concern, indicating that current evidence is insufficient to determine whether the levels of exhaled vapor are safe to involuntarily exposed bystanders.<ref name=WHOPosition2014/> The report stated that "it is unknown if the increased exposure to toxicants and particles in exhaled aerosol will lead to an increased risk of disease and death among bystanders."<ref name=WHOPosition2014/> E-cigarette vapor has notably fewer toxicants than cigarette smoke and is likely to pose less harm to users or bystanders.<ref name=Grana2014/>
 Nonsmokers exposed to e-cigarette aerosol produced by a machine and pumped into a room were found to have detectable levels of the nicotine [[metabolite]] [[cotinine]] in their blood.<!-- <ref name=Grana2014/> --> The same study stated that 80% of nicotine is normally absorbed by the user, so these results may be higher than in actual second hand exposure.<ref name=Grana2014/>
@@ Line 56: / Line 57: @@
 ==Effects during pregnancy==
-A 2014 review stated there are concerns about pregnant women exposure to e-cigarette vapor through direct use or via exhaled vapor.<ref name=Grana2014/> {{Asof|2014}}, there is no conclusions on the possible hazards of pregnant women using e-cigarettes, and there is a developing research on the negative effects of nicotine on [[prenatal]] brain development.<ref name=Drummond2014/> A 2014 review concluded no amount of nicotine is safe for pregnant women.<ref name=Suter2014/> Prenatal exposure has been associated with obesity, diabetes, high cholesterol and high blood pressure in minors.<ref name=WorldLungFederation2014/> {{Asof|2014}}, the long-term issues of e-cigarettes on both mother and unborn baby are unknown.<ref name=Suter2014>{{cite journal|last1=Suter|first1=Melissa A.|last2=Mastrobattista|first2=Joan|last3=Sachs|first3=Maike|last4=Aagaard|first4=Kjersti|title=Is There Evidence for Potential Harm of Electronic Cigarette Use in Pregnancy?|journal=Birth Defects Research Part A: Clinical and Molecular Teratology|year=2014|pages=n/a–n/a|issn=15420752|doi=10.1002/bdra.23333|pmid=25366492}}</ref> There are concerns about the health impacts of pediatric exposure to second-hand and third-hand e-cigarette vapor.<ref name=Durmowicz2014/> The 2014 [[Surgeon General of the United States]] report has found "that nicotine adversely affects maternal and fetal health during pregnancy, and that exposure to nicotine during fetal development has lasting adverse consequences for brain development."<ref name=Brandon2015/> The belief that e-cigarettes are safer than traditional cigarettes could increase their use for pregnant women.<ref name=EbbertAgunwamba2015/> The toxic effects identified with e-cigarette refill liquids on stem cells may be interpreted as embryonic death or birth defects.<ref name=EbbertAgunwamba2015/>
+A 2014 review stated there are concerns about pregnant women exposure to e-cigarette vapor through direct use or via exhaled vapor.<ref name=Grana2014/> {{Asof|2014}}, there is no conclusions on the possible hazards of pregnant women using e-cigarettes, and there is a developing research on the negative effects of nicotine on [[prenatal]] brain development.<ref name=Drummond2014/> A 2014 review concluded no amount of nicotine is safe for pregnant women.<ref name=Suter2014/> {{Asof|2014}}, the long-term issues of e-cigarettes on both mother and unborn baby are unknown.<ref name=Suter2014>{{cite journal|last1=Suter|first1=Melissa A.|last2=Mastrobattista|first2=Joan|last3=Sachs|first3=Maike|last4=Aagaard|first4=Kjersti|title=Is There Evidence for Potential Harm of Electronic Cigarette Use in Pregnancy?|journal=Birth Defects Research Part A: Clinical and Molecular Teratology|year=2014|pages=n/a–n/a|issn=15420752|doi=10.1002/bdra.23333|pmid=25366492}}</ref> There are concerns about the health impacts of pediatric exposure to second-hand and third-hand e-cigarette vapor.<ref name=Durmowicz2014/> The 2014 [[Surgeon General of the United States]] report has found "that nicotine adversely affects maternal and fetal health during pregnancy, and that exposure to nicotine during fetal development has lasting adverse consequences for brain development."<ref name=Brandon2015/>
 ==Environmental impact==
 <!-- Environmental impact -->
-There is limited information available on any [[environmental issue]]s connected to the production, usage, and disposal of e-cigarette models that use cartridges.<ref name=Chang2014/> No formal studies have been done to evaluate the environmental effects of making or disposing of any part of an e-cigarettes including the batteries or nicotine production.<ref name=Chang2014/> {{Asof|2014}}, it is uncertain if the nicotine in e-liquid is [[United States Pharmacopeia]]-grade nicotine, a tobacco extract, or a synthetic nicotine when questioning the environmental impact of how it is made.<ref name=Chang2014/> It is not clear which manufacturing methods are used to make the nicotine used in e-cigarettes.<ref name=Chang2014/> The emissions from making nicotine could be considerable from manufacturing if not appropriately controlled.<ref name=Chang2014/> Some e-cigarette brands that use cartridges state their products are ‘eco-friendly’ or ‘green’, despite the absence of any supporting studies.<ref name=Chang2014/> Some writers contend that such marketing may raise sales and increase e-cigarette interest, particularly among minors.<ref name=Chang2014/> It is unclear how many traditional cigarettes are comparable to using one e-cigarette that uses a cartridge for the average user.<ref name=Chang2014/> Information is limited on energy and materials used for production of e-cigarettes versus traditional cigarettes, for comparable use.<ref name=Chang2014/> E-cigarettes can be made manually put together in small factories, or they can be made in automated lines on a much bigger scale.<ref name=Chang2014/> Larger plants will produce greater emissions to the surrounding environment, and thus will have a greater environmental impact.<ref name=Chang2014/> Although some brands have began recycling services for their e-cigarette cartridges the prevalence of recycling is unknown, as is the prevalence of information provided by manufacturers on how to recycle disposable parts.<ref name=Chang2014/> Some brands have also began recycling services for their e-cigarette batteries.<ref name=Chang2014>{{cite journal|last1=Chang|first1=H.|title=Research gaps related to the environmental impacts of electronic cigarettes|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii54–ii58|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051480|pmc=3995274|pmid=24732165}}</ref>
+There is limited information available on any [[environmental issue]]s connected to the production, usage, and disposal of e-cigarette models that use cartridges.<ref name=Chang2014/> No formal studies have been done to evaluate the environmental effects of making or disposing of any part of an e-cigarettes including the batteries or nicotine production.<ref name=Chang2014/> {{Asof|2014}}, it is uncertain if the nicotine in e-liquid is [[United States Pharmacopeia]]-grade nicotine, a tobacco extract, or a synthetic nicotine when questioning the environmental impact of how it is made.<ref name=Chang2014/> It is not clear which manufacturing methods may be used by the industry to make nicotine that are used in e-cigarettes.<ref name=Chang2014/> The emissions from making nicotine could be considerable from manufacturing if not appropriately controlled.<ref name=Chang2014/> Some e-cigarette brands that use cartridges state their products are ‘eco-friendly’ or ‘green’, despite the absence of any supporting studies.<ref name=Chang2014/> It is unclear how many traditional cigarettes are comparable to using one e-cigarette that uses a cartridge for the average user.<ref name=Chang2014/> Information is limited on energy and materials used for production of e-cigarettes versus traditional cigarettes, for comparable use.<ref name=Chang2014/> Although some brands have began recycling services for their e-cigarette cartridges; the prevalence of recycling, as well as the prevalence of recycling information on expandable e-cigarette containers, is unknown.<ref name=Chang2014/> Some brands have also began recycling services for their e-cigarette batteries.<ref name=Chang2014>{{cite journal|last1=Chang|first1=H.|title=Research gaps related to the environmental impacts of electronic cigarettes|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii54–ii58|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051480|pmc=3995274|pmid=24732165}}</ref>
 == Fires, explosions, and other battery-related malfunctions ==
@@ Line 76: / Line 77: @@
 Nicotine overdose from e-liquid is another potential risk. In December 2014, a one-year-old child in [[Fort Plain, New York]] died after an accidental ingestion of nicotine liquid.<ref name=Mohney>Mohney, Gillian, "[http://abcnews.go.com/Health/childs-death-liquid-nicotine-reported-vaping-gains-popularity/story?id=27563788 First Child's Death From Liquid Nicotine Reported as 'Vaping' Gains Popularity]", ''[[ABC News]]'', December 12, 2014.</ref> A man died in 2012 after injecting himself with nicotine liquid.<ref name=Mohney/> The [[American Association of Poison Control Centers]] recorded 3,638 "exposure" incidents relating to liquid nicotine as of November 30, 2014.<ref name=Mohney/>
+Use-related concerns with e-liquids also include leaks or spills and contact with contaminants in the e-liquid.<ref name=Yang2014>{{cite journal|last1=Yang|first1=L.|last2=Rudy|first2=S. F.|last3=Cheng|first3=J. M.|last4=Durmowicz|first4=E. L.|title=Electronic cigarettes: incorporating human factors engineering into risk assessments|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii47–ii53|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051479|pmid=24732164}}</ref>
-Because there is a lack of production standards and controls, the e-liquid cleanliness frequently is not dependable, and testing of some products has shown the existence of toxic substances.<ref name=BrownCheng2014/> The [[German Cancer Research Center]] in Germany released a report stating that e-cigarettes cannot be considered safe, in part due to technical flaws that have been found. This includes leaking cartridges, accidental contact with nicotine when changing cartridges, and potential of unintended overdose.<ref name=GermanCancerResearchCenter>{{cite web|title=Electronic Cigarettes – An Overview|url=http://www.dkfz.de/en/presse/download/RS-Vol19-E-Cigarettes-EN.pdf|publisher=German Cancer Research Center}}</ref> The [[Therapeutic Goods Administration]] (TGA) of Australia has stated that, "Some overseas studies suggest that electronic cigarettes containing nicotine may be dangerous, delivering unreliable doses of nicotine (above or below the stated quantity), or containing toxic chemicals or carcinogens, or leaking nicotine. Leaked nicotine is a poisoning hazard for the user of electronic cigarettes, as well as others around them, particularly children."<ref>{{cite web|title=Electronic cigarettes|url=http://www.tga.gov.au/community-qa/electronic-cigarettes|publisher=Therapeutic Goods Administration}}</ref> The nicotine in e-liquid can be hazardous to infants.<ref name=BrownCheng2014>{{cite journal|last1=Brown|first1=C. J.|last2=Cheng|first2=J. M.|title=Electronic cigarettes: product characterisation and design considerations|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii4–ii10|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051476|pmid=24732162}}</ref> Even a portion of e-liquid may be lethal to a little child.<ref name=Chapman2015/> An accidental ingestion of only 6 mg may be lethal to children.<ref name=JimenezRuiz2014/><ref name=GermanCancerResearchCenter/> Use-related concerns with e-liquids also include leaks or spills and contact with contaminants in the e-liquid.<ref name=Yang2014>{{cite journal|last1=Yang|first1=L.|last2=Rudy|first2=S. F.|last3=Cheng|first3=J. M.|last4=Durmowicz|first4=E. L.|title=Electronic cigarettes: incorporating human factors engineering into risk assessments|journal=Tobacco Control|volume=23|issue=Supplement 2|year=2014|pages=ii47–ii53|issn=0964-4563|doi=10.1136/tobaccocontrol-2013-051479|pmid=24732164}}</ref> Nicotine toxicity is a concern when e-cigarette solutions are swallowed intentionally by grownups as a suicidal overdose.<ref name=AHA2014/> A lethal dose for grownups is from 30 – 60 mg.<ref name=Dagaonkar2014/>
 ==References==