Electronic nicotine delivery systems (ENDS): A convenient means of smoking?

Electronic nicotine delivery systems (ENDS), which are becoming increasingly popular in many parts of the world, have recently become more sophisticated in terms of their more active content and better controlled vaporisation. This review begins by describing how cigarette smoking led to the development of ENDS as a means of combatting nicotine addiction. ENDS are usually categorised as belonging to one of only three main generations, but a fourth has been added in order to differentiate the latest, most powerful, most advanced and innovative that have improved heating efficiency. Descriptions of the principal substances contained in ENDS are followed by considerations concerning the risk of toxicity due to the presence of albeit low concentrations of such a variety of compounds inhaled over a long time, and the increasingly widespread use of ENDS as a means of smoking illicit drugs. We also review the most widely used pharmacotherapeutic approaches to smoking cessation, and recent epidemiological data showing that ENDS can help some people to stop smoking. However, in order to ensure their appropriate regulation, there is a need for higher-quality evidence concerning the health effects and safety of ENDS, and their effectiveness in discouraging tobacco smoking.

Acetal Formation of Flavoring Agents with Propylene Glycol in E-Cigarettes: Impacts on Indoor Partitioning and Thirdhand Exposure.

The widespread use of flavored e-cigarettes has led to a significant rise in teenage nicotine use. In e-liquids, the flavor carbonyls can form acetals with unknown chemical and toxicological properties. These acetals can cause adverse health effects on both smokers and nonsmokers through thirdhand exposure. This study aims to explore the impacts of these acetals formed in e-cigarettes on indoor partitioning and thirdhand exposure. Specifically, the acetalization reactions of commonly used flavor carbonyls in laboratory-made e-liquids were monitored using proton nuclear magnetic resonance (1H NMR) spectroscopy. EAS-E Suite and polyparameter linear free energy relationships (PP-LFERs) were employed to estimate the partitioning coefficients for species. Further, a chemical two-dimensional partitioning model was applied to visualize the indoor equilibrium partitioning and estimate the distribution of flavor carbonyls and their acetals in the gas phase, aerosol phase, and surface reservoirs. Our results demonstrate that a substantial fraction of carbonyls were converted into acetals in e-liquids and their chemical partitioning was significantly influenced. This study shows that acetalization is a determinant factor in the exposure and toxicology of harmful carbonyl flavorings, with its impact extending to both direct exposure to smokers and involuntary exposure to nonsmokers.

Identification and Characterization of Synthetic Nicotine Product Promotion and Sales on Instagram Using Natural Language Processing.

INTRODUCTION: There has been a rapid proliferation of synthetic nicotine products in recent years, despite newly established regulatory authority and limited research into its health risks. Previous research has implicated social media platforms as an avenue for nicotine product unregulated sales. Yet, little is known about synthetic nicotine product content on social media. We utilized natural language processing to characterize the sales of synthetic nicotine products on Instagram. METHODS: We collected Instagram posts by querying Instagram hashtags (e.g., "#tobaccofreenicotine) related to synthetic nicotine. Using BERT, collected posts were categorized into thematically related topic clusters. Posts within topic clusters relevant to study aims were then manually annotated for variables related to promotion and selling (e.g., cost discussion, contact information for offline sales). RESULTS: A total of 7,425 unique posts were collected with 2,219 posts identified as related to promotion and selling of synthetic nicotine products. Nicotine pouches (52.9%, n=1174), ENDS (30.6%, n=679), and flavored e-liquids (14.1%, n=313) were most commonly promoted. 16.1% (n=345) of posts contained embedded hyperlinks and 5.8% (n=129) provided contact information for purported offline transactions. Only 17.6% (n=391) of posts contained synthetic nicotine specific health warnings. CONCLUSIONS: In the United States, synthetic nicotine products can only be legally marketed if they have received premarket authorization from the FDA. Despite these prohibitions, Instagram appears to be a hub for potentially unregulated sales of synthetic and "tobacco-free" products. Efforts are needed by platforms and regulators to enhance content moderation and prevent unregulated online sales of existing and emerging synthetic nicotine products. IMPLICATIONS: There is limited clinical understanding of synthetic nicotine's unique health risks and how these novel products are changing over time due to regulatory oversight. Despite synthetic nicotine specific regulatory measures, such as the requirement for premarket authorization and FDA warning letters issued to unauthorized sellers, access to and promotion of synthetic nicotine is widely occurring on Instagram, a platform with over 2 billion users and one that is popular among youth and young adults. Activities include direct-to-consumer sales from questionable sources, inadequate health warning disclosure, and exposure with limited age restrictions, all conditions necessary for the sale of various tobacco products. Notably, the number of these Instagram posts increased in response to the announcement of new FDA regulations. In response, more robust online monitoring, content moderation, and proactive enforcement is needed from platforms who should work collaboratively with regulators to identify, report, and remove content in clear violation of platform policies and federal laws. Regulatory implementation and enforcement should prioritize digital platforms as conduits for unregulated access to synthetic nicotine products and other future novel and emerging tobacco products.

Nicotine transport across calu-3 cell monolayer: effect of nicotine salts and flavored e-liquids.

OBJECTIVE: This study aimed to investigate the transport capability of nicotine across Calu-3 cell monolayer in various nicotine forms, including nicotine freebase, nicotine salts, and flavored e-liquids with nicotine benzoate. SIGNIFICANCE: Nicotine is rapidly absorbed from the respiratory system into systemic circulation during e-cigarettes use. However, the mechanism of nicotine transport in the lung has not been well understood yet. This study may offer critical biological evidence and have implications for the use and regulation of e-cigarettes. METHODS: The viability of Calu-3 cells after administration of nicotine freebase, nicotine salts and representative e-liquid were evaluated using the MTT assay, and the integrity of the Calu-3 cell monolayer was evaluated by transepithelial electrical resistance measurement and morphological analysis. Further, the nicotine transport capacity across the Calu-3 cell monolayer in various formulations of nicotine was investigated by analysis of nicotine transport amount. RESULTS: The findings indicated that nicotine transport occurred passively and was time-dependent across the Calu-3cell monolayer. In addition, the nicotine transport was influenced by the type of nicotine salts and their respective pH value. The nicotine benzoate exhibited the highest apparent permeability coefficient (Papp), and higher nicotine-to-benzoic acid ratios led to higher Papp values. The addition of flavors to e-liquid resulted in increased Papp values, with the most significant increment being observed in tobacco-flavored e-liquid. CONCLUSIONS: In summary, the transport capability of nicotine across the Calu-3 cell monolayer was influenced by the pH values of nicotine salts and flavor additives in e-liquids.

Two Fast GC-MS Methods for the Measurement of Nicotine, Propylene Glycol, Vegetable Glycol, Ethylmaltol, Diacetyl, and Acetylpropionyl in Refill Liquids for E-Cigarettes.

The use of e-cigarettes (ECs) has become increasingly popular worldwide, even though scientific results have not established their safety. Diacetyl (DA) and acetylpropionyl (AP), which can be present in ECs, are linked with lung diseases. Ethyl maltol (EM)-the most commonly used flavoring agent-can be present in toxic concentrations. Until now, there is no methodology for the determination of nicotine, propylene glycol (PG), vegetable glycerin (VG), EM, DA, and acetylpropionyl in e-liquids that can be used as a quality control procedure. Herein, gas chromatography coupled with mass spectrometry (GC-MS) was applied for the development of analytical methodologies for these substances. Two GC-MS methodologies were developed and fully validated, fulfilling the standards for the integration in a routine quality control procedure by manufacturers. As proof of applicability, the methodology was applied for the analysis of several e-liquids. Differences were observed between the labeled and the experimental levels of PG, VG, and nicotine. Three samples contained EM at higher concentrations compared to the other samples, while only one contained DA. These validated methodologies can be used for the quality control analysis of EC liquid samples regarding nicotine, PG, and VG amounts, as well as for the measurement of the EM.

Quantitation of Flavor Compounds in Refill Solutions for Electronic Cigarettes Using HS-GCxIMS and Internal Standards.

New regulations on the use of flavor compounds in tobaccoless electronic cigarettes require comprehensive analyses. Gas chromatography coupled ion mobility spectrometry is on the rise as an analytical technique for analyzing volatile organic compounds as it combines sensitivity, selectivity, and easy usage with a full-range screening. A current challenge is the quantitative GCxIMS-analysis. Non-linear calibration methods are predominantly used. This work presents a new calibration method using linearization and its corresponding fit based on the relation between the reactant and analyte ions from the chemical ionization. The analysis of e-liquids is used to compare the presented calibration with an established method based on a non-linear Boltzmann fit. Since e-liquids contain matrix compounds that have been shown to influence the analyte signals, the use of internal standards is introduced to reduce these effects in GCxIMS-analysis directly. Different matrix mixtures were evaluated in the matrix-matched calibration to improve the quantitation further. The system's detection and quantitation limits were determined using a separate linear calibration. A matrix-matched calibration series of 29 volatile compounds with 12 levels were used to determine the concentration of these substances in a spiked, flavorless e-liquid and a banana-flavored e-liquid, validating the quality of the different calibrations.

Nearly 20 000 e-liquids and 250 unique flavour descriptions: an overview of the Dutch market based on information from manufacturers.

OBJECTIVES: Flavours increase attractiveness of electronic cigarettes and stimulate use among vulnerable groups such as non-smoking adolescents. It is important for regulators to monitor the market to gain insight in, and regulate the range of e-liquid flavours that is available to consumers. E-liquid manufacturers are required to report key product information to authorities in the European Member States in which they plan to market their products. This information was used to provide an overview of e-liquid flavour descriptions marketed in the Netherlands in 2017. METHODS: Two researchers classified 19 266 e-liquids into the 16 main categories of the e-liquid flavour wheel, based on information from four variables in the European Common Entry Gate system. Flavour descriptions were further specified in subcategories. RESULTS: For 16 300 e-liquids (85%), sufficient information was available for classification. The categories containing the highest number of e-liquids were fruit (34%), tobacco (16%) and dessert (10%). For all e-liquids, excluding unflavoured ones, 245 subcategories were defined within the main categories. In addition to previously reported subcategories, various miscellaneous flavours such as sandwich, buttermilk and lavender were identified. CONCLUSIONS: In 2017, ~20 000 e-liquids were reported to be marketed in the Netherlands, in 245 unique flavour descriptions. The variety of marketed flavour descriptions reflects flavour preference of e-cigarette users as described in literature. Our systematic classification of e-liquids by flavour description provides a tool for organising the huge variety in market supply, serves as an example for other countries to generate similar overviews and can support regulators in developing flavour regulations.

Electronic Cigarette Refill Liquids: Nicotine Content, Presence of Child-Resistant Packaging, and in-Shop Compounding.

PURPOSE: To expand on our 2015 study of the nicotine content accuracy of e-liquids, including salts, and the presence of child-resistant packaging. We also describe compounding in shop (CIS). DESIGN AND METHODS: We analyzed samples from 35 shops. CIS processing was observed. Descriptive statistics summarized the data, and inference was performed. RESULTS: Actual nicotine content was significantly less than the identified content, on average, with a mean percent deviation 34.0% below the identified content. Only 3.8% of the samples' actual nicotine content was within 10% of the identified content; the maximum deviation was 213.2%. Of eight uniquely packaged samples, including designs resembling pop cans, ice cream cones, etc., the mean percent deviation was -39.6%; none were within 10% of the identified content. Eight shops compounded samples. After removing outlier values, significant differences were found in the percent deviations between the CIS and non-CIS free-base samples. A significantly higher percentage of CIS samples had nicotine content > 10% above the identified content, and none were within 10%. One shop visually estimated the nicotine quantities to add, e-liquids were not always relabeled to reflect new nicotine levels, and protective materials were not always worn during compounding. Child-resistant packaging was not present for one third of the samples. CONCLUSIONS: Labeling of nicotine content in e-liquids remains inaccurate, child-resistant packaging is inconsistent, and CIS is problematic. Effective e-liquid regulation is needed to protect public health. PRACTICE IMPLICATIONS: Nurses should educate families about the serious health risks of e-liquids and advocate for increased e-liquid regulations.

ICP-MS Determination of 23 Elements of Potential Health Concern in Liquids of e-Cigarettes. Method Development, Validation, and Application to 37 Real Samples.

The lack of interest in the determination of toxic elements in liquids for electronic cigarettes (e-liquids) has so far been reflected in the scarce number of accurate and validated analytical methods devoted to this aim. Since the strong matrix effects observed for e-liquids constitute an exciting analytical challenge, the main goal of this study was to develop and validate an ICP-MS method aimed to quantify 23 elements in 37 e-liquids of different flavors. Great attention has been paid to the critical phases of sample pre-treatment, as well as to the optimization of the ICP-MS conditions for each element and of the quantification. All samples exhibited a very low amount of the elements under investigation. Indeed, the sum of their average concentration was of ca. 0.6 mg kg-1. Toxic elements were always below a few tens of a µg per kg-1 and, very often, their amount was below the relevant quantification limits. Tobacco and tonic flavors showed the highest and the lowest concentration of elements, respectively. The most abundant elements came frequently from propylene glycol and vegetal glycerin, as confirmed by PCA. A proper choice of these substances could further decrease the elemental concentration in e-liquids, which are probably barely involved as potential sources of toxic elements inhaled by vapers.

Toxicity assessment of electronic cigarettes.

Sale of electronic cigarette (e-cigarette) products has exponentially increased in the past decade, which raise concerns about its safety. This updated review provides the available toxicology profile of e-cigarettes, summarizing evidence from in vitro and in vivo studies. Data regarding which components in e-liquids exhibit potential toxicities are inconsistent. Some studies have reported that nicotine plays a significant role in inducing adverse outcomes and that solvents alone do not induce any adverse effects. However, other studies have suggested that nicotine is not associated with any adverse outcomes, whereas solvents and flavorings are the key components to elicit considerable deleterious effects on cells or animals. In addition, most of the studies that have compared the toxicity of e-cigarettes with tobacco cigarettes have suggested that e-cigarettes are less toxic than tobacco cigarettes. Nevertheless, scientific evidence regarding the toxicity profile of e-cigarette is insufficient owing to the lack of a standardized research approach. In the future, scientific toxicology data derived from standardized testing protocols including nicotine, ingredients analysis, the various e-cigarette devices made from different materials are urgently needed for thorough toxicology assessment. This review aims to update the toxicity profiles, identify knowledge gaps, and outline future directions for e-cigarettes research, which would greatly benefit public health professionals.

On the potential harmful effects of E-Cigarettes (EC) on the developing brain: The relationship between vaping-induced oxidative stress and adolescent/young adults social maladjustment.

INTRODUCTION: Evidence suggests that in convenience stores across the United States (U.S), sales of e-cigarettes (EC) continue to grow, indicating their rising popularity. ECs have been touted as a means for traditional cigarette (TC) smokers to quit smoking. However, the dramatic increase in the number of adolescents and young adults using e-cigarettes (vaping) in America is a cause for concern as their long-term effects remain unknown. METHODS: Search was done by accessing PubMed/Medline, EBSCO, and PsycINFO databases. The search string used was "(Cigarettes OR E-Cigarettes* OR Vaping) AND (Oxidative Stress* OR Reactive Oxygen Species (ROS)) AND (Adolescents OR Teens OR Young Adults)". The electronic databases were searched for titles or abstracts containing these terms in all published articles between January 1, 1970, and June 30, 2019. Over 3000 articles were found in the first round of search which was filtered to 129 articles. RESULTS: Oxidative Stress is a critical underlying molecular factor that drives the harmful effects of traditional cigarettes. The developing brain is particularly vulnerable to the harmful effects of oxidative stress and e-cigarettes just like traditional cigarettes induces oxidative stress. Many e-cigarette components including the flavoring, vapor, e-liquids and metallic coil, trigger oxidative stress, indicating that both nicotine and non-nicotine e-cigarette use may be harmful. CONCLUSIONS: E-cigarettes use could potentially play a role in adolescent/young adults social maladjustments including poor learning and academic performance, increased aggressive and impulsive behavior, poor sleep quality, attention deficits, impaired memory, and cognition, and increased depression and suicidal ideation. The government, parents, school authorities and clinicians should be advised on these potentially harmful effects.

Changing patterns of first e-cigarette flavor used and current flavors used by 20,836 adult frequent e-cigarette users in the USA.

BACKGROUND: Understanding the role that flavors play in the population's use of e-cigarettes and the impact that flavored e-cigarette products have on the population's use of more harmful tobacco products, like conventional cigarettes, has been identified by the US Food and Drug Administration (FDA) as a public health research priority. The purpose of the study was to assess the first e-cigarette flavor and current e-cigarette flavors used by a large non-probabilistic sample of adult frequent users of e-cigarettes in the USA and assess how flavor preferences vary by cigarette smoking status and time since first e-cigarette purchase. METHODS: An online survey assessed the first e-cigarette flavor and current e-cigarette flavors used by a non-probabilistic sample of 20,836 adult frequent e-cigarette users in the USA. Differences in e-cigarette flavor preferences between current smokers, former smokers, and never-smokers and trends in the first flavor used across time of e-cigarette use initiation were assessed. RESULTS: The majority (n = 15,807; 76.4%) of sampled frequent e-cigarette users had completely substituted e-cigarettes for conventional cigarettes-"switchers"-and were currently using rechargeable, refillable vaping devices. Among them, the proportion of first e-cigarette purchases that were fruit-flavored increased from 17.8% of first purchases made before 2011 to 33.5% of first purchases made between June 2015 and June 2016. Tobacco-flavored first purchases almost halved during this time (46.0% pre-2011 to 24.0% between 2015 and 2016). Fruit/fruit beverage (73.9 to 82.9% of sampled users), dessert/pastry (63.5 to 68.5% of sampled users), and candy, chocolate, or sweets (48.7 to 53.4% of sampled users) were the most popular currently used e-cigarette flavors. Tobacco and menthol flavors, the two most popular flavors for initiating e-cigarette use prior to 2013, now rank as the 5th and 6th most popular currently used e-cigarette flavors, respectively. CONCLUSIONS: Adult frequent e-cigarette users in the USA who have completely switched from smoking cigarettes to using e-cigarettes are increasingly likely to have initiated e-cigarette use with non-tobacco flavors and to have transitioned from tobacco to non-tobacco flavors over time. Restricting access to non-tobacco e-cigarette flavors may discourage smokers from attempting to switch to e-cigarettes.

E-cigarette puffing patterns associated with high and low nicotine e-liquid strength: effects on toxicant and carcinogen exposure.

BACKGROUND: Contrary to intuition, use of lower strength nicotine e-liquids might not offer reduced health risk if compensatory puffing behaviour occurs. Compensatory puffing (e.g. more frequent, longer puffs) or user behaviour (increasing the wattage) can lead to higher temperatures at which glycerine and propylene glycol (solvents used in e-liquids) undergo decomposition to carbonyl compounds, including the carcinogens formaldehyde and acetaldehyde. This study aims to document puffing patterns and user behaviour associated with using high and low strength nicotine e-liquid and associated toxicant/carcinogen exposure in experienced e-cigarette users (known as vapers herein). METHODS/DESIGN: A counterbalanced repeated measures design. PARTICIPANTS: Non-tobacco smoking vapers; have used an e-cigarette for ≥3 months; currently using nicotine strength e-liquid ≥12mg/mL and a second or third generation device. INTERVENTION: This study will measure puffing patterns in vapers whilst they use high and low strength nicotine e-liquid under fixed and user-defined settings, each for a week. The 4 counterbalanced conditions are: i) low strength (6mg/mL), fixed settings; ii) low strength user-defined settings; iii) high strength (18mg/mL) fixed settings; iv) high strength user-defined settings. Biomarkers of exposure to toxicants and carcinogens will be measured in urine. In the second phase of this study, toxicant yields will be measured in aerosol generated using a smoking machine operated to replicate the puffing behaviours of each participant. PRIMARY OUTCOMES: i) Puffing patterns (mean puff number, puff duration, inter-puff interval and mL of liquid consumed) and user behaviour (changes to device settings: voltage and air-flow) associated with using high and low strength nicotine e-liquid. ii) Toxicant/carcinogen exposure associated with the puffing patterns/device settings used by our participants. SECONDARY OUTCOMES: i) Subjective effects. ii) comparisons with toxicant exposure from tobacco smoke (using documented evidence) and with recommended safety limits. SAMPLE SIZE: Twenty participants. DISCUSSION: The findings will have important implications for public health messaging regarding the relative risks and subjective effects associated with using high and low strength nicotine e-liquid, and for policy makers regarding regulations on nicotine concentrations in e-liquids.

Trace elements in e-liquids - Development and validation of an ICP-MS method for the analysis of electronic cigarette refills.

Electronic cigarette use has rapidly increased in recent years. In assessing their safety, and in view of coming regulations, trace elements (TE) are among the potentially toxic compounds required to be evaluated in electronic cigarette refill fluids ("e-liquids"). An analytical method using inductively coupled plasma with mass spectrometric detection (ICP-MS) was developed and rigorously validated in order to determine concentrations of 15 TE in 54 e-liquids from a French brand. Despite a significant matrix effect from the main e-liquid constituents, and difficulties related to the current lack of reference materials, our method demonstrated satisfactory linearity, precision and robustness, and permitted the quantification of low concentrations of these 15 elements: lower limits of quantification (LLQ) obtained were ≤4 ppb for all elements except for Ni, Cu and Zn (16 ppb, 20 ppb and 200 ppb, respectively). All TE concentrations in all tested samples were <510 ppb, mostly near or below the LLQs. This method is transposable and is timely for laboratories seeking to meet a prospective demand in light of current or future regulations.

An ingredient co-occurrence network gives insight into e-liquid flavor complexity.

INTRODUCTION: Part of the appeal of e-cigarettes lies in their available flavors. To achieve attractive flavors, e-liquids contain many different flavoring agents, which allow many flavoring combinations. To advance our knowledge of e-liquid flavors and compositions and to evaluate the effect of legislation, we determined whether there are ingredient combinations that are frequently used together. METHODS: We used e-cigarette ingredient data from the European Common Entry Gate system (EU-CEG) as available on 31 December 2022. RESULTS: In e-liquids, we found 214 ingredient pairs with a co-occurrence odds ratio greater than 10. Together, these consisted of 62 unique ingredients. Network analysis revealed that ingredients were grouped together based on their flavor and/or chemical structure. We identified two densely connected regions (clusters) in the network. One consisted of six ingredients with sweet-vanilla-creamy flavors. The second cluster consisted of 13 ingredients. While some of these have fruity flavors, others, such as alkyl carboxylic acids and dimethyl sulfide, are known to have unpleasant flavors. Additional data and literature analyses indicated that alkyl carboxylic acids can contribute to a creamy and sweet-fruity taste, whereas dimethyl sulfide can contribute to a more refined fruity taste. CONCLUSIONS: These results exemplify that the flavor of e-liquids is not just the sum of its parts. Big data analyses on product data can be used to detect such patterns, but expert knowledge and additional data are needed for further interpretation. Monitoring of e-liquid flavors as well as ingredients will remain important to regulate e-liquid product attractiveness.

Development of a Flavor Ingredient Wheel Linking E-Liquid Additives to the Labeled Flavor of Vaping Products.

E-liquids contain combinations of chemicals, with many enhancing the sensory attractiveness of the product. Studies are needed to understand and characterize e-liquid ingredients, particularly flavorings, to inform future research and regulations of these products. We identified common flavor ingredients in a convenience sample of commercial e-liquids using gas chromatography-mass spectrometry. E-liquid flavors were categorized by flavor descriptors provided on the product packaging. A Flavor Ingredient Wheel was developed to link e-liquid flavor ingredients with flavor categories. An analysis of 109 samples identified 48 flavor ingredients. Consistency between the labeled flavor and ingredients used to produce such flavor was found. Our novel Flavor Ingredient Wheel organizes e-liquids by flavor and ingredients, enabling efficient analysis of the link between ingredients and their flavor profiles and allowing for quick assessment of an e-liquid ingredient's flavor profile. Investigating ingredient profiles and identifying and classifying commonly used chemicals in e-liquids may assist with future studies and improve the ability to regulate these products.

Sensitivity of Mouse Lung Nuclear Receptors to Electronic Cigarette Aerosols and Influence of Sex Differences: A Pilot Study.

The emerging concern about chemicals in electronic cigarettes, even those without nicotine, demands the development of advanced criteria for their exposure and risk assessment. This study aims to highlight the sensitivity of lung nuclear receptors (NRs) to electronic cigarette e-liquids, independent of nicotine presence, and the influence of the sex variable on these effects. Adult male and female C57BL/6J mice were exposed to electronic cigarettes with 0%, 3%, and 6% nicotine daily (70 mL, 3.3 s, 1 puff per min/30 min) for 14 days, using the inExpose full body chamber (SCIREQ). Following exposure, lung tissues were harvested, and RNA extracted. The expression of 84 NRs was determined using the RT2 profiler mRNA array (Qiagen). Results exhibit a high sensitivity to e-liquid exposure irrespective of the presence of nicotine, with differential expression of NRs, including one (females) and twenty-four (males) in 0% nicotine groups compared to non-exposed control mice. However, nicotine-dependent results were also significant with seven NRs (females), fifty-three NRs (males) in 3% and twenty-three NRs (female) twenty-nine NRs (male) in 6% nicotine groups, compared to 0% nicotine mice. Sex-specific changes were significant, but sex-related differences were not observed. The study provides a strong rationale for further investigation.

Characterization of an Electronic Nicotine Delivery System (ENDS) Aerosol Generation Platform to Determine Exposure Risks.

Evaluating vaping parameters that influence electronic nicotine delivery system (ENDS) emission profiles and potentially hazardous exposure levels is essential to protecting human health. We developed an automated multi-channel ENDS aerosol generation system (EAGS) for characterizing size-resolved particle emissions across pod- and mod-type devices using real-time monitoring instruments, an exposure chamber, and vaping parameters including different ventilation rates, device type and age, e-liquid formulation, and atomizer setup. Results show the ENDS device type, e-liquid flavoring, and nicotine content can affect particle emissions. In general, pod-type devices have unimodal particle size distributions and higher number emissions, while mod-type devices have bimodal size distributions and higher mass emissions. For pod-type devices, later puff fractions emit lower aerosols, which is potentially associated with the change of coil resistance and power during ageing. For a mod-type device, an atomizer with a lower resistance coil and higher power generates larger particle emissions than an atomizer with a greater resistance coil and lower power. The unventilated scenario produces higher particle emission factors, except for particle mass emission from pod-type devices. The data provided herein indicate the EAGS can produce realistic and reproducible puff profiles of pod- and mod-type ENDS devices and therefore is a suitable platform for characterizing ENDS-associated exposure risks.

Occurrence of metals in e-cigarette liquids: Influence of coils on metal leaching and exposure assessment.

Electronic cigarettes are generally recognized as a safer alternative than conventional cigarettes. Nevertheless, previous research suggests metal (loid) leaching due to coil contact, potentially transferring to the e-liquid and its aerosolized form. In this study, Cr, Cd, Ni, and Pb levels were measured by inductively coupled plasma mass spectrometry (ICP-MS) on 17 samples of e-liquids with different chemical properties (e.g., pH, nicotine content, flavoring, free-base, and nicotine salts). Twelve e-liquids were then put in contact with 36-gauge Kanthal A-1, Nichrome 80, Stainless steel 317 L and disposable coils such as Juul, and Aspire BVC for three days at 200-250 °C for 1 h each day. Metal levels expressed as mean (standard deviation) metal concentration, were below detection (Cd) to very low in bottle samples (Ni ≤ 76 (18); Pb ≤ 16 (1.5); and Cr ≤ 386 (15.6) µg/kg). In the coil extracts, varying concentrations of the same metal (loid) were found, indicating that metal leaching capacity may differ per sample. All samples contained Ni and Cr, followed by Pb to a much lesser extent. Cd levels were mostly below detection limits. Coil + e-liquid combinations with the highest Ni, Cr, and Pb concentrations were: Aspire BVC + Melon 0 mg/mL: Ni = 1.22 E+04 (281); Aspire BVC + Hit Nicotine 40 mg/mL: Cr = 864 (116); and Nichrome 80 + Melon 0 mg/mL: Pb = 56 (5) µg/kg. Overall, results suggest that nicotine salts at 40 mg/mL enhance Cr and Ni transfer. Stainless steel 317 L released very low metal concentrations. A conservative screening level risk characterization showed that 10.5% and 3.5% of the coil extracts may exceed Ni and Cr (III) safe concentrations, respectively. In the aerosol phase, 8.8% of samples might be above Ni equivalent daily dose for chronic exposure and 1.8% for intermediate exposure. Further studies on coil metal leaching could aid in establishing coil manufacturing regulations.