Adverse effects of electronic cigarettes

The short-term and long-term adverse effects from electronic cigarette use remain unclear.[1] The long-term effects of e-cigarette use are unknown.[2][3][4] The risk from serious adverse events, including death, was reported in 2016 to be low.[5] 39 deaths associated with the use of vaping products have been confirmed in the US, as of November 5, 2019.[6] The long-term health consequences from vaping is probably to be slighter greater than nicotine replacement products.[7] They may produce less adverse effects compared to tobacco products.[8] They may cause long-term and short-term adverse effects, including airway resistance, irritation of the airways, eyes redness, and dry throat.[9] Serious adverse events related to e-cigarettes were hypotension, seizure, chest pain, rapid heartbeat, disorientation, and congestive heart failure but it was unclear the degree to which they were the result of e-cigarettes.[10] Less serious adverse effects include abdominal pain, dizziness, headache, blurry vision,[10] throat and mouth irritation, vomiting, nausea, and coughing.[11] Short-term adverse effects reported most often were mouth and throat irritation, dry cough, and nausea.[12]

Nicotine poisoning related to e-cigarettes include ingestion, inhalation, or absorption via the skin or eyes.[13] Accidental poisoning can result from using undiluted concentrated nicotine when mistakenly used as prepared e-liquid.[14] There is a possibility that inhalation, ingestion, or skin contact can expose people to high levels of nicotine.[15] Concerns with exposure to the e-liquids include leaks or spills and contact with contaminants in the e-liquid.[16] Concern exists from the risk of injury associated with e-cigarette explosions for adults and children.[17] The exact causes of such incidents are not yet clear.[18] Pregnant women, breastfeeding mothers, and the elderly are more sensitive to nicotine than other individuals.[19] There are safety issues with the nicotine exposure from e-cigarette use, which may cause addiction and other adverse effects.[20]

Aside from toxicity exposure in normal use, there are also risks from misuse or accidents[21] such as nicotine poisoning (especially among small children[22]),[13] contact with liquid nicotine,[17] fires caused by vaporizer malfunction,[11] and explosions resulting from extended charging, unsuitable chargers, or design flaws.[21] Battery explosions are caused by an increase in internal battery temperature and some have resulted in severe skin burns.[23] There is a small risk of battery explosion in devices modified to increase battery power.[24] There is considerable variation among e-cigarettes and in their liquid ingredients.[25] and thus the contents of the aerosol delivered to the user.[11] Repeated exposure over a long time to e-cigarette vapor poses substantial potential risk.[26] The cytotoxicity of e-liquids varies,[27] and contamination with various chemicals have been detected in the liquid.[28] E-cigarette users who use devices that contain nicotine are exposed to its potentially harmful effects.[20] E-cigarette vapor potentially contains harmful chemicals not found in tobacco smoke.[29]

Adverse effects
Possible adverse effects of vaping.[30]

The short-term and long-term effects from electronic cigarette use remain unclear.[1] As of 2018, the knowledge of possible acute and long-term health effects of aerosols inhaled from e-cigarettes is still limited partially due to incomplete awareness of physical phenomena related to e-cigarette aerosol dynamics.[31] Makers of vaping products state that these products are non-toxic, but they are correlated with a myriad of adverse effects.[32] They may cause long-term and short-term adverse effects, including airway resistance, irritation of the airways, eyes redness, and dry throat.[9] Since vaping is relatively in its infancy, it will probably take decades for long-term harm research to be available.[33] The growing evidence reinforces the idea that persistent and long-term exposure to e-cigarette aerosols possibly affects health adversely.[34] The long-term health consequences from vaping is probably to be slighter greater than nicotine replacement products.[7] A 2016 review found "it is impossible to reach a consensus on the safety of e-cigarettes except perhaps to say that they may be safer than conventional cigarettes but are also likely to pose risks to health that are not present when neither product is used."[35] The wide range of e-cigarette products available to users and the lack of standardization of toxicological approaches towards e-cigarette evaluation complicates the assessment of adverse effects of their use.[36] Adverse effects are mostly associated with short-term use and the reported adverse effects decreased over time.[12] Long-term studies regarding the effects of constant use of e-cigarettes are unavailable.[12] Studies over one year on the effects of exposure to e-cigarettes have not been conducted, as of 2019.[37] The adverse effects of e-cigarettes on people with cancer is unknown.[13] A 2016 Cochrane review found no serious adverse events reported in studies for up to two years,[2] but several serious events were reported as case studies.[22]

They may produce less adverse effects compared to tobacco products.[8] The most frequently reported less harmful effects of vaping compared to smoking were reduced shortness of breath, reduced cough, reduced spitting, and reduced sore throat.[38] Many health benefits are associated with switching from tobacco products to e-cigarettes including decreased weight gain after smoking cessation and improved exercise tolerance.[39] Vaping is possibly harmful by virtue of putting off quitting smoking, serving as a gateway to tobacco use in never-smokers or causing a return to smoking in former smokers.[40] Many people use e-cigarettes to quit smoking, but few succeed.[41] They frequently use both, which increases their health risks by using both products.[41] The long-term research on the safety of dual use of tobacco smoking and vaping are not available.[42] Vaping can hinder smokers from trying to quit, resulting in increased tobacco use and associated health problems.[43] Quitting smoking entirely would probably have much greater beneficial effects to overall health than vaping to decrease the number of cigarettes smoked.[11] A 2017 review found "Because the brain does not reach full maturity until the mid-20s, restricting sales of electronic cigarettes and all tobacco products to individuals aged at least 21 years and older could have positive health benefits for adolescents and young adults."[44] Adverse effects to the health of children is mostly not known.[45] E-cigarettes are a source of potential developmental toxicants.[46] Children subjected to e-cigarettes had a higher likelihood of having more than one adverse effect and effects were more significant, than with children subjected to traditional cigarettes.[45] Significant harmful effects were cyanosis, nausea, and coma, among others.[45]

More serious adverse effects frequently related with smoking cessation including depression, insomnia, and anxiety are uncommon with e-cigarette use.[10] A 2015 study found serious adverse events related to e-cigarettes were hypotension, seizure, chest pain, rapid heartbeat, disorientation, and congestive heart failure but it was unclear the degree to which they were the result of e-cigarettes.[10] Less serious adverse effects include abdominal pain, dizziness, headache, blurry vision,[10] throat and mouth irritation, vomiting, nausea, and coughing.[11] Vaping induces irritation of the pharynx.[43] Short-term adverse effects reported most often were mouth and throat irritation, dry cough, and nausea.[12] The majority of adverse effects reported were nausea, vomiting, dizziness and oral irritation.[21] 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 were dryness of the mouth and throat.[47] Dryness of the mouth and throat is believed to stem from the ability of both propylene glycol and glycerin to absorb water.[48] 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.[13] Vaping may harm neurons and trigger tremors and spasms.[49] The use of e-cigarettes has been found associated with nose bleeding, change in bronchial gene expression, release of cytokines and proinflammatory mediators, and increase in allergic airway inflammation which can exacerbate asthmatic symptoms, thus by elevating infiltration of inflammatory cells including eosinophils into airways.[50] A 2016 study found vaping using an e-liquid containing 23% alcohol was linked to reduced performance on the Purdue Pegboard Test.[51]

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.[22] Two peer-reviewed reports of lipoid pneumonia were related to e-cigarette use, as well as two reports in the media in Spain and the UK.[52] The man from the UK reportedly died from severe lipoid pneumonia in 2011.[52] In August 2019, the Illinois Department of Public Health (IDPH) reported the first death in the US linked to vaping.[53] The person who had died had been recently using an e-cigarette and was hospitalized with serious respiratory problems.[53] As of November 7, 2019, 39 deaths associated with the use of vaping products have been confirmed in 24 states and the District of Columbia: Alabama, California (3), Connecticut, Delaware, District of Columbia, Florida, Georgia (3), Illinois (3), Indiana (3), Kansas (2), Massachusetts (2), Michigan, Minnesota (3), Mississippi, Missouri, Montana, Nebraska, New Jersey, New York, Oregon (2), Pennsylvania, Tennessee (2), Texas, Utah, and Virginia.[6]

Reports to the FDA in 2013 for minor adverse effects identified with using e-cigarettes included headache, chest pain, nausea, and cough.[23] Major adverse events reported to the FDA in 2013 included hospitalizations for pneumonia, congestive heart failure, seizure, rapid heart rate, and burns.[23] However no direct relationship has been proven between these effects and events and e-cigarette use, and some of them may be due to existing health problems.[23] 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.[54] 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.[55] E-cigarettes were associated with fewer adverse effects than nicotine patches.[56] Contact dermatitis from nickel exposure has been reported, following e-cigarette use.[57] No information is available on the effects of long-term e-cigarette use on taste receptors.[24]

Frequent vaping among middle and high school students has been said to be linked to oral symptoms, such as cracked/broken teeth and tongue/cheek pain.[58] Information on the long-term health effects of vaping for adolescent and young adults are scant because of the limited amount of time they have been available.[58] There is fair evidence that coughing and wheezing is higher in adolescents who vape.[59]

Poisoning
Symptoms of nicotine poisoning related to e-cigarette calls to US poison control centers.[60]

Nicotine poisoning related to e-cigarettes include ingestion, inhalation, or absorption via the skin or eyes.[13] Accidental poisoning can result from using undiluted concentrated nicotine when mistakenly used as prepared e-liquids.[14] E-cigarettes involve accidental nicotine exposure in children.[17] Accidental exposures in pediatric patients include ingesting of e-liquids and inhaling of e-cigarette vapors.[17] Choking on e-cigarette components is a potential risk.[17] It was stated in 2014 that an infant died from choking on an e-cigarette component.[61] It is recommended that youth access to e-cigarettes be prohibited.[notes 1][62] Concerns exist regarding poisoning, considering they may appeal to children.[61] E-liquid presents a poisoning risk, particularly for small children, who may see the colorful bottles as toys or candy.[63]

The e-liquid can be toxic if swallowed, especially among small children.[22] Four adults died in the US and Europe, after intentionally ingesting liquid.[52] Two children, one in the US in 2014 and another in Israel in 2013, died after ingesting liquid nicotine.[64] A two year old girl in the UK in 2014 was hospitalized after licking an e-cigarette liquid refill.[65] Death from accidental nicotine poisoning is very uncommon.[66]

Calls to US poison control centers related to e-cigarette exposures involved inhalations, eye exposures, skin exposures, and ingestion, in both adults and young children.[67] Minor, moderate, and serious adverse effects involved adults and young children.[68] Minor effects correlated with e-cigarette liquid poisoning were tachycardia, tremor, chest pain and hypertension.[69] More serious effects were bradycardia, hypotension, nausea, respiratory paralysis, atrial fibrillation and dyspnea.[69] The exact correlation is not fully known between these effects and e-cigarettes.[69] The initial symptoms of nicotine poisoning may include rapid heart rate, sweating, feeling sick, and throwing up, and delayed symptoms include low blood pressure, seizures, and hypoventilation.[70] Rare serious effects included coma, seizure, trouble breathing trouble breathing, and heart attack.[71] Since June 2018, the US FDA observed a slight but noticeable increase in reports of seizures.[72] After examining poison control centers' reports between 2010 and early 2019, the FDA determined that, between the poison control centers and the US FDA, there were a total of 35 reported cases of seizures mentioning use of e-cigarettes within that timeframe.[72] Due to the voluntary nature of these case reports, there may be more instances of seizure in e-cigarette users than have been reported.[72]

Since 2011, accidental poisoning from e-liquids that contain nicotine have grown rapidly in the US.[73] From September 1, 2010, to December 31, 2014, 58% of e-cigarette calls to US poison control centers were related to children 5 years old or less.[68] Exposures for children below the age of 6 is a concern because a small dose of nicotine e-liquid may be fatal.[71] A 2014 Centers for Disease Control and Prevention report found 51.1% of the calls to US poison centers due to e-cigarettes were related to children under age 5, and about 42% of the US poison center calls were related to people age 20 and older.[74] E-cigarette calls had a greater chance to report an adverse effect and a greater chance to report a moderate or major adverse effect than traditional cigarette calls.[68] Most of the e-cigarette and traditional cigarette calls were a minor effect.[68] Severe outcomes were more than 2.5 times more frequent in children exposed to e-cigarettes and nicotine e-liquid than with traditional cigarettes.[75] E-cigarette sales were roughly equivalent to just 3.5% of traditional cigarette sales, but e-cigarettes represented 44% of the total number of e-cigarette and traditional cigarette calls to US poison control centers in December 2014.[68]

Poison control center calls in the US related to e-cigarettes was one call per month in September 2010 to over 200 calls per month in February 2014.[74]

The US poison control centers reported 92.5% of children coming in contact with liquid nicotine was from swallowing during the period from January 2012 to April 2017.[71] From September 1, 2010 to December 31, 2014, the most frequent adverse effects to e-cigarettes and e-liquid reported to US poison control centers were: Ingestion exposure resulted in vomiting, nausea, drowsy, tachycardia, or agitation;[68] inhalation/nasal exposure resulted in nausea, vomiting, dizziness, agitated, or headache;[68] ocular exposure resulted in eye irritation or pain, red eye or conjunctivitis, blurred vision, headache, or corneal abrasion;[68] multiple routes of exposure resulted in eye irritation or pain, vomiting, red eye or conjunctivitis, nausea, or cough;[68] and dermal exposure that resulted in nausea, dizziness, vomiting, headache, or tachycardia.[68] The ten most frequent adverse effects to e-cigarettes and e-liquid reported to US poison control centers were vomiting (40.4%), eye irritation or pain (20.3%), nausea (16.8%), red eye or conjunctivitis (10.5%), dizziness (7.5%), tachycardia (7.1%), drowsiness (7.1%), agitation (6.3%), headache (4.8%), and cough (4.5%).[68] In nine reported calls, exposed individuals stated the device leaked.[68] In five reported calls, individuals used e-liquid for their eyes rather than use eye drops.[68] In one reported call, an infant was given the e-liquid by an adult who thought it was the infant's medication.[68] There were also reports of choking on e-cigarette components.[17]

From January 1, 2016, and April 30, 2016, the American Association of Poison Control Centers (AAPCC) reported 623 exposures related to e-cigarettes.[41] In 2016 AAPCC reported there were a total of 2,907 exposures regarding e-cigarettes and liquid nicotine.[76] The yearly nicotine exposure rate in the US involving children went up by 1398.2% from 2012 to 2015, and later dropped by 19.8% from 2015 to 2016.[71] The AAPCC reported 3,067 exposures relating to e-cigarettes and liquid nicotine in 2015, and 3,783 in 2014.[77] As of October 31, 2018, there were a total of 2,555 exposures regarding e-cigarettes and liquid nicotine in 2018.[76] The US National Poison Control database showed that in 2015 more than 1000 needed medical attention from being exposed to nicotine e-liquid.[57] Most exposures in 2015 were related to children under the age of 5.[57] The reported e-cigarette poisonings to medical centres in the UK most often happen in children under the age of five.[78] Toxic effects for children under the age of five in the UK are typically short in length and not severe.[78] From September 1, 2010 to December 31, 2014, there were at least 5,970 e-cigarette calls to US poison control centers.[68] Calls to US poison control centers related to e-cigarettes increased between September 2010 to February 2014, and of the total number of cigarettes and e-cigarettes calls, e-cigarette calls increased from 0.3% to 41.7%.[56] Calls to US poison controls centers related to e-cigarette liquid poisoning increased from 1 in September 2010 to 215 for the month of February 2014.[69] E-cigarette calls was 401 for the month of April 2014.[68] The National Poison Data System stated that exposures to e-cigarettes and liquid nicotine among young children is rising significantly.[79] 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.[21] Calls associated with e-cigarette poisoning in Texas found that 57% was associated with children under the age of 5.[9] They were accidental with 96% where they lived, 85% from swallowing, and 11% from skin contact.[9]

In 2017, the US Food and Drug Administration states that the e-cigarette aerosol can still cause problems for the user and their pets.[80] Some studies have shown that the aerosol made by these devices may expose the user and, therefore, their pets to higher-than-normal amounts of nicotine and other toxic chemicals, like formaldehyde.[80] E-cigarettes use capsules that can contain nicotine.[80] Some of these capsules can be re-filled using a special liquid.[80] Sometimes, pets—mainly dogs—find the capsules and bite them or get into the liquid refilling solution.[80] In a March 15, 2016, letter to the editor of the Journal of the American Veterinary Medical Association, the Texas Poison Center Network reported 11 cases of dogs being exposed to e-cigarettes or refills.[80] Moreover, there is no antidote for nicotine poisoning.[80] If someone's pet gets into an e-cigarette, nicotine capsule, or the liquid refilling solution, it is an emergency, according to the FDA.[80] Get him or her to the veterinarian or to a veterinary emergency clinic as quickly as possible, according to the FDA.[80] The Animal Poison Control Center states that all the nicotine toxicity cases in 2012 included 4.6% of e-cigarettes causes and it increased to 13.6% in 2013.[81]

Fruit flavored e-liquids.

There is a possibility that inhalation, ingestion, or skin contact can expose people to high levels of nicotine.[15] Concerns with exposure to the e-liquids include leaks or spills and contact with contaminants in the e-liquid.[16] This may be especially risky to children, pregnant women, and nursing mothers.[15] The FDA intends to develop product standards around concerns about children's exposure to liquid nicotine.[82] E-liquid exposure whether intentional or unintentional from ingestion, eye contact, or skin contact can cause adverse effects such as seizures, anoxic brain trauma, throwing up, and lactic acidosis.[83] The liquid does quickly absorb into the skin.[84] Local irritation can be induced by skin or mucosal nicotine exposure.[85] The nicotine in e-liquid can be hazardous to infants.[86] Even a portion of e-liquid may be lethal to a little child.[87] An excessive amount of nicotine for a child that is capable of being fatal is 0.1–0.2 mg/kg of body weight.[15] Less than a 1 tablespoon of contact or ingestion of e-liquid can cause nausea, vomiting, cardiac arrest, seizures, or coma.[88] An accidental ingestion of only 6 mg may be lethal to children.[89][90]

Children are susceptible to ingestion due to their curiosity and desire for oral exploration.[75] Children could confuse the fruity or sweet flavored e-liquid bottles for fruit juices.[9] E-liquids are packed in colorful containers[68] and children may be attracted to the flavored liquids.[91] More youth-oriented flavors include "My Birthday Cake" or "Tutti Frutti Gumballs".[64] Many nicotine cartridges and bottles of liquid are not child-resistant to stop contact or accidental ingestion of nicotine by children.[8] "Open" e-cigarette devices, with a refillable tank for e-liquids, are believed to be the biggest risk to young children.[88] If flavored e-cigarettes are let alone, pets and children could be attracted to them.[92] The FDA states that children are curious and put all sorts of things in their mouths.[93] Even if you turn away for a few seconds, they can quickly get into things that could harm them.[93] The FDA recommends that adults can help prevent accidental exposure to e-liquids by always putting their e-cigarettes and e-liquids up and away—and out of kids' and pets' reach and sight—every time you use them.[93] The FDA recommends to also ask family members, house guests, and other visitors who vape to keep bags or coats that hold e-cigarettes or e-liquids up and away and out of reach and sight of children and pets.[93] They recommend for children old enough to understand, explain to them that these products can be dangerous and should not be touched.[93] The FDA states to tell kids that adults are the only people who should handle these products.[93]

As part of ongoing efforts to protect youth from the dangers of nicotine and tobacco products, the US FDA and the Federal Trade Commission announced on May 1, 2018, they issued 13 warning letters to manufacturers, distributors, and retailers for selling e-liquids used in e-cigarettes with labeling and/or advertising that cause them to resemble kid-friendly food products, such as juice boxes, candy or cookies, some of them with cartoon-like imagery.[94] Several of the companies receiving warning letters were also cited for illegally selling the products to minors.[94] "No child should be using any tobacco product, and no tobacco products should be marketed in a way that endangers kids – especially by using imagery that misleads them into thinking the products are things they would eat or drink. Looking at these side-to-side comparisons is alarming. It is easy to see how a child could confuse these e-liquid products for something they believe they have consumed before – like a juice box. These are preventable accidents that have the potential to result in serious harm or even death. Companies selling these products have a responsibility to ensure they are not putting children in harm's way or enticing youth use, and we'll continue to take action against those who sell tobacco products to youth and market products in this egregious fashion," the FDA Commissioner Dr. Scott Gottlieb, said in 2018.[94] E-liquids have been sold in packaging that looks similar to Tree Top-brand juice boxes, Reddi-wip whipped cream, and Sour Patch Kids gummy candy.[95]

The US FDA announced on August 23, 2018 that all 17 manufacturers, distributors and retailers that were warned by the agency in May, have stopped selling the nicotine-containing e-liquids used in e-cigarettes with labeling or advertising resembling kid-friendly food products, such as juice boxes, candy or cookies that were identified through warning letters as being false or misleading.[96] Following the warning letters in May, the FDA worked to ensure the companies took appropriate corrective action – such as no longer selling the products with the misleading labeling or advertising – and issued close-out letters to the firms. The agency expects some of the companies may sell the products with revised labeling that addresses the concerns expressed in the warning letters.[96] "Removing these products from the market was a critical step toward protecting our kids. We can all agree no kid should ever start using any tobacco or nicotine-containing product, and companies that sell them have a responsibility to ensure they aren’t enticing youth use. When companies market these products using imagery that misleads a child into thinking they’re things they’ve consumed before, like a juice box or candy, that can create an imminent risk of harm to a child who may confuse the product for something safe and familiar," said FDA Commissioner Scott Gottlieb.[96]

Nicotine toxicity is of concern when e-cigarette solutions are swallowed intentionally by adults as a suicidal overdose.[97] Seizures or convulsions are known potential side effects of nicotine toxicity and have been reported in the scientific literature in relation to intentional or accidental swallowing of e-liquid.[72] Six people attempted suicide by injecting e-liquid.[52] One adolescent attempted suicide by swallowing the e-liquid.[17] Three deaths were reported to have resulted from swallowing or injecting e-liquid containing nicotine.[52] An excessive amount of nicotine for an adult that is capable of being fatal is 0.5–1 mg/kg of body weight.[15] An oral lethal dose for adults is about 30–60 mg.[38] However the widely used human LD50 estimate of around 0.8 mg/kg was questioned in a 2013 review, in light of several documented cases of humans surviving much higher doses; the 2013 review suggests that the lower limit resulting in fatal events is 500–1000 mg of ingested nicotine, which is equivalent to 6.5–13 mg/kg orally.[98] Reports of serious adverse effects associated with acute nicotine toxicity that resulting in hospitalization were very uncommon.[99] Death from intentional nicotine poisoning is very uncommon.[66] Clear labeling of devices and e-liquid could reduce unintentional exposures.[68] Child-proof packaging and directions for safe handling of e-liquids could minimize some of the risks.[86] Some vaping companies willingly used child-proof packaging in response to the public danger.[61] In January 2016, the Child Nicotine Poisoning Prevention Act of 2015 was passed into law in the US,[100] which requires child-proof packaging.[101] The nicotine exposure rate in the US has since dropped by 18.9% from August 2016 to April 2017, following the Child Nicotine Poisoning Prevention Act of 2015, a federal law mandating child-resistant packaging for e-liquid, came into effect, on July 26, 2016.[71] The states in the US that did not already have a law, experienced a notable decline in the average number of exposures during the 9 months after the Child Nicotine Poisoning Prevention Act of 2015 came into effect compared to before it became law.[71] E-liquids have been observed in 2016 to include a press-and-turn feature similar to what is used for aspirin.[61] E-liquids that were normally available in bottles that were not regarded as child-resistant, have been reported in 2016.[61]

There was inconsistent labeling of the actual nicotine content on e-liquid cartridges from some brands,[11] and some nicotine has been found in ‘no nicotine' liquids.[28] A 2015 PHE report noted overall the labelling accuracy has improved.[102] Most inaccurately-labelled examples contained less nicotine than stated.[102] Due to nicotine content inconstancy, it is recommended that e-cigarette companies develop quality standards with respect to nicotine content.[20]

Because of the lack of production standards and controls, the pureness of e-liquid are generally not dependable, and testing of some products has shown the existence of harmful substances.[86] 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.[89] This includes leaking cartridges, accidental contact with nicotine when changing cartridges, and potential of unintended overdose.[89] 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."[103]

Cannabinoid-enriched e-liquids require lengthy, complex processing, some being readily available online despite lack of quality control, expiry date, conditions of preservation, or any toxicological and clinical assessment.[104] It is assumed that vaporizing cannabinoids at lower temperatures is safer because it produces smaller amounts of toxicants than the hot combustion of a cannabis cigarette.[104] The health effects specific to vaping these cannabis preparations is largely unknown.[104]

Concern exists from the risk of injury associated with e-cigarette explosions for adults and children.[17] The exact causes of such incidents are not yet clear.[18] Most e-cigarettes use lithium batteries, the improper use of which may result in accidents.[21] Most fires caused by vaporing devices are a result of the lithium batteries becoming too hot and igniting.[105] Defective e-cigarette batteries have been known to cause fires and explosions.[106] The chance of an e-cigarette blast resulting in burns and projectile harms greatly rises when using low-quality batteries, if stored incorrectly or was altered by the user.[107] Inexpensive manufacturing with poor quality control could account for some of the explosions.[108] It has been recommended that manufacturing quality standards be imposed in order to prevent such accidents.[21] Better product design and standards could probably reduce some of the risks.[16] It is recommended that users be informed of appropriate charging and storage methods.[109] In the event the lithium ion substances leak from the battery as a result of an e-cigarette blast, first aid is recommended to prevent additional chemical reaction.[109] An e-cigarette blast can induce serious burns and harms that need thorough and lengthy medical treatment particularly when a device goes off in hands, mouths, or pockets.[110] A 2017 review found "The electrolyte liquid within the lithium ion battery cells is at risk for overheating, thus building pressure that may exceed the capacity of the battery casing. This "thermal runway" can ultimately result in cell rupture or combustion."[111] Metal objects, including coins or keys, can cause a short circuit when kept with batteries, which can result in overheating of the battery.[111] It is recommended to use insulated protective cases for batteries not in use to lessen the potential risk related to thermal runaway.[112] Swallowing e-cigarette batteries can be toxic.[113]

Graphic from an October 2014 United States Fire Administration (USFA) report entitled Electronic Cigarette Fires and Explosions.[114] The USFA said that 25 fires and explosions in the US were the result of e-cigarette use between 2009 and August 2014.[114]

The numbers of medical reports from harms resulting from vaping have continued to increase since 2016.[108] Some batteries are not well designed, are made with poor quality components, or have defects.[23] Major injuries have occurred from battery explosions and fires.[11] Fires caused by e-cigarettes appear to be increasingly frequent.[105] Direct harms from an e-cigarette blast include hand harms, face harms, waist/groin harms, and inhalation harms.[105] Indirect harms happened when the vaporing device set on fire another object and resulted in a house fire, followed by harm from fire burns or inhalation.[105] E-cigarette explosions have resulted in burns, lost teeth, neck fractures, and battery acid contact to the face, mouth, and eyes.[5] The extent of the burns varied from 1% to 8% total body surface area, were reported and most commonly occurred in the lower extremity, hands, head and neck, and genitalia.[111] The extent of the burn was mainly deep partial and full thickness.[111] E-cigarette explosion harms correlated with malfunctioning of the device can result in minor total body surface area 2nd and 3rd degree burns.[115] Around 50% needed surgical management for the burn.[111] This was due to the extent of the injury.[111] The most common harms are burns as a result of explosion in the pocket and harms to the face.[105] A 2017 review found "Several of the reported cases show that 'the battery in pocket' precedes the incident. The damp environment in the pocket may have sufficient moisture to start a chemical reaction within the lithium-ion battery and the presence of metal objects can produce short-circuit which can over heat the battery leading to an explosion."[109] Flame burns, chemical burns, and blast injuries have occurred as a result of the e-cigarette battery overheating.[116] A man endured a unilateral corneoscleral laceration with prolapsed iris tissue and hyphemato to the eye area when an e-cigarette exploded in his mouth.[5] A young man endured bilateral corneal burns to the eye area when an e-cigarette exploded near his chest.[5] A man lost his life when his charging e-cigarette blew up and caught on fire next to oxygen equipment.[5] House and car fires and skin burns have resulted from some of the explosions.[23] The explosions were the result of extended charging, use of unsuitable chargers, or design flaws.[21] There is a possible risk to bystanders from e-cigarette explosions.[5] There is also a risk of property damage as a result of flammable materials catching on fire from an e-cigarette explosion.[5] A March 2016 research article assembled reports by US government agencies and in the media of 92 e-cigarette blasts, fire, or overheating events, with related injuries in 47 individuals.[117] Prominent harms included 2 cervical vertebral fractures, 1 palate fracture, 3 instances of damaged teeth, 33 thermal burns, 4 chemical burns, and 5 lacerations.[117]

Graphic from a July 2016 United States Fire Administration (USFA) report entitled Electronic Cigarette Fires and Explosions in the United States 2009 – 2016.[114] There has been an increase in the number of severe and moderate injuries resulting from e-cigarette explosions and fires since 2014.[114] The USFA noted that this appears to correlate well with the e-cigarette sales trend.[114]

Between January 2015 and May 2016, 35 burns and correlated injuries were caused by e-cigarette explosions.[111] Between January 2009 and December 31, 2016, 195 separate incidents of explosion and fire involving an e-cigarette were reported by the US media.[114] These incidents resulted in 133 acute injuries.[114] Of these injuries, 38 (29 percent) were severe.[114] Sixty-one incidents occurred when either the device or spare batteries for the device were in a pocket.[114] Sixty incidents occurred while the device was being used.[114] Forty-eight incidents occurred while the battery in the device was being charged.[114] Eighteen incidents occurred while the device or battery was stored.[114] In seven incidents, it is not reported whether the e-cigarette was in use, stored, or being charged.[114] One incident occurred during transportation on a cargo aircraft.[114] Media reports generally characterize these incidents as explosions.[114] While there is generally a brief period of overheating and off-gassing at the onset of the event, the events tend to occur suddenly, and are accompanied by loud noise, a flash of light, smoke, flames, and often vigorous ejection of the battery and other parts.[114] A number of the media reports state that the battery or other components of the device were ejected under pressure and "flew across the room," often igniting combustible items where they landed.[114]

The United States Fire Administration stated in 2014 that 25 fires and explosions in the US were caused by e-cigarettes between 2009 and August 2014.[114] This list is not considered to be complete because it is very possible that there were events that were not disclosed to the fire department or mentioned in the media.[114] Up to 2014, twenty events happened when charging the battery in the e-cigarette.[114] Two events happened during use.[114] In two events, it is unclear whether the device was in use, not in use or was charging.[114] One event happened while being transported on a cargo aircraft.[114] Several burns were reported.[114] Two serious harms were the result of devices exploding in users' mouths.[114] A 2017 review found that "The U.S. Fire Administration reports that 80% of e-cigarette explosions occurred while the battery was being charged. The report revealed that many of the e-cigarettes were being charged by power adaptors that were not provided by the manufacturer, subjecting the battery to an inappropriately high current, which led to thermal runaway and subsequent explosion and/or fire. This problem is potentially further exacerbated by third-party vendors who assemble e-cigarettes from noncompatible parts that may not meet the manufacturers' specifications."[117] The shape of these devices is another concern.[117] They are likely to be cylindrical, with the least strongest structural points at both ends.[117] In the event there is a breach in the battery seal, the pressure inside the e-cigarette can quickly build, launching the ends of the device with a great abundance of force.[117]

The United States Fire Administration stated in 2017 that of the reported fire and explosion incidents involving e-cigarettes, 128 (66 percent) resulted in ignition of nearby contents such as clothing, carpets, drapes, bedding, couches, or vehicle seats.[114] Users were generally nearby when the incident occurred, were alerted by the sound of the explosion, and were able to take action to extinguish the fires while they were still small.[114] In 91 incidents, the fire spread was minor, meaning that the scorching or flames either self-extinguished or were extinguished very quickly by persons nearby.[114] Typically, in these incidents, the burned areas were 6 inches or less in diameter.[114] In 27 incidents, the fire spread was moderate, where the burned area was larger than 6 inches in diameter, but the fire was extinguished by occupants before the fire department arrived.[114] In 10 incidents, the fire spread was major and involved significant portions of a building, and required suppression by the fire department.[114] Typically, these incidents are what the fire service refers to as "room and contents" type fires, or larger.[114] In 67 of the incidents (34 percent), there was no fire spread, or fire spread was not evident in the reports reviewed.[114]

E-cigarette device explodes in man's pocket while on bus in California.[118]

Even though there are knowns risks with unregulated lithium batteries causing serious harm, importing e-cigarettes to the UK is still not restricted and they do not conform to the British Standards, which may increase their chance of resulting in fire and blowing up.[109] There has been a rise in the number of burns due to blasts of the e-cigarettes battery in South Wales and South West England.[109] In the UK fire service call-outs had risen, from 43 in 2013 to 62 in 2014.[119] A 2015 PHE report concluded that the risks of fire from e-cigarettes "appear to be comparable to similar electrical goods".[120] A 2018 PHE report found six case studies involving e-cigarettes with burns in the UK.[121] Every person were male and 33 years was the average age.[121] In five cases, they received burn harms resulting from an e-cigarette blast in their pants pocket.[121] One case happened while coins and the e-cigarette were in the same pocket.[121] Another case happened when the e-cigarette was being charged.[121] Harms included burns accounting for 1–7% of the complete body surface region.[121] Harms happened to the thigh, genitals, foot, and hands.[121] Chemical burns from the battery was included in one case.[121] Since e-cigarettes are not subjected to product safety testing, they may not have safety designs to avoid overheating, thermal runaway, and battery failure including fire and explosions.[5] There is inadequate product labeling to inform users of the possible serious harms.[5] The risk from serious adverse events was reported in 2016 to be low, but the aftermath may be disastrous in respect to an e-cigarette blast.[5] Numerous stories about the e-cigarette blasts were reported in the news media and victims have filed lawsuits to make restitution from the blasts.[52] Adverse events may be under-reported because reports to the FDA is voluntary.[5]

A 35-year-old otherwise healthy male sustained a 2% total body surface area burn to his right lateral thigh when an e-cigarette device in the right back pocket of his pants spontaneously combusted, burning a hole through his pants.[122]

In January 2015 the US Federal Aviation Administration issued a safety alert to air carriers that e-cigarettes should not be allowed in checked baggage after a review of fire safety issues, including two fires caused by e-cigarettes in checked baggage.[123][124] The International Civil Aviation Organization, a United Nations agency, also recommends prohibiting e-cigarettes in checked luggage.[123] 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.[123] In 2015 the US Department of Transportation prohibited storage of e-cigarettes in checked baggage on airplanes to avoid damage and injury due to an explosion.[52] In-flight use of e-cigarettes is prohibited in the US.[124] A 2017 review stated "Passengers are allowed to carry e-cigarettes with them onto planes, but are not allowed to charge their batteries during flight."[43]

Individuals sent to Saint Louis Hospital Burn Center in Paris, France from June 2016 to July 2017 for harms resulting from e-cigarettes were ten.[108] Four individuals were admitted to the hospital and six of them received care at an Outpatient Burn Clinic.[108] All of them had burns of at least one arm or leg.[108] In 2014 a 72-year-old male with pulmonary fibrosis was hospitalized for 5 days at the Maisonneuve-Rosemont Hospital in Montreal with facial burns that happened after his nasal prongs caught on fire from using an e-cigarette while on oxygen therapy.[125] Several burn events during vaping while on home oxygen therapy have happened, leading Health Canada in 2014 to release a warning of fire risk to oxygen therapy users from vaping.[125] The heating element in vaping devices reaches a high temperature which can possibly ignite in the presence of oxygen.[125] Vaping while on oxygen therapy is not recommended.[125]

E-cigarette-related fires and explosions are a new risk to people and pets.[80] In 2016, the FDA Center for Tobacco Products reviewed and summarized reports from other US government agencies, the news media, and scientific articles about e-cigarette-related fires and explosions, finding that some events have resulted in life-threatening injury, and permanent disfigurement or disability.[80] Although there were no reports of pets being injured, the risk still exists.[80] Pets that chew on the devices may potentially puncture the cartridges or batteries, or they may inadvertently turn on the devices.[80] The US Food and Drug Administration recommends to keep e-cigarettes and all other tobacco products out of reach of children and pets at all times.[80]

Users may alter many of the devices, such as using them to administer other drugs like cannabis.[11] E-liquid mixing is another way users tamper with e-cigarettes.[126] Mixing liquid in an unclean area runs the risk of contamination.[10] Users may add various flavorings and diluents.[126] Vodka or other forms of alcohol may also be added.[126] The addition of alcohol or nicotine could expose the user to more toxicants, especially when added in combinations.[126] Some ingredients in e-liquids could be flammable; this risk is more of concern for users who are inexperienced or do not use protective gear.[126] Users can adjust the voltage of some e-cigarettes.[126] The amount of vapor produced is controlled by the power of the battery, which has led some users to adjust their e-cigarettes to increase battery power to obtain a stronger nicotine "hit", but there is a small risk of battery explosion.[24] Some users add more or larger batteries to nonadjustable e-cigarettes, which may lead to battery leakage or explosion.[126] The FDA stated to only use batteries recommended for use with the device.[18] The FDA recommended to replace the batteries if they get damaged or wet.[18] The extent to which teens are altering e-cigarettes, such as dripping the liquids onto the atomizer to get more nicotine intake, is not known.[17]

5 Tips to Help Avoid Vape Battery Explosions.[127]
Case reports involving e-cigarette (EC) health effects.[128]
Patient demographics (age, sex, country) Pre-existing medical history Smoking history Presentation/signs Treatment EC device/refill fluid info Diagnosis Health outcome Other notes & comments Source
Systemic effects respiratory
42, F, USA 7 mo. history dyspnea, productive cough, subjective fevers, asthma, rheumatoid arthritis, fibromyalgia, schizoaffective disorder, hypertension. Respiratory symptoms coincided with EC use 7 mo. prior. N/A 7 mo. history of dyspnea, productive cough, subjective fever. Mild tachycardia Abstained EC use; prescribed medication No EC brand, EC refill fluid specified. 7 mo. history of EC use (2) Exogenous lipoid pneumonia due to EC use. Symptoms improved after abstained EC use; chest radiograph showed mild diffusion impairment but no permanent damage. First respiratory case report attributed to EC use. Three other known cases of lipoid pneumonia linked to EC have been reported. McCauley et al. (2012)
43, M, FR Pulmonary lung adenocarcinoma and isolated brain metastasis. 45 pk-yr, history; cessation attempt w/ nic. patch (21 mg) and cont. Smoking 20 cig/day. Bronchial syndrome associated w/ deterioration of pulmonary function tests after starting EC use. Abstained EC use La dynamique (CIGARTEX); EC refill fluids: Kentucky and Eastern (19 mg/ml). Vaped 25 ×/day, 5–6 puffs/session (125–150/day). Subacute bronchial toxicity After 48 h. improvement in cough, sputum, breathlessness; by day 7 all symptoms resolved. Hureaux et al. (2014)
20, M, USA Previously healthy; family history of pulmonary embolism N/A Shortness of breath, tachycardia. Prescribed medications No EC brand, EC refill fluid specified. Acute eosinophilic pneumonia Resolved health effects with medical care and treatment Trigger undesired resp. effects in previously healthy individual. Thota and Latham (2014)
43, M, US History of hypertension. Unspecified 7 yr. smoking history. Shortness of breath, pleuritic chest pain. Breathing treatments and antibiotic treatments. No EC brand, EC refill fluid specified. Pneumonia and bilateral pleural effusions. Dismissed after two days hospitalization and resolved. Fourth case of pneumonia and first case of pleurisy Moore et al. (2015)
60, M, USA N/A Unspecified smoking history Shortness of breath, pleuritic Medical care received No EC brand specified Unspecified flavors with diacetyl Acute lipoid pneumonia. Dismissed after two days hospitalization and resolved. Second case of lipoid pneumonia in USA Atkins and Drescher (2015)
31, F, USA N/A Unspecified smoking history Shortness of breath Medical care received No EC brand, EC refill fluid specified. Inhalation injury and suspected hypersensitivity Dismissed and in two days health effects resolved. Inhalation of diacetyl in EC refill fluids is a health concern. Modi et al. (2015)
Gastrointestinal
35, M, USA 1.5 year history of pan-ulcerative colitis (UC); began 4 wks. after smoking cessation. Past smoker; details not provided. Before EC use: daily bloody bowel movements w/ severe incontinence EC use initiated No EC brand, EC refill fluid specified mean 105 puffs/day (range: 45–191). Effects for 12 weeks Relapsed medically refractive UC after EC use. EC use was associated w/ steroid-free clinical remission in patient UC. EC use w/ smoking cessation helped symptoms. Lee et al. (2013)
49, F, FR UC affecting rectum and rectum and sigmoid colon (diag. 2004); Hysterectomy for endometriosis (diag. 2008) 20 cigarettes/day for 20 yrs. UC symptoms began 3 mo. after patient quit smoking; bloody diarrhea. Patient resumed smoking 9 mo. after UC diagnosis No EC brand info; 30 mg liquid nicotine/day w/ use of disposable cartridges of 10 ml every 5 days at 16 mg/ml Smoking dependent UC Clinical remission within a few days of resumed smoking Indicates nicotine may not be the only factor with protective effects for UC. Camus et al. (2014)
1 day old infant, M, USA Gastrointestinal bleeding N/A Abdominal distention, respiratory distress. Double barrel ileostomy w/ subsequent surgery procedures N/A; suspected cause due to in utero exposure, mother using EC ~ 30–50 ×/day; ~ 50–70 ×/day. No EC brand, EC refill fluid specified. Isolated chronic necrotizing enterocolitis. At 6 month infant recovered; 9 month development milestone met. First pregnancy health effect linked to EC Gillen and Saltzman (2014)
Cardiovascular
70, F, USA Hypertension, hyperlipidemia osteoarthritis, allergic rhinitis, remote history of breast adenocarcinoma; right hip fracture, hip during arthroplasty. 40 pack-year history; attempted cessation in preceding 5–6 months Subsequent hematoma drainage, patient developed 3 ep. of asymptomatic acute atrial fibrillation (AF) Patient asked to discontinue EC use. No EC brand, EC refill fluid specified Paroxysmal AF Eliminated episodes of AF for remainder of hospitalization. Although the patient has significant medical history, all AF ep. occurred only EC use. Monroy et al. (2012)
24, M, TR Previously healthy 1 pack/day for 4 yrs.; 1 mo. cessation attempt. Chest pain 4 h prior to liquid nicotine use. Prescribed med. No EC brand specified; tobacco flavored nicotine concentration 16 mg/day use. Acute myocardial infarction Evaluated one month later and free of symptoms. Myocardial infarction in individuals < 30 yr. of age is rare. Kivrak et al. (2014)
Neurological
39, M, FR Previously healthy 60 cig/day for 20 yrs. 7 day history of headaches and 2 seizures. Prescribed med and abstained EC use; cont smoking 10–15 cig/day w/ nicotine patch. No EC brand specified; Nicotine concentration was 12 mg/ml. Reversible cerebral vaso-constriction syndrome. Headache resolved by day 3, no recurrence of seizures. First neurological negative case report associated with EC use. Vannier et al. (2015)
Immune
28, M, GR Chronic idiopathic neutrophilia CIN) since 2005; hyperlipidemia treated w/ med.; no other history of infection, trauma, or fever. Smoker since 1996; 9 pack-yr After EC use, patient quit smoking in 10 days and leukocyte and C reactive protein normalized in 6 mo. Prescribed med. for elevated LDL levels, cont. EC use No EC brand specified; nicotine concentration 9 mg/ml Smoking cessation w/ EC use reversed CIN. First positive health affected attributed to EC use. Farsalinos and Romagna (2013)
Accidental nicotine poisonings
10 mo. old infant, M, USA N/A N/A Vomiting, tachycardia grunting respirations, truncal ataxia developed after ingestion of EC refill fluid. Unspecified medical treatment. N/A; affected accidental ingestion of Wintergreen EC refill fluid w/ nicotine (18 mg/ml) but unknown PG, glycerin, and flavoring concentrations. Nicotine poisonings Recovered baseline health after 6 h of ingesting EC refill fluid. First reported case of nicotine poisoning in a young child in literature. Bassett et al. (2014)

Nicotine
Possible side effects of nicotine.[129]
A 2015 comparative risk analysis of drugs found the nicotine's margin of exposure (MOE) values were in a lower risk range than cocaine, heroin, and alcohol, whereas its MOE values was in a higher risk range than MDMA, methamphetamine, and methadone.[130] Shown above is the MOE for daily drug use from the analysis.[130]

Pregnant women, breastfeeding mothers, and the elderly are more sensitive to nicotine than other individuals.[19] There are safety issues with the nicotine exposure from e-cigarette use, which may cause addiction and other adverse effects.[20] Nicotine is regarded as a potentially lethal poison.[13] Concerns exist that vaping can be harmful by exposing users to toxic levels of nicotine.[13] At low amounts, it has a mild analgesic effect.[19] At sufficiently high doses, nicotine may result in nausea, vomiting, diarrhea, salivation, bradyarrhythmia, and possibly seizures and hypoventilation.[131] High doses can induce deleterious effects on the growth of osteoblasts.[132] Higher-doses leads to loss of nicotinic receptor specificity and induces cholinergic toxicity.[85] The highest-doses can lead to coma.[85] 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.[13] The health effects of nicotine in infants and children are unclear.[131]

E-cigarettes provide nicotine to the blood quicker than nicotine inhalers.[38] The levels were above that of nicotine replacement product users.[13] E-cigarettes seem to have a pharmacokinetic nicotine profile closer to nicotine replacement products than with traditional cigarettes.[133] How efficiently different e-cigarettes give nicotine is unclear.[13] Serum cotinine levels are comparable to that of traditional cigarettes,[134] but are inharmonious and rely upon the user and the device.[135] Blood nicotine levels raised more gradually and took more time to get to peak concentration with e-cigarettes than with traditional cigarettes.[136] Vaping was found to have comparable levels of nicotine urinary metabolites to those who were tobacco and smokeless tobacco product users.[46] Though, the oxidative nicotine metabolites were less in those who were vaping.[46] Evidence indicates that some vaping products may deliver the same amount of nicotine as traditional cigarettes.[44] There is fair evidence that chance and degree of dependence are less for e-cigarettes than traditional cigarettes, according to a 2018 National Academies of Sciences, Engineering, and Medicine report.[137] It not clear the level of addictiveness of e-cigarettes, compared with traditional cigarettes, according to a 2018 PHE report.[138] The report also stated "nicotine addictiveness depends on a number of factors including presence of other chemicals, speed of delivery, pH, rate of absorption, the dose, and other aspects of the nicotine delivery system, environment and behaviour."[139] Users vaping without using nicotine exhibited symptoms of dependence, according to a 2015 study.[140] E-cigarette packages and advertisements require health warnings under US law, stating "WARNING: This product contains nicotine. Nicotine is an addictive chemical."[44]

Graphic from the 2018 Centers for Disease Control and Prevention's report entitled Why Is Nicotine Unsafe for Kids, Teens, and Young Adults?[141]

See also

Notes
  1. A 2019 review states, "Experts who favor abstinence contend that if ENDS regulations are too lax, the e-cigarette industry will repeat tobacco manufacturer offences including using media to target youth and misleading the public through false safety claims. They point out that ENDS contain harmful chemicals, lack safety oversight, may renormalize smoking behaviors, and if unchecked, could provide a gateway to tobacco. From this perspective, ENDS may compromise existing tobacco control efforts and have a negative public health impact. Conversely, from a harm reduction perspective, advocates argue that ENDS provide a safer alternative to smoking, especially for smokers who do not desire to quit or find it difficult to do so. They are concerned that over-regulation will extinguish the ENDS market and eliminate the potential for a public health benefit."[3]

Bibliography
  • McNeill, A; Brose, LS; Calder, R; Bauld, L; Robson, D (February 2018). "Evidence review of e-cigarettes and heated tobacco products 2018" (PDF). UK: Public Health England. pp. 1–243.
  • Stratton, Kathleen; Kwan, Leslie Y.; Eaton, David L. (January 2018). Public Health Consequences of E-Cigarettes (PDF). National Academies of Sciences, Engineering, and Medicine. National Academies Press. pp. 1–774. doi:10.17226/24952. ISBN 978-0-309-46834-3. PMID 29894118.
  • McNeill, A; Brose, LS; Calder, R; Hitchman, SC; Hajek, P; McRobbie, H (August 2015). "E-cigarettes: an evidence update" (PDF). UK: Public Health England. pp. 1–113.
  • "Electronic Nicotine Delivery Systems and Electronic Non-Nicotine Delivery Systems (ENDS/ENNDS)" (PDF). World Health Organization WHO. August 2016. pp. 1–11.
  • Wilder, Natalie; Daley, Claire; Sugarman, Jane; Partridge, James (April 2016). "Nicotine without smoke: Tobacco harm reduction". UK: Royal College of Physicians. pp. 1–191.

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