User:QuackGuru/Sand 7

https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed_citedin&from_uid=29765089&filter=pubt.booksdocs&filter=pubt.meta-analysis&filter=pubt.review&filter=pubt.systematicreview [1] E-cigarettes can emit formaldehyde at high levels under conditions that have been reported to be non-averse to users

https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed_citedin&from_uid=34610237&filter=pubt.booksdocs&filter=pubt.meta-analysis&filter=pubt.review&filter=pubt.systematicreview [2] Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography-High-Resolution Mass Spectrometry

PMID: 36384212 PMCID: PMC9668543 (available on 2023-11-17) DOI: 10.1002/14651858.CD010216.pub7 ^[1]

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Read again to add more content.[5] ^[3]

The chemical composition of the electronic cigarette aerosol varies significantly across and within brands.^{[note 1]}^[4] Limited data exists regarding their chemistry.^[4] The aerosol of e-cigarettes is generated when the e-liquid comes in contact with a coil heated to a temperature of roughly 100–250 °C (212–482 °F) within a chamber, which is thought to cause pyrolysis of the e-liquid and could also lead to decomposition of other liquid ingredients.^{[note 2]}^[6] The aerosol (mist^[7]) produced by an e-cigarette is commonly but inaccurately called vapor.^{[note 3]}^[4] The e‑cigarette aerosol is absorbed through the lungs, and at this point it rapidly travels through the heart and subsequently delivers nicotine to the brain within a matter of a few seconds.^[9] Nicotine in the brain of e-cigarette users is typically between 0.05 and 0.5 μM.^[10] The use of an e-cigarette simulates the action of smoking,^[11] but without tobacco combustion.^[12] The e-cigarette aerosol somewhat resembles cigarette smoke.^[13] E-cigarettes do not produce aerosol between puffs.^[14] Both smoke and carbon monoxide are not generated,^[15] although insignificant quantities of incomplete combustion products are produced.^[16]

The e-cigarette aerosol usually contains propylene glycol, glycerin, nicotine, flavors, aroma transporters, and other substances.^{[note 4]}^[18] The levels of nicotine, tobacco-specific nitrosamines (TSNAs), aldehydes, metals, volatile organic compounds (VOCs), flavors, and tobacco alkaloids in e-cigarette aerosols vary greatly.^[4] The yield of chemicals found in the e-cigarette aerosol varies depending on, several factors, including the e-liquid contents, puffing rate, and the battery voltage.^{[note 5]}^[20] About 250 chemicals have been found in e-cigarette vapors.^[21] There is emerging evidence indicating that over a thousand chemicals can be present in the e-liquid and aerosol.^[22] There is also a variety of unknown chemicals in the e-cigarette aerosol.^[23]

Metal parts of e-cigarettes in contact with the e-liquid can contaminate it with metal particles.^[24] Heavy metals and metal nanoparticles have been found in tiny amounts in the e-cigarette aerosol.^{[note 6]}^[24] Once aerosolized, the ingredients in the e-liquid go through chemical reactions that form new compounds not previously found in the liquid.^[26] Many chemicals, including carbonyl compounds, such as formaldehyde can inadvertently be produced when the nichrome wire (heating element) that touches the e-liquid is heated and chemically reacted with the liquid.^[27] Propylene glycol-containing liquids produced the most amounts of carbonyls in e-cigarette vapors.^[27] In 2015, e-cigarettes companies attempted to reduce the formation of formaldehyde and metal substances of the e-cigarette vapor by producing an e-liquid in which propylene glycol is replaced by glycerin.^[28]

Propylene glycol and glycerin are oxidized to create aldehydes that are also found in cigarette smoke when e-liquids are heated and aerosolized at a voltage higher than 3 V.^[4] Depending on the heating temperature, the carcinogens in the e-cigarette aerosol may surpass the levels of cigarette smoke.^[26] Reduced voltage e-cigarettes generate very low levels of formaldehyde.^[27] Initial studies reported that formaldehyde was formed during the vaping process under high heat conditions.^[29] Although some of the more recent e-cigarette devices limit temperature in an attempt to minimize this, multiple reports have documented the formation of acetaldehyde, acrolein, diacetyl, and formaldehyde under a wide range of conditions.^[29] As e-cigarette engineering evolves, the later-generation and "hotter" devices could expose users to greater amounts of carcinogens.^[8]

Background

There is a debate on the composition, and the subsequent health burden, of tobacco smoke compared with electronic cigarette vapor.^[31] Tobacco smoke is a complex, dynamic and reactive mixture containing around 5,300 chemicals.^[32] In contrast, about 250 chemicals have been found in e-cigarette vapors.^[21] Previously, over 80 chemicals have been found in e-liquids and e-cigarette vapors^[15] and 42 chemicals have been found in the e-cigarette vapors in 2016.^[33] There is emerging evidence indicating that over a thousand chemicals can be present in the e-liquid and aerosol.^[22] There is also a variety of unknown chemicals in the e-cigarette aerosol.^[23] E-cigarette vapor contains many of the known harmful toxicants found in traditional cigarette smoke, such as formaldehyde, cadmium, and lead, though usually at a reduced percentage.^[34]

There are substances in e-cigarette vapor that are not found in tobacco smoke^[35] such as propylene glycol and/or glycerin.^[23] Furthermore, at least 50 chemicals have been detected in e-liquids that were not found in traditional cigarettes.^[36] These were (+)-aromadendrene, (Z)-3-Hexen-1-ol, 1-Methyl phenanthrene, 1,3-Butanediol, 1,3-Propanediol, 2-Acetylpyrrole, 2,3-Dimethylpyrazine, 2,3-Pentanedione, 2,3,5-Trimethylpyrazine, 3-Methyl-1-butanol, acetic acid, benzyl acetate, benzyl alcohol, butyl butyrate, camphor, cinnamaldehyde, cinnamyl alcohol, coumarin, methyl cyclopentenolone, diacetyl, diethylene glycol, ethyl butyrate, ethyl maltol, ethyl vanillin, ethylene glycol, glycerin, hydroxyacetone, i-Butyric acid, Isobutyl acetate, isoamyl acetate, isopentyl isovalerate, L-Menthyl acetate, Limonene, maltol, menthone, methyl anthranilate, methyl cinnamate, methyl salicylate, myosmine, n-Hexanol, nicotyrine, o-Tolualdehyde, p-Cymene, propylene glycol, safrole, thujone (consisting of α- and β-diastereomers), trans-2-hexen-1-ol, vanillin, β–Damascone, and γ–Decalactone.^[36]

Researchers are part of the conflict, with some opposing and others supporting of e-cigarette use.^[37] The public health community is divided, even polarized, over how the use of these devices will impact the tobacco epidemic.^[38] One of the myths pushed by the vaping industry is that the e-liquid flavors are largely colorings and flavorings, which can be eaten without harm.^[39] But eating is not the same as inhaling.^[39] In fact, propylene glycol and flavorings have been shown to be toxic to airway epithelial cells in vitro and in vivo.^[39] A 2019 review states, "Researchers have disproved claims by e-cigarette manufacturers that e-cigarette aerosols are only water vapor, glycerol, and PG and can be used safely in all environments."^[40] A 2022 review states that "misinformation from the online marketing of vapes (e-cigarettes) by manufacturers, retailers, and social media influencers has claimed that e-cigarettes contain only water vapor and are harmless."^[41] Proponents of e-cigarettes think that these devices contain merely "water vapour" in the e-cigarette aerosols, but this view is refuted by the evidence.^[42] Non-users may be exposed to nicotine^[43] and toxicants from the e-cigarette emissions.^[44]^[45] Because of the diversity of the e-cigarettes in the marketplace, the amount of e-cigarette vapor non-users are exposed to is unknown.^[46]

List of hazardous tobacco smoke components with their cancer and non-cancer inhalation risk values.^[32]
Smoke component	Cancer risk (mg m⁻³)^{[nb 1]}	Institute	Non-cancer risk (mg m⁻³)^{[nb 2]}	Endpoint	Institute
1,1,1-Trichloro-2,2-bis(4-chlorophenyl)ethane (DDT)	0.0001	U.S. EPA
1,1-Dimethylhydrazine	2E-06	ORNL
1,3-Butadiene	0.0003	U.S. EPA	0.002	reproduction	U.S. EPA
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)	0.00026	Cal EPA
2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAaC)	2.9E-05	Cal EPA
2-Amino-3-methylimidazo[4,5-b]quinoline (IQ)	2.5E-05	Cal EPA
2-Amino-6-methyl[1,2-a:3′,2″-d]imidazole (GLu-P-1)	7.1E-06	Cal EPA
2-Aminodipyrido[1,2-a:3′,2″-d]imidazole (GLu-P-2)	2.5E-05	Cal EPA
2-Aminonaphthalene	2E-05	Cal EPA
2-Nitropropane		Cal EPA	0.02	liver, focal vacuolization and nodules	U.S. EPA
2-Toluidine	0.0002	Cal EPA
3-Amino-1,4-dimethyl-5H-pyrido [4,3-b]indole (Trp-P-1)	1.4E-06	Cal EPA
3-Amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2)	1.1E-05	Cal EPA
4-Aminobiphenyl	1.7E-06	Cal EPA
5-Methylchrysene	9.1E-06	Cal EPA
7H-Dibenzo(c,g)carbazole	9.1E-06	Cal EPA
2-Amino-9H-pyrido[2,3-b]indole (AaC)	8.8E-05	Cal EPA
Acetaldehyde	0.0045	U.S. EPA	0.009	nasal olfactory epithelial lesions	U.S. EPA
Acetamide	0.0005	Cal EPA
Acetone			30	neurological effects	ATSDR
Acetonitrile			0.06	mortality	U.S. EPA
Acrolein			2E-05	nasal lesions	U.S. EPA
Acrylamide	0.008
Acrylic acid			0.001	nasal olfactory epithelium degeneration	U.S. EPA
Acrylonitrile	0.00015	U.S. EPA	0.002	respiratory effects	U.S. EPA
Ammonia			0.1	respiratory effects	U.S. EPA
Aniline	B2—probable human carcinogen	U.S. EPA	0.001	immune-related	U.S. EPA
Arsenic	2.3E-06	U.S. EPA
Benz[a]anthracene	9.1E-05	Cal EPA
Benzene	0.0013	U.S. EPA	0.0098	decreased lymphocyte count	ATSDR
Benzo[a]pyrene	9.1E-06	Cal EPA
Benzo[j]fluoranthene	9.1E-05	Cal EPA
Beryllium	4.2E-06
Cadmium	5.6E-06	U.S. EPA
Carbazole	0.0018	NATA
Carbon disulfide			0.1	effects on CNS	HC
Carbon monoxide			10	cardiotoxic	Cal EPA
Chloroform	0.00043	U.S. EPA	0.1	liver changes	ATSDR
Chromium VI	8.3E-07	U.S. EPA	0.0001	lower respiratory effects	U.S. EPA
Chrysene	0.00091	Cal EPA
Cobalt			0.0005	respiratory functions	RIVM
Copper			0.001	lung and immune system effects	RIVM
Di(2-ethylhexyl) phthalate	0.0042	Cal EPA
Dibenzo[a,i]pyrene	9.1E-07	Cal EPA
Dibenzo[a,h]acridine	9.1E-05	Cal EPA
Dibenzo[a,h]anthracene	8.3E-06	Cal EPA
Dibenzo[a,j]acridine	9.1E-05	Cal EPA
Dibenzo[a,h]pyrene	9.1E-07	Cal EPA
Dibenzo[a,l]pyrene	9.1E-07	Cal EPA
Dibenzo[a,e]pyrene	9.1E-06	Cal EPA
Dibenzo[c,g]carbazole	9.1E-06	Cal EPA
Dimethylformamide			0.03	digestive disturbances; minimal hepatic changes	U.S. EPA
Ethyl carbamate	3.5E-05	Cal EPA
Ethylbenzene			0.77	liver and kidney effects	RIVM
Ethylene oxide	0.00011	Cal EPA
Ethylenethiourea	0.00077	Cal EPA
Formaldehyde	0.00077	U.S. EPA	0.01	nasal irritation	ATSDR
Hexane			0.7	neurotoxicity	U.S. EPA
Hydrazine	2E-06	U.S. EPA	0.005	fatty liver changes	ATSDR
Hydrogen cyanide			0.003	CNS and thyroid effects	U.S. EPA
Hydrogen sulfide			0.002	nasal lesions	U.S. EPA
Indeno[1,2,3-c,d]pyrene	9.1E-05	Cal EPA
Isopropylbenzene			0.4	increased kidney, adrenal gland weights	U.S. EPA
Lead	0.00083	Cal EPA	0.0015	not applicable	U.S. EPA
Manganese			5E-05	neurobehavioral	U.S. EPA
m-Cresol			0.17	CNS	RIVM
Mercury			0.0002	nervous system	U.S. EPA
Methyl chloride			0.09	cerebellar lesions	U.S. EPA
Methyl ethyl ketone			5	developmental toxicity	U.S. EPA
Naphthalene			0.003	nasal effects	U.S. EPA
N-nitrosodi-n-butylamine (NBUA)	6.3E-06	U.S. EPA
N-nitrosodimethylamine (NDMA)	7.1E-07	U.S. EPA
Nickel			9E-05	chronic active inflammation and lung fibrosis	ATSDR
Nitrogen dioxide			0.1	not applicable	U.S. EPA
N-nitrosodiethanolamine	1.3E-05	Cal EPA
N-nitrosodiethylamine	2.3E-07	U.S. EPA
N-nitrosoethylmethylamine	1.6E-06	Cal EPA
N-Nitrosonornicotine (NNN)	2.5E-05	Cal EPA
N-Nitroso-N-propylamine	5E-06	Cal EPA
N-nitrosopiperidine	3.7E-06	Cal EPA
N-nitrosopyrrolidine	1.6E-05	U.S. EPA
n-Propylbenzene			0.4	increased organ weight	U.S. EPA
o-Cresol	C- possible human carcinogen	U.S. EPA	0.17	decreased body weight, neurotoxicity	RIVM
p-, m-Xylene			0.1	respiratory, neurological, developmental	U.S. EPA
p-Benzoquinone	C- possible human carcinogen	U.S. EPA	0.17	CNS	RIVM
p-Cresol	C- possible human carcinogen	U.S. EPA	0.17	CNS	RIVM
Phenol			0.02	liver enzymes, lungs, kidneys, and cardiovascular system	RIVM
Polonium-210	925.9	ORNL^{[nb 3]}
Propionaldehyde			0.008	atrophy of olfactory epithelium	U.S. EPA
Propylene oxide	0.0027	U.S. EPA
Pyridine			0.12	odour threshold	RIVM
Selenium			0.0008	respiratory effects	Cal EPA
Styrene			0.092	body weight changes and neurotoxic effects	HC
Toluene			0.3	colour vision impairment	ATSDR
Trichloroethylene	82	HC	0.2	liver, kidney, CNS effects	RIVM
Triethylamine			0.007	n.a.	U.S. EPA
Vinyl acetate			0.2	nasal lesions	U.S. EPA
Vinyl chloride	0.0011	U.S. EPA

↑ Cancer inhalation risk values provide an excess lifetime exposure risk, in this case the human lung cancer risk at a 1 in 100,000 (E-5) level.
↑ Noncancer inhalation risk values indicate levels and exposure times at which no adverse effect is expected; here values for continuous lifetime exposure are listed.
↑ Unit risk in risk/pCi = 1.08E-08.

Composition

E-cigarette design

The engineering design of an e-cigarette

An exploded view of an e-cigarette with transparent clearomizer and changeable dual-coil head.^[47] This model allows for a wide range of settings.^[47]

E-cigarette components include a mouthpiece, a cartridge (liquid storage area), a heating element or atomizer, a microprocessor, a battery, and some of them have a LED light at the tip.^[48] They are disposable or reusable devices.^[49] Disposable ones are not rechargeable and typically cannot be refilled with a liquid.^[49] There are a diverse range of disposable and reusable devices, resulting in broad variations in their structure and their performance.^[49] Since many devices include interchangeable components, users have the ability to alter the nature of the inhaled vapor.^[49] For the majority of e-cigarettes many aspects are similar to their traditional counterparts such as giving nicotine to the user.^[50]

Vaping style

The so called "Mouth to Lung" vaping style is the most frequent one among vapers and currently remains typical of initiating users, most of them ex-smokers or current smokers.^[51] It involves mouth cavity retention followed by lung inhalation, a puffing mechanics roughly similar to that of cigarette smoking, thus being well suited for the design of early generation vaping devices (cigalikes, clearomizer models) and currently it is practiced in pods and tank models used as starter kits.^[51]

The "Direct to Lung" style that avoids the mouth retention of Mouth to Lung is typically practiced by more experimented and younger vapers.^[51] It involves a much deeper inhalation than Mouth to Lung, which translates into more intense puffing parameters: airflow rates of 200 mL/s, puff volumes of 500 mL (or even more), as well as longer puff times, resulting in much larger mass of inhaled aerosol.^[51] As opposed to the Mouth to Lung style, Direct to Lung style bears no resemblance to tobacco cigarette puffing (as opposed to vapers, smokers tend to avoid a Direct to Lung style because tobacco smoke is a strong irritant).^[51] Evidently, the heating element of vaping devices appropriate for this puffing regime must be able to deliver much higher power (combined with lower electric resistance) to generate the needed larger aerosol mass for a usage characterized by larger airflows for its inhalation.^[51]

Aerosol production

Vapor production basically entails preprocessing, vapor generation, and postprocessing.^[49] First, the e-cigarette is activated by pressing a button or other devices switch on by an airflow sensor or other type of trigger sensor.^[49] Then, power is released to an LED, other sensors, and other parts of the device, and to a heating element or other kind of vapor generator.^[49] Subsequently, the e-liquid flows by capillary action to the heating element or other devices to the e-cigarette vapor generator.^[49] Second, the e-cigarette vapor processing entails vapor generation.^[49] The e-cigarette vapor is generated when the e-liquid is vaporized by the heating element or by other mechanical methods.^[49] The last step of vapor processing happens as the e-cigarette vapor passes through the main air passage to the user.^[49] For some advanced devices, before inhaling, the user can adjust the heating element temperature, air flow rate or other features.^[49]

The use of an e-cigarette simulates the action of smoking,^[11] with a vapor that somewhat resembles cigarette smoke.^[13] Pod mods create a minimal amount of visible aerosol.^[52] E-cigarettes do not involve tobacco combustion,^[12] and they do not produce vapor between puffs.^[14] Both smoke and carbon monoxide are not generated.^[15] They do not produce sidestream smoke or sidestream vapor.^[20] Because the boiling points of the propylene glycol (188 °C), glycerin (290 °C), and nicotine (247 °C) are fairly low, the battery heating temperature of e-cigarettes is typically designed to not involve burning.^[16] Because of this, insignificant quantities of incomplete combustion products are produced.^[16] The e-cigarette is thus promoted as a device for getting people high on nicotine without having the consequences of tobacco smoke incomplete combustion products.^[16] The e‑cigarette aerosol is absorbed through the lungs, and at this point it rapidly travels through the heart and subsequently delivers nicotine to the brain within a matter of a few seconds.^[9] Nicotine in the brain of e-cigarette users is typically between 0.05 and 0.5 μM.^[10] E-cigarette users can often inhale more than 100 puffs in a day.^[53]

The liquid within the chamber of an e-cigarette is heated to roughly 100-250 °C to create an aerosolized vapor.^[6] This is thought to result in pyrolysis of the e-liquid and could also lead to decomposition of other liquid ingredients.^[6] The aerosol (mist^[7]) produced by an e-cigarette is commonly but inaccurately called vapor.^[4] 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.^[4]

Power output

The power output of the e-cigarette is correlated to the voltage and resistance (P = V²/R, in watts), which is one aspect that impacts the production and the amount of toxicants of e-cigarette vapors.^[54] The power generated by the heating coil is not based solely on the voltage because it also relies upon the current, and the resultant temperature of the e-liquid relies upon the power output of the heating element.^[6] The production of vapor also relies upon the boiling point of the solvent.^[54] Propylene glycol boils at 188 °C, while glycerin boils at 290 °C.^[54] The higher temperature reached by glycerin may impact the toxicants emitted by the e-cigarette.^[54] The boiling point for nicotine is 247 °C.^[55] Each e-cigarette company's designs generate different amounts of heating power.^[56] The evidence indicates that larger capacity tanks, increasing the coil temperature, and dripping configurations seem to be end user modified designs adopted by e-cigarette companies.^[49] Variable voltage e-cigarettes can raise the temperature within the device to allow users to adjust the e-cigarette vapor.^[7] No firm information is available on the temperature differences in variable voltage devices.^[7] The length of time that the e-cigarette vapor is being heated within the device also affects the e-cigarette vapor properties.^[49] When the temperature of the heating element rises, the temperature of the e-cigarette vapor in the air rises.^[49] The hotter air can support more e-liquid air density.^[49]

Manufacturing standards

E-cigarettes have a wide array of engineering designs.^[49] The differences in e-cigarette manufacturing materials are broad and unknown.^[46] Regulations have not been established for e-cigarette companies to keep a record of or report their components.^[46] Concern exists over lack of quality control.^[57] E-cigarette companies often lack manufacturing standards^[58] or standards are non-existent.^[59] Some e-cigarettes are designed and manufactured to a high standard.^[60] The manufactured standards of e-cigarettes are not equivalent to pharmaceutical products.^[61] Improved manufacturing standards could reduce the levels of metals and other chemicals found in e-cigarette vapor.^[62] Quality control is influenced by market forces.^[63] The engineering designs typically affect the nature, number, and size of particles generated.^[64]

Particulate matter

High amounts of vapor particle deposition are believed to enter into the lungs with each puff because the particle size in e-cigarette vapors is within the respiratory range.^[66] After a puff, the inhaled vapor changes in the size distributions of particles in the lungs.^[4] This results in smaller exhaled particles.^[4] E-cigarette vapor is made up of fine and ultrafine particles of particulate matter.^[67] The particulate matter consists of solid and liquid droplets.^[45] Vaping^{[note 7]} generates particulate matter 2.5 μm or less in diameter (PM_2.5), but at notably less concentrations compared to cigarette smoke.^[67] Particle concentrations from vaping ranged from 6.6 to 85.0 μg/m³.^[64] Particle-size distributions of particulate matter from vaping differ across studies.^[4] The longer the puff duration the greater the amount of particles produced.^[64] The greater the amount of nicotine in the e-liquid the greater the amount of particles produced.^[64] Flavoring does not influence the particle emissions.^[64] The various kinds of devices such as cig-a-likes, medium-sized vaporizers, tanks, or mods may function at different voltages and temperatures.^[67] Thus, the particle size of the e-cigarette vapor can vary, due to the device used.^[68] Comparable to cigarette smoke, the particle size distribution mode^{[note 8]} of e-cigarette vapor ranged from 120 to 165 nm, with some vaping devices producing more particles than cigarette smoke.^[64]

Basic e-cigarette operation

Nicotine and other content

Exactly what the e-cigarette vapor consists of varies significantly in composition and concentration across and within brandss.^[4] The Royal College of General Practitioners stated in 2016 that "To date 42 chemicals have been detected in ENDS aerosol – though with the ENDS market being unregulated there is significant variation between devices and brands."^[33] Limited data exists regarding their chemistry.^[4] The e-cigarette vapor usually contains propylene glycol, glycerin, nicotine, flavors, aroma transporters, and other substances.^[18] The yield of chemicals found in the e-cigarette vapor varies depending on, several factors, including the e-liquid contents, puffing rate, and the battery voltage.^[20] A 2017 review found that "Adjusting battery wattage or the inhaled airflow modifies the amount of vapor and chemical density in each puff."^[70] A high amount of e-liquid contains propylene glycol and/or glycerin.^[4] E-liquid nicotine concentrations vary.^[71] Some e-cigarettes are made with synthetic nicotine.^[72] Synthetic nicotine predominately contains a blend of equal proportions of S-nicotine enantiomers and R-nicotine enantiomers.^[73] In 2022, Puff Bars had been using synthetic nicotine.^[74] The levels of solvents and flavors are not provided on the labels of e-liquids, according to many studies.^[5] Limited but consistent data indicates that flavoring agents are at levels above the National Institute for Occupational Safety and Health safety limit.^[56] The amount of nicotine stated on the labels of e-liquids can be very different from analyzed samples.^[4] Some e-liquids sold as nicotine-free contained nicotine, and some of them were at substantial levels.^[57] E-liquids were purchased from retailers and via online for a 2013 study.^[75] The analyzed liquids nicotine levels in a 2013 study were between 14.8 and 87.2 mg/mL and the actual amount varied from the stated amount by as much as 50%.^[75]

The main chemical found in the e-cigarette vapor is propylene glycol.^[55] A 2013 study, under close to real-life conditions in an emission test chamber, using a test subject who took six forceful puffs from an e-cigarette, resulted in a high level of propylene glycol released into the air.^[67] The next greatest amount in the e-cigarette vapor was nicotine.^[55] Possibly, 60–70% of the nicotine is vaporized.^[76] E-cigarettes without nicotine is also available.^[77] Via nicotine-containing e-cigarettes, nicotine is absorbed through the upper and lower respiratory tract.^[78] A greater amount of nicotine is possibly absorbed through oral mucosa and upper airways.^[79] The composition of the e-liquid may affect nicotine delivery.^[79] E-liquid containing glycerin and propylene glycol delivers nicotine more efficiently than a glycerin-based liquid with the same amount of nicotine.^[79] It is believed that propylene glycol vaporizes quicker than glycerin, which subsequently transports a higher amount of nicotine to the user.^[79]

Vaping appears to give less nicotine per puff than cigarette smoking.^[80] Early devices typically delivered low amounts of nicotine than that of traditional cigarettes, but newer devices containing a high amount of nicotine in the liquid may deliver nicotine at amounts similar to that of traditional cigarettes.^[81] Similar to traditional cigarettes, e-cigarettes rapidly delivers nicotine to the brain.^[82] The peak concentration of nicotine delivered by e-cigarettes is comparable to that of traditional cigarettes.^[83] E-cigarettes take longer to reach peak concentration than with traditional cigarettes,^[83] but they provide nicotine to the blood quicker than nicotine inhalers.^[84] The yield of nicotine users obtain is similar to that of nicotine inhalers.^[85] Newer e-cigarette models deliver nicotine to the blood quicker than with older devices.^[86] E-cigarettes with more powerful batteries can delivery a higher level of nicotine in the e-cigarette vapor.^[63] Some research indicates that experienced e-cigarette users can obtain nicotine levels similar to that of smoking.^[87] Some vapers^{[note 9]} can obtain nicotine levels comparable to smoking, and this ability generally improves with experience.^[2] E‐cigarettes users still may be able to obtain similar blood nicotine levels compared with traditional cigarettes, particularly with experienced smokers, but it takes more time to obtain such levels.^[88]

Cig-a-likes are usually first-generation e-cigarettes, tanks are commonly second-generation e-cigarettes, tanks that let vapers adjust the voltage setting are third-generation e-cigarettes,^[2] and tanks that have the ability for sub ohm (Ω) vaping and to set temperature control limits are fourth-generation devices.^[89] Vaping nicotine using e-cigarettes differs from smoking traditional cigarettes in many ways.^[47] First-generation e-cigarettes are often designed to simulate smoking traditional cigarettes; they are low-tech vaporizers with a limited number of settings.^[47] First-generation devices usually deliver a smaller amount nicotine.^[19] Second-generation and third-generation e-cigarettes use more advanced technology; they have atomizers (i.e., heating coils that convert e-liquids into vapor) which improve nicotine dispersal and house high capacity batteries.^[47] Third-generation and fourth-generation devices represent a diverse set of products and, aesthetically, constitute the greatest departure from the traditional cigarette shape, as many are square or rectangular and feature customizable and rebuildable atomizers and batteries.^[90] Cartomizers are similar in design to atomizers; their main difference is a synthetic filler material wrapped around the heating coil.^[47] Clearomizers are now commonly available and similar to cartomizers, but they include a clear tank of a larger volume and no filler material; additionally they have a disposable head containing the coil(s) and wicks.^[47]

Vaping enthusiasts often begin with a cig-a-like first-generation device and tend to move towards using a later-generation device with a larger battery.^[91] Cig-a-likes and tanks were among the most popular devices in 2016.^[92] There has been a gradual increase of consumer preference for low powered pod devices in the US, the UK and Germany, as well as increasing popularity of low powered disposable devices, especially among young adults and teenagers.^[51] By 2018, pod mods were the most popular devices in the US.^[93] Cig‐a‐likes deliver a low amount of nicotine, and the majority of pre‐filled cartridge devices, mainly offered by the tobacco industry, deliver a low amount of nicotine.^[2] Tanks vaporize nicotine normally more effectively, and there are a greater selection of flavors and levels of nicotine, and are generally used by experienced users.^[2] Pod mods provide greater nicotine concentrations than previous models and they nearly emulate the pharmacokinetic characteristics of delivering nicotine like cigarettes,^[2] and provide nicotine as a nicotine salt.^[3] Under five minutes of cig-a-like vaping, blood nicotine levels can elevate to about 5 ng/ml, while under 30 minutes of using 2 mg of nicotine gum, blood nicotine levels ranged from 3–5 ng/ml.^[87] Under five minutes of using tank systems by experienced vapers, the elevation in blood nicotine level can be 3–4 times greater.^[87] Many devices lets the user use interchangeable components, which result in variations in the e-cigarette vaporized nicotine.^[49] One of the primary features of the more recent generation of devices is that they contain larger batteries and are capable of heating the liquid to a higher temperature, potentially releasing more nicotine, forming additional toxicants, and creating larger clouds of particulate matter.^[90] A 2017 review found "Many e-cig users prefer to vape at high temperatures as more aerosol is generated per puff. However, applying a high voltage to a low-resistance heating coil can easily heat e-liquids to temperatures in excess of 300 °C; temperatures sufficient to pyrolyze e-liquid components."^[94]

E-cigarette mouthpiece with particles of insoluble apparently thermally decomposed tobacco extract from the aerosol^[95]

Evidence of thermally decomposed material on the wick (of an e-cigarette) in proximity to the heating element^[95]

The amount of nicotine uptake from second-hand e-cigarette exposure is comparable to that of traditional cigarette smoke.^[96] The nicotine levels in the e-cigarette vapor greatly varies across companies.^[97] The nicotine levels in the e-cigarette vapor also varies greatly either from puff-to-puff or among devices of the same company.^[4] Nicotine intake across users using same device or liquid varies substantially.^[98] Puffing characteristics differ between smoking and vaping.^[99] Vaping typically require more 'suck' than cigarette smoking.^[100] Factors that influence the level of blood nicotine concentrations include nicotine content in a device; how well the nicotine is vapored from the liquid reservoir; and additives that may contribute to nicotine intake.^[81] Nicotine intake from vaping also relies upon the habits of the user.^[101] Other factors that influence nicotine intake include engineering designs, battery power, and vapor pH.^[81] For instance, some e-cigarettes have e-liquids that contain amounts of nicotine comparable to other companies, though the e-cigarette vapor contains far less amounts of nicotine.^[81] Puffing behavior substantially varies.^[102] New e-cigarette users tend to take shorter puffs than experienced users which may result in less nicotine intake.^[98] Among experienced users there is a wide range in puffing time.^[26] Some experienced users may not adapt to increase their puffing time.^[98] Inexperienced users vape less forcefully than experienced users.^[103] E-cigarettes share a common design, but construction variations and user alterations generate varied nicotine delivery.^[49] Lowering the heater resistance probably increases the nicotine concentration.^[54] Some 3.3 V vaping devices using low-resistance heating elements such as an ohm of 1.5, containing 36 mg/mL liquid nicotine can obtain blood nicotine levels after 10 puffs that may be higher than with traditional cigarettes.^[54] A 2015 study evaluated "a variety of factors that can influence nicotine yield and found that increasing power output from 3 to 7.5 W (an approximately 2.5-fold increase), by increasing the voltage from 3.3 to 5.2 V, led to an approximately 4- to 5-fold increase in nicotine yield."^[54]

A 2015 study, using a model to approximate indoor air workplace exposure, anticipates greatly reduced exposure to nicotine from e-cigarettes than traditional cigarettes.^[104] A 2016 World Health Organization (WHO) report found "nicotine in SHA [second-hand aerosol] has been found between 10 and 115 times higher than in background air levels."^[105] A 2015 Public Health England (PHE) report concluded that e-cigarettes "release negligible levels of nicotine into ambient air".^[104] A 2016 Surgeon General of the United States report stated that the exposure to nicotine from e-cigarette vaping is not negligible and is higher than in non-smoking environments.^[90] Vaping generates more surrounding air levels of particulate matter and nicotine in indoor areas than background air levels.^[106] The use of e-cigarettes in indoor environments leads to high levels of fine and ultrafine particles similar to tobacco cigarettes.^[107] Extended indoor e-cigarette use in rooms that are not sufficiently ventilated could surpass occupational exposure limits to the inhaled metals.^[108]

The e-cigarette vapor may also contain tiny amounts of toxicants, carcinogens, and heavy metals.^[64] The majority of toxic chemicals found in e-cigarette vapor are below 1% of the corresponding levels permissible by workplace exposure standards,^[77] but the threshold limit values for workplace exposure standards are generally much higher than levels considered satisfactory for outdoor air quality.^[64] Some chemicals from exposures to the e-cigarette vapor could be higher than workplace exposure standards.^[94] A 2018 PHE report stated that the toxicants found in e-cigarette vapor are less than 5% and the majority are less than 1% in comparison with traditional cigarettes.^[109] The levels of toxic chemicals in e-cigarette vapor is in some cases similar to that of nicotine replacement products.^[110] Although several studies have found lower levels of carcinogens in e-cigarette aerosol compared to smoke emitted by traditional cigarettes, the mainstream and second-hand e-cigarette aerosol has been found to contain at least ten chemicals that are on California's Proposition 65 list of chemicals known to cause cancer, birth defects, or other reproductive harm, including acetaldehyde, benzene, cadmium, formaldehyde, isoprene, lead, nickel, nicotine, N-Nitrosonornicotine, and toluene.^[111] Free radicals produced from frequent e-cigarette use is estimated to be greater than compared to air pollution.^[112]

pH of e-cigarette liquid

The pH of a solution impacts the exposure to nicotine from e-cigarettes.^[113] The pH of e-liquids can differ.^[93] A reduced nicotine pH diminishes the bitterness and unfavorable taste, letting users to breathe in deeply with the absence of dealing with displeasing sensations which leads to a greater lung deposition of the aerosol and better absorption of nicotine into the lungs.^[93] Juul devices mainly use protonated nicotine, rather than the free-base nicotine used in other kinds of e-cigarettes.^[114] Protonated nicotine has a reduced pH, which may make nicotine simpler to breathe in.^[114] Juul devices can provide nicotine at levels similar to cigarettes.^[114] A 2018 study on teens pod mod users found greater concentrations of the nicotine metabolite cotinine, in contrary to a different 2018 study of traditional teen cigarette smokers.^[114] A 2015 study discovered that in a pH solution of 5.16 the percentage of unprotonated versus protonated nicotine was 2.5% versus 97.5%, and in a pH solution of 9.66 the percentage was the opposite, measuring 97.7% versus 2.3%.^[93] Flavors may influence nicotine absorption by altering the pH.^[45]

Flavoring in e-cigarette liquid

There are over 7,700 commercially available e-liquids, most of which have not been tested.^[116] The diversity of e-liquids has reached even greater heights since 2014, with one 2021 survey based in the Netherlands reporting nearly 20,000 unique e-liquid formulations.^[117] There are numerous flavors (e.g., fruit, vanilla, caramel, coffee, etc.^[7]) of e-liquid available.^[11] Commonly available e-liquid flavors include fruit, candy, and dessert flavors.^[118] There are also flavorings that resemble the taste of cigarettes.^[11] Names of the e-liquid flavors include Cotton Candy from Vape Dudes, Peaches N Cream from Drip, and Euphoria from Cosmic Fog.^[119] Diacetyl, because of its buttery flavor and favorable chemical attributes, has been used in e-liquid preparations, including in CooCoo Coconut and Tutti Frutti flavors.^[96] Some e-liquids sold as diacetyl-free contained detectable levels of diacetyl.^[96]

E-liquid companies are not mandated to list all flavoring additives as a part of the ingredients list.^[120] E-liquids contain numerous unknown chemicals.^[39] The percentages and formula of flavors differ^[121] and flavoring mixtures are generally made up of proprietary blends of ingredients.^[96] Flavoring additives in e-liquids are derived from the food industry, and are generally recognized as safe (GRAS) only for oral ingestion, and include benzaldehyde, cinnamaldehyde, diacetyl, ortho-vanillin, coumarin, pentanedione, acetoin, maltol, eucalyptol, ethyl vanillin, dl-menthol, and flavoring enhancers.^[122] Cinnamaldehyde, 2,5-Dimethylpyrazine (chocolate taste), and 2,3-Pentanedione are regularly used for flavoring.^[123] Essential oils are also utilized (e.g., mint, cloves, etc.) for flavor in the e-liquids.^[53] A complex flavor like "Crispy cake with lemon cream and meringue", requires an assortment of flavoring ingredients.^[53] Hundreds of various flavor substances have been identified in e-liquids.^[124] Several of them are present in most of the e-liquids in the marketplace.^[124] To give a cooling sensation that is free from the minty or menthol taste, e-cigarette manufacturers or companies, such as Puff Bar, are using synthetic coolants, such as WS-23 and WS-3, in their e-liquids.^[125] This includes Ice Dragon and Raspberry Ice flavors.^[125]

In November 2018, Juul stopped selling cucumber, crème, fruit, and mango flavors in US traditional retail shops.^[126] This happened while facing continuing pressure from the US Food and Drug Administration.^[126] As a result, mint flavor soared in sales.^[126] In October 2019, Juul discontinued the sale of the majority of their flavors to traditional and online retailers.^[126] This included mint but did not include menthol and tobacco flavors.^[126] Other businesses immediately exploited the preceding events and introduced Juul-compatible pods in an assortment of popular Juul flavors like mango and cucumber.^[126] Cucumber, creme, fruit, and mango Juul pod flavors are still being sold in other countries.^[127]

Flavoring in e-cigarette aerosol

Numerous chemical constituents in e-cigarette flavors, such as glycidol, acetol, and diacetyl, have been detected in e-cigarette vapors.^[128] High amounts of flavoring agents have been found in e-cigarette vapors.^[94] A 2019 report suggested that users of menthol and mint-flavored e-cigarettes may be exposed to higher levels of pulegone than that is considered acceptable by the US FDA for intake in food, and even higher than in smokers of conventional menthol cigarettes.^[129]

Cherry-flavored e-cigarette vapor contained higher amounts of benzaldehyde in comparison to tobacco smoke.^[130] Flavoring substances from roasted coffee beans have been found in the e-cigarette vapor.^[18] The aroma chemicals acetamide and cumarine have been found in the e-cigarette vapor.^[131]

Cinnamaldehyde is one of the most prevalent flavors in e-liquids, and it-has been found in e-cigarette aerosols.^[124] A 2020 review states that "Several flavor chemicals may pyrolyze or react with other components of EC liquids and produce new, potentially harmful chemicals. For instance, flavor aldehydes, including benzaldehyde, cinnamaldehyde, citral, ethyl vanillin and vanillin rapidly react with PG after mixing, producing aldehyde PG acetals, detected in many commercial e-liquids."^[124] Flavor additives contribute to most of the aldehydes produced during e-cigarette usage.^[123] Synthetic cooling agents (e.g., WS-3 and WS-23) have been detected in the e-cigarette vapors.^[125]

Dripping and dabbing

E-cigarette vapor can contain a range of toxicants, and since they have been be used in methods unintended by the producer such as dripping or mixing liquids, this could result in generating greater levels of toxicants.^[132] "Dripping", where the liquid is dripped directly onto the atomizer, could yield a higher level of nicotine when the liquid contains nicotine, and also a higher level of chemicals may be generated from heating the other contents of the liquid, including formaldehyde.^[132] Dripping may result in higher levels of aldehydes.^[133] Considerable pyrolysis might occur during dripping.^[6] The practice of super-heating the liquid by dripping and dabbing it onto a torch-flamed spike (nail) using specific devices designed for inhalation of the concentrated vapors produced by the procedure may also lead to production of toxic new agents.^[134]

Operation conditions

Emissions of certain compounds increased over time during use as a result of increased residues of polymerization by-products around the coil.^[135] As the devices age and get dirty, the constituents they produce may become different.^[49] Proper cleaning or more routine replacement of coils may lower emissions by preventing buildup of residual polymers.^[135]

Production of byproducts in the aerosol significantly increases as a device is consuming e-liquid that is progressively "aging", even without depletion.^[51] Available evidence seems to suggest that maintenance of optimal operation conditions (e.g., adequate wick saturation and avoiding excessive coil heating) is associated with lower levels of carbonyls.^[120]

The literature suggests that the age of the coil influences carbonyl production, with higher carbonyl emissions associated with older devices or components.^[120] To minimize potential toxicant exposure, a 2020 review recommends that e-cigarette manufacturers should select high-quality metals, minimize soldering parts, and recommended timing of coil replacement as a function of coil use.^[120]

Corrosion

A 2020 study examined the concentrations of metals in cartridges and pods of old devices.^[136] In all cases the older cartridges showed higher metal levels, thus indicating that longer storage time makes corrosion and leaching extremely likely.^[136] A 2022 review states that the four months between purchase and analysis in the devices and cartridges tested by a 2022 study, together with finding very high metal levels only in a single combination of pod/cartridge (Vuse Alto flavor Mint-sation), clearly favors corrosion effects over the alternative explanations suggested by the authors of the studies (product variability, heating effects, pH of e-liquids).^[136]

It is possible that leaching and corrosion might be more prevalent in closed systems because their cartridges are more likely to undergo longer storage time between their manufacturing and usage.^[136] Open devices are not stored with e-liquid and the delay between purchase, e-liquid filling and its vaporization for usage is typically shorter (below one or two days), thus reducing the likelihood of leaching and corrosion.^[136] While most users typically consume these products within the next few days after their purchase, the lack of proper maintenance by users might cause leaching, corrosion, and degradation problems.^[136]

Metals and other content

An intact e-cigarette rebuilder atomizer

The unassembled components of an e-cigarette rebuilder atomizer

The contribution of e-cigarettes to metal/metalloid exposure is not fully understood, particularly because of the rapidly changing nature of devices and e-liquids.^[137] Device design, e-liquid composition, and operation preferences can affect the metal/metalloid levels that e-cigarettes deliver to users.^[137] Substantial diversness exists across products and, in particular, across e-liquids that are in contact with the heating coil.^[137] There is evidence that aerosols have higher metal/metalloid levels than the unused e-liquids have.^[137] These findings indicate that higher metal/metalloid levels in aerosol samples are, at least in part, due to the metal/metalloid components of the devices.^[137] Manufacturing procedures could constitute a major contribution to potential metal impurities and could influence metal/metalloid release during vaping.^[137]

Metal parts of e-cigarettes in contact with the e-liquid can contaminate it with metal particles.^[24] The temperature of the atomizer can reach up to 500 °F.^[138] The atomizer contains metals and other parts where the liquid is kept, and an atomizer head is made of a wick and metal coil which heats the liquid.^[139] Due to this design, some metals potentially are found in the e-cigarette vapor.^[139] E-cigarette devices differ in the amount of metals in the e-cigarette vapor.^[140] This may be associated with the age of various cartridges, and also what is contained in the atomizers and coils.^[140] Usage behavior may contribute to variations in the specific metals and amounts of metals found in e-cigarette vapor.^[141] An atomizer made of plastics could react with e-liquid and leach plasticizers.^[139] The amounts and kinds of metals or other materials found in the e-cigarette vapor is based on the material and other manufacturing designs of the heating element.^[142] E-cigarettes devices can be made with ceramics, plastics, rubber, filament fibers, and foams, to which some can be found in the e-cigarette vapor.^[142] E-cigarette parts, including exposed wires, wire coatings, solder joints, electrical connectors, heating element material, and vitreous fiber wick material, account for the second significant source of substances, of which users may be exposed.^[19] Metal and silicate particles, some of which are at higher levels than in traditional cigarettes, have been detected in e-cigarette aerosol, resulting from degradation from the metal coil used to heat the solution.^[143] Other materials used are Pyrex glass rather than plastics and stainless steel rather than metal alloys.^[144]

Metals and metal nanoparticles have been found in tiny amounts in e-cigarette vapor.^[24] In comparison to cigarette smoke, e-cigarette vapor generally produces high levels of nanoparticles and less larger particles (below 10 μM).^[124] All tested e-cigarettes generate nanoparticles.^[30] Aluminum,^[64] antimony,^[145] barium,^[139] boron,^[145] cadmium,^[146] chromium,^[4] cobalt,^[147] copper,^[24] iron,^[24] lanthanum,^[145] lead,^[146] magnesium,^[148] manganese,^[139] mercury,^[149] nickel,^[146] potassium,^[145] silicate,^[24] silver,^[24] sodium,^[148] strontium,^[139] tin,^[24] titanium,^[139] zinc,^[139] and zirconium have been found in e-cigarette vapor.^[139] Arsenic may leach from the device itself and may end up in the liquid, and then the e-cigarette vapor.^[150] Arsenic have been found in some e-liquids, and in e-cigarette vapor.^[145]

Considerable differences in exposure to metals have been identified from the e-cigarettes tested, particularly metals such as cadmium, lead, and nickel.^[139] Poor quality first-generation e-cigarettes produce several metals in their vapor, in some cases the amounts were greater than with cigarette smoke.^[24] A 2013 study found metal particles in the e-cigarette vapor were at concentrations 10-50 times less than permitted in inhalation medicines.^[18] Vaping devices that use rechargeable batteries with a voltage ranging from 3 to 6 can heat a metal coil as high as 1000 °C, which is higher than the boiling points of various metals such as cadmium and zinc.^[152] As a result, the e-cigarette vapors have been shown to contain heavy metals greatly surpassing health-related limits.^[152] E-cigarette users were found to have greater serum concentrations of certain rare-earth elements such as selenium, silver, vanadium, and lanthanides in comparison with traditional cigarette users.^[124]

A 2018 study found significantly higher amounts of metals in e-cigarette vapor samples in comparison with the e-liquids before they came in contact with the customized e-cigarettes that were provided by everyday e-cigarette users.^[153] Lead and zinc were 2,000% higher and chromium, nickel, and tin were 600% higher.^[153] The e-cigarette vapor levels for nickel, chromium, lead, manganese surpassed occupational or environmental standards for at least 50% of the samples.^[153] The same study found 10% of the e-liquids tested contained arsenic and the amounts remained about the same as the e-cigarette vapor.^[153] The average amounts of exposure to cadmium from 1,200 e-cigarette puffs were found to be 2.6 times lower than the chronic Permissible Daily Exposure (PDE) from inhalation medications, outlined by the US Pharmacopeia.^[139] One sample tested resulted in daily exposure 10% greater than chronic PDE from inhalation medications, while in four samples the amounts were comparable to outdoor air levels.^[139] Cadmium and lead have been found in the e-cigarette vapor at 2–3 times greater levels than with a nicotine inhaler.^[24] A 2015 study stated the amount of copper have been found to be six times greater than with cigarette smoke.^[62] A 2013 study stated the levels of nickel have been found to be 100 times higher than cigarette smoke.^[154] A 2014 study stated the levels of silver have been found to be at a greater amount than with cigarette smoke.^[62] Increased amounts of copper and zinc in vapor generated by some e-cigarettes may be the result of corrosion on the brass electrical connector as indicated in particulates of copper and zinc in e-liquid.^[19] In addition, a tin solder joint may be subjected to corrosion, which may result in increased amounts of tin in some e-liquids.^[19]

Generally, low levels of contaminates from the devise irself may include metals from the heating coils, solders, and wick.^[112] The metals nickel, chromium, and copper coated with silver have been used to make the normally thin-wired e-cigarette heating elements.^[81] The atomizers and heating coils possibly contain aluminum.^[139] They likely account for most of the aluminum in the e-cigarette vapor.^[139] The chromium used to make the atomizers and heating coils is probably the origin of the chromium.^[139] Copper is commonly used to make atomizers.^[139] Atomizers and heating coils commonly contain iron.^[139] Cadmium, lead, nickel, and silver originated from the heating element.^[155] Silicate particles may originate from the fiberglass wicks.^[156] Silicate nanoparticles have been found in vapors generated from the fiberglass wicks.^[25] Tin may originate from the e-cigarette solder joints.^[64] Nickel potentially found in the e-cigarette vapor may originate from the atomizer and heating coils.^[139] The nanoparticles can be produced by the heating element or by pyrolysis of chemicals directly touching the wire surface.^[112] Chromium, iron, tin, and nickel nanoparticles potentially found in the e-cigarette vapor can originate from the e-cigarette heating coils.^[142] Copper nanoparticles have been found in the e-cigarette vapor.^[157] Kanthal and nichrome are frequently used heating coils which may account for chromium and nickel in the e-cigarette vapor.^[139] Metals can originate from the "cartomizer" from the later-generation devices where an atomizer and cartridge are constructed into one unit.^[158] Metal and glass particles can be created and vaporized because of the heating of the liquid with glass fiber.^[20]

Carbonyls and other content

E-cigarette makers do not fully disclose information on the chemicals that can be released or synthesized during use.^[4] The chemicals in the e-cigarette vapor can be different than with the liquid.^[158] Once vaporized, the ingredients in the e-liquid go through chemical reactions that form new compounds not previously found in the liquid.^{[note 10]}^[26] Many chemicals, including carbonyl compounds, such as formaldehyde, acetaldehyde, acrolein, and glyoxal can inadvertently be produced when the nichrome wire (heating element) that touches the e-liquid is heated and chemically reacted with the liquid.^[27] Several degradation breakdown products have been linked to the carrier solvents glycerin and propylene glycol.^[160] Glycidol and acrolein are mainly generated by glycerin degradation, whereas acetol and 2-propen-1-ol are generated mainly from propylene glycol.^[160] Unidentified toxicants may be produced when the e-liquid is combined with multiple substances and other contaminants.^[161] Acrolein and other carbonyls have been found in e-cigarette vapors that were created by unmodified e-cigarettes, indicating that formation of these compounds could be more common than previously thought.^[6]

A 2017 review found "Increasing the battery voltage from 3.3 V to 4.8 V doubles the amount of e-liquid vapourized and increases the total aldehyde generation more than threefold, with acrolein emission increasing tenfold."^[112] A 2014 study stated that "increasing the voltage from 3.2–4.8 V resulted in a 4 to >200 times increase in the formaldehyde, acetaldehyde, and acetone levels".^[27] The amount of carbonyl compounds in e-cigarette aerosols varies substantially, not only among different brands but also among different samples of the same products, from 100-fold less than tobacco to nearly equivalent values.^[90]

The propylene glycol-containing liquids produced the most amounts of carbonyls in e-cigarette aerosols.^[27] When a propylene glycol aerosol is formed by heating and atomization, decomposition products may be formed, including acetic acid, lactic acid, and propanol.^[162] Propylene glycol could turn into propylene oxide when heated and aerosolized.^{[note 11]}^[64]^[88] Glycerin may generate acrolein when heated at hotter temperatures.^{[note 12]}^[18] Some e-cigarette products had acrolein identified in the e-cigarette vapor, at greatly lower amounts than in cigarette smoke.^[18] Several e-cigarette companies have replaced glycerin and propylene glycol with ethylene glycol.^[5] In 2014, a significant number of e-cigarette companies began to use water and glycerin as replacement for propylene glycol.^[31] In 2015, e-cigarette companies attempted to reduce the formation of formaldehyde and metal substances of the e-cigarette vapor by producing an e-liquid in which propylene glycol is replaced by glycerin.^[28]

Acetol,^[163] beta-nicotyrine,^[84] butanal,^[27] crotonaldehyde,^[128] farnesol,^[164] glyceraldehyde,^[19] glycidol,^[42] glyoxal,^[165] dihydroxyacetone,^[42] dioxolanes,^[19] lactic acid,^[19] methylglyoxal,^[166] myosmine,^[84] oxalic acid,^[19] propanal,^[167] pyruvic acid,^[19] and vinyl alcohol isomers have been found in the e-cigarette vapor.^[42] Hydroxymethylfurfural and furfural have been found in the e-cigarette vapors.^[168] The amounts of furans in the e-cigarette vapors were highly associated with power of the e-cigarette and amount of sweetener.^[168] The amount of carbonyls vary greatly among different companies and within various samples of the same e-cigarettes.^[27] Oxidants and reactive oxygen species (OX/ROS) have been found in the e-cigarette vapor.^[6] OX/ROS could react with other chemicals in the e-cigarette vapor because they are highly reactive, causing alterations its chemical composition.^[6] E-cigarette vapor have been found to contain OX/ROS at about 100 times less than with cigarette smoke.^[6] A 2018 review found e-cigarette vapor containing reactive oxygen radicals seem to be similar to levels in traditional cigarettes.^[169]

Contamination with various chemicals have been identified.^[7] Some products contained trace amounts of the drugs tadalafil and rimonabant.^[7] The amount of either of these substances that is able to transfer from liquid to vapor phase is low.^[171] Pesticides were detected in the e-cigarette aerosols.^[172] Flame retardants were also found in e-cigarette aerosols.^[3]

m-Xylene, p-Xylene, o-Xylene, ethyl acetate, ethanol, methanol, pyridine, acetylpyrazine, 2,3,5-trimethylpyrazine, octamethylcyclotetrasiloxane,^[173] catechol, m-Cresol, and o-Cresol have been found in the e-cigarette vapor.^[173] A 2017 study found that "The maximum detected concentrations of benzene, methanol, and ethanol in the samples were higher than their authorized maximum limits as residual solvents in pharmaceutical products."^[173] Trace amounts of toluene^[146] and xylene have been found in the e-cigarette vapor.^[24] Polycyclic aromatic hydrocarbons (PAHs),^[24] aldehydes, volatile organic compounds (VOCs), phenolic compounds, tobacco alkaloids, o-Methyl benzaldehyde, 1-Methyl phenanthrene, anthracene, phenanthrene, pyrene, and cresol have been found in the e-cigarette vapor.^[4] While the cause of these differing concentrations of minor tobacco alkaloids is unknown, Lisko and colleagues (2015) speculated potential reasons may derive from the e-liquid extraction process (i.e., purification and manufacturing) used to obtain nicotine from tobacco, as well as poor quality control of e-liquid products.^[90] In some studies, small quantities of VOCs including styrene have been found in the e-cigarette vapor.^[158] A 2014 study found the amounts of PAHs were above specified safe exposure limits.^[174]

Low levels of isoprene, acetic acid, 2-butanodione, acetone, propanol, and diacetin, and traces of apple oil (3-methylbutyl-3-methylbutanoate) have been found in the e-cigarette vapor.^[64] Acrylonitrile and ethylbenzene have been found in the e-cigarette vapor.^[175] Benzene and 1,3-Butadiene have been found in the e-cigarette vapor at many-fold lower than in cigarette smoke.^[142] Some e-cigarettes contain diacetyl and acetaldehyde in the e-cigarette vapor.^[176] Diacetyl and acetylpropionyl have been found at greater levels in the e-cigarette vapor than is accepted by the National Institute for Occupational Safety and Health,^[177] although diacetyl and acetylpropionyl are normally found at lower levels in e-cigarettes than with traditional cigarettes.^[177] A 2018 PHE report stated that diacetyl was identified at hundreds of times in lesser amounts than found in cigarette smoke.^[178] A 2016 WHO report found that acetaldehyde from second-hand vapor was between two and eight times greater compared to background air levels.^[105]

Tobacco-specific nitrosamines and impurities

Nicotine-containing e-liquids are extracted from tobacco that may contain impurities.^[18] The nicotine impurities in the e-liquid varies greatly across companies.^[97] Since e-liquid production is not rigorously regulated, some e-liquids can have amounts of impurities higher compared to limits for pharmaceutical-grade nicotine products.^[158]

Tobacco-specific nitrosamines (TSNAs) such as nicotine-derived nitrosamine ketone (NNK) and N-Nitrosonornicotine (NNN) and tobacco-specific impurities have been found in the e-cigarette vapor at very low levels,^[146] comparable to amounts found in nicotine replacement products.^[24] A 2014 study that tested 12 e-cigarette devices found that most of them contained tobacco-specific nitrosamines in the e-cigarette vapor.^[179] In contrast, the one nicotine inhaler tested did not contain tobacco-specific nitrosamines.^[179] N-Nitrosoanabasine and N'-Nitrosoanatabine have been found in the e-cigarette vapor at lower levels than cigarette smoke.^[180] Tobacco-specific nitrosamines (TSNAs), nicotine-derived nitrosamine ketone (NNK), N-Nitrosonornicotine (NNN), and N′-nitrosoanatabine have been found in the e-cigarette vapor at different levels between different devices.^[15] Tobacco-specific impurities such as cotinine, nicotine-N'-oxides (cis and trans isomers), and beta-nornicotyrine are believed to be the result of bacterial action or oxidation during the extracting of nicotine from tobacco.^[158] Nicotyrine can be created through oxidization after the opening of a refillable e-liquid.^[52] The percentage of nicotyrine to nicotine in the e-liquid as well as the e-cigarette aerosol goes up as time passes.^[52]

Formaldehyde

An e-cigarette with a variable voltage battery

A pen-style second-generation e-cigarette

A 2016 WHO report found that formaldehyde from second-hand vapor was around 20% greater compared to background air levels.^[105] Normal usage of e-cigarettes generates very low levels of formaldehyde.^[181] Different power settings reached significant differences in the amount of formaldehyde in the e-cigarette vapor across different devices.^[182] Later-generation e-cigarette devices can create greater amounts of carcinogens.^[8] Some later-generation e-cigarettes let users increase the volume of vapor by adjusting the battery output voltage.^[27]

Depending on the heating temperature, the carcinogens in the e-cigarette vapor may surpass the levels of cigarette smoke.^[26] E-cigarettes devices using higher voltage batteries can produce carcinogens including formaldehyde at levels comparable to cigarette smoke.^[183] The later-generation and "tank-style" devices with higher voltages (5.0 V^[26]) could produce formaldehyde at comparable or greater levels than in cigarette smoke.^[8] A 2015 study hypothesized from the data that at high voltage (5.0 V), a user, "vaping at a rate of 3 mL/day, would inhale 14.4 ± 3.3 mg of formaldehyde per day in formaldehyde-releasing agents."^[26] The 2015 study used a puffing machine showed that a third-generation e-cigarette turned on to the maximum setting would create levels of formaldehyde between five and 15 times greater than with cigarette smoke.^[184] E-cigarette vapor can contain formaldehyde at levels five to 15 times higher than traditional cigarettes.^[185]

Studies have established that free aldehydes are produced during regular use conditions, although formaldehyde hemiacetal production increases dramatically with battery output.^[117] It has been suggested that e-cigarette users tend to stay clear of the harsh taste that is related to the creation of aldehydes during excessive heating or dry puffing.^[6] But e-cigarette users may "learn" to overcome the unpleasant taste due to elevated aldehyde formation, when the nicotine craving is high enough.^[6] Initial studies reported that formaldehyde was formed during the vaping process under high heat conditions.^[29] Although some of the more recent e-cigarette devices limit temperature in an attempt to minimize this, multiple reports have documented the formation of acetaldehyde, acrolein, diacetyl, and formaldehyde under a wide range of conditions.^[29] A 2018 study "shows that carbonyl formation can be catalyzed by e-cigarette metal heating coil materials, enabling carbonyl formation at coil temperatures far below those associated with the dry puff phenomenon."^[3] A 2018 study regarding "coil temperature and wicking variables also resulted in the conclusion that concerning levels of formaldehyde in frequent e-cigarette users can be produced at relatively low power levels, and within the range of operating temperatures observed by human subjects to afford sensorially pleasant conditions, i.e., not under dry-puff conditions."^[3] Stronger powered e-cigarette devices may increase the levels of the aldehydes produced.^[186] High voltage e-cigarettes are capable of producing large amounts of carbonyls.^[27] Reduced voltage (3.0 V^[4]) e-cigarettes had e-cigarette aerosol levels of formaldehyde and acetaldehyde roughly 13 and 807-fold less than with cigarette smoke.^[27]

Unlabeled ingredients

Unlabeled ingredients present in the aerosols of the e-cigarette devices include carbonyls (acetaldehyde, acrolein, formaldehyde) and heavy metals (arsenic, chromium, copper, iron, manganese, nickel, lead, selenium, strontium, zinc).^[164]

Pathogens

E-liquid used in e-cigarettes have been found to be contaminated with fungi and bacteria, in many studies.^[58] The coil can also become contaminated with fungus and bacteria.^[187] The contamination from microbial toxins may occur prior to use.^[188] There was 27% bacterial and 81% fungal contamination of single use and refillable e-liquids from 75 different e-cigarette products.^[39] The contamination with B-D-glucan and endotoxin was from popular US vape liquids.^[188] Compared to fruit flavored e-liquids, the levels of B-D-glucan were detected at 10 and 3.5 times greater in tobacco and menthol flavored e-liquids.^[189] Compared to the e-liquids, the levels of endotoxin were detected at 3.2 times greater in the cartridges.^[189]

A 2019 study found a noticeable effect of e-cigarette vapor on the development of biofilm from the lung pathogens and discharge of cytokines.^[189] In comparison to never-smokers, the oral microbiome of vapers exhibited a considerably greater bacterial operational taxonomic units of species and a considerable variation in bacterial communities.^[189] There is a strong relationship between the bacterial taxa in the saliva and nicotine vaping, and oral bacterial infection was greatly increased from being exposed to the aerosols of the e-cigarette.^[189]

Psychoactive substances

E-cigarettes are also used to inhale illegal drugs.^[190] E-cigarettes are being used to inhale 3,4-methylenedioxymethamphetamine (MDMA), cocaine powder, crack cocaine, synthetic cathinones, mephedrone, α-PVP, synthetic cannabinoids, opioids, heroin, fentanyl, tryptamines, and ketamine.^[191] Tetrahydrocannabinol (THC) and cannabinoid (CBD) oils are common drugs that are added to e-liquids to inhale.^[190] Cannabis plants, which are used to obtain THC, can soak up metals from the soil.^[192] Other chemicals that are added to e-liquids are benzoylmethylecgonine (cocaine), gamma-hydroxybutyric acid (GHB), heroin, fentanyl, 3,4-methylenedioxyamphetamine (MDA), and methamphetamine.^[190]

2019–2020 vaping lung illness outbreak

A 2020 review states that there has been an outbreak of a vaping-induced lung injury.^[193] Cartridges containing THC and CBD have been introduced to the market.^[193] These cartridges predominantly use carriers such as mineral oil and medium-chain triglycerides.^[193] The components of the inhaled vaping products also included vitamin E acetate, which is suspected of being one of the causes of inducing pulmonary toxicity—leading to acute lung injury.^[193] A 2020 study found more 500 chemicals contained in illicit THC vape cartridges that were retrieved from people with a vaping-induced lung injury.^[194] In contrast to CBD-infused and medical-grade vape cartridges, several of these chemicals were exclusive to illicit THC vape cartridges.^[194] These chemicals that were exclusive to illicit THC vape cartridges include decane, 2,2-dimethoxybutane, tetramethyl silicate, siloxanes, methyl and ethyl esters, in addition to vitamin E acetate and other acetates.^[194]

Pesticides, oils, diluents, plasticizers, and several other toxicants have been found in Illegally sold THC vaping products that were linked to this outbreak.^[195] Mutiple chemicals were detected in the liquids of the counterfeit cartridges used by people who were diagnosed with a vaping-induced lung injury.^[195] These included pesticide residues such as myclobutanil and piperonyl butoxide-d9, bifenazate, bifenthrin, 2,2-dimethoxybutane, tetramethyl silicate, decane, methyl esters, ethyl esters, siloxanes, and acetates, in addition to pine rosin acids, pine rosin derived methyl esters, dipropylene glycol dibenzoate isomers, and sucrose acetate isobutyrate substances.^[195] Chemicals identified in the aerosol produced from counterfeit cartridges are, but not limited to, n-butane, benzene, xylene, pentene, ethanol, acetone, ethylbenzene and toluene, PCP-polycaprolactone/household substances such as methacrolein, acetaldehyde, crotonaldehyde, and formaldehyde, other toxic chemicals such as acrolein, pentadiene compounds, hexane compounds, and methyl vinyl ketone, and metals including silicon, copper, nickel, and lead.^[195]

Comparison of levels of metals in e-cigarette aerosol

Amounts of metals from e-cigarette use compared with regulatory safety limits∗^[139]
Metals	EC01	EC02	EC03	EC04	EC05	EC06	EC07	EC08	EC09	EC10	EC11	EC12	EC13	Average
Cadmium; per 1200 puffs	1.2	1.04	1.04	0	0.16	1.6	0	0.48	0	1.2	0.08	0	NM	0.57
Permissible Daily Exposure; (United States Pharmacopeia)	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5
Chromium; per 1200 puffs	0	0	0	0	0	0	0	0	0	0	0	0	0.84	0.06
Permissible Daily Exposure; (United States Pharmacopeia)	25	25	25	25	25	25	25	25	25	25	25	25	25
Copper; per 1200 puffs	0	0	0	0	0	0	0	0	0	0	0	0	24.36	1.87
Permissible Daily Exposure; (United States Pharmacopeia)	70	70	70	70	70	70	70	70	70	70	70	70	70
Lead; per 1200 puffs	0.32	0.32	0.4	0.08	0.24	0.08	0.16	4.4	0.56	0.32	0.16	0.08	2.04	0.70
Permissible Daily Exposure; (United States Pharmacopeia)	5	5	5	5	5	5	5	5	5	5	5	5	5
Nickel; per 1200 puffs	0.88	0.96	0.32	0	0	0	0.48	0.72	0.16	0	0	0	0.6	0.32
Permissible Daily Exposure; (United States Pharmacopeia)	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5
Manganese; per 1200 puffs	0	0	0	0	0	0	0	0	0	0	0	0	0.24	0.02
Minimal Risk Level; Agency for Toxic; Substances and Disease Registry	6	6	6	6	6	6	6	6	6	6	6	6	6
Aluminum; per 1200 puffs	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	47.28	47.28
Recommended Exposure Limit; National Institute for Occupational Safety and Health	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500
Barium; per 1200 puffs	0	0	0	0	0	0	0	0	0	0	0	0	1.44	0.11
Recommended Exposure Limit; National Institute for Occupational Safety and Health	4,150	4,150	4,150	4,150	4,150	4,150	4,150	4,150	4,150	4,150	4,150	4,150	4,150
Iron; per 1200 puffs	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	62.4	62.40
Recommended Exposure Limit; National Institute for Occupational Safety and Health	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500
Tin; per 1200 puffs	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	4.44	4.44
Recommended Exposure Limit; National Institute for Occupational Safety and Health	16,600	16,600	16,600	16,600	16,600	16,600	16,600	16,600	16,600	16,600	16,600	16,600	16,600
Titanium; per 1200 puffs	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	0.24	0.24
Recommended Exposure Limit; National Institute for Occupational Safety and Health	2,490	2,490	2,490	2,490	2,490	2,490	2,490	2,490	2,490	2,490	2,490	2,490	2,490
Zinc; per 1200 puffs	0	0	0	0	0	0	0	0	0	0	0	0	6.96	0.54
Recommended Exposure Limit; National Institute for Occupational Safety and Health	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500
Zirconium; per 1200 puffs	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	0.84	0.84
Recommended Exposure Limit; National Institute for Occupational Safety and Health	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500	41,500

Abbreviations: EC, electronic cigarette; NM, not measured.^[139]
∗The findings are a comparison between e-cigarette daily usage and the regulatory limits of chronic Permissible Daily Exposure from inhalation medications outlined by the US Pharmacopeia for cadmium, chromium, copper, lead and nickel, the Minimal Risk Level outlined by the Agency for Toxic Substances and Disease Registry for manganese and the Recommended Exposure Limit outlined by the National Institute for Occupational Safety and Health for aluminum, barium, iron, tin, titanium, zinc and zirconium,^[139] referring to a daily inhalation volume of 20 m³ air and a 10-h volume of 8.3 m³; values are in μg.^[139]

Chemical analysis of e-cigarette cartridges, solutions, and aerosol

Studies involving chemical analysis of e-cigarette cartridges, solutions, and aerosol.^[196]
Authors (Reference)	E-cigarette brand	Substances tested	Analysis	Key finding
Studies reporting positive or neutral impact of e-cigarettes, vaping, or harm reduction based on the absence or presence of specific toxicants
Laugesen (9) (Research funded by Runyan)	Runyon	TSNA	LC-MS	TSNAs are present but at levels much lower than in conventional cigarettes and too small to be carcinogenic
		MAO-A and B inhibitors	Fluorometric assay	MAO-A and B are inhibited by tobacco smoke but unaffected by e-cigarette fluid
		PAH	GS-MS	Polycyclic aromatic hydrocarbons undetectable
		Heavy metals	ICP-MS	Heavy metals were undetectable
		CO	CO analyzer	Exhaled carbon monoxide does not increase after e-cigarette use
McAuley et al. (11)	Brand not indicated.	TSNA	GC/MS	TSNA, PAH, diethylene glycol, VOC, and carbonyls in e-cigarette aerosol were all negligible compared to cigarette smoke.
		PAH	GC/MS
		Diethylene Glycol	GC/MS
		VOC	HS-GC/MS
		Carbonyls	HPLC-UV
Pellegrino et. al. (56)	Italian brand of e-cigarettes	Particulate matter	Particle counter and smoking machine	Particulate matter is lower in e-cigarette aerosol compared to cigarette smoke
Goniewicz et al. (53)	Eleven brands of Polish and one brand of English e-cigarettes	Carbonyls	HPLC-DAD	TSNA, VOC, and carbonyl compounds were determined to be between 9 and 450 times lower in e-cigarettes aerosol compared to conventional cigarette smoke
		VOC	GC-MS
		TSNA	UPLC-MS
		Heavy metals	ICP-MS	Heavy metals present in e-cigarette aerosol
Kim and Shin (55)	105 Replacement liquid brands from 11 Korean e-cigarette companies	TSNA	LC-MS	TSNAs are present at low levels in e-cigarette replacement liquids
Schripp et al. (54)	Three unidentified brands	VOC	GC-MS	VOC in e-cigarette cartridges, solutions, and aerosolized aerosol were low or undetectable compared to conventional cigarettes
		Particulate matter	Particle counter and smoking machine	Particulate matter is lower in e-cigarette aerosol compared to cigarette smoke
Studies reporting negative impact of e-cigarettes, vaping, or harm reduction based on presence of specific toxicants
Westenberger (4) FDA study	Njoy	TSNA	LC-MS	TSNA present
	Smoking everywhere	Diethylene glycol	GC-MS	Diethylene glycol present
		Tobacco specific impurities	GC-MS	Tobacco specific impurities present
Trehy et al. (58) FDA study	Njoy	Nicotine related impurities	HPLC-DAD	Nicotine related impurities present
	Smoking everywhere
	CIXI
	Johnson creek
Hadwiger et al. (57) FDA study	Brand not indicated	Amino-tadalafil	HPLC-DAD-MMI-MS	Amino-tadalafil present
		Rimonabant		Rimonabant present
Williams et al. (50)	Brand not indicated	Heavy metals	ICP-MS	Heavy metal and silicate particles present in e-cigarette aerosol
		Silicate particles	Particle counter and smoking machine, light and electron microscopy, cytotoxicity testing, x-ray microanalysis

Abbreviations: TSNA, tobacco specific nitrosoamines; LC-MS, liquid chromatography-mass spectrometry; MAO-A and B, monoamineoxidase A and B; PAH, polycyclic aromatic hydrocarbons; GS-MS, gas chromatography – mass spectrometry; ICP-MS, inductively coupled plasma – mass spectrometry; CO, carbon monoxide, VOC, volatile organic compounds; UPLC-MS, ultra-performance liquid chromatography-mass spectrometry; HPLC-DAD-MMI-MS, high performance liquid chromatography-diode array detector-multi-mode ionization-mass spectrometry.^[196]

Aldehydes in e-cigarette aerosol

Aldehydes in aerosols of e-cigarettes∗^[4]
Study	Units	Formaldehyde	Acetaldehyde	Acrolein	o-Methyl benzaldehyde	Acetone
Goniewicz et al.	μg/150 puffs	3.2±0.8 to	2.0±0.1 to	N.D. to	1.3±0.8 to	N.T.
Ohta et al.	mg/m³	260	<LOQ	<LOQ	N.T.	N.T.
Uchiyama et al.	mg/m³	8.3	11	9.3	N.T.	2.9
Laugesen	ppm/38 mL puff	0.25	0.34	N.D. to 0.33	N.T.	0.16

∗Abbreviations: <LOQ, below the limit of quantitation but above the limit of detection; N.D., not detected; N.T., not tested.^[4]

Tobacco-specific nitrosamines in nicotine-containing products

Tobacco-specific nitrosamines in various nicotine-containing products∗^[12]
Item	NNN (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone)	NNK (N'-nitrosonornicotine)	NAT (N'-nitrosoanatabine)	NAB (N'-nitrosoanabasine)
Nicorette gum (4 mg)	2.00	Not detected	Not detected	Not detected
NicoDerm CQ patch (4 mg)	Not detected	8.00	Not detected	Not detected
E-cigarettes	3.87	1.46	2.16	0.69
Swedish snus	980.00	180.00	790.00	60.00
Winston (full)	2200.00	580.00	560.00	25.00
Marlboro (full)	2900.00	960.00	2300.00	100.00

∗ng/g, but not for gum and patch.^[12] ng/gum piece is for gum and ng/patch is for patch.^[12]

Comparison of levels of toxicants in e-cigarette aerosol

Amounts of toxicants in e-cigarette aerosol compared with nicotine inhaler and cigarette smoke^[26]
Toxicant	Range of content in nicotine inhaler mist (15 puffs∗)	Content in aerosol from 12 e-cigarettes (15 puffs∗)	Content in traditional cigarette micrograms (μg) in smoke from one 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	—

Abbreviations: μg, microgram; ng, nanogram; ND, not detected.^[26]
∗Fifteen puffs were chosen to estimate the nicotine delivery of one traditional cigarette.^[26]

Each e-cigarette cartridge, which varies across manufacturers, and each cartridge produces 10 to 250 puffs of vapor.^[197] This correlates to 5 to 30 traditional cigarettes.^[197] A puff usually lasts for 3 to 4 seconds.^[112] A 2014 study found there is wide differences in daily puffs in experienced vapers, which typically varies from 120 to 225 puffs per day.^[112] From puff-to-puff e-cigarettes do not provide as much nicotine as traditional cigarettes.^[198] A 2016 review found "The nicotine contained in the aerosol from 13 puffs of an e-cigarette in which the nicotine concentration of the liquid is 18 mg per milliliter has been estimated to be similar to the amount in the smoke of a typical tobacco cigarette, which contains approximately 0.5 mg of nicotine."^[199]

Regulation recommendations

A 2020 systematic review recommends that regulation is needed to inform e-cigarette users of possible metal/metalloid exposure through vaping as well as to prevent metal/metalloid exposure during e-cigarette use.^[137]

Notes

↑ A 2014 review found "Wide ranges in the levels of chemical substances such as tobacco-specific nitrosamines, aldehydes, metals, volatile organic compounds, phenolic compounds, polycyclic aromatic hydrocarbons, flavours, solvent carriers, tobacco alkaloids and drugs have been reported in e-cigarette refill solutions, cartridges, aerosols and environmental emissions."^[4]
↑ A 2014 review found "there is enough heat generated during puffing to cause the fluid to decompose and/or components of the device to pyrolyze, whereby toxic/carcinogenic substances may be formed."^[5]
↑ The term vapor is a misnomer due to the fact that the aerosol generated by e-cigarettes has both a particulate and gas phase.^[8]
↑ E-cigarette aerosol is composed of droplets of e-liquids, which contain mainly propylene glycol, glycerin, nicotine, water, flavorings (if added to e-liquid), preservatives and also small amounts of by-products of thermal decomposition of some of these constituents.^[17]
↑ A 2017 review found "The physical composition of the aerosol can be altered by many factors: the temperature of the metal coil, rate of e-liquid flow through the heated coil, chemical composition of the coil, the coil connection to the power source, the wicking material transporting e-liquid and the hot aerosol contacts."^[19]
↑ A 2017 review found "As e-cig metal components undergo repeated cycles of heating and cooling, traces of these metal components can leech into the e-liquid, causing the device to emit metallic nanoparticles."^[25]
↑ The activity of puffing an aerosolized liquid and then exhaling it is known as "vaping."^[8]
↑ Horiba states, "The mode is the peak of the frequency distribution, or it may be easier to visualize it as the highest peak seen in the distribution. The mode represents the particle size (or size range) most commonly found in the distribution."^[69]
↑ The user is referred to as a "vaper."^[8]
↑ The presence of new chemicals are formed from the heating process and the e-liquid flavoring.^[159]
↑ A 2017 review found "When heated to high temperatures, as can occur with the use of advanced EC devices, propylene glycol can form thermal dehydration products such as acetaldehyde, formaldehyde, and propylene oxide."^[112]
↑ A 2017 review found "Thermal decomposition of e-cigarette solvents results in release of toxic metals, and formation of an array of organic compounds such as acrolein from glycerol, and propylene oxide from propylene glycol."^[76]

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.
National Academies of Sciences, Engineering, and Medicine; et al. (Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems) (23 January 2018). Stratton, Kathleen; Kwan, Leslie Y.; Eaton, David L. (eds.). Public Health Consequences of E-Cigarettes. Washington, DC: National Academies Press. pp. 1–774. doi:10.17226/24952. ISBN 978-0-309-46834-3. PMID 29894118.{{cite book}}: CS1 maint: multiple names: authors list (link) CS1 maint: ref duplicates default (link) Summary
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.
"State Health Officer's Report on E-Cigarettes: A Community Health Threat" (PDF). California Tobacco Control Program. California Department of Public Health. January 2015. pp. 1–21. This article incorporates text from this source, which is in the public domain.

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↑ Cherian, Sujith V.; Kumar, Anupam; Estrada-Y-Martin, Rosa M. (2020). "E-Cigarette or Vaping Product-Associated Lung Injury: A Review". The American Journal of Medicine. 133 (6): 657–663. doi:10.1016/j.amjmed.2020.02.004. ISSN 0002-9343. PMID 32179055.
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↑ National Academies of Sciences, Engineering, and Medicine 2018, p. 188, TABLE 5-6 Volatile Compounds Detected in E-Cigarette Aerosol.
↑ ^164.0 ^164.1 Bautista, Malia; Mogul, Allison S.; Fowler, Christie D. (14 August 2023). "Beyond the label: current evidence and future directions for the interrelationship between electronic cigarettes and mental health". Frontiers in Psychiatry. 14. doi:10.3389/fpsyt.2023.1134079. PMC 10460914. PMID 37645635. {{cite journal}}: Check |pmc= value (help) This article incorporates text available under the CC BY 4.0 license.
↑ WHO 2016, p. 2.
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↑ ^168.0 ^168.1 National Academies of Sciences, Engineering, and Medicine 2018, p. 196, Other Toxicants, Furans.
↑ Lødrup Carlsen, Karin C.; Skjerven, Håvard O.; Carlsen, Kai-Håkon (2018). "The toxicity of E-cigarettes and children's respiratory health". Paediatric Respiratory Reviews. 28: 63–67. doi:10.1016/j.prrv.2018.01.002. ISSN 1526-0542. PMID 29580719.
↑ "Electronic Cigarettes – What is in e-cigarette aerosol?" (PDF). Centers for Disease Control and Prevention. 22 February 2018.
↑ Palazzolo, Dominic L. (November 2013). "Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review". Frontiers in Public Health. 1 (56): 56. doi:10.3389/fpubh.2013.00056. PMC 3859972. PMID 24350225. This article incorporates text by Dominic L. Palazzolo available under the CC BY 3.0 license.
↑ Szumilas, Paweł; Wilk, Aleksandra; Szumilas, Kamila; Karakiewicz, Beata (6 February 2022). "The Effects of E-Cigarette Aerosol on Oral Cavity Cells and Tissues: A Narrative Review". Toxics. MDPI AG. 10 (2): 74. doi:10.3390/toxics10020074. ISSN 2305-6304. PMC 8878056. PMID 35202260.
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↑ Wilder 2016, p. 84.
↑ Huang, Shu-Jie; Xu, Yan-Ming; Lau, Andy T. Y. (2017). "Electronic cigarette: A recent update of its toxic effects on humans". Journal of Cellular Physiology. 233 (6): 4466–4478. doi:10.1002/jcp.26352. ISSN 0021-9541. PMID 29215738. S2CID 3556795.
↑ Syamlal, Girija; Jamal, Ahmed; King, Brian A.; Mazurek, Jacek M. (2016). "Electronic Cigarette Use Among Working Adults — United States, 2014". MMWR. Morbidity and Mortality Weekly Report. 65 (22): 557–561. doi:10.15585/mmwr.mm6522a1. ISSN 0149-2195. PMID 27281058.
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↑ "Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Restrictions on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products". Federal Register. United States Food and Drug Administration. 81 (90): 28974–29106. 10 May 2016.
↑ Collaco, Joseph M. (2015). "Electronic Use and Exposure in the Pediatric Population". JAMA Pediatrics. 169 (2): 177–182. doi:10.1001/jamapediatrics.2014.2898. PMC 5557497. PMID 25546699.
↑ McNeill 2015, p. 77.
↑ Galper Grossman, Sharon (18 July 2019). "Vape Gods and Judaism—E-cigarettes and Jewish Law". Rambam Maimonides medical journal. Rambam Health Corporation. 10 (3): e0019. doi:10.5041/rmmj.10372. ISSN 2076-9172. PMC 6649778. PMID 31335312. This article incorporates text by Sharon Galper Grossman available under the CC BY 3.0 license.
↑ Heldt, Nathan A.; Reichenbach, Nancy; McGary, Hannah M.; Persidsky, Yuri (February 2021). "Effects of Electronic Nicotine Delivery Systems and Cigarettes on Systemic Circulation and Blood-Brain Barrier". The American Journal of Pathology. 191 (2): 243–255. doi:10.1016/j.ajpath.2020.11.007. PMC 7863131. PMID 33285126.
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↑ Breitbarth, Andreas K.; Morgan, Jody; Jones, Alison L. (2018). "E-cigarettes—An unintended illicit drug delivery system". Drug and Alcohol Dependence. 192: 98–111. doi:10.1016/j.drugalcdep.2018.07.031. ISSN 0376-8716. PMID 30245461.
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External links

[53] Cancer inhalation risk values provide an excess lifetime exposure risk, in this case the human lung cancer risk at a 1 in 100,000 (E-5) level.

[54] Noncancer inhalation risk values indicate levels and exposure times at which no adverse effect is expected; here values for continuous lifetime exposure are listed.

[55] Unit risk in risk/pCi = 1.08E-08.

[5] A 2014 review found "Wide ranges in the levels of chemical substances such as tobacco-specific nitrosamines, aldehydes, metals, volatile organic compounds, phenolic compounds, polycyclic aromatic hydrocarbons, flavours, solvent carriers, tobacco alkaloids and drugs have been reported in e-cigarette refill solutions, cartridges, aerosols and environmental emissions."^[4]

[7] A 2014 review found "there is enough heat generated during puffing to cause the fluid to decompose and/or components of the device to pyrolyze, whereby toxic/carcinogenic substances may be formed."^[5]

[11] The term vapor is a misnomer due to the fact that the aerosol generated by e-cigarettes has both a particulate and gas phase.^[8]

[21] E-cigarette aerosol is composed of droplets of e-liquids, which contain mainly propylene glycol, glycerin, nicotine, water, flavorings (if added to e-liquid), preservatives and also small amounts of by-products of thermal decomposition of some of these constituents.^[17]

[24] A 2017 review found "The physical composition of the aerosol can be altered by many factors: the temperature of the metal coil, rate of e-liquid flow through the heated coil, chemical composition of the coil, the coil connection to the power source, the wicking material transporting e-liquid and the hot aerosol contacts."^[19]

[31] A 2017 review found "As e-cig metal components undergo repeated cycles of heating and cooling, traces of these metal components can leech into the e-liquid, causing the device to emit metallic nanoparticles."^[25]

[77] The activity of puffing an aerosolized liquid and then exhaling it is known as "vaping."^[8]

[80] Horiba states, "The mode is the peak of the frequency distribution, or it may be easier to visualize it as the highest peak seen in the distribution. The mode represents the particle size (or size range) most commonly found in the distribution."^[69]

[99] The user is referred to as a "vaper."^[8]

[172] The presence of new chemicals are formed from the heating process and the e-liquid flavoring.^[159]

[176] A 2017 review found "When heated to high temperatures, as can occur with the use of advanced EC devices, propylene glycol can form thermal dehydration products such as acetaldehyde, formaldehyde, and propylene oxide."^[112]

[177] A 2017 review found "Thermal decomposition of e-cigarette solvents results in release of toxic metals, and formation of an array of organic compounds such as acrolein from glycerol, and propylene oxide from propylene glycol."^[76]

[Hartmann-BoyceMcRobbie2022-1] Hartmann-Boyce, Jamie; Lindson, Nicola; Butler, Ailsa R; McRobbie, Hayden; Bullen, Chris; Begh, Rachna; Theodoulou, Annika; Notley, Caitlin; Rigotti, Nancy A; Turner, Tari; Fanshawe, Thomas R; Hajek, Peter (17 November 2022). "Electronic cigarettes for smoking cessation". Cochrane Database of Systematic Reviews. 2022 (12). doi:10.1002/14651858.CD010216.pub7. PMC 9668543. PMID 36384212. {{cite journal}}: Check |pmc= value (help)

[Hartmann-BoyceMcRobbie2021-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 Hartmann-Boyce, Jamie; McRobbie, Hayden; Lindson, Nicola; Bullen, Chris; Begh, Rachna; Theodoulou, Annika; Notley, Caitlin; Rigotti, Nancy A; Turner, Tari; Butler, Ailsa R; Fanshawe, Thomas R; Hajek, Peter (29 April 2021). "Electronic cigarettes for smoking cessation". Cochrane Database of Systematic Reviews. 2021 (6). doi:10.1002/14651858.CD010216.pub5. ISSN 1465-1858. PMC 8092424. PMID 33913154.

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v t e Electronic cigarettes
General topics	Construction pod mod Environmental impact Marketing Regulation Safety Cloud-chasing Composition of the aerosol Vape shop
Brands and companies	Blu eCigs Dragonite International Elf Bar Juul Logic Lost Mary NJOY Openvape Pax Labs Puff Bar R. J. Reynolds Vapor Company Ten Motives Veev Vuse
Controversy	Health effects Positions of medical organizations List of vaping bans in the United States Vaping-associated pulmonary injury 2019–2020 vaping lung illness outbreak Nicotine salt
See also	Flavored tobacco Nicotine poisoning Effects of nicotine on human brain development Nicotine marketing
Category Cigarettes Smoking