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In recent years, the tobacco- and/or nicotine-containing product (TNP) portfolio has expanded to include products such as e-vapor products, heated tobacco products, and nicotine pouches. Although scientific papers and regulatory requirements/recommendations related to the assessment of product use behavior and exposure to product use have been published for these novel TNPs, there is great diversity in the terminology used to characterize and assess these types of products. The aim of this paper is to define the terms and methods used for assessing product use behavior and exposure, with the objective to suggest a uniform application of terms used by scientists working in this field of research. This publication is the work product of a cross-industry work item commissioned by the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) Product Use Behaviour and Biomarkers Subgroups.

Encouraging adult smokers who are uninterested or unwilling to quit, and would otherwise continue to smoke, to transition to potentially less harmful nicotine products such as electronic nicotine delivery systems (ENDS) may positively impact population health. However, counterbalancing this benefit is the societal concern that ENDS may be used by never smokers and youth and serve as a 'gateway' into cigarette smoking. Data were analysed from two independent surveys of the prevalence and perceptions of myblu ENDS use in the United States. Total sample size was 22,232 young adults and 23,264 adults. Being curious to use myblu was 1.6-2.0 times more likely in young adult current smokers than young adult never smokers. This likelihood was 2.8 times greater for adult current smokers compared with adult never smokers in the perceptions survey, while in the prevalence survey, there was no difference between adult current and never smokers. Intentions to use myblu were significantly greater in young adult current smokers compared with young adult never smokers in both surveys and in adults in the prevalence survey. In all surveys and age cohorts, 124 of 45,496 participants (0.1% of the total survey population) reported first using myblu prior to smoking cigarettes and went on to become established smokers. Curiosity and intentions to use myblu were generally higher in current smokers compared with never smokers. There was minimal evidence to suggest the existence of a 'gateway' effect to established cigarette smoking among never-smoking myblu users., (© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Background: Greater nicotine delivery is associated with higher nicotine concentrations in electronic nicotine delivery system (ENDS) liquids. However, there is a current debate as to whether this leads to increased dependence and mitigates ENDS public health potential., Methods: Self-reported dependence among users of myblu ENDS containing different nicotine concentrations was examined with data from a multiwave cross-sectional survey of US young adults and adults. Questions examined responses related to dependence measures and participants' most often used myblu ENDS nicotine concentration (low: 0%, 1% and 1.2%; medium: 2%, 2.4% and 2.5%; or high: 3.6% and 4%)., Results: A global general linear model using nicotine concentration, age and days myblu that was used in the past 30 revealed a significant difference in PROMIS scores among nicotine concentration groups (F = 4.07, p = 0.02). However, pairwise comparisons to examine which specific groups differed significantly from others showed no significant differences. Logistic regression demonstrated that strong past 30-day cravings to use myblu among participants using high or medium nicotine concentrations were not significantly different from those using a low concentration (ORs 0.66 [0.42, 1.03], p = 0.07 and 0.95 [0.49, 1.82], p = 0.98, respectively). Time to daily first use for high or medium nicotine concentration users was not significantly different from those using a low concentration (ORs 0.89 [0.70, 1.14], p = 0.35 and 0.84 [0.57, 1.25], p = 0.40, respectively)., Conclusions: Use of myblu ENDS with different nicotine concentrations is not associated with differing levels of dependence. Our findings contradict the notion that high ENDS e-liquid nicotine levels generate increased dependence., (© 2022 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Electronic nicotine delivery systems (ENDS) offer adult combustible cigarette smokers an alternative, potentially reduced harm, mode of nicotine delivery, attributed to fewer and reduced levels of harmful and potentially harmful constituents (HPHCs) in their aerosols compared to cigarette smoke. These two identical, randomised, open label, two-part studies aimed to compare levels of 15 biomarkers of exposure (BoE) to selected HPHCs associated with tobacco smoking in healthy US adult smoker subjects (n = 72). Following 9 days of exclusive use of a range of allocated myblu ™ ENDS variants, subjects' levels of 14 non-nicotine BoE were substantially reduced compared to baseline values (combustible cigarette use), in the range of 46-97%. BoE reductions were sustained in subjects who continued myblu use exclusively (n = 25) for a further 5 days, and returned to near baseline levels in subjects who returned to exclusive combustible cigarette use (n = 21). Dual users (n = 24) demonstrated reductions in BoE to a lesser extent than with exclusive myblu use. Measured nicotine equivalents did not significantly change throughout the study. These data suggest exclusive use of ENDS provides adult smokers seeking an alternative to combustible cigarettes with substantial reductions in HPHC exposures whilst achieving satisfying levels of nicotine delivery. Dual use involving substitution of cigarettes may also provide some of this advantage, but to lesser extent. Overall, the data contribute to the weight of evidence that ENDS are an important tool in tobacco harm reduction for adult smokers unwilling to or uninterested in quitting smoking. Study 1: NCT04430634, study 2: NCT04429932, clinicaltrials.gov (10-06-2020)., (© 2021. The Author(s).)

Background: Electronic cigarettes (e-cigarettes) have been characterised as significantly less harmful than cigarettes by many health agencies and regulators globally. In this study, we examined to what extent perceived relative harms of e-cigarettes compared to cigarettes have changed in the USA., Methods: We analysed the data from the longitudinal and nationally representative, Population Assessment of Tobacco and Health Study to assess the relative perceived harm of e-cigarettes amongst US adults between 2013 and 2016., Results: The proportion of US adults who correctly perceived e-cigarettes as less harmful than cigarettes decreased each year from 41.1% (CI 40.1-42.1%) in 2013-2014, 31.5% (CI 30.8-32.2%) in 2014-2015 and 25.3% (CI 24.6-26.0%) in 2015-2016. Concurrently, the proportion of US adults who perceived e-cigarettes as equally, or more, harmful than cigarettes increased from 53.7% (CI 52.3-55.1%), 64.9% (CI 63.6-66.2%) to 72.7% (CI 71.5-73.9%) respectively. The proportion of US adults who held negative relative harm perceptions of e-cigarettes increased regardless of current smoking or vaping status by 24.6% and 29.6% respectively within 3 years. In Wave 3, the proportion of current smokers who perceived the relative harm of e-cigarettes as less harmful was lower at 29.3% (CI 28.2-30.4%) compared to current e-cigarette users at 43.5% (CI 40.3-46.7%). Former smokers who used e-cigarettes and believed that they were equally, or more, harmful than cigarettes in 2014-2015 had significantly higher rates of smoking relapse in the following year, 29% and 37% (p < 2.2e-16), respectively, compared to those with positive relative harm perceptions who reported relapse rates of 19%., Conclusions: In this study, the proportion of US adults who incorrectly perceived e-cigarettes as equal to, or more, harmful than cigarettes increased steadily regardless of smoking or vaping status. Current adult smokers appear to be poorly informed about the relative risks of e-cigarettes yet have potentially the most to gain from transitioning to these products. The findings of this study emphasise the urgent need to accurately communicate the reduced relative risk of e-cigarettes compared to continued cigarette smoking and clearly differentiate absolute and relative harms. Further research is required to elucidate why the relative harm of e-cigarettes is misunderstood and continues to deteriorate.

Introduction: There are fundamental differences between electronic cigarettes (e-cigarettes) and conventional cigarette product categories with regards to potential environmental exposures, notably that e-cigarettes do not contain tobacco or generate side-stream emissions. Here we assess the spatial and temporal patterns of exhaled e-cigarette aerosol at a bystander's position, and compare it with conventional cigarette smoke emissions., Methods: Smokers were asked to use e-cigarettes or smoke conventional cigarettes in a room-simulating chamber. Volunteers used the products at different distances from a heated mannequin, representing a bystander, and under different room ventilation rates. Aerosol particle concentrations and size distributions at the bystander's position were measured., Results: For both product categories, the particle concentrations registered following each puff were in the same order of magnitude. However, for e-cigarettes the particle concentration returned rapidly to background values within seconds; for conventional cigarettes it increased with successive puffs, returning to background levels after 30-45 minutes. Unlike for the e-cigarette devices tested, such temporal variation was dependent on the room ventilation rate. Particle size measurements showed that exhaled e-cigarette particles were smaller than those emitted during smoking conventional cigarettes and evaporated almost immediately after exhalation, thus affecting the removal of particles through evaporation rather than displacement by ventilation., Conclusions: Significant differences between emissions from the tested e- and conventional cigarettes are reported. Exhaled e-cigarette particles are liquid droplets evaporating rapidly; conventional cigarette smoke particles are far more stable and linger., Implications: • Several factors potentially influencing particle behavior after exhalation of e-cigarette aerosols or emitted during smoking conventional cigarettes were studied.• Differences in particle size between those exhaled following use of e-cigarettes and those emitted during smoking of conventional cigarettes were observed.• E-cigarette particle concentrations decreased rapidly following exhalation due to evaporation.• The removal of particles following smoking conventional cigarettes was much slower and was dependent on the room ventilation rate., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Since it was first required to measure and to report NFDPM and nicotine yields in a limited number of countries, there has been an increasing trend for more testing and reporting requirements. Historically, the ISO 3308 smoking regime has been used to determine NFDPM and nicotine yields. However recommendations from the World Health Organization, now include the use of two smoking regimes such as the ISO 3308 and the WHO TobLabNet Official Method SOP01, the latter being considered as an intense smoking regime. Considering the increase in data produced and similarities between some smoke constituents formed during combustion, we explored possible correlations between emissions under intense and less intense smoking conditions. A set of 22 commercial cigarettes was tested. Eighty five smoke constituents were determined under both intense and less intense regimes. In addition 36 tobacco constituents, 14 cigarette design parameters and eight cigarette burning features were determined. A computational process was designed to implement multiple linear regression analyses enabling the identification of the best subsets of explanatory variables among emissions under intense conditions, cigarette design parameters, tobacco constituents and burning parameters. We succeeded in building simple linear models, involving four to six variables, while reaching satisfactory goodness of fit and R-squared values ranging from 0.87 to 1.00. Our findings suggest, in the range of products tested, that the additional data gained by using a second smoking regime does not necessarily increase the volume of information and consequently does not necessarily improve knowledge. This study supports the premise that the application of two smoking regimes does not produce a more comprehensive product characterisation compared to using one., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The effect of smoking intensity on cigar smoke emissions was assessed under a range of puff frequencies and puff volumes. In order to potentially reduce emissions variability and to identify patterns as accurately as possible, cigar weights and diameters were measured, and outliers were excluded prior to smoking. Portions corresponding to 25%, 50%, 75% and 100% of the cigar, measured down to the butt length, were smoked under several smoking conditions, to assess nicotine, CO and water yields. The remaining cigar butts were analysed for total alkaloids, nicotine, and moisture. Results showed accumulation effects during the burning process having a significant impact on smoke emission levels. Condensation and evaporation occur and lead to smoke emissions dependent on smoking intensity. Differences were observed for CO on one side as a gas phase compound and nicotine on the other side as a particulate phase compound. For a given intensity, while CO emission increases linearly as the cigar burns, nicotine and water emissions exhibited an exponential increase. Our investigations showed that a complex phenomena occurs during the course of cigar smoking which makes emission data: difficult to interpret, is potentially misleading to the consumer, and inappropriate for exposure assessment. The results indicate that, tobacco content and physical parameters may well be the most robust basis for product characterisation and comparison rather than smoke emission., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rationale: Due to the recent rapid increase in electronic cigarette (e-cigarette) use worldwide, there is a strong scientific but also practical interest in analyzing e-cigarette aerosols. Most studies to date have used standardized but time-consuming offline technologies. Here a proof-of-concept for a fast online quantification setup based on proton transfer reaction mass spectrometry (PTR-MS) is presented., Methods: The combination of a novel sampling interface with a time-of-flight PTR-MS instrument specially designed for three scenarios is introduced: (i) mainstream aerosol analysis (aerosol that the user inhales prior to exhalation), and analysis of exhaled breath following (ii) mouth-hold (no inhalation) and (iii) inhalation of e-cigarette aerosols. A double-stage dilution setup allows the various concentration ranges in these scenarios to be accessed., Results: First, the instrument is calibrated for the three principal constituents of the e-cigarettes' liquids, namely propylene glycol, vegetable glycerol and nicotine. With the double-stage dilution the instrument's dynamic range was easily adapted to cover the concentration ranges obtained in the three scenarios: 20-1100 ppmv for the mainstream aerosol characterisation; 4-300 ppmv for the mouth-hold; and 2 ppbv to 20 ppmv for the inhalation experiment., Conclusions: It is demonstrated that the novel setup enables fast, high time resolution e-cigarette studies with online quantification. This enables the analysis and understanding of any puff-by-puff variations in e-cigarette aerosols. Large-scale studies involving a high number of volunteers will benefit from considerably higher sample throughput and shorter data processing times., (© 2016 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.)

Airborne chemicals in the indoor environment arise from a wide variety of sources such as burning fuels and cooking, construction materials and furniture, environmental tobacco smoke as well as outdoor sources. To understand the contribution of exhaled e-cigarette aerosol to the pre-existing chemicals in the ambient air, an indoor air quality study was conducted to measure volatile organic compounds (including nicotine and low molecular weight carbonyls), polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines and trace metal levels in the air before, during and after e-cigarette use in a typical small office meeting room. Measurements were compared with human Health Criteria Values, such as indoor air quality guidelines or workplace exposure limits where established, to provide a context for potential bystander exposures. In this study, the data suggest that any additional chemicals present in indoor air from the exhaled e-cigarette aerosol, are unlikely to present an air quality issue to bystanders at the levels measured when compared to the regulatory standards that are used for workplaces or general indoor air quality.

There has been rapid growth in the use of electronic cigarettes ("vaping") in Europe, North America and elsewhere. With such increased prevalence, there is currently a debate on whether the aerosol exhaled following the use of e-cigarettes has implications for the quality of air breathed by bystanders. Conducting chemical analysis of the indoor environment can be costly and resource intensive, limiting the number of studies which can be conducted. However, this can be modelled reasonably accurately based on empirical emissions data and using some basic assumptions. Here, we present a simplified model, based on physical principles, which considers aerosol propagation, dilution and extraction to determine the potential contribution of a single puff from an e-cigarette to indoor air. From this, it was then possible to simulate the cumulative effect of vaping over time. The model was applied to a virtual, but plausible, scenario considering an e-cigarette user and a non-user working in the same office space. The model was also used to reproduce published experimental studies and showed good agreement with the published values of indoor air nicotine concentration. With some additional refinements, such an approach may be a cost-effective and rapid way of assessing the potential exposure of bystanders to exhaled e-cigarette aerosol constituents.

When smoking cigarettes under an intense regime with a combination of 100% ventilation blocking and high flow rates, as currently mandated by Health Canada, significant increases in filter temperatures and disproportionately high levels of mainstream smoke water and moisture accumulating in the spent filter were found when compared to other smoking regimes, especially for highly filter ventilated cigarettes. These effects have been reported to decrease cigarette firmness during the course of smoking, to alter filtration properties and efficiencies and to confound the measurement of particulate matter. The high filter temperatures generated also lead to significant amounts of vapour phase compounds desorbing from carbon filters and an over-estimation of the yields of these components. Less adsorption on or more desorption from carbon filters was found for compounds with the highest volatility. Therefore, yield data from the intense regime may not reflect the effectiveness of cigarette design features to reduce certain smoke components that occurs when products are smoked under conditions closer to those used by the majority of smokers in real world situations. In addition, a combination of these interacting factors may explain the worse level of between-laboratory reproducibility data for particulate matter measurement obtained during intense machine smoking. Among-laboratory data variability for vapour phase components, other than carbon monoxide, and for particulate phase components, other than nicotine, still needs to be evaluated in collaborative studies. Before proposing smoking regimes as tools to evaluate smoke emissions, it is essential to understand these various interacting factors and subsequent uncontrolled effects that such regimes can generate and the limitations of their use. These observations imply that higher tolerances may need to be set and taken into account when smoking under the intense regime before deciding that, for a given product, there are real differences between the yields determined in different laboratories., (Copyright © 2010 Elsevier Inc. All rights reserved.)

GCxGC is now recognized as the most suited analytical technique for the characterization of complex mixtures of volatile compounds; it is implemented worldwide in academic and industrial laboratories. However, in the frame of comprehensive analysis of non-target analytes, going beyond the visual examination of the color plots remains challenging for most users. We propose a strategy that aims at classifying chromatograms according to the chemical composition of the samples while determining the origin of the discrimination between different classes of samples: the discriminant pixel approach. After data pre-processing and time-alignment, the discriminatory power of each chromatogram pixel for a given class was defined as its correlation with the membership to this class. Using a peak finding algorithm, the most discriminant pixels were then linked to chromatographic peaks. Finally, crosschecking with mass spectrometry data enabled to establish relationships with compounds that could consequently be considered as candidate class markers. This strategy was applied to a large experimental data set of 145 GCxGC-MS chromatograms of tobacco extracts corresponding to three distinct classes of tobacco., (Copyright © 2010 Elsevier B.V. All rights reserved.)

A fast method for the measurement of metabolites of pyrene in urine was improved by HPLC with fluorescence detector using "heart-cut" technique. This method can quantify the total amount of pyrene metabolites corresponding to glucuronic acid and sulfate conjugates as well as free 1-OH-Py. The hydrolyzed biological fluid was directly injected into the chromatographic system, via a column-switching system. Pre-treatment and analysis were performed within 0.5 and 9 min, respectively. Enzymatic hydrolysis has been optimized to not exceed 2 h. The best response function, in the 0.2-10 ng/mL range, is the linear regression, bringing simplicity, good accuracy, and low LOQ. The intra- and interday precision values were inferior to 1 and 2%, respectively. The proposed method provided a simple, convenient, and practical procedure to determine the level of the main urinary pyrene metabolites in biological samples.

Microemulsion electrokinetic chromatography (MEEKC) coupled with a diode-array detector was developed for the simultaneous analysis of natural steroidal compounds, withanolides including withaferin A, withacnistin and iochromolide. Optimal resolution was obtained with a microemulsion consisting of 70 mM octane, 800 mM 1-butanol, 100 mM sodium dodecyl sulfate (SDS), and 10 mM phosphate-borate buffer (pH 7) using a fused-silica capillary at 25 kV and 40 degrees C. Since this technique is not compatible with mass spectrometry detection, a capillary electrochromatographic method was developed to separate the investigated withanolides. The effects of mobile phase composition and pH were systematically investigated. Complete separation was obtained with a capillary electrochromatography (CEC) Hypersil C18 bonded silica column (packed length, 25 cmx100 microm ID and 375 microm OD), packed with 3 microm particles. The mobile phase consisted of formic acid-ammonia, pH 8 / acetonitrile (40/60 v/v); the voltage was set at 25 kV and the temperature at 20 degrees C. Under these conditions, resolution of these closely related compounds, including the critical pair withacnistin and iochromolide, was achieved in less than 5 min. The separations by MEEKC and CEC were compared with that obtained by reversed-phase liquid chromatography and showed similar retention order, indicating the analogy of the retention mechanism of these techniques. To further improve specificity and sensitivity, the developed CEC method was interfaced with electrospray ionization mass spectrometry using a Teflon connection between the CEC column and a void fused-silica capillary. Finally, the described methods were applied to the qualitative analysis of withanolides in Iochroma gesnerioides plant extract.

Benzodiazepines, namely flunitrazepam and its three major metabolites, were successfully separated by microemulsion electrokinetic chromatography. Separation was achieved using an untreated fused-silica capillary (48 cm (effective length 40 cm) x 50 num) at 25 kV; detection was performed by UV at 220 nm. The microemulsion system consisted of 70 mM octane, 800 mM 1-butanol, 80 mM sodium dodecyl sulfate (SDS) and 10 mM borate buffer, pH 9. Very high efficiencies (up to 400 000 plates) and resolution better than 3 were achieved. Since this technique is not compatible with mass spectrometry (MS) detection, a capillary electrochromatographic (CEC) method was developed to separate flunitrazepam and its metabolites. The effects of mobile phase composition and pH as well as voltage and temperature were systematically investigated. The optimized CEC method allowed the baseline separation of the investigated compounds. For the on-line coupling of CEC with electrospray ionization-mass spectrometry, the column was connected to a void fused-silica capillary using a Teflon connection. This configuration was found efficient and suitable for hyphenation of commercial CEC and MS instrumentation using commercially available CEC columns.

We describe the analysis of two potent anti-human immunodeficiency virus reverse transcriptase (RT-HIV) inhibitors, zidovudine (AZT) and stavudine (d4T), among a pool of natural nucleosides (A, C, G, U, T) by capillary zone electrophoresis (CZE)-ionspray-tandem mass spectrometry (MS/MS) in positive ion mode. Several volatile formic acid-ammonia buffers having the same ionic strength (50 mM) but different pH values varying in the 9-11 pH range were prepared and tested to determine the best electrophoretic migration conditions. Quantitative CZE-MS/MS analysis was performed using selected reaction monitoring (SRM) mode. Finally, this CZE-MS/MS procedure opens the possibility for future determination of several nucleoside RT-HIV inhibitors in cell pool samples.