Characterisation of vaping liquids used in vaping devices across four countries: results from an analysis of selected vaping liquids reported by users in the 2016 ITC Four Country Smoking and Vaping Survey.

OBJECTIVES: This study presents an analysis of vaping products (VPs) purchased in the USA, Canada, England and Australia and assesses whether differences in regulations were associated with differences in the chemical composition of the VPs. METHODS: April-September 2017, a total of 234 VP refill liquids and prefilled cartridges were purchased in convenience samples of retail locations in each country. Products were chosen from brands and styles most commonly reported by current VP users in the 2016 ITC Four Country Smoking and Vaping Survey. All products were tested for nicotine, tobacco-specific nitrosamines (TSNAs), minor tobacco alkaloids, organic acids and flavouring chemicals. RESULTS: Consistent with the laws in Canada and Australia at the time of product purchase, nicotine was not detected in any of the VPs (n=10 in Canada; n=15 in Australia). US liquids (n=54) had a mean nicotine concentration of 16.2 mg/mL, (range=0.0-58.6) and English liquids (n=166) had a mean concentration of 11.9 mg/mL ((range=0.0-31.2) F(3244)=12.32, p<0.001). About 5% of English samples exceeded the UK's 20 mg/mL nicotine limit. Substantial country differences were observed in levels ofTSNAs, with the USA being higher than elsewhere. Of all products tested, 18.8% contained at least one organic acid. Liquids purchased in England contained far more identifiable flavouring chemicals than those in the other countries. CONCLUSIONS: VP composition, particularly with respect to nicotine and flavouring, varies by country, likely reflecting both marketplace preferences and country-specific regulations. There are differences between nicotine levels claimed on the package and actual levels, particularly in England.

Effects of 'Ice' flavoured e-cigarettes with synthetic cooling agent WS-23 or menthol on user-reported appeal and sensory attributes.

BACKGROUND: This clinical experiment tested the effects of exposure to e-cigarettes with WS-23 or menthol cooling additives on user appeal and sensory attributes, and, secondarily, whether WS-23 effects generalised across base characterising flavour, nicotine concentration, or nicotine/tobacco product use status. METHODS: In this within-participant double-blind experiment, adult tobacco/nicotine users administered standardised puffs of 18 different e-cigarette solutions in randomised sequences using a pod-style device. Each of three base characterising e-cigarette flavour solutions ('bold tobacco', 'mango,' 'wintergreen') in both 2% and 4% concentrations of nicotine benzoate salt were manipulated by adding either: (1) Menthol (0.5%), (2) WS-23 (0.75%) or (3) No cooling agent. After each administration, participants rated 3 appeal and 5 sensory attributes (0-100 scales). RESULTS: Participants (n=84; M(SD)=38.6 (13.6) years old) were either exclusive e-cigarette (25.0%), cigarette (36.9%) or dual (38.1%) users. WS-23 versus no coolant products produced higher liking, willingness to use again, smoothness, and coolness and lower disliking, bitterness, and harshness ratings (|B|difference range: 4.8 to 20.1; ps<0.005). Menthol (vs no coolant) increased willingness to use again and reduced harshness and coolness (ps<0.05). Flavours with WS-23 (vs menthol) were rated as smoother, cooler and less harsh (ps<0.05). Coolant effects did not differ by base flavour, nicotine concentration, or tobacco use status. CONCLUSIONS: Adding synthetic coolant WS-23 to e-cigarettes appears to make the vaping user experience more appealing, regardless of characterising base flavour. Regulatory agencies should be aware that the manufacturing process of adding synthetic coolants may increase the attractiveness of various e-cigarette products.Cite Now.

Removal of mango-flavoured Juul pods created opportunity for adulterated mango Juul-compatible pods with altered chemical constituents.

INTRODUCTION: Juul is a leading electronic cigarette (e-cigarette) brand in the USA. By November 2019, Juul pre-emptively limited online and in-store sales of non-tobacco or menthol-flavoured pods ahead of impending flavour bans. Since this removal, sale of mango-flavoured Juul-compatible pods was introduced to the market by smaller companies. The aim of this study was to compare chemical constituents of original Juul mango pods with mango-flavoured Juul-compatible pods. METHODS: Juul and 16 brands of Juul-compatible mango-flavoured pods were purchased online in May 2018 (original Juul) and November 2019 (Juul-compatible), after Juul voluntarily removed their flavoured pods from the market. Liquid was extracted from pods and analysed using chromatography and mass spectrometry methods for nicotine concentration, solvent ratios, nicotine salt identification, as well as flavouring identification and quantitation. RESULTS: Juul-compatible pods had a significantly lower average nicotine concentration compared with original Juul pod (42.8±8.9 vs 57.2±0.9 mg/mL, p<0.0001). Nicotine benzoate was used in original Juul pod and all Juul-compatible pods. The propylene glycol to vegetable glycerin volumetric ratio of Juul-compatible pods averaged 55:45, while the original Juul pod was 35:65 (p<0.0001). Total number of flavouring chemicals detected was significantly higher in Juul-compatible pods as compared with Juul (p<0.0001). In Juul-compatible pods, average concentrations of benzyl alcohol (fruity flavouring) were 0.8±1.3 mg/mL, approximately 27 times higher than in original Juul pod (p<0.0001). CONCLUSIONS: Adulterated Juul-compatible products may expose e-cigarette consumers to more chemical constituents at higher concentrations than previously found in the original product, despite similarity in product design.

Evolution of tobacco products: recent history and future directions.

Declines in cigarette smoking prevalence in many countries and the consolidation of the tobacco industry have prompted the introduction of other forms of nicotine delivery. These include electronic nicotine delivery systems (ENDS), heated tobacco products (HTPs) and oral nicotine products (ONPs). Evolving over time, some of these products now deliver nicotine at levels comparable to cigarettes and may serve as effective substitutes for smokers. However, certain products, especially ENDS like JUUL, have also appealed to youth and non-smokers, prompting concerns about expanding nicotine use (and potentially nicotine addiction). The tobacco industry could shift away from primarily promoting cigarettes to promoting ENDS, HTPs and/or ONPs, though at this time it continues to heavily promote cigarettes in low and middle-income countries. Differing regulatory regimes may place upward and downward pressures on both cigarettes and these newer products in terms of population use, and may ultimately drive the extent to which cigarettes are or are not displaced by ENDS, HTPs and/or ONPs in the coming decade.

Assessing use of inhalable nicotine products within complex markets: the dilemma of heated tobacco products.

The introduction of electronic inhalable products, such as nicotine vaping products (NVPs) and heated tobacco products (HTPs), has further diversified the nicotine market landscape. This poses unique challenges in measuring self-reported nicotine use behaviours, which have been the hallmark of tobacco surveillance systems. This paper raises concerns of potential measurement error for electronic inhalable product use in surveys due to similarities in product design between NVPs and HTPs, as well as changing trends in cannabis administration. We identify several strategies for addressing this issue (eg, including descriptive preambles in surveys that differentiate product classes from one another; incorporating survey questions that probe beyond an initial question regarding product use). In the absence of comprehensive validation studies, caution is warranted when interpreting survey results that rely on self-reported HTP use.

Characteristics and changes over time of nicotine vaping products used by vapers in the 2016 and 2018 ITC Four Country Smoking and Vaping Surveys.

OBJECTIVES: Regulation of nicotine vaping products (NVPs) varies between countries, impacting the availability and use of these products. This study updated the analyses of O'Connor et al on types of NVPs used and examined changes in NVP features used over 18 months in four countries with differing regulatory environments. DESIGN: Data are from 4734 adult current vapers in Australia, Canada, England and the USA from Waves 1 (2016) and 2 (2018) of the International Tobacco Control Four Country Smoking and Vaping Survey. NVP characteristics included device description, adjustable voltage, nicotine content and tank size. Longitudinal analyses (n=1058) assessed movement towards or away from more complex/modifiable NVPs. A logistic regression was used to examine factors associated with changes in device description from 2016 to 2018. RESULTS: Like 2016, box-tanks were the most popular NVP (37.3%) in all four countries in 2018. Over 80% of vapers continued using the same NVP and nicotine content between waves, though movement tended towards more complex/modifiable devices (14.4% of vapers). Box-tank users, exclusive daily vapers and older vapers were most likely to continue using the same device description. Certain NVPs and features differed by country, such as higher nicotine contents in the USA (11.5% use 21+ mg/mL) and greater device stability over time in Australia (90.8% stability). CONCLUSIONS: Most vapers continued using the same vaping device and features over 18 months. Differences in NVP types and features were observed between countries, suggesting that differing NVP regulations affect consumer choices regarding the type of vaping device to use.

Emerging Chemicals of Health Concern in Electronic Nicotine Delivery Systems.

Electronic nicotine delivery systems (ENDS), by virtue of their highly engineered construction (plastics, glass, e-liquids), may contain a number of emerging chemicals of concern (ECCs), including phthalates, phenolic compounds, and flame retardants. Current knowledge regarding the safety of ENDS may underestimate the health risks from ECCs. In this study, we examined the types and levels of those three groups of chemicals in the components and parts of ENDS devices, including refill liquids, tanks/cartridges, atomizers, drip tips/mouthpieces, and sealing materials. Our results suggest that phthalates were the most prevalent chemicals in all tested samples, followed by parabens and organophosphate flame retardants (OPFRs). Particularly, all measured chemicals had significantly higher detection rates in cartridges/tanks, drip tips/mouthpieces, and sealing materials in contrast to e-liquids and coil samples. Among all those three types of ENDS components, phthalates generally had the highest concentrations (0.279-3790 ng/unit) in the drip tip/mouthpiece samples, followed by the sealing materials (0.380-508.8 ng/unit) and the empty tank/cartridge samples (up to 761.7 ng/unit). For parabens, highest concentrations were observed in drip tip/mouthpiece samples (1.152-130.1 ng/unit), followed by sealing materials (0.220-30.08 ng/unit) and the tank/cartridge samples (1.794-34.24 ng/unit). For OPFRs, tris(1,3-dichloro-2-propyl) phosphate had the highest concentrations (39.40-774.1 ng/unit) in all component samples. High concentrations (20.25-260.4 ng/unit) were also observed for several OPFRs in sealing materials and drip tip/mouthpiece samples. These findings will contribute to addressing the information gaps pertinent to the presence of ECCs in ENDS and will warrant further studies for understanding the potential negative health effects and to what extent those chemicals may cause potential negative health effects when using the ENDS. The findings will also contribute to developing evidence-based standards for the regulatory control of the types and levels of ECCs in ENDS products.

Association of smoking and electronic cigarette use with wheezing and related respiratory symptoms in adults: cross-sectional results from the Population Assessment of Tobacco and Health (PATH) study, wave 2.

BACKGROUND: Wheezing is a symptom of potential respiratory disease and known to be associated with smoking. Electronic cigarette use ('vaping') has increased exponentially in recent years. This study examined the cross-sectional association of vaping with wheezing and related respiratory symptoms and compare this association with smokers and dual users. METHODS: The Population Assessment of Tobacco and Health study wave 2 data collected from October 2014 to October 2015 with 28 171 adults were used. The cross-sectional association of vaping with self-reported wheezing and related respiratory symptoms relative to smokers and dual users of tobacco and electronic cigarettes were studied using multivariable logistic and cumulative logistic regression models with consideration of complex sampling design. RESULTS: Among the 28 171 adult participants, 641 (1.2%) were current vapers who used e-cigarettes exclusively, 8525 (16.6%) were current exclusive smokers, 1106 (2.0%) were dual users and 17 899 (80.2%) were non-users. Compared with non-users, risks of wheezing and related respiratory symptoms were significantly increased in current vapers (adjusted OR (aOR)=1.67, 95% CI: 1.23 to 2.15). Current vapers had significantly lower risk in wheezing and related respiratory symptoms compared with current smokers (aOR=0.68, 95% CI: 0.53 to 0.87). No significant differences were found between dual users and current smokers in risk of wheezing and related respiratory symptoms (aOR=1.06, 95% CI: 0.91 to 1.24). CONCLUSIONS: Vaping was associated with increased risk of wheezing and related respiratory symptoms. Current vapers had lower risk in wheezing and related respiratory symptoms than current smokers or dual users but higher than non-users. Both dual use and smoking significantly increased the risk of wheezing and related respiratory symptoms.

Examining the relationship of vaping to smoking initiation among US youth and young adults: a reality check.

BACKGROUND: The 2018 National Academies of Sciences, Engineering, and Medicine Report found substantial evidence that electronic cigarette use (vaping) by youth is strongly associated with an increased risk of ever using cigarettes (smoking) and moderately associated with progressing to more established smoking. However, the Report also noted that recent increases in vaping have been associated with declining rates of youth smoking. This paper examines the temporal relationship between vaping and youth smoking using multiple data sets to explore the question of whether vaping promotes smoking initiation in the USA. METHODS: Using publicly available, nationally representative data on smoking and vaping among youth and young adults, we conducted a trend line analysis of deviations from long-term trends in smoking starting from when vaping became more prevalent. RESULTS: There was a substantial increase in youth vaping prevalence beginning in about 2014. Time trend analyses showed that the decline in past 30-day smoking prevalence accelerated by two to four times after 2014. Indicators of more established smoking rates, including the proportion of daily smokers among past 30-day smokers, also decreased more rapidly as vaping became more prevalent. CONCLUSIONS: The inverse relationship between vaping and smoking was robust across different data sets for both youth and young adults and for current and more established smoking. While trying electronic cigarettes may causally increase smoking among some youth, the aggregate effect at the population level appears to be negligible given the reduction in smoking initiation during the period of vaping's ascendance.

Transitions in electronic cigarette use among adults in the Population Assessment of Tobacco and Health (PATH) Study, Waves 1 and 2 (2013-2015).

INTRODUCTION: This study assessed patterns of e-cigarette and cigarette use from Wave 1 to Wave 2 among adult e-cigarette users at Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study. METHODS: We examined changes in e-cigarette use frequency at Wave 2 among adult e-cigarette users at Wave 1 (unweighted n=2835). Adjusted prevalence ratios (aPR) were calculated using a predicted marginal probability approach to assess correlates of e-cigarette discontinuance and smoking abstinence at Wave 2. RESULTS: Half (48.8%) of adult e-cigarette users at Wave 1 discontinued their use of e-cigarettes at Wave 2. Among dual users of e-cigarettes and cigarettes at Wave 1, 44.3% maintained dual use, 43.5% discontinued e-cigarette use and maintained cigarette smoking and 12.1% discontinued cigarette use at Wave 2, either by abstaining from cigarette smoking only (5.1%) or discontinuing both products (7.0%). Among dual users at Wave 1, daily e-cigarette users were more likely than non-daily users to report smoking abstinence at Wave 2 (aPR=1.40, 95% CI 1.02 to 1.91). Using a customisable device (rather than a non-customisable one) was not significantly related to smoking abstinence at Wave 2 (aPR=1.14, 95% CI 0.81 to 1.60). CONCLUSIONS: This study suggests that e-cigarette use patterns are highly variable over a 1-year period. This analysis provides the first nationally representative estimates of transitions among US adult e-cigarette users. Future research, including additional waves of the PATH Study, can provide further insight into long-term patterns of e-cigarette use critical to understanding the net population health impact of e-cigarettes in USA.

Cytotoxic effects of heated tobacco products (HTP) on human bronchial epithelial cells.

BACKGROUND: Heated tobacco product(s) (HTP), also called heat-not-burn products, are a re-emerging class of tobacco products that purport to reduce health risk compared with smoking combustible tobacco products. This study examined the potential toxic effects of inhaling emissions from an HTP in comparison with electronic and combustible tobacco cigarettes. METHODS: Inhalation toxicity of HTP (IQOS; tobacco flavour), e-cigarette (MarkTen; tobacco flavour) and tobacco cigarette (Marlboro Red) was examined in vitro using an air-liquid interface with human bronchial epithelial cells (H292). Cells were exposed directly to 55 puffs from the e-cigarette, 12 puffs from the HTP and 8 puffs from the tobacco cigarette to equilibrate nicotine delivery to the cells across products. Cytotoxicity was measured using neutral red uptake and trypan blue assays. Cytotoxic effects of each tested product (HTP, e-cigarette and tobacco cigarette) were compared with an air control. Release of inflammatory markers (cytokines) was measured using ELISA. RESULTS: The HTP showed higher cytotoxicity compared with the air controls using the neutral red assay. The HTP also showed higher cytotoxicity than the e-cigarette, but lower cytotoxicity than the combustible cigarettes using the same assay. A significant increase in cytokines levels, compared with air controls, was observed postexposure to tobacco smoke but not to emissions from HTP or e-cigarette aerosol. DISCUSSION: Using limited cytotoxic measures, the HTP showed reduced cytotoxicity relative to a combustible cigarette but higher toxicity than an e-cigarette. More comprehensive testing is needed to determine long-term effects of inhaling emissions from HTP.

Tobacco smoking decreases plasma concentration of the emerging cardiovascular risk marker, L-homoarginine.

BACKGROUND: Tobacco smoking is one of the most important risk factors for cardiovascular disease (CVD) and few biomarkers have been linked to the increased risk of CVD and tobacco smoking. Tobacco smoke has been shown to elevate the plasma levels of asymmetric dimethylarginine (ADMA), a metabolite of L-arginine and an endogenous inhibitor of endothelial nitric oxide synthase. The other potential biomarker that has not been studied to date is L-homoarginine, a homolog of L-arginine. The aim of this study was to evaluate the effects of cigarette smoking on L-homoarginine and other CVD biomarkers. METHODS AND RESULTS: In a cross-sectional study of 231 healthy male volunteers, we measured plasma levels of L-homoarginine, L-arginine, and ADMA using the HPLC method. In smokers, we found that plasma L-homoarginine levels were 16.7% lower compared with nonsmokers after adjusting for age, body mass index, plasma creatinine, and metal blood levels (P<0.05). Plasma ADMA levels were only 6.0% higher in smokers when compared with the levels found in nonsmokers (P>0.05). CONCLUSIONS: Our results suggest that, in contrast to ADMA, there is a strong association between exposure to tobacco smoke and plasma L-homoarginine levels. Further research in this field is needed to explain the mechanisms of the relationship of low L-homoarginine levels, smoking, and cardiovascular health.

Carbonyl compounds in electronic cigarette vapors: effects of nicotine solvent and battery output voltage.

INTRODUCTION: Glycerin (VG) and propylene glycol (PG) are the most common nicotine solvents used in e-cigarettes (ECs). It has been shown that at high temperatures both VG and PG undergo decomposition to low molecular carbonyl compounds, including the carcinogens formaldehyde and acetaldehyde. The aim of this study was to evaluate how various product characteristics, including nicotine solvent and battery output voltage, affect the levels of carbonyls in EC vapor. METHODS: Twelve carbonyl compounds were measured in vapors from 10 commercially available nicotine solutions and from 3 control solutions composed of pure glycerin, pure propylene glycol, or a mixture of both solvents (50:50). EC battery output voltage was gradually modified from 3.2 to 4.8V. Carbonyl compounds were determined using the HPLC/DAD method. RESULTS: Formaldehyde and acetaldehyde were found in 8 of 13 samples. The amounts of formaldehyde and acetaldehyde in vapors from lower voltage EC were on average 13- and 807-fold lower than in tobacco smoke, respectively. The highest levels of carbonyls were observed in vapors generated from PG-based solutions. Increasing voltage from 3.2 to 4.8V resulted in a 4 to more than 200 times increase in formaldehyde, acetaldehyde, and acetone levels. The levels of formaldehyde in vapors from high-voltage device were in the range of levels reported in tobacco smoke. CONCLUSIONS: Vapors from EC contain toxic and carcinogenic carbonyl compounds. Both solvent and battery output voltage significantly affect levels of carbonyl compounds in EC vapors. High-voltage EC may expose users to high levels of carbonyl compounds.

Levels of selected carcinogens and toxicants in vapour from electronic cigarettes.

SIGNIFICANCE: Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. They are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapour generated from e-cigarettes. The aim of this study was to screen e-cigarette vapours for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines and heavy metals. MATERIALS AND METHODS: Vapours were generated from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapours into a solid or liquid phase and analysed with chromatographic and spectroscopy methods. RESULTS: We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9-450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product. CONCLUSIONS: Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study. (To view this abstract in Polish and German, please see the supplementary files online.).

[Plasma lipid concentration in smoking and nonsmoking male adults treated from alcohol addiction]. / Zmiany profilu lipidowego w osoczu mezczyzn o róznym statusie palenia tytoniu leczonych z powodu uzaleznienia od alkoholu.

Alcohol drinking and tobacco smoking affect plasma lipid levels and are both independent risk factors of cardiovascular diseases. Alcohol and nicotine addictions are more common among man than women in Poland. The aim of the study was to evaluate changes in plasma lipid levels after cessation of heavy drinking in smoking and nonsmoking Polish male adults. Subjects were recruited from individuals who participated in an inpatient addiction program following alcohol detoxification. We recruited 119 male adults: 48 non-smokers in age between 31 and 60 years (mean 48.7 +/- 8.8) and 71 smokers in age between 30 and 60 years (mean 46.1 +/- 7.8). Each subjects provided three blood samples: at baseline, after 3 weeks, and after 6 weeks of treatment. Plasma samples were analyzed for lipids by manual precipitation and automatic enzymatic methods. Changes in plasma lipid concentrations were analyzed using two-way analysis of variances with repeated measures with smoking status as between subjects factor and time post alcohol cessation as within-subject factors. All analyses were adjusted for age, and BMI. We found that plasma levels of HDL decreased in smoking and nonsmoking subjects by 30% and 24%, respectively (p < 0.001). In smoking subjects, plasma levels of triglycerides and LDL increased significantly after 6 weeks post cessation of heavy drinking cessation by 17% and 16%, respectively (p = 0.001). We also found that total cholesterol levels remained high in smoking subjects, but decreased significantly by 7% (p = 0.022) in nonsmoking subjects after 6 weeks post cessation of heavy drinking. We concluded that cigarette smoking increased LDL and inhibited the decline in plasma cholesterol among subjects addicted to alcohol following cessation of heavy drinking. Alcohol addiction therapy should be complemented with smoking cessation to prevent increase in cardiovascular risk.

[Electronic cigarette--a safe substitute for tobacco cigarette or a new threat?]. / Elektroniczny papieros--bezpieczny substytut papierosa czy nowe zagrozenie?

The aim of this paper was to summarize up-to-date data on the new emerging nicotine containing product 'electronic cigarette', commonly referred as e-cigarette. We presented data on prevalence and popularity of various brands and models on domestic markets. Development of the new products with technical and chemical modifications was also described. We reviewed studies on chemical composition and efficacy of nicotine delivery from e-cigarettes and discussed its potential use as nicotine replacement for tobacco cigarettes. Regulatory policies on e-cigarette sale as nicotine containing product were also discussed. We concluded that e-cigarette might be an effective harm reduction tool but little is known about its safety, especially when used for a long time. Despite many positive findings from surveys among e-cigarettes users, there is need for comprehensive state-of-the-at clinical trials to show efficacy of e-cigarette as smoking cessation tool.