Health effects of electronic cigarettes: Difference between revisions

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{{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/> 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>


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".<ref name=Brandon2015/> Nicotine is actually hard to get rid of from surfaces.<ref name=Brandon2015/> 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.<ref name=Brandon2015/> 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."<ref>{{cite journal|last1=Bam|first1=T. S.|last2=Bellew|first2=W.|last3=Berezhnova|first3=I.|last4=Jackson-Morris|first4=A.|last5=Jones|first5=A.|last6=Latif|first6=E.|last7=Molinari|first7=M. A.|last8=Quan|first8=G.|last9=Singh|first9=R. J.|last10=Wisotzky|first10=M.|title=Position statement on electronic cigarettes or electronic nicotine delivery systems [Official statement]|journal=The International Journal of Tuberculosis and Lung Disease|date=1 January 2014|volume=18|issue=1|pages=5–7|doi=10.5588/ijtld.13.0815}}</ref>
E-cigarettes pose many safety concerns to children.<ref name=England2015/> Indoor surfaces can accumulate nicotine where e-cigarettes were used, which may be inhaled by children, particularly youngsters, long after they were used.<ref name=England2015/> 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".<ref name=Brandon2015/> Nicotine is actually hard to get rid of from surfaces.<ref name=Brandon2015/> 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.<ref name=Brandon2015/> 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."<ref>{{cite journal|last1=Bam|first1=T. S.|last2=Bellew|first2=W.|last3=Berezhnova|first3=I.|last4=Jackson-Morris|first4=A.|last5=Jones|first5=A.|last6=Latif|first6=E.|last7=Molinari|first7=M. A.|last8=Quan|first8=G.|last9=Singh|first9=R. J.|last10=Wisotzky|first10=M.|title=Position statement on electronic cigarettes or electronic nicotine delivery systems [Official statement]|journal=The International Journal of Tuberculosis and Lung Disease|date=1 January 2014|volume=18|issue=1|pages=5–7|doi=10.5588/ijtld.13.0815}}</ref>


== Effects during pregnancy ==
== Effects during pregnancy ==

Revision as of 00:02, 24 March 2015

The use of electronic cigarettes (e-cig or e-cigarette), personal vaporizer (PV) or electronic nicotine delivery system (ENDS) raises concerns regarding health effects.[1] The risks involved are uncertain,[2][3] as there is little data regarding health effects,[4] and considerable variability between vaporizers and in the composition, concentration and quality of their liquid ingredients and thus the contents of the "vapor" delivered to the user.[2][5][6] The limited evidence suggests that e-cigarettes are probably safer than traditional cigarettes.[6] A 2014 review recommended that e-cigarettes should be regulated for consumer safety.[1]

They appear to be similar in toxicity to other nicotine replacement products, but there is not enough data to draw conclusions.[7] The evidence suggests that the US Food and Drug Administration (FDA) accepted products such as a nicotine inhaler 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."[9] There are also risks from misuse or accidents such as accidental fires caused by vaporizer malfunction, other vaporizer design issues, or accidental contact with liquid nicotine.[5][10][11] 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]

E-cigarette users are exposed to potentially harmful nicotine.[12] The risk is probably low from the inhalation of propylene glycol and glycerol.[13] The levels of toxic substances in the vapor were found to be 1 to 2 orders of magnitude smaller than in cigarette smoke but greater than from a nicotine inhaler.[5] A 2014 Cochrane review found no serious adverse effects reported in trials.[14] Less serious adverse effects from e-cigarette use can include throat and mouth inflammation, vomiting, nausea, and cough.[5] As of 2015, the short and long term effects from using e-cigarettes remain unclear.[15]

The aerosol (mist[16]) emitted from an e-cigarette is commonly but inaccurately called vapor.[12] 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.[5] 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] E-cigarette vapor has notably fewer toxicants than cigarette smoke and is likely to pose less harm to users or bystanders.[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.[17]

Health effects

Health benefits and concerns

The emerging phenomenon of e-cigarettes is raising concerns among the health community, pharmaceutical industry, and other groups.[1] For example, they are concerned about the unknown health risks from the use of e-cigarettes over the long-term.[1] A 2014 review recommended that e-cigarettes should be adequately regulated for consumer safety.[1] Another 2014 review stated that the regulation of these products should be examined in view of the "reported adverse health effects".[18] 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."[18] Moreover, a WHO report in 2009 cautioned that the "safety of e-cigarettes is not confirmed."[18]

In several countries advertising for e-cigarettes has been monetarily restricted until safety and efficacy clinical trials are conclusive.[19] A 2014 systematic review found that the limited evidence suggests that e-cigarettes are probably safer than tobacco smoke.[10] No definite conclusions can be made regarding the safety of e-cigarettes because of various methodological issues, conflicts of interest, a limited number of studies, and disagreements in the conclusions of research.[20] However, e-cigarettes cannot be regarded as simply harmless.[20] A policy statement by the American Association for Cancer Research and the American Society of Clinical Oncology has reported that "The benefits and harms must be evaluated with respect to the population as a whole, taking into account the effect on youth, adults, nonsmokers, and smokers."[21]

Scientific studies advocate caution before designating e-cigarettes as beneficial but vapers continue to believe they are beneficial.[22] Many users assume that e-cigarettes are healthier than traditional cigarettes for personal use or for other people.[23] Generally, some users are concerned about the possible adverse health effects or toxicity of e-cigarettes.[23] The lack of research on the risks and possible benefits has resulted in precautionary policymaking in the U.S.[24]

In August 2014, the Forum of International Respiratory Societies stated that e-cigarettes have not been demonstrated to be safe.[25] 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.[26] 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."[27] 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.[28]

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."[29] 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."[30] 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."[31] The American Diabetes Association states "There is no evidence that e-cigarettes are a healthier alternative to smoking."[32] Health Canada has stated that, "their safety, quality, and efficacy remain unknown."[33] 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."[34] 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."[35]

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."[36] 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."[37] 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."[38] 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.[39]

Adverse effects

A 2014 Cochrane review found no serious adverse effects from e-cigarette have been reported in trials.[14] Reports to the Food and Drug Administration (FDA) for minor adverse effects identified with using e-cigarettes include headache, chest pain, nausea, and cough.[40] Major adverse effects reported to the FDA included hospitalizations for pneumonia, congestive heart failure, seizure, rapid heart rate, and burns.[40] However no direct relationship has been proven between these effects and e-cigarette use, and some of them may be due to health problems that were present before.[40] 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.[41] Adverse effect are mostly associated with a short term of use, and their frequency was significantly lower after 52 weeks of use.[41] Long-term studies regarding the effects of e-cigarettes after chronic exposure are unavailable.[41] 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.[18] 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.[42] Since e-cigarettes are intended to be used repeatedly, they can conveniently be used for an extended period of time, which may contribute to increased adverse effects.[43] 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.[22] The adverse effects of e-cigarettes on people with cancer is unknown.[21] As of 2015, the short and long term effects from using e-cigarettes remain unclear.[15]

In youth, e-cigarette use risks involve accidental nicotine exposure.[11] 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.[11] In the United States, a child died after ingesting liquid nicotine.[44] A 2014 editorial stated that e-cigarettes have concentrated liquids that are packed in colorful containers and combined with flavors that appear to be made to attract children.[45] It was concluded that it is recommended that e-cigarettes be kept in a safe place, where children and pets do not have access them.[45]

Poisoning associated with e-cigarettes may happen by ingestion, inhalation, or absorption.[21] 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%.[46] These calls were in connection to both adults and children.[46] E-cigarettes were associated with fewer adverse effects than nicotine patches.[46] 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.[47] 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]

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

There is a possibility of high levels of nicotine exposure, in regard to e-cigarette cartridges, from inhalation, ingestion, or skin contact while replacing or handling of the e-cigarette cartridges.[51] This may be especially risky to children, pregnant women, and nursing mothers.[51] Indoor surfaces can accumulate nicotine where e-cigarettes were used.[52] Use-related concerns with e-liquids also include leaks or spills and contact with contaminants in the e-liquid.[50] 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.[53] 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.[54] 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."[55]

Nicotine toxicity is a concern when e-cigarette solutions are swallowed intentionally by grownups as a suicidal overdose.[56] A man died in 2012 after injecting himself with nicotine liquid.[57] An excessive amount of nicotine for an adult that is capable of being fatal is 0.5–1 mg/kg of body weight.[51] A lethal dose for grownups is from 30 – 60 mg.[22] The American Association of Poison Control Centers recorded 3,638 "exposure" incidents relating to liquid nicotine as of November 30, 2014.[57] In mass doses, nicotine may result in nausea, vomiting, diarrhea, salivation, bradyarrhythmia, and possibly seizures and hypoventilation.[52] The nicotine in e-liquid can be hazardous to infants.[53] Even a portion of e-liquid may be lethal to a little child.[58] In December 2014, a one-year-old child in Fort Plain, New York died after an accidental ingestion of nicotine liquid.[57] An excessive amount of nicotine for a child that is capable of being fatal is 0.1–0.2mg/kg of body weight.[51] An accidental ingestion of only 6 mg may be lethal to children.[39][54]

Toxicology

Carcinogenicity

Chart showing various toxicants as measured in cigarette and e-cigarette smoke.[59]

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.[60] 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.[61] The amounts of TSNAs present were on par with a nicotine inhaler.[60] 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.[60][62] 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.[63]

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.[64] Further concerns were raised over inconsistent amounts of nicotine delivered when drawing on the device.[62] 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 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."[65] 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."[66] The chemicals and toxic substances included in e-cigarettes have not been completely disclosed and their safety is not guaranteed.[51] 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."[12] Few of the methods used to analyze the chemistry of e-cigarettes in the studies the review evaluated were validated.[12]

Nicotine

The nicotine molecule.

Nicotine is regarded as a potentially lethal poison.[21] Concerns exist that e-cigarette user exposure to toxic levels of nicotine may be harmful.[21] Research suggests that experienced e-cigarettes users are able to get as much nicotine from e-cigarettes as traditional cigarettes.[21] The levels were above that of nicotine replacement product users.[21] 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.[21] 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.[21] How efficiently different e-cigarettes give nicotine is unclear.[21] New generation e-cigarettes gives nicotine more effectively than first generation e-cigarettes.[40] Studies suggest that inexperienced users obtain moderate amounts of nicotine from e-cigarettes.[67] Newer e-cigarettes with more concentrated nicotine liquids may deliver nicotine at levels similar to traditional cigarettes.[21] E-cigarettes with stronger batteries heat solutions to higher temperatures, which may raise blood nicotine levels to those of traditional cigarettes.[56]

Serum nicotine levels identified are inharmonious and rely upon the user and the device.[8] Although some e-cigarettes are nicotine free, surveys demonstrate that 97% of e-cigarette users use products that contain nicotine.[21] 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.[16] Due to nicotine content inconstancy, it is recommended that e-cigarette companies develop quality standards with respect to nicotine content.[12] Serum cotinine levels are comparable to that of traditional cigarettes.[68] The nicotine delivered from e-cigarettes enters the body slower than traditional cigarettes.[69] E-cigarettes provide nicotine to the blood quicker than nicotine inhalers.[22]

It is not fully understood the long-term health impacts of the main chemicals nicotine and propylene glycol in the vapor.[70] There are safety issues with the nicotine exposure from e-cigarettes, which has the possibility of causing addiction and other adverse effects.[12] 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."[70] Nicotine can cause high blood pressure and abnormal heart rhythms.[65] Nicotine drops estrogen levels and has been associated with early menopause in women.[65] 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.[65] Nicotine use during adolescence may damage brain development.[58] The Centers for Disease Control and Prevention (CDC) stated the possible negative impact between nicotine and brain development in youth is a concern.[71] 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."[56] The health effects of nicotine in infants and children are unclear.[52]

Propylene glycol and other chemicals

The propylene glycol molecule.

The primary base ingredients of the liquid solution is propylene glycol and glycerin. Being exposed to propylene glycol may cause irritation to the eyes and respiratory tract. If propylene glycol is heated and aerosolized, it may produce propylene oxide, which the International Agency for Research on Cancer (IARC) states is probably carcinogenic to humans.[5] The risk from the inhalation of propylene glycol and glycerol is probably low.[13] The long-term effects of inhaled propylene glycol has not been studied.[23] Some research states that propylene glycol emissions may cause respiratory irritation and raise the likelihood to develop asthma.[72] To lessen the risks, e-cigarettes companies are using purified water and glycerin instead of propylene glycol for aerosol production.[72] When heated at hotter temperatures glycerol may generate harmful acrolein.[13] Acrolein may induce irritation to the upper respiratory tract.[5] 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.[73] The essential propylene glycol and/or glycerol mixture may consist of natural or artificial substances to provide it flavor.[16] Some of these substances are regarded as toxic and a number of them resemble known carcinogens.[16] Generally, flavoring additives are imprecisely described, using terms such as "vegetable flavoring".[16] Although they are approved for human consumption there are no studies on the short- or long-term effects of inhaling them.[16] Some artificial flavors have been demonstrated as being cytotoxic.[16] Cinnamaldehyde has been documented as a highly cytotoxic material in cinnamon-flavored refill solutions.[40] Diacetyl and acetyl propionyl are correlated with respiratory disease if inhaled, which have been detected in flavored liquid solutions.[40] A study has demonstrated that a balsamic flavored e-cigarette with no nicotine is capable of triggering a proinflammatory cytokine release in lung epithelial cells and keratinocytes.[51]

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.[18] The propylene glycol-containing liquids produced the most amounts of carbonyls in e-cigarette aerosols.[18] The IARC has categorized formaldehyde as a human carcinogen, and acetaldehyde is categorized as a potential carcinogenic to humans.[18] These materials may cause harmful health effects; though, in the majority of cases, the amounts inhaled are less than those in traditional cigarettes.[18] A 2014 review found "most E-cigarettes contain large concentrations of propylene glycol, a known irritant when inhaled. Little is known about the health impact of long-term inhalation of propylene glycol. At high temperatures, propylene glycol can oxidize and form toxic compounds such as formaldehyde and acetaldehyde."[51] Nearly all e-cigarettes evaluated, toxic and irritation-causing carbonyl substances were identified.[51] This included formaldehyde, acetaldehyde, and acrolein.[51] The majority of e-cigarettes evaluated included carcinogenic TSNAs; heavy metals such as cadmium, nickel, and lead; and the carcinogen toluene.[51] However, in comparison to traditional cigarette smoke, the toxic substance levels identified in e-cigarette vapor were 9- to 450-fold less.[51] The levels of toxic substances in the vapor were found to be 1 to 2 orders of magnitude smaller than in cigarette smoke but greater than from a nicotine inhaler.[5]

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.[74] Users may alter many of the devices, such as using them to administer other drugs like cannabis.[5] Battery output voltage influences the level of the carbonyl substances in the vapor.[18] A few new e-cigarettes let users boost the amount of vapor and nicotine provided by modifying the battery output voltage.[18] For example, a study demonstrated "that increasing the voltage from 3.2–4.8 V resulted in a 4 to >200 times increase in the formaldehyde, acetaldehyde, and acetone levels."[18] Thus, high-voltage e-cigarettes is capable of subjecting users to large amounts of carbonyl substances.[18] Reduced voltage e-cigarettes had e-cigarette aerosol levels of formaldehyde and acetaldehyde roughly 13 and 807-fold less than indicated in traditional cigarette smoke.[18] Devices using higher voltages can produce carcinogens including formaldehyde at levels found in cigarette smoke.[75] 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] 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.[16] 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.[16] There is limited peer-reviewed data about the toxicity of e-cigarettes for a complete toxicological evaluation.[74] The cytotoxicity from using e-cigarettes is unknown.[76]

Effects on breathing and lung function

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.[16] The risks, especially to the lungs, are not fully understood and are of concern to public health authorities.[77][78][79] 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.[80] 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.[73] 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]

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.[22] Comparable to a traditional cigarette, e-cigarette particles are tiny enough to enter the alveoli, enabling nicotine absorption.[40] The immediate effects of e-cigarettes after 5 minutes of use on pulmonary function resulted in considerable increases in resistance to lung airflow.[40] Short-term physiological effects include increases in blood pressure and heart rate.[15] 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.[41] The long-term effects regarding respiratory flow resistance are unknown.[41]

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.[19] This is due to the minute nicotine particles in the vapor, which permit quick delivery into the bloodstream.[19] 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.[19] Some case reports documented the possible cardiovascular adverse effects from using e-cigarettes, the majority associated was with improper use.[19] 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.[19] 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.[72] A 2015 review found e-cigarettes may induce acute lung disease.[15] The effect on population health from e-cigarettes is unknown.[8]

Ultrafine particles

E-cigarettes produce particles, in the form of an aerosol.[12][81] The aerosol (mist[16]) produced by an e-cigarette is commonly but inaccurately called vapor.[12] 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.[12] The word "vaping" is not technically accurate when applied to e-cigarettes.[81] The aerosol is made-up of liquid sub-micron particles of condensed vapor; thus, the users of these devices are rather "aerosolizing."[81] The aerosol the e-cigarette produces resembles cigarette smoke.[12] 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."[12] 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.[16] Different devices generate different particle sizes and cause different depositions in the respiratory tract, even from the same nicotine liquid.[75] A 2014 review found that the aerosol particle concentration is 5 times lower from an e-cigarette 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.[68] The potential harm to bystanders from e-cigarettes is unknown.[82] 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.[80] 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.[80] 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.[73] 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."[83]

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] The vapor from e-cigarettes appears similar to tobacco smoke.[30] Only what is exhaled by e-cigarettes users enters the surrounding air.[13] Since e-cigarettes involve an aerosolization process, it is suggested that no meaningful amounts of carbon monoxide are emitted.[69] Thus, cardiocirculatory effects caused by carbon monoxide are not likely.[69] However, in an experimental study, e-cigarettes increased levels of carcinogenic polycyclic aromatic hydrocarbons in the surrounding air.[69] There is a concern that some of the mainstream vapor exhaled by e-cigarette users can be inhaled by bystanders, particularly indoors.[51] Passive inhalation of vapor might have significant adverse effects.[51] However, it has been demonstrated that e-cigarettes causes nonusers to be exposed to nicotine.[51] Thus, e-cigarettes used indoors can involuntarily expose bystanders to nicotine but not to tobacco-related combustion toxicants.[51] E-cigarettes used in indoor environments can put at risk nonsmokers to elevated levels of nicotine and aerosol emissions.[8] 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 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]

E-cigarettes are marketed as "free of primary and second-hand smoke risk" due to no carbon monoxide or tar is expected to be generated during use.[84] However, there is a concern for the health impact of nicotine and other added ingredients.[84] 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.[19] The dense vapor consists of liquid sub-micron droplets.[81] The liquid particles condenses into a viewable fog.[16] 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.[16] This is because of fast revaporization at room temperature.[16] 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] 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."[58] A policy statement by the UK's Faculty of Public Health has stated, "A key concern for everyone in public health is that children and young people are being targeted by mass advertising of e-cigarettes. There is a danger that e-cigarettes will lead to young people and non-smokers becoming addicted to nicotine and smoking. Evidence from the US backs up this concern."[85]

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] 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."[86]

E-cigarettes pose many safety concerns to children.[52] Indoor surfaces can accumulate nicotine where e-cigarettes were used, which may be inhaled by children, particularly youngsters, long after they were used.[52] 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".[21] Nicotine is actually hard to get rid of from surfaces.[21] 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.[21] 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."[87]

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.[88] E-cigarette are assumed to be dangerous to the fetus during pregnancy if e-cigarettes are used by the mother.[89] Prenatal exposure has been associated with obesity, diabetes, high cholesterol and high blood pressure in minors.[65] As of 2014, the long-term issues of e-cigarettes on both mother and unborn baby are unknown.[88] There are concerns about the health impacts of pediatric exposure to second-hand and third-hand e-cigarette vapor.[11] 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."[21] The belief that e-cigarettes are safer than traditional cigarettes could increase their use for pregnant women.[40] The toxic effects identified with e-cigarette refill liquids on stem cells may be interpreted as embryonic death or birth defects.[40] Since e-cigarettes are not validated as cessation tools, may contain nicotine at inconsistent levels and added ingredients that are possibly harmful, allowing e-cigarettes to be used among pregnant women to decrease smoking puts this group at considerable risk.[52]

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.[17] 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.[17] 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.[17] It is not clear which manufacturing methods are used to make the nicotine used in e-cigarettes.[17] The emissions from making nicotine could be considerable from manufacturing if not appropriately controlled.[17] Some e-cigarette brands that use cartridges state their products are ‘eco-friendly’ or ‘green’, despite the absence of any supporting studies.[17] Some writers contend that such marketing may raise sales and increase e-cigarette interest, particularly among minors.[17] It is unclear how many traditional cigarettes are comparable to using one e-cigarette that uses a cartridge for the average user.[17] Information is limited on energy and materials used for production of e-cigarettes versus traditional cigarettes, for comparable use.[17] E-cigarettes can be made manually put together in small factories, or they can be made in automated lines on a much bigger scale.[17] Larger plants will produce greater emissions to the surrounding environment, and thus will have a greater environmental impact.[17] Although some brands have begun 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.[17] Some brands have also began recycling services for their e-cigarette batteries.[17] A 2014 review found "disposable e-cigarettes might cause an electrical waste problem."[69]

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External links

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