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Health effects of electronic cigarettes

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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, 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] 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]

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

Chart showing various toxicants as measured in cigarette and e-cigarette smoke.[28]

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]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."[34]

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 lethal poison, however at the low amount of nicotine provided by e-cigarettes fatal overdose from use is unlikely..[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] 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. 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] 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.[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.[39] A serious concern is the outcome of nicotine on the growing adolescent brain.[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.[38]

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] 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]

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.[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, 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, 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, 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, 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] 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] Some journalists contend that such marketing may raise sales and increase e-cigarette interest, particularly among minors.[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 is unknown.[14] Some brands have also began recycling services for their e-cigarette batteries.[14] A 2014 review found that "The prevalence of recycling instructions on disposable e-cigarette packages, as well as how frequently disposable e-cigarettes are recycled, is unknown."[14]

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]

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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