Tobacco Regulatory Science Research Articles

Parsing Intra- and Inter-Individual Covariation Between the Sensory Attributes and Appeal of E-Cigarettes: Associations and Gender Differences.

Perceived sensory attributes of e-cigarettes may associate with their appeal. However, limited studies have accounted for individuals' variability in sensory attributes or have addressed how associations of sensory attributes with appeal may differ by gender. Individuals (n = 119, 32.8% female) who currently used combustible cigarettes and/or e-cigarettes attended one laboratory session in which they completed a standardized e-cigarette puffing procedure according to a 10 Flavor (green apple, strawberry, chocolate, vanilla, menthol, koolada, peppermint, spearmint, subtle tobacco, and full-flavored tobacco) × 2 Nicotine Formulation (free-base, salt) double-blind factorial design. The mean nicotine concentration was 23.4 (SD = 0.9) mg/mL in the nicotine salt formulations and 23.8 (SD = 1.7) mg/mL in the free-base formulations. Following each trial, participants completed ratings of sensory attributes (sweet, smooth, cool, bitter, harsh) and appeal (mean of liking, disliking [reverse-scored], and willingness-to-use-again ratings). Sensory attributes were partitioned into between-person and within-person variables. Gender was tested as a moderator of associations of sensory attributes with appeal. Sweet, smooth, and cool sensory attributes positively associated with appeal at the between- and within-person level (ps < .001). Bitter and harsh negatively associated with appeal at the between- and within-person level (ps < .001). The associations of between-person sweet, smooth, and cool ratings with appeal was larger in males compared to females. The associations of within-person smooth, bitter, and harsh with appeal was larger in females compared to males. This study showed important gender differences in associations of sensory attributes and appeal. While evidence suggests that sensory attributes may contribute to the appeal of e-cigarettes, there is little experimental evidence accounting for individual variability in sensory attributes and whether sensory attribute-appeal associations differ by gender. The current study provides evidence that average sweet, cool, and smooth ratings positively associated with appeal and that these associations were larger in males. Within-person bitter, harsh, and smooth ratings significantly associated with appeal in both genders, but these associations were larger in females compared to males. Data from the current report reinforces the need for researchers to study gender stratified effects in tobacco regulatory science.

Study on the Relationship between Supervisors' Remuneration in Listed Companies and Tobacco Control Measures

Objectives: At present, the theoretical study on supervisors' remuneration under the Company Law is still too principled, and many "chaos" occur in the remuneration practices for supervisors. First, the lack of clear understanding of the incentive function and institutional specificities of supervisors' remuneration results in many problems in the application of supervisors' remuneration in practice, as well as the ignoration of the Board of Supervisors in corporation governance. Second, rather than reaching the intended effect, the legislative approach of authorized "blank" intentionally adopted under the Company Law leaves an inducement for the ineffective supervision of supervisors in practice. Third, there is not only a lack of theoretically self-consistent discussion on the special problems of concurrent supervisors and employee supervisors' remuneration, but also a divorce of the institutional structure and application from good expectations. If the research background of the problem is placed in "tobacco regulatory science", it will be found that there is no inevitable connection between supervisors' compliance expectations and remuneration, but mainly depends on the provisions of legislation. Going back and forth between theory and practice of supervisors' remuneration, this paper combs and interprets the issue of supervisors' remuneration from the perspective of the legislative provisions and theoretical study under the Company Law, and analyzes the difference between the reality and the necessity of the Company Law with respect to the issue of supervisors' remuneration in the light of the legal principle of the Company Law, with the view to improvement of the rules of the Company Law.

World Digital CurrencyandTobacco Regulatory Science New Paradigm

Objectives: Based on the times analysis, we proposethe world digital currency, proposesthe world digital currency tentative plan. The so-called world digital currency is may distribute one kind of world digital currency, or as its initial digital nationality currency, as well as its initial other form like company or personal digital currency. Then has analyzed the digital currency competition, pointed out the digital currency the competition, is take the national digital currency strategy competition as the foundation, must formulate the good national digital currency strategy, at last we put forward thenew tobacco regulatory science paradigm.

NIH Tobacco Research and the Emergence of Tobacco Regulatory Science.

This study explores how the emergence of FDA-funded Tobacco Regulatory Science (TRS) research complements and perhaps influenced the direction of tobacco research supported by NIH. New NIH- and FDA-funded tobacco projects awarded in fiscal years (FY) 2011-2020 were identified using internal NIH databases of awarded grants. Project abstracts and research aims were coded by the authors to characterize research domains and tobacco products studied. Between FY 2011 and 2020, NIH funded 1032 and FDA funded 322 new tobacco projects. For the years and grant activity codes studied, the number of new NIH tobacco projects declined while FDA's increased; combined the number of new projects held steady. Much of NIH research included smoking combustibles (43.7%). The most common products in FDA research were cigarettes (74.8%) and e-cigarettes/ENDS (48.1%). Most NIH (58.6%) and FDA (67.7%) projects included research on the determinants of tobacco use. Another area of apparent overlap was health effects (29.5% NIH and 30.1% FDA). Projects unique to NIH included treatment interventions (33.3%), disease pathology/progression (17.8%) and neurobiology (18.9%). A minority of both NIH and FDA projects included populations particularly vulnerable to tobacco product use. In total, support for new tobacco research supported by NIH and FDA combined remained steady for the time period covered, though there was a concomitant decline in NIH tobacco projects with the increase in FDA-funded TRS projects for the activity codes studied. Despite the apparent overlap in some areas, both NIH and FDA support research that is unique to their respective missions. NIH continues to support tobacco research that falls within and outside of FDA's regulatory authorities. This research still is needed not only to bolster the evidence base for regulatory decisions at the national and state levels, but also to advance a comprehensive scientific agenda that can inform multiple levels of influence on tobacco control, use and addiction. It will be important to continue monitoring FDA-funded TRS and NIH-funded tobacco research portfolios to ensure that the level of support for and focus of the research is sufficient to address the burden of tobacco-related morbidity and mortality.

Electronic Nicotine Delivery Systems (ENDS) Use and Pregnancy II: Perinatal Outcomes Following ENDS Use During Pregnancy.

This review examines the risk of adverse perinatal outcomes following electronic nicotine delivery system (ENDS) use during pregnancy, and considers whether there are sufficient data to support ENDS as a harm reduction approach during pregnancy. Seven papers assessed perinatal outcomes following ENDS use during pregnancy. There was evidence that ENDS use was associated with increased risk for some adverse perinatal outcomes (e.g., small for gestational age). However, the repeated use of data sets, insufficient data (e.g., timing of ENDS use, type of ENDS products used), and limited samples size, contributed to mixed findings on the degree to which ENDS use (alone or in combination with combustible cigarettes (CC)) impacts the risk of adverse perinatal outcomes relative to CC smoking alone. The current data are still insufficient to support ENDS as a harm reduction approach, though findings do warrant concern and more detailed investigation of ENDS use during pregnancy. Future research directions, as well as implications for clinical recommendations and tobacco regulatory science are discussed.

How Does Social Media Exposure and Engagement Influence College Students’ Use of ENDS Products? A Cross-lagged Longitudinal Study

ABSTRACT Electronic nicotine delivery systems (ENDS) products have been marketed heavily on social media throughout the past years, which exerts great influence on young adults’ ENDS use. Despite scholars’ pioneering efforts in investigating the influence of tobacco and nicotine products marketing on young adults’ vaping behavior, scholarly attention has been paid primarily to passive exposure to rather than active engagement with the information on social media. In addition, the majority of existing research has been cross-sectional or focused on the unidirectional path from marketing information to behavior. To extend previous research in tobacco regulatory science on new media, we examined the bidirectional associations between self-reported exposure to and engagement with tobacco and nicotine products messaging on social media, and subsequent use of ENDS products one year later among a large, diverse sample of young adults. Results from cross-lagged panel analyses indicated that pro-tobacco/ENDS engagement and advertising exposure elevated risk whereas anti-tobacco/ENDS engagement decreased risk for the subsequent use of ENDS products one year later. On the other hand, the use of ENDS products positively predicted both pro- and anti-tobacco/ENDS engagement one year later. Findings provide empirical support for the reasoned action approach and the confirmation bias rooted in cognitive dissonance theory through rigorous longitudinal examination. Our findings not only point to the imperativeness of and offer guidance for regulating marketing information on social media, but also suggest social media as a promising platform to prevent young adults from initiating ENDS product use.

Methods Development and Modeling Research: Contributions to Advancing TRS and Informing Regulations

The US Food and Drug Administration's (FDA) Center for Tobacco Products (CTP) funds a wide range of research studies. Methods development and modeling research (MDMR) are 2 areas of interest, as they can help advance tobacco regulatory science (TRS) by fostering data synthesis and exploration of complex relationships. Our analyses of the CTP portfolio found that 13% of publications focused on MDMR, and the most commonly addressed CTP priority research domains were knowledge, attitudes, and behaviors, and toxicity and carcinogenicity. MDMR publications were cited by 1,186 publications, 5 FDA proposed rules and guidance documents, and 3 dockets. MDMR publications are characterized as foundational research and help build the evidence base that informs policy. While MDMR represents a small portion of the CTP research portfolio, they have made important contributions to advancing TRS and informing regulatory actions.

Reducing tobacco use among women of childbearing age: Contributions of tobacco regulatory science and tobacco control.

Tobacco use has unique, adverse health consequences for reproductive-aged women, particularly should these women become pregnant. Thus, successful efforts to reduce tobacco use among this population have strong potential to improve public health and reduce health disparities. The present review examines contributions to reducing tobacco use among women of childbearing age spanning the domains of tobacco regulatory science and tobacco control from the passage of the Family Smoking Prevention and Tobacco Control Act in 2009 through September 2019. In the domain of tobacco regulatory science, such efforts include research conducted by various National Institutes of Health/Food and Drug Administration (FDA)-supported Tobacco Centers of Regulatory Science, epidemiological surveillance studies, as well as studies examining the potential impact of tobacco regulatory policies currently under consideration by the FDA (e.g., reduced nicotine content cigarettes, health warning labels). Tobacco control efforts within this same 10-year timeframe include developments in pharmacological and psychosocial approaches to promoting tobacco cessation, mHealth interventions, and tobacco control policy. Emerging issues pertinent to ongoing efforts to reduce tobacco use within the domains of both tobacco regulatory science and tobacco control are also reviewed, including e-cigarettes, comorbid health conditions, course of tobacco and other drugs of abuse, and obstacles to the dissemination and implementation of evidence-based treatment and policy. Although the past decade has seen numerous important contributions to reducing tobacco use among reproductive-aged women within both domains, existing obstacles must be surmounted to continue reducing tobacco use and protecting health among this population. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Predicting the mutagenic potential of chemicals in tobacco products using in silico toxicology tools

Tobacco products contain thousands of chemicals, including addictive and toxic chemicals. We utilized in silico toxicology tools to predict in a validation test and in a separate screening test, the mutagenic potential of chemicals reported in tobacco products and tobacco smoke. Different publicly available (quantitative) structure–activity relationship (Q)SAR software platforms were used in this study. The models were validated against 900 chemicals relevant to tobacco for which experimental Ames mutagenicity data are available from public sources. The predictive performance of the individual and combined (Q)SAR models was evaluated using various performance metrics. All the (Q)SAR models represented >95% of the tobacco chemical space indicating a high potential for screening tobacco products. All the models performed well and predicted mutagens and nonmutagens with 75–95% accuracy, 66–94% sensitivity and 73–97% specificity. Subsequently, in a screening test, a combination of complementary SAR-based and QSAR-based models was used to predict the mutagenicity of 6820 chemicals catalogued in tobacco products and/or tobacco smoke. More than 1200 chemicals identified in tobacco products are predicted to have mutagenic potential, with 900 potential mutagens in tobacco smoke. This research demonstrates the validity of in silico (Q)SAR tools to make mutagenicity predictions for chemicals in tobacco products and/or tobacco smoke, and suggest they hold utility as screening tools for hazard identification to inform tobacco regulatory science.

Method Validation Approaches for Analysis of Constituents in ENDS.

We assessed how many peer-reviewed publications reporting chemical quantities and/or yields from electronic nicotine delivery systems (ENDS) have included adequate method validation characteristics in the publication for appropriate interpretation of data quality for informing tobacco regulatory science. We searched 5 databases (Web of Knowledge, PubMed, SciFinder, Embase, EBSCOhost) for ENDS publications between January 2007 and September 2018. Of the 283 publications screened, 173 publications were relevant for analysis. We identified the publications that report a certain degree of control in data quality, ie, the publications that report marginally validated methods (MVMs). MVMs refer to the methods that: (1) report 3 or more International Conference on Harmonisation (ICH) method validation characteristics, (2) state the method was validated, (3) cite their own previous publication(s) that report MVMs, or (4) use a method within the accreditation scope of an accredited laboratory. Overall, 97 publications (56%) report MVMs in their studies. This percentage also reflects the publication distribution for the majority of the 28 chemicals measured by MVMs. This study highlights the need for reporting sufficient validation characteristics following appropriate guidance to ensure the accuracy and reliability of the published analytical data for proper data interpretations that may support policy.

Agent-based Modeling in Tobacco Regulatory Science: Exploring 'What if' in Waterpipe Smoking.

Waterpipe tobacco smoking (WTS) is an emerging public health crisis, particularly among youth and young adults. Different from the use of other tobacco products and e-cigarettes, WTS tends to be a social activity occurring among friends or persons associated with social networks. In this paper, we review a potential strategy for WTS-related research. As a bottom-up computational model, agent-based modeling (ABM) can simulate the actions and interactions of agents, as well as the dynamic interactions between agents and their environments, to gain an understanding of the functioning of a system. ABM is particularly useful for incorporating the influence of social networks in WTS, and capturing people's space-time activity and the spatial distribution of WTS venues. Comprehensive knowledge of WTS-related behaviors at the individual level is needed to take advantage of ABM and use it to examine policies such as the interaction between WTS and cigarette smoking and the effect of flavors used in waterpipe tobacco. Longitudinal and WTS-specific surveys and laboratory experiments are particularly helpful to understand WTS basic mechanisms and elicit individual preferences, respectively. We argue that the uniqueness of WTS makes ABM a promising tool to be used in WTS-related research, as well as understanding use of other tobacco products.

PhenX: Environment measures for Tobacco Regulatory Research

ObjectiveA Working Group (WG) of tobacco regulatory science experts identified measures for the tobacco environment domain.MethodsThis article describes the methods by which measures were identified, selected, approved and placed in...

PhenX: Host: Biobehavioral measures for tobacco regulatory research

A working group (WG) of experts from diverse fields related to nicotine and tobacco addiction was constituted to identify constructs and measures for the PhenX (Phenotypes and eXposures) Tobacco Regulatory...

Not Quite the Rule, But No Longer the Exception: Multiple Tobacco Product Use and Implications for Treatment, Research, and Regulation.

The patterns of tobacco product use in the United States have changed during the past several decades. Currently, a large proportion of tobacco users report using multiple tobacco products (MTPs). The prevalence of MTP use varies significantly by cigarette smoking frequency, as well: nearly half (46.9%) of all non-daily smokers report using other tobacco products within the past 30 days. Despite this, much of extant tobacco dependence treatment efforts, tobacco regulatory science research, and tobacco product research, in general, has focused largely on single product use (ie, cigarette smoking). To effectively design interventions and model the potential impact of regulations on tobacco products aimed at reducing tobacco use, as well as effectively study tobacco users, it is essential to consider actual use patterns in the population of tobacco users. Implications: MTP use is increasingly common in the United States. This commentary highlights the impact that MTP use has for efforts to treat tobacco dependence, tobacco regulatory science efforts, as well as on tobacco research, in general.

Harmonizing Cigar Survey Data Across Tobacco Centers of Regulatory Science, Center for Tobacco Products, and Population Assessment of Tobacco and Health Studies: The Cigar Collaborative Research Group.

IntroductionCigars are a popular tobacco product of choice for youth and young adults. Despite growing interest in cigar research, there are gaps in the available literature limiting an ability to set evidence-based policies. Too small research samples, the heterogeneity of types of cigars when asking a single question about use, makes analyzing data difficult. Given the Food and Drug Administration’s (FDA’s) authority granted in 2016 to regulate cigars, and its popularity, data to better understand use and preference for cigars will help FDA set appropriate regulatory policies.MethodsWe harmonized cigar survey data previously collected by five independent tobacco regulatory science survey research projects. Data supplying participants included three Tobacco Centers of Regulatory Science, one Center for Tobacco Products grantee, and data from Population Assessment of Tobacco and Health (PATH) study’s public use dataset.ResultsAnalyzing 92 data variables from across five studies, and applying a rigorous data harmonization protocol, we report findings on 24 key cigar use variables. The step by step protocol for harmonizing is presented. Selected findings showing strict reproducibility across all five studies reveal youth 17–19 years at highest risk for cigar initiation; relative reproducibility shows males more likely to try cigars than females but with significant differences in magnitude across studies; and areas of inconsistent reproducibility are revealed when evaluating brand preferences.ConclusionHarmonizing data from multiple sources fosters a broader view of the robustness and generalizability of survey data than that from a single source. These observations raise awareness to look for the highest degree of reproducibility among and across data sources to inform policy.ImplicationsHarmonizing data from discrete datasets provides insights into cigar initiation and use and is presented showing opportunities, challenges, and solutions. Comparing observational data from PATH and four independent research studies provides a best-practices approach and example of data synthesis for the tobacco research community. The dataset of five studies offers a look at the degree of confidence in analyzing harmonized survey results. Variable conclusions raise the need to strive for the highest degree of reproducibility, to best understand the behaviors of cigar users, and allow for the future development of the most effective interventions to alter tobacco use patterns.

Tobacco Use Topography and Etiology

Tobacco regulatory science seeks in part to reduce harm of new tobacco products. Part of this interest is to help chronic adult smokers switch to potentially less harmful products, while not facilitating use of these modified risk tobacco products by nonusers (particularly teens). Studies to discern a lack of interest in reduced harm products are conducted on emerging adults as a proxy for teens. The present empirical review explores the topography and etiology of tobacco use among emerging adults compared to teens to discern whether they might be a reasonable proxy for such reduced harm studies. Both teens and emerging adults view combustible and e-cigarette smoking as disapproved of by peers and are likely to process tobacco marketing information similarly. I conclude that while some differences do exist (e.g., emerging adults are in a period of escalating use and dependence, whereas teens are relatively likely to be initiating use), emerging adults may indeed be a reasonable proxy, at least for current reduced harm studies.

Implementing and Evaluating a Mentor Training to Improve Support for Early-Career Scholars in Tobacco Regulatory Science.

To implement and evaluate a blended online and in-person training to help mentors of early-career researchers appreciate the complexities of Tobacco Regulatory Science (TRS), refine TRS mentoring skills, and become acquainted with resources for providing effective guidance to TRS mentees. TRS mentors engaged in a two-part pilot test of the training program. Authors evaluated both the online and in-person training using retrospective pre-post evaluations, which measure learning at the conclusion of a training program, and post-program focus groups. Twenty learners completed the online training, and 16 learners attended the in-person training module. Nine participants completed evaluations for the online module, and 12 participants completed evaluations for the in-person module. Program assessments revealed that participants found that the training achieved its overall goals. The majority of respondents (87.5%) rated the online portion of the training as valuable. For the in-person training, participants reported statistically significant improvements regarding confidence in: helping mentees to identify skills and training to effectively pursue TRS, assisting mentees in weighing career trajectories, and guiding mentees in conducting research responsive to TRS regulatory priorities. The novel mentoring program was well received by faculty seeking to strengthen skills for mentoring early-career TRS researchers to navigate the complex landscape of TRS, explore diverse funding opportunities, and discern potential career trajectories. It provided unique content to address issues outside the traditional tobacco research training curriculum and offered specific information on regulatory policies, priorities, and opportunities. This research documents the deployment and evaluation of a blended online and in-person training program for investigators mentoring early-career researchers working in TRS. Our assessment discovered that participants found the training to be valuable to their overall mentoring objectives. The training comprises a novel curriculum for investigators engaged in mentoring early-career researchers in a unique field, thus filling a deficit in the published literature by presenting a curriculum that has been customized to the unique needs of TRS mentors.

A review of tobacco regulatory science research on vulnerable populations

In 2013 the U.S. Food and Drug Administration and National Institutes of Health established fourteen Tobacco Centers of Regulatory Science (TCORS) to advance scientific knowledge relevant to conducting evidence-based tobacco regulation. This report reviews TCORS-funded research with adult vulnerable populations. The literature search included a list of all TCORS-funded publications compiled by the TCORS coordinating center; all TCORS were requested to share publications not in the coordinating-center's list. Only TCORS-funded reports describing an empirical study with an adult vulnerable population published in a peer-reviewed journal between September 2013 and June 2018 were included. 71 reports met inclusion criteria; 39% (28/71) examined tobacco use among those with mental health and medical comorbidities, 34% (24/71) socioeconomic disadvantage, 31% (22/71) women of reproductive age, 30% (21/71) racial/ethnic minorities, 18% (13/71) rural residents, and 3% (2/71) each among active military/veterans and sexual/gender minorities. Regarding scientific domains, 63% (45/71) investigated behavior, 37% (26/71) addiction, 24% (17/71) health effects, 20% (14/71) impact analyses, 18% (13/71) toxicity, 8% (6/71) marketing influences, and 7% (5/71) communications. Totals exceed 100% because some reports addressed multiple populations/domains. TCORS funding has generated a substantial, multidisciplinary body of new scientific knowledge on tobacco use in adult vulnerable populations. However, considerable variability was noted in the amount of research conducted across the various vulnerable populations and scientific domains. Most notably, relatively few studies focused on active military/veterans or sexual/gender minorities, and the scientific domains of marketing influences and communications were conspicuously underrepresented. These are important knowledge gaps to address going forward.

Research on Youth and Young Adult Tobacco Use, 2013-2018, From the Food and Drug Administration-National Institutes of Health Tobacco Centers of Regulatory Science.

The Tobacco Centers of Regulatory Science, CENIC, and COMET have had a high output of scientific articles since 2013. These Centers are unique in that the FDA supports science specifically to guide future regulatory actions. The 258 articles that have focused on youth and/or young adults are providing data for regulatory actions by the FDA related to the key priority areas such as the addictiveness of non-cigarette products, the effects of exposure to electronic cigarette marketing on initiation and cessation, and the impact of flavored products on youth and young adult tobacco use. Future regulations to reduce tobacco use will be guided by the cumulative evidence. These Centers are one innovative mechanism to promote important outcomes to advance tobacco regulatory science.

Metal concentrations in electronic cigarette aerosol: Effect of open-system and closed-system devices and power settings

BackgroundElectronic cigarettes (E-cigarettes) generate aerosol containing metal contaminants. Our goals were to quantify aerosol metal concentrations and to compare the effects of power setting and device type (closed-system vs. open-system) on metal release. MethodsAerosol samples were collected from two closed-system devices (a cigalike and pod) and two open-system devices (mods). Each open-system device was operated at three different power settings to examine the effect of device power on metal release. Concentrations of 14 metals in e-cigarette aerosol collected via droplet deposition were measured using inductively coupled plasma mass spectroscopy. Aerosol metal concentrations were reported as mass fractions (μg/kg) in the e-liquid. ResultsFor open-system device 1 (OD1), median arsenic (As), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), antimony (Sb), tin (Sn), and zinc (Zn) concentrations increased 14, 54, 17, 30, 41, 96, 14, 81, 631, and 7-fold when the device power was increased from low (20 W) to intermediate (40 W) setting. When the power was further increased from intermediate (40 W) to high (80 W) setting, concentrations of As, Cr, Cu, Mn, Ni, and Sb did not change significantly. For open-system device 2 (OD2), Cr and Mn concentrations increased significantly when device power was increased from low (40 W) to intermediate (120 W) setting, and then decreased significantly when power was further increased from intermediate (120 W) to high (200 W) setting. Among the four devices, aerosol metal concentrations were higher for the open-system than the closed-system devices, except for aluminum (Al) and uranium (U). For Cr, median (interquartile range) concentrations (μg/kg) from the open-system devices were 2.51 (1.55, 4.23) and 15.6 (7.88, 54.5) vs. 0.39 (0.05, 0.72) and 0.41 (0.34, 0.57) for the closed-system devices. For Ni, concentrations (μg/kg) from the open-system devices were 793 (508, 1169) and 2148 (851, 3397) vs. 1.32 (0.39, 3.35) and 11.9 (10.7, 22.7) from the closed-system devices. Inhalation of 0% and 100% of samples from OD1, 7.4% and 88.9% from OD2 by typical e-cigarette users would exceed chronic minimum risk levels (MRL) of Mn and Ni, respectively. No MRL exceedance was predicted for the closed-system devices. A large fraction of users of OD1 (100%) and OD2 (77.8%) would be exposed to Ni levels higher than those from reference tobacco cigarette 3R4F. ConclusionsOur findings suggest that power setting and device type affect metal release from devices to aerosol which would subsequently be inhaled by users. Metal concentrations from open-system devices first increased with device power, and then leveled off for most metals. Open-system devices generate aerosol with higher metal concentrations than closed-system devices. These findings inform tobacco regulatory science, policy makers and health professionals on potential metal health risks associated with e-cigarette use, design and manufacturing.