Electronic Nicotine Delivery Systems Products Research Articles

Nicotine-Containing Electronic Nicotine Delivery Systems (ENDS) Use in the United States, Stratified by Age, National Survey on Drug Use and Health, 2021

Background: Electronic nicotine delivery system (ENDS) use is prevalent in the United States, especially among youth and young adults. It is important to monitor current ENDS use and identify at-risk groups, particularly among tobacco naïve individuals. Methods: Using data from the 2021 National Survey on Drug Use and Health, we examined the prevalence of past 30-day nicotine/tobacco ENDS use and correlates, stratified by age. Results: The prevalence of past 30-day ENDS use was as follows: ages 12-17 (5.0%), ages 18-20 (13.5%), ages 21-25 (14.6%), ages 26-34 (7.2%), and ages ≥35 (2.5%). Among youth ages 12-17, female respondents were more likely to report past 30-day ENDS use compared to male respondents (aOR = 1.41, 95% CI = 1.01-1.97). Among all adult age groups, current cigarette smoking status was associated with an increased likelihood of current ENDS use, versus never smoking. Among all age groups, those reporting non-Hispanic Black, non-Hispanic Other, and Hispanic race/ethnicity had a decreased likelihood of past 30-day ENDS use versus non-Hispanic White respondents, while past-year drug/alcohol use disorder, versus no use disorder, was associated with an increased likelihood of past 30-day ENDS use. Conclusions: ENDS use was most prevalent among young adults and least prevalent among persons ages ≥35. Most youth who reported ENDS use also reported never smoking cigarettes—compared to adults who reported ENDS use, who primarily reported current or former cigarette smoking. Our findings—which have identified characteristics of those most likely to use ENDS products—have the potential to inform screening and targeted intervention efforts aimed at reducing ENDS use.

Flavor and Device Choices Among People Who Use ENDS: Results From the PATH Study

IntroductionIn guidance published in February 2020, the FDA described their intent to prioritize enforcement against the sale of flavored cartridge-based electronic nicotine delivery systems (ENDS) except tobacco and menthol flavors. This guidance was specific to cartridge-based ENDS and did not apply to other ENDS types or e-liquids sold in the United States (U.S.). It remains unknown if use of certain types of ENDS devices and flavors changed following the publication of this guidance. MethodsThis analysis includes PATH Study data from Wave 5 (W5, 2018-2019) and Wave 6 (W6, 2021) and examines cross-sectional estimates of 1) use of flavored ENDS and 2) use of different device types. All analyses in this study were stratified by self-reported age (youth – aged 12-17 years at W5 and aged 14-17 years at W6, and adults – aged 18-20, 21-24, and 25+). Analyses were conducted in 2023-2024. ResultsAmong adults aged 21 years and over, there were significant increases in the use of menthol or mint flavored ENDS. There were no substantial changes in flavors of ENDS used among youth or adults aged 18-20 years. Among all age groups, the use of cartridge-based ENDS was lower in 2021 than 2018–2019, with a notable shift to disposable-style ENDS. ConclusionsFederal-level tobacco control actions taken in the U.S. in early 2020 prioritized enforcement against “any flavored, cartridge-based ENDS product (other than a tobacco- or menthol-flavored ENDS product)”. Based on this analysis, there was a shift following the policy to menthol or mint-flavored ENDS and disposable-style ENDS.

Flavored Tobacco User Characteristics in U.S. young Adults: Wave 5 of the Population Assessment of Tobacco and Health Study

Introduction: Flavorings are one of the major appealing factors of current tobacco products, especially for young adults. They constantly evolve, and new flavorings are introduced to the market every year, but little is known about user profiles of flavored tobacco products (FTPs). Methods: We analyzed young adult (ages 18–24) tobacco product users (N = 4,707) from Wave 5 of the Population Assessment of Tobacco and Health Study. We applied bivariate analyses to compare individuals who use FTP and non-FTPs by different flavor types (i.e., menthol/mint, fruit, candy/sweets, and tobacco). Parameter estimates were weighted by applying the sample and replicate weights for the complex study design to produce population-representative estimates. Results: Sixty percent of the current combustible tobacco users and 90% of electronic nicotine delivery systems (ENDS) users were FTP users. FTP users were more likely to be multiple product users than non-FTP users. Being non-Hispanic White, drinking alcohol in the past year, experiencing internalizing problems in the past month, and having tobacco dependence were associated with FTP use. Flavored ENDS users had different sociodemographic characteristics by flavor types but did not differ significantly in vaping-related behaviors (e.g., frequency). Also, preferred flavors differed among tobacco user groups (i.e., ENDS, hookah, and cigars). Conclusions: FTPs appear to be gaining popularity among young adults and tend to show co-use with multiple tobacco products and other substances. Future studies are warranted to monitor the risk factors of young adult FTP use, especially in the context of flavor ban on ENDS products.

Content analysis of conversations on Reddit: reactions to FDA’s ENDS prioritized enforcement policy

IntroductionOn January 2, 2020, the FDA announced a policy focused in part on prioritizing enforcement of flavored (other than tobacco- or menthol-flavored) cartridge-based electronic nicotine delivery systems (ENDS) without premarket authorization.MethodsWe used a query to identify Reddit conversations relevant to the policy from January 2 to May 6, 2020. Our sample included 576 posts (46 posts and 530 accompanying comments). Two analysts coded posts for mentions of use behaviors (e.g., switching, quitting), purchasing behaviors (e.g., purchasing from retailer new to the user), and flavored products. We summarized frequencies of coded data and provided illustrative quotes.ResultsOnly 21.0% (121/576) of posts mentioned use behavior. Switching behavior was the most common use behavior mentioned (50.4%, 61/121). Most switching behavior posts focused on ENDS-related switching (91.8%, 56/61). The most common ENDS-related switching behaviors mentioned were switching to an open tank (45.9%, 28/61) or device with refillable pods/cartridges (44.3%, 27/61); 8.2% (5/61) mentioned switching to disposables. Just 15.5% (89/576) of posts mentioned purchasing behavior, with the most common being purchasing from a retailer new to the user (32.6%, 29/89). Only 6.8% (39/576) of posts mentioned specific flavors.ConclusionReddit posts about the policy commonly discussed switching to non-cartridge-based ENDS products, such as open tank systems or disposable devices, and purchasing products from different online sources that were still selling these products. Findings suggest that publicly available Reddit data can complement data from traditional sources (e.g., surveys, sales) to understand potential unintended consequences associated with policies by exploring the public’s reactions.

“I’m both smoking and vaping”: a longitudinal qualitative study of US young adults who tried to quit smoking cigarettes by using electronic cigarettes

ObjectiveTo describe how young adults use electronic cigarettes (electronic nicotine delivery systems (ENDS)) for smoking cessation and reasons why they may or may not successfully quit smoking.MethodsLongitudinal qualitative data were...

Harmful and Potentially Harmful Constituents Analysis of North American ENDS

Summary The objective of this study was to create a North American e-cigarette, or electronic nicotine delivery system (ENDS), market map representative of the 2020 and 2021 commercial market for analysis of harmful and potentially harmful constituents (HPHCs) and other chemicals in aerosol. The study consisted of 14 brands (seven closed pod-based, four open (refillable) pod-based, two cigalike, one disposable) and analyzed multiple e-liquid formulations per brand with varying labelled nicotine concentrations and flavors, equating to 35 unique tested ENDS. Aerosol was generated using two puffing regimes (ISO 27068 and intense) and analyzed for primary constituents, metals, carbonyls, and glycidol in a head-to-head comparison in the same testing laboratory. Nicotine yields per puff ranged from 0.045 mg/puff for the lowest yielding ENDS under the ISO 27068 puffing regime to 1.11 mg/puff for the highest yielding ENDS under intense puffing conditions. For carbonyls, all ENDS generated quantifiable amounts of acetaldehyde, acrolein, and formaldehyde in collected aerosol, irrespective of puffing regime, with an increase in yields observed under intense puffing compared to ISO 27068 puffing for the majority of tested ENDS. For metals, the ENDS aerosol yielded nickel (Ni) ranging from below limits of detection (BLOD) to >30 ng/puff, while quantifiable levels of chromium (Cr), copper (Cu), and lead (Pb) were only associated with select ENDS. All tested ENDS aerosol contained quantifiable glycidol ranging from 0.003 to >1.00 µg/puff for ISO 20768 and 0.005 to 1.10 µg/puff for intense puffing regimes. As a category, ENDS aerosol showed significantly reduced levels of HPHCs compared to 1R6F combustible cigarette (CC) smoke on a per nicotine basis. However, there was variability among ENDS and the aerosol of some ENDS products produced increased levels of specific HPHCs (e.g., formaldehyde and nickel) compared to 1R6F CC smoke. The observed HPHC variations appear to be primarily dependent on device design. In summary, this work is one of the most comprehensive analyses of HPHCs for North American ENDS using validated analytical methods in the same test facility for a head-to-head comparison.

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination.

β-Nicotyrine (β-Nic) is a unique minor alkaloid constituent in electronic nicotine delivery systems (ENDS) that is derived from nicotine (Nic) degradation and can reach 25% of Nic concentrations in ENDS aerosol. β-Nic slows Nic metabolism and prolongs systemic Nic exposure, which may alter the discriminability of Nic. The present study sought to examine β-Nic has interoceptive effects itself, and if it alters the subjective effects ENDS products within a drug-discrimination paradigm. The pharmacodynamics of β-Nic were examined in vitro, and a nicotine discrimination paradigm was used to determine if β-Nic (0 - 5.0 mg/kg) shares discriminative stimulus properties with Nic (0.2 mg/kg) in male (n = 13) and female (n = 14) rats after 10- & 60-min β-Nic pretreatment delays. A second group of rats was trained to discriminate β-Nic and Nornicotine (Nornic) from saline to determine if β-Nic alone has interoceptive properties and whether they are similar to Nornic. β-Nic had similar binding affinity and efficacy at the α4β2 nicotinic receptor subtype as Nornic, ~50% of Nic efficacy. However, β-Nic only weakly substituted for Nic during substitution testing in female rats, but not males, whereas Nornic fully substituted for Nic. Combination testing at the 10 and 60-min pretreatment intervals showed that β-Nic dose-dependently increased the duration of nicotine's discriminative stimulus effects, especially at the 60-min delay. Drug naïve rats could reliably discriminate Nornic, but not β-Nic, from Sal. β-Nic increased and prolonged the interoceptive stimulus properties of Nic, suggesting it may alter to the abuse liability of ENDS through its ability to slow Nic metabolism.

National longitudinal tobacco product discontinuation rates among US youth from the PATH Study: 2013–2019 (waves 1–5)

ObjectiveDetermine longitudinal tobacco product discontinuation rates among youth (ages 12–17 years) in the USA between 2013 and 2019.MethodsThe Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort...

Associations between social media engagement and young adults’ subsequent onset of ENDS dependence symptoms one year later

BackgroundYoung adults are more vulnerable than older adults to engagement with online tobacco marketing and to the use of electronic nicotine delivery systems (ENDS) products. Our study examined the longitudinal associations between engagement with pro- and anti-tobacco information on social media (SM) and young adults’ subsequent onset of symptoms of dependence on ENDS products one year later, which remain unclear. MethodsParticipants were college students in the Marketing and Promotions Across Colleges in Texas study. We analyzed data collected in spring 2018 (wave 8, baseline) and spring 2019 (wave 9), which involves 1,764 college students (Mean age = 24.48, 34.8% White) who reported having ever used any ENDS products but no ENDS dependence symptoms at baseline. Logistic regression analyses were conducted to examine the associations between pro- and anti-engagement with tobacco information at baseline and onset of ENDS dependence symptoms at one-year follow-up, controlling for baseline sociodemographic characteristics and tobacco smoking status. We also examined participant sex and depressive symptoms as moderators of the aforementioned associations. ResultsEngagement with both pro- (Odds Ratio = 1.73, p < 0.05) and anti- (Odds Ratio = 1.36, p < 0.05) tobacco information at baseline predicted the subsequent onset of symptoms of dependence on ENDS products one year later. The association between pro-engagement and subsequent onset of ENDS dependence symptoms was stronger among females than males (Exp(β) = 3.21, p < 0.05). Depressive symptomology did not moderate any of the associations. ConclusionsFindings suggest that engaging with tobacco information on SM, regardless of its valence, serves as a risk factor for the development of subsequent dependence symptoms among young adult ever ENDS users. Considering the uncertainty of ENDS products’ health effects, regulation of SM is encouraged to reduce young adults’ (re)posting thoughts or comments about the advantages of ENDS products.

Assessment of abuse liability and switching potential of menthol-flavored pod-based electronic nicotine delivery systems among US adults who smoke cigarettes

BackgroundMenthol-flavored electronic nicotine delivery systems (ENDS) are a focus of public health and regulatory policy considerations. The abuse liability of five menthol-flavored pod-based ENDS was compared to combustible cigarettes, and switching potential of ENDS was also evaluated. Methods215 US adults who smoke cigarettes (34.4% female; mean age[SD]=29.60[8.75]; 40.9% non-Hispanic White; mean cigarettes/day[SD]=12.04[8.52]) completed a randomized 6-arm within-person cross-over product-use study. Participants used five pod-based menthol-flavored ENDS (JUUL2 Polar Menthol 1.5%, JUUL2 Prototype Fresh Menthol 3.0%, JUUL Menthol 5.0%, Vuse Alto Menthol 5.0%, NJOY Ace Menthol 5.0%) and their usual brand (UB) cigarette for 20minutes ad libitum. After each product use, subjective reinforcing effects relevant to abuse liability and associated with switching away from cigarettes (e.g., satisfaction, product liking) were assessed. ResultsAll ENDS products were rated substantially and statistically significantly lower than UB cigarette on measures of subjective reinforcing effects (ps<0.001). Satisfying effects of JUUL2 1.5% were rated significantly higher than other ENDS products. JUUL2 Prototype 3.0% and Vuse Alto 5.0% did not significantly differ (ps>0.05), and both were rated significantly higher than JUUL 5.0% and NJOY Ace 5.0% (ps<0.05). Differences in subjective responses to study products did not significantly differ by preference for menthol cigarettes or by current ENDS use. ConclusionsAbuse liability of all menthol-flavored ENDS in this study was substantially lower than combustible cigarettes. Abuse liability of JUUL2 1.5% was within the range of currently marketed pod-based menthol-flavored ENDS products. JUUL2 1.5% likely has high potential for facilitating switching among US adults who smoke.

Switching Away From Smoking and Reduction in Cigarette Consumption Among U.S. Adult Purchasers of the JUUL System Across 24 Months Including Diverse Subpopulations Disproportionately Affected by Cigarette Smoking.

Electronic nicotine-delivery systems (ENDS) can reduce tobacco-related health risks for adults who smoke cigarettes (AWS) by facilitating complete switching away from cigarettes. However, little is known about ENDS use and switching among subpopulations that have been disproportionately affected by smoking. AWS (age ≥ 21 years) were recruited following their first purchase of a JUUL Starter Kit in 2018. Participants who self-reported switching (no past-30-day cigarette smoking) at 1-, 2-, 3-, 6-, 9-, 12-, 15-, 18-, 21-, and 24-month follow-ups. Percent switched and percent with substantial smoking reduction (≥50% decrease in cigarettes per day among those who continued smoking) were calculated. Analyses focused on racial and ethnic minorities, persons with low income and education levels, sexual minorities, and those with mental and physical health conditions. Overall rates of switching away from cigarettes increased across follow-ups to 51.2% (month-12) to 58.6% (month-24, 87% of whom used ENDS). Among those who continued to smoke at 24 months, 45.4% reduced cigarettes per day by ≥ 50%. Rates of switching and substantial smoking reduction were largely similar across subgroups, with some statistically significant, but small, differences in month-24 switching rates (eg, education, mental and physical health conditions; switch rate range: 42%-57%). AWS demonstrated progressively increasing switching rates over 2 years after purchasing JUUL products. Similar trends in switching and smoking reduction were observed across populations disproportionately affected by smoking. By facilitating switching and smoking reduction, ENDS products such as JUUL may provide an opportunity to reduce smoking-related harm among some populations disproportionately affected by smoking, potentially reducing tobacco-related health disparities. ENDS have the potential to benefit population health if they can replace cigarettes. This benefit must extend to populations disproportionately affected by smoking. In this real-world study, 59% of JUUL purchasers reported complete switching 2 years later (no past-30-day smoking, with most continuing to use ENDS). Furthermore, 45% of those who continued to smoke reduced cigarette consumption by at least half. These rates of switching and smoking reduction were largely comparable across populations disproportionately affected by smoking (defined, eg, by ethnicity and income). ENDS can serve as an effective harm reduction strategy to complement current efforts to reduce tobacco-related disparities.

A Practical Framework for Novel Electronic Nicotine Delivery System Evaluation: Chemical and Toxicological Characterization of JUUL2 Aerosol and Comparison with Reference Cigarettes.

Electronic nicotine delivery systems (ENDSs) are designed as a non-combustible alternative to cigarettes, aiming to deliver nicotine without the harmful byproducts of tobacco combustion. As the category evolves and new ENDS products emerge, it is important to continually assess the levels of toxicologically relevant chemicals in the aerosols and characterize any related toxicology. Herein, we present a proposed framework for characterizing novel ENDS products (i.e., devices and formulations) and determining the reduced risk potential utilizing analytical chemistry and in vitro toxicological studies with a qualitative risk assessment. To demonstrate this proposed framework, long-term stability studies (12 months) analyzing relevant toxicant emissions from six formulations of a next-generation product, JUUL2, were conducted and compared to reference combustible cigarette (CC) smoke under both non-intense and intense puffing regimes. In addition, in vitro cytotoxicity, mutagenicity, and genotoxicity assays were conducted on aerosol and smoke condensates. In all samples, relevant toxicants under both non-intense and intense puffing regimes were substantially lower than those observed in reference CC smoke. Furthermore, neither cytotoxicity, mutagenicity, nor genotoxicity was observed in aerosol condensates generated under both intense and non-intense puffing regimes, in contrast to results observed for reference cigarettes. Following the proposed framework, the results demonstrate that the ENDS products studied in this work generate significantly lower levels of toxicants relative to reference cigarettes and were not cytotoxic, mutagenic, or genotoxic under these in vitro assay conditions.

Are e-cigarettes a safer alternative to reduce incidences of oral cancer?

The rapid increase in the use of electronic nicotine delivery systems (ENDS), such as e-cigarettes and vape pens, has raised concerns about their potential impact on oral health and the risk of oral cancer. Despite their popularity and claims of being a safer alternative to traditional smoking, there is a lack of conclusive evidence regarding the detrimental effects of vaping. ENDS were initially introduced as a safer option for smokers, attracting both traditional smokers and adolescents due to appealing flavours. These devices use a battery-powered heating element to aerosolise a liquid containing nicotine, flavourings, formaldehyde, glycerol, and heavy metals. However, the variability in product composition and design makes it challenging to establish reliable toxicity profiles. This commentary aims to provide an overview of the existing evidence to inform oral and maxillofacial surgery (OMFS) practitioners about the potential risks associated with vaping on oral health and cancer. Data was extracted from ten recent studies, which included systematic reviews, meta-analyses, literature reviews, cross-sectional analyses, and in-vitro studies. While e-cigarettes have fewer carcinogens than traditional cigarettes, concerns remain about their potential for DNA damage. Reported oral symptoms related to e-cigarette use include dry mouth, irritation, pain, oral ulcers, nicotine-related conditions, and accidents resulting from device malfunctions. ENDS exposure has been linked to oral health issues like dysbiosis, inflammation, periodontal disease, and alterations in the oral microbiome. In-vitro studies have shown that e-cigarettes can induce DNA damage, oxidative stress, and genotoxicity in oral cells. Although direct causality between e-cigarettes and oral cancer remains unclear, there are case reports of oral cancer in heavy e-cigarette users without other traditional risk factors. Additionally, some ENDS components, such as formaldehyde and acetaldehyde, are known human carcinogens, potentially posing a nasopharyngeal cancer risk. ENDS use may increase chemotherapy resistance and alter immune-related gene expression, potentially facilitating HPV-16 infection. Moreover, there is concern that ENDS use could lead to future tobacco smoking among adolescents. The variability in ENDS products further complicates assessing their oral health effects. Based on current evidence, ENDS should not be considered 'safe'. The authors recommend documenting ENDS consumption and emphasise the need for extensive research to better understand their effects on oral cavity tissues. Clinicians should remain vigilant and educate patients about the potential risks associated with vaping to make informed decisions about their oral health.

Abuse liability of two electronic nicotine delivery systems compared with combustible cigarettes and nicotine gum from an open-label randomized crossover study

An assessment of the likelihood of use and abuse potential for new tobacco products is an important part of tobacco product regulation in the United States and abroad. This paper reports the results of a randomized, open-label, crossover clinical study that assessed factors related to product adoption and abuse liability (AL), comparing two closed electronic nicotine delivery system (ENDS) products to combustible cigarettes and nicotine gum, high- and low-AL comparator products, respectively. During an 11-day confinement period that included multiple product familiarization sessions, healthy adult smokers participated in AL test sessions to evaluate the abuse liability of each product. During these test sessions, changes in subjective measures; speed and amount of nicotine uptake; and maximum changes in physiological effects before, during, and after use of each assigned product were assessed over 4 h. Positive subjective effects measures scores such as product-liking and overall intent to use again were highest for cigarettes, followed by the Vuse ENDS, with nicotine gum consistently having the lowest scores. The PK results (Cmax and Tmax) of the Vuse ENDS products are between UB cigarettes and nicotine gum, which correlates with the subjective effects. All nicotine uptake measures for the Vuse ENDS products were lower than that of usual brand (UB) cigarettes, including peak nicotine uptake and overall nicotine uptake, and were either similar to or lower than nicotine gum. The time course of nicotine uptake after use of the ENDS was more similar to that of combustible cigarettes than nicotine gum. The results indicate that the AL of each ENDS product is lower than that of UB cigarettes and similar to that of nicotine gum.

Depressive symptoms prospectively increase risk for new onset cigarette and ENDS dependence symptoms

Little research has examined the new onset of cigarette and Electronic Nicotine Delivery System (ENDS) dependence symptoms among young adults. This study aims to 1) examine new onset cigarette and ENDS dependence symptoms over a 4.5-year period and 2) examine how depressive symptoms impact new onset dependence symptoms among young adults. Participants were drawn from 24 colleges in Texas who were participating in a multi-wave cohort study (2014–2019). The present study included 4536 participants aged 18–25 who did not report cigarette or ENDS dependence symptoms at wave 1 (64.1% female; 65.2% non-white; m age = 20.62 [SD = 1.80] at wave 1). Cox’s regression models were employed to determine the hazard of new onset cigarette and ENDS dependence symptoms overall and the impact of depressive symptoms. Models controlled for sociodemographic factors and other tobacco product use. 14.4% of participants reported new onset cigarette dependence symptoms and 14.6% reported new onset ENDS dependence symptoms over the 4.5 years of the study. Depressive symptoms significantly predicted increased risk for new onset cigarette (HR = 1.30, CI = [1.21, 1.39]) and ENDS (HR = 1.20, CI = [1.12, 1.29]) dependence symptoms. Young adults exhibited dependence symptoms for cigarettes and ENDS products at similar rates across the 4.5 years of the study. Elevated depressive symptoms increased risk of new onset cigarette and ENDS dependence symptoms, advancing evidence for the self-medication hypothesis. Tobacco and nicotine prevention and cessation programs and messaging are needed particularly among young adults who experience depressive symptoms.

Motives for using electronic nicotine delivery systems (ENDS) as a cessation tool are associated with tobacco abstinence at 1-year follow-up: A prospective investigation among young adults in the United States Air Force

IntroductionSmokers use electronic nicotine delivery systems (ENDS), including e-cigarettes, as a harm reduction strategy even though the Food and Drug Administration (FDA) has not approved them for tobacco cessation. The limited literature about ENDS use for cigarette cessation is concerning for the U.S. military, which is largely comprised of young adults at increased risk for tobacco use. Thus, the current study aims to evaluate use of ENDS products as a cessation tool in relation to point-prevalence tobacco abstinence at one-year follow-up in a cohort of 8,901 U.S. Air Force personnel attending entry-level job training from March 2016 to April 2019. MethodsA propensity-score adjusted multinomial logistic regression model was used to assess the association between the baseline motives for ENDS use (i.e., for cigarette cessation versus alternative reasons) and tobacco use at the one-year follow-up (cigarette use, non-cigarette tobacco product use, and tobacco abstinence) among those reporting history of cigarette use at baseline. ResultsSmokers reporting ENDS use for cigarette cessation were more likely to be abstinent at one-year follow-up (Odds Ratio[OR] = 1.62, 95% CI: 1.06–2.49, P =.03) as well as quit using non-cigarette tobacco products (OR = 2.11, 95% CI: 1.65–2.70, P <.001) than those reporting ENDS use for alternative reasons. ConclusionsCurrent tobacco users are recommended to use FDA-approved products for smoking cessation, such as nicotine replacement therapy. However, given the high prevalence of cigarette use among military populations, ENDS may provide a useful alternative harm reduction strategy for this high-risk population.

Determination of chemical constituent yields in e-cigarette aerosol using partial and whole pod collections, a comparative analysis.

Literature reports the chemical constituent yields of electronic nicotine delivery systems (ENDS) aerosol collected using a range of aerosol collection strategies. The number of puffs to deplete an ENDS product varies widely, but collections often consist of data from the first 50-100 puffs. However, it is not clear whether these discrete puff blocks are representative of constituent yields over the life of a pod. We aimed to assess the effect of differing aerosol collection strategies on reported yields for select chemical constituents in the aerosol of closed pod-based ENDS products. Constituents analyzed were chosen to reflect important classes of compounds from the Final Premarket Tobacco Product Application Guidance. Yields were normalized to total device mass loss (DML). Collection strategies that consisted of partial pod collection were valid for determining yields of constituents whose DML normalized yields were consistent for the duration of pod life. These included primary aerosol constituents, such as propylene glycol, glycerol, and nicotine, and whole pod yields could be determined from initial puff blocks. However, changes were observed in the yields of some metals, some carbonyl compounds, and glycidol over pod life in a chemical constituent and product dependent manner. These results suggest that collection strategies consisting of initial puff block collections require validation per chemical constituent/product and are not appropriate for chemical constituents with variable yields over pod life. Whole pod collection increased sensitivity and accuracy in determining metal, carbonyl, and glycidol yields compared to puff block-based collection methodologies for all products tested.

Tobacco Product Marketing Orders and Online Marketing and Sale of Unauthorized ENDS Products

This study characterizes online marketing of unauthorized electronic nicotine delivery systems (ENDS).

Comparison of the toxicological potential of two JUUL ENDS products to reference cigarette 3R4F and filtered air in a 90-day nose-only inhalation toxicity study.

Electronic nicotine delivery systems (ENDS) are generally recognized as less harmful alternatives for those who would otherwise continue to smoke cigarettes. The potential toxicity of aerosols generated from JUUL Device and Virginia Tobacco (VT3) or Menthol (ME3) JUULpods at 3.0% nicotine concentration was assessed in rats exposed at target aerosol concentrations of 1400μg/L for up to 6h/day on a 5 day/week basis for at least 90 days (general accordance with OECD 413). 3R4F reference cigarette smoke (250μg/L) and Filtered Air were used as comparators. JUUL ENDS product aerosol exposures at >5x the 3R4F cigarette smoke level resulted in greater plasma nicotine and cotinine levels (up to 2x). Notable cigarette smoke related effects included pronounced body weight reductions in male rats, pulmonary inflammation evidenced by elevated lactate dehydrogenase, pro-inflammatory cytokines and neutrophils in bronchoalveolar lavage fluid, increased heart and lung weights, and minimal to marked respiratory tract histopathology. In contrast, ENDS aerosol exposed animals had minimal body weight changes, no measurable inflammatory changes and minimal to mild laryngeal squamous metaplasia. Despite the higher exposure levels, VT3 and ME3 did not result in significant toxicity or appreciable respiratory histopathology relative to 3R4F cigarette smoke following 90 days administration.

Analytical approaches for the evaluation of data deficient simulated leachable compounds in ENDS products: a case study.

Leachable investigations are routinely undertaken across a range of sectors (e.g., pharmaceuticals, medical devices, etc.) to determine whether chemicals from a container closure system transfer into a product under normal conditions of use. For Electronic Nicotine Delivery Systems (ENDS) the container closure system includes all materials in contact with the e-liquid that is aerosolized and subsequently inhaled by the user. Currently, there is no guidance for conducting leachable studies for ENDS products, however, there are relevant guidance documents for orally inhaled drug products that can be applied to an ENDS container closure system. We present a case study of the analytical investigation of two leachable compounds identified in simulated leachable studies using aged JUULpods filled with unflavored e-liquid (PG/VG/nicotine/benzoic acid). Both compounds had limited toxicological information and were considered data deficient. A qualitative analysis of the aerosol collected from aged commercial JUULpods (Virginia Tobacco and Menthol), using a similar analytical method (LC-MS/MS) used in the simulated leachable studies, showed no trace or detectable levels of either leachable compound. Therefore, this qualitative analysis did not provide semi-quantitative values for the data-deficient leachable compounds necessary to support toxicological risk assessment. Further, no commercial authentic standards or reasonable synthetic route were available due to the molecular size and structural complexity of the compounds. Instead, method limits were established using an alternative approach to standard ICH guidelines. The experimentally determined method limit of quantitation, using spiked samples of simulated leachable e-liquid, provided conservative semi-quantitative values for each data deficient leachable compound in the aerosol that enabled a transfer efficiency from e-liquid to aerosol to be estimated. The transfer efficiency of each leachable compound was experimentally determined to be less than 2% based on the limit of quantitation, which then could be used to define a relevant exposure limit for the toxicological risk assessment. This work details a novel analytical approach for determining the transfer efficiency of data deficient leachable compounds from ENDS container closure systems into the ENDS aerosol to support toxicological health risk assessments.