# Health effects of electronic cigarettes

The health effects of e-cigarettes (e-cigarettes) are generally claimed to be less harmful than those of smoking, but worse than not smoking at all. However, health effects are a function of inhaled materials, of associated behavior changes (notably traditional cigarette smoking), of how and how often the products are used, over what period, manufacturing/distribution quality control, marketing, the regulatory environment, and the actual user population.
Overall, a 2025 US study that analyzed data from the National Vital Statistics System (NVSS), the Behavioral Risk Factor Surveillance System (BRFSS), the National Health Interview Survey (NHIS), and the National Survey on Drug Use and Health (NSDUH) concluded that e-cigarettes had preserved 677,000 life–years from 2011 to 2019.
The public health community is divided over the use of these devices to reduce/prevent smoking. As of 2017 they were not approved by the US Centers for Disease Control and Prevention (CDC) as a smoking cessation product, and in 2020 became regulated as a tobacco product (despite not containing tobacco). However, In the United Kingdom, a 2021 review by Public Health England (PHE) reported vaping to be around 95% less harmful than smoking.
E-cigarette use (vaping) carries some level of health risks. Reported risks (compared to not smoking) include exposure to toxic chemicals, increased likelihood of respiratory and cardiovascular diseases, accelerated cancer development, reduced lung function, reduced cardiac muscle function, increased inflammation, increased drug dependency, and damage to the central nervous system. Misuse, accidents, and product malfunction issues increase risks such as nicotine poisoning, contact with liquid nicotine, and fires.

## E-cigarettes

An electronic cigarette (e-cigarette), or vape, is a device that simulates smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank. Instead of smoke, the user inhales vapor. As such, using an e-cigarette is often called "vaping".
Various e-liquids offer different nicotine strengths and flavors.
Common ingredients are propylene glycol, glycerin, flavorings, and nicotine. Propylene glycol and glycerin typically comprise 95% , with the remaining 5% combining flavorings, nicotine, and other additives. Flavorings may contain menthol, sugars, esters, and pyrazines. Flavor components include diacetyl, acetoin, and 2,3-pentanedione (buttery flavor), eucalyptol, camphor and cyclohexanone (minty flavor), cinnamaldehyde (cinnamon flavor), benzaldehyde (cherry or almond flavor), cresol (leathery or medicinal flavor), butyraldehyde (chocolate flavor), and isoamyl acetate (banana flavor), methyl salicylate, pulegone, ethyl salicylate, eugenol, diphenyl ether, and coumarin. A 2017 review added 1,3-butanediol, 1,3-propanediol, ethylene and diethylene glycol, safrole, ethyl vanillin, and α-thujone to the list of ingreidents.
Caffeinated e-liquids typically contain considerably less caffeine than dietary products. E-liquids are available with vitamins or cannabis flavors. E-cigarettes (mods) are available that can vaporize herbs, oils, or fruits. Dual-function devices handle both concentrates and e-liquids using multiple cartridges.
More than 90% of e-liquids contain nicotine. Some are unflavored. Water replaces propylene glycol in some products. E-liquids may contain THC or other cannabinoids. Some e-liquids contain a little alcohol.
E-liquids are not required to use only US Pharmacopeia grade nicotine, a tobacco plant, or tobacco dust extract, or a synthetic nicotine. Nicotine levels vary. A user survey reported that 97% of respondents used nicotine e-liquids.
In 2009, FDA reported tobacco-specific nitrosamines (TSNAs), diethylene glycol, cotinine, anabasine, myosmine, and beta-nicotyrine in e-liquids. TSNAs N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosoanabasine, and nitrosoanatabine were detected in five e-liquid samples from two companies at levels comparable to other nicotine replacement products. TSNAs present in tobacco smoke were reported in trace amounts. A 2013 review of other e-liquids did not detect diethylene glycol. The majority of the e-liquids analyzed contained NNN from 0.34 to 60.08 μg/L and NNK from 0.22 to 9.84 μg/L. The FDA warned several e-cigarette companies for selling e-cartridges and refill solutions containing active pharmaceutical ingredients such as rimonabant (Zimulti) for weight loss purposes and reducing smoking, and tadalafil (for erictile dysfunction). FDA analyses reported the presence of am,ino-tadalafil rather than tadalafil, and rimonabant and one of its oxidative products.
E-liquids often contain unknown and/or undisclosed substances.
Poor quality control may allow nicotine and TSNAs to be present in e-liquids labelled 'no nicotine'. Some e-liquid were reported to contain low levels of anthracene, phenanthrene, 1-methyl phenanthrene and pyren. A 2015 study reported hydrocarbons, terpenic compounds and aldehydes, particularly formaldehyde and acrolein in some e-liquids.

## Risk context

When evaluating the health effects of some activity, a reasonable question is "what is the practical alternative?" If the alternatives are worse, then the activity must be measured against the alternatives. If the alternative is smoking, the answer might be different than if the alternative is simply to avoid nicotine. This is because the health impacts of smoking are strongly negative, while the impacts of avoiding nicotine entirely are positive.

### Smoking

E-cigarette vapor does not contain tobacco and does not involve combustion, therefore users do not encounter several harmful constituents of tobacco smoke, such as ash, tar, and carbon monoxide. A 2014 review concluded 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. However, e-cigarette vapor has components not present in traditional cigarettes, which potentially offset some of these benefits.
Smokers can use e-cigarettes for various purposes. As an aid to quitting smoking, vaping is a temporary activity that reduces smoking and terminates once the smoker has completed the transition away from nicotine. To the extent that vaping aids the transition, its health effects are positive.
Alternatively, smokers can substitute vaping for smoking without intending to transition. In this context, vaping is still preferred. However, if vaping is used as a way to get nicotine in situations where smoking is not convenient, vaping may negatively affect health.
Other smoker-transition aids are available and may offer better safety and/or effectiveness profiles then vaping. Given equal effectiveness, relatively safety considerations would become paramount. However, a large-scale 2025 analysis indicated that other smoking cessation products are less effective at aiding transition than vaping.

### Abstinence

Vaping presents health risks that are definitionally higher than those of simple abstinence, as no independent health benefits have been reported, while nicotine and cannabis have well-established harms. This comparison is relevant because some never-smokers adopt e-cigarettes for these drugs. Once dependence is established, users may be more likely to take up smoking.

## Individual effects

Health effects for non-smokers must be considered in absolute terms for long-term use as well as the risk of transition into traditional cigarettes, while for smokers the relative risks are paramount, and if used as a quitting aid, any short-term effects are most important.

### Non-smokers

E-cigarettes create nicotine dependence in non-smokers. E-cigarettes may act as a gateway drug to smoking, particularly among youth. Pregnant or nursing women and the elderly are more sensitive to nicotine than other individuals.

### Smokers

Used to transition to abstinence, e-cigarettes end the consumption of nicotine and the other harmful substances in tobacco smoke and later any harmful e-liquid ingredient. However, if abstinence is not achieved, e-cigarettes could mean increased nicotine dependence (by adding vaping to smoking) and ongoing harm from other e-liquid ingredients.
Health benefits associated with transitioning from smoking to vaping include decreased post-smoking weight gain and improved exercise tolerance.
Even a partially successful transition may allow smokers to reduce their cigarette consumption with related health benefits. A 2022 Cochrane review concluded that vaping increased quit rates compared to e-cigarettes without nicotine and compared to nicotine replacement therapy, although it did not compare vaping to other methods.
The relative safety of electronic versus conventional cigarettes is disputed. 2015$^{:76}$ and 2018 Public Health England (PHE) reports claimed that vaping is "at least 95% less harmful than smoking".$^{:175}$ The Royal College of Physicians, the Royal Society for Public Health, and the National Health Service backed these claims. The estimate was limited by "lack of hard evidence for the harms of most products on most of the criteria". The research was funded by EuroSwiss Health and was criticized for its weak methodology, lack of specific evidence, and for financial ties to the tobacco industry. The estimate was disputed in medical journals. Reviews in 2016 and 2018 claimed that the harm from e-cigarettes is much higher than the "95% safer" figure.
A 2025 RCP review reported that e-cigarettes sold in England (which allow nicotine strength of no more than 20 mg/ml) are unlikely to exceed 5% of the harm of cigarettes for non-pregnant adults. This claim is consistent with the 2018 view of the US National Academies of Sciences, Engineering, and Medicine.

### General

Device defects can result in e.g., battery explosions and may cause burns or other injuries.
Concentrated e-liquid exposure can come by leaks or spills. Nicotine poisoning can occur by ingestion, inhalation, or absorption via the skin or eyes.
A 2018 review concluded that exposure to second-hand vapor can reduce lung function.
A 2015 review concluded that adverse effects are mostly associated with short-term use and the reported adverse effects decreased over time.

### Neurological

Many effects on the nervous and the sensory systems are possibly related to nicotine overdose or withdrawal. A 2016 study reported that an e-liquid containing 23% alcohol was linked to reduced performance on the Purdue Pegboard Test. A 2017 study reported harm to neurons along with tremors and spasms.

### Injuries

E-cigarettes typically use lithium batteries, which may cause injury if defective or misused. A 2015 PHE report concluded that fire risks from e-cigarettes "appear to be comparable to similar electrical goods".$^{:83–84}$ A 2016 study reported that the explosion risk was low.
E-liquid ingredients may be flammable.
A 2014 review claimed that some users add more or larger batteries to nonadjustable e-cigarettes, which may lead to battery leakage or explosion.
Another 2016 study assembled reports of 92 explosion, fire, or overheating events, with related injuries in 47 individuals. Prominent harms included 2 cervical vertebral fractures, 1 palate fracture, 3 instances of damaged teeth, 33 thermal burns, 4 chemical burns, and 5 lacerations. A 2017 study reported that most e-cigarette fires are triggered by batteries overheating and igniting.$^{:Summary,Conclusion14-1.,9}$ In 2018 PHE reported six UK case studies involving e-cigarettes with burns.$^{:144}$
An e-cigarette explosion or fire can induce serious burns and harms.$^{:149}$ Explosions have resulted in lost teeth, neck fractures, and burns from combustion and/or battery acid. Reported burns covered from 1% to 8% of body area. They were most commonly reported in the lower extremity, hands, head and neck, and genitalia. Explosions in some cases produced 2nd and 3rd degree burns. A 2018 review concluded that some 50% needed surgical management.
A 2017 review observed that several reported injury cases occurred while the e-cigarette was carried in a pocket. The pocket may have sufficient moisture to start a chemical reaction within the lithium-ion battery, while the presence of metal objects can create a short-circuit, leading to an explosion. Burn risk extends to bystanders.
The United States Fire Administration reported 195 occasions of e-cigarette fires and explosions between January 2009 and December 2016. These incidents resulted in 133 acute injuries, of which 38 (29%) were severe. A 2017 review concluded that 80% of e-cigarette explosions occurred during battery charging, many by 3rd-party power adaptors that used inappropriately high charge rates that led to thermal runaway. Some vendors assembled e-cigarettes from incompatible parts.
Burn events while on home oxygen therapy have been reported, leading Health Canada in 2014 to warn of fire risk. The heating element in vaping devices can get hot enough to ignite in the presence of oxygen.

### Poisoning

E-cigaratte nicotine poisoning occurs via ingestion, inhalation, or absorption via the skin or eyes.
Such poisoning is apparently rare, suggested by the fact that reviews highlight individual cases. In 2014, an infant died from choking on an e-cigarette component. As of 2016 four adults were reported to have died in the US and Europe after intentionally ingesting e-liquid. Two children, one in the US in 2014 and another in Israel in 2013, died after ingesting liquid nicotine. A two-year-old girl in the UK in 2014 was hospitalized after licking an e-cigarette liquid refill.
A 2022 concluded that toxicity can come from aerosols containing toxic chemicals or excessive concentrations of nicotine as an e-liquid.
A 2014 review concluded that users may alter e-liquid contents, adding substances such as alcohol or nicotine, possibly making them toxic.
As of 2014, calls to US poison control centers involved inhalations, eye exposures, skin exposures, and ingestion, in both adults and children. A 2016 study reported minor, moderate, and serious adverse effects. Minor effects correlated with e-liquid poisoning were tachycardia, tremor, chest pain and hypertension. More serious effects were bradycardia, hypotension, nausea, respiratory paralysis, atrial fibrillation and dyspnea. Initial symptoms included rapid heart rate, sweating, feeling sick, and vomiting. Delayed symptoms included low blood pressure, seizures, and hypoventilation. Rare serious effects included coma, seizure, trouble breathing, and heart attack. After examining poison control centers' reports between 2010 and early 2019, FDA reported that, between the poison control centers and FDA, 35 cases of seizures mentioned use of e-cigarettes.
From 2011-2019, cases of accidental poisoning from nicotine e-liquids grew rapidly in the US. From 1 September 2010, to 31 December 2014, 58% of e-cigarette calls to US poison control centers were related to children under 6. In 2014 Centers for Disease Control and Prevention (CDC) reported that 51.1% of the calls to US poison centers due to e-cigarettes were related to children under age 5, and while 42% of calls were related to people age 20 and older. 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. Severe outcomes were more than 2.5 times more frequent in children exposed to e-cigarettes and nicotine e-liquid than with traditional cigarettes.
US poison control centers reported that 92.5% of children who came in contact with nicotine e-liquid swallowed it during the period from January 2012 to April 2017.
Most frequent adverse effects from ingestion :
| Effect | Frequency (%) |
| 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 |
| cough | 4.5 |
In 2016 American Association of Poison Control Centers (AAPCC) reported 2,907 exposures regarding e-cigarettes and liquid nicotine. The yearly nicotine exposure rate in the US involving children went up by 1,398% from 2012 to 2015, later dropping by 20% from 2015 to 2016. In 2017 the National Poison Data System stated that exposures to e-cigarettes and liquid nicotine among young children was rising significantly.

### Respiratory

As of 2015, the long-term lung function effects of vaping were unknown.$^{:12}$ A 2014 study reported that limited evidence suggests that e-cigarettes produce less short-term effects on lung function than traditional cigarettes. As of 2015 many e-liquid ingredients had not been examined in the lung.
As of 2017 e-cigarette effects on asthma and other respiratory diseases had not been assessed.
A 2015 review concluded that e-cigarettes may induce acute lung disease.
A 2018 study reported correlations between vaping and pleural effusions. A 2015 study reported that e-cigarette vapors can induce oxidative stress in lung endothelial cells. A 2016 review concluded that e-cigarette vapor that triggered constant lung inflammation could result in lung pathogenesis and induce diseases such as chronic obstructive pulmonary disease and fibrosis. A 2018 review concluded that e-cigarette vapors can result in acute endothelial cell injury, but the long-term effects were uncertain.$^{:Summary,7}$ A 2017 review concluded "Exposure to nicotine that was specifically generated by the use of e-cigarettes, was shown to promote oxidative stress and impairment of autophagy, which in turn serves as a potential mechanism leading to development of chronic obstructive pulmonary disease." A 2014 case report observed the correlation between sub-acute bronchiolitis and vaping. After quitting vaping the symptoms improved. Vaping causes bronchospasm. Adolescents who vaped had a higher frequency of chronic bronchitis symptoms.
A 2015 review reported that the long-term effects regarding respiratory flow resistance were unknown. A 2014 review concluded that e-cigarettes reduced lung function, but much less than traditional cigarettes. A 2015 clinician's guide stated that 5 minutes of vaping considerably increased lung airflow resistance. A 2013 review concluded that a single e-cigarette increased airway resistance.
A 2014 study reported higher levels of exhaled nitric oxide, which was associated with lung inflammation. A 2014 review concluded that harmful effects to cardiovascular and respiratory functions after short-term use of e-cigarettes were appreciably milder than traditional cigarettes. A 2015 review concluded that short-term use increased respiratory resistance compared to traditional cigarettes.
A 2018 study reported that adolescent vapers with asthma or other respiratory ailments could have greater odds of increasing respiratory symptoms and aggravations.$^{:Vulnerable/SusceptiblePopulations,CysticFibrosis,448}$ In 2018 PHE reported "There have been some studies with adolescents suggesting respiratory symptoms among EC experimenters. However, small scale or uncontrolled switching studies from smoking to vaping have demonstrated some respiratory improvements."{$^{:174}$ A 2017 review concluded "among a population of 11th-grade and 12th-grade students in California, vaping was associated with twice the risk of respiratory symptoms, and the risk increased with more frequent e-cigarette use."
E-cigarette particles are small enough to enter the alveoli and to go deep in the lungs and enter into systemic circulation. A 2017 study reported that vapor containing particulate matter with a diameter of 2.5 μm enters the circulation via the cardiopulmonary system, with a large deposit in the respiratory tract. A 2014 review concluded that metal nanoparticles can deposit in the alveolar sacs with possible pulmonary toxicity. A 2015 study reported that particle sizes differ across devices with impacts on respiratory tract depositions, and without regard to e-liquid.
A 2019 case study of hard-metal pneumoconiosis cannabis vapers reported cobalt, nickel, aluminum, manganese, lead, and chromium in the vapor. Metal-induced toxicity in the lung can result in long-term/permanent lung scarring.
A 2018 review concluded that exposure to vapor has adverse effects on lungs and pulmonary function. Repeated acrolein exposure causes chronic pulmonary inflammation, reduction of host defense, neutrophil inflammation, mucus hypersecretion, and protease-mediated lung tissue damage, which are linked to the development of chronic obstructive pulmonary disease (COPD). Although e-cigarette aerosol also exposes users to highly oxidizing free radicals, their chemical characteristics is unclear.
It further reported that vapers experienced decreased expression of immune-related genes in their nasal cavities, more so than smokers. By contrast, vaping upregulates expression of platelet-activating factor receptor (PAFR) in nasal epithelial cells; PAFR is an important molecule involved in the ability of S. pneumoniae, (leading cause of bacterial pneumonia), to attach to cells.
A 2020 study reported that vaping led to lung injuries that include hypersensitivity pneumonitis (HP), diffuse alveolar hemorrhage (DAH), acute eosinophilic pneumonia (AEP), diffuse alveolar damage, organizing pneumonia (OP), lipoid pneumonia, and giant cell interstitial pneumonia (GIP). A 2016 study reported that adverse effects may include airway resistance, irritation of the airways, eyes redness, dry throat, and increase in allergic airway inflammation with elevated infiltration of inflammatory cells including eosinophils into airways. A 2015 study reported that the most reported short-term adverse effects were mouth and throat irritation, dry cough, and nausea. Another 2016 study reported nose bleeds, change in bronchial gene expression, release of cytokines and proinflammatory mediators.

#### Youth

A 2016 review concluded that nicotine exposure harms youths' growing brains. Vaping is associated with a positive association of vaping and chronic bronchitis among US high school juniors and seniors; which persisted among former users. Vaping was associated with an increased diagnosis of asthma and asthma-related school absences among Korean never-smoker high school students. A 2018 review concluded that child vapers had a higher likelihood of more and more significant adverse effects than child smokers. Significant harmful effects included cyanosis, nausea, and coma.

#### 2019–2020 vaping lung injury outbreak

An outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) began in 2019 among users of illegal, unregulated cannabis vaping products, almost exclusively in the United States. The first cases were identified in Illinois and Wisconsin in April 2019; as of 18 February 2020, a total of 2,807 hospitalized cases, including 68 deaths, had been confirmed. According to the U.S. Centers for Disease Control (CDC), "Vitamin E acetate is strongly linked to the EVALI outbreak...Evidence is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC or non-THC products".
Cases peaked in September 2019, and declined thereafter. The decline led CDC to stop reporting EVALI cases in February 2020, but as of December 2020, continued to monitor cases arriving in emergency departments. Some states continued to record new EVALI cases. As of January 2022, California had reported at least 40 cases diagnosed after February 2020. As of March 2022, EVALI cases continued to be diagnosed. At least 73 cases were diagnosed in Utah after February 2020.

### Cardiovascular

A 2018 review concluded that the specific role of nicotine in cardiovascular disease had not been established.
A 2023 review concluded that vaping causes significant, potentially harmful effects on many cardiovascular parameters. A 2024 review attributed cardiovascular effects to oxidative stress, inflammation, endothelial dysfunction, atherosclerosis, hemodynamic effects, and platelet function. A 2019 review reported limited evidence of vaping's adverse impacts on endothelial function and arterial hardening. A 2017 review concluded that vaping could exacerbate adverse cardiovascular effects among those who already have cardiovascular disease. Studies of aldehydes, particulates, and flavorings reported mixed impacts on cardiovascular health. A 21017 review stated that low amounts of aldehydes are a health concern, particularly among individuals with cardiovascular disease. A 2014 review concluded that while vaping reduces cardiac muscle function and increases inflammation, these changes were non-significant. A 2017 review concluded that vapor particles can enter circulation via the airways.
Many vapor components impact atherosclerosis. Case reports from 2014 documented possible cardiovascular adverse effects, mostly via improper use. However ,these effects were reduced compared to traditional cigarettes.
A 2016 review concluded that vaping generates sympathomimetic effects. A 2016 review concluded that there could be a risk for conditions such as tachycardia-induced cardiomyopathy. A 20154 clinician's review reported that short-term effects included increases in blood pressure and heart rate. A 2017 review concluded that these increases among smokers who vaped was lower than with smoking. A 2016 study reported vaping increased aortic stiffness in people with no cardiovascular risk factors, an d that the increase was lower than smoking. A 2017 review concluded that habitual vaping was associated with oxidative stress and a shift towards cardiac sympathetic activity, which are both associated with a risk of developing cardiovascular disease. A 2017 review highlighted an association between 2.5 μm particulate exposure and cardiovascular disease.
A 2018 review noted that nicotine is not the only biologically active component in e-cigarette aerosol. Vapor particles are of broadly similar size to those in traditional cigarettes. These particles can be biologically active, trigger inflammatory processes, and are directly implicated in causing cardiovascular disease and acute cardiovascular events. Their dose-response effect is nonlinear, with substantial increases in cardiovascular risk with even low exposure levels. Vapor induces platelet activation, aggregation, and adhesion, which are associated with increased cardiovascular risk. These changes produce rapid deterioration of vascular function. E-cigarette and traditional cigarette smoking in individuals with no known cardiovascular disease exhibit similar inhibition of artery dilation in response to the need for more blood flow. This change reflects damage to vascular endothelium and increases the risk of long-term heart disease and an acute event such as a myocardial infarction (heart attack). Vaping is accompanied by a shift in balance of the autonomic (reflex) nervous system toward sympathetic predominance, which is also associated with increased cardiac risk. Daily vaping is correlated with an increased risk of myocardial infarction in health surveys.

#### Other

A 2015 doctor guide mentioned major adverse events that included hospitalizations for pneumonia, congestive heart failure, seizure, rapid heart rate, and burns. However, no causal relationship to vaping was proven.

##### Gastrointestinal (GI) system

A mucosal intestinal barrier separates the external and internal environments within the body. This barrier allows water, ions, solutes, and nutrients to cross the barrier while excluding bacteria and toxins. Tight junctions (TJ) help with the construction and permeability of the barrier in the gut by firmly securing joints. Chronic, repetitive exposure to e-cigarettes damages this barrier by breaking the TJs, which causes gut inflammation, ,assage of bacteria. altering gene expression. A 2021 study reported that chronic use of nicotine-free e-cigarettes still caused inflammation and decreased TJ markers.
A 2022 study reported that common GI health effects include nausea, vomiting, gastrointestinal discomfort, xerostomia, oral mucositis, gum bleeding, gingivitis, gastric burning, altered bowel habits, and acid reflux. Chronic exposure also drives inflammation in the colon.

##### Nervous system

A 2024 review concluded that nicotine exposure has detrimental effects on the nervous system, especially during adolescence. Exposure during developmental stages changes brain structure and function. Vaping is linked to impairment of cognitive processes, increased mood disorders and addiction, damage to functions such as memory, reasoning, impulse control, and attention. A 202 study reported lower gene expression, reducing occludin, which compromises the stability and strength of the blood-brain-barrier, resulting in neurovascular dysfunction, neuroinflammation, and cognitive defects. A 2010 study reported that short-term nicotine use excites the autonomic ganglia nerves and autonomic nerves.

##### Oral cavity

A 2018 review reported little evidence indicating that vaping is less damaging than smoking for periodontal disease$^{:Summary,Conclusion12-1.,9}$ and can lead to increased risk of periodontal disease.j A 2017 review concluded that nicotine and flavorings may damage periodontal ligaments, stem cells, and gingival fibroblasts in cultures from aldehydes and/or carbonyls from vapor. A 2016 clinicians guide state that e-cigarettes could harm the periodontium because of the effects of nicotine on gum tissues and the immune system. A 2021 study reported that vaping resulted in nicotine stomatitis, hairy tongue, angular cheilitis, and oral mucosal lesions. E-cigarettes are not implicated in cancer.

### Cannabinoids

Cannabinoid-enriched e-liquids require sophisticated processing, and may lack information on quality control, expiry date, conditions of preservation, or toxicological/clinical assessment. It is assumed that vaporizing cannabinoids at lower temperatures is safer because it produces smaller amounts of toxicants than a traditional cigarette. As of 2015 the health effects specific cannabinoid vaping were unknown. However, cannabinoid e-cigarettes mixed with other diluents and chemicals was associated with EVALI, although a 2017 study rejected this.

## Public health effects

Various studies rate the public health impacts of vaping as far less negative than those of smoking.

### Second-hand vapor

E-cigarette emissions are not comparable to cigarette smoke as their chemical composition is completely different. Vapor content varies depending on the e-liquid, the device, and usage. $^{:84}$ Exhaled vapor consists of mixtures of nicotine, ultrafine particles, primarily propylene glycol, glycerin, flavorings, and aroma transporters, aldehydes, and volatile organic chemicals (VOC) that form a visible fog. The vapor has a half-life of about 10 seconds; smoke lasts 100 times longer. A 2014 study reported that e-cigarettes increased levels of carcinogenic polycyclic aromatic hydrocarbons in the surrounding air.
Vapor particles are larger than smoke particles, with a mean droplet size of 600 nm (inhaled) and 300 nm (exhaled) along with particles with a diameter of around 2.5 μm. Exhaled vapor concentration is 5 times lower than cigarette smoke. Particle density measured 6 to 880 times lower.
One 2015 study reported that exhaled vapor might have significant adverse effects. Another reported that e-cigarettes that do not contain nicotine may also generate hazardous vapors and could present a second-hand risk. A third reported that vapor may include propylene glycol aerosols at levels that can cause eye and respiratory irritation and exceed California Environmental Protection Agency standards. A 2017 study reported that people living with e‐cigarette users had increased salivary nicotine concentrations. Another reported that some non-users reported adverse effects from second-hand vapor.
A 2016 survey reported that nearly half of middle and high school students had been exposed.
As of 2014 neither the long-term nor short-term health effects from exhaled vapor were known. A 2017 review concluded that the few studies that examined the effect of indoor air quality on human test subjects in natural settings produced inconsistent results. As of 2018 limited only information of the effects of exhaled vapor on children was available.
Between January 2012 and December 2014, FDA published 35 adverse effect reports regarding second-hand vapor exposure.
A 2018 study reported PM$_{2.5}$ levels in a large hotel event room (4,023m$^3$) increased from 2–3 μg/m$^3$ to as high as 819 μg/m$^3$ (interquartile range: 761–975 μg/m$^3$) when 59–86 people were vaping. This level exceeded the US Environmental Protection Agency annual time-weighted standard for PM$_{2.5}$ of 12 μg/m$^3$.
A 2018 review concluded that bystanders absorb nicotine when people around them use e-cigarettes at levels comparable with exposure to second-hand smoke. It included a study comparing non-smokers living with vapers, with smokers, and non-users (controls). That study found cotinine (a nicotine metabolite) levels in urine were significantly elevated in the first two groups vs the controls, but were not significantly different, despite the fact that air pollution levels in the smokers' homes was much higher than in the vapers' homes (geometric mean air nicotine concentrations of 0.13 μg/m$^3$ in vapers' homes, 0.74 μg/m$^3$ in smokers' homes, and 0.02 μg/m$^3$ in the control homes). A 2014 practice guideline by NPS MedicineWise stated that serum cotinine levels were similar in bystanders exposed to either vapour or smoke.
In 2014, several groups came out against e-cigarettes. 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 e-cigarettes leads to emission of fine and ultrafine inhalable liquid particles, nicotine and cancer-causing substances into indoor air." The American Industrial Hygiene Association concluded that "e-cigarettes are not emission-free and that their pollutants could be of health concern for users and those who are exposed secondhand....[T]heir use in the indoor environment should be restricted, consistent with current smoking bans, until and unless research documents that they will not significantly increase the risk of adverse health effects to room occupants." Similarly, in 2016 the American Society of Heating, Refrigeration and Air-Conditioning Engineers (ASHRAE) updated its standard for "Ventilation for Acceptable Indoor Air Quality" to incorporate emissions from e-cigarettes into the definition of "environmental tobacco smoke," which is incompatible with acceptable indoor air quality. A 2017 French "experts statement" recommended banning vaping indoors in public and working areas.
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. 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." A 2016 WHO report stated, "While some argue that exposure to SHA [second-hand aerosol] is unlikely to cause significant health risks, they concede that SHA can be deleterious to bystanders with some respiratory pre-conditions. It is nevertheless reasonable to assume that the increased concentration of toxicants from SHA over background [air] levels poses an increased risk for the health of all bystanders."$^{:4}$
A 2013 British Medical Association (BMA) report stated "concerns that the use of e-cigarettes could threaten the norm of not smoking in public places and workplaces". Several medical organizations advocate that vaping be banned in public places and workplaces. A 2014 review concluded it is safe to infer that their effects on bystanders are minimal in comparison to traditional cigarettes. E-cigarette vapor has notably fewer toxicants than cigarette smoke.
A 2015 California Department of Public Health report stated that vapour "has been reported 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."$^{:1}$
A 2017 study reported that some chemicals could violate workplace safety standards. A review of convention studies concluded that second-hand vapor may be significant, particularly for workers who repeatedly encounter it. Exposure studies suggest that indoor vaping is higher than the smoke-free level put forth by the US Surgeon General and the WHO Framework Convention on Tobacco Control.$^{:SecondhandExposuretoE-CigaretteAerosol,Synthesis,84}$
By contrast, a 2014 review concluded that vaping probably much less harmful than traditional cigarettes. Another 2014 review suggested that vapor contaminant levels do not exceed workplace safety standards, and are mostly below 1% of permissible levels. However, workplace standards do not consider more vulnerable groups such as those in poor health, children, and infants. 2 015 PHE report concluded that e-cigarettes "release negligible levels of nicotine into ambient air with no identified health risks to bystanders".$^{:65}$

### Direct exposure

Direct exposure happens via e-liquid inhalation, ingestion, skin contact, or vapor residue accumulation on surfaces. Direct exposure is almost always inadvertent, and results from improper product use. Exposure can involve much higher concentrations than exhaled vapor.
Exposure may involve a leaking or spilled e-liquid cartridge or bottle.
E-liquid quickly absorbs into the skin and local irritation can follow. Less than 1 tablespoon can cause adverse effects such as seizures, anoxic brain trauma, vomiting, lactic acidosis,$^{:Summary,Conclusion14-2.,9}$ cardiac arrest, seizures, or coma. A potentially fatal dose for a child is 0.1–0.2 mg/kg of body weight, or 6 mg. A fatal dose for an adult is 0.5–1 mg/kg or about 30–60 mg. However the widely-used human LD$_{50}$ estimate of around 0.8 mg/kg was questioned in a 2013 review, in light of documented cases of humans surviving much higher doses; the lower fatal limit was 500–1000 mg of ingested nicotine, which is equivalent to 6.5–13 mg/kg orally.

#### Vapor build-up

E‐cigarettes can be unsafe to non-users via third-hand exposure, including children, pregnant women, nursing mothers, casino employees, housekeeping employees, and vulnerable groups.
In one scenario, indoor surfaces can accumulate nicotine-laden vapor residue. However, the extent of such contamination has not been established. A 2015 PHE report stated that an infant would have to lick 30 square meters to be exposed to 1 mg of nicotine.$^{:65}$ As with any potential hazard, childhood exploratory behavior creates risks not faced by others.

#### Risks to children

Children are more likely to mistake a colorful e-liquid container for a juice container. The US mandates child-proof packaging.

#### Self-harm

As of 2019 a few incidents of intentional self-harm by ingesting or injecting e-liquids had been reported. Death from intentional nicotine poisoning is almost unknown.$^{:63}$

### Pets

In 2017, FDA stated that e-cigarette aerosols can cause problems for both users and their pets. Some studies reported that aerosols may provide exposure to higher-than-normal amounts of nicotine and other toxic chemicals, such as formaldehyde. E-cigarettes typically use capsules to contain nicotine. Pets may find and bite them or expose themselves to the liquid refilling solution. In a 15 March 2016, letter to the editor of the Journal of the American Veterinary Medical Association, the Texas Poison Center Network reported 11 cases of dog exposures to e-cigarettes or refills. The Animal Poison Control Center stated that among nicotine toxicity cases in 2012, 4.6% related to e-cigarettes, which increased to 13.6% in 2013.

## Toxicology

The long-term health impacts of vaping are unknown, particularly given the variety of EC devices, e‑liquids, and consumption patterns. This specifically applies to nicotine and propylene glycol. Limited peer-reviewed data restricts the scope of toxicological evaluation; their cytotoxicity is unknown. A 2014 review concluded that few e-cigarettes had undergone a thorough toxicology evaluation and testing. A 2013 study claimed that they were similar in toxicity to other nicotine replacement products, but this was disputed.$^{:87}$ In 2013 the UK National Health Service noted that toxic chemical levels were 0.1% of cigarette smoke.

### Toxicant comparisons

E-cigarettes supply nicotine and other toxins at rates far below traditional cigarettes and other nicotine delivery systems:
E-cigarette toxicants compared with nicotine inhaler and cigarette smoke :
| Toxicant | Nicotine inhaler mist (15 puffs∗) | E-cigarettes (15 puffs∗) | 1 cigarette |
| Formaldehyde (μg) | 0.2 | 0.2-5.61 | 1.6-52 |
| Acetaldehyde (μg) | 0.11 | 0.11-1.36 | 52-140 |
| Acrolein (μg) | ND | 0.07-4.19 | 2.4-62 |
| o-Methylbenzaldehyde (μg) | 0.07 | 0.13-0.71 | — |
| Toluene (μg) | ND | ND-0.63 | 8.3-70 |
| p- and m-Xylene (μg) | ND | ND-0.2 | — |
| NNN (ng) | ND | ND-0.00043 | 0.0005-0.19 |
| Cadmium (ng) | 0.003 | ND-0.022 | — |
| Nickel (ng) | 0.019 | 0.011-0.029 | — |
| Lead (ng) | 0.004 | 0.003-0.057 | — |

### Carcinogenicity

Concerns about carcinogenicity arise from both nicotine and from other vapor chemicals.

#### Nicotine

Evidence from in vitro and animal research does not indicate carcinogenicity in vivo. A 2014 Surgeon General report stated that the only relevant randomized trial "does not indicate a strong role for nicotine in promoting carcinogenesis in humans". It concluded that data is insufficient "to conclude that nicotine causes or contributes to cancer in humans, but there is evidence showing possible oral, esophageal, or pancreatic cancer risks". $^{:116}$ However, a 2014 study suggested that vaping may be a risk factor for lung cancer. Nicotine in the form of nicotine replacement products is reported to be less of a cancer risk than smoking,$^{:115}$ and they vaping had not been shown to be associated with cancer.
As of 2015 it was not possible to conclude that nicotine itself is a complete carcinogen. In mice studies with NNK as an initiator, nicotine was reported to act as a promoter after injection or dermal absorption, but not after oral administration. In drinking water experiments, considerable first-pass metabolism of nicotine occurred before nicotine entered systemic circulation. As a result, serum concentration is much lower after ingestion than after intraperitoneal injection administration.
However, nicotine has been reported to promote metastasis by causing cell cycle progression, epithelial-to-mesenchymal transition, migration, invasion, angiogenesis, and avoidance of apoptosis. Nicotine promotes the growth of blood vessels, which can supply tumors and speed tumor growth. As of 2015, long-term vaping had not been assessed for malignancy in individuals with a susceptibility for tumor growth. The effects of nicotine on the sympathoadrenal system could stimulate growth in cancers already present.

##### Potential accelerant

Multiple in vitro experiments reported that nicotine in concentrations as low as 1 μM decreased the anti-proliferative and pro-apoptotic effects exerted by chemotherapeutics on multiple malignant cell lines. These effects were partially reverted by exposure to α-bungarotoxin (α-BTX), a α7-nAChR inhibitor. During radiotherapy (RT), nicotine administration was reported to increase survival of H460 and A549 lung cancer cells. This effect was likewise reduced by addition of α-BTX prior to nicotine addition and radiation. On this basis, it may be expected that use of nicotine products during cancer treatment reduces the effects due to reactions following interaction of nicotine with α7-nAChR.
Evidence from in vitro studies on cell cultures, rodents and humans inclusive of epidemiological studies indicate that nicotine may contribute in cancer development by stimulating important processes. Nicotine acts primarily by activation of nicotine acetylcholine receptors (NAR) and nicotine binds to these receptors with a higher affinity than acetylcholine. Furthermore, the tobacco-specific nitrosamines (TSNAs) NNN (N′-nitrosonornicotine) and the potent lung carcinogen NNK (4-(metylnitrosamino)-1-(3-pyridyl)-1-butanon) may be formed from nicotine after oral administration. E-cigarettes deliver NNK. Some evidence indicates that the NNK dose-response curve for cancer is highly nonlinear, with substantial risk at low doses.
A 2015 study reported that urine from vapers had low levels of NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), which may suggest that endogenous formation of TSNA after nicotine inhalation is negligible. That data indicates that TSNA may be formed internally after absorption of nicotine through the oral mucous membranes and through the skin, while formation after lung absorption may be negligible. Thus, the toxicokinetics of nicotine may depend on the administration route.
The interaction of nicotine with NARs activates signaling pathways that trigger multiple reactions, such as increased cell proliferation and cell survival. Although NARs are the primary receptors, nicotine binding to β-ARs and EGFRs may also be important. Nicotine induces epithelial–mesenchymal transition, which is one of the vital steps for the acquisition of malignant phenotype. This transition allows the cell to acquire migratory properties, which may facilitate cancer metastases.
In May 2014, Cancer Research UK stated that very preliminary unpublished results "suggest that e-cigarettes promote tumour growth in human cells."
Nicotine enhanced tumor growth and progression after injection of malignant cells in mice. Enhancements were reported both after exposure by intraperitoneal injection, oral, and skin administration. Moreover, cotinine did also enhance tumor growth. Nicotine may inhibit antitumor immune response. It has been reported that exposure to nicotine adversely affects dendritic cells, a cell type that has an important role in anticancer immunosurveillance. Moreover, in studies on xenograft in mice, nicotine was reported to reduce the effects of radiotherapy and chemoradiotherapy.
No long-term research considers the cancer risk related to the relatively small level of exposure to the identified carcinogens in e-cigarette vapor. Their long-term use is anticipated to raise the risk of developing lung cancer.$^{:3}$ A 2015 study reported carcinogenicity was mainly evident in the lungs, mouth, and throat, which may be associated with nitrosamines, propylene glycol, and some flavoring additives. A 2019 review associated vaping with a possible risk of head and neck cancers.
Since e-liquids are made from tobacco they may contain impurities such cotinine, anabasine, anatabine, myosmine and beta-nicotyrine. The health implications of suchimpurities are not known. A 2016 review concluded, "impurities and nicotine degradation products such as nicotine-cis-N-oxide, nicotine-trans-N-oxide, myosmine, anabasine, and anatabine, which are very carcinogenic, can be reported in e-cigarette refill liquids. The molecules can lead to mutations in genes such as Ras (vital function in signal transduction of cell proliferation), p53 and retinoblastoma (with roles as tumour suppressors) as these molecules can form adducts with cellular DNA." The majority of e-cigarettes evaluated included carcinogenic TSNAs; heavy metals such as cadmium, nickel, and lead; and the carcinogen toluene. However, in comparison to traditional cigarette smoke, the toxic substance levels identified in e-cigarette vapor were 9- to 450-fold less.
Nicotine promotes endothelial cell migration, proliferation, survival, tube formation, and nitric oxide (NO) production in vitro, mimicking the effect of other angiogenic growth factors. In 2001, it was reported that nicotine was a potent angiogenic agent at tissue and plasma concentrations similar to those induced by light to moderate smoking. Angiogenic effects on tumor cells were found in breast, colon, and lung cancers. Similar results were demonstrated in in vivo mouse models of lung cancer, where nicotine significantly increased tumor size and numbers in the lung, and enhanced metastasis. At high enough concentration levels, nicotine becomes cytotoxic.

### DNA damage

Nicotine has been reported to damage DMA, assessed by the Escherichia colipol A+/pol− test. A 2015 review concluded that nicotine decreases tumor suppressor Chk2, which is otherwise activated by DNA damage. The Chk2 decrease suggests that nicotine may be capable of overriding DNA damage checkpoint activation, disrupting genetic surveillance, and increasing oncogenesis risks. One 2018 study reported strong evidence that some vapor substances such as formaldehyde and acrolein can induce DNA damage and mutagenesis.$^{:Summary,Conclusion10-4.,8}$
Nicotine can induce chromosomal aberration, chromatid exchange, single-strand DNA strand breaks, and micronuclei in vitro. Oxidative stress is probably involved since the effects are reduced in the presence of antioxidants. The effects decrease after co-incubation with a NAR antagonist, indicating a receptor-dependent pathway for oxidative stress induction.
Vapor triggered DNA strand breaks and lowered cell survival in vitro, regardless of nicotine content. A 2013 study reported that some vapor samples had cytotoxic effects on cardiac muscle cells, (albeit less than those of cigarette smoke). A 2016 review concluded that vapor had adverse effects on primary airway epithelial cells and tumor cell lines, and other epithelial cell lines, that ranged from reducing viability, increase in production of inflammatory mediators and oxidative stress, reduced antimicrobial defences and increased pro-carcinogenic events.

### Propylene glycol and glycerin

The primary base ingredients of e-liquids are propylene glycol and glycerin. About 20% to 27% of propylene glycol and glycerin-based liquid particles are inhaled. A 2016 study reported that 6% of nicotine, 8% of propylene glycol, and 16% of glycerin was exhaled.$^{:162}$ As of 2014 the long-term effects of inhaled propylene glycol and glycerin were unknown. Exposure to propylene glycol may cause eye and respiratory tract irritation. Heated and aerosolized propylene glycol can turn into propylene oxide, which the International Agency for Research on Cancer (IARC) labels a possible human carcinogen. A 2014 review concluded that the risk from propylene glycol and glycerin inhalation is probably low, although they have not been demonstrated to be safe. A 2013 German Cancer Center report stated that long-term indoor inhalation of propylene glycol could increase childhood asthma risks. As of 2014, some companies replaced propylene glycol with water and glycerin. A 2019 study reported that inhaled glycerin could cause lipoid pneumonia. A 2017 review concluded that propylene glycol and glycerin increased the amount of hydrogen peroxide.

#### Acrolein

Some e-liquids produced acrolein in the aerosol (a probable carcinogen), possibly from heated glycerin. A 2014 review concluded that acrolein levels were reduced by 60% in dual users and 80% for those that completely switched to e-cigarettes when compared to traditional cigarettes. Another 2014 review concluded that acrolein may induce irritation to the upper respiratory tract, while a 2014 study reported harm to the lining of the lungs. A 2017 review concluded that acrolein induces oxidative stress and inflammation, disrupting lung endothelial cell barrier function and may lead to chronic obstructive pulmonary disease. Another 2017 review stated, "based on the average of 120 puffs/day reported in the literature, our calculated levels of acrolein emitted by e‐cigarette users per day were reported to vary between 0.00792 and 8.94 ppm/day."

#### Oxidants/reactive oxygen species

A 2015 study reported that vapor created oxidants and reactive oxygen species (OX/ROS). OX/ROS could react with other vaporized substances because they are highly reactive. E-cigarettes were reported to contain OX/ROS at about 100 times less than in cigarette smoke. A 2014 study reported that e-liquids from a specific manufacturer contained greater amounts of ethylene glycol than glycerin or propylene glycol, although ethylene glycol was not permitted for use in products meant for human consumption.

### Flavorings

Flavored e-liquids contain additional substances in part to disguise nicotine's bitter taste. Their health effects are not entirely known, given limited toxicological data. A 2017 study reported that flavorings can be a significant part of toxicants. Each flavoring has a different chemical composition. A 2015 study reported varied cytotoxicity of e-liquids, ranging from little to significant cytotoxicity. The liquids contain aromatic substances such as tobacco, fruit, vanilla, caramel, and coffee. Typically, these additives are imprecisely described, using terms such as "vegetable flavoring". Although they are approved for human consumption no studies assess the short-term or long-term effects of inhaling them. As of 2016 their safety had not been assessed by the US Flavor and Extract Manufacturers Association (FEMA). As of 2018 the majority of flavorings in e-liquids had not been investigated for inhalation toxicity.$^{:Summary,4}$ A 2017 review stated that FEMAhad identified 1037 flavoring agents as potential respiratory hazards due to volatility and respiratory irritant properties. Common flavoring agents on that list include diacetyl, acetoin, 2,3-pentanedione (buttery), camphor and cyclohexanone (minty), benzaldehyde (cherry or almond), cinnamaldehyde (cinnamon), cresol (leathery) or medicinal (chocolate), and isoamyl acetate (banana). As of 2017 the four most commonly reported flavoring additives were vanillin, ethyl maltol, ethyl vanillin, and menthol. A 2017 review stated, "the implication by manufacturers that flavoring ingredients used in e-cigarettes and related devices (e.g. hookahs) are safe for inhalation because they have FEMA GRAS™ status for use in food has been stated to be 'false and misleading' by FEMA."
Many flavorings are irritants. $^{:3}$ The limited available data suggest that the majority of flavorings could lead to significant health risks from long-term use, particularly those that are sweet. Some e-liquids contain large amounts of flavorings. A 2016 study of 30 e-cigarette products in the US market reported that 13 were more than 1% flavoring chemicals by weight, some of which were of potential toxicological concern (e.g., cause respiratory irritation). Some flavorings are toxic and some resemble known carcinogens. A 2016 study of five flavorings across six types of e-cigarettes reported that flavorings significantly affected the in vitro toxicity profile. Some artificial flavorings are known cytotoxins. Unflavored vapor is less cytotoxic than flavored vapor.$^{:82}$ A 2012 study reported that in embryonic and adult cellular models, some flavorings not reported in tobacco smoke were cytotoxic. The caffeine exposures from vaping are considerably less than caffeinated beverages. Limited information is available regarding the effects of inhaling caffeine.$^{:OtherToxicants,Caffeine,197}$ The evidence is unclear that particular flavorings carry health risks, though some may increase such risks.$^{:19}$
Cinnamaldehyde has been described as highly cytotoxic. Cinnamaldehyde has been detected in flavorings such as cinnamon, tobacco, sweet (e.g. caramel), and fruit.$^{:ExposuretoFlavorings,175}$ A 2014 review concluded that cinnamaldehyde was cytotoxic at amounts 400 times less than those allowed EPA. Coffee and cinnamon flavorings are reported to be the most toxic. A 2017 review concluded that they were carcinogenic or toxic, and could contribute to cardiopulmonary diseases and neurodegenerative disorders. Only sparse evidence directly associates cinnamon inhalations with asthma. Some e-liquids containing cinnamaldehyde stimulate TRPA1, which might induce effects on the lung. In human lung fibroblasts, cinnamon roll flavoring resulted in a noticeable rise in the amount of inflammatory cytokine IL-8.
A 2019 case report described an 18-year-old patient using a Juul device with mint-flavored pods in the days before episodes of pneumothorax. A 2019 study that sampled e-cigarette delivery systems reported that Juul pods were the only product to demonstrate in vitro cytotoxicity from both nicotine and flavoring chemical content, in particular ethyl maltol. As of 2017 limited data described the effects of menthol inhalation. Some flavorings may increase lung toxicity or lung inflammation in part by producing free radicals and inflammation.
E-liquids contain possibly toxic aldehydes and reactive oxygen species (ROS). Many flavorings are known aldehydes, such as anisaldehyde, cinnamaldehyde, and isovaleraldehyde. Saccharides in sweet e-liquid flavorings generate furans and aldehydes when vaporized.$^{:FLAVORINGS,172}$ The consequences of aldehyde-containing flavorings on pulmonary surfaces are unknown. A 2012 study reported that butterscotch flavoring was highly toxic with one liquid while two others had low toxicity. A 2014 in vitro study showed that menthol flavorings have a damaging effect on human periodontal ligament fibroblast growth. Methanol increased the amount of hydrogen peroxide. A 2017 study reported a variety of flavoring-initiated inflammatory cytokines in lung cell cultures, of which acetoin and maltol were among the strongest. A 2014 in vitro study demonstrated that vaping of a balsamic flavoring without nicotine activated the release of proinflammatory cytokines in lung epithelial cells and keratinocytes. Other additives may reduce the irritation on the pharynx. It is possible that flavorings may worsen harmful effects such as diminished cell viability, escalated rates of apoptosis, escalated DNA strand breaks, alterations in cell morphology and intensified inflammatory mediator production.
Flavorings that contain diacetyl and acetyl propionyl are used for butter, chocolate, milk, toffee, or menthol flavorings. Diacetyl occurs in flavorings such as caramel, butterscotch, watermelon, pina colada, and strawberry. A 2016 study reported that 39 of 51 flavored e-cigarettes contained diacetyl. The American Lung Association recommended in 2016 that the FDA require that diacetyl and other chemicals be banned from e-cigarettes. Diacetyl and acetyl propionyl are associated with bronchiolitis obliterans. A 2018 PHE report stated that e-liquids containing diacetyl are not likely to present a considerable risk.$^{:159}$ A 2015 review recommended specific regulation of diacetyl and acetyl propionyl, which have been associated with respiratory harm when inhaled. Exposure to diacetyl produces morphological liver alterations according to animal studies. Diacetyl and acetyl-propionyl have been reported in concentrations above those recommended by the US National Institute for Occupational Safety and Health. Diacetyl is reported at lower levels in e-cigarettes than in traditional cigarettes.
2, 3-pentanedione is an α-diketone that is chemically and structurally similar to diacetyl. A 2016 report stated that it had become a popular replacement for diacetyl, although it had been shown to cause airway epithelial damage similar to diacetyl. A 2016 review concluded that liquids that use butyric acid in place of diacetyl and acetyl propionyl, could have negative health effects. Another 2016 review surfaced concerns that e-liquid additives might lead to diseases such as popcorn lung.
Cherry flavorings contain a benzaldehyde, a main ingredient for many fruit flavorings. Benzaldehyde can irritate the eyes and respiratory mucous membranes. The irritants butyl acetate, diethyl carbonate, benzoic acid, quinoline, bis(2-ethylhexyl) phthalate, and 2,6-dimethyl phenol were present as undeclared ingredients in the e-liquid. A 2010 study reported weight loss drug rimonabant in e-liquids. The drug has been linked to seizures and suicides. The same study reported that e-liquid can contain amino-tadalafil which is a component of Cialis, used for erectile dysfunction. This and other pharmacologic compounds present some degree of risk.$^{:OtherToxicants,PharmaceuticalDrugs,197}$
In 2015 CDC tested 36 e-cigarette products for 10 flavoring compounds commonly used as additives in tobacco products. Measurable levels of eucalyptol and pulegone were reported in menthol-flavored varieties for all manufacturers. Menthol concentrations ranged from 3,700 to 12,000 μg/g, similar to those reported in traditional cigarettes. Menthol was reported at low concentrations in 40% of the tobacco-flavored nonmenthol products tested. Other flavoring compounds reported were camphor, methyl, salicylate, pulegone, cinnamaldehyde (CAD), and eugenol. A 2016 study analyzed 30 e-cigarette products and reported that 13 contained more than 1% flavoring chemicals by weight. Among the chemicals identified were aldehydes (e.g., benzaldehyde and vanillin), which are primary respiratory tract irritants. Tobacco-flavored e-liquids were derived from flavoring chemicals (e.g., bubble gum and cotton candy flavoring) rather than tobacco extract. Various candy and fruit flavored e-liquids exhibited cytotoxic or mutagenic effects in vitro.

### Formaldehyde

IARC categorized formaldehyde as a human carcinogen, and acetaldehyde is categorized as a potential human carcinogen. Formaldehyde induced DNA damage and inhibited DNA repair. Acetaldehyde generated DNA crosslinking, which impedes metabolic functions, including DNA replication, repair, recombination, transcription and chromatin remodeling. Aldehydes may cause harm. A 2016 study reported that e-liquids without flavoring generated no aldehydes, which indicated that flavorings were causing the creation of aldehydes, according to a 2018 PHE report.$^{:160}$
Chemicals can be inadvertently produced, especially carbonyls such as formaldehyde, acetaldehyde, acrolein, and glyoxal when the nichrome wire (heating element) reaches a high enough temperature. Potentially hazardous carbonyls have been identified in aerosols at temperatures above 200 °C. Propylene glycol-containing liquids produced the most amounts of carbonyls. A 2014 study reported toxic chemical vapor levels at 1 to 2 orders of magnitude smaller than with cigarette smoke, but greater than from a nicotine inhaler. A 2015 study reported toxic and irritation-causing carbonyls, although measured levels of toxic chemicals were inconsistent. The study reported that toxicant levels may be higher than with cigarette smoke.
A 2017 study reported that battery output voltage positively influenced carbonyl vapor levels. A 2015 study reported that e-cigarettes using higher voltages (5.0 V) can emit carcinogens including formaldehyde at levels comparable to cigarette smoke, creating a lifetime cancer risk 5 to 15 times greater than long-term smoking. while lower voltages (3.0 V) produce levels of formaldehyde and acetaldehyde roughly 13 and 807-fold less than in cigarette smoke. Elevated aldehyde formation has an unpleasant taste, leading users to avoid it. The average amount of formaldehyde in vapor from high-voltage devices is higher than the average from cigarettes. Another 2015 study reported that "dripping", where the e-liquid is dripped directly onto the atomizer, can create carbonyls.
The amount of formaldehyde expected to be inhaled by the user is disputed. In 2015 PHE reported that normal vaping generates low levels of aldehydes. Normal usage also generates low levels of formaldehyde.$^{:77,82}$ However, users detect and avoid the "dry puff", leading them to conclude, "There is no indication that EC users are exposed to dangerous levels of aldehydes."$^{:77–78}$ In 2018 PHE reported that at normal temperatures, aldehyde levels were negligible compared with smoke.$^{:158}$

### Nicotine

Nicotine is classified as a poison, and it is "extremely hazardous". However, at doses typically used by consumers, it presents little if any hazard to the user. A 2018 Cochrane Collaboration review lists nine main adverse events related to nicotine replacement therapy: headache, dizziness, lightheadedness, nausea, vomiting, gastrointestinal symptoms, insomnia, abnormal dreams, non-ischemic palpitations and chest pain, skin reactions, oral/nasal reactions, and hiccups. Many of these were also common in the placebo group without nicotine. Palpitations and chest pain were deemed "rare" and there was no evidence of an increased number of serious cardiac problems compared to the placebo group, even in people with established cardiac disease. The common side effects from nicotine exposure are listed in the table below. Serious adverse events due to the use of nicotine replacement therapy are extremely rare. At low amounts, it has a mild analgesic effect. However, at sufficiently high doses, nicotine may result in nausea, vomiting, diarrhea, salivation, bradycardia, and possibly seizures, hypoventilation, and death.
Common side effects of nicotine use according to route of administration and dosage form :
| Route of administration | Dosage form | Associated side effects of nicotine |
| Buccal | Nicotine gum | Indigestion, nausea, hiccups, traumatic injury to oral mucosa or teeth, irritation or tingling of the mouth and throat, oral mucosal ulceration, jaw-muscle ache, burping, gum sticking to teeth, unpleasant taste, dizziness, lightheadedness, headache, and insomnia. |
| Buccal | Lozenge | Nausea, dyspepsia, flatulence, headache, upper respiratory tract infections, irritation (i.e., a burning sensation), hiccups, sore throat, coughing, dry lips, and oral mucosal ulceration. |
| Transdermal | Transdermal patch | Application site reactions (i.e., pruritus, burning, or erythema), diarrhea, dyspepsia, abdominal pain, dry mouth, nausea, dizziness, nervousness or restlessness, headache, vivid dreams or other sleep disturbances, and irritability. |
| Intranasal | Nasal spray | Runny nose, nasopharyngeal and ocular irritation, watery eyes, sneezing, and coughing. |
| Oral inhalation | Inhaler | Dyspepsia, oropharyngeal irritation (e.g., coughing, irritation of the mouth and throat), rhinitis, and headache. |
| All (nonspecific) | All (nonspecific) | Peripheral vasoconstriction, tachycardia (i.e., fast heart rate), elevated blood pressure, increased alertness and cognitive performance. |

#### Cigarettes and nicotine replacement products

E-cigarettes increase serum nicotine levels quicker than nicotine replacement products, but more gradually than traditional cigarettes. A 2014 review concluded that e-cigarettes have a pharmacokinetic nicotine profile closer to nicotine replacement products than to traditional cigarettes.
Another 2014 review concluded that serum cotinine levels were comparable to traditional cigarettes, but varied by usage pattern and device.
A 2017 study reported that vaping produced comparable levels of nicotine urinary metabolites to tobacco and smokeless tobacco products. However, oxidative nicotine metabolites were less in vapers.
A 2017 review concluded that some vaping products delivered the same amount of nicotine as traditional cigarettes.
In 2018 the National Academies of Sciences, Engineering, and Medicine reported that the degree of dependence is less for e-cigarettes than traditional cigarettes.$^{:Summary,Conclusion8-2.,7}$

### Aerosol composition

The chemical composition of e-cigarette aerosols varies. As of 2014 limited chemistry data existed. E-cigarette aerosol is generated when the e-liquid reaches a temperature of roughly 100–250 °C within a chamber, which causes pyrolysis and possible decomposition of other liquid ingredients. The levels of nicotine, TSNAs, aldehydes, metals, volatile organic compounds (VOCs), flavorings, and tobacco alkaloids in e-cigarette vapors vary greatly. The yield of chemicals reported in the e-cigarette vapor varies depending on, several factors, including the e-liquid contents, puffing rate, and the battery voltage.
E-cigarettes consist of fine and ultrafine particles of particulate matter, in the form of an aerosol. The aerosol (mist) produced by an e-cigarette is commonly but inaccurately called vapor. 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. The word "vaping" is not technically accurate when applied to e-cigarettes. The aerosol is made-up of liquid sub-micron particles of condensed vapor; thus, the users of these devices are rather "aerosolizing." This aerosol that is produces looks like cigarette smoke to some extent. After a puff, inhalation of the aerosol travels from the device into the mouth and lungs. The composition of e-liquids varies widely due to the extensive range of nicotine levels and flavoring additives used in these products, which result in a variety of chemical combinations.
A 2014 review concluded that the particles produced from vaping are comparable in particle-size distribution and number of particles to cigarette smoke, with the majority in the ultrafine range. Some e-cigarettes released more particles than cigarette smoke. Fine particles can be chemically intricate and non-uniform. Particle composition and size was mostly unknown. These uncertainties limited the ability to compare e-cigarette vapor and traditional cigarettes. In 2014 WHO reported e-cigarettes release a lower concentration of particles than traditional cigarettes.

### Metals

As of 2014 evidence on the long-term exposure of metals was limited. Metals including nickel, cadmium, lead, chromium, nickel, tin, and silicate have been reported in e-cigarette vapor. The device could contribute small amounts of metals in the liquid and vapor, because their metal parts contact the e-liquid.
A 2014 review concluded that it was unlikely that metal contamination was a serious health risk. A 2018 PHE report stated, "[e-cigarettes] that generate minimal metal emissions should become an industry standard."$^{:162}$ In 2014 the American Heart Association referenced low levels of metals in emissions. A 2014 review concluded metal particls from various components of e-cigarettes appeared in vapor, with potential exposures higher than smoke. A 2013 study reported metal particles in the aerosol were at levels 10-50 times less than permitted in inhalation medicines. A 2014 review found no evidence of vapor contamination with metals that would justify a health concern.
A 2016 study reported that metals can be carcinogenic, nephrotoxic, neurotoxic, and hemotoxic. A 2018 study reported that copper nanoparticles can induce mitochondrial and DNA injury in lung fibroblasts. DNA repair can be impeded by vaporized titanium dioxide nanoparticles as demonstrated by single-strand DNA breaks and oxidative stress in the DNA of A549 cells. Heavy metals are correlated with serious health issues. Inhaling lead can induce serious neurologic injury, notably to the growing brains of children.
A 2015 report by the American College of Physicians stated that metals may adversely affect the nervous system. A 2016 review concluded that metals reported in vapor may induce cell damage and initiate inflammatory cytokine such as in human lung fibroblasts. A 2017 review concluded, "E-cigarette aerosols and copper nanoparticles induced mitochondrial ROS production, mitochondrial stress (reduced stability of OxPhos electron transport chain (ETC) complex IV subunit) and DNA fragmentation in lung fibroblasts." A 2013 review concluded that metallic nanoparticles are associated with respiratory distress and disease. A 2017 review linked cadmium to low sperm density.
A 2023 review concluded that the evidence about metals in vapor was not sufficient to create a firm conclusion. It highlighted that prior smoking history was not always appropriately considered in these studies due to long half-life for some metals.

### First-generation devices

Compared to traditional cigarettes, older devices typically produced much lower blood nicotine levels, although a 2014 study reported plasma nicotine concentration which comparable to that of traditional cigarettes. A 2014 study reported that nicotine delivered from e-cigarettes entered the body slower than traditional cigarettes. A 2014 review concluded that inexperienced users obtained moderate amounts of nicotine from e-cigarettes.

#### Tank/adjustable devices

Tank or adjustable e-cigarettes, as well as concentrated nicotine liquids, may deliver nicotine at levels similar to traditional cigarettes. The American Heart Association reported in 2014 that some e-cigarette tank devices with stronger batteries achieve higher temperatures, which may raise nicotine levels. A 2017 study reported that nicotine delivery compared to previous generation had increased by 35-72%, elevating heart rates comparable to traditional cigarettes. As of 2017 fourth-generation devices had not been heavily researched.

### Concerns

The health effects of long-term nicotine use are unknown. While myriad studies have been conducted, many questions remain unresolved, including impurities in e-liquids,$^{:MinorTobaccoAlkaloids,193}$ effects of nicotine,

#### Youth concerns

Exposure to e-cigarette components in a susceptible time period of brain development could induce persistent behavioral changes. The FDA stated in 2019 that some vapers experienced seizures; most reports involved youth or young adult users.

#### Pregnancy/lactation

A 2016 review concluded that pregnant/breastfeeding women should not substitute cigarettes with e-cigarettes due to the uncertainty about ingredients. The FDA has not approved e-cigarettes as a smoking cessation aid. One study reported increased irritability among infants in those exposed to e-cigarettes or smoking.
A 2022 study recommended quitting smoking altogether through smoking cessation therapy rather than turning to e-cigarettes as an alternative. The U.S. Preventive Services Task Force (USPSTF) recommended that pregnant women adopt behavioral interventions for quitting.

## Public perceptions
### Versus smoking

A 2017 review noted that the public found vaping to be safer than smoking.
A 2014 review concluded that few users are concerned about potential adverse health effects. A 2016 German survey reported that 21% consider vaping to be less harmful than smoking, 46% just as harmful, 16% thought they were more harmful, while 17% gave no answer.$^{:189}$ As of 2018, under 50% of adults in the UK believe vaping is less harmful than smoking.$^{:20}$
A 2014 worldwide survey reported that 88% of respondents perceived vaping to be less harmful than smoking and 11% believed that vaping was absolutely harmless.
% of adult smokers who believed that vaping is as risky or more risky than smoking (2017)$^{:188}$ :
| Country | Date | % |
| Republic of Korea | 2016 | 66% |
| US | 2016 | 37% |
| Netherlands | 2015 | 32% |
| Canada | 2016 | 30% |
| UK | 2016 | 24% |
| Australia | 2016 | 22% |
| Uruguay | 2014 | 19% |
| Malaysia | 2013 | 70% |
| Zambia | 2014 | 57% |
| Thailand | 2012 | 54% |
| Mexico | 2014 to 2015 | 38% |
| Bangladesh | 2014 to 2015 | 37% |
| Brazil | 2012 to 2013 | 22% |
| China | 2013 to 2015 | 15% |
The largest age group contributing to the use and purchase of e-cigarettes are young adults, which include an age range from teens to 30's. A questionnaire examining college students demonstrated that current users believe that e-cigarettes are more convenient and taste and smell better than traditional tobacco products. Another notable result was the trend among current electronic cigarette users to have reported no previous use of tobacco. This would be contraindicative of what the original claims of e-cigarettes manufacturers when they were introduced to the market. While a majority of electronic cigarette users state the understanding of possible harm to their health, there is also the belief that they are safer than other forms of tobacco.

### Relating to pregnancy

A 2015 PHE report noted a nation-wide US survey among adults that reported 11% thought vaping during pregnancy was less harmful than smoking, 51% thought it was as harmful, 12% thought it was more harmful, while 26% were unsure.$^{:190}$ A 2017 review concluded that the majority of survey respondents perceived vaping can carry health risks to mother and child, and that vaping was less harmful than smoking.

### Relating to youth

Over the 2015-2017 period, multiple surveys reported that youth believe vaping to be a safe substitute for smoking. A 2016 study reported that flavored vapes reduced the perception of tobacco use danger among youth. Another 2016 study reported that tobacco flavor increased harm perception while fruit and sweet flavors decreased harm perception among UK adolescents. Similarly, a 2016 study in the US reported that, for US adolescents, fruit-flavored e-cigarettes were perceived to be less harmful than tobacco flavored ones. E-cigarettes were the most commonly used nicotine delivery system youth as of the 2023 National Youth Tobacco Survey. E-cigarette use in high school students was reported to be decreasing despite increasing in middle school; about 2.8 million American youth use any tobacco product.

## Gallery

* Images of E-cigarette battery explosion injuries