1. bookVolume 30 (2021): Issue 2 (May 2021)
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01 Jan 1992
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4 times per year
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access type Open Access

Evidence From the Scientific Assessment of Electronic Cigarettes and Their Role in Tobacco Harm Reduction

Published Online: 20 May 2021
Page range: 63 - 108
Received: 09 Feb 2021
Accepted: 04 May 2021
Journal Details
License
Format
Journal
First Published
01 Jan 1992
Publication timeframe
4 times per year
Languages
English
Summary

While smoking remains a main global cause of preventable morbidity and mortality, a potential inflection point has arrived where it could become possible for non-combustible nicotine products to displace cigarettes and reduce risk for smokers who transition completely from smoking. These have proven consumer satisfaction and are now widely and increasingly available globally. One of the most prominent of these nicotine products are electronic cigarettes (ECs), which are used daily by millions of current and former smokers. The category is not without controversy as these products are not risk free and can cause nicotine dependence. The differing interpretation of science assessing ECs has transpired into inconsistent regulation and product standards, providing an environment for its fragmented manufacturing base which allows for variable product quality and in turn, product quality variability has impacted on how they are viewed. In this review, we assess published scientific evidence to evaluate whether, on balance, ECs fulfil a tobacco harm reduction role by reducing health risks relative to smoking and providing a viable alternative for smokers while having limited appeal to non-smokers.

INTRODUCTION

Smoking remains an important cause of preventable morbidity and mortality (1). The World Health Organization (WHO) currently estimates that worldwide, around 1.3 billion adults smoke (2). The overwhelming majority of the disease risk is acknowledged to come from compounds formed during combustion of tobacco at very high temperatures (~950 °C) (3, 4). Of roughly 6,500 compounds (5), about 150 are known toxicants (6) that contribute to smoking-related diseases, such as cardiovascular and respiratory diseases, and cancers. These toxicants also increase the risk of disability and death by other diseases; risks rising with increasing duration of regular smoking. However, excess risks are substantially reversible with smoking cessation (7). Nevertheless, not all nicotine users want to quit, and others find it difficult to do so.

In 2010, the WHO published its Framework Convention on Tobacco Control (FCTC) treaty (8), creating aspirational policy goals for the 181 member states that ratified it. Traditionally, WHO has taken an absolute tobacco control approach to smoking, despite article 1(d) in the FCTC advocating for harm reduction strategies. Since its publication, many countries have implemented the associated guidelines to varying degrees. Since these goals were published, various alternative nicotine products have become commercially available (e.g., electronic cigarettes (ECs), tobacco-free nicotine pouches, and other vapour products), which has led to increasing consideration of the concept of tobacco harm reduction. Harm reduction initiatives involving alternatives to smoking must aim to protect youth and non-smokers from uptake, including by regulation of products, advertising, promotion, and sponsorship (9). This principle involves reducing the risk to smokers by offering satisfactory alternative products with lower risk profiles (10,11,12,13). For example, in Sweden, where there is high prevalence of snus use, daily smoking prevalence is one of the lowest in Europe. Only 7% of the adult population were daily smokers in 2020 (14). Snus is less harmful to health than smoking (15), and Swedish men, who are the predominant snus users, have among the lowest rates of lung cancer incidence and tobacco-related mortality worldwide (16). The potential role of snus in a tobacco harm reduction strategy has been recognised by the US Food and Drug Administration (FDA), granting modified risk orders for eight snus products in 2019 (17, 18).

A widely available alternative nicotine product is ECs. Use of ECs is commonly known as vaping and users are known as vapers. These products heat a liquid (termed e-liquid) containing ingredients that function as carriers (e.g., propylene glycol (PG) and vegetable glycerin (VG)) and may contain flavours and/or nicotine. Compared with tobacco combustion, e-liquids are heated to only around 250 °C and release an aerosol that is much less complex than cigarette smoke, having substantially fewer and lower concentrations of compounds (19,20,21,22). Systematic reviews indicate substantially decreased disease risk compared with smoking through greatly reduced exposure to toxicants and carcinogens (23,24,25,26,27,28), although the risks are not wholly eliminated nor yet fully characterised. Several governments, including those in the UK (24, 29), Canada (30), and New Zealand (31) support use of ECs as reduced-risk alternatives to smoking.

Where manufacturing is actively regulated and monitoring systems are in place, EC quality tends to be high (32) and numbers of reported adverse and serious adverse events leading to morbidity or mortality are low (33). By contrast, if poorly made or illegal products are allowed to enter markets, they substantially increase the risks of adverse events. In the electronic vapour acute lung injury (EVALI) crisis in the USA in 2019, non-regulated e-liquid containing vitamin E acetate and medium-chain triglycerides that are often used in consumption of cannabis and tetrahydrocannabidiol were illegally used as additives, causing severe lung injury in some users (34, 35). This tragedy killed 68 people and injured over 2,000.

This review paper considers the role of ECs in tobacco harm reduction. It provides a high-level account of the evolution of EC design, safety and performance, and methods of testing. Scientific evidence is assessed in relation to acute and long-term health risks associated with EC use. Finally, it discusses how ECs perceptions and use behaviours could impact a harm reduction strategy as well as how available evidence can be used to evaluate health outcomes at population level.

PRODUCT DESIGN AND REGULATION
EC design basics

ECs were introduced to the market in 2004 and came to prominence around 2010. Despite this short period, the types of devices have cycled through several generations (Figure 1) (28), in each of which many different devices are available (36). From simple closed, low-power ‘cig-a-like’ devices (generation one), they transformed to refillable long-term use (generation two) and modifiable (generation three) systems, and further to discreet closed system devices with many safety features and improved nicotine delivery (generation four; Figure 1).

Figure 1

Schematic illustration of e-cigarette devices showing disposable 1st generation (cig-a-like) e-cigarettes, 2nd generation with refillable system, 3rd generation customizable ECs, and 4th generation e-cigarettes closed systems.

The basic elements of ECs are a battery connected to a heating element and an e-liquid reservoir. In first generation, single-piece cig-a-like products, all parts are encased into one (usually disposable) unit. The three-piece open systems of generations two and three consist of a separate battery, e-liquid cartridge, and atomizer (vaporizes the e-liquid), and parts and components may be swapped to customize the vaping experience (e.g., by increasing voltage, tank size, and/or e-liquid strength and flavour). Fourth-generation two-piece products consist of a battery and a cartomizer (a combined e-liquid cartridge and atomizer), which is the only exchangeable part. EC emissions may differ by product characteristics and operation and user behaviour (28). Many manufacturers’ design changes have been based on feedback from users searching for products that can meet their nicotine preference with sufficient satisfaction to enable them to replace cigarettes while favouring safety and flexibility (21, 36). In most countries, cig-a-like devices account for only 15% of the EC market, except in the USA, where they are used by around 50% of vapers (37).

The most common reasons for smokers rejecting ECs relate to performance (mimicking smoking and effectiveness at lessening cravings for smoking), but other common reasons are ease of use. In a survey published by Action on Smoking and Health (ASH) (38), 7% of users stopped using ECs because of difficulties in replacing components, refilling e-liquid, or due to leaking. Wadsworth et al. (39) found that the ease of using cig-a-like ECs (confidence in nicotine dose, no refilling required, ease of availability compared with later-generation devices, etc.) made them a popular first device for vapers. By contrast, third-generation modifiable models were considered “bulky” or “scary”. However, cig-a-likes (39) and e-cigarettes in general (40) were often found to be unsatisfactory.

An unpleasant problem is so-called dry wicking, more commonly known as “dry puff”, which is caused when the wick in the atomizer is not saturated, leading to the coil becoming overheated and thermal breakdown of solvents in e-liquid (41,42,43,44,45,46,47). The dry wick effect can occur when the e-liquid runs out and the user puffs deeply or if the voltage on modifiable devices is too high for the heating system. While this phenomenon is thought to increase the emission of toxicants (42), it causes a very unpleasant acrid taste (48) that is generally viewed as sufficiently arresting to prevent harm (24). In generation four products, some manufacturers have introduced pre-set power settings to help users to vary their vaping experience while avoiding dry wicking. For example, a distiller-plate heating system, which heats the e-liquid directly and replaces the coil and wick system, has increased nicotine delivery while minimizing the risk of dry puffs (21).

Use of flavours

Thousands of flavours are available for ECs, and even within individual flavours, many variations in formulations exist. Sensorial aspects, such as sweetness, coolness, and vapour visibility or smoothness, play important parts in product acceptability (49,50,51). A systematic review by Zare et al. (52) found that all vapers preferred flavoured ECs, particularly sweet flavours, irrespective of age group. Adult consumers identify taste and variety of flavours as important characteristics of ECs (53). Most first-time purchases of ECs and e-liquids contain fruit flavours (54, 55). However, some studies suggest that flavours could be a determinant for adolescents trying ECs and, potentially, transitioning to smoking (56) or that flavours could reinforce the reward obtained from nicotine vaping products, increasing their potential for abuse liability (57, 58). An ASH survey (59) found that fruit flavours have overtaken both tobacco flavours and mint as the preferred e-liquid, accounting for nearly one-third of flavoured e-liquids used, and those using fruits or sweet flavours were more likely than tobacco flavour users to vape in order to quit smoking (60).

Product regulation

In many countries, ECs are regulated (in around 100 countries) (61), but the regulations are inconsistent and generally cover marketing, labelling, ingredients, and/or taxation, leading to highly variable product standards globally. However, only six countries have no regulations beyond minimum age for purchase (61). Marketing authorizations or product notifications/marketing applications may be required before products can enter the market. Pre-market authorizations involve the regulator giving permission for marketing after review of an application, placing some of the responsibility for a product on the regulator. By contrast, with product notifications/marketing applications, while the regulator may act on information provided, responsibility for the product remains with the submitter. The European Parliament, the US Food and Drug Administration (FDA), and various other national authorities request data on ingredients and various compounds in emissions, including types, quantities, and origins. Forty-two countries have banned ECs, most frequently based on the perceived risk of youth nicotine addiction or the potential that yet unknown long-term effects of vaping might outweigh any health benefits (61,62,63,64).

In the USA, regulation of ECs was introduced in 2016 (65). All new tobacco products, including ECs despite their lack of tobacco leaves, are subject to approval via Pre-Market Tobacco Product Applications (PMTA) (66). Manufacturers that wish to be able to claim that an individual tobacco product (but not a product class) reduces risk to health compared with smoking must also make a Modified Risk Tobacco Product Application (67, 68). Each submission requires a dossier with description and formulation of the product, description of non-clinical and clinical research findings relating to the effects of the product on tobacco-related diseases and other health-related conditions, how it will be used, as well as, examples of labelling and a description of how the product would be marketed. So far, numerous Pre-Market Tobacco Product Applications have been made for ECs but no Modified Risk Tobacco Product Application submission for ECs has yet been approved by the FDA. Dossier review times are expected to run into several years, making it likely the market will not easily benefit from product improvements as the category develops. In the EU, the Tobacco Products Directive 2014/40/EU (TPD2) regulates the manufacture, sale, and marketing of tobacco products (69). It incorporates a product notification system and aims “to facilitate the smooth functioning of the internal market for tobacco and related products, taking as a base a high level of health protection”. The first factor requires an assessment of the product relative to the products already on the market, whereas the second focuses on the safety of the product itself. The TPD2 sets certain minimum safety and quality requirements, including, but not limited to, maximum nicotine concentration (20 mg/mL) and maximum volumes for cartridges, tanks, and nicotine liquid containers (2 mL), child-resistant and tamper proof features on devices and e-liquid bottles, and refilling systems that prevent leaking. These are, in addition to EU safety regulations on restriction of hazardous substances in electrical and electronic equipment products (70), the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation (71), testing requirements for electrical parts, and monitoring and reporting of adverse events (69). TPD2 is expected to be revised in the mid-2020s.

In most countries, advertising and marketing of ECs is highly controlled in terms of where and what information may be displayed and how. In the UK, the Committee of Advertising Practice does not allow advertising of ECs to make medicinal claims (e.g., can help with smoking cessation) unless they have marketing authorization from the Medicines and Healthcare Products Regulatory Agency, and messages must not appeal to youth or encourage non-smokers or non-nicotine-users to use ECs (72). In the US, modified risk claims can be made only for products authorized by the FDA via the Modified Risk Tobacco Product Application process (73). A few countries, like Canada and New Zealand, allow promotion of the use of ECs as less harmful alternatives to tobacco smoking by providing balanced risk information for consumers (74, 31).

As well as top-line requirements, further detail on interpretation and compliance are provided by regulatory guidance documents, national, regional, and international technical product standards, and voluntary industry codes. Technical committees creating standardised safety and quality guidance for ECs have been set up at the International Organization for Standardization (ISO) and the European Committee for Standardization (CEN), involving experts from industry, regulators, consumers, and other relevant stakeholders. Each has published two technical standards on generating emissions for measurements, what to measure in emissions, device safety, and analytical methods for measuring the main components in e-liquids (75,76,77,78). Further guidelines are being developed on electrical safety, manufacturing, ingredients, additional emissions and e-liquid measurement methods, consumer information, and labelling. Adoption of product standards is important to consumers to inform them about the quality of ECs, and to regulators and industry to clarify methodologies and data generated for marketing applications. Specifically, a framework of testing standards for ECs has been proposed, as many methods used had simply been adapted from cigarette testing methods. This will enable clearer comparison of aerosol yields within and across different product categories, including cigarettes (79).

PRODUCT SAFETY AND STEWARDSHIP

When ECs were first introduced, concerns were expressed about e-liquid after the number of calls to poison centres reporting exposure and irritation of skin or eyes with contact rose (80,81,82), but the risk of incidents has been reduced by changes in product design and labelling, e.g., non-spill e-liquid cartridges in closed ECs, improved information for use of open, refillable ECs and measures to take when accidental spills do occur, and testing of appropriate concentration ranges for ingredients. Nevertheless, some of the measures that could increase the safety are, for example, by developing child-resistant mechanisms for puff-activated products. For open products, the tanks should be child resistant and refilling could be leak-free, such as with a dock-and-lock mechanism.

Exploding devices and batteries occur infrequently but have led to severe burns and projectile injuries. These events are generally related to use of inappropriate chargers not supplied with the product that deliver too much current to the battery, leading to thermal runaway and generation of flammable and explosive gases (83). Well-designed products should meet international standards for protection against overcharging (76) and ensure sufficient venting capacity of the battery compartment. Likewise, battery quality should comply with existing international standards. EC products in Europe are covered directly by Electromagnetic Compatibility (EMC) Directive (2014/30/EU) (84) and Restriction of the Use of Certain Hazardous Substances (RoHS) Directive (2011/65/EU) (85), as indicated by the CE marking. Additionally, aspects of the General Product Safety (GPS) Directive (2001/95/EC) apply (86). The GPS sets out safety requirements for all consumer products being placed on the European market (and allows the use of adjacent standards, such as within the low-voltage-device safety standards, to control failure modes and risks), but is not itself associated with CE marking. Occasionally, battery explosions have been caused by improper storage or modification by users (28), and this issue requires further user education.

The European Committee for Standardization provides practical and enforceable requirements related to electrical safety, leakage and breakage, child resistance and some high-level device material considerations (76). ECs continue to be a developing product category and best practice guidance will thus require regular updating.

Product stewardship for ECs has been developed by several EC manufacturers to address materials and ingredients, interactions of the e-liquid and the device (e.g., aerosol laboratory and clinical testing), and post-marketing surveillance (e.g., customer feedback or complaints, product sustainability, etc.). A potential approach for toxicological stewardship of ECs is summarised in Panel 1 (87,88,89). The need for purity requirements and exclusion of ingredients with certain toxicological properties has gained widespread recognition (90). However, the basic principle that the dose determines the level of toxicological risk seems often to be forgotten, leading to purported adverse effects in the literature based on in vitro cytotoxicity or other effects without human exposure contextualisation. (91).

EC stewardship toxicological best practice.

Nicotine and humectants should be of pharmaceutical grade purity

Flavourings should be food grade purity

Protect consumers from ingredients identified as carcinogens, mutagens, reprotoxicants, and respiratory allergens

Manufacturers should maintain an additional negative list of ingredients that have been proven to be unsuitable for use in vaping products (e.g., diacetyl, vitamin E acetate, triglycerides) and follow regulatory guidance about any other substance

Toxicological risk assessments should be performed for each e-liquid to demonstrate ingredients and concentrations in e-liquid are supportable

Conduct chemical and toxicological assessments of aerosol for every device and e-liquid variant (can benefit from a bridging approach)

Besides addressing ingredient selection, an e-liquid toxicological risk assessment should determine whether the levels of the ingredients are suitable for the intended use (92, 93). In vitro assessments, such as cytotoxicity tests, and comparison to reference materials enable quantitative translation of effects to real-life situations.

Additionally, a robust stewardship process should monitor consumer complaints and analyse them to ensure safety and engagement with the product continuous improvement process.

INVESTIGATION OF ACUTE AND LONG-TERM HEALTH RISKS

Multiple scientific frameworks for risk assessment have been presented that outline the approach for investigating the risk profile of non-combustible tobacco and nicotine products (13, 94,95,96). Broadly, all frameworks are underpinned by investigation of acute and long-term risk from using ECs in studies assessing chemistry, toxicology and clinical outcomes, and also by the perceptions and behaviours of users and non-users of ECs. In this section, we present published data from multi-disciplinary scientific studies of ECs generated within product assessment frameworks and investigating acute and long-term risks from using ECs.

Chemical and physical characterization

Compounds of interest in ECs have often been based on smoking toxicant emissions (97) and many studies use smoking as a comparator, meaning that smoke toxicants have been the focus of most assessments so far (98,99,100,101,102). Investigational approaches are, therefore, evolving in response to emerging evidence and growing understanding of EC aerosol composition.

The EU TPD2 stipulates chemical emissions testing for multiple priority compounds, including acetaldehyde, acrolein, and formaldehyde (84). The US FDA has identified 92 harmful or potentially harmful constituents (HPHCs) in addition to nicotine (103) and public comment was recently sought on the proposal to add a further 19 compounds to the list (104). However, to our knowledge, only one study has investigated the emissions of these additional HPHCs (22). In practice, it has been suggested that Pre-Market Tobacco Product Applications should report at least 32 compounds (66). ECs generally do not reach temperatures higher than 250 °C during normal use or more than 350 °C under dry wicking conditions (105). However, a huge variety of devices and e-liquids exist (106) and many different puffing conditions and analytical techniques have been used to assess them (42, 107,108,109), but, overall, results indicate significantly lower levels of toxicants in EC aerosols than in cigarette smoke (20, 22, 43, 44, 102, 110, 111).

Methodological considerations in vaping products analytical testing

Despite the relative simplicity of EC aerosol, consideration must be given to aerosol collection methods and measurement of specific analytes. For example, a review of papers that measured carbonyl emissions from ECs showed many variations in the measurement techniques, including puffing regime, aerosol collection, and analytical methodology, making data comparisons difficult (41, 42). Reducing variability would maximize sensitivity of reported values (43). The CORESTA Recommended Method No 81 (112) includes standardised puffing conditions for ECs that have now been used in multiple emissions testing studies (20,21,22, 113,114,115).

Potential contamination from the testing environment (e.g., the presence of volatile organic species in occupational and residential room air) is a well-documented phenomenon. Indoor air quality reference values have been established for several species (20). The presence of an analyte in a laboratory reagent used for testing, for example carbonyls in 2,4-dinitrophenylhydrazine, is also well recognized (43). Given the low levels of most compounds in EC emissions, use of air and blank controls and management of the chemical background of the testing environment are crucial to provide context (e.g., contribution of non-product-related compounds of interest) and minimize errors in the analytical data (20, 116). Reporting control data as standard will improve interpretability of results.

Sources of toxicants in e-liquids and aerosol

The number of components in e-liquids is estimated to be around 113 (28) compared with around 600 in tobacco cigarettes (109). In high-quality manufactured ECs, the main sources of toxicants in aerosol are attributed to impurities in liquid, degradation of the e-liquid ingredients, and device components. Most compounds associated with e-liquid formulation are either not detected or are very close to the limit of quantification (113, 117).

Impurities and leaching

Carbonyl compound levels can increase with increasing flavour content. Retail flavours were added to a 1:1 PG-VG mixture at 5–50% (v/v) and carbonyl compound levels increased linearly by 1.3–10.5 times (118). However, these concentrations are not representative of commercial e-liquid formulations and were sampled in a non-standard puffing regime. In flavours derived from the extraction of cured tobacco leaf, major tobacco-derived toxicants (e.g., tobacco-specific nitrosamines and nitrates) were present at very low levels compared to those in tobacco products but whether these transferred to aerosol was not assessed (100). E-liquid components can cause unintended formation of toxicants, such as acetoin leading to formation of diacetyl (119). Reduction of toxicants in e-liquid, directly or by avoiding reactions with other components, may be achieved with good stewardship during product development (87). Metals in e-liquid are generally impurities or are leached from the cartomiser or device materials through contact (120,121,122), but this occurrence is generally restricted to earlier EC designs (123,124,125,126). A selection of results from studies investigating metals in different devices has been compiled in Table 1. In a study of 15 trace elements in 27 different e-liquids from one manufacturer, samples contained fewer than 10 ppb or concentrations below the lower level of quantification for all elements except aluminium, chromium, copper, antimony, and zinc (127).

Comparison of metal levels in e-cigarette vapour versus cigarette smoke from published studies analysed.

Category Device/Cigarette Regime No. of puffs Metals Units Source

Mercury Cadmium Lead Chromium Nickel Arsenic Selenium
Cigarette 1R6F HCI 4.68 76.1 BLQ BLD BLD BLQ BLD ng/cig Jaccard et al. (342)
Cigarette 3R4F HCI 4.92 93.2 BLQ BLD BLD BLQ BLD ng/cig Jaccard et al. (342)
EC Gen 1 Various 70 / 1.8 / 10c 150 N/A 0.01–0.22 0.03–0.57 N/A 0.11–0.29 N/A N/A μg/150 puffs a Goniewicz et al. (44)
Cig-a-like 10 N/A N/A 0.017 0.007 0.05 N/A N/A μg/10 puffs a Williams et al. (123)
EC Gen 2/3 Open tank N/A 0.05–0.16 6.88–541 0.39–15.6 1.32–2148 0.1–1.59 N/A μg/kga Zhao et al. (130)
EC Gen 3 Liquids in reference CRM81 N/A < 0.06 < 0.05–0.12 < 0.09–1.58 < 1.08–1.54 < 0.12–1.33 N/A ng/puffa Belushkin et al. (116)
EC Gen 4 Closed system N/A 0.04–0.05 0.88–6.88 0.39–0.41 1.32–11.9 0.09–0.10 N/A μg/kga Zhao et al. (130)
myblub CRM81 150 BLQ BLD BLD BLD BLQ BLQ 0.00024 μg/puff O'Connell et al. (343)

Median

tobacco flavour, 1.6% nicotine

puff volume / duration / interval

Abbreviations: BLD

below limit of detection

BLQ

below limit of quantification

CRM81

CORESTA recommended method number 81

EC

electronic cigarette

EC

Gen electronic cigarette generation

HCI

Health Canada intense machine smoking regime

N/A

not analyzed

Kamilari et al. (128) found levels of metals below those defined by regulatory authorities for inhaled medicines in 22 e-liquids from various markets. Na et al. (129) reported that levels of some metals increased and transferred to aerosol after e-liquid was in contact with coils and open-system atomizers for 7 days, but this circumstance would be unusual for most EC users. Ratios of metals before and after use differed, indicating transfer of metals into aerosol in six liquids (129). However, generally, heavy metals do not seem to transition to aerosol (44). Belushkin et al. (116) found higher concentrations of heavy metals in aerosol than in air blanks in only two samples of e-liquid among a wide range of products from multiple manufacturers. Similarly, Margham et al. (20), found that the measured metals in EC aerosol were not significantly different from those in air blanks. High-powered and open-system devices are likely to have higher metal content in aerosol than closed systems (130), but none of the metal content is likely to generate significant adverse health effects (131). Fowles et al. (132) concluded in a review that metals in vapour could constitute a health risk to EC users but that high product standards can minimize exposure and reduced health risks associated with metals in EC aerosol.

Thermal degradation

Aldehyde formation may be influenced by e-liquid ingredients, overheating and dry wicking (41,42,43,44,45,46,47) and e-liquid oxidation through direct contact with the nickel-chromium heater coil (133,134) are the dominant causes. Improved coil designs and wicking materials that enhance e-liquid flow to the heaters can reduce the risk of these phenomena (135,136,137). In fourth-generation ECs, the levels of the key carbonyls of concern – formaldehyde, acetaldehyde, and acrolein – are greatly reduced compared to those in cigarette smoke (22). Table 2 illustrates the complexity of comparisons due to the differences in methodological and reporting approaches.

Comparison of carbonyl levels in e-cigarette vapour versus cigarette smoke from published studies.

Category Device/Cigarette Regime No. of puffs Carbonyls Units Reference

Formaldehyde Acetaldehyde Acetone Acrolein Propionaldehyde Crotonald ehyde MEK Butyraldehyde
Cigarette 1R6F HCI 9.1 4.879 158.9 62.31 14.51 13.74 4.484 15.93 3.08 μg/puff (22)
Cigarette Benson & Hedges Sky Blue HCI 8.1 5.235 177.4 65.68 15.93 15.43 5.321 17.41 4.469 μg/puff (22)
EC Gen1 Various 70 / 1.8 / 10* 150 3.2–56.1 2.0–13.6 N/A 0–41.9 N/A N/A N/A N/A μg/150 puffs (44)
EC Gen 2 Various open tank 55 / 4 / 30* 10 0.9–2.7 0.3–1.7 N/A 0.7–1.9 N/A N/A N/A N/A μg/10 puffs (344)
EC Gen 2/3 Open tank/NHOSS “Lounge” model (no nic./16 mg/mL nic.) CRM81 96 0.37–1.48 0.16–0.96 N/A 0.05–2.1 1 N/A N/A N/A N/A ng/mL puff (113)
EC Gen 3/4 ePen CRM81 122 106 73 70 LOQ N/A N/A 8 ng/puff (20)
EC Gen 4 JUUL rich tobacco (20 mg/mL) CRM81 112 76 3 13 N/A N/A N/A N/A ng/puff (114)
JUUL rich tobacco (18 mg/mL) CRM81 11 12 36 7 N/A N/A N/A N/A ng/puff (114)
myblu (tobacco flavour, 1.6% nic.) CRM81 150 < 2.63 < 17.5 < 8.75 < 4.38 < 4.38 < 4.38 < 4.38 < 4.38 μg/150 puffs (115)
Vype ePen 2 (18 mg/mL nic.) CRM81 268 230 135.8 346 96.2 BLD BLD BLD ng/puff (22)
Vype ePen 3 (BAT 18 mg/mL nic.) CRM81 52.8 NQ 111 BLD NQ BLD BDL BLD ng/puff (22)

Puff volume / duration / interval

Abbreviations: BLD

below limit of detection

LOQ

Limit of quantitation

CRM81

CORESTA Recommended Method No81

EC

electronic cigarette

EC Gen

electronic cigarette generation

HCI

Health Canada intense machine smoking regime

MEK

methyl ethyl ketone

N/A

not analysed

Nic.

nicotine

NQ

not quantified

Nicotine salts in e-liquids have lower volatility than free-base nicotine, enabling enhanced nicotine delivery without increased irritation during vaping (138). Pharmacokinetic assessments indicate that the concentration of nicotine delivered is close to that in cigarette smoke, and the efficiency of delivery is improved compared with e-liquids containing free-base nicotine (139,140,141). At least six different acids have been identified in e-liquid formulations, alone or in combination, but the most common are lactic, benzoic, and levulinic acids (142). Nicotine benzoate is one of the most thermally stable organic acids but can decarboxylate under high temperatures to form benzene or phenol (143). Only one study has shown such degradation in ECs, and this effect was limited to high-powered open systems (144).

Second-hand exposure to vaping aerosol

Harmful health effects from secondhand smoke exposure have been widely reported (145). Although EC aerosol is much simpler than cigarette smoke and does not generate side-stream smoke, bystanders are still exposed to exhaled compounds, especially in indoor conditions.

Studies investigating the extent and nature of this exposure have tended to measure volatile organic compounds, CO2, particulate matter (generally PM2.5 or PM10.0), ultrafine particles, and nicotine. Some studies have found increased concentrations of particulate matter after vaping in indoor settings (146,147,148), but generally conclude that exposure is lower compared to cigarette smoke (149, 150) and is less likely to be harmful to bystanders than second hand smoke (28, 29, 151,152,153). The absolute risk from passive exposure to EC aerosol specially in vulnerable populations, like children, pregnant women and people with impaired respiratory and cardiovascular systems, requires further assessment (151).

Toxicological assessment

As explained in the product stewardship section (see p. 66–67), robust toxicological approaches guided by regulation are essential to screen ingredients and complex mixtures (92, 154). In the screening phase, in silico approaches can be useful to identify hazards from known substances in e-liquids and to estimate toxicity of substances for which toxicological profiles are not well characterised (155). Zarini et al. (156) used an in silico approach to develop quantitative structure-activity relationship models from data in the literature and toxicological databases in order to prioritize e-liquid ingredients according to potential acute toxicity. They used this approach to classify 264 e-liquid ingredients and flavours according to European classification labelling and packaging criteria and recommended this method to generate information for use in a weight-of-evidence approach (156).

Substances of potential concern identified through in silico toxicology should be investigated by in vitro and in vivo methods, including toxicological assays where appropriate, to calculate thresholds of concern (157). The US FDA still recommends in vivo studies when assessing acute effects in the respiratory system (158). The European Chemicals Agency (ECHA) (159) favours a weight-of-evidence approach, reflecting changing attitudes and laws in multiple countries about moving toxicology analysis away from animal testing towards innovative high-throughput and cell-culture platforms.

In vitro studies range from traditional toxicological models adapted from smoke exposure studies (160) to three-dimensional cell-culture models that recreate organotypic tissue (161, 162). Multiple studies have investigated acute and chronic toxicological risk of ECs (163, 164), including testing for mutagenicity (91, 115, 165,166,167), cytotoxicity (potency) (91, 115, 168,169,170,171), genotoxicity (91, 115, 172,173,174), oxidative stress (175, 176), and wound healing (177).

Traditional toxicological tests yield complex results and are affected by variability found between and within cell lines, limited translatability to the in vivo assays, and a lack of benchmarks to contextualize the findings (171, 178). Additionally, results might be affected by the diversity of EC designs, as found in a critical review of toxicological in vivo and in vitro studies by Wang et al. (164). Overall, though, the weight of evidence indicates that ECs present lower risks to users and bystanders than conventional cigarettes (179).

Broader toxicological approaches, such as systems toxicology, may be applied. Systems toxicology employs data from techniques like transcriptomics or proteomics from exposed cells to investigate pathways involved in oxidative stress, inflammation, cell proliferation, or DNA damage, and may highlight previously unidentified potential risks (180,181,182,183).

Computational risk assessment methodologies have been proposed to compare cancer potencies across tobacco products (47, 184). Cancer potency can be calculated from EC chemical emissions data and enable comparisons between products by factoring consumer exposure to different products. Stephens (47) suggested that ECs only have 0.004 times the carcinogenicity of cigarette smoke whilst still being 10.7 times more carcinogenic than nicotine inhalers.

Assessment of clinical and health effects of vaping

Smoking increases health risks to cardiovascular, respiratory, and other systems soon after the onset of smoking, with the risks of death, disease, and disability rising with increasing duration of use. However, these excess risks are largely reversible with smoking cessation (7). Acute measurements of circulation and lung function may improve within 3–9 months of quitting, and coronary heart disease excess risk due to smoking is halved after 1 year and completely reversed by around 15 years (2, 185). The aim of assessing clinical effects of smoking, therefore, is not only to investigate damage caused but also to assess whether changing behaviour can reduce these excess risks and/or lead to functional benefits.

Nicotine pharmacokinetic studies

Satisfactory nicotine delivery is critical to the acceptability of ECs. Despite the popularity of later-generation ECs, many users relapse to smoking alone or alongside EC use (dual use) raising concerns about the viability of ECs as a long-term alternative to cigarettes (186,187,188,189). Data from 1,489 current adult smokers reported they discontinued using ECs mostly because the experience was not close enough to smoking and cravings were not reduced (189). Later-generation EC designs have attempted to address these issues through use of higher power, improved coil heating elements, and nicotine delivery without irritation (190).

Pharmacokinetic clinical trials are often used to investigate safety, nicotine delivery, and acceptability of ECs. These studies assess the likelihood of product-related adverse effects, describe the concentration-time profile for nicotine, and provide insights into the relationship between nicotine concentration and specific responses (e.g., urge for product, craving, and product liking/satisfaction). Pharmacokinetic endpoints estimated from these studies can be used to make comparisons between different EC products and with other product classes (e.g., combustible cigarettes and nicotine replacement therapies (NRTs)).

The average maximum concentration (Cmax) of nicotine with smoking is 10–21 ng/mL, depending on the “tar” and nicotine yield of the cigarette (191,192,193,194,195,196,197). For NRT, Cmax is generally in the range 2–18 ng/mL, depending on the nicotine concentration, type of device, and usage (198,199,200). Early pharmacokinetic studies using first-generation (cig-a-like) ECs with similar nicotine concentrations to NRT and a fixed puffing protocol for 5 min reported Cmax of 1.3–17 ng/mL (201,202,203). Second- and third-generation ECs improved nicotine delivery under similar conditions (Cmax 4–12.8 ng/mL) (100, 201, 204,205,206). Fourth-generation ECs using protonated nicotine have substantially lessened or even closed the nicotine bioavailability gap between cigarette smoke and EC vapour (139, 207, 208). For instance, Ebajemito et al. (139) assessed nicotine delivery in participants who switched from smoking to vaping at several nicotine concentrations and with and without nicotine salts. The Cmax for e-liquid (30 mg/mL nicotine) containing nicotine salt reached 14.1 ng/mL compared with 14.5 ng/mL for a 7-mg ISO “tar” cigarette. Another study conducted by O’Connell et al. (140) found a similar delivery profile for an EC containing a 40-mg nicotine lactate e-liquid formulation.

Product use also has an impact on nicotine delivery, with more experienced users achieving greater nicotine concentrations (209, 210). Finally, satisfaction with e-liquid formulations containing nicotine might be limited by sensorial aspects, as nicotine content and flavour strength seem to correlate with harshness or throat irritation and perception of bitterness (51). Together, these findings could explain the results from some studies suggesting that ECs are more successful than NRT in providing smokers a satisfactory alternative to cigarettes (211, 212). Table 3 summarises some of the findings from Pharmacokinetic studies according to EC type/generation.

Summary of pharmacokinetic, pharmacodynamic, vital signs profiles of combustible cigarettes, e-cigarettes (first to fourth generation), and nicotine-replacement therapy.

Reference Product type (nicotine concentration) Pharmacokinetic parameters Pharmacodynamic parameters Vital signs



Cmax (ng/mL) Tmax (min) AUC (ng•min/mL) Cravings Urge to smoke Sensory evaluation/satisfaction Heart rate (bpm) Systolic BP (mm Hg) Diastolic BP (mm Hg)
Combustible cigarettes
Digard et al., 2013 (195) Lucky Strike Red (14.6 mg) 12.8 7.20 14.8 N/A N/A N/A N/A N/A N/A
Yan & D’Ruiz, 2015 (345) Marlboro Gold King Size (0.8 mg) 15.84S29.23 N/A N/A N/A N/A N/A 4.26 increase in heart rate 5.74 change in systolic BP 6.78 change in diastolic BP
Ebajemito et al., 2020 (139) Benson & Hedges Sky 14.5 (ad libitum) 5.00 660.0 N/A N/A Increased product satisfaction compared to e-cigarettes Heart rate increased and decreased in similar trends to PK profiles N/A N/A
Blue (7 mg ISO tar) 13.7 (fixed puff) 7.00 631.0
First-generation e-cigarettes (cig-a-like)
Hajek et al., 2017 (346) Vuse (48 mg/mL); 13.6 4.0 244.9 N/A N/A N/A N/A N/A N/A
Gamucci (16 mg/mL); 9.7 6.0 169.9
Blu (18 mg/mL); 9.1 6.0 173.1
Vype (16.8 mg/mL); 8.5 6.0 161.0
E-lites (24 mg/mL); 7.8 6.0 157.6
Puritane (20 mg/mL) 7.5 4.0 144.4
Bullen et al., 2010 (198) Ruyan V8 (16 mg/mL) 1.3 19.6 N/A No difference in withdrawal symptoms between the e-cigarette and inhalator Greater decrease in desire to smoke compared to 0 mg placebo (not significant when adjusted for multiple comparisons) N/A N/A N/A N/A
Vansickel et al., 2010 (347) NJOY NPRO (18 mg/mL); Hydro (16 mg/mL) N/A N/A N/A Some abstinence symptoms suppressed Decrease in urge to smoke compared to sham condition No effect on sensory evaluation No significant change was reported between study products N/A N/A
Nides et al., 2014 (202) NJOY King Bold (26 mg/mL) 3.5–5.1 30 s–30 min 0.67–0.57 Reduction in craving with the highest decrease immediately after product use, followed by steady incremental increases in craving N/A N/A Heart rate increased through the 10-min mark after the beginning first puffs, then gradually declined towards baseline. Mean increases in heart rate 5 and 10 min after the first series of puffs were 2.4 and 5.3 bpm N/A N/A
Yan & D’Ruiz, 2015 (345) Blu (16 mg/mL, two formulations); Blu (24 mg/mL, three formulations) 10–17 N/A N/A N/A N/A N/A 1.87–4.09 bpm increase in heart rate following product use 1.13–3.78change in systolic BP 3.17–6.783change in diastolic BP
Farsalinos et al., 2014 (201) V2 (18 mg/mL) 2.0 (fixed puff) and (ad libitum) N/A N/A Similar levels to craving reduction observed compared to third-generation EC N/A Burning throat sensation was significantly lower compared to third-generation EC N/A N/A N/A
Voos et al., 2019 (348) V2 (11.7 mg/mL) Green smoke (19.4 mg/mL) 4.07 13 88.60 N/A Low ratings on perceived smoking urge relief Low satisfaction and sensory ratings N/A N/A N/A
4.16 10 121.9
Second-generation e-cigarettes
Voos et al., 2019 (348) Mod iTazte (29.9 mg/mL) 6.6 10 272.3 N/A Provided perceived smoking urge relief High satisfactionrating, taste, pleasantness, harshness (“throat hit”), and speed of effect N/A N/A N/A
Hajek et al., 2017 (346) KangerTech EVOD (20 mg/mL) 9.9 6.0 200.6 N/A N/A N/A N/A N/A N/A
Third-generation e-cigarettes
Farsalinos et al., 2014 (201) EVIC device with EVOD cartomizer (18 mg/mL) 4.00 (defined) 21.0 (ad libitum) N/A N/A Similar levels of craving reduction observed compared to first-generation EC N/A Burning throat sensation was significantly higher compared to first-generation EC N/A N/A N/A
Hajek et al., 2017 (346) Innokin (20 mg/mL) 11.9 6 232.1 N/A N/A N/A N/A N/A N/A
Voos et al., 2019 (348) eGO V2 Pro (29.9 mg/mL) 5.52 10 121.9 N/A Provided fastest perceived urge relief compared to first- and second-generation EC High satisfaction rating, taste, pleasantness, harshness (“throat hit”), and speed of effect. N/A N/A N/A
Ebajemito et al., 2020 (139) Vype ePen (18 mg/mL) 4.79 7.0 267.0 N/A N/A Poor satisfaction compared to fourth-generation EC Heart rate increased and decreased in similar trends to PK profiles N/A N/A
Fourth-generation e-cigarettes
O’Connell et al., 2019 (140) myblu 25 mg/mL (free-base) 5.05 8.03 99.99 N/A Higher Cmax was associated with greater relief on urge to smoke Similar sensorial perception was reported across all products N/A N/A N/A
myblu 16 mg/mL (salt); 6.51 6.97 118.5
myblu 25 mg/mL (salt); 7.58 6.03 125.2
myblu 40 mg/mL (salt); 10.27 7.90 190.7
blu PRO 48 mg/mL (salt) 4.85 6.91 84.84
Ebajemito et al., 2020 (139) Vype ePen3 18 mg/mL (freebase; ad lib); 6.38 7.0 325 N/A N/A Higher Cmax was linked to increased satisfaction, except for the 30-mg/mL product Heart rate increased and decreased in similar trends to pharmaco-kinetic profiles N/A N/A
Vype ePen3 18 mg/mL (med salt; ad lib); 10.8 5.0 429
Vype ePen3 30 mg/mL (high salt; ad lib); 14.1 5.0 533
Vype ePen3 18 mg/mL (med salt; fixed puff); 5.64 5.0 326
Vype ePen3 12 mg/mL (low salt; ad lib) 5.97 7.0 284
Nicotine-replacement therapy
Digard et al., 2013 (195) Nicotine gum (4.2 mg) 9.10 45.0 13.1* N/A N/A All products had little effect on the sensory parameter assessed N/A N/A N/A
Lunell & Curvall, 2011 (349) Nicotine Polarilex gum (4 mg) 12.8 N/A 3190 Craving decreased similarly to snus Urges to smoke decreased similarly with snus Salivation and throat burn were rated higher for the 4 mg gum vs snus Mean 20 min increase of heart rate 9.3 (± 9.6), 8.9 (± 6.4), and 9.9 (± 5.1) bpm for 9.9 mg snus, 8.7 mg snus, and nicotine gum, respectively N/A N/A
Dautzenberg et al., 2007 (350) 1 mg Nicotinell lozenges 2.30 66.0 8.30 * N/A N/A N/A N/A N/A N/A
2 mg Nicotinell lozenges 4.80 48.0 15.8 *
2 mg Nicorette gum 2.90 48.0 10.6 *
Choi et al., 2003 (351) 4 mg nicotine lozenges 10.8 66.0 44.0 * N/A N/A N/A N/A N/A N/A
4 mg nicotine gum 10.0 54.0 34.6 *
Hansson et al., 2017 (199) 6 mg nicotine gum 13.8 30.0 46.2 * N/A N/A N/A N/A N/A N/A
4 mg nicotine gum 10.1 30.0 30.2 *
2 mg nicotine gum 5.90 30.0 17.1 *
4 mg nicotine lozenge 9.30 45.0 35.3 *
Kraiczi et al., 2011 (352) 1 mg nicotine mouth spray 3.30 10.0 6.60 N/A N/A N/A N/A N/A N/A
2 mg nicotine mouth spray 5.30 12.5 12.2
4 mg nicotine mouth spray 9.10 10.0 23.7
4 mg nicotine lozenge 7.00 45.0 24.3
4 mg nicotine gum 7.80 30.0 21.1
Sukhija et al., 2018 (200) 4 mg lozenges prototype I 18.18 66.0 87.13 * N/A N/A N/A N/A N/A N/A
4 mg lozenges prototype II 18.11 66.0 85.69 *
4 mg lozenges prototype III (I, II, III had different dissolutions) 17.11 66.0 84.59 *
4 mg Nicorette lozenges 18.67 66.0 90.03 *
Molander & Lunell, 2001 (353) 2 mg nicotine sublingual tablet 13.2 20 12.4 * N/A N/A N/A N/A N/A N/A
2 mg Nicorette gum 14.4 20 13.5
Lunell et al., 2020 (354) 4 mg Nicorette gum 12.8 46.0 52.1 N/A N/A N/A N/A N/A N/A
Bullen et al. (198) Nicorette inhalator (10 mg) 2.10 32.0 N/A No significant decrease in craving compared to placebo or first-generation EC No significant decrease in craving compared to placebo or first-generation EC N/A N/A N/A N/A
Goldenson et al. (355) Fixed puff N/A N/A 59 mg/mL silica wick provided highest level of satisfaction followed by 18 mg/mL silica wick, 18 mg/mL coil wick and 9 mg/mL coil wick N/A N/A N/A
JUUL 59 mg/mL with silica wick 9.3 6.2 5.0 *
JUUL 18 mg/mL with silica wick 3.2 6.3 1.7 *
JUUL 18 mg/mL with cotton wick 3.3 5.8 1.8 *
JUUL 9 mg/mL with cotton wick 2.1 6.6 1.2 *
Ad libitum puff
JUUL 59 mg/mL with silica wick 8.3 6.4 4.6 *
JUUL 18 mg/mL with silica wick 3.5 6.5 1.8 *
JUUL 18 mg/mL with cotton wick 3.3 7.1 2.1 *
JUUL 9 mg/mL with cotton wick 2.3 6.7 1.2 *

Abbreviations: BP

= blood pressure

Cmax

= maximum concentration

EC

= electronic cigarette

Tmax

= time to maximum concentration

bpm

= beats per minute

PK

= pharmacokinetic

AUC

= area under the curve

N/A

= not analyzed

Reported in ng@h/mL

Biomarkers of exposure

Biomarkers of exposure (BoEs) to cigarette smoke have long been used to assess the effects of tobacco consumption. Exposure to nicotine and aerosol toxicants is assessed by measurement of nicotine metabolites and toxicant concentrations in biological samples, most often in urine. In most EC studies, reductions in toxicant exposure are benchmarked against cigarette smoke and, therefore, the panels of BoEs are based on compounds known to be present in cigarette smoke. The FDA workshop identified the measurement of BoE for nicotine and 19 HPHCs, including nicotine and tobacco alkaloids, carbon monoxide, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, volatile organic compounds, carcinogenic aromatic amines, and metals (213).

Multiple studies have assessed changes in BoEs after study participants’ exposure to EC aerosol (Table 4). In interventional studies, which are generally randomised studies, participants are assigned to use a small number of products or different categories of products (214,215,216,217). Observational studies are often larger and assess products chosen or already used by the consumers (218,219,220,221). Interpretation and extrapolation of results from some randomised studies has been hindered by lack of appropriate descriptions of products used in the study (222), exclusion of appropriate controls to provide context (215, 217), and small sample sizes that limit generalizability (216, 222).

Clinical studies of e-cigarettes.

Reference Study design/product Study arms (subgroups) Conclusions
Shahab et al., 2017b (221) Cross-sectional study, using unspecified EC or NRT products for ≥ 6 months Smokers (n = 37)Dual use NRT (n = 36)Dual use EC (n = 36)NRT (n = 36)EC (n = 36) NNAL, 3HPMA, AAMA, CYMA, MHBMA3, HEMA were expressed as proportions of levels in the smoker arm. Significantly lower levels of all biomarkers were observed for EC only users (2.9–43.5% decrease) that were similar to those in NRT only users. NRT and EC dual users presented similar biomarker levels to the smoking group
Lorkiewicz et al., 2019 (216) Cross-sectional study, using unspecified ECs or smokeless products No tobacco (n = 12)ECs (n = 12)smokers (n = 12)smokeless tobacco (n = 12) The EC users showed higher levels of xylene, cyanide, styrene, ethylbenzene, and acrolein metabolites than non-tobacco users, but lower levels for toluene and acrolein metabolites. Levels of VOC metabolites in the smokeless tobacco group were similar to those in the non-tobacco group
Czoli et al., 2019 (214) Three-period crossover design where dual users (smoked ≥ 5 cigarettes per day and used an EC at least once a day for the past 7 days) to either EC > smoking > no tobacco or smoking > EC > no tobacco, with each condition lasting for 7 days Dual users (n = 48) 1-HOP was significantly higher during the smoking period than during dual use but was lower during EC use. NNAL levels decreased significantly from dual use, by 30% during EC use and by 35% during cessation but did not change during smoking
Hecht et al., 2015 (226) Cross-sectional study comparing biomarker levels in smoker to ECs switchers (≥ 2 months) with those in smokers from three previously published studies (Carmella et al. 2009; Hatsukami et al. 2010; Zarth et al. 2014) EC users (n = 28) All biomarkers (1-HOP, total NNAL, 3HPMA, 2HPMA, HMPMA, and SPMA) were significantly lower in EC users than in smokers
Mcrobbie et al., 2015 (217) Switching study in which smokers switched to ECs or dual use EC users (n = 16)Dual use (n = 18) 3HPMA in urine showed significant reductions at 4 weeks after switching compared with baseline (ECs 79%, dual use 60%)
Goniewicz et al., 2017 (215) Switching study in which smokers switched to ECs dual use for 2 weeks then ECs only for 2 weeks Smokers switching to ECs (n = 20) Significant reductions were seen after 2 weeks in urine biomarkers of exposure to NNAL and eight VOC metabolite levels (50–69%) and fluorene (42–82%), butnot in those for pyrene, phenanthrene, and naphthalene
Cravo et al. 2016 (225) Parallel study in which smokers were randomly assigned in a ratio of 3:1 to switch to an EC (tobacco or menthol flavour) or continue smoking for 12 weeks Switch to EC (n = 306)continue smoking (n = 102) After 12 weeks, 3-HPMA, S-PMA and total NNAL in urine were reduced by around 30% compared with baseline in those who switched to ECs, whereas noreductions were among those who continued smoking
O’Connell et al., 2016 (245)D’Ruiz et al., 2017 (232)D’Ruiz et al., 2016 (356) Parallel study of smokers switching to ECs or dual use during 6 days in clinic Rechargeable EC tobacco flavour (n = 15)rechargeable EC cherry flavour (n = 15)disposable EC cherryflavour (n = 15)dual use with rechargeable EC tobacco flavour (n = 15)dual use with rechargeable EC cherry flavour (n = 15)dual use with disposable EC cherry flavour (n = 15)cessation (n = 15) Biomarkers: all urine biomarker measures (total NNAL, 3-HPMA, HMPMA, CEMA, 1-OHP, NNN, MHBMA, S-PMA) were significantly reduced compared to baseline in all groups, except MHBMA in the cherry disposable dual use group; levels in dual users were significantly higher than those in the cessation groupSpirometry: small changes seen in FVC from baseline to Day 5 (!0.5% to 3.1%) but were significant for tobacco and cherry rechargeable EC only users, while FEV1changes (!1.5% to 6.0%) were significant increases for the tobacco and cherry rechargeable EC only users and cherry rechargeable dual usersExhaled CO: reduced across all study groups, by around 89% in EC only and cessation groups and around 26% in dual user groupsExhaled FeNO: increased by 45.8–63.4% in EC only groups and 55%in the cessation group, but not in dual user groups (differences from the tobacco rechargeable and cherry disposable EC only groups were significant)Systolic blood pressure: changes varied across groups, but significant reductions in mornings seen for cherry flavour dual users, and in rechargeable tobaccoEC only usersDiastolic blood pressure: reduced significantly in mornings forrechargeable tobacco dual users and cherry rechargeable EC only usersHeart rate: reductions observed in the cessation group, rechargeable tobacco EC only group and rechargeable cherry product EC only and dual use groups
Sakamaki-Ching et al., 2020 (222) Cross-sectional study of age and gender matched participants, assessing spot urine samples from EC users, smokers and non-smokers for metals (antimony, cadmium, copper, indium, lead, nickel, rubidium, selenium, silver, titanium, and zinc), metal exposure, and BOPH EC users (n = 20)smokers (n = 13)non-smokers (n = 20) Metals: biomarkers for seleniumwere significantly higher in ECusers than in non-smokers or smokers with means 54.0, 41.8, and 39.7 μg/g creatinine, respectively, and were significantly increased for zinc in EC userscompared to non-smokers (584.5 vs413.6 mg/g creatinine) but not compared to smokers (470.7 mg/g creatinine)Metal exposure: metallothionein was significantly greater in ECusers than in non-smokers (mean 3761 vs1129 pg/mg creatinine) but similar to that in smokers (4096 pg/mg creatinine)BOPH: concentrations were increased in EC users when compared to non-smokers but not smokers (8-OHdG 442.8 vs221.6 and 388 ng/mg creatinine; 8-isoprostane 750.8 vs411.2 and 784.2 ng/mg creatinine)
Campagna et al., 2016 (357)Cibella et al., 2016 (229) Longitudinal study (52 weeks) of smokers switching to ECs with different concentrations of nicotine 2.4% nicotine (n = 49)1.8% nicotine (n = 50)0% nicotine (n = 40) 82 participants continued smoking, 34 significantly reduced thenumber of cigarettes smoked, and 18 quit smoking after switchingExhaled CO: decreased significantly in quitters and smokers whoreduced cigarette consumption from week 12Exhaled FeNO: increased significantly in quitters from week 12FEV1, FVC and FEV1/FVC ratio: not affected by smoking status (continued, reduced, or quit)FEF25–75%: significantly increased among quitters
Polosa et al., 2016 (220) Retrospective chart review study of changes in respiratory outcomes over 2 years in patients with COPD who were daily EC users (without combustible cigarettes) or smokers, matched for age and sex Baseline COPD GOLDstage 1 (smokers n = 3; EC users n = 2)stage 2 (smokers n = 5; EC users n = 6)stage 3 (smokers n = 11; EC users n = 10)stage 4 (smokers n = 5; EC users n = 6) FEV1, FVC and ratio FEV1/FVC ratio did not change from baseline values in either EC users or smokers, whereas COPD exacerbations were reduced and 6-min walking test scores increased compared with baseline in the EC users group but not the smoking group
Pulvers et al., 2018 (358) Switch study of smokers switching to an EC for 30 days with choice of seven flavours and two nicotine concentrations (12 or 24 mg/mL) Smokers (n = 37) Cigarette consumption: decreased significantly from mean 24.8 days to 14.0 days per month and mean 8.7 to 4.4 cigarettes per day, with six participants quitting, 21 becoming dual users and the remaining 10 sporadic EC only usersBiomarkers: NNAL, PMA, CNEMA decreased significantly from baseline, whereas HEMA, MMA, 3-HPMA, 2-HPMA, AAMA and HPMMA did notExhaled CO: decreased significantlySmoking dependence: decreased significantly from baseline
Aherrera et al., 2017 (218) Cross sectional study of nickel and chromium concentrations in EC users EC users (n = 59) Concentrations in urine, saliva, and breath: were below the limit of detection for nickel in 4.7%, 3.2% and 3.1% of samples, respectively, and for chromium in 7.8%, 1.6% and 56.3% of samplesWeekly consumption, time to first vape, voltage of device, number of coil changes per month, and levels in aerosol, dispenser, and tank had effectsNickel concentrations in urine were associated with time to first vape, coil changes, and concentrations in aerosol; in saliva were only associated with concentrations in aerosol and in tank, and in breath showed no associationsChromium in saliva was associated with cotinine in urine and concentrations in aerosol, tank, and dispenser
Wieslander et al., 2001 (231) Symptoms study after experimental exposure of healthy non-asthmatic volunteers to propylene glycol mist for 1 min Healthy volunteers (n = 27) Symptom VAS ratings: showed significant increase of ocular irritation, throat irritation, and dyspnoea but no effects on solvent smell or other symptomsLung function: FEV1, FVC, FEV1/FVC ratio, PEF did not change significantly from before to after exposureTear film stability: break-up time decreased significantly after exposure from 38 to 28 sDose response: throat dryness was 47% in the low exposure groupbut 100% in the high exposure group, where VAS ratings were also higher
Goniewicz et al., 2018 (219) Cross-sectional analysis of population in longitudinal Population Assessment of Tobacco and Health (PATH) study for biomarker concentrations Smokers (n = 2411)EC users (n = 247)dual users (n = 792)never tobacco users (n = 1655) NNAL: concentrations were significantly lower in never-smokers than in EC users and in both groups compared with smokers (geometric mean 0.921 vs4.887 and 203.5 pg/mg creatinine), whereas dual users had higher levels than smokers (262.2 pg/mg creatinine)Other tobacco specific nitrosamines: NAT, NAB, and NNN in EC users were above the limit of quantification for 12%, 15% and 34%of samples, respectively and were all higher than those in never tobacco users but significantly lower than those in smokersMetal exposure: beryllium wasfound only in 3–9% of samples; cadmium was higher in EC users than in never tobacco users (0.193 vs 0.149 ng/mg creatinine) but lower than in smokers and dual users (0.277 and 0.280 ng/mg creatinine, respectively); lead was elevated in EC users compared to never users (0.432 vs 0.351 ng/mg creatinine) but was highest in smokers and dual users (0.500 and 0.479 ng/mg creatinine, respectively); strontium differed only between dual users and smokers (130.5 vs 113.7 ng/mg creatinine); and no differences in concentrations between groups were found for cobalt, manganese or thalliumTobacco alkaloids: anabasine and anatabine concentrations were significantly lower in EC users than in dual users or smokers but similar to those in never tobacco usersTotal inorganic arsenic: significantly higher in EC users than in smokers and dual users (0.053 vs 0.048 and 0.045 ug/mg creatinine) but not different to never tobacco users (0.054 ug/mg creatinine)PAHs: of seven biomarkers of PAHexposure only 1-hydroxypyrene was elevated in EC users compared to never tobacco users, while all were significantly higher in smokers and five were higher in dual usersVOCs: of 20 biomarkers four were significantly elevated in EC users compared with never tobacco users (AMCA 1.5 times, BMA 1.1 times, CYHA 1.3 times, and CYMA 3.0 times*), although CYHA could only be detected in 3% of never tobacco users and 14% of EC users; 17 biomarkers were higher in smokers than in EC users by 1.4–31.0 times
Oliveri et al., 2020 (234) Cross-sectional observational study comparing biomarkers of exposure and BOPH in ex-smoker (≥10 cigarettes per day for ≥10 years) EC users (≥6 months) with current smokers Smokers (n = 62)ex-smoker EC users (n = 132) Biomarkers of exposure: concentrations of total NNAL, nicotine equivalents, 3HPMA, and COHb were lower in EC users than smokersBOPH: of white blood cells, HDL cholesterol, 11-dehydrothromboxane B2, 8-epi-prostaglandin F2α, and sICAM-1, lower concentrations were found in EC users for 11-dehydrothromboxane B2 (471.4 vs 664.8 ng/g creatinine), 8-epi-prostaglandin F2α (288.6 vs374.1 ng/g creatinine), and sICAM-1 (224.5 vs266.4 ng/mL), although differences for the latter were observed only for cartridge based ECs and not tank-base ECs
Piper et al., 2019 (227) Baseline assessments for longitudinal observational cohort study (2 years) of smokers versus EC dual users Smokers (n = 166)dual users (n = 256) In dual users, lower mean valueswere seen than in smokers for smoking duration (22.1 vs25.6 years), daily cigarette consumption (12.5 vs15.8), Fagerström nicotine dependence (4.15 vs 4.81), smoking within 30 min of waking (79.4% vs67.3%), and levels of NNAL (453.31 vs 340.99 pg/mL), whereas smoking starting age, motivation to quit, exhaled CO, the Wisconsin Inventory of Smoking Dependence Motives, and cotinine biomarkers did not differ significantly
Round et al., 2019 (223) Randomized, controlled, open-label, forced switch parallel group study in smokers of menthol and non-menthol cigarettes who switched to an EC or nicotine gum, to measure biomarkers of exposure after 5 days Smoker to EC (n = 38)smoker to nicotine gum (n = 39)menthol smoker to menthol EC (n = 40)menthol smoker to nicotine gum (n = 41) In all switching groups, total nicotine equivalents in urine, cotinine in plasma, and all biomarkers of tobacco smoke exposure decreased except for 3-OH-B[a]P in the smoker to nicotine gum group (reductions were ECs 30.4–95.5%, menthol ECs 35.7–97.7%, and nicotine gum 20–99.2%)
Song et al., 2020 Cross-sectional study of lung inflammation, measured by cell counts, cytokines, genome-wide gene expression and DNA methylation in bronchoalveolar lavage and brushings, in never smokers, EC users and smokers Never-smokers (n = 42)EC users (n = 15)smokers (n = 16) Most inflammatory cell counts and cytokine concentrations in EC users were intermediate between those of smokers and never-smokers, while most biomarkers were similar to those for never smokers, as were differential gene expression and DNA methylation

Abbreviations: BOPH

biomarkers of potential harm

COPD

chronic obstructive pulmonary disease

EC

electronic cigarette

FEF25–75%

mid-expiratory flow rate

FEV1

forced expiratory volume in 1 s

FVC

forced vital capacity

GOLD

Global Initiative for Chronic Obstructive Lung Disease

PAHs

polycyclic aromatic hydrocarbons

PEF

peak expiratory flow rate

VAS

visual analogue scale

VOC

volatile organic compound

1-HOP

1-hydroxypyrene

2-HPMA

2-hydroxypropylmercapturic acid

3-HPMA

3-hydroxypropyl mercapturic acid

AAMA

2-cyanoethylmercapturic acid

AMCA

N-acetyl-S-(N-methylcarbamoyl)-L-cysteine

BMA

S-benzylmercapturic acid

CEMA

2-cyanoethylmercapturic acid

CNEMA

2-cyanoethylmercapturic acid

COHb

carboxyhemoglobin

CYHA

N-acetyl-S-(1-cyano-2-hydroxyethyl)-L-cysteine

CYMA

N-acetyl-S-(2-cyanoethyl)-L-cysteine

HEMA

2-hydroxyethylmercapturic acid

HMPMA

3-hydroxy-1-methylpropylmercapturic acid

HPMMA

N-acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine

MHBMA

monohydroxy-3-butenyl mercapturic acid

MMA

methylmercapturic acid

NAB

N-nitrosoanabasine

NAT

N-nitrosoanatabine

NNAL

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol

NNN

N-nitrosonornicotine

NRT

nicotine replacement therapy

PMA

phenylmercapturic acid

S-PMA

S-phenylmercapturic acid

Biomarkers of exposure to N,N-dimethylformamide, isocyantes, toluene, and acrylonitrile.

Some of the larger and longer-term studies provide a clearer picture. In a switching study of 153 smokers who switched from cigarettes to a cig-a-like EC or nicotine gum, Round et al. (223) assessed a comprehensive panel of BoEs. They found significant reductions across all BoEs in the EC arm, while nicotine levels were higher than in those using nicotine gum. A cross-sectional study by Shahab et al. (221) compared exposure to carcinogens and toxicants in long-term smokers with those in former smokers who had used ECs or NRT exclusively for at least 6 months and in dual users who had smoked combustible cigarettes plus used ECs or NRT for at least 6 months. The sample size was 181, with 36–37 in each group. Nicotine intake was similar for all study groups, but BoE concentrations were significantly lower in the exclusive NRT and EC groups than in any group including smokers. NNAL, a BoE associated with lung cancer, was lower in the EC only group than in all other groups. Walele et al. (224) performed a 2-year ambulatory study as continuation of a 12-week residential study in which smokers had switched to a cig-a-like EC or continued smoking (225). They compared changes in BoE to acrolein, benzene, and NNK over time in 209 participants. BoE concentrations among smokers who switched to the EC fell substantially within roughly 1 month and remained at similar levels over 2 years. A very large cross-sectional biomarker analysis based on the US PATH observational study, with biomarker data for more than 5,000 participants classified as smokers, EC users, dual users, and never tobacco users showed lower BoE levels of tobacco-specific nitrosamines in the EC users group than in smokers (219). Exposure to metals, such as beryllium, cadmium, and lead, were lower in EC users than in cigarette smokers but higher than in never tobacco users. There were no differences across groups for cobalt, manganese, or thallium. All seven BoEs for polycyclic aromatic hydrocarbons and 17 of 20 volatile organic compounds BoEs were significantly higher in smokers than in the other groups. In a comparison of exclusive smokers and exclusive EC users, levels of exposure to total NNAL and carbon monoxide were significantly lower in vapers, including below the level of detection in 30% of cases (206). There is also some evidence of reversibility of effects in ex-smokers who had switched entirely to ECs for at least 2 months (226). Goniewicz et al. (215) evaluated seven nicotine metabolites and 17 BoEs in urine samples of 20 cigarette smokers before and after switching exclusively to ECs for 2 weeks and found significantly reduced concentrations of 12 of the biomarkers following switching.

Large observational studies are more representative in terms of demographics and the EC category (219, 227). However, assessment of usage patterns can be complex in ambulatory studies yet not reflect real-world use in confinement settings where product use can be controlled. In all studies, especially large observational studies, the numbers of BoEs that may be assessed might be hampered by resource availability.

Overall, measurement of BoEs appears to reflect toxicant delivery differences observed in chemistry assessments.

Biomarkers of potential harm

Disease-associated biomarkers known as biomarkers of potential harm (BoPHs) could provide valuable information characterising the risk of tobacco products. BoPHs were defined by the Institute of Medicine as the “measurement of an effect due to exposure; these include early biological effects, alterations in morphology, structure, or function, and clinical symptoms consistent with harm; also includes ‘preclinical changes” (11). Chang et al. (228) describe in detail BoPH in the context of tobacco product assessment as well as the types of BoPHs identified during this FDA public workshop. Table 4 also summarizes results from studies evaluating biomarkers of potential harm.

Usability of BoPHs to characterize risk associated with ECs is underpinned by reversibility of smoking harm achieved through complete cessation of tobacco products. Most clinical studies compare disease-associated BoPHs in vapers against those in smokers and a cessation group used as a reference. Many BoPHs are not smoking specific or even disease specific, so contextualization against effects observed in cessation groups is crucial to evaluate validity and biological relevance.

The same shortcomings observed in BoE studies are often found in BoPH studies but are often accentuated due to the non-specific nature of the biomarkers, leading to smaller effect sizes, i.e. requiring larger sample sizes. Other important factors to consider when designing these types of studies is to ensure their time frame is long enough for assessment of biomarker reversibility, as many BoPHs may take months to reveal significant changes.

Few BoPH studies have been done in EC users, and most are cross-sectional and compare self-reported vapers with smokers. No standard panel of BoPHs has been established, but most studies focus on end points related to cancer, cardiovascular disease, the respiratory system, oxidative stress, and inflammation.

Spirometry measurements of lung function, like forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), have been used as surrogate end points for COPD. Most studies comparing FEV1, FVC, or ratio of FEV1 to FVC in healthy vapers and smokers have shown no significant differences (229,230,231). Cibella et al. (229) did, however, report significant increases of forced expiratory flow at 25–75% of FVC as well as fractional exhaled nitric oxide. D’Ruiz et al. (232) observed some significant changes for FEV1 and FVC 5 days after smokers switched to an EC in a clinical setting, but, unexpectedly, saw no change in the cessation group.

For cancer, besides BoEs like NNAL and volatile organic compounds, studies overwhelmingly present lower levels of BoPHs in vapers than in smokers but higher than in cessation groups. Other BoPHs, such as the inflammation biomaker 8-epi-prostaglandin F, have also been associated with lung cancer (233), and levels are significantly lower in exclusive vapers than in smokers (234). Similarly, a cross-sectional study by Song et al. (235) concluded that most inflammatory BoPHs and cytokine concentrations in EC users were intermediate between those of smokers and non-smokers. In contrast, levels of 8-hydroxy-2'-deoxyguanosine, a biomarker for oxidative stress (236), have been reported to be higher in EC users than in non-smokers and not different to those in smokers (222).

Improvements in vascular health markers have been reported in smokers who switched to ECs for 1 month, particularly among women (237). Various BoPHs, such as 8-isoprostane (238) and 11-dehydro-thromboxane B2 (239), have been associated with cardiovascular disease. Differences have been reported between smokers and vapers for 11-dehydro-thromboxane B2 (234) but not for 8-isoprostane (222). Some reports have pointed to EC use as a potential cause of endothelial dysfunction (240) and heart rate variability (241, 242). In the PATH study, the association between vaping and heart failure was investigated, and the researchers concluded that respondents suffering heart failure had higher odds of being dual users than exclusive EC users (243). A comparison of vapers and/or dual users’ odds of suffering heart failure against those in smokers or never smokers would be of interest.

Most clinical studies assessing ECs have been small and with designs that limit interpretation and generalizability of conclusions. Studies should include appropriate controls, such as a cessation group (including people using NRT), as recommended by the Institute of Medicine (11), to provide context and determine the relevance of changes in relation to the time frame of the study. Much larger and longer-term studies assessing real-world behaviours are needed to fully understand the effects of switching to ECs, as the changes to health might take much longer to manifest than those traceable by other biomarkers in the short term (244).

Dual use

Whether dual use of combustible cigarettes and ECs provides beneficial changes to the harmful effects of smoking remains unclear. For instance, 5 days after switching half of cigarette consumption to ECs, slight decreases (7–38%) were seen in eight of nine urinary BoE, but concentrations of nicotine equivalents increased by 1–20% (245). In a 7-day switching study, only small reductions in BoEs were found in dual users, with much more substantial reductions seen in exclusive vapers or non-users of any tobacco product (214). In long-term dual users, Shahab et al. (221) found a similar pattern of increased concentrations of nicotine and nicotine equivalent, with little to no reduction in biomarkers of exposure. In contrast, a large study in long-term users by Goniewicz et al. (219), in which average cigarette consumption in a dual use group was 15.1 and in a smoking group was 15.4, found BoEs in the group of dual users to be higher than in exclusive smokers, with NNAL on average 23% higher in dual users. However, this study showed a dose-response relationship, with BoE levels being significantly higher in dual users who smoked daily than in those who smoked occasionally, independently of whether they vaped occasionally or daily.

Pregnancy and reproductive toxicology

Animal studies have suggested that nicotine has potential teratogenic effects, although the evidence for harmful effects on fetal development and birth outcomes in humans remains unclear (246). NRT is recommended for consideration in pregnant women who have been unable to quit smoking by behavioural changes (247, 248), but increased metabolism of nicotine during pregnancy might affect adherence to nicotine therapy (246, 249, 250). The relative risks of vaping during pregnancy are untested in randomised trials (246), and most data are descriptive and derived from surveys.

Physicians are an important source of information about the risks of nicotine and pregnancy, and women are likely to view them as being able to provide similarly reliable information about vaping. However, without objective data and with developments in devices likely outstripping published evidence, providing objective advice can be difficult (251). Women who use ECs while pregnant seem most commonly to believe that they are less harmful to mothers and babies than combustible cigarettes (although not completely harmless) and that use will help with quitting smoking (26, 252, 253). However, social stigma is viewed as a barrier to EC use in public (252).

Some argue that as the toxicology of ECs is similar to that of NRT (223, 254) it is likely to be a safer alternative to smoking in pregnant women. However, the amount of nicotine consumed via ECs could be as high as that consumed via combustible cigarettes (139, 207, 208, 255) and higher than received from NRT products and dose-effect data are unavailable.

Much more formal and standardised research is needed in this area, particularly on the safety of different nicotine levels, the risks of nicotine dependence among pregnant women who want to quit smoking but have been unable to, and adherence to prevent a return to smoking.

Mental health

Smoking prevalence is higher among people with mental health illnesses and conditions than in the general population, particularly those with severe mental illness or distress (256, 257). Rates of ever having tried vaping also seem to be higher (258), particularly among people with schizo-affective disorders and bipolar disorder (26). Among smokers with severe mental illness, strong associations were found with EC use, education level, and wish to quit smoking (quit attempt in the previous 6 months) (259).

Misconceptions among health professionals that smokers with severe mental illness are either not willing to quit or will suffer worsening symptoms as a result of doing so is hindering provision of adequate quitting options (260, 261). As well as NRT and supportive behavioural counselling, ASH (262) suggests that ECs could be considered for this subgroup of the population.

Formal studies are needed in this area to clarify the role that ECs could play in tobacco harm reduction.

Oral health

Tobacco consumption is associated with oral diseases (263), but whether ECs lessen or contribute to the burden is unclear. A study investigating numerous end points (plaque index, bleeding on probing, probing depth, clinical attachment loss, number of missing teeth, and gingival crevicular fluid levels of pro-inflammatory cytokine) found consistent significant differences between smokers and never-smokers, whereas there was no difference between the vapers and never smokers (264). However, in a pilot study, some biomarkers associated with antimicrobial activity and inflammation were increased in EC users compared with in never smokers (265). The findings from these two studies appear to synthesize the conclusion from a systematic review, in which 99 publications investigating ECs and oral health (mouth, throat, periodontal, dental, cytotoxic/genotoxic/oncological, oral microbiome, and traumatic/accidental injury) were assessed (266). Cosmetically, ECs lead to less tooth enamel staining than cigarette smoke. This difference might have social benefits to former smokers who have switched to ECs (267, 268).

Overall, the evidence suggested that while switching from smoking to ECs mitigates some smoking-induced symptoms, a wide range of oral issues could be associated with vaping. However, most of the evidence in the area is weak, with studies so far not specifically designed to assess oral health outcomes.

PERCEPTIONS AND BEHAVIOURS - USER DEMOGRAPHICS

Perception of risks associated with ECs can be an important determinant of product use (269). Misconceptions about the harmfulness of ECs versus combustible cigarettes seems to be a growing reason among smokers to reject them (38, 59). In this section we review studies investigating perceptions about ECs and nicotine use behaviours associated with those perceptions.

Consumer perception studies

A survey conducted in six European countries suggested that among respondents who were aware of ECs in 2016, 58.5% perceived them to be as risky or of higher risk than cigarettes, increasing to 61.8% in 2018 (270). Only around a quarter of respondents perceived reduced risk with ECs (28.6% and 28.4% in 2016 and 2018, respectively). A similar increasing trend in perceived high risk of ECs was seen in a US survey, where 11.5% (95% CI 10.0–13.2%) of adults viewed them to be as harmful as smoking in 2012 but 36.4% (35.1–37.7%) did so in 2017 (271). The importance of risk perception amongst vapers is clear, as shown in another study where dual users who perceived ECs as being less harmful than smoking were more likely to be exclusive vapers after 1 year than those who did not perceive them as less harmful (7.5% vs 2.7%, adjusted odds ratio 2.9, 95% CI 1.7–4.8) (269). It is worth noting that, according to an analysis based on the PATH study, the proportion of US adults perceiving e-cigarettes as harmful or more than cigarettes steadily increased from 53.7% to 72.7% between 2014 and 2016 (272). Other perceptions, such as product addictiveness, social acceptability, potential to harm others, and environmental impact, may also affect product choice. The most common reasons to use ECs among adults and youth in one survey were smoking cessation and novelty, respectively (273). In another study, the two main reasons for using ECs by current and former smokers were perceptions that they could be helpful to quit and were less harmful than smoking (274). In a Europe-wide survey in 2014, the main reasons given for use of ECs were to stop or reduce smoking and being able to use them in places where smoking was banned (275), while in 2020, reducing tobacco consumption was still the main reason for using ECs followed by believing they were less harmful than cigarettes (14). In the UK, ASH (276) reported that the three main reasons for vaping were as an aid to quit smoking, remain abstinent from smoking, and save money.

Switching to ECs and abuse liability

One criticism of ECs is their inefficacy for sustaining exclusive vaping and propensity to facilitate dual usage (277). These views, in part at least, were based on early studies of products providing low nicotine delivery and hence low user satisfaction (278). While ECs are not marketed as smoking cessation products, a large 1-year study in the UK showed that the smoking abstinence rate among people who switched to later-generation ECs was roughly double that among those who switched completely to NRT (212).

For smokers attempting to quit smoking, higher reward from ECs could help them to completely transition away from combustible cigarettes, as frequency of use of vaping products has been positively associated with becoming a former smoker with quit durations of 2–6 years (188, 279). However, increases in nicotine exposure could raise concerns about the abuse liability of ECs.

Abuse liability is the likelihood of engaging in persistent and problematic use of a substance that will lead to undesirable consequences (280). High nicotine delivery via ECs could increase the risk of abuse liability. However, if ECs can provide a viable alternative to cigarettes, they might have a public health benefit (24, 281, 282) and some degree of abuse liability might be acceptable (283, 284). A standard methodology has been established to assess the abuse liability of pharmaceuticals (285) and is largely adaptable for tobacco products (280, 286). This type of study is likely to be most relevant in countries where high concentrations of nicotine are allowed in e-liquids, such as the USA (287). In a prospective direct comparison of ECs with smoking and NRT (nicotine gum), Stiles et al. (96) found that while their study showed ECs probably had some degree of abuse liability, it was much closer to that of NRT than to combustible cigarettes. This conclusion was reinforced at category level by the analyses of symptoms of dependence collected through national US surveys, the Population Assessment of Tobacco and Health (PATH) (288, 289) and the National Adult Tobacco Survey (290). Both identified dependence symptoms in EC users but to a substantially lesser degree than in smokers. Another retrospective study, based on the International Tobacco Control database, investigated differences in symptoms of dependence between vaping and non-vaping ex-smokers in four countries (USA, UK, Australia, and Canada) (291). Vapers were more likely to perceive themselves as very addicted to smoking, but at the same time to feel more confident about remaining abstinent from smoking and to experience fewer urges to smoke than non-vapers.

Vapers demographics - uptake by young people and potential gateway effects

Vaping products have experienced an increase in popularity all around the World. In Europe estimated vaping prevalence increased from 1.5% in 2014 to 1.8% in 2017 (292). Ever use ranged widely from 5.5% to 56.5% and was highest in younger age groups, with studies reporting consumption from respondents ranging from 10–24 years old. In the USA a larger study with 158,626 participants (293) reported ever use of vaping products of 14.8%, 12.8%, 9.4%, 7.0%, 2.3% in the age groups 18–24, 25–34, 35–44, 45–64, ≥65 years, respectively, while regular use (use in ≥20 of the previous 30 days) was more comparable across the same age groups (1.3%, 1.3%, 1.2%, 1.0%, 0.4%, respectively). In the UK, where uptake of ECs has been high, ever use in 2019 was estimated to be 16.5%, 20.1%, 12.3%, 10.8%, 5.2% in the age groups 16–24, 25–34, 35–49, 50–59, ≥60 years and 3.3%, 9.2%, 7.3%, 7.1%, 3.0%, respectively were regular users (294). Prevalence of vaping is generally lower among women than men, as for smoking (292, 295). Most vapers smoke or have smoked in the past. Vapers without smoking history account for a very small proportion of all vapers (26, 292, 294, 296,297,298).

Youth EC initiation has taken centre stage in the EC scientific world since the US Surgeon General declared EC use among youth “an epidemic” (299). Public Health England's (PHE) annual review estimated that EC prevalence with use of once per week or less was around 5% among 11–18-year olds, but varied by age. Prevalence among 11-year olds was 1% up to 5% among 15 year olds (26). A large 2017 review of surveys involving 60,000 children aged 11–16 years in the UK suggested that the prevalence of more frequent regular use (at least weekly) was 3%, even though proportions of 7–18% had ever tried ECs (300). Most young people regularly using ECs were already smokers, and among never smokers, only 0.1–0.5% regularly used ECs. In the US, uptake seems to be higher, with 13.1% of middle-school and high-school students nationally reported to be current EC users in 2015–2017, although most users (76.7%) also used at least one other tobacco product (301). However, smoking initiation rates among youth in the US reached the lowest recorded rate of 2.29% in 2018 (302), and similar patterns have been observed across European countries where ECs are widely available (303). Friend or caregiver smoking seems to increase the likelihood of children trying ECs, as does lower socioeconomic status (304, 305). Differing perceptions of risks have been found across subgroups of young people (e.g., classified by ethnic origin or sexuality) (306), but little work has been done on social factors (307), and this area needs greater attention.

Gateway theory originates in the use of a psychoactive drug being viewed as increasing the likelihood of using further drugs. When applied to vaping, it describes changes in a biological and/or behavioural pathway seen with use of a lower-risk product, such as an EC, increasing the risk of smoking combustible cigarettes for a higher reward (308). This theory has been cited to support the banning or restriction of access to EC products and liquids containing nicotine, for instance in Australia (309), but it is not backed up by reliable evidence (29, 310, 311). Application of such policies risk denying adult smokers the opportunity to switch to ECs and might increase relapse to smoking or smoking initiation (312). Kasza et al. (313) analysed the US PATH study database from 2013 to 2016 and found that ever users of ECs aged 12–17 years were more likely to have smoked in the previous 30 days at follow-up (adjusted odds ratio 3.4, 95% CI 2.4–4.7%). However, the likelihood of smoking was increased by use of any other tobacco product, including hookahs and smokeless tobacco. EC use was similarly increased by smoking (adjusted odds ratio 2.9, 95% CI 2.1–4.0%). Thus, changing to smoking could be explained by youth experimentation and propensity to risk (314, 315). Concurrent use of nicotine products has also been reported by Auf et al. (316). However, national surveys do not suggest any gateway effect. Studies from the USA (288, 302, 317), UK, New Zealand (318) and Canada (319), have concluded that (i) smoking usually precedes vaping; (ii) regular vaping is rare amongst never smokers; (iii) not all adolescent vapers used nicotine and dependence was lower than for smokers; (iv) since vaping has been introduced, smoking rates have continued to decline. The Canadian study concluded, “when it comes to smoking cigarettes, very few smoked cigarettes in addition to vaping and fewer still believe they started smoking after they had started vaping” (319).

Use behaviour studies

Consumer use behaviour studies can provide an understanding of puffing topography, potential nicotine uptake, and variability in patterns of usage between different EC types and users (37, 320). The data are crucial for understanding how consumers use products and play a key part in setting the scientific framework for assessing risk potential. EC use differs significantly from cigarette smoking, although more information is needed on topography, perceptions, and behaviours. The US FDA recommends conducting “actual use” studies in “real-world conditions” within their Modified Risk Tobacco Product Application guidelines (73).

Consumer use behaviour studies should adhere to the principles of good clinical research practice, which aim to protect the wellbeing of participants and ensure appropriate study execution and data traceability. Attempts are being made to establish independent ethics committees that can weigh risks against (participant and society) benefits of use behaviour studies conducted with consumer products. Such committees would ensure that the rights, safety, and wellbeing of trial participants prevail over the interests of researchers, science, and society by providing participants with adequate information on study products; details of the study in a scientifically sound protocol; obtaining informed consent from every participant prior to participation; ensuring that the data generated are stored, recorded, handled, and accurately interpreted, verified, and reported by implementing quality systems and procedures.

In a typical EC use behaviour study, volunteers who have given informed consent are trained in the use of the products where necessary to ensure familiarity and are provided with the test product for use at home over a fixed period. Consumption patterns at home are self-reported while periodic attendance at a study site might also be required to assess puffing behaviour with a topography device (320, 321). Questionnaires might be used to obtain feedback about the sensory experience of vaping, satisfaction with selected attributes, and overall acceptability (322). Results from typical topography studies have been summarised in Table 5.

Mouthpiece-based ad libitum topography measurement of various electronic cigarette types.

Reference Electronic cigarette type Mode of activation Topography device Mean (± SD) puff characteristics


No. of pieces Components Rechargeable device Refillable cartridge Description No. of puffs per session Puff volume (mL) Puff duration (s) Puff interval (s)
Behar et al., 2015 (359) 1 All-in-one No No Blu Puff actuated CReSSmicro 33 (± 8) 56 (± 22) 2.75 (± 0.96) 16.9 (± 8.2)
Cunningham et al., 2016 (320) 1 All-in-one Yes No Cig-a-like Puff actuated Modified SA7 21.1 (± 14.9) 52.2 (± 21.6) 2.0 (± 0.7) 23.2 (± 10.6)
Norton et al., 2014 (360) 2 Battery & cartomizer Yes No Cig-a-like Puff actuated CReSSmicro 8.7 (± 1.6) 118.2 (± 13.3) 3.0 (± 1.6) 29.6 (± 11.7)
Lee et al., 2015 (361) 2 Battery & cartomizer Yes No Cig-a-like Puff actuated CReSSmicro 21.3 (± 2.4) 63.3 (± 23.4) 2.9 (± 0.9) 22.1 (± 22.0)
Behar et al., 2015 (359) 2 Battery & cartomizer Yes No V2 Puff actuated CReSSmicro 31 (± 8) 45 (± 22) 2.54 (± 1.04) 18.9 (± 7.3)
Cunningham et al., 2016 (320) 2 Battery & cartomizer Yes No Vype ePen Button activated Modified SA7 16.1 (± 8.0) 83.0 (± 44.3) 2.2 (± 0.9) 29.3 (± 19.2)
Jones et al., 2020 (322) 2 Battery & cartomizer Yes No IS1.0(T) Button activated Modified SA7 63.6 (± 36.2) 41.2 (± 17.0) 1.5 (± 0.6) 23.3 (± 17.3)

Hammond et al. (323) concluded that ECs topography studies “show a high degree of stability in puffing behaviour within the same subject over time, but considerable variability between e-cigarettes users”. Thus, more-granular information is needed to improve the accuracy of topography data and how they relate to nicotine exposure in users’ everyday environments. To enable the collection of real-life data over longer periods of time, attempts have been made to incorporate topography devices into ECs that record various attributes and transmit data via an internet-enabled electronic device to cloud data platforms (Table 6). Further work is needed to validate the accuracy and reliability of the data generated by these connected ECs compared to traditional instruments, but they seem not to substantially affect puffing behaviour (324).

Connected e-cigarette-based ad libitum topography measurement of various e-cigarette types.

Reference Electronic cigarette type Mode of activation Topography device Mean (± SD) puff characteristics


No. of pieces Components Rechargeable device Refillable cartridge Description No. of puffs per session Puff volume (mL) Puff duration (s) Puff interval (s)
Robinson et al., 2015 (362) 2 Battery & cartomizer Yes No Closed Puff actuated Wireless personal use monitor 225 ± 59 133 ± 90 3.5 ± 1.8 42.7 ± 12.1
Robinson et al., 2016 (363) 2 Battery & cartomizer Yes No Closed Puff actuated Wireless personal use monitor 78 ± 162 65.4 ± 24.8 2.0 ± 0.6 NR
Dawkins et al., 2016 (364) 3 Battery, cartridge & atomizer Yes Yes Mod Puff actuated Connected e-cigarette 70.7 ± 34.4per session NR 5.2 ± 1.4 NR
Farsalinos et al., 2018 (344) 3 Battery, cartridge & atomizer Yes Yes Mod Puff actuated Connected e-cigarette 57 ± 14.9per session NR 4.6 ± 1.0 NR
Lee et al., 2018 (365) 2 Battery & cartomizer Yes No Closed Puff actuated Wireless personal use monitor 13.7per session 110.3 13.7 38.1

Topography data can be used to improve understanding of baseline characteristics related to EC use, which can then be used to establish representative vaping machine protocols. While standardization of regimes would be valuable to industry, academics, and regulators, no single regime is likely to represent true human behaviour or produce emissions linked closely enough to human exposure given the wide range of puffing behaviours. CORESTA Recommended Method No 81 lays out the essential requirements necessary to generate and collect EC aerosol for analytical testing purposes (112), but the parameters do not reflect intense use.

Rather than using maximum settings for intense regimes, parameters for puff duration, volume, frequency, profile, and number, battery charge status, coil or atomiser age, voltage setting, ventilation setting, and device orientation should be based on representative human usage data. These parameters are not all independent and improved understanding of how different combinations affect the amount of aerosol generated will be central to defining protocols for testing and regulating ECs.

BRIDGING STUDIES

Given the pace of EC innovation, providing the amount of data required for regulatory decisions while a product remains relevant is not always possible. Borrowed from the pharmaceutical industry, the concept of bridging applies the best practice data from an existing product to the design of a similar product and updates only data pertinent to modifications (95). For example, for ‘biosimilars’ in Europe, data from a reference drug are supplied and the only new data are those which show that the new variant does not diverge in safety or efficacy from the reference (325). In ECs this can be translated to maintaining product safety while ensuring the new variant does not increase health risks to users and non-users. Regulatory bodies, such as the FDA, recognize the potential of this approach for ECs as long as it is supported by a rationale and justification (66).

Thus, for an EC variant of an existing product, if the changes do not affect factors like age, gender, race of users or cultural environmental factors, data could be reused from studies using earlier models of the product and new bridging data should be only required only for those aspects which could potentially be affected by the changes.

POPULATION MODELLING

Modelling has become important to support risk-benefit assessments and policy decisions in tobacco control because it provides projections based on credible simplifications of complex mechanisms underlying nicotine use. The strength of modelling resides in the capability of processing many parameters with complex interactions rather than looking at one aspect of an issue at a time. Additionally, the impact of inputs’ uncertainty may be assessed. A wide range of topics in relation to tobacco control and harm reduction has been assessed, from the impact of taxation of cigarettes (326) to banning menthol cigarettes in the USA (327). In assessment of potential health benefits or burdens from commercialization of ECs, models have been used to consider morbidity or mortality at the population level, including EC use versus smoking in adults and youth, possible effects of different proportions of dual use, and complete displacement of cigarettes by ECs.

There are two main types of nicotine population models. First, microsimulation models aggregate changes at the individual level (328). Various parameters can be set to reflect individual characteristics and interactions between the units (people). Macrosimulations involve groups of people considered to be homogenous individuals with respect to the main factors affecting the outcome (329). Macrosimulations can be further separated into two main categories: birth cohort models (330) and system models (331). In birth cohort models, a group of homogenous individuals born in a specific year (e.g., smokers born in 1960) is followed up until death or a timepoint. The potential impact of introducing different scenarios involving ECs is projected, and effects are compared to the counterfactual scenario of no change (i.e., the status quo, generally a scenario with cigarettes only). System models use information about past demographic and smoking patterns to generate projections of mortality or morbidity. As before, a status quo scenario in which ECs have never existed is compared to an alternative scenario in which they are commercialized. The most common outcome is the numbers of life-years lost or saved as a compound measure of prolonged life across the entire population. Lee et al. (332) have described various models used for modified tobacco product risk assessment, including strengths and weaknesses. Conclusions from some of these models have been summarised in Table 7.

Population modelling studies.

Reference Focus and assumptions Conclusions
Levy et al., 2018 (334) Status quo scenario developed to project smoking rates and health outcomesin the absence of vaping, compared with substitution models in which combustible cigarette use is largely replaced by vaping over a 10-year period Projections show that a strategy of replacing cigarette smokingwith vaping would yield substantial life-year gains, even under pessimistic assumptionsregarding cessation, initiation and relative harm
Levy et al., 2017 (366) Alteration in smoking patterns caused by transitions from trialof e-cigarettes to established vaping (exclusive or dual use) and effects of cessation at later ages in a 1997 birth cohort; measured by estimated public health impact on deaths and life-years lost incorporating evidence-informed parameter estimates Conservative assumptions indicated reductions of 21% in smoking-attributable deaths and of 20% in life-years lost with established vaping compared to no vaping. Health gains from vaping were especially sensitive to vaping risks and use rates among those who were otherwise likely to smoke cigarettes
Levy et al., 2019 (367) Cohort-specific simulation model of the impact of e-cigarettes containing nicotine on smoking cessation by adult smokers and premature deaths and life-years lost, by gender in two US birth cohorts aged 30 or 50 years in 2012 Vaping was projected to have a net positive impact on population health over a wide range of plausible levels of use (transitions to dual, exclusive, andno e-cigarette use) and vaping risks, although net impact wassensitive to parameter estimates
Warner & Mendez, 2019 (333) Dynamic model that tracked smoking status in the US adult population and smoking-related deaths over time and the effects of vaping-induced smoking initiation and cessation on life-years saved or lost to the year 2070 Health benefits were strongly suggested for e-cigarette use, interms of their potential to increase adult smoking cessation, that exceeded risks to healthresulting from increasing the number of youthful smoking initiators
Petrović-van der Deen et al., 2019 (368) Multistate life-table model of 16 tobacco-related diseases thatsimulated lifetime quality-adjusted life-years and health-system costs at a 0% discount rate, incorporating transitions from never, former, and current smoker states to and fromregular vaping and based on literature estimates for relative risk of disease incidence for vaping vs. smoking A regulatory environment permissive of vaping achieved net health-gain and cost savings, although uncertainty intervals were wide
Cherng et al., 2016 (336) Agent-based model examining hypothetical scenarios of e-cigarette use by smoking status and e-cigarette effects on smoking initiation and smoking cessation With current patterns of e-cigarette use by smoking status and the heavy concentration of e-cigarette use among current smokers, simulated effects of e-cigarettes on smoking cessation generated substantiallylarger changes to smoking prevalence than on smoking initiation
Soneji et al., 2018 (337) Monte Carlo stochastic simulation model of expected years of life gained or lost due to effects of e-cigarette use on smoking cessation among current smokers and transition to long-term cigarette smoking among never smokers in 2014US population, with model parameters drawn from census counts, national healthand tobacco use surveys, and published literature The existing evidence and optimistic assumptions about the relative harm of e-cigarette use compared to cigarette smoking, suggest that e-cigarette usecurrently represents more population-level harm than benefit
Kalkhoran & Glantz, 2015 (369) A base case model using data on reported cigarette and e-cigarette use patterns in the US and UK to quantify transitionsfrom no cigarette or e-cigarette use to never use of either, cigarette use, e-cigarette use, dual use, or quit If e-cigarette use increased only among smokers interested in quitting vsmore quit attempts and no increased initiation of e-cigarette use among non-smokers or e-cigarettes were taken up only by youth who would have smoked conventional cigarettes, population-level health benefits were estimated regardless of e-cigarette health costs. Conversely, scenarios in which e-cigarette promotion led to renormalisation of cigarette smoking or ECs were used primarily by youth who never would have smoked, net health harms were estimated across all e-cigarette health costs. In other scenarios, the net health effects varied by the health costs of e-cigarettes
Hill & Camacho, 2017 (338) System Dynamics Model representing UK population. Assumes the risk of dual users is the same as smokers and any benefit obtained from quitting is lost if there is a relapse to smoking. Provide projections to 2050. The results suggest that by 2050, smoking prevalence in adults could be as low as 12.4% in the core model and 9.7% (including dual users) in the counterfactual. Smoking-related mortality would be 8.4% and 8.1%, respectively.

Most studies are based on data from the US adult population. Warner and Mendez (333) used a system model representing this population, based on demographics and smoking status, and made projections to 2070. The status quo scenario was that ECs had never existed and was compared against three variants of an alternative scenario in which ECs were available, involving EC-associated changes in smoking initiation, smoking cessation, and health effects. In all three scenarios the model suggested positive gains ranging from nearly 583,000 to 3.3 million life-years saved based on the most optimistic and most conservative assumptions, respectively.

Levy et al. (334) used two birth cohorts of smokers (1962 and 1982) to compare only cigarette smoking against replacement of cigarettes with ECs at different rates. In the status quo model, smoking was calculated to cause 390,632 cumulative premature deaths and 4,577,882 life-years lost in men and 135,468 premature deaths and 1,628,491 life-years lost in women. In the 1982 birth cohort, if only 5% of smokers transitioned to dual use or exclusive EC use per year and the risks associated with ECs were 5% of those associated with smoking, premature deaths and life-years lost would decrease by 69,585 and 1,048,763, respectively, in men and 26,104 and 433,872 in women. For the 1962 cohort under the same assumptions, the model also projects fewer premature deaths and fewer life-years lost. In another model using a 2001 birth cohort, Levy et al. (334) assessed scenarios in which vaping would reduce smoking prevalence to 5% (optimistic) or 10% (pessimistic) by 2026. In the pessimistic scenario, cumulative reductions of 19.5 million premature deaths and 161.9 million fewer life-years lost were projected with the introduction of ECs. In the optimistic scenario, the values would be 24.4 million and 227.8 million, respectively.

A model used by Bachand et al. (335) suggested that if only 2% of smokers switched completely to a lower-risk product in all age-groups, population survival would be significantly enhanced by 3,127 lives. Survival would increase with the growing proportion of complete switchers. The gain would also offset unintended exposure patterns, such as use of lower-risk products leading to cigarette smoking initiation by never users or dual use by smokers. Credibility of these outcomes were reinforced by Cherng et al. (336), who concluded that simulated effects of ECs on smoking cessation would generate substantially greater decreases in smoking prevalence than increases in smoking initiation.

Not all model projections based on US data have been favourable to ECs. Soneji et al. (337) projected between 1.3 and 1.15 million life-years lost by introducing ECs. This opposition in directionality to most of the other modelling efforts could be due to over-pessimistic inputs with high gateway effects into smoking from vaping and low quitting rates from smoking to vaping. This study highlights the importance of using not only possible but credible inputs based on robust scientific data.

Beyond the USA, Hill and Camacho (338) used a system dynamics model to estimate differences in effects from 2000 to 2050 between the introduction and no introduction of ECs in the UK. It was assumed that there would be no reduction in risk for dual users and any benefit gained by switching would be lost for people who relapsed to smoking. The model still suggested a beneficial impact from introducing ECs, with smoking-related deaths in 2050 projected to fall to 8.4% in the status quo scenario compared with 8.1% in the vaping scenario, and to 11.2% versus 10.5% in people younger than 75 years.

In summary, a wide range of models have been used to assess the potential impact of commercialization of ECs and, when credible inputs are considered, these models have pointed to an overall health benefit at the population level.

DISCUSSION

Despite extensive variation in EC devices and e-liquid formulations (106), in the absence of tobacco combustion, EC aerosol is much simpler than cigarette smoke and the numbers and concentrations of compounds present are substantially lower (19,20,21,22). To promote comparability and interpretability, testing of ECs should be performed using appropriate puffing parameters (42, 75,76,77,78, 112) and always with the measurement of air blanks to contextualize contamination by laboratory-based toxicants (20).

Frequently, flavouring ingredients are not fully listed on packaging. To maximize safety, manufacturers should restrict flavours to ingredients that are food grade or generally recognised as safe (339), and perform appropriate testing when the toxicological profile is not well characterised (87). Of note, many ingredients have not been tested for safety when consumed by aerosolization and inhalation and/or when heated, and effects might not transfer reliably from ingestion. For example, diacetyl, which gives a butterscotch flavour, is safe to eat but when inhaled in large amounts in popcorn factories was associated with bronchiolitis obliterans, also known as popcorn lung. As a result, this flavouring is banned in ECs in many countries, although testing at the very low levels that would be required has not been performed (93). Such safety aspects of EC design and ingredients continue to evolve through manufacturers product stewardship, and are being reflected in regulatory guidance (106). A wide range of assessment methods, including toxicological assays (88), three-dimensional organotypic models (161, 169, 181), and in silico risk assessments (47) can be useful to guide product design and standards. The consolidation and standardization of methods and endorsements of testing frameworks by regulators will be important next steps to increase product quality within the EC category.

The gold standard to investigate EC-associated health risks are clinical and epidemiological studies. However, clinical studies are expensive and, therefore, primarily conducted through sponsorship by large manufacturers, which could bias studies towards well-designed and highly stewarded products. While epidemiological outcomes can be difficult to unveil, as it might take many years to observe significant changes, reversibility of harm from smoking as well as epidemiological effects might be further complicated by the fluidity between products among nicotine users. For exposure to toxicants, reduced levels of BoEs in exclusive vapers have been confirmed at population level, even with heterogeneity in products and how they are used (219), and BoPH and biomarkers of biological effect studies suggest a reduction of risk of acute health effects caused by smoking (340). Further work is required, particularly on endothelial dysfunction, oxidative stress, and cancer.

In conclusion, the harm reduction potential of ECs will be maximized by complete displacement of cigarettes. Two aspects will have a critical impact on the effectiveness of ECs to displace smoking.

First will be the manufacture of robust, high-quality products that compete with conventional cigarettes by satisfying consumers through product performance, sensorial characteristics, and nicotine delivery, while striking a balance against abuse liability. Manufacturers must use these and all other tools they have, including flavours, to make ECs a more attractive proposition to adults than smoking.

Second, public health institutions must unambiguously and accurately inform smokers about the likely reduced risk character of ECs compared with cigarettes. The UK has seen some public health institutions openly supporting ECs as lower risk alternatives to smoking. In 2019, more than 50% of all vapers in the UK used ECs exclusively (294) and smoking prevalence reached a record minimum of 15.8%, down from 16.6% in 2018 (341). Consolidating this trend, the proportion of former smokers in 2019 was the highest recorded at 62.5% (341).

Despite all evidence supporting ECs as reduced risk products as part of a smoking harm reduction framework, outright bans and restrictions of ECs or flavoured e-liquids continue in many countries, and others are introducing restrictions, for example on flavours, that are not supported by scientific evidence. The main reasons being used to ban or legislate against ECs are underage usage and the hypothesis of a gateway effect. However, irresponsible marketing of vaping products has led to a situation of distrust between governments and the vaping industry and is an area that needs to be addressed. As this topic is highly controversial, it may deviate from the scientific focus of this review. It is mentioned as it clearly can have an impact on initiation, but it deserves a publication of its own.

At population level, national surveys do not suggest any gateway effect, and smoking initiation rates among youth in the US also indicate the absence of such an effect and the lowest rates of smoking initiation on record in 2018 (2.29%) (302). Similar patterns have been observed across European countries where ECs are widely available (303) and are also suggested by a study commissioned by Health Canada (319). Regulation of all aspects limiting the efficacy of ECs as an alternative to smoking should be considered with caution, as such measures could reduce the attractiveness of ECs for smokers and reignite smoking initiation (312).

CONCLUSIONS

Regulatory strategies must promote quality in product development led by robust stewardship which is essential to identify and eliminate, or minimize potential hazards

Vapour products have been soundly demonstrated to be able to reduce exposure to toxicants found in conventional cigarette smoke among smokers who transition completely to vapour products

Emerging evidence in biomarkers of effect point to lower risk for most smoking-related disease endpoints, with further research required particularly for cardio-vascular endpoints, where there are conflicting data.

Vapour products must offer a compelling alternative to smoking to attract smokers, including flavours while mitigating products’ youth appeal

Research suggests lower abuse liability from vaping products in comparison with conventional cigarettes

Gateway effect claims are generally not sustained by public data which show lowest levels of smoking initiation ever recorded in key markets such as the US and UK.

Figure 1

Schematic illustration of e-cigarette devices showing disposable 1st generation (cig-a-like) e-cigarettes, 2nd generation with refillable system, 3rd generation customizable ECs, and 4th generation e-cigarettes closed systems.
Schematic illustration of e-cigarette devices showing disposable 1st generation (cig-a-like) e-cigarettes, 2nd generation with refillable system, 3rd generation customizable ECs, and 4th generation e-cigarettes closed systems.

Comparison of carbonyl levels in e-cigarette vapour versus cigarette smoke from published studies.

Category Device/Cigarette Regime No. of puffs Carbonyls Units Reference

Formaldehyde Acetaldehyde Acetone Acrolein Propionaldehyde Crotonald ehyde MEK Butyraldehyde
Cigarette 1R6F HCI 9.1 4.879 158.9 62.31 14.51 13.74 4.484 15.93 3.08 μg/puff (22)
Cigarette Benson & Hedges Sky Blue HCI 8.1 5.235 177.4 65.68 15.93 15.43 5.321 17.41 4.469 μg/puff (22)
EC Gen1 Various 70 / 1.8 / 10* 150 3.2–56.1 2.0–13.6 N/A 0–41.9 N/A N/A N/A N/A μg/150 puffs (44)
EC Gen 2 Various open tank 55 / 4 / 30* 10 0.9–2.7 0.3–1.7 N/A 0.7–1.9 N/A N/A N/A N/A μg/10 puffs (344)
EC Gen 2/3 Open tank/NHOSS “Lounge” model (no nic./16 mg/mL nic.) CRM81 96 0.37–1.48 0.16–0.96 N/A 0.05–2.1 1 N/A N/A N/A N/A ng/mL puff (113)
EC Gen 3/4 ePen CRM81 122 106 73 70 LOQ N/A N/A 8 ng/puff (20)
EC Gen 4 JUUL rich tobacco (20 mg/mL) CRM81 112 76 3 13 N/A N/A N/A N/A ng/puff (114)
JUUL rich tobacco (18 mg/mL) CRM81 11 12 36 7 N/A N/A N/A N/A ng/puff (114)
myblu (tobacco flavour, 1.6% nic.) CRM81 150 < 2.63 < 17.5 < 8.75 < 4.38 < 4.38 < 4.38 < 4.38 < 4.38 μg/150 puffs (115)
Vype ePen 2 (18 mg/mL nic.) CRM81 268 230 135.8 346 96.2 BLD BLD BLD ng/puff (22)
Vype ePen 3 (BAT 18 mg/mL nic.) CRM81 52.8 NQ 111 BLD NQ BLD BDL BLD ng/puff (22)

Population modelling studies.

Reference Focus and assumptions Conclusions
Levy et al., 2018 (334) Status quo scenario developed to project smoking rates and health outcomesin the absence of vaping, compared with substitution models in which combustible cigarette use is largely replaced by vaping over a 10-year period Projections show that a strategy of replacing cigarette smokingwith vaping would yield substantial life-year gains, even under pessimistic assumptionsregarding cessation, initiation and relative harm
Levy et al., 2017 (366) Alteration in smoking patterns caused by transitions from trialof e-cigarettes to established vaping (exclusive or dual use) and effects of cessation at later ages in a 1997 birth cohort; measured by estimated public health impact on deaths and life-years lost incorporating evidence-informed parameter estimates Conservative assumptions indicated reductions of 21% in smoking-attributable deaths and of 20% in life-years lost with established vaping compared to no vaping. Health gains from vaping were especially sensitive to vaping risks and use rates among those who were otherwise likely to smoke cigarettes
Levy et al., 2019 (367) Cohort-specific simulation model of the impact of e-cigarettes containing nicotine on smoking cessation by adult smokers and premature deaths and life-years lost, by gender in two US birth cohorts aged 30 or 50 years in 2012 Vaping was projected to have a net positive impact on population health over a wide range of plausible levels of use (transitions to dual, exclusive, andno e-cigarette use) and vaping risks, although net impact wassensitive to parameter estimates
Warner & Mendez, 2019 (333) Dynamic model that tracked smoking status in the US adult population and smoking-related deaths over time and the effects of vaping-induced smoking initiation and cessation on life-years saved or lost to the year 2070 Health benefits were strongly suggested for e-cigarette use, interms of their potential to increase adult smoking cessation, that exceeded risks to healthresulting from increasing the number of youthful smoking initiators
Petrović-van der Deen et al., 2019 (368) Multistate life-table model of 16 tobacco-related diseases thatsimulated lifetime quality-adjusted life-years and health-system costs at a 0% discount rate, incorporating transitions from never, former, and current smoker states to and fromregular vaping and based on literature estimates for relative risk of disease incidence for vaping vs. smoking A regulatory environment permissive of vaping achieved net health-gain and cost savings, although uncertainty intervals were wide
Cherng et al., 2016 (336) Agent-based model examining hypothetical scenarios of e-cigarette use by smoking status and e-cigarette effects on smoking initiation and smoking cessation With current patterns of e-cigarette use by smoking status and the heavy concentration of e-cigarette use among current smokers, simulated effects of e-cigarettes on smoking cessation generated substantiallylarger changes to smoking prevalence than on smoking initiation
Soneji et al., 2018 (337) Monte Carlo stochastic simulation model of expected years of life gained or lost due to effects of e-cigarette use on smoking cessation among current smokers and transition to long-term cigarette smoking among never smokers in 2014US population, with model parameters drawn from census counts, national healthand tobacco use surveys, and published literature The existing evidence and optimistic assumptions about the relative harm of e-cigarette use compared to cigarette smoking, suggest that e-cigarette usecurrently represents more population-level harm than benefit
Kalkhoran & Glantz, 2015 (369) A base case model using data on reported cigarette and e-cigarette use patterns in the US and UK to quantify transitionsfrom no cigarette or e-cigarette use to never use of either, cigarette use, e-cigarette use, dual use, or quit If e-cigarette use increased only among smokers interested in quitting vsmore quit attempts and no increased initiation of e-cigarette use among non-smokers or e-cigarettes were taken up only by youth who would have smoked conventional cigarettes, population-level health benefits were estimated regardless of e-cigarette health costs. Conversely, scenarios in which e-cigarette promotion led to renormalisation of cigarette smoking or ECs were used primarily by youth who never would have smoked, net health harms were estimated across all e-cigarette health costs. In other scenarios, the net health effects varied by the health costs of e-cigarettes
Hill & Camacho, 2017 (338) System Dynamics Model representing UK population. Assumes the risk of dual users is the same as smokers and any benefit obtained from quitting is lost if there is a relapse to smoking. Provide projections to 2050. The results suggest that by 2050, smoking prevalence in adults could be as low as 12.4% in the core model and 9.7% (including dual users) in the counterfactual. Smoking-related mortality would be 8.4% and 8.1%, respectively.

Clinical studies of e-cigarettes.

Reference Study design/product Study arms (subgroups) Conclusions
Shahab et al., 2017b (221) Cross-sectional study, using unspecified EC or NRT products for ≥ 6 months Smokers (n = 37)Dual use NRT (n = 36)Dual use EC (n = 36)NRT (n = 36)EC (n = 36) NNAL, 3HPMA, AAMA, CYMA, MHBMA3, HEMA were expressed as proportions of levels in the smoker arm. Significantly lower levels of all biomarkers were observed for EC only users (2.9–43.5% decrease) that were similar to those in NRT only users. NRT and EC dual users presented similar biomarker levels to the smoking group
Lorkiewicz et al., 2019 (216) Cross-sectional study, using unspecified ECs or smokeless products No tobacco (n = 12)ECs (n = 12)smokers (n = 12)smokeless tobacco (n = 12) The EC users showed higher levels of xylene, cyanide, styrene, ethylbenzene, and acrolein metabolites than non-tobacco users, but lower levels for toluene and acrolein metabolites. Levels of VOC metabolites in the smokeless tobacco group were similar to those in the non-tobacco group
Czoli et al., 2019 (214) Three-period crossover design where dual users (smoked ≥ 5 cigarettes per day and used an EC at least once a day for the past 7 days) to either EC > smoking > no tobacco or smoking > EC > no tobacco, with each condition lasting for 7 days Dual users (n = 48) 1-HOP was significantly higher during the smoking period than during dual use but was lower during EC use. NNAL levels decreased significantly from dual use, by 30% during EC use and by 35% during cessation but did not change during smoking
Hecht et al., 2015 (226) Cross-sectional study comparing biomarker levels in smoker to ECs switchers (≥ 2 months) with those in smokers from three previously published studies (Carmella et al. 2009; Hatsukami et al. 2010; Zarth et al. 2014) EC users (n = 28) All biomarkers (1-HOP, total NNAL, 3HPMA, 2HPMA, HMPMA, and SPMA) were significantly lower in EC users than in smokers
Mcrobbie et al., 2015 (217) Switching study in which smokers switched to ECs or dual use EC users (n = 16)Dual use (n = 18) 3HPMA in urine showed significant reductions at 4 weeks after switching compared with baseline (ECs 79%, dual use 60%)
Goniewicz et al., 2017 (215) Switching study in which smokers switched to ECs dual use for 2 weeks then ECs only for 2 weeks Smokers switching to ECs (n = 20) Significant reductions were seen after 2 weeks in urine biomarkers of exposure to NNAL and eight VOC metabolite levels (50–69%) and fluorene (42–82%), butnot in those for pyrene, phenanthrene, and naphthalene
Cravo et al. 2016 (225) Parallel study in which smokers were randomly assigned in a ratio of 3:1 to switch to an EC (tobacco or menthol flavour) or continue smoking for 12 weeks Switch to EC (n = 306)continue smoking (n = 102) After 12 weeks, 3-HPMA, S-PMA and total NNAL in urine were reduced by around 30% compared with baseline in those who switched to ECs, whereas noreductions were among those who continued smoking
O’Connell et al., 2016 (245)D’Ruiz et al., 2017 (232)D’Ruiz et al., 2016 (356) Parallel study of smokers switching to ECs or dual use during 6 days in clinic Rechargeable EC tobacco flavour (n = 15)rechargeable EC cherry flavour (n = 15)disposable EC cherryflavour (n = 15)dual use with rechargeable EC tobacco flavour (n = 15)dual use with rechargeable EC cherry flavour (n = 15)dual use with disposable EC cherry flavour (n = 15)cessation (n = 15) Biomarkers: all urine biomarker measures (total NNAL, 3-HPMA, HMPMA, CEMA, 1-OHP, NNN, MHBMA, S-PMA) were significantly reduced compared to baseline in all groups, except MHBMA in the cherry disposable dual use group; levels in dual users were significantly higher than those in the cessation groupSpirometry: small changes seen in FVC from baseline to Day 5 (!0.5% to 3.1%) but were significant for tobacco and cherry rechargeable EC only users, while FEV1changes (!1.5% to 6.0%) were significant increases for the tobacco and cherry rechargeable EC only users and cherry rechargeable dual usersExhaled CO: reduced across all study groups, by around 89% in EC only and cessation groups and around 26% in dual user groupsExhaled FeNO: increased by 45.8–63.4% in EC only groups and 55%in the cessation group, but not in dual user groups (differences from the tobacco rechargeable and cherry disposable EC only groups were significant)Systolic blood pressure: changes varied across groups, but significant reductions in mornings seen for cherry flavour dual users, and in rechargeable tobaccoEC only usersDiastolic blood pressure: reduced significantly in mornings forrechargeable tobacco dual users and cherry rechargeable EC only usersHeart rate: reductions observed in the cessation group, rechargeable tobacco EC only group and rechargeable cherry product EC only and dual use groups
Sakamaki-Ching et al., 2020 (222) Cross-sectional study of age and gender matched participants, assessing spot urine samples from EC users, smokers and non-smokers for metals (antimony, cadmium, copper, indium, lead, nickel, rubidium, selenium, silver, titanium, and zinc), metal exposure, and BOPH EC users (n = 20)smokers (n = 13)non-smokers (n = 20) Metals: biomarkers for seleniumwere significantly higher in ECusers than in non-smokers or smokers with means 54.0, 41.8, and 39.7 μg/g creatinine, respectively, and were significantly increased for zinc in EC userscompared to non-smokers (584.5 vs413.6 mg/g creatinine) but not compared to smokers (470.7 mg/g creatinine)Metal exposure: metallothionein was significantly greater in ECusers than in non-smokers (mean 3761 vs1129 pg/mg creatinine) but similar to that in smokers (4096 pg/mg creatinine)BOPH: concentrations were increased in EC users when compared to non-smokers but not smokers (8-OHdG 442.8 vs221.6 and 388 ng/mg creatinine; 8-isoprostane 750.8 vs411.2 and 784.2 ng/mg creatinine)
Campagna et al., 2016 (357)Cibella et al., 2016 (229) Longitudinal study (52 weeks) of smokers switching to ECs with different concentrations of nicotine 2.4% nicotine (n = 49)1.8% nicotine (n = 50)0% nicotine (n = 40) 82 participants continued smoking, 34 significantly reduced thenumber of cigarettes smoked, and 18 quit smoking after switchingExhaled CO: decreased significantly in quitters and smokers whoreduced cigarette consumption from week 12Exhaled FeNO: increased significantly in quitters from week 12FEV1, FVC and FEV1/FVC ratio: not affected by smoking status (continued, reduced, or quit)FEF25–75%: significantly increased among quitters
Polosa et al., 2016 (220) Retrospective chart review study of changes in respiratory outcomes over 2 years in patients with COPD who were daily EC users (without combustible cigarettes) or smokers, matched for age and sex Baseline COPD GOLDstage 1 (smokers n = 3; EC users n = 2)stage 2 (smokers n = 5; EC users n = 6)stage 3 (smokers n = 11; EC users n = 10)stage 4 (smokers n = 5; EC users n = 6) FEV1, FVC and ratio FEV1/FVC ratio did not change from baseline values in either EC users or smokers, whereas COPD exacerbations were reduced and 6-min walking test scores increased compared with baseline in the EC users group but not the smoking group
Pulvers et al., 2018 (358) Switch study of smokers switching to an EC for 30 days with choice of seven flavours and two nicotine concentrations (12 or 24 mg/mL) Smokers (n = 37) Cigarette consumption: decreased significantly from mean 24.8 days to 14.0 days per month and mean 8.7 to 4.4 cigarettes per day, with six participants quitting, 21 becoming dual users and the remaining 10 sporadic EC only usersBiomarkers: NNAL, PMA, CNEMA decreased significantly from baseline, whereas HEMA, MMA, 3-HPMA, 2-HPMA, AAMA and HPMMA did notExhaled CO: decreased significantlySmoking dependence: decreased significantly from baseline
Aherrera et al., 2017 (218) Cross sectional study of nickel and chromium concentrations in EC users EC users (n = 59) Concentrations in urine, saliva, and breath: were below the limit of detection for nickel in 4.7%, 3.2% and 3.1% of samples, respectively, and for chromium in 7.8%, 1.6% and 56.3% of samplesWeekly consumption, time to first vape, voltage of device, number of coil changes per month, and levels in aerosol, dispenser, and tank had effectsNickel concentrations in urine were associated with time to first vape, coil changes, and concentrations in aerosol; in saliva were only associated with concentrations in aerosol and in tank, and in breath showed no associationsChromium in saliva was associated with cotinine in urine and concentrations in aerosol, tank, and dispenser
Wieslander et al., 2001 (231) Symptoms study after experimental exposure of healthy non-asthmatic volunteers to propylene glycol mist for 1 min Healthy volunteers (n = 27) Symptom VAS ratings: showed significant increase of ocular irritation, throat irritation, and dyspnoea but no effects on solvent smell or other symptomsLung function: FEV1, FVC, FEV1/FVC ratio, PEF did not change significantly from before to after exposureTear film stability: break-up time decreased significantly after exposure from 38 to 28 sDose response: throat dryness was 47% in the low exposure groupbut 100% in the high exposure group, where VAS ratings were also higher
Goniewicz et al., 2018 (219) Cross-sectional analysis of population in longitudinal Population Assessment of Tobacco and Health (PATH) study for biomarker concentrations Smokers (n = 2411)EC users (n = 247)dual users (n = 792)never tobacco users (n = 1655) NNAL: concentrations were significantly lower in never-smokers than in EC users and in both groups compared with smokers (geometric mean 0.921 vs4.887 and 203.5 pg/mg creatinine), whereas dual users had higher levels than smokers (262.2 pg/mg creatinine)Other tobacco specific nitrosamines: NAT, NAB, and NNN in EC users were above the limit of quantification for 12%, 15% and 34%of samples, respectively and were all higher than those in never tobacco users but significantly lower than those in smokersMetal exposure: beryllium wasfound only in 3–9% of samples; cadmium was higher in EC users than in never tobacco users (0.193 vs 0.149 ng/mg creatinine) but lower than in smokers and dual users (0.277 and 0.280 ng/mg creatinine, respectively); lead was elevated in EC users compared to never users (0.432 vs 0.351 ng/mg creatinine) but was highest in smokers and dual users (0.500 and 0.479 ng/mg creatinine, respectively); strontium differed only between dual users and smokers (130.5 vs 113.7 ng/mg creatinine); and no differences in concentrations between groups were found for cobalt, manganese or thalliumTobacco alkaloids: anabasine and anatabine concentrations were significantly lower in EC users than in dual users or smokers but similar to those in never tobacco usersTotal inorganic arsenic: significantly higher in EC users than in smokers and dual users (0.053 vs 0.048 and 0.045 ug/mg creatinine) but not different to never tobacco users (0.054 ug/mg creatinine)PAHs: of seven biomarkers of PAHexposure only 1-hydroxypyrene was elevated in EC users compared to never tobacco users, while all were significantly higher in smokers and five were higher in dual usersVOCs: of 20 biomarkers four were significantly elevated in EC users compared with never tobacco users (AMCA 1.5 times, BMA 1.1 times, CYHA 1.3 times, and CYMA 3.0 times*), although CYHA could only be detected in 3% of never tobacco users and 14% of EC users; 17 biomarkers were higher in smokers than in EC users by 1.4–31.0 times
Oliveri et al., 2020 (234) Cross-sectional observational study comparing biomarkers of exposure and BOPH in ex-smoker (≥10 cigarettes per day for ≥10 years) EC users (≥6 months) with current smokers Smokers (n = 62)ex-smoker EC users (n = 132) Biomarkers of exposure: concentrations of total NNAL, nicotine equivalents, 3HPMA, and COHb were lower in EC users than smokersBOPH: of white blood cells, HDL cholesterol, 11-dehydrothromboxane B2, 8-epi-prostaglandin F2α, and sICAM-1, lower concentrations were found in EC users for 11-dehydrothromboxane B2 (471.4 vs 664.8 ng/g creatinine), 8-epi-prostaglandin F2α (288.6 vs374.1 ng/g creatinine), and sICAM-1 (224.5 vs266.4 ng/mL), although differences for the latter were observed only for cartridge based ECs and not tank-base ECs
Piper et al., 2019 (227) Baseline assessments for longitudinal observational cohort study (2 years) of smokers versus EC dual users Smokers (n = 166)dual users (n = 256) In dual users, lower mean valueswere seen than in smokers for smoking duration (22.1 vs25.6 years), daily cigarette consumption (12.5 vs15.8), Fagerström nicotine dependence (4.15 vs 4.81), smoking within 30 min of waking (79.4% vs67.3%), and levels of NNAL (453.31 vs 340.99 pg/mL), whereas smoking starting age, motivation to quit, exhaled CO, the Wisconsin Inventory of Smoking Dependence Motives, and cotinine biomarkers did not differ significantly
Round et al., 2019 (223) Randomized, controlled, open-label, forced switch parallel group study in smokers of menthol and non-menthol cigarettes who switched to an EC or nicotine gum, to measure biomarkers of exposure after 5 days Smoker to EC (n = 38)smoker to nicotine gum (n = 39)menthol smoker to menthol EC (n = 40)menthol smoker to nicotine gum (n = 41) In all switching groups, total nicotine equivalents in urine, cotinine in plasma, and all biomarkers of tobacco smoke exposure decreased except for 3-OH-B[a]P in the smoker to nicotine gum group (reductions were ECs 30.4–95.5%, menthol ECs 35.7–97.7%, and nicotine gum 20–99.2%)
Song et al., 2020 Cross-sectional study of lung inflammation, measured by cell counts, cytokines, genome-wide gene expression and DNA methylation in bronchoalveolar lavage and brushings, in never smokers, EC users and smokers Never-smokers (n = 42)EC users (n = 15)smokers (n = 16) Most inflammatory cell counts and cytokine concentrations in EC users were intermediate between those of smokers and never-smokers, while most biomarkers were similar to those for never smokers, as were differential gene expression and DNA methylation

Comparison of metal levels in e-cigarette vapour versus cigarette smoke from published studies analysed.

Category Device/Cigarette Regime No. of puffs Metals Units Source

Mercury Cadmium Lead Chromium Nickel Arsenic Selenium
Cigarette 1R6F HCI 4.68 76.1 BLQ BLD BLD BLQ BLD ng/cig Jaccard et al. (342)
Cigarette 3R4F HCI 4.92 93.2 BLQ BLD BLD BLQ BLD ng/cig Jaccard et al. (342)
EC Gen 1 Various 70 / 1.8 / 10c 150 N/A 0.01–0.22 0.03–0.57 N/A 0.11–0.29 N/A N/A μg/150 puffs a Goniewicz et al. (44)
Cig-a-like 10 N/A N/A 0.017 0.007 0.05 N/A N/A μg/10 puffs a Williams et al. (123)
EC Gen 2/3 Open tank N/A 0.05–0.16 6.88–541 0.39–15.6 1.32–2148 0.1–1.59 N/A μg/kga Zhao et al. (130)
EC Gen 3 Liquids in reference CRM81 N/A < 0.06 < 0.05–0.12 < 0.09–1.58 < 1.08–1.54 < 0.12–1.33 N/A ng/puffa Belushkin et al. (116)
EC Gen 4 Closed system N/A 0.04–0.05 0.88–6.88 0.39–0.41 1.32–11.9 0.09–0.10 N/A μg/kga Zhao et al. (130)
myblub CRM81 150 BLQ BLD BLD BLD BLQ BLQ 0.00024 μg/puff O'Connell et al. (343)

Summary of pharmacokinetic, pharmacodynamic, vital signs profiles of combustible cigarettes, e-cigarettes (first to fourth generation), and nicotine-replacement therapy.

Reference Product type (nicotine concentration) Pharmacokinetic parameters Pharmacodynamic parameters Vital signs



Cmax (ng/mL) Tmax (min) AUC (ng•min/mL) Cravings Urge to smoke Sensory evaluation/satisfaction Heart rate (bpm) Systolic BP (mm Hg) Diastolic BP (mm Hg)
Combustible cigarettes
Digard et al., 2013 (195) Lucky Strike Red (14.6 mg) 12.8 7.20 14.8 N/A N/A N/A N/A N/A N/A
Yan & D’Ruiz, 2015 (345) Marlboro Gold King Size (0.8 mg) 15.84S29.23 N/A N/A N/A N/A N/A 4.26 increase in heart rate 5.74 change in systolic BP 6.78 change in diastolic BP
Ebajemito et al., 2020 (139) Benson & Hedges Sky 14.5 (ad libitum) 5.00 660.0 N/A N/A Increased product satisfaction compared to e-cigarettes Heart rate increased and decreased in similar trends to PK profiles N/A N/A
Blue (7 mg ISO tar) 13.7 (fixed puff) 7.00 631.0
First-generation e-cigarettes (cig-a-like)
Hajek et al., 2017 (346) Vuse (48 mg/mL); 13.6 4.0 244.9 N/A N/A N/A N/A N/A N/A
Gamucci (16 mg/mL); 9.7 6.0 169.9
Blu (18 mg/mL); 9.1 6.0 173.1
Vype (16.8 mg/mL); 8.5 6.0 161.0
E-lites (24 mg/mL); 7.8 6.0 157.6
Puritane (20 mg/mL) 7.5 4.0 144.4
Bullen et al., 2010 (198) Ruyan V8 (16 mg/mL) 1.3 19.6 N/A No difference in withdrawal symptoms between the e-cigarette and inhalator Greater decrease in desire to smoke compared to 0 mg placebo (not significant when adjusted for multiple comparisons) N/A N/A N/A N/A
Vansickel et al., 2010 (347) NJOY NPRO (18 mg/mL); Hydro (16 mg/mL) N/A N/A N/A Some abstinence symptoms suppressed Decrease in urge to smoke compared to sham condition No effect on sensory evaluation No significant change was reported between study products N/A N/A
Nides et al., 2014 (202) NJOY King Bold (26 mg/mL) 3.5–5.1 30 s–30 min 0.67–0.57 Reduction in craving with the highest decrease immediately after product use, followed by steady incremental increases in craving N/A N/A Heart rate increased through the 10-min mark after the beginning first puffs, then gradually declined towards baseline. Mean increases in heart rate 5 and 10 min after the first series of puffs were 2.4 and 5.3 bpm N/A N/A
Yan & D’Ruiz, 2015 (345) Blu (16 mg/mL, two formulations); Blu (24 mg/mL, three formulations) 10–17 N/A N/A N/A N/A N/A 1.87–4.09 bpm increase in heart rate following product use 1.13–3.78change in systolic BP 3.17–6.783change in diastolic BP
Farsalinos et al., 2014 (201) V2 (18 mg/mL) 2.0 (fixed puff) and (ad libitum) N/A N/A Similar levels to craving reduction observed compared to third-generation EC N/A Burning throat sensation was significantly lower compared to third-generation EC N/A N/A N/A
Voos et al., 2019 (348) V2 (11.7 mg/mL) Green smoke (19.4 mg/mL) 4.07 13 88.60 N/A Low ratings on perceived smoking urge relief Low satisfaction and sensory ratings N/A N/A N/A
4.16 10 121.9
Second-generation e-cigarettes
Voos et al., 2019 (348) Mod iTazte (29.9 mg/mL) 6.6 10 272.3 N/A Provided perceived smoking urge relief High satisfactionrating, taste, pleasantness, harshness (“throat hit”), and speed of effect N/A N/A N/A
Hajek et al., 2017 (346) KangerTech EVOD (20 mg/mL) 9.9 6.0 200.6 N/A N/A N/A N/A N/A N/A
Third-generation e-cigarettes
Farsalinos et al., 2014 (201) EVIC device with EVOD cartomizer (18 mg/mL) 4.00 (defined) 21.0 (ad libitum) N/A N/A Similar levels of craving reduction observed compared to first-generation EC N/A Burning throat sensation was significantly higher compared to first-generation EC N/A N/A N/A
Hajek et al., 2017 (346) Innokin (20 mg/mL) 11.9 6 232.1 N/A N/A N/A N/A N/A N/A
Voos et al., 2019 (348) eGO V2 Pro (29.9 mg/mL) 5.52 10 121.9 N/A Provided fastest perceived urge relief compared to first- and second-generation EC High satisfaction rating, taste, pleasantness, harshness (“throat hit”), and speed of effect. N/A N/A N/A
Ebajemito et al., 2020 (139) Vype ePen (18 mg/mL) 4.79 7.0 267.0 N/A N/A Poor satisfaction compared to fourth-generation EC Heart rate increased and decreased in similar trends to PK profiles N/A N/A
Fourth-generation e-cigarettes
O’Connell et al., 2019 (140) myblu 25 mg/mL (free-base) 5.05 8.03 99.99 N/A Higher Cmax was associated with greater relief on urge to smoke Similar sensorial perception was reported across all products N/A N/A N/A
myblu 16 mg/mL (salt); 6.51 6.97 118.5
myblu 25 mg/mL (salt); 7.58 6.03 125.2
myblu 40 mg/mL (salt); 10.27 7.90 190.7
blu PRO 48 mg/mL (salt) 4.85 6.91 84.84
Ebajemito et al., 2020 (139) Vype ePen3 18 mg/mL (freebase; ad lib); 6.38 7.0 325 N/A N/A Higher Cmax was linked to increased satisfaction, except for the 30-mg/mL product Heart rate increased and decreased in similar trends to pharmaco-kinetic profiles N/A N/A
Vype ePen3 18 mg/mL (med salt; ad lib); 10.8 5.0 429
Vype ePen3 30 mg/mL (high salt; ad lib); 14.1 5.0 533
Vype ePen3 18 mg/mL (med salt; fixed puff); 5.64 5.0 326
Vype ePen3 12 mg/mL (low salt; ad lib) 5.97 7.0 284
Nicotine-replacement therapy
Digard et al., 2013 (195) Nicotine gum (4.2 mg) 9.10 45.0 13.1* N/A N/A All products had little effect on the sensory parameter assessed N/A N/A N/A
Lunell & Curvall, 2011 (349) Nicotine Polarilex gum (4 mg) 12.8 N/A 3190 Craving decreased similarly to snus Urges to smoke decreased similarly with snus Salivation and throat burn were rated higher for the 4 mg gum vs snus Mean 20 min increase of heart rate 9.3 (± 9.6), 8.9 (± 6.4), and 9.9 (± 5.1) bpm for 9.9 mg snus, 8.7 mg snus, and nicotine gum, respectively N/A N/A
Dautzenberg et al., 2007 (350) 1 mg Nicotinell lozenges 2.30 66.0 8.30 * N/A N/A N/A N/A N/A N/A
2 mg Nicotinell lozenges 4.80 48.0 15.8 *
2 mg Nicorette gum 2.90 48.0 10.6 *
Choi et al., 2003 (351) 4 mg nicotine lozenges 10.8 66.0 44.0 * N/A N/A N/A N/A N/A N/A
4 mg nicotine gum 10.0 54.0 34.6 *
Hansson et al., 2017 (199) 6 mg nicotine gum 13.8 30.0 46.2 * N/A N/A N/A N/A N/A N/A
4 mg nicotine gum 10.1 30.0 30.2 *
2 mg nicotine gum 5.90 30.0 17.1 *
4 mg nicotine lozenge 9.30 45.0 35.3 *
Kraiczi et al., 2011 (352) 1 mg nicotine mouth spray 3.30 10.0 6.60 N/A N/A N/A N/A N/A N/A
2 mg nicotine mouth spray 5.30 12.5 12.2
4 mg nicotine mouth spray 9.10 10.0 23.7
4 mg nicotine lozenge 7.00 45.0 24.3
4 mg nicotine gum 7.80 30.0 21.1
Sukhija et al., 2018 (200) 4 mg lozenges prototype I 18.18 66.0 87.13 * N/A N/A N/A N/A N/A N/A
4 mg lozenges prototype II 18.11 66.0 85.69 *
4 mg lozenges prototype III (I, II, III had different dissolutions) 17.11 66.0 84.59 *
4 mg Nicorette lozenges 18.67 66.0 90.03 *
Molander & Lunell, 2001 (353) 2 mg nicotine sublingual tablet 13.2 20 12.4 * N/A N/A N/A N/A N/A N/A
2 mg Nicorette gum 14.4 20 13.5
Lunell et al., 2020 (354) 4 mg Nicorette gum 12.8 46.0 52.1 N/A N/A N/A N/A N/A N/A
Bullen et al. (198) Nicorette inhalator (10 mg) 2.10 32.0 N/A No significant decrease in craving compared to placebo or first-generation EC No significant decrease in craving compared to placebo or first-generation EC N/A N/A N/A N/A
Goldenson et al. (355) Fixed puff N/A N/A 59 mg/mL silica wick provided highest level of satisfaction followed by 18 mg/mL silica wick, 18 mg/mL coil wick and 9 mg/mL coil wick N/A N/A N/A
JUUL 59 mg/mL with silica wick 9.3 6.2 5.0 *
JUUL 18 mg/mL with silica wick 3.2 6.3 1.7 *
JUUL 18 mg/mL with cotton wick 3.3 5.8 1.8 *
JUUL 9 mg/mL with cotton wick 2.1 6.6 1.2 *
Ad libitum puff
JUUL 59 mg/mL with silica wick 8.3 6.4 4.6 *
JUUL 18 mg/mL with silica wick 3.5 6.5 1.8 *
JUUL 18 mg/mL with cotton wick 3.3 7.1 2.1 *
JUUL 9 mg/mL with cotton wick 2.3 6.7 1.2 *

Mouthpiece-based ad libitum topography measurement of various electronic cigarette types.

Reference Electronic cigarette type Mode of activation Topography device Mean (± SD) puff characteristics


No. of pieces Components Rechargeable device Refillable cartridge Description No. of puffs per session Puff volume (mL) Puff duration (s) Puff interval (s)
Behar et al., 2015 (359) 1 All-in-one No No Blu Puff actuated CReSSmicro 33 (± 8) 56 (± 22) 2.75 (± 0.96) 16.9 (± 8.2)
Cunningham et al., 2016 (320) 1 All-in-one Yes No Cig-a-like Puff actuated Modified SA7 21.1 (± 14.9) 52.2 (± 21.6) 2.0 (± 0.7) 23.2 (± 10.6)
Norton et al., 2014 (360) 2 Battery & cartomizer Yes No Cig-a-like Puff actuated CReSSmicro 8.7 (± 1.6) 118.2 (± 13.3) 3.0 (± 1.6) 29.6 (± 11.7)
Lee et al., 2015 (361) 2 Battery & cartomizer Yes No Cig-a-like Puff actuated CReSSmicro 21.3 (± 2.4) 63.3 (± 23.4) 2.9 (± 0.9) 22.1 (± 22.0)
Behar et al., 2015 (359) 2 Battery & cartomizer Yes No V2 Puff actuated CReSSmicro 31 (± 8) 45 (± 22) 2.54 (± 1.04) 18.9 (± 7.3)
Cunningham et al., 2016 (320) 2 Battery & cartomizer Yes No Vype ePen Button activated Modified SA7 16.1 (± 8.0) 83.0 (± 44.3) 2.2 (± 0.9) 29.3 (± 19.2)
Jones et al., 2020 (322) 2 Battery & cartomizer Yes No IS1.0(T) Button activated Modified SA7 63.6 (± 36.2) 41.2 (± 17.0) 1.5 (± 0.6) 23.3 (± 17.3)

Connected e-cigarette-based ad libitum topography measurement of various e-cigarette types.

Reference Electronic cigarette type Mode of activation Topography device Mean (± SD) puff characteristics


No. of pieces Components Rechargeable device Refillable cartridge Description No. of puffs per session Puff volume (mL) Puff duration (s) Puff interval (s)
Robinson et al., 2015 (362) 2 Battery & cartomizer Yes No Closed Puff actuated Wireless personal use monitor 225 ± 59 133 ± 90 3.5 ± 1.8 42.7 ± 12.1
Robinson et al., 2016 (363) 2 Battery & cartomizer Yes No Closed Puff actuated Wireless personal use monitor 78 ± 162 65.4 ± 24.8 2.0 ± 0.6 NR
Dawkins et al., 2016 (364) 3 Battery, cartridge & atomizer Yes Yes Mod Puff actuated Connected e-cigarette 70.7 ± 34.4per session NR 5.2 ± 1.4 NR
Farsalinos et al., 2018 (344) 3 Battery, cartridge & atomizer Yes Yes Mod Puff actuated Connected e-cigarette 57 ± 14.9per session NR 4.6 ± 1.0 NR
Lee et al., 2018 (365) 2 Battery & cartomizer Yes No Closed Puff actuated Wireless personal use monitor 13.7per session 110.3 13.7 38.1

U.S. Department of Health and Human Services (HHS): Smoking Cessation: A Report of the Surgeon General; 2020. Available at: https://www.hhs.gov/sites/default/files/2020-cessation-sgr-full-report.pdf (accessed July 6, 2020) U.S. Department of Health and Human Services (HHS) Smoking Cessation: A Report of the Surgeon General 2020 Available at: https://www.hhs.gov/sites/default/files/2020-cessation-sgr-full-report.pdf (accessed July 6, 2020) Search in Google Scholar

World Health Organization (WHO): Tobacco: Health Benefits of Smoking Cessation; 2020. Available at: https://www.who.int/tobacco/quitting/benefits/en/ (accessed April 29, 2020) World Health Organization (WHO) Tobacco: Health Benefits of Smoking Cessation 2020 Available at: https://www.who.int/tobacco/quitting/benefits/en/ (accessed April 29, 2020) Search in Google Scholar

Baker, R.R. and L.J. Bishop: The Pyrolysis of Tobacco Ingredients; J. Anal. Appl. Pyrolysis 71 (2004) 223–311. DOI: 10.1016/j.jaap.2004.10.01 BakerR.R. BishopL.J. The Pyrolysis of Tobacco Ingredients J. Anal. Appl. Pyrolysis 71 2004 223 311 10.1016/j.jaap.2004.10.01 Open DOISearch in Google Scholar

Gottlieb, S. and M. Zeller: A Nicotine-Focused Framework for Public Health; N. Engl. J. Med. 377 (2017) 1111–1114. DOI: 10.1056/NEJMp1707409 GottliebS. ZellerM. A Nicotine-Focused Framework for Public Health N. Engl. J. Med. 377 2017 1111 1114 10.1056/NEJMp1707409 Open DOISearch in Google Scholar

Rodgman, A. and T.A. Perfetti: The Chemical Components of Tobacco and Tobacco Smoke; CRC Press, Boca Raton, FL, USA, 2013. RodgmanA. PerfettiT.A. The Chemical Components of Tobacco and Tobacco Smoke CRC Press Boca Raton, FL, USA 2013 Search in Google Scholar

Fowles, J. and E. Dybing: Application of Toxicological Risk Assessment Principles to the Chemical Constituents of Cigarette Smoke; Tob. Control 12 (2003) 424–430. DOI: 10.1136/tc.12.4.424 FowlesJ. DybingE. Application of Toxicological Risk Assessment Principles to the Chemical Constituents of Cigarette Smoke Tob. Control 12 2003 424 430 10.1136/tc.12.4.424 Open DOISearch in Google Scholar

Fagerström, K.: The Epidemiology of Smoking: Health Consequences and Benefits of Cessation; Drugs 62, Suppl. 2 (2002) 1–9. DOI: 10.2165/00003495-200262002-00001 FagerströmK. The Epidemiology of Smoking: Health Consequences and Benefits of Cessatio Drugs 62 Suppl. 2 2002 1 9 10.2165/00003495-200262002-00001 Open DOISearch in Google Scholar

World Health Organization (WHO): Partial Guidelines for Implementation of Articles 9 and 10 of the WHO Framework Convention on Tobacco Control. Regulation of the Contents of Tobacco Products and of Tobacco Product Disclosures; 2010. Available at: https://www.who.int/fctc/guidelines/Guideliness_Articles_9_10_rev_240613.pdf#:~:text=The%20purpose%20of%20the%20guidelines%20is%20to%20assist,evidence%20and%20the%20experience%20of%20Parties%2C%20propose%20measures (accessed September 7, 2020) World Health Organization (WHO) Partial Guidelines for Implementation of Articles 9 and 10 of the WHO Framework Convention on Tobacco Control Regulation of the Contents of Tobacco Products and of Tobacco Product Disclosures 2010 Available at: https://www.who.int/fctc/guidelines/Guideliness_Articles_9_10_rev_240613.pdf#:~:text=The%20purpose%20of%20the%20guidelines%20is%20to%20assist,evidence%20and%20the%20experience%20of%20Parties%2C%20propose%20measures (accessed September 7, 2020) Search in Google Scholar

World Health Organization Framework Convention on Tobacco Control (FCTC): Conference of the Parties to the WHO Framework Convention on Tobacco Control. Sixth Session; Moscow, Russian Federation, 13–18 October, 2014. Available at: https://apps.who.int/gb/fctc/PDF/cop6/FCTC_COP6(9)-en.pdf?ua=1 (accessed April 29, 2020) World Health Organization Framework Convention on Tobacco Control (FCTC) Conference of the Parties to the WHO Framework Convention on Tobacco Control. Sixth Session Moscow Russian Federation 13–18 October 2014 Available at: https://apps.who.int/gb/fctc/PDF/cop6/FCTC_COP6(9)-en.pdf?ua=1 (accessed April 29, 2020) Search in Google Scholar

Bates, C.: Tobacco Harm Reduction – A Note to WHO's Expert Committee; 2013. Available at: https://www.clivebates.com/tobacco-harm-reduction-a-note-to-whos-expert-commitee (accessed September 7, 2020) BatesC. Tobacco Harm Reduction – A Note to WHO's Expert Committee 2013 Available at: https://www.clivebates.com/tobacco-harm-reduction-a-note-to-whos-expert-commitee (accessed September 7, 2020) Search in Google Scholar

Stratton, K., P. Shetty, R. Wallace, and S. Bondurant: Clearing the Smoke: The Science Base for Tobacco Harm Reduction—Executive Summary; Tob. Control 10 (2001) 189–195. DOI: 10.1136/tc.10.2.189 StrattonK. ShettyP. WallaceR. BondurantS. Clearing the Smoke: The Science Base for Tobacco Harm Reduction—Executive Summary Tob. Control 10 2001 189 195 10.1136/tc.10.2.189 Open DOISearch in Google Scholar

Rodu, B. and W.T. Godshall: Tobacco Harm Reduction: An Alternative Cessation Strategy for Inveterate Smokers; Harm Reduct. J. 3 (2006) 37. DOI: 10.1186/1477-7517-3-37 RoduB. GodshallW.T. Tobacco Harm Reduction: An Alternative Cessation Strategy for Inveterate Smokers Harm Reduct. J. 3 2006 37 10.1186/1477-7517-3-37 Open DOISearch in Google Scholar

Institute of Medicine: Scientific Standards for Studies on Modified Risk Tobacco Products; The National Academies Press, Washington, DC, USA, 2012. DOI: 10.17226/13294 Institute of Medicine Scientific Standards for Studies on Modified Risk Tobacco Products The National Academies Press Washington, DC, USA 2012 10.17226/13294 Open DOISearch in Google Scholar

European Commission: Special Eurobarometer 506. Attitudes of Europeans Towards Tobacco and Electronic Cigarettes; 2021. Available at https://ec.europa.eu/commfrontoffice/publicopinion/index.cfm/survey/getsurveydetail/instruments/special/surveyky/2240 (accessed April 11, 2021) European Commission Special Eurobarometer 506. Attitudes of Europeans Towards Tobacco and Electronic Cigarettes 2021 Available at https://ec.europa.eu/commfrontoffice/publicopinion/index.cfm/survey/getsurveydetail/instruments/special/surveyky/2240 (accessed April 11, 2021) Search in Google Scholar

Clarke, E., K. Thompson, S. Weaver, J. Thompson, and G. O’Connell: Snus: A Compelling Harm Reduction Alternative to Cigarettes; Harm Reduct. J. 16 (2019) 62. DOI: 10.1186/s12954-019-0335-1 ClarkeE. ThompsonK. WeaverS. ThompsonJ. O’ConnellG. Snus: A Compelling Harm Reduction Alternative to Cigarettes Harm Reduct. J. 16 2019 62 10.1186/s12954-019-0335-1 Open DOISearch in Google Scholar

Ferlay, J., M. Ervik, F. Lam, M. Colombet, L. Mery, M. Piñeros, A. Znaor, I. Soerjomataram, and F. Bray: Cancer Today (Powered by GLOBCAN 2018). Available at: https://publications.iarc.fr/Databases/Iarc-Cancerbases/Cancer-Today-Powered-By-GLOBOCAN-2018--2018 (accessed September 7, 2020) FerlayJ. ErvikM. LamF. ColombetM. MeryL. PiñerosM. ZnaorA. SoerjomataramI. BrayF. Cancer Today (Powered by GLOBCAN 2018) Available at: https://publications.iarc.fr/Databases/Iarc-Cancerbases/Cancer-Today-Powered-By-GLOBOCAN-2018--2018 (accessed September 7, 2020) Search in Google Scholar

U.S. Food and Drug Administration (FDA): FDA Grants First-Ever Modified Risk Orders to Eight Smokeless Tobacco Products; FDA News relase, October 22, 2019. Available at: https://www.fda.gov/news-events/press-announcements/fda-grants-first-ever-modified-risk-orders-eight-smokeless-tobacco-products (accessed January 25, 2021) U.S. Food and Drug Administration (FDA) FDA Grants First-Ever Modified Risk Orders to Eight Smokeless Tobacco Products FDA News relase October 22 2019 Available at: https://www.fda.gov/news-events/press-announcements/fda-grants-first-ever-modified-risk-orders-eight-smokeless-tobacco-products (accessed January 25, 2021) Search in Google Scholar

U.S. Food and Drug Administration (FDA): FDA Authorizes Modified Risk Tobacco Products; 2019. Available at: https://www.fda.gov/tobacco-products/advertising-and-promotion/fda-authorizes-modified-risk-tobacco-products (accessed January 25, 2021) U.S. Food and Drug Administration (FDA) FDA Authorizes Modified Risk Tobacco Products 2019 Available at: https://www.fda.gov/tobacco-products/advertising-and-promotion/fda-authorizes-modified-risk-tobacco-products (accessed January 25, 2021) Search in Google Scholar

Marco, E. and J.O. Grimalt: A Rapid Method for the Chromatographic Analysis of Volatile Organic Compounds in Exhaled Breath of Tobacco Cigarette and Electronic Cigarette Smokers; J. Chromatogr. A 1410 (2015) 51–59. DOI: 10.1016/j.chroma.2015.07.094 MarcoE. GrimaltJ.O. A Rapid Method for the Chromatographic Analysis of Volatile Organic Compounds in Exhaled Breath of Tobacco Cigarette and Electronic Cigarette Smokers J. Chromatogr. A 1410 2015 51 59 10.1016/j.chroma.2015.07.094 Open DOISearch in Google Scholar

Margham, J., K. McAdam, M. Forster, C. Liu, C. Wright, D. Mariner, and C. Proctor: Chemical Composition of Aerosol from an E-Cigarette: A Quantitative Comparison with Cigarette Smoke; Chem. Res. Toxicol. 29 (2016) 1662–1678. DOI: 10.1021/acs.chemrestox.6b00188 MarghamJ. McAdamK. ForsterM. LiuC. WrightC. MarinerD. ProctorC. Chemical Composition of Aerosol from an E-Cigarette: A Quantitative Comparison with Cigarette Smoke Chem. Res. Toxicol. 29 2016 1662 1678 10.1021/acs.chemrestox.6b00188 Open DOISearch in Google Scholar

Nicol, J., R. Fraser, L. Walker, C. Liu, J. Murphy, and C.J. Proctor: Comprehensive Chemical Characterization of the Aerosol Emissions of a Vaping Product Based on a New Technology; Chem. Res. Toxicol. 33 (2020) 789–799. DOI: 10.1021/acs.chemrestox.9b00442 NicolJ. FraserR. WalkerL. LiuC. MurphyJ. ProctorC.J. Comprehensive Chemical Characterization of the Aerosol Emissions of a Vaping Product Based on a New Technology Chem. Res. Toxicol. 33 2020 789 799 10.1021/acs.chemrestox.9b00442 Open DOISearch in Google Scholar

Cunningham, A., K. McAdam, J. Thissen, and H. Digard: The Evolving E-cigarette: Comparative Chemical Analyses of E-Cigarette Vapor and Cigarette Smoke; Front. Toxicol. 2 (2020) 586674. DOI: 10.3389/ftox.2020.586674 CunninghamA. McAdamK. ThissenJ. DigardH. The Evolving E-cigarette: Comparative Chemical Analyses of E-Cigarette Vapor and Cigarette Smoke Front. Toxicol. 2 2020 586674 10.3389/ftox.2020.586674 Open DOISearch in Google Scholar

Hartmann-Boyce, J., H. McRobbie, N. Lindson, C. Bullen, R. Begh, A. Theodoulou, C. Notley, N.A. Rigotti, T. Turner, A.R. Butler, T.R. Fanshawe, and P. Hajek: Electronic Cigarettes for Smoking Cessation; Cochrane Database Syst. Rev. 10 (2020) CD010216. DOI: 10.1002/14651858.CD010216.pub4 Hartmann-BoyceJ. McRobbieH. LindsonN. BullenC. BeghR. TheodoulouA. NotleyC. RigottiN.A. TurnerT. ButlerA.R. FanshaweT.R. HajekP. Electronic Cigarettes for Smoking Cessation Cochrane Database Syst. Rev. 10 2020 CD010216 10.1002/14651858.CD010216.pub4 Open DOISearch in Google Scholar

McNeill, A., L.S. Brose, R. Calder, S.C. Hitchman, P. Hajek, and H. McRobbie: E-Cigarettes: An Evidence Update. A Report Commissioned by Public Health England; 2015. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/733022/Ecigarettes_an_evidence_update_A_report_commissioned_by_Public_Health_England_FINAL.pdf (accessed April 15, 2021) McNeillA. BroseL.S. CalderR. HitchmanS.C. HajekP. McRobbieH. E-Cigarettes: An Evidence Update. A Report Commissioned by Public Health England 2015 Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/733022/Ecigarettes_an_evidence_update_A_report_commissioned_by_Public_Health_England_FINAL.pdf (accessed April 15, 2021) Search in Google Scholar

McNeill, A., L.S. Brose, R. Calder, L. Bauld, and D. Robson: Vaping in England: An Evidence Update. A Report Commissioned by Public Health England; 2019. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/821179/Vaping_in_England_an_evidence_update_February_2019.pdf (accessed April 15, 2021) McNeillA. BroseL.S. CalderR. BauldL. RobsonD. Vaping in England: An Evidence Update. A Report Commissioned by Public Health England 2019 Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/821179/Vaping_in_England_an_evidence_update_February_2019.pdf (accessed April 15, 2021) Search in Google Scholar

McNeill, A., L.S. Brose, R. Calder, L. Bauld, and D. Robson: Vaping in England: An Evidence Update Including Mental Health and Pregnancy. A Report Commissioned by Public Health England; 2020. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/869401/Vaping_in_England_evidence_update_March_2020.pdf (accessed April 15, 2021) McNeillA. BroseL.S. CalderR. BauldL. RobsonD. Vaping in England: An Evidence Update Including Mental Health and Pregnancy. A Report Commissioned by Public Health England 2020 Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/869401/Vaping_in_England_evidence_update_March_2020.pdf (accessed April 15, 2021) Search in Google Scholar

McRobbie, H., C. Bullen, J. Hartmann-Boyce, and P. Hajek: Electronic Cigarettes for Smoking Cessation and Reduction; Cochrane Database Syst. Rev. 12 (2014) CD010216. DOI: 10.1002/14651858.CD010216.pub2 McRobbieH. BullenC. Hartmann-BoyceJ. HajekP. Electronic Cigarettes for Smoking Cessation and Reduction Cochrane Database Syst. Rev. 12 2014 CD010216 10.1002/14651858.CD010216.pub2 Open DOISearch in Google Scholar

National Academies of Sciences Engineering and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems: Public Health Consequences of E-Cigarettes; edited by D.L. Eaton, L.Y. Kwan and K. Stratton, National Academies Press, Washington, DC, USA, 2018. DOI: 10.17226/24952 National Academies of Sciences Engineering and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems Public Health Consequences of E-Cigarettes edited by EatonD.L. KwanL.Y. StrattonK. National Academies Press Washington, DC, USA 2018 10.17226/24952 Open DOISearch in Google Scholar

McNeill, A., L.S. Brose, R. Calder, L. Bauld, and D. Robson: Evidence Review of E-Cigarettes and Heated Tobacco Products 2018. A Report Commissioned by Public Health England; 2018. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/684963/Evidence_review_of_e-cigarettes_and_heated_tobacco_products_2018.pdf (accessed April 15, 2021) McNeillA. BroseL.S. CalderR. BauldL. RobsonD. Evidence Review of E-Cigarettes and Heated Tobacco Products 2018. A Report Commissioned by Public Health England 2018 Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/684963/Evidence_review_of_e-cigarettes_and_heated_tobacco_products_2018.pdf (accessed April 15, 2021) Search in Google Scholar

Government of Canada: Tobacco and Vaping Products Act (TVPA); 2018. Available at: https://www.canada.ca/en/health-canada/services/health-concerns/tobacco/legislation/federal-laws/tobacco-act.html (accessed January 25, 2021) Government of Canada Tobacco and Vaping Products Act (TVPA) 2018 Available at: https://www.canada.ca/en/health-canada/services/health-concerns/tobacco/legislation/federal-laws/tobacco-act.html (accessed January 25, 2021) Search in Google Scholar

New Zealand Ministry of Health: Vaping Facts; 2019. Available at: https://vapingfacts.health.nz (accessed August 13, 2020) New Zealand Ministry of Health Vaping Facts 2019 Available at: https://vapingfacts.health.nz (accessed August 13, 2020) Search in Google Scholar

Girvalaki, C., A. Vardavas, M. Tzatzarakis, C.N. Kyriakos, K. Nikitara, A.M. Tsatsakis, and C.I. Vardavas: Compliance of E-Cigarette Refill Liquids with Regulations on Labelling, Packaging and Technical Design Characteristics in Nine European Member States; Tob. Control 29 (2020) 531–536. DOI: 10.1136/tobaccocontrol-2019-055061 GirvalakiC. VardavasA. TzatzarakisM. KyriakosC.N. NikitaraK. TsatsakisA.M. VardavasC.I. Compliance of E-Cigarette Refill Liquids with Regulations on Labelling, Packaging and Technical Design Characteristics in Nine European Member States Tob. Control 29 2020 531 536 10.1136/tobaccocontrol-2019-055061 Open DOISearch in Google Scholar

Seitz, C.M. and Z. Kabir: Burn Injuries Caused by E-Cigarette Explosions: A Systematic Review of Published Cases; Tob. Prev. Cessat. 4 (2018) 32. DOI: 10.18332/tpc/94664 SeitzC.M. KabirZ. Burn Injuries Caused by E-Cigarette Explosions: A Systematic Review of Published Cases Tob. Prev. Cessat. 4 2018 32 10.18332/tpc/94664 Open DOISearch in Google Scholar

Blount, B.C., M.P. Karwowski, P.G. Shields, M. Morel-Espinosa, L. Valentin-Blasini, M. Gardner, M. Braselton, C.R. Brosius, K.T. Caron, D. Chambers, J. Corstvet, E. Cowan, V.R. De Jesús, P. Espinosa, C. Fernandez, C. Holder, Z. Kuklenyik, J.D. Kusovschi, C. Newman, G.B. Reis, J. Rees, C. Reese, L. Silva, T. Seyler, M.A. Song, C. Sosnoff, C.R. Spitzer, D. Tevis, L. Wang, C. Watson, M.D. Wewers, B. Xia, D.T. Heitkemper, I. Ghinai, J. Layden, P. Briss, B.A. King, L.J. Delaney, C.M. Jones, G.T. Baldwin, A. Patel, D. Meaney-Delman, D. Rose, V. Krishnasamy, J.R. Barr, J. Thomas, and J.L. Pirkle: Lung Injury Response Laboratory Working Group: Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI; N. Engl. J. Med. 382 (2020) 697–705. DOI: 10.1056/NEJMoa1916433 BlountB.C. KarwowskiM.P. ShieldsP.G. Morel-EspinosaM. Valentin-BlasiniL. GardnerM. BraseltonM. BrosiusC.R. CaronK.T. ChambersD. CorstvetJ. CowanE. De JesúsV.R. EspinosaP. FernandezC. HolderC. KuklenyikZ. KusovschiJ.D. NewmanC. ReisG.B. ReesJ. ReeseC. SilvaL. SeylerT. SongM.A. SosnoffC. SpitzerC.R. TevisD. WangL. WatsonC. WewersM.D. XiaB. HeitkemperD.T. GhinaiI. LaydenJ. BrissP. KingB.A. DelaneyL.J. JonesC.M. BaldwinG.T. PatelA. Meaney-DelmanD. RoseD. KrishnasamyV. BarrJ.R. ThomasJ. PirkleJ.L. Lung Injury Response Laboratory Working Group: Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI N. Engl. J. Med. 382 2020 697 705 10.1056/NEJMoa1916433 Open DOISearch in Google Scholar

Centers for Disease Control and Prevention (CDC): Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products; 2020. Available at: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html (accessed September 7, 2020) Centers for Disease Control and Prevention (CDC) Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products 2020 Available at: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html (accessed September 7, 2020) Search in Google Scholar

Williams, M. and P. Talbot: Design Features in Multiple Generations of Electronic Cigarette Atomizers; Int. J. Environ. Res. Public Health 16 (2019) 2904. DOI: 10.3390/ijerph16162904 WilliamsM. TalbotP. Design Features in Multiple Generations of Electronic Cigarette Atomizers Int. J. Environ. Res. Public Health 16 2019 2904 10.3390/ijerph16162904 Open DOISearch in Google Scholar

Cahours, X. and K. Prasad: A Review of Electronic Cigarette Use Behaviour Studies; Beitr. Tabakforsch. Int. 28 (2018) 81–92. DOI: 10.2478/cttr-2018-0009 CahoursX. PrasadK. A Review of Electronic Cigarette Use Behaviour Studies Beitr. Tabakforsch. Int. 28 2018 81 92 10.2478/cttr-2018-0009 Open DOISearch in Google Scholar

Action on Smoking and Health (ASH): ASH Fact Sheet: Use of Electronic Cigarettes (Vapourisers) Among Adults in Great Britain; 2017. Available at: https://www.zougla.gr/file.ashx?fid=2207534 (accessed April 29, 2020) Action on Smoking and Health (ASH) ASH Fact Sheet: Use of Electronic Cigarettes (Vapourisers) Among Adults in Great Britain 2017 Available at: https://www.zougla.gr/file.ashx?fid=2207534 (accessed April 29, 2020) Search in Google Scholar

Wadsworth, E., J. Neale, A. McNeill, and S.C. Hitchman: How and Why Do Smokers Start Using E-Cigarettes? Qualitative Study of Vapers in London, UK; Int. J. Environ. Res. Public Health 13 (2016) 661–674. DOI: 10.3390/ijerph13070661 WadsworthE. NealeJ. McNeillA. HitchmanS.C. How and Why Do Smokers Start Using E-Cigarettes? Qualitative Study of Vapers in London, UK Int. J. Environ. Res. Public Health 13 2016 661 674 10.3390/ijerph13070661 Open DOISearch in Google Scholar

Weaver, S.R., J.W. Health, D.L Ashley, J. Huang, T.F. Pechacek, and M.P. Erikson: What are the Reasons that Smokers Reject ENDS? A National Probability Survey of U.S. Adult Smokers, 2017–2018; Drug Alcohol Depend. 211 (2020) 107855. DOI: 10.1016/j.drugalcdep.2020.107855 WeaverS.R. HealthJ.W. AshleyD.L HuangJ. PechacekT.F. EriksonM.P. What are the Reasons that Smokers Reject ENDS? A National Probability Survey of U.S. Adult Smokers, 2017–2018 Drug Alcohol Depend. 211 2020 107855 10.1016/j.drugalcdep.2020.107855 Open DOISearch in Google Scholar

Beauval, N., M. Verrièle, A. Garat, I. Fronval, R. Dusautoir, S. Anthérieu, G. Garçon, J.M. Lo-Guidice, D. Allorge, and N. Locoge: Influence of Puffing Conditions on the Carbonyl Composition of E-Cigarette Aerosols; Int. J. Hyg. Environ. Health 222 (2019) 136–146. DOI: 10.1016/j.ijheh.2018.08.015 BeauvalN. VerrièleM. GaratA. FronvalI. DusautoirR. AnthérieuS. GarçonG. Lo-GuidiceJ.M. AllorgeD. LocogeN. Influence of Puffing Conditions on the Carbonyl Composition of E-Cigarette Aerosols Int. J. Hyg. Environ. Health 222 2019 136 146 10.1016/j.ijheh.2018.08.015 Open DOISearch in Google Scholar

Farsalinos, K.E. and G. Gillman: Carbonyl Emissions in E-Cigarette Aerosol: A Systematic Review and Methodological Considerations; Front. Physiol. 8 (2018) 1119. DOI: 10.3389/fphys.2017.01119 FarsalinosK.E. GillmanG. Carbonyl Emissions in E-Cigarette Aerosol: A Systematic Review and Methodological Considerations Front. Physiol. 8 2018 1119 10.3389/fphys.2017.01119 Open DOISearch in Google Scholar

Flora, J.W., N. Meruva, C.B. Huang, C.T. Wilkinson, R. Ballentine, D.C. Smith, M.S. Werley, and W.J. McKinney: Characterization of Potential Impurities and Degradation Products in Electronic Cigarette Formulations and Aerosols; Regul. Toxicol. Pharmacol. 74 (2016) 1–11. DOI: 10.1016/j.yrtph.2015.11.009 FloraJ.W. MeruvaN. HuangC.B. WilkinsonC.T. BallentineR. SmithD.C. WerleyM.S. McKinneyW.J. Characterization of Potential Impurities and Degradation Products in Electronic Cigarette Formulations and Aerosols Regul. Toxicol. Pharmacol. 74 2016 1 11 10.1016/j.yrtph.2015.11.009 Open DOISearch in Google Scholar

Goniewicz, M.L., J. Knysak, M. Gawron, L. Kosmider, A. Sobczak, J. Kurek, A. Prokopowicz, M. Jablonska-Czapla, C. Rosik-Dulewska, C. Havel, P. Jacob III, and N. Benowitz: Levels of Selected Carcinogens and Toxicants in Vapour from Electronic Cigarettes; Tob. Control 23 (2014) 133–139. DOI: 10.1136/tobaccocontrol-2012-050859 GoniewiczM.L. KnysakJ. GawronM. KosmiderL. SobczakA. KurekJ. ProkopowiczA. Jablonska-CzaplaM. Rosik-DulewskaC. HavelC. JacobP.III BenowitzN. Levels of Selected Carcinogens and Toxicants in Vapour from Electronic Cigarettes Tob. Control 23 2014 133 139 10.1136/tobaccocontrol-2012-050859 Open DOISearch in Google Scholar

Jensen, R.P., R.M. Strongin, and D.H. Peyton: Solvent Chemistry in the Electronic Cigarette Reaction Vessel; Sci. Rep. 7 (2017) 42549. DOI: 10.1038/srep42549 JensenR.P. StronginR.M. PeytonD.H. Solvent Chemistry in the Electronic Cigarette Reaction Vessel Sci. Rep. 7 2017 42549 10.1038/srep42549 Open DOISearch in Google Scholar

Ogunwale, M.A., M. Li, M.V. Ramakrishnam Raju, Y. Chen, M.H. Nantz, D.J. Conklin, and X.A. Fu: Aldehyde Detection in Electronic Cigarette Aerosols; ACS Omega 2 (2017) 1207–1214. DOI: 10.1021/acsomega.6b00489 OgunwaleM.A. LiM. Ramakrishnam RajuM.V. ChenY. NantzM.H. ConklinD.J. FuX.A. Aldehyde Detection in Electronic Cigarette Aerosols ACS Omega 2 2017 1207 1214 10.1021/acsomega.6b00489 Open DOISearch in Google Scholar

Stephens, W.E.: Comparing the Cancer Potencies of Emissions from Vapourised Nicotine Products Including E-Cigarettes with Those of Tobacco Smoke; Tob. Control 27 (2018) 10–17. DOI: 10.1136/tobaccocontrol-2017-053808 StephensW.E. Comparing the Cancer Potencies of Emissions from Vapourised Nicotine Products Including E-Cigarettes with Those of Tobacco Smoke Tob. Control 27 2018 10 17 10.1136/tobaccocontrol-2017-053808 Open DOISearch in Google Scholar

Farsalinos, K.E., G. Romagna, D. Tsiapras, S. Kyrzopoulos, and V. Voudris: Evaluation of Electronic Cigarette Use (Vaping) Topography and Estimation of Liquid Consumption: Implications for Research Protocol Standards Definition and for Public Health Authorities’ Regulation; Int. J. Environ. Res. Public Health 10 (2013) 2500–2514. DOI: 10.3390/ijerph10062500 FarsalinosK.E. RomagnaG. TsiaprasD. KyrzopoulosS. VoudrisV. Evaluation of Electronic Cigarette Use (Vaping) Topography and Estimation of Liquid Consumption: Implications for Research Protocol Standards Definition and for Public Health Authorities’ Regulation Int. J. Environ. Res. Public Health 10 2013 2500 2514 10.3390/ijerph10062500 Open DOISearch in Google Scholar

Kim, H., J. Lim, S.S. Buehler, M.C. Brinkman, N.M. Johnson, L. Wilson, K.S. Cross, and P.I. Clark: Role of Sweet and Other Flavours in Liking and Disliking of Electronic Cigarettes; Tob. Control 25 (2016) ii55–ii61. DOI: 10.1136/tobaccocontrol-2016-053221 KimH. LimJ. BuehlerS.S. BrinkmanM.C. JohnsonN.M. WilsonL. CrossK.S. ClarkP.I. Role of Sweet and Other Flavours in Liking and Disliking of Electronic Cigarettes Tob. Control 25 2016 ii55 ii61 10.1136/tobaccocontrol-2016-053221 Open DOISearch in Google Scholar

Laverty, A.A., C.I. Vardavas, and F.T. Filippidis: Design and Marketing Features Influencing Choice of E-Cigarettes and Tobacco in the EU; Eur. J. Public Health 26 (2016) 838–841. DOI: 10.1093/eurpub/ckw109 LavertyA.A. VardavasC.I. FilippidisF.T. Design and Marketing Features Influencing Choice of E-Cigarettes and Tobacco in the EU Eur. J. Public Health 26 2016 838 841 10.1093/eurpub/ckw109 Open DOISearch in Google Scholar

Pullicin, A.J., H. Kim, M.C. Brinkman, S.S. Buehler, P.I. Clark, and J. Lim: Impacts of Nicotine and Flavoring on the Sensory Perception of E-cigarette Aerosol; Nicotine Tob. Res. 22 (2020) 806–813. DOI: 10.1093/ntr/ntz058 PullicinA.J. KimH. BrinkmanM.C. BuehlerS.S. ClarkP.I. LimJ. Impacts of Nicotine and Flavoring on the Sensory Perception of E-cigarette Aerosol Nicotine Tob. Res. 22 2020 806 813 10.1093/ntr/ntz058 Open DOISearch in Google Scholar

Zare, S., M. Nemati, and Y. Zheng: A Systematic Review of Consumer Preference for E-Cigarette Attributes: Flavor, Nicotine Strength, and Type; PLoS One 13 (2018) e0194145. DOI: 10.1371/journal.pone.0194145 ZareS. NematiM. ZhengY. A Systematic Review of Consumer Preference for E-Cigarette Attributes: Flavor, Nicotine Strength, and Type PLoS One 13 2018 e0194145 10.1371/journal.pone.0194145 Open DOISearch in Google Scholar

Baweja, R., K.M. Curci, J. Yingst, S. Veldheer, S. Hrabovsky, S.J. Wilson, T.T. Nichols, T. Eissenberg, and J. Foulds: Views of Experienced Electronic Cigarette Users; Addict. Res. Theory 24 (2016) 80–88. DOI: 10.3109/16066359.2015.1077947 BawejaR. CurciK.M. YingstJ. VeldheerS. HrabovskyS. WilsonS.J. NicholsT.T. EissenbergT. FouldsJ. Views of Experienced Electronic Cigarette Users Addict. Res. Theory 24 2016 80 88 10.3109/16066359.2015.1077947 Open DOISearch in Google Scholar

Berg, C.J.: Preferred Flavors and Reasons for E-Cigarette Use and Discontinued Use Among Never, Current, and Former Smokers; Int. J. Public Health 61 (2016) 225–236. DOI: 10.1007/s00038-015-0764-x BergC.J. Preferred Flavors and Reasons for E-Cigarette Use and Discontinued Use Among Never, Current, and Former Smokers Int. J. Public Health 61 2016 225 236 10.1007/s00038-015-0764-x Open DOISearch in Google Scholar

Russell, C., N. McKeganey, T. Dickson, and M. Nides: Changing Patterns of First E-Cigarette Flavor Used and Current Flavors Used by 20,836 Adult Frequent E-Cigarette Users in the USA; Harm Reduct. J. 15 (2018) 33. DOI: 10.1186/s12954-018-0238-6 RussellC. McKeganeyN. DicksonT. NidesM. Changing Patterns of First E-Cigarette Flavor Used and Current Flavors Used by 20,836 Adult Frequent E-Cigarette Users in the USA Harm Reduct. J. 15 2018 33 10.1186/s12954-018-0238-6 Open DOISearch in Google Scholar

Chen, J.C., B. Das, E.L. Mead, and D.L.G. Borzekowski: Flavored E-cigarette Use and Cigarette Smoking Susceptibility Among Youth; Tob. Regul. Sci. 3 (2017) 68–80. DOI: 10.18001/TRS.3.1.7 ChenJ.C. DasB. MeadE.L. BorzekowskiD.L.G. Flavored E-cigarette Use and Cigarette Smoking Susceptibility Among Youth Tob. Regul. Sci. 3 2017 68 80 10.18001/TRS.3.1.7 Open DOISearch in Google Scholar

Audrain-McGovern, J., A.A. Strasser, and E.P. Wileyto: The Impact of Flavoring on the Rewarding and Reinforcing Value of E-Cigarettes with Nicotine Among Young Adult Smokers; Drug Alcohol Depend. 166 (2016) 263–267. DOI: 10.1016/j.drugalcdep.2016.06.030 Audrain-McGovernJ. StrasserA.A. WileytoE.P. The Impact of Flavoring on the Rewarding and Reinforcing Value of E-Cigarettes with Nicotine Among Young Adult Smokers Drug Alcohol Depend. 166 2016 263 267 10.1016/j.drugalcdep.2016.06.030 Open DOISearch in Google Scholar

Krishnan-Sarin S., B.G. Green, G. Kong, D.A. Cavallo, P. Jatlow, R. Gueorguieva, E. Buta, and S.S. O’Malley: Studying the Interactive Effects of Menthol and Nicotine Among Youth: An Examination Using E-Cigarettes; Drug Alcohol Depend. 180 (2017) 193–199. DOI: 10.1016/j.drugalcdep.2017.07.044 Krishnan-SarinS. GreenB.G. KongG. CavalloD.A. JatlowP. GueorguievaR. ButaE. O’MalleyS.S. Studying the Interactive Effects of Menthol and Nicotine Among Youth: An Examination Using E-Cigarettes Drug Alcohol Depend. 180 2017 193 199 10.1016/j.drugalcdep.2017.07.044 Open DOISearch in Google Scholar

Action on Smoking and Health (ASH): Use of Electronic Cigarettes (Vapourisers) Among Adults in Great Britain; 2019. Available at: https://ash.org.uk/information-and-resources/fact-sheets/statistical/use-of-e-cigarettes-among-adults-in-great-britain-2019 (accessed April 29, 2020) Action on Smoking and Health (ASH) Use of Electronic Cigarettes (Vapourisers) Among Adults in Great Britain 2019 Available at: https://ash.org.uk/information-and-resources/fact-sheets/statistical/use-of-e-cigarettes-among-adults-in-great-britain-2019 (accessed April 29, 2020) Search in Google Scholar

Gravely, S., K.M. Cummings, D. Hammond, E. Lindblom, D.M. Smith, N. Martin, R. Loewen, R. Borland, A. Hyland, M.E. Thompson, C. Boudreau, K. Kasza, J. Ouimet, A.C.K. Quah, R.J. O’Connor, and G.T. Fong: The Association of E-Cigarette Flavors with Satisfaction, Enjoyment, and Trying to Quit or Stay Abstinent from Smoking Among Regular Adult Vapers from Canada and the United States: Findings from the 2018 ITC Four Country Smoking and Vaping Survey; Nicotine Tob. Res. 22 (2020) 1831–1841. DOI: 10.1093/ntr/ntaa095 GravelyS. CummingsK.M. HammondD. LindblomE. SmithD.M. MartinN. LoewenR. BorlandR. HylandA. ThompsonM.E. BoudreauC. KaszaK. OuimetJ. QuahA.C.K. O’ConnorR.J. FongG.T. The Association of E-Cigarette Flavors with Satisfaction, Enjoyment, and Trying to Quit or Stay Abstinent from Smoking Among Regular Adult Vapers from Canada and the United States: Findings from the 2018 ITC Four Country Smoking and Vaping Survey Nicotine Tob. Res. 22 2020 1831 1841 10.1093/ntr/ntaa095 Open DOISearch in Google Scholar

Institute for Global Tobacco Control: Country Laws Regulating E-Cigarettes: A Policy Scan; 2020. Available at: https://www.globaltobaccocontrol.org/e-cigarette_policyscan (accessed April 29, 2020) Institute for Global Tobacco Control Country Laws Regulating E-Cigarettes: A Policy Scan 2020 Available at: https://www.globaltobaccocontrol.org/e-cigarette_policyscan (accessed April 29, 2020) Search in Google Scholar

Bond, C.M. and A.R. Barry: Do the Benefits of Electronic Cigarettes Outweigh the Risks?; Can. J. Hosp. Pharm. 71 (2018) 44–47. BondC.M. BarryA.R. Do the Benefits of Electronic Cigarettes Outweigh the Risks? Can. J. Hosp. Pharm. 71 2018 44 47 Search in Google Scholar

Rambaran, K., S. Sakhamuri, and L. Pinto Pereira: E-Cigarettes: Banning Flavours is Better Than an Outright Ban; Lancet Respir. Med. 7 (2019) e37. DOI: 10.1016/S2213-2600(19)30359-5 RambaranK. SakhamuriS. Pinto PereiraL. E-Cigarettes: Banning Flavours is Better Than an Outright Ban Lancet Respir. Med. 7 2019 e37 10.1016/S2213-2600(19)30359-5 Open DOISearch in Google Scholar

Strombotne, K., J. Buckell, and J.L. Sindelar: Do JUUL and E-Cigarette Flavours Change Risk Perceptions of Adolescents? Evidence from a National Survey; Tob. Control 30 (2020) 199–205. DOI: 10.1136/tobaccocontrol-2019-055394 StrombotneK. BuckellJ. SindelarJ.L. Do JUUL and E-Cigarette Flavours Change Risk Perceptions of Adolescents? Evidence from a National Survey Tob. Control 30 2020 199 205 10.1136/tobaccocontrol-2019-055394 Open DOISearch in Google Scholar

U.S. Food and Drug Administration (FDA) and Department of Health and Human Services (HHS): 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; 2016. Available at: https://www.federalregister.gov/documents/2016/05/10/2016-10685/deeming-tobacco-products-to-be-subject-to-the-federal-food-drug-and-cosmetic-act-as-amended-by-the (accessed January 6 2021). U.S. Food and Drug Administration (FDA) and Department of Health and Human Services (HHS) 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 2016 Available at: https://www.federalregister.gov/documents/2016/05/10/2016-10685/deeming-tobacco-products-to-be-subject-to-the-federal-food-drug-and-cosmetic-act-as-amended-by-the (accessed January 6 2021). Search in Google Scholar

U.S. Department of Health and Human Services (HHS), Food and Drug Administration (FDA) Center for Tobacco Products: Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems. Guidance for Industry; 2019. Available at: https://www.fda.gov/media/127853/download (accessed August 4, 2020) U.S. Department of Health and Human Services (HHS), Food and Drug Administration (FDA) Center for Tobacco Products Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems Guidance for Industry 2019 Available at: https://www.fda.gov/media/127853/download (accessed August 4, 2020) Search in Google Scholar

U.S. Food and Drug Administration (FDA): Section 907 of the Federal Food, Drug, and Cosmetic Act – Tobacco Product Standards; 2018. Available at: https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/section-907-federal-food-drug-and-cosmetic-act-tobacco-product-standards (accessed September 7, 2020) U.S. Food and Drug Administration (FDA) Section 907 of the Federal Food, Drug, and Cosmetic Act – Tobacco Product Standards 2018 Available at: https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/section-907-federal-food-drug-and-cosmetic-act-tobacco-product-standards (accessed September 7, 2020) Search in Google Scholar

U.S. Food and Drug Administration (FDA): Modified Risk Tobacco Products; 2020. Available at: https://www.fda.gov/tobacco-products/advertising-and-promotion/modified-risk-tobacco-products (accessed January 25, 2021). U.S. Food and Drug Administration (FDA) Modified Risk Tobacco Products 2020 Available at: https://www.fda.gov/tobacco-products/advertising-and-promotion/modified-risk-tobacco-products (accessed January 25, 2021). Search in Google Scholar

The European Parliament and the Council of the European Union: Directive 2014/40/EU of the European Parliament and of the Council of 3 April 2014 on the Approximation of the Laws, Regulations and Administrative Provisions of the Member States Concerning the Manufacture, Presentation and Sale of Tobacco and Related Products and Repealing Directive 2001/37/EC; Official Journal of the European Union L127 (2014) 1–38. The European Parliament and the Council of the European Union Directive 2014/40/EU of the European Parliament and of the Council of 3 April 2014 on the Approximation of the Laws, Regulations and Administrative Provisions of the Member States Concerning the Manufacture, Presentation and Sale of Tobacco and Related Products and Repealing Directive 2001/37/EC Official Journal of the European Union L127 2014 1 38 Search in Google Scholar

European Commission: Restriction of Hazardous Substances in Electrical and Electronic Equipment (RoHS); 2017. Available at: https://ec.europa.eu/environment/waste/rohs_eee/index_en.htm (accessed January 6, 2021) European Commission Restriction of Hazardous Substances in Electrical and Electronic Equipment (RoHS) 2017 Available at: https://ec.europa.eu/environment/waste/rohs_eee/index_en.htm (accessed January 6, 2021) Search in Google Scholar

European Agency for Safety and Health at Work (EUOSHA): Regulation (EC) No 1907/2006 - Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH); 2006. Available at: https://osha.europa.eu/en/legislation/directives/regulation-ec-no-1907-2006-of-the-european-parliament-and-of-the-council (accessed January 6 2021). European Agency for Safety and Health at Work (EUOSHA) Regulation (EC) No 1907/2006 - Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) 2006 Available at: https://osha.europa.eu/en/legislation/directives/regulation-ec-no-1907-2006-of-the-european-parliament-and-of-the-council (accessed January 6 2021). Search in Google Scholar

Committee of Advertising Practice (ASA-CAP): Can E-Cigarettes Claim to be Healthy?; 2018. Available at: https://www.asa.org.uk/news/can-e-cigarettes-claim-to-be-healthy.html (accessed September 7 2020). Committee of Advertising Practice (ASA-CAP) Can E-Cigarettes Claim to be Healthy? 2018 Available at: https://www.asa.org.uk/news/can-e-cigarettes-claim-to-be-healthy.html (accessed September 7 2020). Search in Google Scholar

U.S. Department of Health and Human Services (HHS), Food and Drug Administration (FDA) Center for Tobacco Products: Guidance for Industry Modified Risk Tobacco Product Applications. Draft Guidance; 2012. U.S. Department of Health and Human Services (HHS), Food and Drug Administration (FDA) Center for Tobacco Products Guidance for Industry Modified Risk Tobacco Product Applications Draft Guidance 2012 Search in Google Scholar

Government of Canada: Vaping Product Regulations; 2018. Available at: https://www.canada.ca/en/health-canada/services/smoking-tobacco/vaping/product-safety-regulation.html (accessed April 29, 2020) Government of Canada Vaping Product Regulations 2018 Available at: https://www.canada.ca/en/health-canada/services/smoking-tobacco/vaping/product-safety-regulation.html (accessed April 29, 2020) Search in Google Scholar

European Committee for Standardization (CEN): CEN TR 17236:2018. Electronic Cigarettes and E-Liquids – Constituents to be Measured in the Aerosol of Vaping Products; 2018. Available at: https://standards.cen.eu/dyn/www/f?p=204:110:0::::FSP_PROJECT,FSP_ORG_ID:66961,1958025&cs=1CB5A86D99D10CD6A32BE1C35C52F2D34 (accessed September 7, 2020) European Committee for Standardization (CEN) CEN TR 17236:2018. Electronic Cigarettes and E-Liquids – Constituents to be Measured in the Aerosol of Vaping Products 2018 Available at: https://standards.cen.eu/dyn/www/f?p=204:110:0::::FSP_PROJECT,FSP_ORG_ID:66961,1958025&cs=1CB5A86D99D10CD6A32BE1C35C52F2D34 (accessed September 7, 2020) Search in Google Scholar

European Committee for Standardization (CEN): CEN/TS 17287:2019. Requirements and Test Methods for Electronic Cigarette Devices; 2019. Available at: https://standards.cen.eu/dyn/www/f?p=204:110:0::::FSP_PROJECT:65461&cs=11304D006B6DAFFEE8110B2710FD7478A (accessed September 7, 2020) European Committee for Standardization (CEN) CEN/TS 17287:2019. Requirements and Test Methods for Electronic Cigarette Devices 2019 Available at: https://standards.cen.eu/dyn/www/f?p=204:110:0::::FSP_PROJECT:65461&cs=11304D006B6DAFFEE8110B2710FD7478A (accessed September 7, 2020) Search in Google Scholar

International Organization for Standardization (ISO): ISO 20768:2018. Vapour Products – Routine Analytical Vaping Machine – Definitions and Standard Conditions; ISO, Geneva, Switzerland, 2018. Available at: https://www.iso.org/standard/69019.html (accessed September 7, 2020). International Organization for Standardization (ISO) ISO 20768:2018. Vapour Products – Routine Analytical Vaping Machine – Definitions and Standard Conditions ISO Geneva, Switzerland 2018 Available at: https://www.iso.org/standard/69019.html (accessed September 7, 2020). Search in Google Scholar

International Organization for Standardization (ISO): ISO 20714:2019. E-Liquid – Determination of Nicotine, Propylene Glycol and Glycerol in Liquids Used in Electronic Nicotine Delivery Devices – Gas Chromatographic Method; 2019. Available at: https://www.iso.org/standard/68905.html (accessed September 7, 2020). International Organization for Standardization (ISO) ISO 20714:2019. E-Liquid – Determination of Nicotine, Propylene Glycol and Glycerol in Liquids Used in Electronic Nicotine Delivery Devices – Gas Chromatographic Method 2019 Available at: https://www.iso.org/standard/68905.html (accessed September 7, 2020). Search in Google Scholar

Belushkin, M., M. Esposito, G. Jaccard, C. Jeannet, A. Korneliou, and D. Tafin Djoko: Role of Testing Standards in Smoke-Free Product Assessments; Regul. Toxicol. Pharmacol. 98 (2018) 1–8. DOI: 10.1016/j.yrtph.2018.06.021 BelushkinM. EspositoM. JaccardG. JeannetC. KorneliouA. Tafin DjokoD. Role of Testing Standards in Smoke-Free Product Assessments Regul. Toxicol. Pharmacol. 98 2018 1 8 10.1016/j.yrtph.2018.06.021 Open DOISearch in Google Scholar

Chatham-Stephens, K., R. Law, E. Taylor, P. Melstrom, R. Bunnell, B. Wang, B. Apelberg, and J.G. Schier: Notes from the Field: Calls to Poison Centers for Exposures to Electronic Cigarettes – United States, September 2010-February 2014; MMWR Morb. Mortal. Wkly. Rep. 63 (2014) 292–293. Chatham-StephensK. LawR. TaylorE. MelstromP. BunnellR. WangB. ApelbergB. SchierJ.G. Notes from the Field: Calls to Poison Centers for Exposures to Electronic Cigarettes – United States, September 2010-February 2014 MMWR Morb. Mortal. Wkly. Rep. 63 2014 292 293 Search in Google Scholar

McCague, Y.: Ocular Chemical Burns Secondary to Accidental Administration of E-Cigarette Liquid; Adv. Emerg. Nurs. J. 40 (2018) 104–109. DOI: 10.1097/TME.0000000000000183 McCagueY. Ocular Chemical Burns Secondary to Accidental Administration of E-Cigarette Liquid Adv. Emerg. Nurs. J. 40 2018 104 109 10.1097/TME.0000000000000183 Open DOISearch in Google Scholar

Jamison, A. and D. Lockington: Ocular Chemical Injury Secondary to Electronic Cigarette Liquid Misuse; JAMA Ophthalmol. 134 (2016) 1443. DOI: 10.1001/jamaophthalmol.2016.3651 JamisonA. LockingtonD. Ocular Chemical Injury Secondary to Electronic Cigarette Liquid Misuse JAMA Ophthalmol. 134 2016 1443 10.1001/jamaophthalmol.2016.3651 Open DOISearch in Google Scholar

Brownson, E.G., C.M. Thompson, S. Goldsberry, H.J. Chong, J.B. Friedrich, T.N. Pham, S. Arbabi, G.J. Carrougher, and N.S. Gibran: Explosion Injuries from E-Cigarettes; N. Engl. J. Med. 375 (2016) 1400–1402. DOI: 10.1056/NEJMc1608478 BrownsonE.G. ThompsonC.M. GoldsberryS. ChongH.J. FriedrichJ.B. PhamT.N. ArbabiS. CarrougherG.J. GibranN.S. Explosion Injuries from E-Cigarettes N. Engl. J. Med. 375 2016 1400 1402 10.1056/NEJMc1608478 Open DOISearch in Google Scholar

The European Parliament and the Council of the European Union: Directive 2014/30/EU of the European Parliament and of the Council of 26 February 2014 on the Harmonisation of the Laws of the Member States Relating to Electromagnetic Compatibility; Official Journal of the European Union L96 (2014) 79–106. The European Parliament and the Council of the European Union Directive 2014/30/EU of the European Parliament and of the Council of 26 February 2014 on the Harmonisation of the Laws of the Member States Relating to Electromagnetic Compatibility Official Journal of the European Union L96 2014 79 106 Search in Google Scholar

The European Parliament and the Council of the European Union: Directive 2011/65/EU of the European Parliament and of the Council of 8 June 2011 on the Restriction of the Use of Certain Hazardous Substances in Electrical and Electronic Equipment; Official Journal of the European Union L174 (2011) 88–110. The European Parliament and the Council of the European Union Directive 2011/65/EU of the European Parliament and of the Council of 8 June 2011 on the Restriction of the Use of Certain Hazardous Substances in Electrical and Electronic Equipment Official Journal of the European Union L174 2011 88 110 Search in Google Scholar

The European Parliament and the Council of the European Union: Directive 2001/95/EC of the European Parliament and of the Council of 3 December 2001 on General Product Safety; Official Journal of the European Union L0095 (2001) 1–23. The European Parliament and the Council of the European Union Directive 2001/95/EC of the European Parliament and of the Council of 3 December 2001 on General Product Safety Official Journal of the European Union L0095 2001 1 23 Search in Google Scholar

Costigan, S. and C. Meredith: An Approach to Ingredient Screening and Toxicological Risk Assessment of Flavours in E-Liquids; Regul. Toxicol. Pharmacol. 72 (2015) 361–369. DOI: 10.1016/j.yrtph.2015.05.018 CostiganS. MeredithC. An Approach to Ingredient Screening and Toxicological Risk Assessment of Flavours in E-Liquids Regul. Toxicol. Pharmacol. 72 2015 361 369 10.1016/j.yrtph.2015.05.018 Open DOISearch in Google Scholar

Costigan, S. and J. Lopez-Belmonte: An Approach to Allergy Risk Assessments for E-Liquid Ingredients; Regul. Toxicol. Pharmacol. 87 (2017) 1–8. DOI: 10.1016/j.yrtph.2017.04.003 CostiganS. Lopez-BelmonteJ. An Approach to Allergy Risk Assessments for E-Liquid Ingredients Regul. Toxicol. Pharmacol. 87 2017 1 8 10.1016/j.yrtph.2017.04.003 Open DOISearch in Google Scholar

Iskandar, A.R., I. Gonzalez-Suarez, S. Majeed, D. Marescotti, S. Sewer, Y. Xiang, P. Leroy, E. Guedj, C. Mathis, J.P. Schaller, P. Vanscheeuwijck, S. Frentzel, F. Martin, N.V. Ivanov, M.C. Peitsch, and J. Hoeng: A Framework for In Vitro Systems Toxicology Assessment of E-Liquids; Toxicol. Mech. Methods 26 (2016) 392–416. DOI: 10.3109/15376516.2016.1170251 IskandarA.R. Gonzalez-SuarezI. MajeedS. MarescottiD. SewerS. XiangY. LeroyP. GuedjE. MathisC. SchallerJ.P. VanscheeuwijckP. FrentzelS. MartinF. IvanovN.V. PeitschM.C. HoengJ. A Framework for In Vitro Systems Toxicology Assessment of E-Liquids Toxicol. Mech. Methods 26 2016 392 416 10.3109/15376516.2016.1170251 Open DOISearch in Google Scholar

American E-Liquid Manufacturing Standards Association: E-Liquid Manufacturing Standards; 2014. Available at: http://www.aemsa.org/wp-content/uploads/2014/02/AEMSA-Standards_Version-1-8.pdf (accessed September 7, 2020) American E-Liquid Manufacturing Standards Association E-Liquid Manufacturing Standards 2014 Available at: http://www.aemsa.org/wp-content/uploads/2014/02/AEMSA-Standards_Version-1-8.pdf (accessed September 7, 2020) Search in Google Scholar

Go, Y.Y., J.Y. Mun, S.-W. Chae, J. Chang, and J.-J. Song: Comparison Between In Vitro Toxicities of Tobacco- and Menthol-Flavored Electronic Cigarette Liquids on Human Middle Ear Epithelial Cells; Sci. Rep. 10 (2020) 2544. DOI: 10.1038/s41598-020-59290-y GoY.Y. MunJ.Y. ChaeS.-W. ChangJ. SongJ.-J. Comparison Between In Vitro Toxicities of Tobacco- and Menthol-Flavored Electronic Cigarette Liquids on Human Middle Ear Epithelial Cells Sci. Rep. 10 2020 2544 10.1038/s41598-020-59290-y Open DOISearch in Google Scholar

Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT): Framework for Risk Assessment of Flavouring Compounds in Electronic Nicotine (and Non-Nicotine) Delivery Systems (E(N)NDS – E-Cigarettes); 2020. Available at: https://cot.food.gov.uk/sites/default/files/frameworkforriskassessingflavourings_0.pdf (accessed January 26, 2021) Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) Framework for Risk Assessment of Flavouring Compounds in Electronic Nicotine (and Non-Nicotine) Delivery Systems (E(N)NDS – E-Cigarettes) 2020 Available at: https://cot.food.gov.uk/sites/default/files/frameworkforriskassessingflavourings_0.pdf (accessed January 26, 2021) Search in Google Scholar

Farsalinos, K. and G. Lagoumintzis: Toxicity Classification of E-Cigarette Flavouring Compounds Based on European Union Regulation: Analysis of Findings from a Recent Study; Harm Reduct. J. 16 (2019) 48. DOI: 10.1186/s12954-019-0318-2 FarsalinosK. LagoumintzisG. Toxicity Classification of E-Cigarette Flavouring Compounds Based on European Union Regulation: Analysis of Findings from a Recent Study Harm Reduct. J. 16 2019 48 10.1186/s12954-019-0318-2 Open DOISearch in Google Scholar

Berman, M.S., G. Connolly, M.K. Cummings, M.V. Djordjevic, D.K. Hatsukami, J.E. Henningfield, M. Myers, R.J. O’Connor, M. Parascandola, V. Rees, J.M. Rice, and P.G. Shields: Providing a Science Base for the Evaluation of Tobacco Products; Tob. Regul. Sci. 1 (2015) 76–93. DOI: 10.18001/TRS.1.1.8 BermanM.S. ConnollyG. CummingsM.K. DjordjevicM.V. HatsukamiD.K. HenningfieldJ.E. MyersM. O’ConnorR.J. ParascandolaM. ReesV. RiceJ.M. ShieldsP.G. Providing a Science Base for the Evaluation of Tobacco Products Tob. Regul. Sci. 1 2015 76 93 10.18001/TRS.1.1.8 Open DOISearch in Google Scholar

Murphy, J., M. Gaça, F. Lowe, E. Minet, D. Breheny, K. Prasad, O. Camacho, I.M. Fearon, C. Liu, C. Wright, K. McAdam, and C. Proctor: Assessing Modified Risk Tobacco and Nicotine Products: Description of the Scientific Framework and Assessment of a Closed Modular Electronic Cigarette; Regul. Toxicol. Pharmacol. 90 (2017) 342–357. DOI: 10.1016/j.yrtph.2017.09.008 MurphyJ. GaçaM. LoweF. MinetE. BrehenyD. PrasadK. CamachoO. FearonI.M. LiuC. WrightC. McAdamK. ProctorC. Assessing Modified Risk Tobacco and Nicotine Products: Description of the Scientific Framework and Assessment of a Closed Modular Electronic Cigarette Regul. Toxicol. Pharmacol. 90 2017 342 357 10.1016/j.yrtph.2017.09.008 Open DOISearch in Google Scholar

Smith, M.R., B. Clark, F. Lüdicke, J.P. Schaller, P. Vanscheeuwijck, J. Hoeng, and M.C. Peitsch: Evaluation of the Tobacco Heating System 2.2. Part 1: Description of the System and the Scientific Assessment Program; Regul. Toxicol. Pharmacol. 81, Suppl. 2 (2016) S17–S26. DOI: 10.1016/j.yrtph.2016.07.006 SmithM.R. ClarkB. LüdickeF. SchallerJ.P. VanscheeuwijckP. HoengJ. PeitschM.C. Evaluation of the Tobacco Heating System 2.2. Part 1: Description of the System and the Scientific Assessment Program Regul. Toxicol. Pharmacol. 81 Suppl. 2 2016 S17 S26 10.1016/j.yrtph.2016.07.006 Open DOISearch in Google Scholar

Geiss, O., I. Bianchi, and J. Barerro-Morena: Correlation of Volatile Carbonyl Yields Emitted by E-Cigarettes with the Temperature of the Heating Coil and the Perceived Sensorial Quality of the Generated Vapours; Int. J. Hyg. Environ. Health 219 (2016) 268–277. DOI: 10.1016/j.ijheh.2016.01.004 GeissO. BianchiI. Barerro-MorenaJ. Correlation of Volatile Carbonyl Yields Emitted by E-Cigarettes with the Temperature of the Heating Coil and the Perceived Sensorial Quality of the Generated Vapours Int. J. Hyg. Environ. Health 219 2016 268 277 10.1016/j.ijheh.2016.01.004 Open DOISearch in Google Scholar

Etter, J.-F., E. Zäther, and S. Svensson: Analysis of Refill Liquids for Electronic Cigarettes; Addiction 108 (2013) 1671–1679. DOI: 10.1111/add.12235 EtterJ.-F. ZätherE. SvenssonS. Analysis of Refill Liquids for Electronic Cigarettes Addiction 108 2013 1671 1679 10.1111/add.12235 Open DOISearch in Google Scholar

Kim, H.-J. and H.-S. Shin: Determination of Tobacco-Specific Nitrosamines in Replacement Liquids of Electronic Cigarettes by Liquid Chromatography-Tandem Mass Spectrometry; J. Chromatogr. A 1291 (2013) 48–55. DOI: 10.1016/j.chroma.2013.03.035 KimH.-J. ShinH.-S. Determination of Tobacco-Specific Nitrosamines in Replacement Liquids of Electronic Cigarettes by Liquid Chromatography-Tandem Mass Spectrometry J. Chromatogr. A 1291 2013 48 55 10.1016/j.chroma.2013.03.035 Open DOISearch in Google Scholar

Farsalinos, K.E., I.G. Gillman, M.S. Melvin, A.R. Paolantonio, W.J. Gardow, K.E. Humphries, S.E. Brown, K. Poulas, and V. Voudris: Nicotine Levels and Presence of Selected Tobacco-Derived Toxins in Tobacco Flavoured Electronic Cigarette Refill Liquids; Int. J. Environ. Res. Public Health 12 (2015) 3439–3452. DOI: 10.3390/ijerph120403439 FarsalinosK.E. GillmanI.G. MelvinM.S. PaolantonioA.R. GardowW.J. HumphriesK.E. BrownS.E. PoulasK. VoudrisV. Nicotine Levels and Presence of Selected Tobacco-Derived Toxins in Tobacco Flavoured Electronic Cigarette Refill Liquids Int. J. Environ. Res. Public Health 12 2015 3439 3452 10.3390/ijerph120403439 Open DOISearch in Google Scholar

Lisko, J.G., H. Tran, S.B. Stanfill, B.C. Blount, and C.H. Watson: Chemical Composition and Evaluation of Nicotine, Tobacco Alkaloids, pH, and Selected Flavors in E-Eigarette Cartridges and Refill Solutions; Nicotine Tob. Res. 17 (2015) 1270–1278. DOI: 10.1093/ntr/ntu279 LiskoJ.G. TranH. StanfillS.B. BlountB.C. WatsonC.H. Chemical Composition and Evaluation of Nicotine, Tobacco Alkaloids, pH, and Selected Flavors in E-Eigarette Cartridges and Refill Solutions Nicotine Tob. Res. 17 2015 1270 1278 10.1093/ntr/ntu279 Open DOISearch in Google Scholar

Tayyarah, R. and G.A. Long: Comparison of Select Analytes in Aerosol from E-Cigarettes with Smoke from Conventional Cigarettes and with Ambient Air; Regul. Toxicol. Pharmacol. 70 (2014) 704–710. DOI: 10.1016/j.yrtph.2014.10.010 TayyarahR. LongG.A. Comparison of Select Analytes in Aerosol from E-Cigarettes with Smoke from Conventional Cigarettes and with Ambient Air Regul. Toxicol. Pharmacol. 70 2014 704 710 10.1016/j.yrtph.2014.10.010 Open DOISearch in Google Scholar

U.S. Food and Drug Administration (FDA): Harmful and Potentially Harmful Constituents (HPHCs); Available at https://www.fda.gov/tobacco-products/products-ingredients-components/harmful-and-potentially-harmful-constituents-hphcs (accessed April 11, 2021) U.S. Food and Drug Administration (FDA) Harmful and Potentially Harmful Constituents (HPHCs) Available at https://www.fda.gov/tobacco-products/products-ingredients-components/harmful-and-potentially-harmful-constituents-hphcs (accessed April 11, 2021) Search in Google Scholar

U.S. Federal Register: A Notice by the U.S. Food and Drug Administration (FDA): Harmful and Potentially Harmful Constituents in Tobacco Products; Established List, Proposed Additions; Request for Comments; Federal Register (2019) 84 FR 38032. Available at: https://www.federalregister.gov/documents/2019/08/05/2019-16658/harmful-and-potentially-harmful-constituents-in-tobacco-products-established-list-proposed-additions (accessed May 10, 2021) U.S. Federal Register: A Notice by the U.S. Food and Drug Administration (FDA) Harmful and Potentially Harmful Constituents in Tobacco Products; Established List, Proposed Additions; Request for Comments Federal Register (2019) 84 FR 38032. Available at: https://www.federalregister.gov/documents/2019/08/05/2019-16658/harmful-and-potentially-harmful-constituents-in-tobacco-products-established-list-proposed-additions (accessed May 10, 2021) Search in Google Scholar

Zhao, T., S. Shu, Q. Guo, and Y. Zhu: Effects of Design Parameters and Puff Topography on Heating Coil Temperature and Mainstream Aerosols in Electronic Cigarettes; Atmos. Environ. 134 (2016) 61–69. DOI: 10.1016/j.atmosenv.2016.03.027 ZhaoT. ShuS. GuoQ. ZhuY. Effects of Design Parameters and Puff Topography on Heating Coil Temperature and Mainstream Aerosols in Electronic Cigarettes Atmos. Environ. 134 2016 61 69 10.1016/j.atmosenv.2016.03.027 Open DOISearch in Google Scholar

Ward, A.M., R. Yaman, and J.O. Ebbert: Electronic Nicotine Delivery System Design and Aerosol Toxicants: A Systematic Review; PLoS One 15 (2020) e0234189. DOI: 10.1371/journal.pone.0234189 WardA.M. YamanR. EbbertJ.O. Electronic Nicotine Delivery System Design and Aerosol Toxicants: A Systematic Review PLoS One 15 2020 e0234189 10.1371/journal.pone.0234189 Open DOISearch in Google Scholar

Bansal, V. and K.H. Kim: Review on Quantitation Methods for Hazardous Pollutants Released by E-Cigarette (EC) Smoking; Trends Analyt. Chem. 78 (2016) 120–133. DOI: 10.1016/j.trac.2016.02.015 BansalV. KimK.H. Review on Quantitation Methods for Hazardous Pollutants Released by E-Cigarette (EC) Smoking Trends Analyt. Chem. 78 2016 120 133 10.1016/j.trac.2016.02.015 Open DOISearch in Google Scholar

Cheng, T.: Chemical Evaluation of Electronic Cigarettes; Tob. Control 23, Suppl. 2 (2014) ii11–ii17. DOI: 10.1136/tobaccocontrol-2013-051482 ChengT. Chemical Evaluation of Electronic Cigarettes To. Control 23 Suppl. 2 2014 ii11 ii17 10.1136/tobaccocontrol-2013-051482 Open DOISearch in Google Scholar

Strongin, R.M.: E-Cigarette Chemistry and Analytical Detection; Annu. Rev. Anal. Chem. 12 (2019) 23–39. DOI: 10.1146/annurev-anchem-061318-115329 StronginR.M. E-Cigarette Chemistry and Analytical Detection Annu. Rev. Anal. Chem. 12 2019 23 39 10.1146/annurev-anchem-061318-115329 Open DOISearch in Google Scholar

Lauterbach, J.H. and M. Laugesen: Comparison of Toxicant Levels in Mainstream Aerosols Generated by Ruyan® Electronic Nicotine Delivery Systems (ENDS) and Conventional Cigarette Products; Poster #1861 presented at the Society of Toxicology 51st Annual Meeting & ToxExpo, San Francisco, CA, USA, March 2012. LauterbachJ.H. LaugesenM. Comparison of Toxicant Levels in Mainstream Aerosols Generated by Ruyan® Electronic Nicotine Delivery Systems (ENDS) and Conventional Cigarette Products Poster #1861 presented at the Society of Toxicology 51st Annual Meeting & ToxExpo San Francisco, CA, USA March 2012 Search in Google Scholar

Lauterbach, J.H., M. Laugesen, and J.D. Ross: Suggested Protocol for Estimation of Harmful and Potentially Harmful Constituents in Mainstream Aerosols Generated by Electronic Nicotine Delivery Systems (ENDS); Poster #1860 presented at the Society of Toxicology 51st Annual Meeting & ToxExpo, San Francisco, CA, USA, March 2012. LauterbachJ.H. LaugesenM. RossJ.D. Suggested Protocol for Estimation of Harmful and Potentially Harmful Constituents in Mainstream Aerosols Generated by Electronic Nicotine Delivery Systems (ENDS) Poster #1860 presented at the Society of Toxicology 51st Annual Meeting & ToxExpo San Francisco, CA, USA March 2012 Search in Google Scholar

Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA): CORESTA Recommended Method No 81. Routine Analytical Machine for E-Cigarette Aerosol Generation and Collection – Definitions and Standard Conditions; 2015. Available at: https://www.coresta.org/sites/default/files/technical_documents/main/CRM_81.pdf (accessed April 29, 2020) Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) CORESTA Recommended Method No 81. Routine Analytical Machine for E-Cigarette Aerosol Generation and Collection – Definitions and Standard Conditions 2015 Available at: https://www.coresta.org/sites/default/files/technical_documents/main/CRM_81.pdf (accessed April 29, 2020) Search in Google Scholar

Beauval, N., S. Antherieu, M. Soyez, N. Gengler, N. Grova, M. Howsam, E.M. Hardy, M. Fischer, B.M.R. Appenzeller, J.F. Goossens, D. Allorge, G. Garçon, J.M. Lo-Guidice, and A. Garat: Chemical Evaluation of Electronic Cigarettes: Multicomponent Analysis of Liquid Refills and Their Corresponding Aerosols; J. Anal. Toxicol. 41 (2017) 670–678. DOI: 10.1093/jat/bkx054 BeauvalN. AntherieuS. SoyezM. GenglerN. GrovaN. HowsamM. HardyE.M. FischerM. AppenzellerB.M.R. GoossensJ.F. AllorgeD. GarçonG. Lo-GuidiceJ.M. GaratA. Chemical Evaluation of Electronic Cigarettes: Multicomponent Analysis of Liquid Refills and Their Corresponding Aerosols J. Anal. Toxicol. 41 2017 670 678 10.1093/jat/bkx054 Open DOISearch in Google Scholar

Mallock, N., H.L. Trieu, M. Macziol, S. Malke, A. Katz, P. Laux, F. Henkler-Stephani, J. Hahn, C. Hutzler, and A. Luch: Trendy E-Cigarettes Enter Europe: Chemical Characterization of JUUL Pods and its Aerosols; Arch. Toxicol. 94 (2020) 1985–1994. DOI: 10.1007/s00204-020-02716-3 MallockN. TrieuH.L. MacziolM. MalkeS. KatzA. LauxP. Henkler-StephaniF. HahnJ. HutzlerC. LuchA. Trendy E-Cigarettes Enter Europe: Chemical Characterization of JUUL Pods and its Aerosols Arch. Toxicol. 94 2020 1985 1994 10.1007/s00204-020-02716-3 Open DOISearch in Google Scholar

Rudd, K., M. Stevenson, R. Wieczorek, J. Pani, E. Trelles-Sticken, O. Dethloff, L. Czekala, L. Simms, F. Buchanan, G. O’Connell, and T. Walele: Chemical Composition and In Vitro Toxicity Profile of a Pod-Based E-Cigarette Aerosol Compared to Cigarette Smoke; Appl. In Vitro Toxicol. 6 (2020) 11–41. DOI: 10.1089/aivt.2019.0015 RuddK. StevensonM. WieczorekR. PaniJ. Trelles-StickenE. DethloffO. CzekalaL. SimmsL. BuchananF. O’ConnellG. WaleleT. Chemical Composition and In Vitro Toxicity Profile of a Pod-Based E-Cigarette Aerosol Compared to Cigarette Smoke Appl. In Vitro Toxicol. 6 2020 11 41 10.1089/aivt.2019.0015 Open DOISearch in Google Scholar

Belushkin, M., D. Tafin Djoko, M. Esposito, A. Korneliou, C. Jeannet, M. Lazzerini, and G. Jaccard: Selected Harmful and Potentially Harmful Constituents Levels in Commercial E-Cigarettes; Chem. Res. Toxicol. 33 (2020) 657–668. DOI: 10.1021/acs.chemrestox.9b00470 BelushkinM. Tafin DjokoD. EspositoM. KorneliouA. JeannetC. LazzeriniM. JaccardG. Selected Harmful and Potentially Harmful Constituents Levels in Commercial E-Cigarettes Chem. Res. Toxicol. 33 2020 657 668 10.1021/acs.chemrestox.9b00470 Open DOISearch in Google Scholar

Wagner, K.A., J.W. Flora, M.S. Melvin, K.C. Avery, R.M. Ballentine, A.P. Brown, and W.J. McKinney: An Evaluation of Electronic Cigarette Formulations and Aerosols for Harmful and Potentially Harmful Constituents (HPHCs) Typically Derived from Combustion; Regul. Toxicol. Pharmacol. 95 (2018) 153–160. DOI: 10.1016/j.yrtph.2018.03.012 WagnerK.A. FloraJ.W. MelvinM.S. AveryK.C. BallentineR.M. BrownA.P. McKinneyW.J. An Evaluation of Electronic Cigarette Formulations and Aerosols for Harmful and Potentially Harmful Constituents (HPHCs) Typically Derived from Combustion Regul. Toxicol. Pharmacol. 95 2018 153 160 10.1016/j.yrtph.2018.03.012 Open DOISearch in Google Scholar

Qu, Y., K.-H. Kim, and J.-E. Szulejko: The Effect of Flavor Content in E-Liquids on E-Cigarette Emissions of Carbonyl Compounds; Environ. Res. 166 (2018) 324–333. DOI: 10.1016/j.envres.2018.06.013 QuY. KimK.-H. SzulejkoJ.-E. The Effect of Flavor Content in E-Liquids on E-Cigarette Emissions of Carbonyl Compounds Environ. Res. 166 2018 324 333 10.1016/j.envres.2018.06.013 Open DOISearch in Google Scholar

Vas, C.A., A. Porter, and K. McAdam: Acetoin is a Precursor to Diacetyl in E-Cigarette Liquids; Food Chem. Toxicol. 133 (2019) 110727. DOI: 10.1016/j.fct.2019.110727 VasC.A. PorterA. McAdamK. Acetoin is a Precursor to Diacetyl in E-Cigarette Liquids Food Chem. Toxicol. 133 2019 110727 10.1016/j.fct.2019.110727 Open DOISearch in Google Scholar

Olmedo, P., W. Goessler, S. Tanda, M. Grau-Perez, S. Jarmul, A. Aherrera, R. Chen, M. Hilpert, J.E. Cohen, A. Navas-Acien, and A.M. Rule: Metal Concentrations in E-Cigarette Liquid and Aerosol Samples: The Contribution of Metallic Coils; Environ. Health Perspect. 126 (2018) 027010. DOI: 10.1289/EHP2175 OlmedoP. GoesslerW. TandaS. Grau-PerezM. JarmulS. AherreraA. ChenR. HilpertM. CohenJ.E. Navas-AcienA. RuleA.M. Metal Concentrations in E-Cigarette Liquid and Aerosol Samples: The Contribution of Metallic Coils Environ. Health Perspect. 126 2018 027010 10.1289/EHP2175 Open DOISearch in Google Scholar

Palazzolo, D.L., A.P. Crow, J.M. Nelson, and R.A. Johnson: Trace Metals Derived from Electronic Cigarette (ECIG) Generated Aerosol: Potential Problem of ECIG Devices That Contain Nickel; Front. Physiol. 7 (2017) 663. DOI: 10.3389/fphys.2016.00663 PalazzoloD.L. CrowA.P. NelsonJ.M. JohnsonR.A. Trace Metals Derived from Electronic Cigarette (ECIG) Generated Aerosol: Potential Problem of ECIG Devices That Contain Nickel Front. Physiol. 7 2017 663 10.3389/fphys.2016.00663 Open DOISearch in Google Scholar

Zervas, E., H. Matsouki, G. Kyriakopoulos, S. Poulopoulos, T. Ioannides, and P. Katsaounou: Transfer of Metals in the Liquids of Electronic Cigarettes; Inhal. Toxicol. 32 (2020) 240–248. DOI: 10.1080/08958378.2020.1776801 ZervasE. MatsoukiH. KyriakopoulosG. PoulopoulosS. IoannidesT. KatsaounouP. Transfer of Metals in the Liquids of Electronic Cigarettes Inhal. Toxicol. 32 2020 240 248 10.1080/08958378.2020.1776801 Open DOISearch in Google Scholar

Williams, M., A. Villarreal, K. Bozhilov, S. Lin, and P. Talbot: Metal and Silicate Particles Including Nano-particles Are Present in Electronic Cigarette Cartomizer Fluid and Aerosol; PLoS One 8 (2013) e57987. DOI: 10.1371/journal.pone.0057987 WilliamsM. VillarrealA. BozhilovK. LinS. TalbotP. Metal and Silicate Particles Including Nano-particles Are Present in Electronic Cigarette Cartomizer Fluid and Aerosol PLoS One 8 2013 e57987 10.1371/journal.pone.0057987 Open DOISearch in Google Scholar

Williams, M., A. To, K. Bozhilov and, P. Talbot: Strategies to Reduce Tin and Other Metals in Electronic Cigarette Aerosol; PLoS One 10 (2015) e0138933. DOI: 10.1371/journal.pone.0138933 WilliamsM. ToA. BozhilovK. TalbotP. Strategies to Reduce Tin and Other Metals in Electronic Cigarette Aerosol PLoS One 10 2015 e0138933 10.1371/journal.pone.0138933 Open DOISearch in Google Scholar

Williams, M., K. Bozhilov, S. Ghai and P. Talbot: Elements Including Metals in the Atomizer and Aerosol of Disposable Electronic Cigarettes and Electronic Hookahs; PLoS One 12 (2017) e0175430. DOI: 10.1371/journal.pone.0175430 WilliamsM. BozhilovK. GhaiS. TalbotP. Elements Including Metals in the Atomizer and Aerosol of Disposable Electronic Cigarettes and Electronic Hookahs PLoS One 12 2017 e0175430 10.1371/journal.pone.0175430 Open DOISearch in Google Scholar

Williams, M., K.N. Bozhilov, and P. Talbot: Analysis of the Elements and Metals in Multiple Generations of Electronic Cigarette Atomizers; Environ. Res. 175 (2019) 156–166. DOI: 10.1016/j.envres.2019.05.014 WilliamsM. BozhilovK.N. TalbotP. Analysis of the Elements and Metals in Multiple Generations of Electronic Cigarette Atomizers Environ. Res. 175 2019 156 166 10.1016/j.envres.2019.05.014 Open DOISearch in Google Scholar

Beauval, N., M. Howsam, S. Antherieu, D. Allorge, M. Soyez, G. Garçon, J.F. Goossens, J.M. Lo-Guidice and, A. Garat: Trace Elements in E-Liquids – Development and Validation of an ICP-MS Method for the Analysis of Electronic Cigarette Refills; Regul. Toxicol. Pharmacol. 79 (2016) 144–148. DOI: 10.1016/j.yrtph.2016.03.024 BeauvalN. HowsamM. AntherieuS. AllorgeD. SoyezM. GarçonG. GoossensJ.F. Lo-GuidiceJ.M. GaratA. Trace Elements in E-Liquids – Development and Validation of an ICP-MS Method for the Analysis of Electronic Cigarette Refills Regul. Toxicol. Pharmacol. 79 2016 144 148 10.1016/j.yrtph.2016.03.024 Open DOISearch in Google Scholar

Kamilari, E., K. Farsalinos, K. Poulas, C.G. Kontoyannis, and M.G. Orkoula: Detection and Quantitative Determination of Heavy Metals in Electronic Cigarette Refill Liquids Using Total Reflection X-Ray Fluorescence Spectrometry; Food Chem. Toxicol. 116 (2018) 233–237. DOI: 10.1016/j.fct.2018.04.035 KamilariE. FarsalinosK. PoulasK. KontoyannisC.G. OrkoulaM.G. Detection and Quantitative Determination of Heavy Metals in Electronic Cigarette Refill Liquids Using Total Reflection X-Ray Fluorescence Spectrometry Food Chem. Toxicol. 116 2018 233 237 10.1016/j.fct.2018.04.035 Open DOISearch in Google Scholar

Na, C.-J., S.-H. Jo, K.-H. Kim, J.-R. Sohn, and Y.-S. Son: The Transfer Characteristics of Heavy Metals in Electronic Cigarette Liquid; Environ. Res. 174 (2019) 152–159. DOI: 10.1016/j.envres.2019.04.025 NaC.-J. JoS.-H. KimK.-H. SohnJ.-R. SonY.-S. The Transfer Characteristics of Heavy Metals in Electronic Cigarette Liquid Environ. Res. 174 2019 152 159 10.1016/j.envres.2019.04.025 Open DOISearch in Google Scholar

Zhao, D., A. Navas-Acien, V. Ilievski, V. Slavkovich, P. Olmedo, B. Adria-Mora, A. Domingo-Relloso, A. Aherrera, N.J. Kleiman, A.M. Rule, and M. Hilpert: Metal Concentrations in Electronic Cigarette Aerosol: Effect of Open-System and Closed-System Devices and Power Settings; Environ. Res. 174 (2019) 125–134. DOI: 10.1016/j.envres.2019.04.003 ZhaoD. Navas-AcienA. IlievskiV. SlavkovichV. OlmedoP. Adria-MoraB. Domingo-RellosoA. AherreraA. KleimanN.J. RuleA.M. HilpertM. Metal Concentrations in Electronic Cigarette Aerosol: Effect of Open-System and Closed-System Devices and Power Settings Environ. Res. 174 2019 125 134 10.1016/j.envres.2019.04.003 Open DOISearch in Google Scholar

Farsalinos, K.E., V. Voudris, and K. Poulas: Are Metals Emitted from Electronic Cigarettes a Reason for Health Concern? A Risk-Assessment Analysis of Currently Available Literature; Int. J. Environ. Res. Public Health 12 (2015) 5215–5232. DOI: 10.3390/ijerph120505215 FarsalinosK.E. VoudrisV. PoulasK. Are Metals Emitted from Electronic Cigarettes a Reason for Health Concern? A Risk-Assessment Analysis of Currently Available Literature Int. J. Environ. Res. Public Health 12 2015 5215 5232 10.3390/ijerph120505215 Open DOISearch in Google Scholar

Fowles, J., T. Barreau, and N. Wu: Cancer and Non-Cancer Risk Concerns from Metals in Electronic Cigarette Liquids and Aerosols; Int. J. Environ. Res. Public Health 17 (2020) 2146. DOI: 10.3390/ijerph17062146 FowlesJ. BarreauT. WuN. Cancer and Non-Cancer Risk Concerns from Metals in Electronic Cigarette Liquids and Aerosols Int. J. Environ. Res. Public Health 17 2020 2146 10.3390/ijerph17062146 Open DOISearch in Google Scholar

Saliba, N.A., A. El Hellani, E. Honein, R. Salman, S. Talih, J. Zeaiter, and A. Shihadeh: Surface Chemistry of Electronic Cigarette Electrical Heating Coils: Effects of Metal Type on Propylene Glycol Thermal Decomposition; J. Anal. Appl. Pyrolysis 134 (2018) 520–525. DOI: 10.1016/j.jaap.2018.07.019 SalibaN.A. El HellaniA. HoneinE. SalmanR. TalihS. ZeaiterJ. ShihadehA. Surface Chemistry of Electronic Cigarette Electrical Heating Coils: Effects of Metal Type on Propylene Glycol Thermal Decomposition J. Anal. Appl. Pyrolysis 134 2018 520 525 10.1016/j.jaap.2018.07.019 Open DOISearch in Google Scholar

Uchiyama, S., K. Ohta, Y. Inaba, and N. Kunugita: Determination of Carbonyl Compounds Generated from the E-Cigarette Using Coupled Silica Cartridges Impregnated with Hydroquinone and 2,4-Dinitrophenylhydrazine, Followed by High-Performance Liquid Chromatography; Anal. Sci. 29 (2013) 1219–1222. DOI: 10.2116/analsci.29.1219 UchiyamaS. OhtaK. InabaY. KunugitaN. Determination of Carbonyl Compounds Generated from the E-Cigarette Using Coupled Silica Cartridges Impregnated with Hydroquinone and 2,4-Dinitrophenylhydrazine, Followed by High-Performance Liquid Chromatography Anal. Sci. 29 2013 1219 1222 10.2116/analsci.29.1219 Open DOISearch in Google Scholar

Farsalinos, K.E., K.A. Kistler, A. Pennington, A. Spyrou, D. Kouretas, and G. Gillman: Aldehyde Levels in E-Cigarette Aerosol: Findings from a Replication Study and from Use of a New-Generation Device; Food Chem. Toxicol. 111 (2018) 64–70. DOI: 10.1016/j.fct.2017.11.002 FarsalinosK.E. KistlerK.A. PenningtonA. SpyrouA. KouretasD. GillmanG. Aldehyde Levels in E-Cigarette Aerosol: Findings from a Replication Study and from Use of a New-Generation Device Food Chem. Toxicol. 111 2018 64 70 10.1016/j.fct.2017.11.002 Open DOISearch in Google Scholar

Gillman, I.G., K. Kistler, E. Stewart, and A.R. Paolantonio: Effect of Variable Power Levels on the Yield of Total Aerosol Mass and Formation of Aldehydes in E-Cigarette Aerosols; Regul. Toxicol. Pharmacol. 75 (2016) 58–65. DOI: 10.1016/j.yrtph.2015.12.019 GillmanI.G. KistlerK. StewartE. PaolantonioA.R. Effect of Variable Power Levels on the Yield of Total Aerosol Mass and Formation of Aldehydes in E-Cigarette Aerosols Regul. Toxicol. Pharmacol. 75 2016 58 65 10.1016/j.yrtph.2015.12.019 Open DOISearch in Google Scholar

Kosmider, L., C.F. Kimber, J. Kurek, O. Corcoran, and L.E. Dawkins: Compensatory Puffing with Lower Nicotine Concentration E-Liquids Increases Carbonyl Exposure in E-Cigarette Aerosols; Nicotine Tob. Res. 20 (2018) 998–1003. DOI: 10.1093/ntr/ntx162 KosmiderL. KimberC.F. KurekJ. CorcoranO. DawkinsL.E. Compensatory Puffing with Lower Nicotine Concentration E-Liquids Increases Carbonyl Exposure in E-Cigarette Aerosols Nicotine Tob. Res. 20 2018 998 1003 10.1093/ntr/ntx162 Open DOISearch in Google Scholar

Leventhal, A.M., D.R. Madden, N. Peraza, S.J. Schiff, L. Lebovitz, L. Whitted, J. Barrington-Trimis, T.B. Mason, M.K. Anderson, and A.P. Tackett: Effect of Exposure to E-Cigarettes with Salt vs Free-Base Nicotine on the Appeal and Sensory Experience of Vaping: A Randomized Clinical Trial; JAMA Netw. Open. 4 (2021) e2032757. DOI: 10.1001/jamanetworkopen.2020.32757 LeventhalA.M. MaddenD.R. PerazaN. SchiffS.J. LebovitzL. WhittedL. Barrington-TrimisJ. MasonT.B. AndersonM.K. TackettA.P. Effect of Exposure to E-Cigarettes with Salt vs Free-Base Nicotine on the Appeal and Sensory Experience of Vaping: A Randomized Clinical Trial JAMA Netw. Open. 4 2021 e2032757 10.1001/jamanetworkopen.2020.32757 Open DOISearch in Google Scholar

Ebajemito, J.K., M. McEwan, N. Gale, O.M. Camacho, G. Hardie, and C.J. Proctor: A Randomised Controlled Single-Centre Open-Label Pharmacokinetic Study to Examine Various Approaches of Nicotine Delivery Using Electronic Cigarettes; Sci. Rep. 10 (2020) 19980. DOI: 10.1038/s41598-020-76610-4 EbajemitoJ.K. McEwanM. GaleN. CamachoO.M. HardieG. ProctorC.J. A Randomised Controlled Single-Centre Open-Label Pharmacokinetic Study to Examine Various Approaches of Nicotine Delivery Using Electronic Cigarettes Sci. Rep. 10 2020 19980 10.1038/s41598-020-76610-4 Open DOISearch in Google Scholar

O’Connell, G., J.D. Pritchard, C. Prue, J. Thompson, T. Verron, D. Graff, and T.A. Walele: A Randomised, Open-Label, Cross-Over Clinical Study to Evaluate the Pharmacokinetic Profiles of Cigarettes and E-Cigarettes with Nicotine Salt Formulations in US Adult Smokers; Intern. Emerg. Med. 14 (2019) 853–861. DOI: 10.1007/s11739-019-02025-3 O’ConnellG. PritchardJ.D. PrueC. ThompsonJ. VerronT. GraffD. WaleleT.A. A Randomised, Open-Label, Cross-Over Clinical Study to Evaluate the Pharmacokinetic Profiles of Cigarettes and E-Cigarettes with Nicotine Salt Formulations in US Adult Smokers Intern. Emerg. Med. 14 2019 853 861 10.1007/s11739-019-02025-3 Open DOISearch in Google Scholar

Talih, S., R. Salman, R. El-Hage, N. Karaoghlanian, A. El-Hellani, N. Saliba, and A. Shihadeh: Effect of Free-Base and Protonated Nicotine on Nicotine Yield from Electronic Cigarettes with Varying Power and Liquid Vehicle; Sci. Rep. 10 (2020) 16263. DOI: 10.1038/s41598-020-73385-6 TalihS. SalmanR. El-HageR. KaraoghlanianN. El-HellaniA. SalibaN. ShihadehA. Effect of Free-Base and Protonated Nicotine on Nicotine Yield from Electronic Cigarettes with Varying Power and Liquid Vehicle Sci. Rep. 10 2020 16263 10.1038/s41598-020-73385-6 Open DOISearch in Google Scholar

Harvanko, A.M., C.M. Havel, P. Jacob III, and N.L. Benowitz: Characterization of Nicotine Salts in 23 Electronic Cigarette Refill Liquids; Nicotine Tob. Res. 22 (2020) 1239–1243. DOI: 10.1093/ntr/ntz232 HarvankoA.M. HavelC.M. JacobP.III BenowitzN.L. Characterization of Nicotine Salts in 23 Electronic Cigarette Refill Liquids Nicotine Tob. Res. 22 2020 1239 1243 10.1093/ntr/ntz232 Open DOISearch in Google Scholar

Moldoveanu, S.C.: Pyrolysis of Organic Molecules with Applications to Health and Environmental Issues; in: Techniques and Instrumentation in Analytical Chemistry, Vol 28, Elsevier Science, Amsterdam, The Netherlands, 2010, pp. 471–526. MoldoveanuS.C. Pyrolysis of Organic Molecules with Applications to Health and Environmental Issues in: Techniques and Instrumentation in Analytical Chemistry 28 Elsevier Science Amsterdam, The Netherlands 2010 471 526 Search in Google Scholar

Pankow, J.F., K. Kim, K.J. McWhirter, W. Luo, J.O. Escobedo, R.M. Strongin, A.K. Duell, and D.H. Peyton: Benzene Formation in Electronic Cigarettes; PLoS One 12 (2017) e0173055. DOI: 10.1371/journal.pone.0173055 PankowJ.F. KimK. McWhirterK.J. LuoW. EscobedoJ.O. StronginR.M. DuellA.K. PeytonD.H. Benzene Formation in Electronic Cigarettes PLoS One 12 2017 e0173055 10.1371/journal.pone.0173055 Open DOISearch in Google Scholar

Cao, S., C. Yang, Y. Gan, and Z. Lu: The Health Effects of Passive Smoking: An Overview of Systematic Reviews Based on Observational Epidemiological Evidence; PLoS One 10 (2015) e0139907. DOI: 10.1371/journal.pone.0139907 CaoS. YangC. GanY. LuZ. The Health Effects of Passive Smoking: An Overview of Systematic Reviews Based on Observational Epidemiological Evidence PLoS One 10 2015 e0139907 10.1371/journal.pone.0139907 Open DOISearch in Google Scholar

Li, L., Y. Lin, T. Xia, and Y. Zhu: Effects of Electronic Cigarettes on Indoor Air Quality and Health; Ann. Rev. Public Health 41 (2020) 363–380. DOI: 10.1146/annurev-publhealth-040119-094043 LiL. LinY. XiaT. ZhuY. Effects of Electronic Cigarettes on Indoor Air Quality and Health Ann. Rev. Public Health 41 2020 363 380 10.1146/annurev-publhealth-040119-094043 Open DOISearch in Google Scholar

Chen, R., A. Aherrera, C. Isichei, P. Olmedo, S. Jarmul, J.E. Cohen, A. Navas-Acien, and A.M. Rule: Assessment of Indoor Air Quality at an Electronic Cigarette (Vaping) Convention; J. Expo. Sci. Environ. Epidemiol. 28 (2018) 522–529. DOI: 10.1038/s41370-017-0005-x ChenR. AherreraA. IsicheiC. OlmedoP. JarmulS. CohenJ.E. Navas-AcienA. RuleA.M. Assessment of Indoor Air Quality at an Electronic Cigarette (Vaping) Convention J. Expo. Sci. Environ. Epidemiol. 28 2018 522 529 10.1038/s41370-017-0005-x Open DOISearch in Google Scholar

Martuzevicius, D., T. Prasauskas, A. Setyan, G. O’Connell, X. Cahours, R. Julien, and S. Colard: Characterization of the Spatial and Temporal Dispersion Differences Between Exhaled E-Cigarette Mist and Cigarette Smoke; Nicotine Tob. Res. 21 (2019) 1371–1377. DOI: 10.1093/ntr/nty121 MartuzeviciusD. PrasauskasT. SetyanA. O’ConnellG. CahoursX. JulienR. ColardS. Characterization of the Spatial and Temporal Dispersion Differences Between Exhaled E-Cigarette Mist and Cigarette Smoke Nicotine Tob. Res. 21 2019 1371 1377 10.1093/ntr/nty121 Open DOISearch in Google Scholar

Czogala, J., M.L. Goniewicz, B. Fidelus, W. Zielinska-Danch, M.J. Travers, and A. Sobczak: Secondhand Exposure to Vapors from Electronic Cigarettes; Nicotine Tob. Res. 16 (2014) 655–662. DOI: 10.1093/ntr/ntt203 CzogalaJ. GoniewiczM.L. FidelusB. Zielinska-DanchW. TraversM.J. SobczakA. Secondhand Exposure to Vapors from Electronic Cigarettes Nicotine Tob. Res. 16 2014 655 662 10.1093/ntr/ntt203 Open DOISearch in Google Scholar

Klepeis, N.E., J. Bellettiere, S.C. Hughes, B. Nguyen, V. Berardi, S. Liles, S. Obayashi, C.R. Hofstetter, E. Blumberg, and M.F. Hovell: Fine Particles in Homes of Predominantly Low-Income Families with Children and Smokers: Key Physical and Behavioral Determinants to Inform Indoor-Air-Quality Interventions; PLoS One 12 (2017) e0177718. DOI: 10.1371/journal.pone.0177718 KlepeisN.E. BellettiereJ. HughesS.C. NguyenB. BerardiV. LilesS. ObayashiS. HofstetterC.R. BlumbergE. HovellM.F. Fine Particles in Homes of Predominantly Low-Income Families with Children and Smokers: Key Physical and Behavioral Determinants to Inform Indoor-Air-Quality Interventions PLoS One 12 2017 e0177718 10.1371/journal.pone.0177718 Open DOISearch in Google Scholar

Bals, R., J. Boyd, S. Esposito, R. Foronjy, P.S. Hiemstra, C.A. Jiménez-Ruiz, P. Katsaounou, A. Lindberg, C. Metz, W. Schober, A. Spira, and F. Blasi: Electronic Cigarettes: A Task Force Report from the European Respiratory Society; Eur. Respir. J. 53 (2019) 1801151. DOI: 10.1183/13993003.01151-2018 BalsR. BoydJ. EspositoS. ForonjyR. HiemstraP.S. Jiménez-RuizC.A. KatsaounouP. LindbergA. MetzC. SchoberW. SpiraA. BlasiF. Electronic Cigarettes: A Task Force Report from the European Respiratory Society Eur. Respir. J. 53 2019 1801151 10.1183/13993003.01151-2018 Open DOISearch in Google Scholar

Cancer Research UK: Cancer Research UK Briefing: Electronic Cigarettes; 2016. Available at: https://www.cancerresearchuk.org/sites/default/files/e-cigarette_briefing_nov_2016_final.pdf (accessed January 26, 2021) Cancer Research UK Cancer Research UK Briefing: Electronic Cigarettes 2016 Available at: https://www.cancerresearchuk.org/sites/default/files/e-cigarette_briefing_nov_2016_final.pdf (accessed January 26, 2021) Search in Google Scholar

Public Health England: Use of E-Cigarettes in Public Places and Workplaces. Advice to Inform Evidence-based Policy Making; 2016. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/768952/PHE-advice-on-use-of-e-cigarettes-in-public-places-and-workplaces.PDF (accessed January 26, 2021) Public Health England Use of E-Cigarettes in Public Places and Workplaces. Advice to Inform Evidence-based Policy Making 2016 Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/768952/PHE-advice-on-use-of-e-cigarettes-in-public-places-and-workplaces.PDF (accessed January 26, 2021) Search in Google Scholar

Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT): Statement on the Potential Toxicological Risks from Electronic Nicotine (and Non-Nicotine) Delivery Systems (E(N)NDS – E-Cigarettes); 2020. Available at: https://cot.food.gov.uk/sites/default/files/2020-09/COTE(N)NDSstatement2020-04.pdf (accessed January 26, 2021) Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) Statement on the Potential Toxicological Risks from Electronic Nicotine (and Non-Nicotine) Delivery Systems (E(N)NDS – E-Cigarettes) 2020 Available at: https://cot.food.gov.uk/sites/default/files/2020-09/COTE(N)NDSstatement2020-04.pdf (accessed January 26, 2021) Search in Google Scholar

Raunio, H.: In Silico Toxicology – Non-Testing Methods; Front. Pharmacol. 2 (2011) 33. DOI: 10.3389/fphar.2011.00033 RaunioH. In Silico Toxicology – Non-Testing Methods Front. Pharmacol. 2 2011 33 10.3389/fphar.2011.00033 Open DOISearch in Google Scholar

Zarini, D., A. Sangion, E. Ferri, E. Caruso, S. Zucchi, A. Orro, and E. Papa: Are In Silico Approaches Applicable as a First Step for the Prediction of E-Liquid Toxicity in E-Cigarettes?; Chem. Res. Toxicol. 33 (2020) 2381–2389. DOI: 10.1021/acs.chemrestox.0c00136 ZariniD. SangionA. FerriE. CarusoE. ZucchiS. OrroA. PapaE. Are In Silico Approaches Applicable as a First Step for the Prediction of E-Liquid Toxicity in E-Cigarettes? Chem. Res. Toxicol. 33 2020 2381 2389 10.1021/acs.chemrestox.0c00136 Open DOISearch in Google Scholar

Merecz-Sadowska, A., P. Sitarek, H. Zielinska-Blizniewska, K. Malinowska, K. Zajdel, L. Zakonnik, and R. Zajdel: A Summary of In Vitro and In Vivo Studies Evaluating the Impact of E-Cigarette Exposure on Living Organisms and the Environment; Int. J. Mol. Sci. 21 (2020) 652. DOI: 10.3390/ijms21020652 Merecz-SadowskaA. SitarekP. Zielinska-BlizniewskaH. MalinowskaK. ZajdelK. ZakonnikL. ZajdelR. A Summary of In Vitro and In Vivo Studies Evaluating the Impact of E-Cigarette Exposure on Living Organisms and the Environment Int. J. Mol. Sci. 21 2020 652 10.3390/ijms21020652 Open DOISearch in Google Scholar

Avila, A.M., I. Bebenek, J.A. Bonzo, T. Bourcier, K.L. Davis Bruno, D.B. Carlson, J. Dubinion, I. Elayan, W. Harrouk, S.L. Lee, D.L. Mendrick, J.C. Merrill, J. Peretz, E. Place, M. Saulnier, R.L. Wange, J. Yao, D. Zhao, and P.C. Brown: An FDA/CDER Perspective on Nonclinical Testing Strategies: Classical Toxicology Approaches and New Approach Methodologies (NAMs); Regul. Toxicol. Pharmacol. 114 (2020) 104662. DOI: 10.1016/j.yrtph.2020.104662 AvilaA.M. BebenekI. BonzoJ.A. BourcierT. Davis BrunoK.L. CarlsonD.B. DubinionJ. ElayanI. HarroukW. LeeS.L. MendrickD.L. MerrillJ.C. PeretzJ. PlaceE. SaulnierM. WangeR.L. YaoJ. ZhaoD. BrownP.C. An FDA/CDER Perspective on Nonclinical Testing Strategies: Classical Toxicology Approaches and New Approach Methodologies (NAMs) Regul. Toxicol. Pharmacol. 114 2020 104662 10.1016/j.yrtph.2020.104662 Open DOISearch in Google Scholar

European Chemicals Agency: In Vitro Methods; 2020. Available at: https://echa.europa.eu/support/registration/how-to-avoid-unnecessary-testing-on-animals/in-vitro-methods (accessed January 6, 2021). European Chemicals Agency In Vitro Methods 2020 Available at: https://echa.europa.eu/support/registration/how-to-avoid-unnecessary-testing-on-animals/in-vitro-methods (accessed January 6, 2021). Search in Google Scholar

Wan, J., M.D. Johnson, J. Schilz, M.V. Djordjevic, J.R. Rice, and P.G. Shields: Evaluation of In Vitro Assays for Assessing the Toxicity of Cigarette Smoke and Smokeless Tobacco; Cancer Epidemiol. Biomarkers Prev. 18 (2009) 3263–3304. DOI: 10.1158/1055-9965.EPI-09-0965 WanJ. JohnsonM.D. SchilzJ. DjordjevicM.V. RiceJ.R. ShieldsP.G. Evaluation of In Vitro Assays for Assessing the Toxicity of Cigarette Smoke and Smokeless Tobacco Cancer Epidemiol. Biomarkers Prev. 18 2009 3263 3304 10.1158/1055-9965.EPI-09-0965 Open DOISearch in Google Scholar

Czekala, L., L. Simms, M. Stevenson, N. Tschierske, A.G. Maione, and T. Walele: Toxicological Comparison of Cigarette Smoke and E-Cigarette Aerosol Using a 3D In Vitro Human Respiratory Model; Regul. Toxicol. Pharmacol. 103 (2019) 314–324. DOI: 10.1016/j.yrtph.2019.01.036 CzekalaL. SimmsL. StevensonM. TschierskeN. MaioneA.G. WaleleT. Toxicological Comparison of Cigarette Smoke and E-Cigarette Aerosol Using a 3D In Vitro Human Respiratory Model Regul. Toxicol. Pharmacol. 103 2019 314 324 10.1016/j.yrtph.2019.01.036 Open DOISearch in Google Scholar

Iskandar, A.R., C. Mathis, F. Martin, P. Leroy, A. Sewer, S. Majeed, D. Kuehn, K. Trivedi, D. Grandolfo, M. Cabanski, E. Guedj, C. Merg, S. Frentzel, N.V. Ivanov, M.C. Peitsch and J. Hoeng: 3-D Nasal Cultures: Systems Toxicological Assessment of a Candidate Modified-Risk Tobacco Product; ALTEX 34 (2017) 23–48. DOI: 10.14573/altex.1605041 IskandarA.R. MathisC. MartinF. LeroyP. SewerA. MajeedS. KuehnD. TrivediK. GrandolfoD. CabanskiM. GuedjE. MergC. FrentzelS. IvanovN.V. PeitschM.C. HoengJ. 3-D Nasal Cultures: Systems Toxicological Assessment of a Candidate Modified-Risk Tobacco Product ALTEX 34 2017 23 48 10.14573/altex.1605041 Open DOISearch in Google Scholar

Breheny, D., D. Thorne, A. Baxter, S. Bozhilova, T. Jaunky, S. Santopietro, M. Taylor, A. Terry, and M. Gaça: The In Vitro Assessment of a Novel Vaping Technology; Toxicol. Rep. 7 (2020) 1145–1156. DOI: 10.1016/j.toxrep.2020.08.016 BrehenyD. ThorneD. BaxterA. BozhilovaS. JaunkyT. SantopietroS. TaylorM. TerryA. GaçaM. The In Vitro Assessment of a Novel Vaping Technology Toxicol. Rep. 7 2020 1145 1156 10.1016/j.toxrep.2020.08.016 Open DOISearch in Google Scholar

Wang, G., W. Liu, and W. Song: Toxicity Assessment of Electronic Cigarettes; Inhal. Toxicol. 31 (2019) 259–273. DOI: 10.1080/08958378.2019.1671558 WangG. LiuW. SongW. Toxicity Assessment of Electronic Cigarettes Inhal. Toxicol. 31 2019 259 273 10.1080/08958378.2019.1671558 Open DOISearch in Google Scholar

Breheny, D., O. Oke, K. Pant, and M. Gaça: Comparative Tumour Promotion Assessment of E-Cigarette and Cigarettes Using the In Vitro Bhas 42 Cell Transformation Assay; Environ. Mol. Mutagen. 58 (2017) 190–198. DOI: 10.1002/em.22091 BrehenyD. OkeO. PantK. GaçaM. Comparative Tumour Promotion Assessment of E-Cigarette and Cigarettes Using the In Vitro Bhas 42 Cell Transformation Assay Environ. Mol. Mutagen. 58 2017 190 198 10.1002/em.22091 Open DOISearch in Google Scholar

Thorne, D., I. Crooks, M. Hollings, A. Seymour, C. Meredith, and M. Gaça: The Mutagenic Assessment of an Electronic-Cigarette and Reference Cigarette Smoke Using the Ames Assay in Strains TA98 and TA100; Mutat. Res. 812 (2016) 29–38. DOI: 10.1016/j.mrgentox.2016.10.005 ThorneD. CrooksI. HollingsM. SeymourA. MeredithC. GaçaM. The Mutagenic Assessment of an Electronic-Cigarette and Reference Cigarette Smoke Using the Ames Assay in Strains TA98 and TA100 Mutat. Res. 812 2016 29 38 10.1016/j.mrgentox.2016.10.005 Open DOISearch in Google Scholar

Thorne, D., M. Hollings, A. Seymour, J. Adamson, A. Dalrymple, M. Ballantyne, and M. Gaca: Extreme Testing of Undiluted E-Cigarette Aerosol In Vitro Using an Ames Air-Agar-Interface Technique; Mutat. Res. Genet. Toxicol. Environ. Mutagen. 828 (2018) 46–54. DOI: 10.1016/j.mrgentox.2018.01.008 ThorneD. HollingsM. SeymourA. AdamsonJ. DalrympleA. BallantyneM. GacaM. Extreme Testing of Undiluted E-Cigarette Aerosol In Vitro Using an Ames Air-Agar-Interface Technique Mutat. Res. Genet. Toxicol. Environ. Mutagen. 828 2018 46 54 10.1016/j.mrgentox.2018.01.008 Open DOISearch in Google Scholar

Azzopardi, D., K. Patel, T. Jaunky, S. Santopietro, O.M. Camacho, J. McAughey, and M. Gaça: Electronic Cigarette Aerosol Induces Significantly Less Cytotoxicity Than Tobacco Smoke; Toxicol. Mech. Methods 26 (2016) 477–491. DOI: 10.1080/15376516.2016.1217112 AzzopardiD. PatelK. JaunkyT. SantopietroS. CamachoO.M. McAugheyJ. GaçaM. Electronic Cigarette Aerosol Induces Significantly Less Cytotoxicity Than Tobacco Smoke Toxicol. Mech. Methods 26 2016 477 491 10.1080/15376516.2016.1217112 Open DOISearch in Google Scholar

Bishop, E., L. Haswell, J. Adamson, S. Costigan, D. Thorne, and M. Gaça: An Approach to Testing Undiluted E-Cigarette Aerosol In Vitro Using 3D Reconstituted Human Airway Epithelium; Toxicol. In Vitro 54 (2019) 391–401. DOI: 10.1016/j.tiv.2018.01.010 BishopE. HaswellL. AdamsonJ. CostiganS. ThorneD. GaçaM. An Approach to Testing Undiluted E-Cigarette Aerosol In Vitro Using 3D Reconstituted Human Airway Epithelium Toxicol. In Vitro 54 2019 391 401 10.1016/j.tiv.2018.01.010 Open DOISearch in Google Scholar

Makwana, O., H. Flockton, G.A. Smith, G.P. Watters, R. Nisar, and W. Fields: Mechanisms of Whole Smoke Conditioned Media Induced Cytotoxicity to Human Aortic Endothelial Cells; Toxicol. In Vitro 58 (2019) 239–244. DOI: 10.1016/j.tiv.2019.03.011 MakwanaO. FlocktonH. SmithG.A. WattersG.P. NisarR. FieldsW. Mechanisms of Whole Smoke Conditioned Media Induced Cytotoxicity to Human Aortic Endothelial Cells Toxicol. In Vitro 58 2019 239 244 10.1016/j.tiv.2019.03.011 Open DOISearch in Google Scholar

Neilson, L., C. Mankus, D. Thorne, G. Jackson, J. DeBay, and C. Meredith: Development of an In Vitro Cytotoxicity Model for Aerosol Exposure Using 3D Reconstructed Human Airway Tissue; Application for Assessment of E-Cigarette Aerosol; Toxicol. In Vitro 29 (2015) 1952–1962. DOI: 10.1016/j.tiv.2015.05.018 NeilsonL. MankusC. ThorneD. JacksonG. DeBayJ. MeredithC. Development of an In Vitro Cytotoxicity Model for Aerosol Exposure Using 3D Reconstructed Human Airway Tissue; Application for Assessment of E-Cigarette Aerosol Toxicol. In Vitro 29 2015 1952 1962 10.1016/j.tiv.2015.05.018 Open DOISearch in Google Scholar

Thorne, D., S. Larard, A. Baxter, C. Meredith, and M. Gaça: The Comparative In Vitro Assessment of E-Cigarette and Cigarette Smoke Aerosols Using the γH2AX Assay and Applied Dose Measurements; Toxicol. Lett. 265 (2017) 170–178. DOI: 10.1016/j.toxlet.2016.12.006 ThorneD. LarardS. BaxterA. MeredithC. GaçaM. The Comparative In Vitro Assessment of E-Cigarette and Cigarette Smoke Aerosols Using the γH2AX Assay and Applied Dose Measurements Toxicol. Lett. 265 2017 170 178 10.1016/j.toxlet.2016.12.006 Open DOISearch in Google Scholar

Thorne, D., R. Leverette, D. Breheny, M. Lloyd, S. McEnaney, J. Whitwell, J. Clements, B. Bombick, and M. Gaça: Genotoxicity Evaluation of Tobacco and Nicotine Delivery Products: Part One. Mouse Lymphoma Assay; Food Chem. Toxicol. 132 (2019) 110584. DOI: 10.1016/j.fct.2019.110584 ThorneD. LeveretteR. BrehenyD. LloydM. McEnaneyS. WhitwellJ. ClementsJ. BombickB. GaçaM. Genotoxicity Evaluation of Tobacco and Nicotine Delivery Products: Part One. Mouse Lymphoma Assay Food Chem. Toxicol. 132 2019 110584 10.1016/j.fct.2019.110584 Open DOISearch in Google Scholar

Thorne, D., R. Leverette, D. Breheny, M. Lloyd, S. McEnaney, J. Whitwell, J. Clements, B. Bombick, and M. Gaça: Genotoxicity Evaluation of Tobacco and Nicotine Delivery Products: Part Two. In Vitro Micronucleus Assay; Food Chem. Toxicol. 132 (2019) 110546. DOI: 10.1016/j.fct.2019.05.054 ThorneD. LeveretteR. BrehenyD. LloydM. McEnaneyS. WhitwellJ. ClementsJ. BombickB. GaçaM. Genotoxicity Evaluation of Tobacco and Nicotine Delivery Products: Part Two. In Vitro Micronucleus Assay Food Chem. Toxicol. 132 2019 110546 10.1016/j.fct.2019.05.054 Open DOISearch in Google Scholar

Ito, S., M. Taylor, S. Mori, D. Thorne, T. Nishino, D. Breheny, M. Gaça, K. Yoshino, and C. Proctor: An Inter-Laboratory In Vitro Assessment of Cigarettes and Next Generation Nicotine Delivery Products; Toxicol. Lett. 315 (2019) 14–22. DOI: 10.1016/j.toxlet.2019.08.004 ItoS. TaylorM. MoriS. ThorneD. NishinoT. BrehenyD. GaçaM. YoshinoK. ProctorC. An Inter-Laboratory In Vitro Assessment of Cigarettes and Next Generation Nicotine Delivery Products Toxicol. Lett. 315 2019 14 22 10.1016/j.toxlet.2019.08.004 Open DOISearch in Google Scholar

Taylor, M., T. Carr, O. Oke, T. Jaunky, D. Breheny, and F. Lowe: E-Cigarette Aerosols Induce Lower Oxidative Stress In Vitro When Compared to Tobacco Smoke; Toxicol. Mech. Methods 6 (2016) 445–467. DOI: 10.1080/15376516.2016.1222473 TaylorM. CarrT. OkeO. JaunkyT. BrehenyD. LoweF. E-Cigarette Aerosols Induce Lower Oxidative Stress In Vitro When Compared to Tobacco Smoke Toxicol. Mech. Methods 6 2016 445 467 10.1080/15376516.2016.1222473 Open DOISearch in Google Scholar

Taylor, M., T. Jaunky, K. Hewitt, D. Breheny, F. Lowe, I.M. Fearon, and M. Gaça: A Comparative Assessment of E-Cigarette Aerosols and Cigarette Smoke on In Vitro Endothelial Cell Migration; Toxicol. Lett. 277 (2017) 123–128. DOI: 10.1016/j.toxlet.2017.06.001 TaylorM. JaunkyT. HewittK. BrehenyD. LoweF. FearonI.M. GaçaM. A Comparative Assessment of E-Cigarette Aerosols and Cigarette Smoke on In Vitro Endothelial Cell Migration Toxicol. Lett. 277 2017 123 128 10.1016/j.toxlet.2017.06.001 Open DOISearch in Google Scholar

Farsalinos, K.E. and R. Polosa: Safety Evaluation and Risk Assessment of Electronic Cigarettes as Tobacco Cigarette Substitutes: A Systematic Review; Ther. Adv. Drug Saf. 5 (2014) 67–86. DOI: 10.1177/2042098614524430 FarsalinosK.E. PolosaR. Safety Evaluation and Risk Assessment of Electronic Cigarettes as Tobacco Cigarette Substitutes: A Systematic Review Ther. Adv. Drug Saf. 5 2014 67 86 10.1177/2042098614524430 Open DOISearch in Google Scholar

Public Health England – Committee on Toxicity (COT): E-Cigarettes Likely to Reduce Harm to Health for Smokers but are not Entirely Risk-Free; 2020. Available at: https://phe-newsroom.prgloo.com/news/e-cigarettes-likely-to-reduce-harm-to-health-for-smokers-but-are-not-entirely-risk-free (accessed January 26, 2021) Public Health England – Committee on Toxicity (COT) E-Cigarettes Likely to Reduce Harm to Health for Smokers but are not Entirely Risk-Free 2020 Available at: https://phe-newsroom.prgloo.com/news/e-cigarettes-likely-to-reduce-harm-to-health-for-smokers-but-are-not-entirely-risk-free (accessed January 26, 2021) Search in Google Scholar

Banerjee, A., L.E. Haswell, A. Baxter, A. Parmar, D. Azzopardi, S. Corke, D. Thorne, J. Adamson, J. Mushonganono, M.D. Gaça, and E. Minet: Differential Gene Expression Using RNA Sequencing Profiling in a Reconstituted Airway Epithelium Exposed to Conventional Cigarette Smoke or Electronic Cigarette Aerosols; Appl. In Vitro Toxicol. 3 (2017) 84–98. DOI: 10.1089/aivt.2016.0024 BanerjeeA. HaswellL.E. BaxterA. ParmarA. AzzopardiD. CorkeS. ThorneD. AdamsonJ. MushonganonoJ. GaçaM.D. MinetE. Differential Gene Expression Using RNA Sequencing Profiling in a Reconstituted Airway Epithelium Exposed to Conventional Cigarette Smoke or Electronic Cigarette Aerosols Appl. In Vitro Toxicol. 3 2017 84 98 10.1089/aivt.2016.0024 Open DOISearch in Google Scholar

Haswell, L.D., A. Baxter, A. Banerjee, I. Verrastro, J. Mushonganono, J. Adamson, D. Thorne, M. Gaça, and E. Minet: Reduced Biological Effect of E-Cigarette Aerosol Compared to Cigarette Smoke Evaluated In Vitro Using Normalized Nicotine Dose and RNA-Seq-Based Toxicogenomics; Sci. Rep. 7 (2017) 888. DOI: 10.1038/s41598-017-00852-y HaswellL.D. BaxterA. BanerjeeA. VerrastroI. MushonganonoJ. AdamsonJ. ThorneD. GaçaM. MinetE. Reduced Biological Effect of E-Cigarette Aerosol Compared to Cigarette Smoke Evaluated In Vitro Using Normalized Nicotine Dose and RNA-Seq-Based Toxicogenomics Sci. Rep. 7 2017 888 10.1038/s41598-017-00852-y Open DOISearch in Google Scholar

Marescotti, D., C. Mathis, V. Belcastro, P. Leroy, S. Acali, F. Martin, R. Dulize, D. Bornand, D. Peric, E. Guedj, L. Ortega Torres, M. Biasioli, M. Fuhrimann, E. Fernandes, F. Frauendorfer, I. Gonzalez Suarez, D. Sciuscio, N.V. Ivanov, M.C. Peitsch, and J. Hoeng: Systems Toxicology Assessment of a Representative E-Liquid Formulation Using Human Primary Bronchial Epithelial Cells; Toxicol. Rep. 7 (2019) 67–80. DOI: 10.1016/j.toxrep.2019.11.016 MarescottiD. MathisC. BelcastroV. LeroyP. AcaliS. MartinF. DulizeR. BornandD. PericD. GuedjE. Ortega TorresL. BiasioliM. FuhrimannM. FernandesE. FrauendorferF. Gonzalez SuarezI. SciuscioD. IvanovN.V. PeitschM.C. HoengJ. Systems Toxicology Assessment of a Representative E-Liquid Formulation Using Human Primary Bronchial Epithelial Cells Toxicol. Rep. 7 2019 67 80 10.1016/j.toxrep.2019.11.016 Open DOISearch in Google Scholar

Titz, B., J. Szostak, A. Sewer, B. Phillips, C. Nury, T. Schneider, S. Dijon, O. Lavrynenko, A. Elamin, E. Guedj, E. Tsin Wong, S. Lebrun, G. Vuillaume, A. Kondylis, S. Gubian, S. Cano, P. Leroy, B. Keppler, N.V. Ivanov, P. Vanscheeuwijck, F. Martin, M.C. Peitsch, and J. Hoeng: Multi-Omics Systems Toxicology Study of Mouse Lung Assessing the Effects of Aerosols from Two Heat-Not-Burn Tobacco Products and Cigarette Smoke; Comput. Struct. Biotechnol. J. 18 (2020) 1056–1073. DOI: 10.1016/j.csbj.2020.04.011 TitzB. SzostakJ. SewerA. PhillipsB. NuryC. SchneiderT. DijonS. LavrynenkoO. ElaminA. GuedjE. Tsin WongE. LebrunS. VuillaumeG. KondylisA. GubianS. CanoS. LeroyP. KepplerB. IvanovN.V. VanscheeuwijckP. MartinF. PeitschM.C. HoengJ. Multi-Omics Systems Toxicology Study of Mouse Lung Assessing the Effects of Aerosols from Two Heat-Not-Burn Tobacco Products and Cigarette Smoke Comput. Struct. Biotechnol. J. 18 2020 1056 1073 10.1016/j.csbj.2020.04.011 Open DOISearch in Google Scholar

Slob, W., L.G. Soeteman-Hernández, W. Bil, Y.C.M. Staal, W.E. Stephens, and R. Talhout: A Method for Comparing the Impact on Carcinogenicity of Tobacco Products: A Case Study on Heated Tobacco Versus Cigarettes; Risk Anal. 40 (2020) 1355–1366. DOI: 10.1111/risa.13482 SlobW. Soeteman-HernándezL.G. BilW. StaalY.C.M. StephensW.E. TalhoutR. A Method for Comparing the Impact on Carcinogenicity of Tobacco Products: A Case Study on Heated Tobacco Versus Cigarettes Risk Anal. 40 2020 1355 1366 10.1111/risa.13482 Open DOISearch in Google Scholar

U.S. Department of Health and Human Services (DHHS): The Health Consequences of Smoking: A Report of the Surgeon General; Centers for Disease Control and Prevention, Atlanta, GA, USA, 2004. Available at: https://www.ncbi.nlm.nih.gov/books/NBK44695/ (accessed May 12, 2021) U.S. Department of Health and Human Services (DHHS) The Health Consequences of Smoking: A Report of the Surgeon General Centers for Disease Control and Prevention Atlanta, GA, USA 2004 Available at: https://www.ncbi.nlm.nih.gov/books/NBK44695/ (accessed May 12, 2021) Search in Google Scholar

El Dib, R., E.A. Suzumura, E.A. Akl, H. Gomaa, A. Agarwal, Y. Chang, M. Prasad, V. Ashoorion, D. Heels-Ansdell, W. Maziak, and G. Guyatt: Electronic Nicotine Delivery Systems and/or Electronic Non-nicotine Delivery Systems for Tobacco Smoking Cessation or Reduction: A Systematic Review and Meta-Analysis; BMJ Open 7 (2017) e012680. DOI: 10.1136/bmjopen-2016-012680 El DibR. SuzumuraE.A. AklE.A. GomaaH. AgarwalA. ChangY. PrasadM. AshoorionV. Heels-AnsdellD. MaziakW. GuyattG. Electronic Nicotine Delivery Systems and/or Electronic Non-nicotine Delivery Systems for Tobacco Smoking Cessation or Reduction: A Systematic Review and Meta-Analysis BMJ Open 7 2017 e012680 10.1136/bmjopen-2016-012680 Open DOISearch in Google Scholar

Hartmann-Boyce, J., H. McRobbie, C. Bullen, R. Begh, L.F. Stead, and P. Hajek: Electronic Cigarettes for Smoking Cessation; Cochrane Database Syst. Rev. 9 (2016) CD010216. DOI: 10.1002/14651858.CD010216.pub3 Hartmann-BoyceJ. McRobbieH. BullenC. BeghR. SteadL.F. HajekP. Electronic Cigarettes for Smoking Cessation Cochrane Database Syst. Rev. 9 2016 CD010216 10.1002/14651858.CD010216.pub3 Open DOISearch in Google Scholar

Kalkhoran, S. and S.A. Glantz: E-Cigarettes and Smoking Cessation in Real-World and Clinical Settings: A Systematic Review and Meta-Analysis; Lancet Respir. Med. 4 (2016) 116–128. DOI: 10.1016/S2213-2600(15)00521-4 KalkhoranS. GlantzS.A. E-Cigarettes and Smoking Cessation in Real-World and Clinical Settings: A Systematic Review and Meta-Analysis Lancet Respir. Med. 4 2016 116 128 10.1016/S2213-2600(15)00521-4 Open DOISearch in Google Scholar

Simonavicius, E., A. McNeil, D. Arnott, and L.S. Brose: What Factors are Associated with Current Smokers Using or Stopping E-Cigarette Use?; Drug Alcohol Depend. 173 (2017) 139–143. DOI: 10.1016/j.drugalcdep.2017.01.002 SimonaviciusE. McNeilA. ArnottD. BroseL.S. What Factors are Associated with Current Smokers Using or Stopping E-Cigarette Use? Drug Alcohol Depend. 173 2017 139 143 10.1016/j.drugalcdep.2017.01.002 Open DOISearch in Google Scholar

Fearon, I.M., A.C. Eldridge, N. Gale, M. McEwan, M.F. Stiles, and E.K. Round: Nicotine Pharmacokinetics of Electronic Cigarettes: A Review of the Literature; Regul. Toxicol. Pharmacol. 100 (2018) 25–34. DOI: 10.1016/j.yrtph.2018.09.004 FearonI.M. EldridgeA.C. GaleN. McEwanM. StilesM.F. RoundE.K. Nicotine Pharmacokinetics of Electronic Cigarettes: A Review of the Literature Regul. Toxicol. Pharmacol. 100 2018 25 34 10.1016/j.yrtph.2018.09.004 Open DOISearch in Google Scholar

Armitage, A., C. Dollery, T. Houseman, E. Kohner, P. Lewis, and D. Turner: Absorption of Nicotine from Small Cigars; Clin. Pharmacol. Ther. 23 (1978) 143–151. DOI: 10.1002/cpt1978232143 ArmitageA. DolleryC. HousemanT. KohnerE. LewisP. TurnerD. Absorption of Nicotine from Small Cigars Clin. Pharmacol. Ther. 23 1978 143 151 10.1002/cpt1978232143 Open DOISearch in Google Scholar

Armitage, A.K., J. Alexander, R. Hopkins, and C. Ward: Evaluation of a Low to Middle Tar/Medium Nicotine Cigarette Designed to Maintain Nicotine Delivery to the Smoker; Psychopharmacology 96 (1988) 447–453. DOI: 10.1007/BF02180022 ArmitageA.K. AlexanderJ. HopkinsR. WardC. Evaluation of a Low to Middle Tar/Medium Nicotine Cigarette Designed to Maintain Nicotine Delivery to the Smoker Psychopharmacology 96 1988 447 453 10.1007/BF02180022 Open DOISearch in Google Scholar

Armitage, A. and D. Turner: Absorption of Nicotine in Cigarette and Cigar Smoke Through the Oral Mucosa; Nature 226 (1970) 1231–1232. DOI: 10.1038/2261231a0 ArmitageA. TurnerD. Absorption of Nicotine in Cigarette and Cigar Smoke Through the Oral Mucosa Nature 226 1970 1231 1232 10.1038/2261231a0 Open DOISearch in Google Scholar

Benowitz, N. and P. Jacob III: Daily Intake of Nicotine During Cigarette Smoking; Clin. Pharmacol. Ther. 35 (1984) 499–504. DOI: 10.1038/clpt.1984.67 BenowitzN. JacobP.III Daily Intake of Nicotine During Cigarette Smoking Clin. Pharmacol. Ther. 35 1984 499 504 10.1038/clpt.1984.67 Open DOISearch in Google Scholar

Digard, H., C. Proctor, A. Kulasekaran, U. Malmqvist, and A. Richter: Determination of Nicotine Absorption from Multiple Tobacco Products and Nicotine Gum; Nicotine Tob. Res. 15 (2013) 255–261. DOI: 10.1093/ntr/nts123 DigardH. ProctorC. KulasekaranA. MalmqvistU. RichterA. Determination of Nicotine Absorption from Multiple Tobacco Products and Nicotine Gum Nicotine Tob. Res. 15 2013 255 261 10.1093/ntr/nts123 Open DOISearch in Google Scholar

Stiles, M.F., L.R. Campbell, D.W. Graff, B.A. Jones, R.V. Fant, and J.E. Henningfield: Pharmacodynamic and Pharmacokinetic Assessment of Electronic Cigarettes, Combustible Cigarettes, and Nicotine Gum: Implications for Abuse Liability; Psychopharmacology 234 (2017) 2643–2655. DOI: 10.1007/s00213-017-4665-y StilesM.F. CampbellL.R. GraffD.W. JonesB.A. FantR.V. HenningfieldJ.E. Pharmacodynamic and Pharmacokinetic Assessment of Electronic Cigarettes, Combustible Cigarettes, and Nicotine Gum: Implications for Abuse Liability Psychopharmacology 234 2017 2643 2655 10.1007/s00213-017-4665-y Open DOISearch in Google Scholar

Stiles, M.F., L.R. Campbell, T. Jin, D.W. Graff, R.V. Fant, and J.E. Henningfield: Assessment of the Abuse Liability of Three Menthol Vuse Solo Electronic Cigarettes Relative to Combustible Cigarettes and Nicotine Gum; Psychopharmacology 235 (2018) 2077–2086. DOI: 10.1007/s00213-018-4904-x StilesM.F. CampbellL.R. JinT. GraffD.W. FantR.V. HenningfieldJ.E. Assessment of the Abuse Liability of Three Menthol Vuse Solo Electronic Cigarettes Relative to Combustible Cigarettes and Nicotine Gum Psychopharmacology 235 2018 2077 2086 10.1007/s00213-018-4904-x Open DOISearch in Google Scholar

Bullen, C., H. McRobbie, S. Thornley, M. Glover, R. Lin, and M. Laugesen: Effect of an Electronic Nicotine Delivery Device (E Cigarette) on Desire to Smoke and Withdrawal, User Preferences and Nicotine Delivery: Randomised Cross-Over Trial; Tob. Control 19 (2010) 98–103. DOI: 10.1136/tc.2009.031567 BullenC. McRobbieH. ThornleyS. GloverM. LinR. LaugesenM. Effect of an Electronic Nicotine Delivery Device (E Cigarette) on Desire to Smoke and Withdrawal, User Preferences and Nicotine Delivery: Randomised Cross-Over Trial Tob. Control 19 2010 98 103 10.1136/tc.2009.031567 Open DOISearch in Google Scholar

Hansson, A., T. Rasmussen, and H. Kraiczi: Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum; Nicotine Tob. Res. 19 (2017) 477–483. DOI: 10.1093/ntr/ntw211 HanssonA. RasmussenT. KraicziH. Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum Nicotine Tob. Res. 19 2017 477 483 10.1093/ntr/ntw211 Open DOISearch in Google Scholar

Sukhija, M., R. Srivastava and A. Kaushik: Pharmacokinetic Characterization of Three Novel 4-mg Nicotine Lozenges; Int. J. Clin. Pharmacol. Ther. 56 (2018) 113–119. DOI: 10.5414/CP203097 SukhijaM. SrivastavaR. KaushikA. Pharmacokinetic Characterization of Three Novel 4-mg Nicotine Lozenges Int. J. Clin. Pharmacol. Ther. 56 2018 113 119 10.5414/CP203097 Open DOISearch in Google Scholar

Farsalinos K.E., A. Spyrou, K. Tsimopoulou, C. Stefopoulos, G. Romagna, and V. Voudris: Nicotine Absorption from Electronic Cigarette Use: Comparison Between First and New-Generation Devices; Sci. Rep. 4 (2014) 4133. DOI: 10.1038/srep04133 FarsalinosK.E. SpyrouA. TsimopoulouK. StefopoulosC. RomagnaG. VoudrisV. Nicotine Absorption from Electronic Cigarette Use: Comparison Between First and New-Generation Devices Sci. Rep. 4 2014 4133 10.1038/srep04133 Open DOISearch in Google Scholar

Nides, M.N., S.J. Leischow, M. Bhatter, and M. Simmons: Nicotine Blood Levels and Short-Term Smoking Reduction with an Electronic Nicotine Delivery System; Am. J. Health Behav. 38 (2014) 265–274. DOI: 10.5993/AJHB.38.2.12 NidesM.N. LeischowS.J. BhatterM. SimmonsM. Nicotine Blood Levels and Short-Term Smoking Reduction with an Electronic Nicotine Delivery System Am. J. Health Behav. 38 2014 265 274 10.5993/AJHB.38.2.12 Open DOISearch in Google Scholar

Walele, T., T. Sharma, R. Savioz, C. Martin, and J. Williams: A Randomised, Crossover Study on an Electronic Vapour Product, a Nicotine Inhalator and a Conventional Cigarette. Part A: Pharmacokinetics; Regul. Toxicol. Pharmacol. 74 (2016) 187–192. DOI: 10.1016/j.yrtph.2015.12.003 WaleleT. SharmaT. SaviozR. MartinC. WilliamsJ. A Randomised, Crossover Study on an Electronic Vapour Product, a Nicotine Inhalator and a Conventional Cigarette. Part A: Pharmacokinetics Regul. Toxicol. Pharmacol. 74 2016 187 192 10.1016/j.yrtph.2015.12.003 Open DOISearch in Google Scholar

St. Helen, G., C. Havel, D.A. Dempsey, P. Jacob III, and N.L. Benowitz: Nicotine Delivery, Retention and Pharmacokinetics From Various Electronic Cigarettes; Addiction 111 (2016) 535–544. DOI: 10.1111/add.13183 St. HelenG. HavelC. DempseyD.A. JacobP.III BenowitzN.L. Nicotine Delivery, Retention and Pharmacokinetics From Various Electronic Cigarettes Addiction 111 2016 535 544 10.1111/add.13183 Open DOISearch in Google Scholar

Vansickel, A.R. and T. Eissenberg: Electronic Cigarettes: Effective Nicotine Delivery After Acute Administration; Nicotine Tob. Res. 15 (2013) 267–270. DOI: 10.1093/ntr/ntr316 VansickelA.R. EissenbergT. Electronic Cigarettes: Effective Nicotine Delivery After Acute Administration Nicotine Tob. Res. 15 2013 267 270 10.1093/ntr/ntr316 Open DOISearch in Google Scholar

Wagener, T.L., E.L. Floyd, I. Stepanov, L.M. Driskill, S.G. Frank, E. Meier, E.L. Leavens, A.P. Tackett, N. Molina, and L. Queimado: Have Combustible Cigarettes Met Their Match? The Nicotine Delivery Profiles and Harmful Constituent Exposures of Second-Generation and Third-Generation Electronic Cigarette Users; Tob. Control 26 (2017) e23–e28. DOI: 10.1136/tobaccocontrol-2016-053041 WagenerT.L. FloydE.L. StepanovI. DriskillL.M. FrankS.G. MeierE. LeavensE.L. TackettA.P. MolinaN. QueimadoL. Have Combustible Cigarettes Met Their Match? The Nicotine Delivery Profiles and Harmful Constituent Exposures of Second-Generation and Third-Generation Electronic Cigarette Users Tob. Control 26 2017 e23 e28 10.1136/tobaccocontrol-2016-053041 Open DOISearch in Google Scholar

Hajek, P., K. Pittaccio, F. Pesola, K. Myers Smith, A. Phillips-Waller, and D. Przulj: Nicotine Delivery and Users’ Reactions to Juul Compared with Cigarettes and Other E-Cigarette Products; Addiction 115 (2020) 1141–1148. DOI: 10.1111/add.14936 HajekP. PittaccioK. PesolaF. Myers SmithK. Phillips-WallerA. PrzuljD. Nicotine Delivery and Users’ Reactions to Juul Compared with Cigarettes and Other E-Cigarette Products Addiction 115 2020 1141 1148 10.1111/add.14936 Open DOISearch in Google Scholar

Ramôa, C.P., M.M. Hiler, T.R. Spindle, A.A. Lopez, N. Karaoghlanian, T. Lipato, A.B. Breland, A. Shihadeh, and T. Eissenberg: Electronic Cigarette Nicotine Delivery Can Exceed That of Combustible Cigarettes: A Preliminary Report; Tob. Control 25 (2016) e6–9. DOI: 10.1136/tobaccocontrol-2015-052447 RamôaC.P. HilerM.M. SpindleT.R. LopezA.A. KaraoghlanianN. LipatoT. BrelandA.B. ShihadehA. EissenbergT. Electronic Cigarette Nicotine Delivery Can Exceed That of Combustible Cigarettes: A Preliminary Report Tob. Control 25 2016 e6 9 10.1136/tobaccocontrol-2015-052447 Open DOISearch in Google Scholar

Fearon, I.M., A. Eldridge, N. Gale, C.J. Shepperd, M. McEwan, O.M. Camacho, M. Nides, K. McAdam, and C.J. Proctor: E-Cigarette Nicotine Delivery: Data and Learnings From Pharmacokinetic Studies; Am. J. Health Behav. 41 (2017) 16–32. DOI: 10.5993/ajhb.41.1.2 FearonI.M. EldridgeA. GaleN. ShepperdC.J. McEwanM. CamachoO.M. NidesM. McAdamK. ProctorC.J. E-Cigarette Nicotine Delivery: Data and Learnings From Pharmacokinetic Studies Am. J. Health Behav. 41 2017 16 32 10.5993/ajhb.41.1.2 Open DOISearch in Google Scholar

Hajek, P., M.L. Goniewicz, A. Phillips, K. Myers Smith, O. West, and H. McRobbie: Nicotine Intake from Electronic Cigarettes on Initial Use and After 4 Weeks of Regular Use; Nicotine Tob. Res. 17 (2015) 175–179. DOI: 10.1093/ntr/ntu153 HajekP. GoniewiczM.L. PhillipsA. Myers SmithK. WestO. McRobbieH. Nicotine Intake from Electronic Cigarettes on Initial Use and After 4 Weeks of Regular Use Nicotine Tob. Res. 17 2015 175 179 10.1093/ntr/ntu153 Open DOISearch in Google Scholar

Cox, S., L. Dawkins, J. Doshi, and J. Cameron: Effects of E-Cigarettes Versus Nicotine Replacement Therapy on Short-Term Smoking Abstinence When Delivered at a Community Pharmacy; Addict. Behav. Rep. 10 (2019) 100202. DOI: 10.1016/j.abrep.2019.100202 CoxS. DawkinsL. DoshiJ. CameronJ. Effects of E-Cigarettes Versus Nicotine Replacement Therapy on Short-Term Smoking Abstinence When Delivered at a Community Pharmacy Addict. Behav. Rep. 10 2019 100202 10.1016/j.abrep.2019.100202 Open DOISearch in Google Scholar

Hajek, P., A. Phillips-Waller, D. Przulj, F. Pesola, K. Myers Smith, N. Bisal, J. Li, S. Parrott, P. Sasieni, L. Dawkins, L. Ross, M. Goniewicz, Q. Wu, and H.J. McRobbie: A Randomized Trial of E-Cigarettes Versus Nicotine-Replacement Therapy; N. Engl. J. Med. 380 (2019) 629–637. DOI: 10.1056/NEJMoa1808779 HajekP. Phillips-WallerA. PrzuljD. PesolaF. Myers SmithK. BisalN. LiJ. ParrottS. SasieniP. DawkinsL. RossL. GoniewiczM. WuQ. McRobbieH.J. A Randomized Trial of E-Cigarettes Versus Nicotine-Replacement Therapy N. Engl. J. Med. 380 2019 629 637 10.1056/NEJMoa1808779 Open DOISearch in Google Scholar

Chang, C.M., S.H. Edwards, A. Arab, A.Y. Del Valle-Pinero, L. Yang, and D.K. Hatsukami: Biomarkers of Tobacco Exposure: Summary of an FDA-Sponsored Public Workshop; Cancer Epidemiol. Biomarkers Prev. 26 (2017) 291–302. DOI: 10.1158/1055-9965.EPI-16-0675 ChangC.M. EdwardsS.H. ArabA. Del Valle-PineroA.Y. YangL. HatsukamiD.K. Biomarkers of Tobacco Exposure: Summary of an FDA-Sponsored Public Workshop Cancer Epidemiol. Biomarkers Prev. 26 2017 291 302 10.1158/1055-9965.EPI-16-0675 Open DOISearch in Google Scholar

Czoli, C.D., G.T. Fong, M.J. Goniewicz, and D. Hammond: Biomarkers of Exposure Among “Dual Users” of Tobacco Cigarettes and Electronic Cigarettes in Canada; Nicotine Tob. Res. 21 (2019) 1259–1266. DOI: 10.1093/ntr/nty174 CzoliC.D. FongG.T. GoniewiczM.J. HammondD. Biomarkers of Exposure Among “Dual Users” of Tobacco Cigarettes and Electronic Cigarettes in Canada Nicotine Tob. Res. 21 2019 1259 1266 10.1093/ntr/nty174 Open DOISearch in Google Scholar

Goniewicz, M.L., M. Gawron, D.M. Smith, M. Peng, P. Jacob III, and N.L. Benowitz: Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study; Nicotine Tob. Res. 19 (2017) 160–167. DOI: 10.1093/ntr/ntw160 GoniewiczM.L. GawronM. SmithD.M. PengM. JacobP.III BenowitzN.L. Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study Nicotine Tob. Res. 19 2017 160 167 10.1093/ntr/ntw160 Open DOISearch in Google Scholar

Lorkiewicz, P., D.W. Riggs, R.J. Keith, D.J. Conklin, Z. Xie, S. Sutaria, B. Lynch, S. Srivastava, and A. Bhatnagar: Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco; Nicotine Tob. Res. 21 (2019) 1228–1238. DOI: 10.1093/ntr/nty089 LorkiewiczP. RiggsD.W. KeithR.J. ConklinD.J. XieZ. SutariaS. LynchB. SrivastavaS. BhatnagarA. Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco Nicotine Tob. Res. 21 2019 1228 1238 10.1093/ntr/nty089 Open DOISearch in Google Scholar

McRobbie, H., A. Phillips, M.L. Goniewicz, K.M. Smith, O. Knight-West, D. Przulj, and P. Hajek: Effects of Switching to Electronic Cigarettes With and Without Concurrent Smoking on Exposure to Nicotine, Carbon Monoxide, and Acrolein; Cancer Prev. Res. 8 (2015) 873–878. DOI: 10.1158/1940-6207.CAPR-15-0058 McRobbieH. PhillipsA. GoniewiczM.L. SmithK.M. Knight-WestO. PrzuljD. HajekP. Effects of Switching to Electronic Cigarettes With and Without Concurrent Smoking on Exposure to Nicotine, Carbon Monoxide, and Acrolein Cancer Prev. Res. 8 2015 873 878 10.1158/1940-6207.CAPR-15-0058 Open DOISearch in Google Scholar

Aherrera, A., P. Olmedo, M. Grau-Perez, S. Tanda, W. Goessler, S. Jarmul, R. Chen, J.E. Cohen, A.M. Rule, and A. Navas-Acien: The Association of E-Cigarette Use with Exposure to Nickel and Chromium: A Preliminary Study of Non-Invasive Biomarkers; Environ. Res. 159 (2017) 313–320. DOI: 10.1016/j.envres.2017.08.014 AherreraA. OlmedoP. Grau-PerezM. TandaS. GoesslerW. JarmulS. ChenR. CohenJ.E. RuleA.M. Navas-AcienA. The Association of E-Cigarette Use with Exposure to Nickel and Chromium: A Preliminary Study of Non-Invasive Biomarkers Environ. Res. 159 2017 313 320 10.1016/j.envres.2017.08.014 Open DOISearch in Google Scholar

Goniewicz, M.L., D.M. Smith, K.C. Edwards, B.C. Blount, K.L. Caldwell, J. Feng, L. Wang, C. Christensen, B. Ambrose, N. Borek, D. van Bemmel, K. Konkel, G. Erives, C.A. Stanton, E. Lambert, H.L. Kimmel, D. Hatsukami, S.S. Hecht, R.S. Niaura, M. Travers, C. Lawrence, and A.J. Hyland: Comparison of Nicotine and Toxicant Exposure in Users of Electronic Cigarettes and Combustible Cigarettes; JAMA Netw. Open 1 (2018) e185937. DOI: 10.1001/jamanetworkopen.2018.5937 GoniewiczM.L. SmithD.M. EdwardsK.C. BlountB.C. CaldwellK.L. FengJ. WangL. ChristensenC. AmbroseB. BorekN. van BemmelD. KonkelK. ErivesG. StantonC.A. LambertE. KimmelH.L. HatsukamiD. HechtS.S. NiauraR.S. TraversM. LawrenceC. HylandA.J. Comparison of Nicotine and Toxicant Exposure in Users of Electronic Cigarettes and Combustible Cigarettes JAMA Netw. Open 1 2018 e185937 10.1001/jamanetworkopen.2018.5937 Open DOISearch in Google Scholar

Polosa, R., J.B. Morjaria, P. Caponnetto, U. Prosperini, C. Russo, A. Pennisi, and C.M. Bruno: Evidence for Harm Reduction in COPD Smokers Who Switch to Electronic Cigarettes; Respir. Res. 17 (2016) 166. DOI: 10.1186/s12931-016-0481-x PolosaR. MorjariaJ.B. CaponnettoP. ProsperiniU. RussoC. PennisiA. BrunoC.M. Evidence for Harm Reduction in COPD Smokers Who Switch to Electronic Cigarettes Respir. Res. 17 2016 166 10.1186/s12931-016-0481-x Open DOISearch in Google Scholar

Shahab, L., M.L. Goniewicz, B.C. Blount, J. Brown, A. McNeill, K.U. Alwis, J. Feng, L. Wang, and R. West: Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-Sectional Study; Ann. Intern. Med.166 (2017) 390–400. DOI: 10.7326/M16-1107 ShahabL. GoniewiczM.L. BlountB.C. BrownJ. McNeillA. AlwisK.U. FengJ. WangL. WestR. Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-Sectional Study Ann. Intern. Med. 166 2017 390 400 10.7326/M16-1107 Open DOISearch in Google Scholar

Sakamaki-Ching, S., M. Williams, M. Hua, J. Li, S.M. Bates, A.N. Robinson, T.W. Lyons, M.L. Goniewicz, and P. Talbot: Correlation Between Biomarkers of Exposure, Effect and Potential Harm in the Urine of Electronic Cigarette Users; BMJ Open Respir. Res. 7 (2020) e000452. DOI: 10.1136/bmjresp-2019-000452 Sakamaki-ChingS. WilliamsM. HuaM. LiJ. BatesS.M. RobinsonA.N. LyonsT.W. GoniewiczM.L. TalbotP. Correlation Between Biomarkers of Exposure, Effect and Potential Harm in the Urine of Electronic Cigarette Users BMJ Open Respir. Res. 7 2020 e000452 10.1136/bmjresp-2019-000452 Open DOISearch in Google Scholar

Round, E.K., P. Chen, A.K. Taylor, and E. Schmidt: Biomarkers of Tobacco Exposure Decrease After Smokers Switch to an E-Cigarette or Nicotine Gum; Nicotine Tob. Res. 21 (2019) 1239–1247. DOI: 10.1093/ntr/nty140 RoundE.K. ChenP. TaylorA.K. SchmidtE. Biomarkers of Tobacco Exposure Decrease After Smokers Switch to an E-Cigarette or Nicotine Gum Nicotine Tob. Res. 21 2019 1239 1247 10.1093/ntr/nty140 Open DOISearch in Google Scholar

Walele, T., J. Bush, A. Koch, R. Savioz, C. Martin, and G. O’Connell: Evaluation of the Safety Profile of an Electronic Vapour Product Used for Two Years by Smokers in a Real-life Setting; Regul. Toxicol. Pharmacol. 92 (2018) 226–238. DOI: 10.1016/j.yrtph.2017.12.010 WaleleT. BushJ. KochA. SaviozR. MartinC. O’ConnellG. Evaluation of the Safety Profile of an Electronic Vapour Product Used for Two Years by Smokers in a Real-life Setting Regul. Toxicol. Pharmacol. 92 2018 226 238 10.1016/j.yrtph.2017.12.010 Open DOISearch in Google Scholar

Cravo, A.S., J. Bush, G. Sharma, R. Savioz, C. Martin, S. Craige, and T.A. Walele: A Randomized, Parallel Group Study to Evaluate the Safety Profile of an Electronic Vapour Product Over 12 Weeks; Regul. Toxicol. Pharmacol. 81 (2016) S1–S14. DOI: 10.1016/j.yrtph.2016.10.003 CravoA.S. BushJ. SharmaG. SaviozR. MartinC. CraigeS. WaleleT.A. A Randomized, Parallel Group Study to Evaluate the Safety Profile of an Electronic Vapour Product Over 12 Weeks Regul. Toxicol. Pharmacol. 81 2016 S1 S14 10.1016/j.yrtph.2016.10.003 Open DOISearch in Google Scholar

Hecht, S.S., S.G. Carmella, D. Kotandeniya, M.E. Pillsbury, M. Chen, B.W. Ransom, R.I. Vogel, E. Thompson, S.E. Murphy, and D.K. Hatsukami: Evaluation of Toxicant and Carcinogen Metabolites in the Urine of E-Cigarette Users Versus Cigarette Smokers; Nicotine Tob. Res. 17 (2015) 704–709. DOI: 10.1093/ntr/ntu218 HechtS.S. CarmellaS.G. KotandeniyaD. PillsburyM.E. ChenM. RansomB.W. VogelR.I. ThompsonE. MurphyS.E. HatsukamiD.K. Evaluation of Toxicant and Carcinogen Metabolites in the Urine of E-Cigarette Users Versus Cigarette Smokers Nicotine Tob. Res. 17 2015 704 709 10.1093/ntr/ntu218 Open DOISearch in Google Scholar

Piper, M.E., T.B. Baker, N.L. Benowitz, K.H. Kobinsky, and D.E. Jorenby: Dual Users Compared to Smokers: Demographics, Dependence, and Biomarkers; Nicotine Tob. Res. 21 (2019) 1279–1284. DOI: 10.1093/ntr/nty231 PiperM.E. BakerT.B. BenowitzN.L. KobinskyK.H. JorenbyD.E. Dual Users Compared to Smokers: Demographics, Dependence, and Biomarkers Nicotine Tob. Res. 21 2019 1279 1284 10.1093/ntr/nty231 Open DOISearch in Google Scholar

Chang, C.M., Y.-C. Cheng, T.M. Cho, E.V. Mishina, A.Y. Del Valle-Pinero, D.M. van Bemmel, and D.K. Hatsukami: Biomarkers of Potential Harm: Summary of an FDA-Sponsored Public Workshop; Nicotine Tob. Res. 21 (2019) 3–13. DOI: 10.1093/ntr/ntx273 ChangC.M. ChengY.-C. ChoT.M. MishinaE.V. Del Valle-PineroA.Y. van BemmelD.M. HatsukamiD.K. Biomarkers of Potential Harm: Summary of an FDA-Sponsored Public Workshop Nicotine Tob. Res. 21 2019 3 13 10.1093/ntr/ntx273 Open DOISearch in Google Scholar

Cibella, F., D. Campagna, P. Caponnetto, M.D. Amaradio, M. Caruso, C. Russo, D.W. Cockcroft, and R. Polosa: Lung Function and Respiratory Symptoms in a Randomized Smoking Cessation Trial of Electronic Cigarettes; Clin. Sci. 130 (2016) 1929–1937. DOI: 10.1042/CS20160268 CibellaF. CampagnaD. CaponnettoP. AmaradioM.D. CarusoM. RussoC. CockcroftD.W. PolosaR. Lung Function and Respiratory Symptoms in a Randomized Smoking Cessation Trial of Electronic Cigarettes Clin. Sci. 130 2016 1929 1937 10.1042/CS20160268 Open DOISearch in Google Scholar

Polosa, R., J.B. Morjaria, P. Caponnetto, M. Caruso, D. Campagna, M.D. Amaradio, G. Ciampi, C. Russo, and A. Fisichella: Persisting Long Term Benefits of Smoking Abstinence and Reduction in Asthmatic Smokers Who Have Switched to Electronic Cigarettes; Discov. Med. 21 (2016) 99–108. PolosaR. MorjariaJ.B. CaponnettoP. CarusoM. CampagnaD. AmaradioM.D. CiampiG. RussoC. FisichellaA. Persisting Long Term Benefits of Smoking Abstinence and Reduction in Asthmatic Smokers Who Have Switched to Electronic Cigarettes Discov. Med. 21 2016 99 108 Search in Google Scholar

Wieslander, G., D. Norbäck, and T. Lindgren: Experimental Exposure to Propylene Glycol Mist in Aviation Emergency Training: Acute Ocular and Respiratory Effects; Occup. Environ. Med. 58 (2001) 649–655. DOI: 10.1136/oem.58.10.649 WieslanderG. NorbäckD. LindgrenT. Experimental Exposure to Propylene Glycol Mist in Aviation Emergency Training: Acute Ocular and Respiratory Effects Occup. Environ. Med. 58 2001 649 655 10.1136/oem.58.10.649 Open DOISearch in Google Scholar

D’Ruiz, C.D., G. O’Connell, D.W. Graff, and X.S. Yan: Measurement of Cardiovascular and Pulmonary Function Endpoints and Other Physiological Effects Following Partial or Complete Substitution of Cigarettes with Electronic Cigarettes in Adult Smokers; Regul. Toxicol. Pharmacol. 87 (2017) 36–53. DOI: 10.1016/j.yrtph.2017.05.002 D’RuizC.D. O’ConnellG. GraffD.W. YanX.S. Measurement of Cardiovascular and Pulmonary Function Endpoints and Other Physiological Effects Following Partial or Complete Substitution of Cigarettes with Electronic Cigarettes in Adult Smokers Regul. Toxicol. Pharmacol. 87 2017 36 53 10.1016/j.yrtph.2017.05.002 Open DOISearch in Google Scholar

Yuan, J.-M., S.G. Carmella, R. Wang, Y.T. Tan, J. Adams-Haduch, Y.T. Gao, and S.S. Hecht: Relationship of the Oxidative Damage Biomarker 8-epi-Prostaglandin F to Risk of Lung Cancer Development in the Shanghai Cohort Study; Carcinogenesis 39 (2018) 948–954. DOI: 10.1093/carcin/bgy060 YuanJ.-M. CarmellaS.G. WangR. TanY.T. Adams-HaduchJ. GaoY.T. HechtS.S. Relationship of the Oxidative Damage Biomarker 8-epi-Prostaglandin F to Risk of Lung Cancer Development in the Shanghai Cohort Study Carcinogenesis 39 2018 948 954 10.1093/carcin/bgy060 Open DOISearch in Google Scholar

Oliveri, D., Q. Liang, and M. Sarkar: Real-World Evidence of Differences in Biomarkers of Exposure to Select Harmful and Potentially Harmful Constituents and Biomarkers of Potential Harm Between Adult E-Vapor Users and Adult Cigarette Smokers; Nicotine Tob. Res. 22 (2020) 1114–1122. DOI: 10.1093/ntr/ntz185 OliveriD. LiangQ. SarkarM. Real-World Evidence of Differences in Biomarkers of Exposure to Select Harmful and Potentially Harmful Constituents and Biomarkers of Potential Harm Between Adult E-Vapor Users and Adult Cigarette Smokers Nicotine Tob. Res. 22 2020 1114 1122 10.1093/ntr/ntz185 Open DOISearch in Google Scholar

Song, M.-A., J.L. Freidenheim, T.M. Brasky, E.A. Mathe, J.P. McElroy, Q.A. Nickerson, S.A. Reisinger, D.J. Smiraglia, D.Y. Weng, K.L. Ying, M.D. Wewers, and P.G. Shields: Biomarkers of Exposure and Effect in the Lungs of Smokers, Nonsmokers, and Electronic Cigarette Users; Cancer Epidemiol. Biomarkers Prev. 29 (2020) 443–451. DOI: 10.1158/1055-9965.EPI-19-1245 SongM.-A. FreidenheimJ.L. BraskyT.M. MatheE.A. McElroyJ.P. NickersonQ.A. ReisingerS.A. SmiragliaD.J. WengD.Y. YingK.L. WewersM.D. ShieldsP.G. Biomarkers of Exposure and Effect in the Lungs of Smokers, Nonsmokers, and Electronic Cigarette Users Cancer Epidemiol. Biomarkers Prev. 29 2020 443 451 10.1158/1055-9965.EPI-19-1245 Open DOISearch in Google Scholar

Valavanidis, A., T. Vlachogianni, and C. Fiotakis: 8-Hydroxy-2'-deoxyguanosine (8-OHdG): A Critical Biomarker of Oxidative Stress and Carcinogenesis; J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 27 (2009) 120–139. DOI: 10.1080/10590500902885684 ValavanidisA. VlachogianniT. FiotakisC. 8-Hydroxy-2'-deoxyguanosine (8-OHdG): A Critical Biomarker of Oxidative Stress and Carcinogenesis J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 27 2009 120 139 10.1080/10590500902885684 Open DOISearch in Google Scholar

George, J., M. Hussain, T. Vadiveloo, S. Ireland, P. Hopkinson, A.D. Struthers, P.T. Donnan, F. Khan, and C.C. Lang: Cardiovascular Effects of Switching from Tobacco Cigarettes to Electronic Cigarettes; J. Am. Coll. Cardiol. 74 (2019) 3112–3120. DOI: 10.1016/j.jacc.2019.09.067 GeorgeJ. HussainM. VadivelooT. IrelandS. HopkinsonP. StruthersA.D. DonnanP.T. KhanF. LangC.C. Cardiovascular Effects of Switching from Tobacco Cigarettes to Electronic Cigarettes J. Am. Coll. Cardiol. 74 2019 3112 3120 10.1016/j.jacc.2019.09.067 Open DOISearch in Google Scholar

de Faria, A.P., R. Modolo, and H. Moreno: Plasma 8-Isoprostane as a Biomarker and Applications to Cardiovascular Disease; in: Biomarkers in Cardiovascular Disease, edited by V. Patel and V. Preedy, Springer, Dordrecht, The Netherlands, 2016. DOI: 10.1007/978-94-007-7741-5_31-1 de FariaA.P. ModoloR. MorenoH. Plasma 8-Isoprostane as a Biomarker and Applications to Cardiovascular Disease in: Biomarkers in Cardiovascular Disease edited by PatelV. PreedyV. Springer Dordrecht, The Netherlands 2016 10.1007/978-94-007-7741-5_31-1 Open DOISearch in Google Scholar

Wang, N., K.C. Vendrov, B.P. Simmons, R.N. Schuck, G.A. Stouffer, and C.R. Lee: Urinary 11-Dehydrothromboxane B2 Levels are Associated with Vascular Inflammation and Prognosis in Atherosclerotic Cardiovascular Disease; Prostaglandins Other Lipid Mediat. 134 (2018) 24–31. DOI: 10.1016/j.prostaglandins.2017.11.003 WangN. VendrovK.C. SimmonsB.P. SchuckR.N. StoufferG.A. LeeC.R. Urinary 11-Dehydrothromboxane B2 Levels are Associated with Vascular Inflammation and Prognosis in Atherosclerotic Cardiovascular Disease Prostaglandins Other Lipid Mediat. 134 2018 24 31 10.1016/j.prostaglandins.2017.11.003 Open DOISearch in Google Scholar

Kuntic, M., M. Oelze, S. Steven, S. Kröller-Schön, P. Stamm, S. Kalinovic, K. Frenis, K. Vujacic-Mirski, M.T. Bayo Jimenez, M. Kvandova, K. Filippou, A. Al Zuabi, V. Brückl, O. Hahad, S. Daub, F. Varveri, T. Gori, R. Huesmann, T. Hoffmann, F.P. Schmidt, J.F. Keaney, A. Daiber, and T. Münzel: Short-Term E-Cigarette Vapour Exposure Causes Vascular Oxidative Stress and Dysfunction: Evidence for a Close Connection to Brain Damage and a Key Role of the Phagocytic NADPH Oxidase (NOX-2); Eur. Heart J. 41 (2020) 2472–2483. DOI: 10.1093/eurheartj/ehz772 KunticM. OelzeM. StevenS. Kröller-SchönS. StammP. KalinovicS. FrenisK. Vujacic-MirskiK. Bayo JimenezM.T. KvandovaM. FilippouK. Al ZuabiA. BrücklV. HahadO. DaubS. VarveriF. GoriT. HuesmannR. HoffmannT. SchmidtF.P. KeaneyJ.F. DaiberA. MünzelT. Short-Term E-Cigarette Vapour Exposure Causes Vascular Oxidative Stress and Dysfunction: Evidence for a Close Connection to Brain Damage and a Key Role of the Phagocytic NADPH Oxidase (NOX-2) Eur. Heart J. 41 2020 2472 2483 10.1093/eurheartj/ehz772 Open DOISearch in Google Scholar

Kerr, D.M.I., K.J.M. Brooksbank, R.G. Taylor, K. Pinel, F.J. Rios, R.M. Touyz, and C. Delles; Acute Effects of Electronic and Tobacco Cigarettes on Vascular and Respiratory Function in Healthy Volunteers: A Cross-Over Study; J. Hypertens. 37 (2019) 154–166. DOI: 10.1097/HJH.0000000000001890 KerrD.M.I. BrooksbankK.J.M. TaylorR.G. PinelK. RiosF.J. TouyzR.M. DellesC. Acute Effects of Electronic and Tobacco Cigarettes on Vascular and Respiratory Function in Healthy Volunteers: A Cross-Over Study J. Hypertens. 37 2019 154 166 10.1097/HJH.0000000000001890 Open DOISearch in Google Scholar

Moheimani, R.S., M. Bhetraratana, K.M. Peters, B.K. Yang, F. Yin, J. Gornbein, J.A. Araujo, and H.R. Middlekauff: Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents; J. Am. Heart Assoc. 6 (2017) e006579. DOI: 10.1161/JAHA.117.006579 MoheimaniR.S. BhetraratanaM. PetersK.M. YangB.K. YinF. GornbeinJ. AraujoJ.A. MiddlekauffH.R. Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents J. Am. Heart Assoc. 6 2017 e006579 10.1161/JAHA.117.006579 Open DOISearch in Google Scholar

Gathright, E.C., W.-C. Wu, and L.A.J. Scott-Sheldon: Electronic Cigarette Use Among Heart Failure Patients: Findings from the Population Assessment of Tobacco and Health Study (Wave 1: 2013–2014); Heart Lung 9 (2020) 229–232. DOI: 10.1016/j.hrtlng.2019.11.006 GathrightE.C. WuW.-C. Scott-SheldonL.A.J. Electronic Cigarette Use Among Heart Failure Patients: Findings from the Population Assessment of Tobacco and Health Study (Wave 1: 2013–2014) Heart Lung 9 2020 229 232 10.1016/j.hrtlng.2019.11.006 Open DOISearch in Google Scholar

Flacco, M.E., M. Ferrante, M. Fiore, C. Marzuillo, C. La Vecchia, M.R. Gualano, G. Liguori, G. Fragassi, T. Carradori, F. Bravi, R. Siliquini, W. Ricciardi, P. Villari, and L. Manzoli: Cohort Study of Electronic Cigarette Use: Safety and Effectiveness After 4 Years of Follow-up; Eur. Rev. Med. Pharmacol. Sci. 23 (2019) 402–412. DOI: 10.26355/eurrev_201901_16789 FlaccoM.E. FerranteM. FioreM. MarzuilloC. La VecchiaC. GualanoM.R. LiguoriG. FragassiG. CarradoriT. BraviF. SiliquiniR. RicciardiW. VillariP. ManzoliL. Cohort Study of Electronic Cigarette Use: Safety and Effectiveness After 4 Years of Follow-up Eur. Rev. Med. Pharmacol. Sci. 23 2019 402 412 10.26355/eurrev_201901_16789 Open DOISearch in Google Scholar

O’Connell, G., D.W. Graff, and C.D. D’Ruiz: Reductions in Biomarkers of Exposure (BoE) to Harmful or Potentially Harmful Constituents (HPHCs) Following Partial or Complete Substitution of Cigarettes with Electronic Cigarettes in Adult Smokers; Toxicol. Mech. Methods 26 (2016) 443–454. DOI: 10.1080/15376516.2016.1196282 O’ConnellG. GraffD.W. D’RuizC.D. Reductions in Biomarkers of Exposure (BoE) to Harmful or Potentially Harmful Constituents (HPHCs) Following Partial or Complete Substitution of Cigarettes with Electronic Cigarettes in Adult Smokers Toxicol. Mech. Methods 26 2016 443 454 10.1080/15376516.2016.1196282 Open DOISearch in Google Scholar

Claire, R., C. Chamberlain, M.-A. Davey, S.E. Cooper, I. Berlin, J. Leonardi-Bee, and T. Coleman: Pharmacological Interventions for Promoting Smoking Cessation During Pregnancy; Cochrane Database Syst. Rev. 3 (2020) CD010078. DOI: 10.1002/14651858.CD010078.pub3 ClaireR. ChamberlainC. DaveyM.-A. CooperS.E. BerlinI. Leonardi-BeeJ. ColemanT. Pharmacological Interventions for Promoting Smoking Cessation During Pregnancy Cochrane Database Syst. Rev. 3 2020 CD010078 10.1002/14651858.CD010078.pub3 Open DOISearch in Google Scholar

The American College of Obstetricians and Gynecologists (ACOG): Committee Opinion No. 807: Smoking Cessation During Pregnancy; 2020. Available at: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/05/tobacco-and-nicotine-cessation-during-pregnancy (accessed September 7, 2020) The American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 807: Smoking Cessation During Pregnancy 2020 Available at: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/05/tobacco-and-nicotine-cessation-during-pregnancy (accessed September 7, 2020) Search in Google Scholar

National Institute for Health and Care Excellence (NICE): Smoking: Harm Reduction; Public Health Guideline [PH 45] 2013. Available at: https://www.nice.org.uk/guidance/PH45 (accessed April 29, 2020) National Institute for Health and Care Excellence (NICE) Smoking: Harm Reduction Public Health Guideline [PH 45] 2013 Available at: https://www.nice.org.uk/guidance/PH45 (accessed April 29, 2020) Search in Google Scholar

Berlin, I., G. Grangé, N. Jacob, and M.-L. Tanguy: Nicotine Patches in Pregnant Smokers: Randomised, Placebo Controlled, Multicentre Trial of Efficacy; BMJ 348 (2014) g1622. DOI: 10.1136/bmj.g1622 BerlinI. GrangéG. JacobN. TanguyM.-L. Nicotine Patches in Pregnant Smokers: Randomised, Placebo Controlled, Multicentre Trial of Efficacy BMJ 348 2014 g1622 10.1136/bmj.g1622 Open DOISearch in Google Scholar

Bowker, K., S. Lewis, T. Coleman, and S. Cooper: Changes in the Rate of Nicotine Metabolism Across Pregnancy: A Longitudinal Study; Addiction 110 (2015) 1827–1832. DOI: 10.1111/add.13029 BowkerK. LewisS. ColemanT. CooperS. Changes in the Rate of Nicotine Metabolism Across Pregnancy: A Longitudinal Study Addiction 110 2015 1827 1832 10.1111/add.13029 Open DOISearch in Google Scholar

Singh, B., M. Hrywna, O.A. Wackowski, C.D. Delnevo, M. Jane Lewis, and M.B. Steinberg: Knowledge, Recommendation, and Beliefs of E-Cigarettes Among Physicians Involved in Tobacco Cessation: A Qualitative Study; Prev. Med. Rep. 8 (2017) 25–29. DOI: 10.1016/j.pmedr.2017.07.012 SinghB. HrywnaM. WackowskiO.A. DelnevoC.D. Jane LewisM. SteinbergM.B. Knowledge, Recommendation, and Beliefs of E-Cigarettes Among Physicians Involved in Tobacco Cessation: A Qualitative Study Prev. Med. Rep. 8 2017 25 29 10.1016/j.pmedr.2017.07.012 Open DOISearch in Google Scholar

Bowker, K., S. Orton, S. Cooper, F. Naughton, R. Whitemore, S. Lewis, L. Bauld, L. Sinclair, T. Coleman, A. Dickinson, and M. Ussher: Views on and Experiences of Electronic Cigarettes: A Qualitative Study of Women Who Are Pregnant or Have Recently Given Birth; BMC Pregnancy Childbirth 18 (2018) 233. DOI: 10.1186/s12884-018-1856-4 BowkerK. OrtonS. CooperS. NaughtonF. WhitemoreR. LewisS. BauldL. SinclairL. ColemanT. DickinsonA. UssherM. Views on and Experiences of Electronic Cigarettes: A Qualitative Study of Women Who Are Pregnant or Have Recently Given Birth BMC Pregnancy Childbirth 18 2018 233 10.1186/s12884-018-1856-4 Open DOISearch in Google Scholar

McCubbin, A., A. Fallin-Bennet, J. Barnett, and K. Ashford: Perceptions and Use of Electronic Cigarettes in Pregnancy; Health Educ. Res. 32 (2017) 22–32. DOI: 10.1093/her/cyw059 McCubbinA. Fallin-BennetA. BarnettJ. AshfordK. Perceptions and Use of Electronic Cigarettes in Pregnancy Health Educ. Res. 32 2017 22 32 10.1093/her/cyw059 Open DOISearch in Google Scholar

Shahab, L., F. Dobbie, R. Hiscock, A. McNeill, and L. Bauld: Prevalence and Impact of Long-Term Use of Nicotine Replacement Therapy in UK Stop-Smoking Services: Finding from the ELONS Study; Nicotine Tob. Res. 20 (2017) 81–88. DOI: 10.1093/ntr/ntw258 ShahabL. DobbieF. HiscockR. McNeillA. BauldL. Prevalence and Impact of Long-Term Use of Nicotine Replacement Therapy in UK Stop-Smoking Services: Finding from the ELONS Study Nicotine Tob. Res. 20 2017 81 88 10.1093/ntr/ntw258 Open DOISearch in Google Scholar

Whittington J.R., P.M. Simmons, A.M. Phillips, S.K. Gammill, R. Cen, E.F. Magann, and V.M. Cardenas: The Use of Electronic Cigarettes in Pregnancy: A Review of the Literature; Obstet. Gynecol. Surv. 73 (2018) 544–549. DOI: 10.1097/OGX.0000000000000595 WhittingtonJ.R. SimmonsP.M. PhillipsA.M. GammillS.K. CenR. MagannE.F. CardenasV.M. The Use of Electronic Cigarettes in Pregnancy: A Review of the Literature Obstet. Gynecol. Surv. 73 2018 544 549 10.1097/OGX.0000000000000595 Open DOISearch in Google Scholar

Prochaska, J.J., S. Das, and K.C. Young-Wolff: Smoking, Mental Illness, and Public Health; Annu. Rev. Public Health 38 (2017) 165–185. DOI: 10.1146/annurev-publhealth-031816-044618 ProchaskaJ.J. DasS. Young-WolffK.C. Smoking, Mental Illness, and Public Health Annu. Rev. Public Health 38 2017 165 185 10.1146/annurev-publhealth-031816-044618 Open DOISearch in Google Scholar

Weinberger, A.H., J. Zhu, J.L. Barrington-Trimis, K. Wyka, and R.D. Goodwin: Cigarette Use, E-Cigarette Use, and Dual Product Use is Higher Among Adults with Serious Psychological Distress in the United States: 2014–2017; Nicotine Tob. Res. 22 (2020) 1875–1882. DOI: 10.1093/ntr/ntaa061 WeinbergerA.H. ZhuJ. Barrington-TrimisJ.L. WykaK. GoodwinR.D. Cigarette Use, E-Cigarette Use, and Dual Product Use is Higher Among Adults with Serious Psychological Distress in the United States: 2014–2017 Nicotine Tob. Res. 22 2020 1875 1882 10.1093/ntr/ntaa061 Open DOISearch in Google Scholar

Cummins, S.E., S.H. Zhu, G.J. Tedeschi, A.C. Gamst, and M.G. Myers: Use of E-Cigarettes by Individuals with Mental Health Conditions; Tob. Control 23 (2014) iii48–iii53. DOI: 10.1136/tobaccocontrol-2013-051511 CumminsS.E. ZhuS.H. TedeschiG.J. GamstA.C. MyersM.G. Use of E-Cigarettes by Individuals with Mental Health Conditions Tob. Control 23 2014 iii48 iii53 10.1136/tobaccocontrol-2013-051511 Open DOISearch in Google Scholar

Peckham, E., M. Mishu, C. Fairhurst, D. Robson, T. Bradshaw, C. Arundel, D. Bailey, P. Heron, S. Ker, and S. Gilbody: E-Cigarette Use and Associated Factors Among Smokers with Severe Mental Illness; Addict. Behav. 108 (2020) 106456. DOI: 10.1016/j.addbeh.2020.106456 PeckhamE. MishuM. FairhurstC. RobsonD. BradshawT. ArundelC. BaileyD. HeronP. KerS. GilbodyS. E-Cigarette Use and Associated Factors Among Smokers with Severe Mental Illness Addict. Behav. 108 2020 106456 10.1016/j.addbeh.2020.106456 Open DOISearch in Google Scholar

Sheals, K., I. Tombor, A. McNeill, and L. Shahab: A Mixed-Method Systematic Review and Meta-Analysis of Mental Health Professionals’ Attitudes Toward Smoking and Smoking Cessation Among People with Mental Illnesses; Addiction 111 (2016) 1536–1553. DOI: 10.1111/add.13387 ShealsK. TomborI. McNeillA. ShahabL. A Mixed-Method Systematic Review and Meta-Analysis of Mental Health Professionals’ Attitudes Toward Smoking and Smoking Cessation Among People with Mental Illnesses Addiction 111 2016 1536 1553 10.1111/add.13387 Open DOISearch in Google Scholar

Siru, R., G.K. Hulse, and R.J. Tait: Assessing Motivation to Quit Smoking in People with Mental Illness: A Review; Addiction 104 (2009) 719–733. DOI: 10.1111/j.1360-0443.2009.02545.x SiruR. HulseG.K. TaitR.J. Assessing Motivation to Quit Smoking in People with Mental Illness: A Review Addiction 104 2009 719 733 10.1111/j.1360-0443.2009.02545.x Open DOISearch in Google Scholar

Action on Smoking and Health (ASH): Fact Sheet No. 12: Smoking and Mental Health; 2019. Available at: https://ash.org.uk/wp-content/uploads/2019/08/ASH-Factsheet_Mental-Health_v3-2019-27-August-1.pdf (accessed April 29, 2020) Action on Smoking and Health (ASH) Fact Sheet No. 12: Smoking and Mental Health 2019 Available at: https://ash.org.uk/wp-content/uploads/2019/08/ASH-Factsheet_Mental-Health_v3-2019-27-August-1.pdf (accessed April 29, 2020) Search in Google Scholar

Reibel, J.: Tobacco and Oral Diseases. Update on the Evidence with Recommendations; Med. Princ. Pract. 12 (2003) 22–32. DOI: 10.1159/000069845 ReibelJ. Tobacco and Oral Diseases. Update on the Evidence with Recommendations Med. Princ. Pract. 12 2003 22 32 10.1159/000069845 Open DOISearch in Google Scholar

BinShabaib, M., S.S. ALHarthi, Z. Akram, J. Khan, I. Rahman, G.E. Romanos, and F. Javed: Clinical Periodontal Status and Gingival Crevicular Fluid Cytokine Profile Among Cigarette-Smokers, Electronic-Cigarette Users and Never-Smokers; Arch. Oral Biol. 102 (2019) 212–217. DOI: 10.1016/j.archoralbio.2019.05.001 BinShabaibM. ALHarthiS.S. AkramZ. KhanJ. RahmanI. RomanosG.E. JavedF. Clinical Periodontal Status and Gingival Crevicular Fluid Cytokine Profile Among Cigarette-Smokers, Electronic-Cigarette Users and Never-Smokers Arch. Oral Biol. 102 2019 212 217 10.1016/j.archoralbio.2019.05.001 Open DOISearch in Google Scholar

Ye, D., S. Gajendra, G. Lawyer, N. Jadeja, D. Pishey, S. Pathagunti, J. Lyons, P. Veazie, G. Watson, S. McIntosh, and I. Rahman: Inflammatory Biomarkers and Growth Factors in Saliva and Gingival Crevicular Fluid of E-cigarette Users, Cigarette Smokers, and Dual Smokers: A Pilot Study; J. Periodontol. 91 (2020) 1274–1283. DOI: 10.1002/JPER.19-0457 YeD. GajendraS. LawyerG. JadejaN. PisheyD. PathaguntiS. LyonsJ. VeazieP. WatsonG. McIntoshS. RahmanI. Inflammatory Biomarkers and Growth Factors in Saliva and Gingival Crevicular Fluid of E-cigarette Users, Cigarette Smokers, and Dual Smokers: A Pilot Study J. Periodontol. 91 2020 1274 1283 10.1002/JPER.19-0457 Open DOISearch in Google Scholar

Yang, I., S. Sandeep, and J. Rodriguez: The Oral Health Impact of Electronic Cigarette Use: A Systematic Review; Crit. Rev. Toxicol. 50 (2020) 97–127. DOI: 10.1080/10408444.2020.1713726 YangI. SandeepS. RodriguezJ. The Oral Health Impact of Electronic Cigarette Use: A Systematic Review Crit. Rev. Toxicol. 50 2020 97 127 10.1080/10408444.2020.1713726 Open DOISearch in Google Scholar

Dalrymple, A., T.C. Badrock, A. Terry, M. Barber, P.J. Hall, D. Thorne, M.D. Gaça, S. Coburn, and C. Proctor: Assessment of Enamel Discoloration In Vitro Following Exposure to Cigarette Smoke and Emissions from Novel Vapor and Tobacco Heating Products; Am. J. Dent. 31 (2018) 227–233. DalrympleA. BadrockT.C. TerryA. BarberM. HallP.J. ThorneD. GaçaM.D. CoburnS. ProctorC. Assessment of Enamel Discoloration In Vitro Following Exposure to Cigarette Smoke and Emissions from Novel Vapor and Tobacco Heating Products Am. J. Dent. 31 2018 227 233 Search in Google Scholar

Dalrymple, A., T.C. Badrock, A. Terry, E.J. Bean, M. Barber, P.J. Hall, S. Coburn, J. McAughey, and J. Murphy: Development of a Novel Method to Measure Material Surface Staining by Cigarette, E-Cigarette or Tobacco Heating Product Aerosols; Heliyon 6 (2020) e05012. DOI: 10.1016/j.heliyon.2020.e05012 DalrympleA. BadrockT.C. TerryA. BeanE.J. BarberM. HallP.J. CoburnS. McAugheyJ. MurphyJ. Development of a Novel Method to Measure Material Surface Staining by Cigarette, E-Cigarette or Tobacco Heating Product Aerosols Heliyon 6 2020 e05012 10.1016/j.heliyon.2020.e05012 Open DOISearch in Google Scholar

Persoskie, A., E.K. O’Brien, and K. Poonai: Perceived Relative Harm of Using E-Cigarettes Predicts Future Product Switching Among US Adult Cigarette and E-Cigarette Dual Users; Addiction 114 (2019) 2197–2205. DOI: 10.1111/add.14730 PersoskieA. O’BrienE.K. PoonaiK. Perceived Relative Harm of Using E-Cigarettes Predicts Future Product Switching Among US Adult Cigarette and E-Cigarette Dual Users Addiction 114 2019 2197 2205 10.1111/add.14730 Open DOISearch in Google Scholar

Gravely, S., P. Driezen, C.N. Kyriakos, M.E. Thompson, J. Balmford, T. Demjén, E. Fernández, U. Mons, Y. Tountas, K. Janik-Koncewicz, W. Zatoński, A.C. Trofor, C.I. Vardavas, G.T. Fong, and the EUREST-PLUS Consortium: European Adult Smokers’ Perceptions of the Harmfulness of E-Cigarettes Relative to Combustible Cigarettes: Cohort Findings from the 2016 and 2018 EUREST-PLUS ITC Europe Surveys; Eur. J. Public Health. 30 (2020) iii38–iii45. DOI: 10.1093/eurpub/ckz215 GravelyS. DriezenP. KyriakosC.N. ThompsonM.E. BalmfordJ. DemjénT. FernándezE. MonsU. TountasY. Janik-KoncewiczK. ZatońskiW. TroforA.C. VardavasC.I. FongG.T. the EUREST-PLUS Consortium European Adult Smokers’ Perceptions of the Harmfulness of E-Cigarettes Relative to Combustible Cigarettes: Cohort Findings from the 2016 and 2018 EUREST-PLUS ITC Europe Surveys Eur. J. Public Health. 30 2020 iii38 iii45 10.1093/eurpub/ckz215 Open DOISearch in Google Scholar

Huang, J., B. Feng, S.R. Weaver, T.F. Pechacek, P. Slovic, and M.P. Eriksen: Changing Perceptions of Harm of E-Cigarette vs Cigarette Use Among Adults in 2 US National Surveys from 2012 to 2017; JAMA Netw. Open 2 (2019) e191047. DOI: 10.1001/jamanetworkopen.2019.1047 HuangJ. FengB. WeaverS.R. PechacekT.F. SlovicP. EriksenM.P. Changing Perceptions of Harm of E-Cigarette vs Cigarette Use Among Adults in 2 US National Surveys from 2012 to 2017 JAMA Netw. Open 2 2019 e191047 10.1001/jamanetworkopen.2019.1047 Open DOISearch in Google Scholar

Malt, L., T. Verron, X. Cahours, M. Guo, S. Weaver, T. Walele, and G. O’Connell: Perception of the Relative Harm of Electronic Cigarettes Compared to Cigarettes Amongst US Adults from 2013 to 2016: Analysis of the Population Assessment of Tobacco and Health (PATH) Study Data; Harm Reduct. J. 17 (2020) 65. DOI: 10.1186/s12954-020-00410-2 MaltL. VerronT. CahoursX. GuoM. WeaverS. WaleleT. O’ConnellG. Perception of the Relative Harm of Electronic Cigarettes Compared to Cigarettes Amongst US Adults from 2013 to 2016: Analysis of the Population Assessment of Tobacco and Health (PATH) Study Data Harm Reduct. J. 17 2020 65 10.1186/s12954-020-00410-2 Open DOISearch in Google Scholar

Romijnders, K.A.G.J., L. van Osch, H. de Vries, and R. Talhout: Perceptions and Reasons Regarding E-Cigarette Use Among Users and Non-Users: A Narrative Literature Review; Int. J. Environ. Res. Public Health 15 (2018) 1190. DOI: 10.3390/ijerph15061190 RomijndersK.A.G.J. van OschL. de VriesH. TalhoutR. Perceptions and Reasons Regarding E-Cigarette Use Among Users and Non-Users: A Narrative Literature Review Int. J. Environ. Res. Public Health 15 2018 1190 10.3390/ijerph15061190 Open DOISearch in Google Scholar

Sussan, T.E., F.G. Shahzad, E. Tabassum, J.E. Cohen, R.A. Wise, M.J. Blaha, J.T. Holbrook, and S. Biswal: Electronic Cigarette Use Behaviors and Motivations Among Smokers and Non-Smokers; BMC Public Health 17 (2017) 686. DOI: 10.1186/s12889-017-4671-3 SussanT.E. ShahzadF.G. TabassumE. CohenJ.E. WiseR.A. BlahaM.J. HolbrookJ.T. BiswalS. Electronic Cigarette Use Behaviors and Motivations Among Smokers and Non-Smokers BMC Public Health 17 2017 686 10.1186/s12889-017-4671-3 Open DOISearch in Google Scholar

European Commission: Special Eurobarometer 429. Attitudes of Europeans Towards Tobacco and Electronic Cigarettes; 2015. Available at: https://ec.europa.eu/commfrontoffice/publicopinion/archives/ebs/ebs_429_en.pdf (accessed January 6 2021). European Commission Special Eurobarometer 429. Attitudes of Europeans Towards Tobacco and Electronic Cigarettes 2015 Available at: https://ec.europa.eu/commfrontoffice/publicopinion/archives/ebs/ebs_429_en.pdf (accessed January 6 2021). Search in Google Scholar

Action on Smoking and Health (ASH): Use of E-Cigarettes (Vaporisers) Among Adults in Great Britain; 2019. Available at: https://ash.org.uk/wp-content/uploads/2019/09/ASH-Factsheet_Adult-ECigs-2019-Final-3.pdf (accessed January 6 2021). Action on Smoking and Health (ASH) Use of E-Cigarettes (Vaporisers) Among Adults in Great Britain 2019 Available at: https://ash.org.uk/wp-content/uploads/2019/09/ASH-Factsheet_Adult-ECigs-2019-Final-3.pdf (accessed January 6 2021). Search in Google Scholar

Mayo Clinic: Quit-Smoking Products: Boost Your Chance of Success; 2020. Available at: https://www.mayoclinic.org/healthy-lifestyle/quit-smoking/in-depth/quit-smoking-products/art-20045599 (accessed September 7, 2020) Mayo Clinic Quit-Smoking Products: Boost Your Chance of Success 2020 Available at: https://www.mayoclinic.org/healthy-lifestyle/quit-smoking/in-depth/quit-smoking-products/art-20045599 (accessed September 7, 2020) Search in Google Scholar

Bullen, C., C. Howe, M. Laugesen, H. McRobbie, V. Parag, J. Williman, and N. Walker: Electronic Cigarettes for Smoking Cessation: A Randomised Controlled Trial; Lancet 382 (2013) 1629–1637. DOI: 10.1016/S0140-6736(13)61842-5 BullenC. HoweC. LaugesenM. McRobbieH. ParagV. WillimanJ. WalkerN. Electronic Cigarettes for Smoking Cessation: A Randomised Controlled Trial Lancet 382 2013 1629 1637 10.1016/S0140-6736(13)61842-5 Open DOISearch in Google Scholar

Farsalinos, K.E. and R. Niaura: E-Cigarettes and Smoking Cessation in the United States According to Frequency of E-Cigarette Use and Quitting Duration: Analysis of the 2016 and 2017 National Health Interview Surveys; Nicotine Tob. Res. 22 (2020) 655–662. DOI: 10.1093/ntr/ntz025 FarsalinosK.E. NiauraR. E-Cigarettes and Smoking Cessation in the United States According to Frequency of E-Cigarette Use and Quitting Duration: Analysis of the 2016 and 2017 National Health Interview Surveys Nicotine Tob. Res. 22 2020 655 662 10.1093/ntr/ntz025 Open DOISearch in Google Scholar

Carter, L.P., M.L. Stitzer, J.E. Henningfield, R.J. O’Connor, K.M. Cummings, and D.K. Hatsukami: Abuse Liability Assessment of Tobacco Products Including Potential Reduced Exposure Products; Cancer Epidemiol. Biomarkers Prev. 18 (2009) 3241–3262. DOI: 10.1158/1055-9965.EPI-09-0948 CarterL.P. StitzerM.L. HenningfieldJ.E. O’ConnorR.J. CummingsK.M. HatsukamiD.K. Abuse Liability Assessment of Tobacco Products Including Potential Reduced Exposure Products Cancer Epidemiol. Biomarkers Prev. 18 2009 3241 3262 10.1158/1055-9965.EPI-09-0948 Open DOISearch in Google Scholar

Caponnetto, P., D. Campagna, G. Papale, C. Russo, and R. Polosa: The Emerging Phenomenon of Electronic Cigarettes; Expert Rev. Respir. Med. 6 (2012) 63–74. DOI: 10.1586/ers.11.92 CaponnettoP. CampagnaD. PapaleG. RussoC. PolosaR. The Emerging Phenomenon of Electronic Cigarettes Expert Rev. Respir. Med. 6 2012 63 74 10.1586/ers.11.92 Open DOISearch in Google Scholar

Hajek, P.: Electronic Cigarettes Have a Potential for Huge Public Health Benefit; BMC Med. 12 (2014) 225. DOI: 10.1186/s12916-014-0225-z HajekP. Electronic Cigarettes Have a Potential for Huge Public Health Benefit BMC Med. 12 2014 225 10.1186/s12916-014-0225-z Open DOISearch in Google Scholar

Hatsukami, D.K.: Ending Tobacco-Caused Mortality and Morbidity: The Case for Performance Standards for Tobacco Products; Tob. Control 22 (2013) i36–i37. DOI: 10.1136/tobaccocontrol-2012-050785 HatsukamiD.K. Ending Tobacco-Caused Mortality and Morbidity: The Case for Performance Standards for Tobacco Products Tob. Control 22 2013 i36 i37 10.1136/tobaccocontrol-2012-050785 Open DOISearch in Google Scholar

Institute of Medicine (IOM): Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research; National Academies Press, Washington, DC, USA, 2011. Institute of Medicine (IOM) Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research National Academies Press Washington, DC, USA 2011 Search in Google Scholar

Walton, K.M., D.B. Abrams, W.C. Bailey, D. Clark, G.N. Connolly, M.V. Djordjevic, T.E. Eissenberg, M.C. Fiore, M.L. Goniewicz, L. Haverkos, S.S. Hecht, J.E. Henningfield, J.R. Hughes, C.A. Oncken, L. Postow, J.E. Rose, K.L. Wanke, L. Yang, and D.K. Hatsukami: NIH Electronic Cigarette Workshop: Developing a Research Agenda; Nicotine Tob. Res. 17 (2015) 259–69. DOI: 10.1093/ntr/ntu214 WaltonK.M. AbramsD.B. BaileyW.C. ClarkD. ConnollyG.N. DjordjevicM.V. EissenbergT.E. FioreM.C. GoniewiczM.L. HaverkosL. HechtS.S. HenningfieldJ.E. HughesJ.R. OnckenC.A. PostowL. RoseJ.E. WankeK.L. YangL. HatsukamiD.K. NIH Electronic Cigarette Workshop: Developing a Research Agenda Nicotine Tob. Res. 17 2015 259 69 10.1093/ntr/ntu214 Open DOISearch in Google Scholar

U.S. Department of Health and Human Services (DHHS), Center for Drug Evaluation and Research: Assessment of Abuse Potential of Drugs: Guidance for Industry; 2017. Available at: https://www.fda.gov/media/116739/download (accessed September 7, 2020) U.S. Department of Health and Human Services (DHHS), Center for Drug Evaluation and Research Assessment of Abuse Potential of Drugs: Guidance for Industry 2017 Available at: https://www.fda.gov/media/116739/download (accessed September 7, 2020) Search in Google Scholar

Maloney, S.F., A. Breland, E.K. Soule, M. Hiler, C. Ramôa, T. Lipato, and T. Eissenberg: Abuse Liability Assessment of an Electronic Cigarette in Combustible Cigarette Smokers; Exp. Clin. Psychopharmacol. 27 (2019) 443–454. DOI: 10.1037/pha0000261 MaloneyS.F. BrelandA. SouleE.K. HilerM. RamôaC. LipatoT. EissenbergT. Abuse Liability Assessment of an Electronic Cigarette in Combustible Cigarette Smokers Exp. Clin. Psychopharmacol. 27 2019 443 454 10.1037/pha0000261 Open DOISearch in Google Scholar

Liu, G., E. Wasserman, L. Kong, and J. Foulds: A Comparison of Nicotine Dependence Among Exclusive E-Cigarette and Cigarette Users in the PATH Study; Prev. Med. 104 (2017) 86–91. DOI: 10.1016/j.ypmed.2017.04.001 LiuG. WassermanE. KongL. FouldsJ. A Comparison of Nicotine Dependence Among Exclusive E-Cigarette and Cigarette Users in the PATH Study Prev. Med. 104 2017 86 91 10.1016/j.ypmed.2017.04.001 Open DOISearch in Google Scholar

Strong, D.R., J. Pearson, S. Ehlke, T. Kirchner, D. Abrams, K. Taylor, W.M. Compton, K.P. Conway, E. Lambert, V.R. Green, L.C. Hull, S.E. Evans, K.M. Cummings, M. Goniewicz, A. Hyland, and R. Niaura: Indicators of Dependence for Different Types of Tobacco Product Users: Descriptive Findings from Wave 1 (2013–2014) of the Population Assessment of Tobacco and Health (PATH) Study; Drug Alcohol Depend. 178 (2017) 257–266. DOI: 10.1016/j.drugalcdep.2017.05.010 StrongD.R. PearsonJ. EhlkeS. KirchnerT. AbramsD. TaylorK. ComptonW.M. ConwayK.P. LambertE. GreenV.R. HullL.C. EvansS.E. CummingsK.M. GoniewiczM. HylandA. NiauraR. Indicators of Dependence for Different Types of Tobacco Product Users: Descriptive Findings from Wave 1 (2013–2014) of the Population Assessment of Tobacco and Health (PATH) Study Drug Alcohol Depend. 178 2017 257 266 10.1016/j.drugalcdep.2017.05.010 Open DOISearch in Google Scholar

Rostron, B.L., M.J. Schroeder, and B.K. Ambrose: Dependence Symptoms and Cessation Intentions Among US Adult Daily Cigarette, Cigar, and E-Cigarette Users, 2012–2013; BMC Public Health 16 (2016) 814. DOI: 10.1186/s12889-016-3510-2 RostronB.L. SchroederM.J. AmbroseB.K. Dependence Symptoms and Cessation Intentions Among US Adult Daily Cigarette, Cigar, and E-Cigarette Users, 2012–2013 BMC Public Health 16 2016 814 10.1186/s12889-016-3510-2 Open DOISearch in Google Scholar

McNeill, A., P. Driezen, S.C. Hitchman, K.M. Cummings, G.T. Fong, R. Borland: Indicators of Cigarette Smoking Dependence and Relapse in Former Smokers Who Vape Compared with Those Who Do Not: Findings from the 2016 International Tobacco Control Four Country Smoking and Vaping Survey; Addiction 114 (2019) 49–60. DOI: 10.1111/add.14722 McNeillA. DriezenP. HitchmanS.C. CummingsK.M. FongG.T. BorlandR. Indicators of Cigarette Smoking Dependence and Relapse in Former Smokers Who Vape Compared with Those Who Do Not: Findings from the 2016 International Tobacco Control Four Country Smoking and Vaping Survey Addiction 114 2019 49 60 10.1111/add.14722 Open DOISearch in Google Scholar

Kapan, A., S. Stefanac, I. Sandner, S. Haider, I. Grabovac, and T.E. Dorner: Use of Electronic Cigarettes in European Populations: A Narrative Review; Int. J. Environ. Res. Public Health 17 (2020) 1971. DOI: 10.3390/ijerph17061971 KapanA. StefanacS. SandnerI. HaiderS. GrabovacI. DornerT.E. Use of Electronic Cigarettes in European Populations: A Narrative Review Int. J. Environ. Res. Public Health 17 2020 1971 10.3390/ijerph17061971 Open DOISearch in Google Scholar

Levy, D.T., Z. Yuan, and Y. Li: The Prevalence and Characteristics of E-Cigarette Users in the U.S.; Int. J. Environ. Res. Public Health 14 (2017) 1200. DOI: 10.3390/ijerph14101200 LevyD.T. YuanZ. LiY. The Prevalence and Characteristics of E-Cigarette Users in the U.S. Int. J. Environ. Res. Public Health 14 2017 1200 10.3390/ijerph14101200 Open DOISearch in Google Scholar

Office for National Statistics: E-Cigarette Use in Great Britain; 2020. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/drugusealcoholandsmoking/datasets/ecigaretteuseingreatbritain (accessed January 6, 2021) Office for National Statistics E-Cigarette Use in Great Britain 2020 Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/drugusealcoholandsmoking/datasets/ecigaretteuseingreatbritain (accessed January 6, 2021) Search in Google Scholar

Piñeiro, B., J.B. Correa, V.N. Simmons, P.T. Harrell, N.S. Menzie, M. Unrod, L.R. Meltzer, and T.H. Brandon: Gender Differences in Use and Expectancies of E-Cigarettes: Online Survey Results; Addict. Behav. 52 (2016) 91–97. DOI: 10.1016/j.addbeh.2015.09.006 PiñeiroB. CorreaJ.B. SimmonsV.N. HarrellP.T. MenzieN.S. UnrodM. MeltzerL.R. BrandonT.H. Gender Differences in Use and Expectancies of E-Cigarettes: Online Survey Results Addict. Behav. 52 2016 91 97 10.1016/j.addbeh.2015.09.006 Open DOISearch in Google Scholar

Andler, R., R. Guignard, J.L. Wilquin, F. Beck, J.B. Richard, and V. Nguyen-Thanh: Electronic Cigarette Use in France in 2014; Int. J. Public Health 61 (2016) 159–65. DOI: 10.1007/s00038-015-0773-9 AndlerR. GuignardR. WilquinJ.L. BeckF. RichardJ.B. Nguyen-ThanhV. Electronic Cigarette Use in France in 2014 Int. J. Public Health 61 2016 159 65 10.1007/s00038-015-0773-9 Open DOISearch in Google Scholar

Farsalinos, K.E., K. Poulas, V. Voudris, and J. Le Houezec: Electronic Cigarette Use in the European Union: Analysis of a Representative Sample of 27 460 Europeans from 28 Countries; Addiction 111 (2016) 2032–2040. DOI: 10.1111/add.13506 FarsalinosK.E. PoulasK. VoudrisV. Le HouezecJ. Electronic Cigarette Use in the European Union: Analysis of a Representative Sample of 27 460 Europeans from 28 Countries Addiction 111 2016 2032 2040 10.1111/add.13506 Open DOISearch in Google Scholar

Filippidis, F.T., V. Gerovasili, and A.A. Laverty: Commentary on Farsalinos et al. (2016): Electronic Cigarette Use in the European Union: Analysis of a Representative Sample of 27 460 Europeans from 28 countries; Addiction 112 (2017) 544–545. DOI: 10.1111/add.13553 FilippidisF.T. GerovasiliV. LavertyA.A. Commentary on Farsalinos et al. (2016): Electronic Cigarette Use in the European Union: Analysis of a Representative Sample of 27 460 Europeans from 28 countries Addiction 112 2017 544 545 10.1111/add.13553 Open DOISearch in Google Scholar

Adams, J.M.: Surgeon General's Advisory on E-Cigarette Use Among Youth; 2018. Available at: https://e-cigarettes.surgeongeneral.gov/documents/surgeon-generals-advisory-on-e-cigarette-use-among-youth-2018.pdf (accessed September 7 2020). AdamsJ.M. Surgeon General's Advisory on E-Cigarette Use Among Youth 2018 Available at: https://e-cigarettes.surgeongeneral.gov/documents/surgeon-generals-advisory-on-e-cigarette-use-among-youth-2018.pdf (accessed September 7 2020). Search in Google Scholar

Bauld, L., A.M. MacKintosh, B. Eastwood, A. Ford, G. Moore, M. Dockrell, D. Arnott, H. Cheeseman, and A. McNeill: Young People's Use of E-Cigarettes Across the United Kingdom: Findings from Five Surveys 2015–2017; Int. J. Environ. Res. Public Health 14 (2017) 973. DOI: 10.3390/ijerph14090973 BauldL. MacKintoshA.M. EastwoodB. FordA. MooreG. DockrellM. ArnottD. CheesemanH. McNeillA. Young People's Use of E-Cigarettes Across the United Kingdom: Findings from Five Surveys 2015–2017 Int. J. Environ. Res. Public Health 14 2017 973 10.3390/ijerph14090973 Open DOISearch in Google Scholar

Anic, G.M., M.D. Sawdey, A. Jamal, and K.F. Trivers: Frequency of Use Among Middle and High School Student Tobacco Product Users – United States, 2015–2017; MMWR Morb. Mortal. Wkly. Rep. 67 (2018) 1353–1357. DOI: 10.15585/mmwr.mm6749a1 AnicG.M. SawdeyM.D. JamalA. TriversK.F. Frequency of Use Among Middle and High School Student Tobacco Product Users – United States, 2015–2017 MMWR Morb. Mortal. Wkly. Rep. 67 2018 1353 1357 10.15585/mmwr.mm6749a1 Open DOISearch in Google Scholar

National Institutes of Health (NIH), National Cancer Institute: Cancer Trends Progress Report: Tobacco Use Initiation; 2020. Available at: https://progressreport.cancer.gov/prevention/smoking_initiation (accessed January 6, 2021) National Institutes of Health (NIH), National Cancer Institute Cancer Trends Progress Report: Tobacco Use Initiation 2020 Available at: https://progressreport.cancer.gov/prevention/smoking_initiation (accessed January 6, 2021) Search in Google Scholar

World Health Organization (WHO): European Tobacco Use: Trends Report 2019; WHO, Regional Office for Europe, 2019. Available at: https://www.euro.who.int/__data/assets/pdf_file/0009/402777/Tobacco-Trends-Report-ENG-WEB.pdf (accessed January 6, 2021) World Health Organization (WHO) European Tobacco Use: Trends Report 2019 WHO, Regional Office for Europe 2019 Available at: https://www.euro.who.int/__data/assets/pdf_file/0009/402777/Tobacco-Trends-Report-ENG-WEB.pdf (accessed January 6, 2021) Search in Google Scholar

Laverty, A.A., E.P. Vamos, and F. Filippidis: Uptake of E-Cigarettes Among a Nationally Representative Cohort of UK Children; Tob. Prev. Cessat. 4 (2018) 16. DOI: 10.18332/tpc/89727 LavertyA.A. VamosE.P. FilippidisF. Uptake of E-Cigarettes Among a Nationally Representative Cohort of UK Children Tob. Prev. Cessat. 4 2018 16 10.18332/tpc/89727 Open DOISearch in Google Scholar

Zhang, X. and J. Pu: E-Cigarette Use Among US Adolescents: Secondhand Smoke at Home Matters; Int. J. Public Health 61 (2016) 209–213. DOI: 10.1007/s00038-015-0784-6 ZhangX. PuJ. E-Cigarette Use Among US Adolescents: Secondhand Smoke at Home Matters Int. J. Public Health 61 2016 209 213 10.1007/s00038-015-0784-6 Open DOISearch in Google Scholar

Vu, T.-H.T., A. Goom, J.L. Hart, H. Tran, R.L. Landry, J.Z. Ma, K.L. Walker, A.L. Giachello, A. Kesh, T.J. Payne, and R.M. Robertson: Socioeconomic and Demographic Status and Perceived Health Risks of E-Cigarette Product Contents Among Youth: Results from a National Survey; Health Promot. Pract. 21 (2020) 148S–156S. DOI: 10.1177/1524839919882700 VuT.-H.T. GoomA. HartJ.L. TranH. LandryR.L. MaJ.Z. WalkerK.L. GiachelloA.L. KeshA. PayneT.J. RobertsonR.M. Socioeconomic and Demographic Status and Perceived Health Risks of E-Cigarette Product Contents Among Youth: Results from a National Survey Health Promot. Pract. 21 2020 148S 156S 10.1177/1524839919882700 Open DOISearch in Google Scholar

Amin, S., A.G. Dunn, and L. Laranjo: Social Influence in the Uptake and Use of Electronic Cigarettes: A Systematic Review; Am. J. Prev. Med. 58 (2020) 129–141. DOI: 10.1016/j.amepre.2019.08.023 AminS. DunnA.G. LaranjoL. Social Influence in the Uptake and Use of Electronic Cigarettes: A Systematic Review Am. J. Prev. Med. 58 2020 129 141 10.1016/j.amepre.2019.08.023 Open DOISearch in Google Scholar

Kozlowski, L. and E.W. Warner: Adolescents and E-Cigarettes: Objects of Concern May Appear Larger Than They Are; Drug Alcohol Depend. 174 (2017) 209–214. DOI: 10.1016/j.drugalcdep.2017.01.001 KozlowskiL. WarnerE.W. Adolescents and E-Cigarettes: Objects of Concern May Appear Larger Than They Are Drug Alcohol Depend. 174 2017 209 214 10.1016/j.drugalcdep.2017.01.001 Open DOISearch in Google Scholar

Australian Government, Department of Health: Personal Importation Scheme; 2015. Available at: https://www.tga.gov.au/personal-importation-scheme (accessed January 4 2021). Australian Government, Department of Health Personal Importation Scheme 2015 Available at: https://www.tga.gov.au/personal-importation-scheme (accessed January 4 2021). Search in Google Scholar

O’Leary, R., M. MacDonald, T. Stockwell, and D. Reist: Clearing the Air: A Systematic Review on the Harms and Benefits of E-Cigarettes and Vapour Devices; Canadian Institute for Substance Use Research, Victoria, BC, 2017. O’LearyR. MacDonaldM. StockwellT. ReistD. Clearing the Air: A Systematic Review on the Harms and Benefits of E-Cigarettes and Vapour Devices Canadian Institute for Substance Use Research Victoria, BC 2017 Search in Google Scholar

Royal College of Physicians: Nicotine Without Smoke: Tobacco Harm Reduction; Royal College of Physicians, London, UK, 2016. Available at: https://bit.ly/3677LeX Royal College of Physicians Nicotine Without Smoke: Tobacco Harm Reduction Royal College of Physicians London, UK 2016 Available at: https://bit.ly/3677LeX Search in Google Scholar

Mendelsohn, C.P. and W. Hall: Does the Gateway Theory Justify a Ban on Nicotine Vaping in Australia?; Int. J. Drug Policy 78 (2020) 102712. DOI: 10.1016/j.drugpo.2020.102712 MendelsohnC.P. HallW. Does the Gateway Theory Justify a Ban on Nicotine Vaping in Australia? Int. J. Drug Policy 78 2020 102712 10.1016/j.drugpo.2020.102712 Open DOISearch in Google Scholar

Kasza, K.A., K.C. Edwards, Z. Tang, C.A. Stanton, E. Sharma, M.J. Halenar, K.A. Taylor, E. Donaldson, L.C. Hull, H. Day, M. Bansal-Travers, J. Limpert, I. Zandberg, L.D. Gardner, H.T. Hammad, N. Borek, H.L. Kimmel, W.M. Compton, and A. Hyland: Correlates of Tobacco Product Initiation Among Youth and Adults in the USA: Findings from the PATH Study Waves 1–3 (2013–2016); Tob. Control 29 (2020) s191–s202. DOI: 10.1136/tobaccocontrol-2020-055671 KaszaK.A. EdwardsK.C. TangZ. StantonC.A. SharmaE. HalenarM.J. TaylorK.A. DonaldsonE. HullL.C. DayH. Bansal-TraversM. LimpertJ. ZandbergI. GardnerL.D. HammadH.T. BorekN. KimmelH.L. ComptonW.M. HylandA. Correlates of Tobacco Product Initiation Among Youth and Adults in the USA: Findings from the PATH Study Waves 1–3 (2013–2016) Tob. Control 29 2020 s191 s202 10.1136/tobaccocontrol-2020-055671 Open DOISearch in Google Scholar

Khouja, J.N., R.E. Wootton, A.E. Taylor, G. Davey Smith, and M.R. Munafò: Association of Genetic Liability to Smoking Initiation with E-Cigarette Use in Young Adults: A Cohort Study; PLoS Med. 18 (2021) e1003555. DOI: 10.1371/journal.pmed.1003555 KhoujaJ.N. WoottonR.E. TaylorA.E. Davey SmithG. MunafòM.R. Association of Genetic Liability to Smoking Initiation with E-Cigarette Use in Young Adults: A Cohort Study PLoS Med. 18 2021 e1003555 10.1371/journal.pmed.1003555 Open DOISearch in Google Scholar

Hall, W. and G. Chan: The “Gateway” Effect of E-Cigarettes May be Explained by a Genetic Liability to Risk-Taking; PLoS Med. 18 (2021) e1003554. DOI: 10.1371/journal.pmed.1003554 HallW. ChanG. The “Gateway” Effect of E-Cigarettes May be Explained by a Genetic Liability to Risk-Taking PLoS Med. 18 2021 e1003554 10.1371/journal.pmed.1003554 Open DOISearch in Google Scholar

Auf, R., M.J. Trepka, M. Selim, Z. Ben Taleb, M. De La Rosa, E. Bastida and M.Á. Cano: E-Cigarette Use is Associated with Other Tobacco Use Among US Adolescents; Int. J. Public Health 64 (2019) 125–134. DOI: 10.1007/s00038-018-1166-7 AufR. TrepkaM.J. SelimM. Ben TalebZ. De La RosaM. BastidaE. CanoM.Á. E-Cigarette Use is Associated with Other Tobacco Use Among US Adolescents Int. J. Public Health 64 2019 125 134 10.1007/s00038-018-1166-7 Open DOISearch in Google Scholar

Evans-Polce, R.J., P. Veliz, C.J. Boyd, and S.B. McCabe: Initiation Patterns and Trends of E-Cigarette and Cigarette Use Among U.S. Adolescents; J. Adolesc. Health 66 (2020) 27–33. DOI: https://doi.org/10.1016/j.jadohealth.2019.07.002 Evans-PolceR.J. VelizP. BoydC.J. McCabeS.B. Initiation Patterns and Trends of E-Cigarette and Cigarette Use Among U.S. Adolescents J. Adolesc. Health 66 2020 27 33 DOI: https://doi.org/10.1016/j.jadohealth.2019.07.002 Search in Google Scholar

Walker, N., V. Parag, S.F. Wong, B. Youdan, B. Broughton, C. Bullen, and R. Beaglehole: Use of E-Cigarettes and Smoked Tobacco in Youth Aged 14–15 Years in New Zealand: Findings from Repeated Cross-Sectional Studies (2014–19); Lancet Public Health 5 (2020) e204–e212. DOI: 10.1016/S2468-2667(19)30241-5 WalkerN. ParagV. WongS.F. YoudanB. BroughtonB. BullenC. BeagleholeR. Use of E-Cigarettes and Smoked Tobacco in Youth Aged 14–15 Years in New Zealand: Findings from Repeated Cross-Sectional Studies (2014–19) Lancet Public Health 5 2020 e204 e212 10.1016/S2468-2667(19)30241-5 Open DOISearch in Google Scholar

Government of Canada: Exploratory Research on Youth Vaping: Final Report / Prepared for Health Canada; Supplier Name: Quorus Consulting Group Inc., Ottawa, Canada, 2020. Available at: http://publications.gc.ca/site/fra/9.886111/publication.html (accessed January, 6 2021) Government of Canada Exploratory Research on Youth Vaping: Final Report / Prepared for Health Canada Supplier Name: Quorus Consulting Group Inc. Ottawa, Canada 2020 Available at: http://publications.gc.ca/site/fra/9.886111/publication.html (accessed January, 6 2021) Search in Google Scholar

Cunningham, A., S. Slayford, C. Vas, J. Gee, S. Costigan, and K. Prasad; Development, Validation and Application of a Device to Measure E-Cigarette Users’ Puffing Topography; Sci. Rep. 6 (2016) 35071. DOI: 10.1038/srep35071 CunninghamA. SlayfordS. VasC. GeeJ. CostiganS. PrasadK. Development, Validation and Application of a Device to Measure E-Cigarette Users’ Puffing Topography Sci. Rep. 6 2016 35071 10.1038/srep35071 Open DOISearch in Google Scholar

Slayford, S.J. and B.E. Frost: A Device to Measure a Smoker's Puffing Topography and Real-Time Puff-by-Puff “Tar” Delivery; Beitr. Tabakforsch. Int. 26 (2014) 74–84. DOI: 10.2478/cttr-2014-0011 SlayfordS.J. FrostB.E. A Device to Measure a Smoker's Puffing Topography and Real-Time Puff-by-Puff “Tar” Delivery Beitr. Tabakforsch. Int. 26 2014 74 84 10.2478/cttr-2014-0011 Open DOISearch in Google Scholar

Jones, J., S. Slayford, A. Gray, K. Brick, K. Prasad, and C.A. Proctor: A Cross-Category Puffing Topography, Mouth Level Exposure and Consumption Study Among Italian Users of Tobacco and Nicotine Products; Sci. Rep. 10 (2020) 12. DOI: 10.1038/s41598-019-55410-5 JonesJ. SlayfordS. GrayA. BrickK. PrasadK. ProctorC.A. A Cross-Category Puffing Topography, Mouth Level Exposure and Consumption Study Among Italian Users of Tobacco and Nicotine Products Sci. Rep. 10 2020 12 10.1038/s41598-019-55410-5 Open DOISearch in Google Scholar

Hammond, D., G.T. Fong, K.M. Cummings, and A. Hyland: Smoking Topography, Brand Switching, and Nicotine Delivery: Results from an In Vivo Study; Cancer Epidemiol. Biomarkers Prev. 14 (2005) 1370–1375. DOI: 10.1158/1055-9965.EPI-04-0498 HammondD. FongG.T. CummingsK.M. HylandA. Smoking Topography, Brand Switching, and Nicotine Delivery: Results from an In Vivo Study Cancer Epidemiol. Biomarkers Prev. 14 2005 1370 1375 10.1158/1055-9965.EPI-04-0498 Open DOISearch in Google Scholar

Spindle, T.R., A.B. Breland, N.V. Karaoghlanian, A.L. Shihadeh, and T. Eissenberg: Preliminary Results of an Examination of Electronic Cigarette User Puff Topography: The Effect of a Mouthpiece-Based Topography Measurement Device on Plasma Nicotine and Subjective Effects; Nicotine Tob. Res. 17 (2015) 142–149. DOI: 10.1093/ntr/ntu186 SpindleT.R. BrelandA.B. KaraoghlanianN.V. ShihadehA.L. EissenbergT. Preliminary Results of an Examination of Electronic Cigarette User Puff Topography: The Effect of a Mouthpiece-Based Topography Measurement Device on Plasma Nicotine and Subjective Effects Nicotine Tob. Res. 17 2015 142 149 10.1093/ntr/ntu186 Open DOISearch in Google Scholar

European Medicines Agency (EMA): Biosimilars in the EU: Information Guide for Healthcare Professionals; 2019. Available at: https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf (accessed January 6, 2021) European Medicines Agency (EMA) Biosimilars in the EU Information Guide for Healthcare Professionals 2019 Available at: https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf (accessed January 6, 2021) Search in Google Scholar

Goodchild, M., A.-M. Perucic, and N. Nargis: Modelling the Impact of Raising Tobacco Taxes on Public Health and Finance; Bull. World Health Organ. 94 (2016) 250–257. DOI: 10.2471/BLT.15.164707 GoodchildM. PerucicA.-M. NargisN. Modelling the Impact of Raising Tobacco Taxes on Public Health and Finance Bull. World Health Organ. 94 2016 250 257 10.2471/BLT.15.164707 Open DOISearch in Google Scholar

Levy, D.T., J.L. Pearson, A.C. Villanti, K. Blackman, D.M. Vallone, R.S. Niaura, and D.B. Abrams: Modeling the Future Effects of a Menthol Ban on Smoking Prevalence and Smoking-Attributable Deaths in the United States; Am. J. Public Health 101 (2011) 1236–1240. DOI: 10.2105/AJPH.2011.300179. LevyD.T. PearsonJ.L. VillantiA.C. BlackmanK. ValloneD.M. NiauraR.S. AbramsD.B. Modeling the Future Effects of a Menthol Ban on Smoking Prevalence and Smoking-Attributable Deaths in the United States Am. J. Public Health 101 2011 1236 1240 10.2105/AJPH.2011.300179 Open DOISearch in Google Scholar

Wallace, R., A. Geller, and V.A. Ogawa: Assessing the Use of Agent-Based Models for Tobacco Regulation. Consensus Study Report; National Academies Press, Washington, DC, USA, 2015. DOI: 10.17226/19018 WallaceR. GellerA. OgawaV.A. Assessing the Use of Agent-Based Models for Tobacco Regulation. Consensus Study Report National Academies Press Washington, DC, USA 2015 10.17226/19018 Open DOISearch in Google Scholar

Vugrin, E.D., B.L. Rostron, S.J. Verzi, N.S. Brodsky, T.J. Brown, C.J. Choiniere, B.N. Coleman, A. Paredes, and B.J. Apelberg: Modeling the Potential Effects of New Tobacco Products and Policies: A Dynamic Population Model for Multiple Product Use and Harm; PLoS One 10 (2015) e0121008. DOI: 10.1371/journal.pone.0121008 VugrinE.D. RostronB.L. VerziS.J. BrodskyN.S. BrownT.J. ChoiniereC.J. ColemanB.N. ParedesA. ApelbergB.J. Modeling the Potential Effects of New Tobacco Products and Policies: A Dynamic Population Model for Multiple Product Use and Harm PLoS One 10 2015 e0121008 10.1371/journal.pone.0121008 Open DOISearch in Google Scholar

Bachand, A.M. and S.I. Sulsky: A Dynamic Population Model for Estimating All-Cause Mortality Due to Lifetime Exposure History; Regul. Toxicol. Pharmacol. 67 (2013) 246–251. DOI: 10.1016/j.yrtph.2013.08.003 BachandA.M. SulskyS.I. A Dynamic Population Model for Estimating All-Cause Mortality Due to Lifetime Exposure History Regul. Toxicol. Pharmacol. 67 2013 246 251 10.1016/j.yrtph.2013.08.003 Open DOISearch in Google Scholar

Levy, D.T., N. Nikolayev, E.A. Mumford, and C. Compton: The Healthy People 2010 Smoking Prevalence and Tobacco Control Objectives: Results from the SimSmoke Tobacco Control Policy Simulation Model (United States); Cancer Causes Control 16 (2005) 359–371. DOI: 10.1007/s10552-004-7841-4 LevyD.T. NikolayevN. MumfordE.A. ComptonC. The Healthy People 2010 Smoking Prevalence and Tobacco Control Objectives: Results from the SimSmoke Tobacco Control Policy Simulation Model (United States) Cancer Causes Control 16 2005 359 371 10.1007/s10552-004-7841-4 Open DOISearch in Google Scholar

Lee, P.N., D. Abrams, A. Bachand, G. Baker, R. Black, O. Camacho, G. Curtin, S. Djurdjevic, A. Hill, D. Mendez, R.S. Muhammad-Kah, J.L. Murillo, R. Niaura, Y.B. Pithawalla, B. Poland, S. Sulsky, L. Wei, and R. Weitkunat: Estimating the Population Health Impact of Recently Introduced Modified Risk Tobacco Products: A Comparison of Different Approaches; Nicotine Tob. Res. 23 (2021) 426–437. DOI: 10.1093/ntr/ntaa102 LeeP.N. AbramsD. BachandA. BakerG. BlackR. CamachoO. CurtinG. DjurdjevicS. HillA. MendezD. Muhammad-KahR.S. MurilloJ.L. NiauraR. PithawallaY.B. PolandB. SulskyS. WeiL. WeitkunatR. Estimating the Population Health Impact of Recently Introduced Modified Risk Tobacco Products: A Comparison of Different Approaches Nicotine Tob. Res. 23 2021 426 437 10.1093/ntr/ntaa102 Open DOISearch in Google Scholar

Warner, K.E. and D. Mendez: E-Cigarettes: Comparing the Possible Risks of Increasing Smoking Initiation with the Potential Benefits of Increasing Smoking Cessation; Nicotine Tob. Res. 21 (2019) 41–47. DOI: 10.1093/ntr/nty062 WarnerK.E. MendezD. E-Cigarettes: Comparing the Possible Risks of Increasing Smoking Initiation with the Potential Benefits of Increasing Smoking Cessation Nicotine Tob. Res. 21 2019 41 47 10.1093/ntr/nty062 Open DOISearch in Google Scholar

Levy, D.T., R. Borland, E.N. Lindblom, M.L. Goniewicz, R. Meza, T.R. Holford, Z. Yuan, Y. Luo, R.J. O’Connor, R. Niaura, and D.B. Abrams: Potential Deaths Averted in USA by Replacing Cigarettes with E-Cigarettes; Tob. Control 27 (2018) 18–25. DOI: 10.1136/tobaccocontrol-2017-053759 LevyD.T. BorlandR. LindblomE.N. GoniewiczM.L. MezaR. HolfordT.R. YuanZ. LuoY. O’ConnorR.J. NiauraR. AbramsD.B. Potential Deaths Averted in USA by Replacing Cigarettes with E-Cigarettes Tob. Control 27 2018 18 25 10.1136/tobaccocontrol-2017-053759 Open DOISearch in Google Scholar

Bachand, A.M., S.I. Sulsky, and G.M. Curtin: Assessing the Likelihood and Magnitude of a Population Health Benefit Following the Market Introduction of a Modified-Risk Tobacco Product: Enhancements to the Dynamic Population Modeler, DPM(+1); Risk Anal. 38 (2018) 151–162. DOI: 10.1111/risa.12819 BachandA.M. SulskyS.I. CurtinG.M. Assessing the Likelihood and Magnitude of a Population Health Benefit Following the Market Introduction of a Modified-Risk Tobacco Product: Enhancements to the Dynamic Population Modeler, DPM(+1) Risk Anal. 38 2018 151 162 10.1111/risa.12819 Open DOISearch in Google Scholar

Cherng, S.T., J. Tam, P.J. Christine, and R. Meza: Modeling the Effects of E-Cigarettes on Smoking Behavior: Implications for Future Adult Smoking Prevalence; Epidemiology 27 (2016) 819–826. DOI: 10.1097/EDE.0000000000000497 CherngS.T. TamJ. ChristineP.J. MezaR. Modeling the Effects of E-Cigarettes on Smoking Behavior: Implications for Future Adult Smoking Prevalence Epidemiology 27 2016 819 826 10.1097/EDE.0000000000000497 Open DOISearch in Google Scholar

Soneji, S.S., H.-Y. Sung, B.A. Primack, J.P. Pierce, and J.D. Sargent: Quantifying Population-Level Health Benefits and Harms of E-Cigarette Use in the United States; PLoS One 23 (2018) e0193328. DOI: 10.1371/journal.pone.0193328 SonejiS.S. SungH.-Y. PrimackB.A. PierceJ.P. SargentJ.D. Quantifying Population-Level Health Benefits and Harms of E-Cigarette Use in the United States PLoS One 23 2018 e0193328 10.1371/journal.pone.0193328 Open DOISearch in Google Scholar

Hill, A. and O.M. Camacho: A System Dynamics Modelling Approach to Assess the Impact of Launching a New Nicotine Product on Population Health Outcomes; Regul. Toxicol. Pharmacol. 86 (2017) 265–278. DOI: 10.1016/j.yrtph.2017.03.012 HillA. CamachoO.M. A System Dynamics Modelling Approach to Assess the Impact of Launching a New Nicotine Product on Population Health Outcomes Regul. Toxicol. Pharmacol. 86 2017 265 278 10.1016/j.yrtph.2017.03.012 Open DOISearch in Google Scholar

U.S. Food and Drug Administration (FDA): Generally Recognized as Safe (GRAS); 2019. Available at: https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras (accessed January 25, 2021) U.S. Food and Drug Administration (FDA) Generally Recognized as Safe (GRAS) 2019 Available at: https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras (accessed January 25, 2021) Search in Google Scholar

Akiyama, Y. and N. Sherwood: Systematic Review of Biomarker Findings from Clinical Studies of Electronic Cigarettes and Heated Tobacco Products; Toxicol. Rep. 8 (2021) 282–294. DOI: 10.1016/j.toxrep.2021.01.014 AkiyamaY. SherwoodN. Systematic Review of Biomarker Findings from Clinical Studies of Electronic Cigarettes and Heated Tobacco Products Toxicol. Rep. 8 2021 282 294 10.1016/j.toxrep.2021.01.014 Open DOISearch in Google Scholar

Office for National Statistics: Adult Smoking Habits in Great Britain; 2020. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/drugusealcoholandsmoking/datasets/adultsmokinghabitsingreatbritain (accessed January 6, 2021) Office for National Statistics Adult Smoking Habits in Great Britain 2020 Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/drugusealcoholandsmoking/datasets/adultsmokinghabitsingreatbritain (accessed January 6, 2021) Search in Google Scholar

Jaccard, G., T. Tafin Djoko, A. Korneliou, R. Stabbert, M. Belushkin, and M. Esposito: Mainstream Smoke Constituents and In Vitro Toxicity Comparative Analysis of 3R4F and 1R6F Reference Cigarettes; Toxicol. Rep. 6 (2019) 222–231. DOI: 10.1016/j.toxrep.2019.02.009 JaccardG. Tafin DjokoT. KorneliouA. StabbertR. BelushkinM. EspositoM. Mainstream Smoke Constituents and In Vitro Toxicity Comparative Analysis of 3R4F and 1R6F Reference Cigarettes Toxicol. Rep. 6 2019 222 231 10.1016/j.toxrep.2019.02.009 Open DOISearch in Google Scholar

O’Connell, G., T. Walele, C. Prue, G. Gillman, X. Cahours, O. Hibbert, and J.D. Pritchard: Chemical Composition of Myblu™ Pod-System E-Cigarette Aerosols: A Quantitative Comparison with Conventional Cigarette Smoke; presented at the 1st Scientific Summit on Tobacco Harm Reduction, Kallithea, Greece, June 2018. Available at: https://imperialbrandsscience.com/wp-content/uploads/2020/02/Chemical-Composition-of-blu-Pod-System-EVP-Aerosols-A-Quantitative-Comparison-with-Conventional-Cigarette-Smoke.pdf (accessed May 8, 2021) O’ConnellG. WaleleT. PrueC. GillmanG. CahoursX. HibbertO. PritchardJ.D. Chemical Composition of Myblu™ Pod-System E-Cigarette Aerosols: A Quantitative Comparison with Conventional Cigarette Smoke presented at the 1st Scientific Summit on Tobacco Harm Reduction Kallithea, Greece June 2018 Available at: https://imperialbrandsscience.com/wp-content/uploads/2020/02/Chemical-Composition-of-blu-Pod-System-EVP-Aerosols-A-Quantitative-Comparison-with-Conventional-Cigarette-Smoke.pdf (accessed May 8, 2021) Search in Google Scholar

Farsalinos, K., K. Poulas, and V. Voudris: Changes in Puffing Topography and Nicotine Consumption Depending on the Power Setting of Electronic Cigarettes; Nicotine Tob. Res. 20 (2018) 993–997. DOI: 10.1093/ntr/ntx219 FarsalinosK. PoulasK. VoudrisV. Changes in Puffing Topography and Nicotine Consumption Depending on the Power Setting of Electronic Cigarettes Nicotine Tob. Res. 20 2018 993 997 10.1093/ntr/ntx219 Open DOISearch in Google Scholar

Yan, X.S. and C. D’Ruiz: Effects of Using Electronic Cigarettes on Nicotine Delivery and Cardiovascular Function in Comparison with Regular Cigarettes; Regul. Toxicol. Pharmacol. 71 (2015) 24–34. DOI: 10.1016/j.yrtph.2014.11.004 YanX.S. D’RuizC. Effects of Using Electronic Cigarettes on Nicotine Delivery and Cardiovascular Function in Comparison with Regular Cigarettes Regul. Toxicol. Pharmacol. 71 2015 24 34 10.1016/j.yrtph.2014.11.004 Open DOISearch in Google Scholar

Hajek, P., D. Przulj, A. Phillips, R. Anderson, and H. McRobbie: Nicotine Delivery to Users from Cigarettes and from Different Types of E-Cigarettes; Psychopharmacology 234 (2017) 773–779. DOI: 10.1007/s00213-016-4512-6 HajekP. PrzuljD. PhillipsA. AndersonR. McRobbieH. Nicotine Delivery to Users from Cigarettes and from Different Types of E-Cigarettes Psychopharmacology 234 2017 773 779 10.1007/s00213-016-4512-6 Open DOISearch in Google Scholar

Vansickel, A.R., C.O. Cobb, M.F. Weaver, and T.E. Eissenberg: A Clinical Laboratory Model for Evaluating the Acute Effects of Electronic “Cigarettes”: Nicotine Delivery Profile and Cardiovascular and Subjective Effects; Cancer Epidemiol. Biomarkers Prev. 19 (2010) 1945–1953. DOI: 10.1158/1055-9965.EPI-10-0288 VansickelA.R. CobbC.O. WeaverM.F. EissenbergT.E. A Clinical Laboratory Model for Evaluating the Acute Effects of Electronic “Cigarettes”: Nicotine Delivery Profile and Cardiovascular and Subjective Effects Cancer Epidemiol. Biomarkers Prev. 19 2010 1945 1953 10.1158/1055-9965.EPI-10-0288 Open DOISearch in Google Scholar

Voos, N., L. Kaiser, M.C. Mahoney, C.M. Bradizza, L.T. Kozlowski, N.L. Benowitz, R.J. O’Connor, and M.L. Goniewicz: Randomized Within-Subject Trial to Evaluate Smokers’ Initial Perceptions, Subjective Effects and Nicotine Delivery Across Six Vaporized Nicotine Products; Addiction 114 (2019) 1236–1248. DOI: 10.1111/add.14602 VoosN. KaiserL. MahoneyM.C. BradizzaC.M. KozlowskiL.T. BenowitzN.L. O’ConnorR.J. GoniewiczM.L. Randomized Within-Subject Trial to Evaluate Smokers’ Initial Perceptions, Subjective Effects and Nicotine Delivery Across Six Vaporized Nicotine Products Addiction 114 2019 1236 1248 10.1111/add.14602 Open DOISearch in Google Scholar

Lunell, E. and M. Curvall: Nicotine Delivery and Subjective Effects of Swedish Portion Snus Compared with 4 mg Nicotine Polacrilex Chewing Gum; Nicotine Tob. Res. 13 (2011) 573–578. DOI: 10.1093/ntr/ntr044 LunellE. CurvallM. Nicotine Delivery and Subjective Effects of Swedish Portion Snus Compared with 4 mg Nicotine Polacrilex Chewing Gum Nicotine Tob. Res. 13 2011 573 578 10.1093/ntr/ntr044 Open DOISearch in Google Scholar

Dautzenberg, B., M. Nides, J.L. Kienzler, and A. Callens: Pharmacokinetics, Safety and Efficacy from Randomized Controlled Trials of 1 and 2 mg Nicotine Bitartrate Lozenges (Nicotinell®); BMC Clin. Pharmacol. 7 (2007) 11. DOI: 10.1186/1472-6904-7-11 DautzenbergB. NidesM. KienzlerJ.L. CallensA. Pharmacokinetics, Safety and Efficacy from Randomized Controlled Trials of 1 and 2 mg Nicotine Bitartrate Lozenges (Nicotinell®) BMC Clin. Pharmacol. 7 2007 11 10.1186/1472-6904-7-11 Open DOISearch in Google Scholar

Choi, J.H., C.M. Dresler, M.R. Norton, and K.R. Strahs: Pharmacokinetics of a Nicotine Polacrilex Lozenge; Nicotine Tob. Res. 5 (2003) 635–644. DOI: 10.1080/1462220031000158690 ChoiJ.H. DreslerC.M. NortonM.R. StrahsK.R. Pharmacokinetics of a Nicotine Polacrilex Lozenge Nicotine Tob. Res. 5 2003 635 644 10.1080/1462220031000158690 Open DOISearch in Google Scholar

Kraiczi, H., A. Hansson, and R. Perfekt: Single-Dose Pharmacokinetics of Nicotine When Given with a Novel Mouth Spray for Nicotine Replacement Therapy; Nicotine Tob. Res. 13 (2011) 1176–1182. DOI: 10.1093/ntr/ntr139 KraicziH. HanssonA. PerfektR. Single-Dose Pharmacokinetics of Nicotine When Given with a Novel Mouth Spray for Nicotine Replacement Therapy Nicotine Tob. Res. 13 2011 1176 1182 10.1093/ntr/ntr139 Open DOISearch in Google Scholar

Molander, L. and E. Lunell: Pharmacokinetic Investigation of a Nicotine Sublingual Tablet; Eur. J. Clin. Pharmacol. 56 (2001) 813–819. DOI 10.1007/s002280000223 MolanderL. LunellE. Pharmacokinetic Investigation of a Nicotine Sublingual Tablet Eur. J. Clin. Pharmacol. 56 2001 813 819 10.1007/s002280000223 Open DOISearch in Google Scholar

Lunell, E., K. Fagerström, J. Hughes, and R. Pendril: Pharmacokinetic Comparison of a Novel Non-Tobacco-Based Nicotine Pouch (ZYN) with Conventional, Tobacco-Based Swedish Snus and American Moist Snuff; Nicotine Tob. Res. 22 (2020) 1757–1763. DOI: 10.1093/ntr/ntaa068 LunellE. FagerströmK. HughesJ. PendrilR. Pharmacokinetic Comparison of a Novel Non-Tobacco-Based Nicotine Pouch (ZYN) with Conventional, Tobacco-Based Swedish Snus and American Moist Snuff Nicotine Tob. Res. 22 2020 1757 1763 10.1093/ntr/ntaa068 Open DOISearch in Google Scholar

Goldenson, N., I.M. Fearon, A.R. Buchhalter, and J.E. Heningfield: An Open-Label, Randomised, Controlled, Crossover Study to Assess Nicotine Pharmacokinetics and Subjective Effects of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in Adult Smokers; Nicotine Tob. Res. (2021) ntab001. DOI: 10.1093/ntr/ntab001 GoldensonN. FearonI.M. BuchhalterA.R. HeningfieldJ.E. An Open-Label, Randomised, Controlled, Crossover Study to Assess Nicotine Pharmacokinetics and Subjective Effects of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in Adult Smokers Nicotine Tob. Res. 2021 ntab001 10.1093/ntr/ntab001 Open DOISearch in Google Scholar

D’Ruiz, C.D., D.W. Graff, and E. Robinson: Reductions in Biomarkers of Exposure, Impacts on Smoking Urge and Assessment of Product Use and Tolerability in Adult Smokers Following Partial or Complete Substitution of Cigarettes with Electronic Cigarettes; BMC Public Health 16 (2016) 543. DOI: 10.1186/s12889-016-3236-1 D’RuizC.D. GraffD.W. RobinsonE. Reductions in Biomarkers of Exposure, Impacts on Smoking Urge and Assessment of Product Use and Tolerability in Adult Smokers Following Partial or Complete Substitution of Cigarettes with Electronic Cigarettes BMC Public Health 16 2016 543 10.1186/s12889-016-3236-1 Open DOISearch in Google Scholar

Campagna, D., F. Cibella, P. Caponnetto, M.D. Amaradio, M. Caruso, J.B. Morjaria, M. Malerba, and R. Polosa: Changes in Breathomics from a 1-Year Randomized Smoking Cessation Trial of Electronic Cigarettes; Eur. J. Clin. Invest. 46 (2016) 698–706. DOI: 10.1111/eci.12651 CampagnaD. CibellaF. CaponnettoP. AmaradioM.D. CarusoM. MorjariaJ.B. MalerbaM. PolosaR. Changes in Breathomics from a 1-Year Randomized Smoking Cessation Trial of Electronic Cigarettes Eur. J. Clin. Invest. 46 2016 698 706 10.1111/eci.12651 Open DOISearch in Google Scholar

Pulvers, K., A.S. Emami, N.L. Nollen, D.R. Romero, D.R. Strong, N.L. Benowitz, and J.S. Ahluwalia: Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes; Nicotine Tob. Res. 20 (2018) 206–214. DOI: 10.1093/ntr/ntw333 PulversK. EmamiA.S. NollenN.L. RomeroD.R. StrongD.R. BenowitzN.L. AhluwaliaJ.S. Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes Nicotine Tob. Res. 20 2018 206 214 10.1093/ntr/ntw333 Open DOISearch in Google Scholar

Behar, R.Z., M. Hua, and P. Talbot: Puffing Topography and Nicotine Intake of Electronic Cigarette Users; PLoS One 10 (2015) e0117222. DOI: 10.1371/journal.pone.0117222 BeharR.Z. HuaM. TalbotP. Puffing Topography and Nicotine Intake of Electronic Cigarette Users PLoS One 10 2015 e0117222 10.1371/journal.pone.0117222 Open DOISearch in Google Scholar

Norton, K.J., K.M. June, and R.J. O’Connor: Initial Puffing Behaviors and Subjective Responses Differ Between an Electronic Nicotine Delivery System and Traditional Cigarettes; Tob. Induc. Dis. 12 (2014) 17. DOI: 10.1186/1617-9625-12-17 NortonK.J. JuneK.M. O’ConnorR.J. Initial Puffing Behaviors and Subjective Responses Differ Between an Electronic Nicotine Delivery System and Traditional Cigarettes Tob. Induc. Dis. 12 2014 17 10.1186/1617-9625-12-17 Open DOISearch in Google Scholar

Lee, Y.H., M. Gawron, and M.L. Goniewicz: Changes in Puffing Behavior Among Smokers Who Switched from Tobacco to Electronic Cigarettes; Addict. Behav. 48 (2015) 1–4. DOI: 10.1016/j.addbeh.2015.04.003 LeeY.H. GawronM. GoniewiczM.L. Changes in Puffing Behavior Among Smokers Who Switched from Tobacco to Electronic Cigarettes Addict. Behav. 48 2015 1 4 10.1016/j.addbeh.2015.04.003 Open DOISearch in Google Scholar

Robinson, R.J., E.C. Hensel, P.N. Morabito, and K.A. Roundtree: Electronic Cigarette Topography in the Natural Environment; PLoS One 10 (2015) e0129296. DOI: 10.1371/journal.pone.0129296 RobinsonR.J. HenselE.C. MorabitoP.N. RoundtreeK.A. Electronic Cigarette Topography in the Natural Environment PLoS One 10 2015 e0129296 10.1371/journal.pone.0129296 Open DOISearch in Google Scholar

Robinson, R.J., E.C. Hensel, K.A. Roundtree, A.G. Difrancesco, J.M. Nonnemaker, and Y.O. Lee: Week Long Topography Study of Young Adults Using Electronic Cigarettes in Their Natural Environment; PloS One 11 (2016) e0164038. DOI: 10.1371/journal.pone.0164038 RobinsonR.J. HenselE.C. RoundtreeK.A. DifrancescoA.G. NonnemakerJ.M. LeeY.O. Week Long Topography Study of Young Adults Using Electronic Cigarettes in Their Natural Environment PloS One 11 2016 e0164038 10.1371/journal.pone.0164038 Open DOISearch in Google Scholar

Dawkins, L.E., C.F. Kimber, M. Doig, C. Feyerabend, and O. Corcoran: Self-Titration by Experienced E-Cigarette Users: Blood Nicotine Delivery and Subjective Effects; Psychopharmacology 233 (2016) 1–9. DOI: 10.1007/s00213-016-4338-2 DawkinsL.E. KimberC.F. DoigM. FeyerabendC. CorcoranO. Self-Titration by Experienced E-Cigarette Users: Blood Nicotine Delivery and Subjective Effects Psychopharmacology 233 2016 1 9 10.1007/s00213-016-4338-2 Open DOISearch in Google Scholar

Lee, Y.O., J.M. Nonnemaker, B. Bradfield, E.C. Hensel, and R.J. Robinson: Examining Daily Electronic Cigarette Puff Topography Among Established and Nonestablished Cigarette Smokers in Their Natural Environment; Nicotine Tob. Res. 20 (2018) 1283–1288. DOI: 10.1093/ntr/ntx222 LeeY.O. NonnemakerJ.M. BradfieldB. HenselE.C. RobinsonR.J. Examining Daily Electronic Cigarette Puff Topography Among Established and Nonestablished Cigarette Smokers in Their Natural Environment Nicotine Tob. Res. 20 2018 1283 1288 10.1093/ntr/ntx222 Open DOISearch in Google Scholar

Levy, D.T., R. Borland, A.C. Villanti, R. Niaura, Z. Yuan, Y. Zhang, R. Meza, T.R. Holford, G.T. Fong, K.M. Cummings, and D.B. Abrams: The Application of a Decision-Theoretic Model to Estimate the Public Health Impact of Vaporized Nicotine Product Initiation in the United States; Nicotine Tob. Res. 19 (2017) 149–159. DOI: 10.1093/ntr/ntw158 LevyD.T. BorlandR. VillantiA.C. NiauraR. YuanZ. ZhangY. MezaR. HolfordT.R. FongG.T. CummingsK.M. AbramsD.B. The Application of a Decision-Theoretic Model to Estimate the Public Health Impact of Vaporized Nicotine Product Initiation in the United States Nicotine Tob. Res. 19 2017 149 159 10.1093/ntr/ntw158 Open DOISearch in Google Scholar

Levy, D.T., Z. Yuan, Y. Li, A.J. Alberg, and K.M. Cummings: A Modeling Approach to Gauging the Effects of Nicotine Vaping Product Use on Cessation from Cigarettes: What Do We Know, What Do We Need to Know?; Addiction 114 (2019) 86–96. DOI: 10.1111/add.14530 LevyD.T. YuanZ. LiY. AlbergA.J. CummingsK.M. A Modeling Approach to Gauging the Effects of Nicotine Vaping Product Use on Cessation from Cigarettes: What Do We Know, What Do We Need to Know? Addiction 114 2019 86 96 10.1111/add.14530 Open DOISearch in Google Scholar

Petrović-van der Deen, F.S., N. Wilson, A. Crothers, C.L. Cleghorn, C. Garner, and T. Blakely: Potential Country-Level Health and Cost Impacts of Legalizing Domestic Sale of Vaporized Nicotine Products; Epidemiology 30 (2019) 396–404. DOI: 10.1097/EDE.0000000000000975 Petrović-van der DeenF.S. WilsonN. CrothersA. CleghornC.L. GarnerC. BlakelyT. Potential Country-Level Health and Cost Impacts of Legalizing Domestic Sale of Vaporized Nicotine Products Epidemiology 30 2019 396 404 10.1097/EDE.0000000000000975 Open DOISearch in Google Scholar

Kalkhoran, S. and S.A. Glantz: Modeling the Health Effects of Expanding E-Cigarette Sales in the United States and United Kingdom: A Monte Carlo Analysis; JAMA Intern. Med. 175 (2015) 1671–1680. DOI: 10.1001/jamainternmed.2015.4209 KalkhoranS. GlantzS.A. Modeling the Health Effects of Expanding E-Cigarette Sales in the United States and United Kingdom: A Monte Carlo Analysis JAMA Intern. Med. 175 2015 1671 1680 10.1001/jamainternmed.2015.4209 Open DOISearch in Google Scholar

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