Home
18.5 Chemicals in e-liquids and e-cigarette aerosols
Foreword

Suggested citation

Download Citation
Winnall, W |Greenhalgh, EM |Bayly, M |Scollo, MM. 18.5 Chemicals in e-liquids and e-cigarette aerosols. In Greenhalgh, EM |Scollo, MM |Winstanley, MH [editors]. Tobacco in Australia: Facts and issues. Melbourne : Cancer Council Victoria; 2019. Available from https://www.tobaccoinaustralia.org.au/chapter-18-e-cigarettes/18-5-chemicals-in-e-liquids-and-e-cigarette-aerosols
Last updated: February 2025

18.5 Chemicals in e-liquids and e-cigarette aerosols

This section focuses on e-cigarette users’ exposure to nicotine and other chemicals found in e-liquids and in the aerosol emitted during e-cigarette use. People may also be exposed to chemicals in a variety of ways during mixing and handling of e-liquids, via the inhalation of secondhand aerosol and through accidental ingestion.

The research in the section has largely tested e-cigarettes that are not on the TGA’s 2025 list of notified products (i.e. products that suppliers have indicated comply with the TGO110 product standard and are lawfully supplied in Australia through pharmacies). See Section 18.13.2.2 for an overview of compliance with TGO110.

18.5.1 Summary of the major conclusions from this section

E-cigarette aerosols contain hundreds of chemicals, with many having associated health and safety concerns. Most of the chemicals with potential toxic effects are present at very low levels, so the dose of each chemical during a single puff of an e-cigarette is low. The low doses of most of these chemicals are not associated with known toxicities, but for many, there is little data available—so this lack of known harms is not a good indicator of lack of risk. Dose, however, is not the only factor affecting the risk of health effects from these chemicals: more frequent use, longer duration of use, the route of entry through the lungs and the mix of many different chemicals with potential to do harm—all increase the risk of harm to e-cigarette users.

The health effects of almost one-third of the chemicals in e-cigarette aerosols are unknown, and over 80% have little information on inhalation toxicity.1 Chemicals where the health concerns have been investigated have generally only been tested in the short term. For most of the chemicals in e-cigarette aerosols, the effects via inhalation are also unknown, and cannot be assumed to be safe.1 There is also great variety in the unregulated construction and use of e-cigarette devices, some of which might be shedding toxic metals from the internal materials such as the heating coil.2 The use of custom- and home-made e-liquid mixes, and the decay of their constituent chemicals over time, also makes it difficult to determine the exact types and doses of chemicals to which users are exposed.

Some chemicals with potential toxic effects have been banned by Australia’s Therapeutic Goods Administration (TGA) in the therapeutic vapes available from pharmacies. Two of these (benzaldehyde and cinnamaldehyde) were found in a high proportion of e-cigarettes available internationally and in e-cigarettes sold in Australia illegally, outside of the regulated pharmacy supply arrangements3 (see Section 18.5.5.3).

Most of the chemicals with toxicity concerns in e-cigarettes are present at considerably lower levels than in conventional cigarettes but this does not mean that e-cigarettes can be assumed to be harmless. Many people who use e-cigarettes have either never smoked, or are dual users of e-cigarettes and conventional cigarettes. Dual use of both products may further increase health risks beyond use of either product alone. For those who use e-cigarettes to quit smoking, some will sustain long-term vaping, the health risks of which are unknown. 

There are known pulmonary and cardiovascular effects for e-cigarette users (see Section 18.6). These health effects are likely to be caused by exposure to the chemicals in e-cigarette aerosols.

Given the lack of data on long-term inhalation toxicity for many e-cigarette chemicals, and the known pulmonary and cardiovascular effects after short-term use, there is currently insufficient evidence to support the safety of long-term e-cigarette use.  

18.5.2 E-liquids and aerosols from e-cigarettes

E-cigarettes heat a mix of chemicals, called an e-liquid, to produce an aerosol that is inhaled by the user. E-cigarettes expose users and those in the vicinity to a variety of chemicals, many of which have specific health concerns.

E-liquids used in e-cigarette devices vary in their contents, mostly due to the wide variety in flavouring chemicals mixed to create e-liquid flavours. E-liquids usually contain numerous flavouring chemicals, solvents and coolants, and some contain nicotine and/or other drugs, such as those derived from cannabis.4 Some e-liquids contain naturally extracted tobacco liquids (NET liquids) mixed with other chemicals.5

The emissions from an e-cigarette are an aerosol, consisting of tiny droplets of chemicals that float in gases, as described for tobacco in Section 12.4.1.1. Tobacco smoke is also an aerosol, but the types and amounts of the chemicals in tobacco emissions differ to those in e-cigarette emissions.4 Mainstream e-cigarette emissions are those that are drawn by the user and inhaled—either through ‘direct-to-lung’ use or collected in the mouth then inhaled into the lungs (‘mouth-to-lung’ use).6

E-cigarettes produce aerosol particles in similar numbers and sizes to those produced by conventional cigarettes. E-cigarette aerosol particles are typically between 11 nm and 560 nm in diameter;4,7-9 a particle size that is expected to be deposited in the small airways and alveoli (air sacs) of the lungs.4 Modelling studies predict that billions of e-cigarette aerosol particles would be deposited throughout the airways after a single two-second puff, more than double the number for conventional cigarettes, with deposition primarily in the alveoli.9,10

Aerosols that are exhaled by the user potentially expose non-users to chemicals in the secondhand aerosol. Unlike cigarettes and other tobacco products that are lit, e-cigarettes produce minimal side-stream emissions (described in Section 12.4.1.2 for tobacco smoke), so secondhand aerosols mostly consist of those exhaled from users. There is conclusive evidence that e-cigarette use results in increased airborne particulate matter pollution in indoor environments.11 Significant increases in propylene glycol, glycerol, nicotine and volatile organic compounds (VOCs) have been detected after indoor e-cigarette use.4

18.5.3 Chemicals detected in e-liquids and e-cigarette aerosols

E-liquids and aerosols from e-cigarettes contain intentionally added chemicals (referred to as ‘ingredients’), contaminants and reaction products from chemical reactions occurring during storage of the e-liquid or during heating to form aerosols.4,12

Chemicals in e-liquids include any of hundreds of different intentionally added ‘ingredients’ such as flavours, coolants and solvents (glycerol and propylene glycol) as well as nicotine. Aside from the chemicals intentionally added, e-liquids contain contaminants and the products of chemical reactions that have occurring during e-liquid during storage.4 See Sections 18.5.3.1 to 18.5.3.3 and Table 18.5.1 below for detailed information on these chemicals.

Chemicals in e-cigarette aerosols include the chemicals from the e-liquids as well as new products produced by chemical reactions during heating of the e-liquid to form an aerosol.4 Most of the chemical content of the e-cigarette aerosols is the glycerol, propylene glycol, water and nicotine, with roughly 3% of constituents being flavours, contaminants and reaction products. See Sections 18.5.3.1 to 18.5.3.3 below for detailed information on these chemicals.

Several comprehensive reviews from Australian and international agencies have examined the evidence predicting the risks of exposure to the chemicals in e-liquids and e-cigarette aerosols. Readers are directed to comprehensive reports published in 2018 by the US National Academies of Science, Engineering and Medicine,13 in 2019 from the National Industrial Chemicals Notification and Assessment Scheme,4 the 2022 report of the National Centre for Epidemiology and Population Health at the ANU11 and the 2022 CEO’s statement from the National Health and Medical Research Council (NHMRC).14,15

In 2019, the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) published a report on the chemistry and health concerns of chemicals that are found in non-nicotine e-cigarettes (referred to here as the ‘NICNAS report’).4 In Australia, non-nicotine e-cigarette chemicals are regarded as industrial chemicals. While it does not formally regulate e-cigarettes, NICNAS has provided in this report an assessment and advice regarding the safety of use of the detected chemicals. The NICNAS report produced lists of chemicals found in e-cigarettes based on thorough literature searches. This report listed chemicals found in one or more brands of e-liquid; not all these chemicals are in every e-cigarette. Chemicals were reported if detected in ready-to-use e-liquids or e-liquid concentrates for dilution.4

The NICNAS report included chemicals that have been detected in e-liquids with and without nicotine: NICNAS considered that the same chemicals are found in both types.4 It considered that the concentration and reactivity of nicotine in e-liquids is such that any reactions are unlikely to substantially alter the chemical composition of other substances in e-liquids. The NICNAS report therefore states that ‘…chemical information obtained from nicotine-containing e-cigarette liquids is also applicable to liquids without nicotine, although consideration should be given to potential confounding chemical effects of nicotine.’4

18.5.3.1 Chemical ‘ingredients’

The NICNAS report identified a total of 243 different chemical ‘ingredients’ in e-liquids and/or e-cigarette aerosols.4 Most of these chemicals were flavourings (235 out of 243). Eight chemicals had other roles, for instance, as solvents. Solvents such as glycerol and propylene glycol constitute the majority of e-liquids, with one study detecting them at 80–97% of the e-cigarette liquid (by weight).16 Individual flavouring chemicals are commonly detected at between 1 mg/ml and 10 mg/ml, but the highest (limonene) was found at over 70 mg/ml (7% by weight). One study found that the typical total proportion of flavourings in e-liquids constituted between 0.26% to 4.3% of the contents.17

Nicotine, synthetic nicotine and nicotine analogues

Nicotine is a common ingredient in e-liquids. As described below in Section 18.5.5.3, most e-liquids and e-cigarettes illegally sold in Australia contain nicotine even if is not included in the labelling. The amount of nicotine in these e-cigarettes and e-liquids varies greatly, from none to over 134 mg/ml (13.4%).18 E-cigarette devices known as pods (described in Section 18.1.1) often contain ‘nicotine salts’. This form of nicotine is protonated (has a proton added to one of the nitrogen atoms in the nicotine molecule) as opposed to the unprotonated ‘free-base’ nicotine used in the original e-cigarettes. Nicotine salts are made by combining acids such as benzoic acid with the nicotine, lowering the pH (which increases acidity). It is thought that nicotine salts form a less harsh taste for the user, allowing a much higher concentration of nicotine in these e-liquids.19 There is evidence that nicotine salts deliver higher blood levels of nicotine for the same concentration of nicotine in the e-liquid.20 More information about different forms of nicotine is in Section 12.4.3.1.

Synthetic nicotine is made in chemical reactions rather than purified from tobacco plants. Some e-cigarettes contain synthetic nicotine or are reported to contain this form of nicotine on their packaging. There is no evidence that synthetic nicotine is safer for users, although some manufacturers make this claim.21 See InDepth 18C.4.1.3 for more information about synthetic nicotine.

An analogue is a molecule that is very similar to but not identical to another. Nicotine analogues are molecules with very similar molecular structure to nicotine and therefore may bind to nicotine receptors, leading to similar physiological effects, including toxicity. See InDepth 18C.4.1.4 for more information about nicotine analogues. Nicotine analogues are likely being used in e-cigarettes to circumvent the regulation of products containing nicotine.22,23

A synthetic nicotine analogue called 6-methylnicotine has been found in numerous different e-cigarettes,22 including products sold in Australia.24 The following is an example of marketing for this type of product, where 6-methylnicotine is referred to as metatine:

 ‘Metatine is a synthetically derived molecule that is structurally similar to, but chemically different from, other vaping alkaloids. Although Metanine produces the same sensation as nicotine and may also be addictive, Metatine is not made or derived from tobacco or nicotine, and Metatine does not consist of or contain nicotine from any source.’

Nicotinamide (also known as niacinamide or nixamide) is a natural nicotine analogue with relatively low toxicity, but it does not bind to the nicotine receptor or produce similar physiological effects to nicotine. Some e-cigarettes are advertised as being ‘nicotine free’ and containing nicotinamide as an active ingredient. This advertising is misleading, as these e-cigarettes have been found to contain a mix of 6-methylnicotine and the nicotinamide.22 The more toxic 6-methylnicotine is likely to be the active ingredient, which was undisclosed for the products in this study.25  

Menthol and other coolants

Menthol, known to have a role in masking the harsh taste of nicotine, is found in some e-liquids. Menthol has an analgesic effect in the upper respiratory tract and it triggers a perception of coolness (see Section 12.7.2). Synthetic cooling agents that are used in foods, called WS-3 (N-ethyl-p-menthane-3-carboxamide) and WS-23 (2-Isopropyl-N,2,3-trimethylbutanamide), have also been found in e-liquids. These synthetic coolants are also sold in separate solutions that may be added to e-liquids that are custom-mixed by the user. They have been found in US e-cigarettes, in those labelled as mint- or menthol-flavoured as well as fruit- and candy-flavoured products. They are also found in popular disposable e-cigarette products.26 WS-23 has also been detected in e-cigarettes found in Australia, and at high levels in some e-liquids and disposable e-cigarettes.27

Other chemicals in e-cigarettes

The full list of these 243 chemical ‘ingredients’ that were found in e-liquids can be found in Tables A2 and A4 of the NICNAS report.4 This does not include contaminants and chemical reaction products described below. Many of the toxic chemicals found in e-liquids are described in Table 18.5.1.

18.5.3.2 Chemical reaction products

The NICNAS report lists 27 chemicals in e-cigarette aerosols predicted to be reaction products—those produced from chemical reactions during the heating and use of the e-cigarette and during storage of the e-liquid after mixing.4 Most of these 27 reaction products are aldehydes (a type of carbonyl compound) such as acetaldehyde, acrolein and formaldehyde, the toxic effects of which are described in Section 12.4.3.2. Aldehydes produced during e-cigarette use are predicted to come from chemical reactions that involve the solvents glycerol and propylene glycol28 and there is evidence that they are also derived from some flavouring compounds.4 A list of these 27 reaction products is available in the NICNAS report.4

Reaction products may also be produced by chemical reactions between flavourings and propylene glycol solvent during storage or as degradation products of flavouring chemicals such as limonene.4

18.5.3.3 Contaminants

The NICNAS report identified 106 chemicals considered to be contaminants. These were detected in the e-liquid, aerosols or both.4

Contaminants found in e-liquids and aerosols mostly consisted of volatile organic compounds (VOCs), pesticides, metals and phthalates.4,29 VOCs are carbon-based chemicals that release molecules as gases, often producing scents. Many VOCs can be toxic at sufficient doses. Metals such as nickel and lead may have leached from the e-cigarette device or be contamination of e-liquid ingredients (see Section 18.5.5.4). Phthalates are small carbon-based molecules used to make plastics, many of which have reproductive toxicity and endocrine disrupting activity with exposure at high doses. Carcinogenic (cancer-causing) polycyclic aromatic hydrocarbons (see Section 12.4.3.6) and N-nitrosamines (Section 12.4.3.7) have also been detected in e-cigarette aerosols at low levels.30-32 Benzene, which can cause cancer, has been detected in e-liquids and aerosols, and found at higher levels when nicotine benzoate salts are used.33 Low amounts of toxic per- and polyfluoroalkyl substances (PFAS, also known as ‘forever chemicals’) have also been found in some e-liquids refills.34

Contaminants in e-liquids and e-cigarette aerosols are usually present at much lower levels than the purposely added ‘ingredients’ and reaction products. However, some contaminants with toxic potential are present at concerning levels. Examples are diethyl phthalate detected at 1.8 mg/mL (0.18%) and propylene oxide at 6.7 mg/mL (0.67%) in e-cigarette liquids.4

Lists of the contaminants in the e-liquids (Table A3) and in e-cigarette aerosols (Table A6) are available in the NICNAS report.4

18.5.3.4 Chemicals in e-cigarettes compared to conventional cigarettes

There is much interest in comparing the types and amounts of chemicals in e-cigarette aerosols to smoke from conventional cigarettes. Lower amounts of some toxic chemicals may imply a lower risk compared to smoking. While there may be health benefits for people who smoke who completely switch to e-cigarettes, many people who vape have never smoked, or use both products (i.e. dual use). (see Sections 18.3.1.2 and 18.7.6).

Most of the chemicals with toxicity concerns in e-cigarettes are present at considerably lower levels than in cigarettes. But this does not mean that e-cigarette use can be assumed to be harmless as the effects of long-term exposure to the chemicals found in e-cigarettes, even at low doses, are unknown. Further, dual use of both products may further increase health risks beyond use of either product alone.35-37

E-cigarette aerosols contain considerably lower amounts of harmful and toxic chemicals compared to conventional cigarette aerosols. An extensive study from 2021 tested carbonyl compounds (including aldehydes such as acetaldehyde and formaldehyde, Section 12.4.3.2) and polycyclic aromatic hydrocarbons (PAHs, Section 12.4.3.6) levels in e-cigarette compared to conventional cigarette and heated tobacco products aerosols. Among the 19 carbonyl compounds tested, 17 were lowest in e-cigarette aerosols. Among the 22 PAHs that were detected, 21 were lowest in e-cigarette aerosols compared to conventional cigarette and heated tobacco products. When comparing average levels of all the compounds in each class, e-cigarettes had a 99% reduction per puff of carbonyl compounds compared to conventional cigarettes, and a 98% reduction per puff of PAHs, many of which are known causes of cancer.38 This study used three different types of e-cigarettes in these comparisons. However, there is a great variety of e-cigarettes and of the ways that they are used, such as differing power settings, as described below in Section 18.5.4. More extensive studies are necessary to comprehensively compare e-cigarette aerosols to conventional cigarettes that take into account the variety of products and modes of use. 

There has been little research that directly compares the levels of toxic metals found in e-cigarette aerosols to conventional cigarettes (see Section 12.4.3.10). Studies of metals in human samples, such as urine and blood, have mostly found similar, if not higher, amounts of metals in samples from e-cigarette users compared to conventional cigarettes.39 Numerous metals present in e-liquids and/or e-cigarette aerosols have associated health concerns, as detailed in Table 18.5.1.

18.5.3.5 Detection of the chemicals in e-cigarettes

Researchers use a variety of laboratory tests to detect specific chemicals in e-cigarettes. The simpler approach is to detect chemicals in e-liquids, before this liquid is heated into an aerosol for inhalation. Analysis of e-liquid refills (where the liquid is sold separately) is more easily and commonly performed than analysis of e-liquids inside disposable devices, which need to be extracted from a sealed device. However, analysis of e-liquids has limitations; the range of chemicals inhaled by the user from the aerosol is different to that found in the e-liquid. E-cigarette aerosols contain the chemicals in e-liquids and the products of pyrolysis and other chemical reactions that occur upon heating, many of which are toxic. Detection of chemicals in the aerosols produced by e-cigarettes is a better indication of the chemicals to which a user is exposed. See also Section 18.6.9 for the chemicals detected in secondhand e-cigarette emissions.

Another approach is to detect chemicals in the urine or saliva of e-cigarette users (see Section 18.5.6 for a discussion of biomarkers). Detecting biomarkers can show which chemicals are taken up into the body. But the drawback to biomarker detection in human samples is that these chemicals could have come from numerous sources, not just e-cigarettes.

Detection of chemicals in e-liquids

Hundreds of independent laboratories have developed bespoke methods to detect specific chemicals in e-liquids.3,26,40 Nicotine, glycerol (vegetable glycerin) and propylene glycol are commonly measured, as are specifical flavourants and toxic contaminants/reaction products such as aldehydes (formaldehyde etc.) and polycyclic aromatic hydrocarbons (benzo[a]pyrene etc.).40 Techniques used in these laboratories include gas chromatography and mass spectroscopy, as described in more detail in Section 12.5.3. Methods have been developed to determine the fraction of nicotine that is free-base or protonated (as in nicotine salts).41,42 Modified mass spectroscopy techniques have been developed to measure a range of toxic metals in e-liquids,43 coolants26 and flavourants,44 and the harmful and potentially harmful constituents that are also found in tobacco smoke.45 Non-targeted approaches using mass spectrometry can identify as a many chemicals as possible in a sample, as an alternative to individual tests for specific compounds.46

An Australian study has used an ageing technique to analyse the effects of time in storage on e-liquids.3 Chemical reactions during e-liquid storage may include thermal decomposition, oxidation, and polymerisation of e-liquid components.3

Standard Operating Procedures (SOPs) have been developed to improve the accuracy of detection of chemicals in e-liquids and reduce variability between different laboratories.47 TobLabNet (Tobacco Laboratory Network, under the World Health Organization) is a global network of government, academic, and independent laboratories that collaborate to strengthen capacity for the testing of tobacco product contents and emissions.48 In addition to measuring chemicals in tobacco smoke, TobLabNet has recently developed methods for measuring chemicals in e-liquids. Their Standard Operating Procedure SOP11 details a method for determining the concentrations of nicotine, propylene glycol and glycerol (vegetable glycerin) in e-liquids.49 This method uses gas chromatography, in which a mixture of chemicals is converted into a gas prior to binding and release from an adsorbent material. This can be coupled with either mass spectrometry or analysis with a flame ionization detector. See Section 12.5.3 for more details. A range of TobLabNet laboratories were able to use both approaches and generate consistent results.50

Detection of chemicals in e-cigarette aerosols

The aerosols created from e-cigarettes consist of gases as well as tiny droplets containing chemicals that float in these gases. Both components need to be collected and analysed for the detection of chemicals in the aerosols that are inhaled by users. An ‘automated vaping machine’ is used to generate and collect aerosols from an e-cigarette. These machines take puffs using a programmed puff duration, volume, puff intervals and device settings such as power usage.51,52 There is difficulty in establishing a standard protocol for these settings, given the wide variety of devices available and the variety in the ways in which people use them. Once aerosols have been collected directly from e-cigarette devices, the analysis of chemicals, contaminants and reaction products in these samples uses similar techniques to those described above for e-liquids.40,45,53-57

18.5.4 Effects of e-cigarette device types and modes of use

The wide range of e-cigarette device types is described in detail in Section 18.1.1.

E-cigarettes generally use battery power to heat a metal coil, that heats the e-liquid, forming an aerosol that is inhaled by the user. E-cigarette devices such as box mods and pod mods are highly customisable, with the ability to change power settings, temperature and airflow. The temperature of the heating element varies between devices and when different settings are used. Heating element temperatures range between approximately 150°C to 350°C under typical usage conditions.58 Chemical exposure from e-cigarette aerosols is affected by the power output, temperature of the heated coil and the airflow settings on the device. An increase in temperature can increase the production of harmful free radicals, carbonyl compounds and benzene produced, as well as some metals.6 Increasing the power settings also increased the damaging ‘free radical’ compounds in human bronchial cells exposed to e-cigarette aerosols in laboratory experiments.38

While the nicotine yield (milligrams of nicotine in the smoke from one cigarette) is a useful measure of nicotine exposure from cigarettes, yield is less relevant for e-cigarettes as the same device or e-liquid mix may be used in multiple sessions, over many days or even weeks. Nicotine delivery for these devices can be measured as nicotine flux: the amount of nicotine delivered per second of use.59 Higher power settings and higher e-liquid concentrations will produce a higher nicotine flux. A study measuring nicotine flux of multiple devices found an nicotine flux range of 3.7 to 110 mg/sec with a mean of 29 mg/sec nicotine.59 With new e-cigarette devices regularly entering the market, the nicotine flux has increased over time. By 2019, nearly 40% of e-cigarettes had a nicotine flux of over 60 mg/sec.59

The toxic gas carbon monoxide was detected in e-cigarette aerosols when high power settings were used.56 Under maximal power (200W) and 4-second puff conditions, the carbon monoxide concentration in aerosols was detected at over 180 ppm, a concentration that exceeds the US National Ambient Air Quality Standards for outdoor carbon monoxide concentration (35 ppm for 1 hour). Lower power settings are recommended by the authors of this study to reduce the risk from inhaling carbon monoxide.56

Under some conditions, a low supply of e-liquid reaches the heating coil leading to an unpleasant user experience called a ‘dry puff’. Dry puff conditions lead to an increased concentration of carbonyls such as formaldehyde in the aerosols.60 If dry puff conditions were always used, this could lead to intake of formaldehyde at much higher levels than cigarettes. However, these conditions are aversive and therefore likely avoided by users. There remains some debate over the ability of e-cigarette to release higher levels of formaldehyde under non dry puff conditions.61

E-cigarette devices set up for ‘direct-to-lung’ use commonly use a higher power setting than devices used for ‘mouth-to-lung’ inhalation, where the aerosols are gathered in the mouth first, before inhalation into the lungs.6 The high surface area of the lungs means that direct-to-lungs use leads to a higher amount of exposure to the chemicals. However, direct-to-lung e-liquid mixes are usually less concentrated to compensate for this.

The concentration of toxic carbonyl compounds in the aerosols may be increased during dripping (adding e-liquid directly to the heating coil) and ‘squonking’ (where an inbuilt squeeze bottle is used to add e-liquid to the heating coil). This effect may be due to an increase in the temperature of the coil.60

A novel e-cigarette device type (ultrasonic cigarette or u-cigarette) that converts e-liquids into aerosols using sonic vibration rather than a heating coil was examined by independent researchers. They concluded that the concentrations of nicotine, aldehydes and other chemicals, as well as the toxic effect of the aerosols on cells grown in the laboratory, provide no evidence that the aerosols from u-cigarettes are less harmful than those from e-cigarettes.62

18.5.5 Health concerns for specific chemicals in e-cigarettes

18.5.5.1 Challenges and limitations in predicting the health effects of e-cigarette use

The health effects of long-term e-cigarette use cannot be directly measured due to the relatively recent introduction of these products into the market. In the absence of direct measurement, health concerns associated with e-cigarette use have been predicted using information on 1) the individual chemicals present in liquids and aerosols, 2) the extent of the exposure and 3) the known health effects of these chemicals. There are multiple issues with this approach that make these predictions challenging.

The risk of toxic effects from exposure to a specific chemical is affected by factors such as the dose of the chemical, the frequency of exposure, the duration of exposure and the route of entry into the body.63 Toxicity may also vary for people of different sexes, ethnicity and age, and be complicated by experiences such as pregnancy or chronic diseases. Furthermore, the effects of chemicals in e-cigarette aerosols occur in the context of a mixture of many different chemicals, which could modify their risks in ways that are difficult to quantify. For example, a mix of numerous chemicals that are capable of mutagenesis (changing the sequence of DNA) can increase the risk of cancer above that of one only, but these risks cannot simply be added together to estimate an overall risk. Similarly, the uptake into the lungs or the bloodstream of one chemical can be modified by the presence of another, modifying its potential to cause harm.64

The extent of exposure is an important factor affecting toxicity.63 For many chemicals, the acute toxicity (from one exposure) and short-term effects have been measured. But the health concerns from long-term and high-frequency exposure, such as from 10 to 20 years of daily low dose exposure, are unknown. The frequency and duration of exposure also differ considerably between users and modes of e-cigarette use, as described in Section 18.5.4. A greater amount of some toxic chemicals has been detected from e-cigarettes used at higher power settings. With higher powered and variable-powered devices becoming more popular,65 it’s possible that future users will be exposed to higher concentrations of chemicals with potential toxicity. Examining the chemicals in e-liquids and e-cigarette aerosols is further complicated by illegal sales of products that do not meet the required product standards, and significant inconsistency between the labelled content and the actual content and concentrations.66,67

Toxicological risk assessments use knowledge of the risks from chemicals exposure to predict the toxic effects of specific chemicals through different routes of exposure.63 Many of these risks are tested in experiments using animals and cells growing in laboratories. The doses that cause toxicity in humans are often quite different to those in animals, and experiments using cell lines do not take into account the effects on the many different cell types present in the body. These experiments are usually only conducted over the short or mid-term, so extrapolating to long-term use at lower dosages is problematic.

For many chemicals present in e-cigarette aerosols, toxicological risk assessments have not been performed for inhalation.1 This is problematic, because the risks from inhalation may be quite different to those from ingestion or skin contact. Many chemicals that are generally regarded as safe at low doses in food cannot be assumed to be safe when inhaled.68 The lungs are uniquely designed to transport gases quickly into the bloodstream. They have the largest exposed surface area of any organ, at 70 to 100 m2 compared to 10 m2 for the digestive system.63 Chemicals that are deposited into the airways and lungs can cause localised damage such as irritation and construction, inflammation, cell death, fibrosis (scar formation) and DNA damage that can lead to cancer.63

18.5.5.2 Risk assessments of chemicals in e-liquids and e-cigarette aerosols

In 2022, the National Health and Medical Research Council (NHMRC) produced a report assessing the toxicological risks of the chemicals in e-liquids and their aerosols1 that were identified by NICNAS4 as described in Section 18.5.3. This report examined existing toxicological risk assessments for the 369 individual chemicals and metals identified by NICNAS (the ingredients, contaminants and reaction products discussed above). The toxicological risk assessments provide an indication of potential harms of these e-cigarette chemicals on an individual level, but do not measure the health effects of long-term e-cigarette use.

Of the 369 substances detected in e-liquids and e-cigarette aerosols:

  • 116 had no risk assessments available, so their risks upon inhalation or other exposure are unknown, and cannot be assumed as safe
  • 42 were harmful by inhalation (described in Table 18.5.1)
  • 8 were known or suspected respiratory sensitisers (that trigger long term lung inflammatory conditions)
  • 203 had other known or suspected health risks.1

Over 80% of the 369 substances had no risk assessments specific to inhalation, so the health concerns of their inhalation are unknown, and cannot be assumed safe.

Of the 253 substances with known or suspected health risks, there were a variety of known or suspected risks, and many had more than one associated risk. Thirty-nine had known or suspected acute toxicity, 82 were known or suspected carcinogens (chemicals that cause cancer), 53 were known or suspected skin irritants and 114 were described as harmful if swallowed.1

Of the 42 chemicals identified as having inhalation toxicity (listed in Table 18.5.1):1

  • 16 were designated as harmful to inhale, such as arsenic, benzyl alcohol and benzaldehyde
  • 11 as being fatal by inhalation (when at sufficient dose), such as acrolein, formaldehyde and mercury
  • 10 are potentially fatal to inhale (when at sufficient dose), such as benzene, toluene and hexane
  • three are described as causing irreversible lung damage, being diacetyl, acetoin and acetyl propionyl
  • two are known to cause damage to organs through prolonged or repeated exposure, being manganese and nickel.

A study published in 2022 tested for some of these 42 chemicals in 65 e-liquids (labelled as non-nicotine) that were sold in Australia.3 This study detected benzyl alcohol, benzaldehyde, furfuraldehyde, nicotine and phenol in one or more of the e-liquids tested.

It is important to note that these toxicological effects would only occur with sufficient exposure doses, durations and frequencies. For many of these chemicals, the extent of exposure is poorly characterised.

18.5.5.3 Health concerns associated with specific chemicals from e-cigarettes

A scoping review of 89 studies was conducted by the NHMRC to estimate the potential for e-cigarette aerosols and/or the individual chemicals in them to cause specific health effects.1 These publications examined general toxicity, cellular toxicity, toxicity to the lungs and to the cardiovascular system. This review concluded that long-term data on inhalation toxicity of e-cigarettes (both nicotine-containing and non-nicotine-containing) remained limited. The evidence on the differential health impacts of a specific flavour, solvent or humectant could not be determined. Likewise, the evidence on the differential health impacts of nicotine-containing or nicotine-free e-cigarettes or e-liquids could also not be determined.1

The inconclusive findings from this report have stemmed from the low doses of these chemicals in e-liquids and aerosols, as well as the sparse information on long-term toxicity and inhalation toxicity. This does not mean that there are no health effects of e-cigarette use. The effects described below only occur under sufficient conditions of exposure, which are poorly defined for e-cigarettes.

Chemicals with known or potential health effects

Most of the chemicals covered by the NHMRC review had known or suspected health risks, such as acute toxicity (effects from a single exposure or short period of exposure), cancer-causing activity (carcinogenicity), skin irritation or were described as harmful if swallowed.1

Among the chemicals known to have fatal effects when at a high enough dose, there are numerous toxic metals and aldehydes (chemicals with carbonyl groups, described in Section 12.4.3.2) (see Table 18.5.1). The metals are most likely to be contaminants and are described further below. Aldehydes, such as formaldehyde, acrolein and crotonaldehyde, can be formed as reaction products during the heating of the e-liquid to create an aerosol. They are also detected in tobacco smoke, but at significantly higher concentrations.12 For tobacco smoke, acrolein and formaldehyde are priority toxicants for regulation recommended by the World Health Organization (see Section 12.5.3). Formaldehyde is a preservative used in embalming solutions and for preserving dead tissue in laboratories.69 It is toxic to the cardiovascular system and has a genotoxic (mutating DNA to cause cancer) effect in lung cells.70,71 Acrolein is an irritant to the human respiratory system, toxic to lung cilia and is likely to be a carcinogen in the lungs.71 Acrolein is toxic to the cardiovascular system and causes oxidative stress in the heart and increases cardiovascular disease risk.70,71 Although the long term health effects of exposure to these aldehydes via e-cigarette aerosols is not yet known, long-term exposure to carcinogenic compounds, even at low concentrations, should be a concern for e-cigarette users. When such exposure occurs via the respiratory system, there are not the same detoxification steps undertaken by the body as those occurring within the digestive system that afford some protection from compounds such as formaldehyde.

Known and suspected carcinogens (cancer-causing chemicals) found in e-cigarette aerosols include butylated hydroxytoluene, limonene, diacetyl, furans, creosol and cyclohexanone.1 Many of these are present at relatively low doses. However, the consequences of inhalation of a mix of many of these chemicals in low doses, but high frequencies for a long duration, are not known. Some carcinogens are believed to be able to promote the formation of cancer with no known lower limit, called linear non-threshold action (LNT). Examples of chemicals with LNT or assumed LNT that have been detected in e-liquids or their aerosols are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and arsenic.1,72

Solvent chemicals, usually propylene glycol and glycerol are the most common constituent of most e-liquids. When heated, these solvents can undergo reactions to form other chemicals, some of which have health concerns. For example, propylene glycol can break down into diacetyl and formaldehyde when heated during e-cigarette use. These chemicals have considerable toxicity but are generally produced at very low levels in e-cigarette aerosols. A study of propylene glycol breakdown products in JUUL emissions (13 different flavours) detected diacetyl at an average of 20 µg/m3 and methylglyoxal at an average of 4,219 µg/m3 (range of 677 to 15,342 µg/m3).73 Methylglyoxal, a respiratory irritant, is therefore present at much higher levels in aerosols, but the long term health effects of exposure to this chemical via the respiratory tract are unknown. One study has shown that methylglyoxal is capable of increasing pro-inflammatory responses in human nasal cells grown in the laboratory.74

Free radicals and reactive oxygen species (ROS) have been found in e-liquids.55 These are a range of molecules that have unpaired electrons, making them highly reactive and damaging to the body. Free radical and ROS exposure is considered to increase the risk of cancer and other diseases. Nicotine salt e-liquids containing benzoic acid have been found to have the highest level of ROS compared to other types of nicotine salts.55

Metal contamination in e-liquids and e-cigarette aerosols

Metal particles are found in e-liquids and in the aerosols produced by e-cigarettes. These metals be leaching from the e-cigarette metal components or they could be contaminants of the chemical ingredients of the e-liquid.

E-cigarettes contain batteries, soldered joints and metallic heating coils of varying designs to heat e-liquids, forming the aerosol.54 The composition of the metal heating elements is un-standardised and reported to have considerable variation.75 Coils are reported made from metal alloys containing chromium, aluminium, iron, manganese, aluminium or nickel, whereas soldered joints and wires may contain copper, zinc, tin or lead.54

Metals such as antimony, aluminium, barium, cadmium, chromium, cobalt, copper, iron, lead, magnesium, manganese, mercury, nickel, tin, tungsten and zinc, as well as the metalloids antimony and arsenic, have been detected in e-liquids and aerosols.1,29,54,75-78 As power settings increase, many of these metals increase in concentration.77 The extent to which these metals derive from the metal components of the e-cigarette device, or from contaminants in the e-liquid is mostly unknown. However, some studies have detected toxic metals (including arsenic, cadmium, chromium, lead and nickel) in the refill e-liquids, indicating that these were not the solely result of leaching from the e-cigarette device components.79 

An analysis of the risks from long term exposure to these metals used published cancer potency factors and non-cancer reference exposure concentrations from the US Environmental Protection Agency and the California Environmental Protection Agency to estimate the range of cancer and non-cancer risks from these metals.75 This study predicted that chromium and nickel were the leading contributors to cancer risk, with minor contributions from cadmium, lead, and arsenic. Assuming an exposure to 2 ml/day, the risks ranged from 5.7 to 30,000 additional cancers per million e-cigarette users. Cancer risks in the mid to upper end of these ranges were stated to exceed acceptable levels. Nickel, chromium, and manganese were the most influential metals driving the risk of non-cancer diseases, with nickel producing the highest risk. The authors concluded that e-cigarettes contaminated with metals in the mid and upper end of the reported ranges pose a significant cancer and non-cancer health risk.75

18.5.5.4 Prohibited chemicals in e-cigarettes sold in Australia

A product standard for vaping products was first implemented in Australia in 2021 (known as TGO110),80 with further amendments coming into effect in 2024 and 2025.81 The product standard details requirements for therapeutic vapes (i.e. those that can be lawfully supplied by pharmacists), including requirements for devices, ingredients, packaging and labelling. See Section 18.13.2.2 for detail on TGO110, including compliance and enforcement efforts.

The product standard sets strict limits (below 10 parts per million; ppm) on eight toxic chemicals due to known health risks, including:82 acetyl propionyl, acetoin, benzaldehyde, cinnamaldehyde, diacetyl, diethylene glycol, DL-alpha-tocopheryl acetate and ethylene glycol.

Testing of e-cigarettes has shown potentially concerning levels of these chemicals. Seven of the 8 prohibited substances were detected in e-liquids and/or their emissions assessed by NICNAS in its report published in 20194 and the NHMRC in its report in 2022,1 which examined vape products globally. Each of these 7 were detected at higher than 10 ppm (10 mg/g, which is approximately 10 mg/ml). These are: acetyl propionyl,83 acetoin,84 benzaldehyde,17 cinnamaldehyde,85 diacetyl,83 diethylene glycol and ethylene glycol.86

In Australia, tests of e-cigarettes prior to implementation of the pharmacy-only supply model in 2024 similarly showed potentially harmful levels of these chemicals. Testing conducted by the TGA of available and imported products that was published online in 2023 showed that 33.7% of the nicotine-containing e-liquids did not comply with the 10 ppm limit for one or more of these prohibited chemicals87

A 2022 study of 65 fresh and aged e-liquids sold in Australia (some of which did not contain nicotine) detected a range of harmful chemicals, including:3

  • benzaldehyde in 60 fresh and 61 aged e-liquids, with concentrations ranging from 11.4 ng/ml to 17.3 mg/ml,
  • cinnamaldehyde in 48 fresh e-liquids (maximum 97.9 mg/ml) and 38 aged e-liquids (maximum 142.5 mg/ml)

Cinnamaldehyde is a flavouring chemical that may degrade into the toxic chemical called styrene. In laboratory experiments, cinnamaldehyde has been shown to impair the function of some immune cells, but the effects of long-term low dose exposure to cinnamaldehyde through e-cigarette use are unknown.88

A study of e-cigarettes that were confiscated in Australian secondary schools in 2022 and 2023 found an average of 40 mg/ml nicotine. Ingredients prohibited under the TGO110 Standard were found in 3.4% of the samples, including moderately high concentrations of ethylene glycol.44

18.5.6 DNA adducts and biomarkers for e-cigarette exposure

Biomarkers for e-cigarette aerosols are substances in the human body that can be measured in a test that will indicate exposure to specific chemicals from e-cigarettes. Biomarkers of e-cigarette exposure can be detected in samples such as saliva and urine. Biomarkers have been very useful in the study of tobacco exposure. They can indicate the dose of a specific chemical exposure, the biological activity, damage or potential for damage and the risk of disease.71 Researchers are starting to use biomarkers to detect exposure to chemicals in e-cigarette users. See Section 12.5.6 for more information about biomarkers.

A 2021 scoping review evaluated the current data from biomarkers and compared exposure among people who smoked, used e-cigarettes or used neither.89 This review found consistent evidence suggesting that biomarkers of some volatile organic compounds (VOCs) (acrylamide and acrylonitrile), metals (beryllium, cadmium, selenium, uranium and zinc) and propylene glycol are higher in e-cigarette users compared with non-users. However, conflicting data meant that it is currently unclear whether e-cigarette users have similar or higher biomarkers of acrolein, benzene, crotonaldehyde, formaldehyde, propylene oxide, toluene, xylene and 1,3-butadiene, and some metals (chromium, lead, nickel, strontium and manganese) compared to non-users.89

In comparisons of e-cigarette users to cigarette smokers: biomarkers of VOCs (acrolein, acrylamide, acrylonitrile, ethylene oxide, vinyl chloride and 1,3-butadiene) were lower in e-cigarette users. However, e-cigarette users and cigarette smokers had similar urinary levels of beryllium, zinc and uranium. There were insufficient data to draw conclusions on the levels of biomarkers for other VOCs (benzene, crotonaldehyde and propylene oxide) and metals (cadmium, chromium, lead, nickel, manganese and strontium).89

Longitudinal studies have shown that people who use e-cigarettes (but not tobacco) have higher urinary levels of lead and cadmium compared to people who have never used these products.90,91 In adolescents, those who more frequently used e-cigarettes had higher levels of lead in their urine than those who used them less frequently.92

E-cigarettes do not contain tobacco, but most contain nicotine that is purified from tobacco plants. Tobacco-derived nicotine may contain small amounts of contaminating carcinogens (cancer-causing substances) from the tobacco. Biomarkers of tobacco-specific carcinogens NNN and NNAL have been detected in the saliva of e-cigarette users at higher levels compared to people who have never used e-cigarettes but lower levels than people who smoke tobacco.93,94

Mutagenic chemicals, such as carcinogens (chemicals that can cause cancer), damage DNA by changing its sequence. Once they enter the body, they are often modified in biochemical reactions before binding to DNA at specific sites (called DNA adducts, see Section 3.3.2.2). DNA adducts could be considered as biomarkers indicating the potential for damage. E-cigarette aerosols can induce DNA strand breaks and oxidative DNA damage cells grown in the laboratory and the formation of DNA adducts in the lung, heart and bladder of mice.95 Consistent with these findings, long-term (54 weeks) exposure to e-cigarette aerosols has been shown to induce lung adenocarcinoma and bladder urothelial hyperplasia in mice.96 DNA-acrolein adducts have been detected in mouth brush samples (taken at dental visits) of e-cigarette users at 9-fold higher amounts than those in non-e-cigarette users.97

 Related reading

Relevant news and research

A comprehensive compilation of news items and research published on this topic (Last updated April 2025)

Read more on this topic

Test your knowledge 

References 

1. National Health and Medical Research Council. Inhalation toxicity of non-nicotine e-cigarette constituents: risk assessments, scoping review and evidence map.  2022. Available from: https://www.nhmrc.gov.au/file/18287/download?token=Z5D5_sam.

2. Olmedo P, Goessler W, Tanda S, Grau-Perez M, Jarmul S, et al. Metal concentrations in e-cigarette liquid and aerosol samples: The contribution of metallic coils. Environmental Health Perspectives, 2018; 126(2):027010. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29467105

3. Larcombe A, Allard S, Pringle P, Mead-Hunter R, Anderson N, et al. Chemical analysis of fresh and aged Australian e-cigarette liquids. Medical Journal of Australia, 2022; 216(1):27-32. Available from: https://www.ncbi.nlm.nih.gov/pubmed/34528266

4. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). Non-nicotine liquids for e-cigarette devices in Australia: chemistry and health concern. Australian Government Department of Health, 2019. Available from: https://www.industrialchemicals.gov.au/sites/default/files/2020-08/Non-nicotine%20liquids%20for%20e-cigarette%20devices%20in%20Australia%20chemistry%20and%20health%20concerns%20%5BPDF%201.21%20MB%5D.pdf.

5. Farsalinos KE, Gillman IG, Melvin MS, Paolantonio AR, Gardow WJ, et al. Nicotine levels and presence of selected tobacco-derived toxins in tobacco flavoured electronic cigarette refill liquids. International Journal of Environmental Research and Public Health, 2015; 12(4):3439-52. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25811768

6. Korzun T, Lazurko M, Munhenzva I, Barsanti KC, Huang Y, et al. E-cigarette airflow rate modulates toxicant profiles and can lead to concerning levels of solvent consumption. ACS Omega, 2018; 3(1):30-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29399647

7. Ingebrethsen BJ, Cole SK, and Alderman SL. Electronic cigarette aerosol particle size distribution measurements. Inhalation Toxicology, 2012; 24(14):976-84. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23216158

8. Mikheev VB, Brinkman MC, Granville CA, Gordon SM, and Clark PI. Real-time measurement of electronic cigarette aerosol size distribution and metals content analysis. Nicotine & Tobacco Research, 2016; 18(9):1895-902. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27146638

9. Manigrasso M, Buonanno G, Fuoco FC, Stabile L, and Avino P. Aerosol deposition doses in the human respiratory tree of electronic cigarette smokers. Environmental Pollution, 2015; 196:257-67. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25463721

10. Manigrasso M, Buonanno G, Stabile L, Morawska L, and Avino P. Particle doses in the pulmonary lobes of electronic and conventional cigarette users. Environmental Pollution, 2015; 202:24-31. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25796074

11. Banks E, Yazidjoglou A, Brown S, Nguyen M, Martin M, et al. Electronic cigarettes and health outcomes: systematic review of global evidence. Report for the Australian Department of Health, 2022, National Centre for Epidemiology and Population Health: Canberra. Available from: https://www.nhmrc.gov.au/sites/default/files/documents/attachments/ecigarettes/Electronic_cigarettes_and_health_outcomes_%20systematic_review_of_evidence.pdf.

12. Margham J, McAdam K, Cunningham A, Porter A, Fiebelkorn S, et al. The chemical complexity of e-cigarette aerosols compared with the smoke from a tobacco burning cigarette. Frontiers in Chemistry, 2021; 9:743060. Available from: https://www.ncbi.nlm.nih.gov/pubmed/34660535

13. National Academies of Sciences Engineering and Medicine. Public health consequences of e-cigarettes. The National Academies Press, Washington, DC 2018. Available from: http://nationalacademies.org/hmd/Reports/2018/public-health-consequences-of-e-cigarettes.aspx.

14. National Health and Medical Research Council. CEO statement on electronic cigarettes.  2022. Available from: https://www.nhmrc.gov.au/health-advice/all-topics/electronic-cigarettes/ceo-statement

15. National Health and Medical Research Council. CEO statement on electronic cigarettes: Plain english summary.  2022. Available from: https://www.nhmrc.gov.au/health-advice/all-topics/electronic-cigarettes/ceo-statement-summary

16. Han S, Chen H, Zhang X, Liu T, and Fu Y. Levels of selected groups of compounds in refill solutions for electronic cigarettes. Nicotine & Tobacco Research, 2016; 18(5):708-14. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26568061

17. Tierney PA, Karpinski CD, Brown JE, Luo W, and Pankow JF. Flavour chemicals in electronic cigarette fluids. Tobacco Control, 2016; 25(e1):e10-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25877377

18. Davis B, Dang M, Kim J, and Talbot P. Nicotine concentrations in electronic cigarette refill and do-it-yourself fluids. Nicotine & Tobacco Research, 2015; 17(2):134-41. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24862971

19. Gholap VV, Kosmider L, Golshahi L, and Halquist MS. Nicotine forms: why and how do they matter in nicotine delivery from electronic cigarettes? Expert Opinion on Drug Delivery, 2020; 17(12):1727-36. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32842785

20. Christen SE, Hermann L, Bekka E, Vonwyl C, Hammann F, et al. Pharmacokinetics and pharmacodynamics of inhaled nicotine salt and free-base using an e-cigarette: A randomized crossover study. Nicotine & Tobacco Research, 2024; 26(10):1313-21. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38597729

21. Berman ML, Zettler PJ, and Jordt SE. Synthetic nicotine: Science, global legal landscape, and regulatory considerations. World Health Organization Technical Report Series, 2023; 1047:35-60. Available from: https://www.ncbi.nlm.nih.gov/pubmed/37745838

22. Erythropel HC, Jabba SV, Silinski P, Anastas PT, Krishnan-Sarin S, et al. High variability in nicotine analog contents, misleading labeling, and artificial sweetener in new e-cigarette products marketed as "FDA-Exempt". medRxiv, 2024. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38766027

23. Jordt SE, Jabba SV, Zettler PJ, and Berman ML. Spree Bar, a vaping system delivering a synthetic nicotine analogue, marketed in the USA as 'PMTA exempt'. Tobacco Control, 2024. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38499343

24. Jenkins C, Kelso C, and Morgan J. 6-Methylnicotine: a new nicotine alternative identified in e-cigarette liquids sold in Australia. Medical Journal of Australia, 2024; 221(6):333-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39188177

25. Jabba SV and Jordt SE. Marketing of nicotinamide as nicotine replacement in electronic cigarettes and smokeless tobacco. Tobacco Prevention & Cessation, 2024; 10. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39132445

26. Jabba SV, Erythropel HC, Torres DG, Delgado LA, Woodrow JG, et al. Synthetic cooling agents in US-marketed e-cigarette refill liquids and popular disposable e-cigarettes: Chemical analysis and risk assessment. Nicotine & Tobacco Research, 2022; 24(7):1037-46. Available from: https://www.ncbi.nlm.nih.gov/pubmed/35167696

27. Jenkins C, Morgan J, and Kelso C. Synthetic cooling agents in Australian-marketed e-cigarette refill liquids and disposable e-cigarettes: Trends follow the U.S. market. Nicotine & Tobacco Research, 2024; 26(3):380-4. Available from: https://www.ncbi.nlm.nih.gov/pubmed/37450895

28. Klager S, Vallarino J, MacNaughton P, Christiani DC, Lu Q, et al. Flavoring chemicals and aldehydes in e-cigarette emissions. Environmental Science & Technology, 2017; 51(18):10806-13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28817267

29. Kopa-Stojak PN and Pawliczak R. Disposable electronic cigarettes - chemical composition and health effects of their use. A systematic review. Toxicology Mechanisms and Methods, 2025; 35(3):250-61. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39513380

30. Beauval N, Antherieu S, Soyez M, Gengler N, Grova N, et al. Chemical evaluation of electronic cigarettes: Multicomponent analysis of liquid refills and their corresponding aerosols. Journal of Analytical Toxicology 2017; 41(8):670-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28985322

31. Margham J, McAdam K, Forster M, Liu C, Wright C, et al. Chemical composition of aerosol from an e-cigarette: A quantitative comparison with cigarette smoke. Chemical Research in Toxicology, 2016; 29(10):1662-78. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27641760

32. Goniewicz ML, Knysak J, Gawron M, Kosmider L, Sobczak A, et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tobacco Control, 2014; 23(2):133-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23467656

33. El Hajj Moussa F, Hayeck N, Hajir S, El Hage R, Salman R, et al. Enhancement of benzene emissions in special combinations of electronic nicotine delivery system liquid mixtures. Chemical Research in Toxicology, 2024; 37(2):227-33. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38241642

34. Kubica P, Majchrzak T, and Vakh C. Unveiling per- and polyfluoroalkyl substances contamination in e-cigarette refill liquids: A comprehensive analytical assessment. Science of The Total Environment, 2025; 960:178297. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39765165

35. Mukerjee R, Hirschtick JL, Arciniega LZ, Xie Y, Barnes GD, et al. ENDS, cigarettes, and respiratory illness: Longitudinal associations among U.S. youth. American Journal of Preventive Medicine, 2024; 66(5):789-96. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38081374

36. Kim CY, Paek YJ, Seo HG, Cheong YS, Lee CM, et al. Dual use of electronic and conventional cigarettes is associated with higher cardiovascular risk factors in Korean men. Scientific Reports, 2020; 10(1):5612. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32221375

37. Wang Y, Sung HY, Lea Watkins S, Lightwood J, Yao T, et al. The association of current exclusive e-cigarette use and dual use of e-cigarettes and cigarettes with psychological distress among U.S. adults. Preventive Medicine Reports, 2023; 36:102425. Available from: https://www.ncbi.nlm.nih.gov/pubmed/37810268

38. Dusautoir R, Zarcone G, Verriele M, Garcon G, Fronval I, et al. Comparison of the chemical composition of aerosols from heated tobacco products, electronic cigarettes and tobacco cigarettes and their toxic impacts on the human bronchial epithelial BEAS-2B cells. Journal of Hazardous Materials, 2021; 401:123417. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32763707

39. Zhao D, Aravindakshan A, Hilpert M, Olmedo P, Rule AM, et al. Metal/metalloid levels in electronic cigarette liquids, aerosols, and human biosamples: A systematic review. Environmental Health Perspectives, 2020; 128(3):36001. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32186411

40. Eshraghian EA and Al-Delaimy WK. A review of constituents identified in e-cigarette liquids and aerosols. Tobacco Prevention & Cessation, 2021; 7:10. Available from: https://www.ncbi.nlm.nih.gov/pubmed/33585727

41. Yassine A, Antossian C, El-Hage R, and Saliba NA. A quick method for the determination of the fraction of freebase nicotine in electronic cigarettes. Chemical Research in Toxicology, 2023; 36(7):1021-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/37406365

42. Harvanko AM, Havel CM, Jacob P, and Benowitz NL. Characterization of nicotine salts in 23 electronic cigarette refill liquids. Nicotine & Tobacco Research, 2020; 22(7):1239-43. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31821492

43. Gray N, Halstead M, Gonzalez-Jimenez N, Valentin-Blasini L, Watson C, et al. Analysis of toxic metals in liquid from electronic cigarettes. International Journal of Environmental Research and Public Health, 2019; 16(22). Available from: https://www.ncbi.nlm.nih.gov/pubmed/31766137

44. Jenkins C, Powrie F, Kelso C, and Morgan J. Chemical analysis and flavour distribution of electronic cigarettes in Australian schools. Nicotine & Tobacco Research, 2024. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39531255

45. Reilly SM, Cheng T, Feng C, and Walters MJ. Harmful and potentially harmful constituents in e-liquids and aerosols from electronic nicotine delivery systems (ENDS). Chemical Research in Toxicology, 2024; 37(7):1155-70. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38924487

46. Tehrani MW, Newmeyer MN, Rule AM, and Prasse C. Characterizing the chemical landscape in commercial e-cigarette liquids and aerosols by liquid chromatography-high-resolution mass spectrometry. Chemical Research in Toxicology, 2021; 34(10):2216-26. Available from: https://www.ncbi.nlm.nih.gov/pubmed/34610237

47. Turina A, Passoni A, Gallus S, Lugo A, Klerx W, et al. On the extension of the use of a standard operating procedure for nicotine, glycerol and propylene glycol analysis in e-liquids using mass spectrometry. Tobacco Induced Diseases, 2024; 22. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39263493

48. World Health Organization. WHO Tobacco Laboratory Network (TobLabNet).  Available from: https://www.who.int/groups/who-tobacco-laboratory-network.

49. Tobacco Laboratory Network. Standard operating procedure for determination of nicotine, glycerol and propylene glycol in e-liquids. WHO TobLabNet Official Method SOP11. Geneva: World Health Organisation, 2021. Available from: https://www.who.int/publications/i/item/9789240022744.

50. Joint Action on Tobacco Control. WP8 - D8.3 Report on the results of inter-laboratory variability of EU MS emission data., Agreement n°: 761297-JATC-HP-JA-03-2016. JATC, 2021. Available from: https://jaotc.eu/wp-content/uploads/2022/03/D8.3-Report-on-the-results-of-inter-laboratory-variability.pdf.

51. Mikheev VB, Buehler SS, Brinkman MC, Granville CA, Lane TE, et al. The application of commercially available mobile cigarette topography devices for e-cigarette vaping behavior measurements. Nicotine & Tobacco Research, 2020; 22(5):681-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30215774

52. Visser WF, Krusemann EJZ, Klerx WNM, Boer K, Weibolt N, et al. Improving the analysis of e-cigarette emissions: detecting human "dry puff" conditions in a laboratory as validated by a panel of experienced vapers. International Journal of Environmental Research and Public Health, 2021; 18(21). Available from: https://www.ncbi.nlm.nih.gov/pubmed/34770036

53. Halstead M, Gray N, Gonzalez-Jimenez N, Fresquez M, Valentin-Blasini L, et al. Analysis of toxic metals in electronic cigarette aerosols using a novel trap design. Journal of Analytical Toxicology, 2020; 44(2):149-55. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31588518

54. Aherrera A, Lin JJ, Chen R, Tehrani M, Schultze A, et al. Metal concentrations in e-cigarette aerosol samples: A comparison by device type and flavor. Environmental Health Perspectives, 2023; 131(12):127004. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38048100

55. Tran LN, Rao G, Robertson NE, Hunsaker HC, Chiu EY, et al. Quantification of free radicals from vaping electronic cigarettes containing nicotine salt solutions with different organic acid types and concentrations. Chemical Research in Toxicology, 2024; 37(6):991-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38778043

56. Casebolt R, Cook SJ, Islas A, Brown A, Castle K, et al. Carbon monoxide concentration in mainstream E-cigarette emissions measured with diode laser spectroscopy. Tobacco Control, 2020; 29(6):652-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31771993

57. Harris T. Physical and chemical characterization of aerosols produced from commercial nicotine salt-based e-liquids. Chemical Research in Toxicology, 2025; 38(1):115-28. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39654291

58. Chen W, Wang P, Ito K, Fowles J, Shusterman D, et al. Measurement of heating coil temperature for e-cigarettes with a "top-coil" clearomizer. PLoS One, 2018; 13(4):e0195925. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29672571

59. El Hourani M, Shihadeh A, Talih S, Eissenberg T, and Group CNFW. Comparison of nicotine emissions rate, 'nicotine flux', from heated, electronic and combustible tobacco products: data, trends and recommendations for regulation. Tobacco Control, 2022. Available from: https://www.ncbi.nlm.nih.gov/pubmed/35086911

60. Farsalinos KE, Voudris V, and Poulas K. E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions. Addiction, 2015; 110(8):1352-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25996087

61. Shihadeh A, Talih S, and Eissenberg T. Commentary on Farsalinos et al. (2015): E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions. Addiction, 2015; 110(11):1861-2. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26395030

62. Omaiye EE, Luo W, McWhirter KJ, and Talbot P. Ultrasonic cigarettes: Chemicals and cytotoxicity are similar to heated-coil pod-style electronic cigarettes. Chemical Research in Toxicology, 2024; 37(8):1329-43. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39051826

63. European Commission. Introduction to Toxicology Available from: https://ec.europa.eu/health/ph_projects/2003/action3/docs/2003_3_09_a21_en.pdf.

64. Stahlmann R and Horvath A. Risks, risk assessment and risk competence in toxicology. German Medical Science, 2015; 13:Doc09. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26195922

65. Farsalinos K. Electronic cigarette evolution: from first to fourth generation products and beyond.  2015. Available from: https://web.archive.org/web/20150708172614/http://gfn.net.co/downloads/2015/Plenary%203/Konstantinos%20Farsalinos.pdf.

66. Brown CJ and Cheng JM. Electronic cigarettes: product characterisation and design considerations. Tobacco Control, 2014; 23 Suppl 2(Suppl 2):ii4-10. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24732162

67. Herrington JS, Myers C, and Rigdon A. Analysis of nicotine and impurities in electronic cigarette solutions and vapor. Restek,  2017. Available from: https://www.restek.com/global/en/articles/analysis-of-nicotine-and-impurities-in-electronic-cigarette-solutions-and-vapor.

68. Kassem NOF, Strongin RM, Stroup AM, Brinkman MC, El-Hellani A, et al. A review of the toxicity of ingredients in e-cigarettes, including those ingredients having the FDA's "Generally Recognized as Safe (GRAS)" regulatory status for use in food. Nicotine & Tobacco Research, 2024; 26(11):1445-54. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38783714

69. Britannica. Formaldehyde.  Available from: https://www.britannica.com/science/formaldehyde.

70. WHO Study Group on Tobacco Product Regulation. Report on the scientific basis of tobacco product regulation: Seventh report of a WHO study group. Geneva: WHO, 2019. Available from: https://www.who.int/publications/i/item/who-study-group-on-tobacco-product-regulation-report-on-the-scientific-basis-of-tobacco-product-regulation-seventh-report-of-a-who-study-group.

71. US Department of Health and Human Services, A report of the Surgeon General: How tobacco smoke causes disease.: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2010. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53017/.

72. Bevan RJ and Harrison PTC. Threshold and non-threshold chemical carcinogens: A survey of the present regulatory landscape. Regulatory Toxicology and Pharmacology, 2017; 88:291-302. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28119000

73. Azimi P, Keshavarz Z, Lahaie Luna M, Cedeno Laurent JG, Vallarino J, et al. An unrecognized hazard in e-cigarette vapor: Preliminary quantification of methylglyoxal formation from propylene glycol in e-cigarettes. International Journal of Environmental Research and Public Health, 2021; 18(2). Available from: https://www.ncbi.nlm.nih.gov/pubmed/33419122

74. Kwak S, Choi YS, Na HG, Bae CH, Song SY, et al. Glyoxal and methylglyoxal as e-cigarette vapor ingredients-induced pro-inflammatory cytokine and mucins expression in human nasal epithelial cells. American Journal of Rhinology & Allergy, 2021; 35(2):213-20. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32746708

75. Fowles J, Barreau T, and Wu N. Cancer and non-cancer risk concerns from metals in electronic cigarette liquids and aerosols. International Journal of Environmental Research and Public Health, 2020; 17(6). Available from: https://www.ncbi.nlm.nih.gov/pubmed/32213824

76. Kapiamba KF, Hao W, Adom S, Liu W, Huang YW, et al. Examining metal contents in primary and secondhand aerosols released by electronic cigarettes. Chemical Research in Toxicology 2022; 35(6):954-62. Available from: https://www.ncbi.nlm.nih.gov/pubmed/35385266

77. Ko TJ and Kim SA. Effect of heating on physicochemical property of aerosols during vaping. International Journal of Environmental Research and Public Health, 2022; 19(3). Available from: https://www.ncbi.nlm.nih.gov/pubmed/35162914

78. Queensland Government. Vaping: results are in.  2023. Available from: https://statements.qld.gov.au/statements/97806.

79. Granata S, Vivarelli F, Morosini C, Canistro D, Paolini M, et al. Toxicological aspects associated with consumption from electronic nicotine delivery system (ENDS): Focus on heavy metals exposure and cancer risk. International Journal of Molecular Sciences, 2024; 25(5). Available from: https://www.ncbi.nlm.nih.gov/pubmed/38473984

80. Therapeutic Goods (Standard for Therapeutic Vaping Goods) (TGO110) Order 2021. Available from: https://www.legislation.gov.au/F2021L00595/latest/text.

81. Therapeutic Goods Legislation Amendment (Standard for Therapeutic Vaping Goods) (TGO110) Instrument 2024 (Cth). Available from: https://www.legislation.gov.au/F2024L01232/asmade/text

82. Therapeutic Goods Administration. Nicotine vaping products and vaping devices: Guidance for the therapeutic goods (standard for nicotine vaping products) (TGO 110) Order 2021 and related matters Version 1.2. Canberra: Government of Australia, 2021. Available from: https://vape-testing.com/wp-content/uploads/2023/07/nicotine-vaping-products-and-vaping-devices_0.pdf.

83. Farsalinos KE, Kistler KA, Gillman G, and Voudris V. Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins. Nicotine & Tobacco Research, 2015; 17(2):168-74. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25180080

84. Varlet V, Farsalinos K, Augsburger M, Thomas A, and Etter JF. Toxicity assessment of refill liquids for electronic cigarettes. International Journal of Environmental Research and Public Health, 2015; 12(5):4796-815. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25941845

85. Behar RZ, Luo W, Lin SC, Wang Y, Valle J, et al. Distribution, quantification and toxicity of cinnamaldehyde in electronic cigarette refill fluids and aerosols. Tobacco Control, 2016; 25(Suppl 2):ii94-ii102. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27633763

86. Hutzler C, Paschke M, Kruschinski S, Henkler F, Hahn J, et al. Chemical hazards present in liquids and vapors of electronic cigarettes. Archives of Toxicology, 2014; 88(7):1295-308. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24958024

87. Therapeutic Goods Administration. Testing of nicotine vaping products. Australian Government, Department of Health,  2022. Available from: https://www.tga.gov.au/testing-nicotine-vaping-products

88. Hickman E, Herrera CA, and Jaspers I. Common e-cigarette flavoring chemicals impair neutrophil phagocytosis and oxidative Burst. Chemical Research in Toxicology 2019; 32(6):982-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31117350

89. Hiler M, Weidner AS, Hull LC, Kurti AN, and Mishina EV. Systemic biomarkers of exposure associated with ENDS use: a scoping review. Tobacco Control, 2023; 32(4):480-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/34732539

90. Batista DR, Coelho LS, Tanni SE, and de Godoy I. Metal in biological samples from electronic cigarette users and those exposed to their second-hand aerosol: a narrative review. Frontiers in Medicine, 2024; 11:1349475. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38841573

91. Dai HD, Reyes S, Buckley J, and Maloney P. Biomarkers of nicotine and toxicant exposure by e-liquid nicotine concentration level among US adult exclusive e-cigarette users. Cancer Epidemiology, Biomarkers & Prevention, 2025; 34(1):42-50. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39387549

92. Kochvar A, Hao G, and Dai HD. Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring. Tobacco Control, 2025. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38684372

93. Melero-Ollonarte JL, Lidon-Moyano C, Perez-Ortuno R, Fu M, Ballbe M, et al. Specific biomarker comparison in current smokers, e-cigarette users, and non-smokers. Addictive Behaviors, 2023; 140:107616. Available from: https://www.ncbi.nlm.nih.gov/pubmed/36680837

94. Taylor E, Simonavicius E, McNeill A, Brose LS, East K, et al. Exposure to tobacco-specific nitrosamines among people who vape, smoke, or do neither: A systematic review and meta-analysis. Nicotine & Tobacco Research, 2024; 26(3):257-69. Available from: https://www.ncbi.nlm.nih.gov/pubmed/37619211

95. Tang MS, Lee HW, Weng MW, Wang HT, Hu Y, et al. DNA damage, DNA repair and carcinogenicity: Tobacco smoke versus electronic cigarette aerosol. Mutation Research - Reviews in Mutation Research, 2022; 789:108409. Available from: https://www.ncbi.nlm.nih.gov/pubmed/35690412

96. Tang MS, Wu XR, Lee HW, Xia Y, Deng FM, et al. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proceedings of the National Academy of Sciences U S A, 2019; 116(43):21727-31. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31591243

97. Cheng G, Guo J, Carmella SG, Lindgren B, Ikuemonisan J, et al. Increased acrolein-DNA adducts in buccal brushings of e-cigarette users. Carcinogenesis, 2022; 43(5):437-44. Available from: https://www.ncbi.nlm.nih.gov/pubmed/35239969

Intro
Chapter 2