Electronic Cigarette Liquids Research Articles

The Role of Electronic Cigarettes in Dental Caries: A Scoping Review.

Dental caries, a predominant childhood and adolescence affliction, has numerous factors implicated in its pathogenesis. Electronic cigarettes (ECs) have recently gained popularity among the younger population. Various factors, such as the EC liquid composition and aerosols, are associated with the development of dental caries. This review explains numerous EC-related factors which may lead to dental caries. An electronic search was conducted in Medline (Pubmed), Scopus, and Embase databases to evaluate the original research investigating the role of ECs in developing dental caries. About 12 included studies in the review indicated that factors such as the composition of e-liquids and aerosols are significant in the progression of dental caries. Specifically, cariogenic sugars such as sucrose, fructose, glucose, aldehydes, and flavors such as menthol, cinnamon, and strawberry in the e-liquids contribute to dental caries. They are toxic to oral commensals such as Streptococcus gordonii, Streptococcus mitis, Streptococcus intermedius, and Streptococcus oralis and promote the proliferation of cariogenic pathogens such as Streptococcus mutans (S. mutans) which causes dental caries. However, further validation of the effects of ECs on the development of dental caries is warranted through clinical trials.

Heated Tobacco Products: Insights into Composition and Toxicity.

Heated tobacco products (HTPs) are novel products that allow users to inhale nicotine by heating (350 °C) reconstituted tobacco rather than combustion (900 °C) as in conventional cigarettes. HTP sticks containing reconstituted tobacco come in various flavours such as menthol, citrus, etc., like electronic cigarette liquids. Thus, the composition of HTP aerosol will also vary according to the flavouring agents added. Overall, the content of toxic chemicals in HTP aerosol appears to be lower than in cigarette smoke. However, the concentrations of more than twenty harmful and potentially harmful constituents have been reported to be higher in HTP aerosol than in cigarette smoke. Further, several toxic compounds not detected in cigarette smoke are also reported in HTP aerosol. Thus, the risks of HTP use remain unknown. Most of the available data on the composition and health effects of mainstream HTP aerosol exposure are generated by the tobacco industry. Few independent studies have reported short-term pathophysiological effects of HTP use. Currently available HTP toxicity data are mainly on the pulmonary and cardiovascular systems. Moreover, there are no long-term toxicity data and, therefore, the claims of the tobacco industry regarding HTPs as a safer alternative to traditional combustible cigarettes are unsubstantiated. Furthermore, HTP aerosol contains the highly addictive substance nicotine, which is harmful to the adolescent brain, developing foetuses, pregnant women, and also adults. Hence, comprehensive studies addressing the safety profiling related to long-term HTP use are warranted. With this background, the following review summarizes the current state of knowledge on HTP toxicity on four broad lines: composition of mainstream HTP aerosol compared to traditional combustible cigarette smoke, biomarkers of HTP exposure, health effects of HTP exposure, and the harm reduction aspect.

The impact ofvaping ethanol-containing electronic cigarette liquids onroadside impairment investigations.

Legal professionals and others have suggested that vaping electronic cigarettes (e-cigs) prior to or during ethanol breath testing may produce false positives. Preliminary breath tests (PBTs) and evidentiary breath tests (EBTs) measure ethanol in exhaled breath and standardized field sobriety tests (SFSTs) are used to assess impairment. Ethanol has been identified in e-cig liquids (e-liquids). Presented are a series of experiments designed to determine the mechanics of vaping ethanol using an e-cig and the effects of vaping ethanol on the SFSTs and breath tests used by law enforcement officers (LEO). Twelve participants (five females, age: 21-32 and seven males, age: 21-55), vaped either one or ten puffs of an e-liquid (0% or 20% ethanol). LEOs assessed impairment using SFSTs (12 and 42 min), PBTs (<1, 27, 32, 37 and 57 min) and EBTs (2, 29, 34, 39 and 59 min) post-vaping. A self-assessment test was administered post-vaping (22 and 52 min). Baseline responses for all measures were collected prior to vaping. Results demonstrated that ethanol in the e-liquids was aerosolized by e-cigs and produced particles that could reach the deep lung tissue based on mean-mass diameter. Ethanol was detected by PBT <3 min after participants vaped one (0.007-0.030 g/210 L) or ten puffs (013-0.074 g/210 L) of a 20% ethanol e-liquid. Ethanol was not detected by PBT at any subsequent time point. Ethanol was not detected by the EBT under any condition. Impairment was not indicated by the SFST. Some subjective effects were reported, but few statistically significant differences between conditions were indicated. A wait period prior to ethanol breath testing is not always mandated, depending on jurisdiction, or observed in all applications, such as workplace testing. The results demonstrate that a wait period must be employed to prevent vaping-related false-positive breath ethanol results.

Electronic cigarettes can damage lingual papillae and taste buds. Can vitamins C and E supplementation reverse this damage?

AimsThis histological study focuses on the impact of electronic cigarette liquid (EC) on lingual papillae, especially taste buds, compare it to nicotine, and investigates the potential of vitamins in reversing these unwanted changes. Main methods40 adult male rats were allocated into 5 groups. Control injected saline intraperitoneally, electronic cigarettes group injected EC-liquid containing nicotine of dose (0.75 mg/kg), electronic cigarette group injected EC-liquid then supplemented orally with vitamins C and E, nicotine group injected pure nicotine of dose (0.75 mg/kg) and lastly nicotine group injected with pure nicotine of dose (0.75 mg/kg) then supplemented orally with vitamins C and E. Keratin surface area and the ratio between taste buds and its epithelial covering surface areas in fungiform papillae were measured. Key findingsHistological examination of EC group revealed abnormal epithelial stratification and mitotic figs. EC plus V group showed intact basal cell layer. N group showed better histological stratification than EC group. Fungiform and circumvallate papillae in EC and N groups showed distorted appearance of taste buds. Histomorphometry analysis showed a significant decrease in taste buds to epithelium surface areas in EC, nicotine, and EC plus V groups, p-value (<0.05). There was no significant difference between control and N plus V groups. SignificanceAdministration of vitamins C and E showed preservation of normal histological features of the lingual mucous membrane. EC caused striking damage to taste buds even after the administration of vitamins. The negative effects of electronic cigarettes are not confined only to the presence of nicotine.

Comparison of Culture Media for In Vitro Expansion of Oral Epithelial Keratinocytes

Background: Expansion of OKF6/TERT-2 oral epithelial cells in vitro is important for studying the molecular biology of disease and pathology affecting the oral cavity. Keratinocyte serum-free medium (KSFM) is the medium of choice for this cell line. This study compares three media for OKF6/TERT-2 cultures: KSFM, Dulbecco’s Modified Eagle Medium/Nutrient Mixture of Hams F-12 (DMEM/F12), and a composite medium comprised of DMEM/F-12 and KSFM (1:1 v/v), referred to as DFK. The toxicological effects of electronic cigarette liquids (e-liquids) on OKF6/TERT-2 cells cultured in these media were also compared. Methods: Cells were cultured in KSFM, DMEM/F12, or DFK, and cellular morphology, growth, wound healing and the gene expression of mucins and tight junctions were evaluated. Additionally, cytotoxicity was determined after e-liquid exposures. Results: Switching from KSFM to DMEM/F12 or DFK 24 h post-seeding leads to typical cellular morphologies, and these cultures reach confluency faster than those in KSFM. Wound-healing recovery occurred fastest in DFK. Except for claudin-1, there is no difference in expression of the other genes tested. Additionally, e-liquid cytotoxicity appears to be amplified in DFK cultures. Conclusions: DMEM/F12 and DFK are alternative media for OKF6/TERT-2 cell culture to study the molecular biology of disease and pathology, provided cells are initially seeded in KSFM.

Rapid detection of nicotine and benzoic acid in e-liquids with surface-enhanced Raman scattering and artificial intelligence-assisted spectrum interpretation

Electronic cigarettes have rapidly gained acceptance recently. Nicotine-containing electronic cigarette liquids (e-liquids) are prohibited in some countries, but are permitted and simply available online in others. A rapid detection method is therefore required for on-site inspection or screening of a large amount of samples. Our previous study demonstrated a surface-enhanced Raman scattering (SERS)-based approach to identify nicotine-containing e-liquids; without any pre-treatment, e-liquid can be directly tested on our solid-phase SERS substrates, made of silver nanoparticle arrays embedded in anodic aluminium oxide nanochannels (Ag/AAO). However, this approach required manual determination of spectral signatures and negative samples should be validated in the second round detection. Here, after examining 406 commercial e-liquids, we refined this approach by developing artificial intelligence (AI)-assisted spectrum interpretations. We also found that nicotine and benzoic acid can be simultaneously detected in our platform. This increased test sensitivity because benzoic acid is usually used in nicotine salts. Around 64% of nicotine-positive samples in this study showed both signatures. Using either cutoffs of nicotine and benzoic acid peak intensities or a machine learning model based on the CatBoost algorithm, over 90% of tested samples can be correctly discriminated with only one round of SERS measurement. False negative and false positive rates were 2.5–4.4% and 4.4–8.9%, respectively, depending on the interpretation method and thresholds applied. The new approach takes only 1 microliter of sample and can be performed in 1–2 min, suitable for on-site inspection with portable Raman detectors. It could also be a complementary platform to reduce samples that need to be analyzed in the central labs and has the potential to identify other prohibited additives.

Electronic Cigarette Users’ Reactions and Responses to a Hypothetical Nicotine Concentration Reduction in Electronic Cigarette Liquids

Background: Regulations limiting nicotine in electronic cigarettes (e-cigarettes) have been proposed or implemented. Little is known about e-cigarette users’ reactions to reducing e-cigarette liquid nicotine concentration. Methods: We used concept mapping to describe e-cigarette users’ reactions to a 50% reduction in the nicotine concentration of their e-cigarette liquids. In 2019, current e-cigarette users who used e-cigarette liquid with greater than 0 mg/ml nicotine concentration completed an online study. Participants (n = 71, mean age = 34.9 (SD = 11.0), 50.7% women), brainstormed statements completing a prompt: “If the e-liquid that I use now in my e-cigarette/vaping device was only available in half the nicotine concentration or amount that I use now, a specific action I would take or a specific reaction I would have is…”, Participants then sorted a final list of 67 statements into piles of similar content and rated statements on how true the statements would be for them. Multidimensional scaling and hierarchical cluster analyses identified thematic clusters. Results: Eight clusters were identified: (1) Replacement Product Seeking, (2) Mental Preparations and Expectations, (3) Use the New Liquid, (4) Information Seeking, (5) Compensation Behaviors, (6) Opportunity for E-Cigarette Reduction, (7) Physical and Psychological Effects, and (8) Replacement with non-E-Cigarette Products and Behaviors. Cluster ratings suggested many participants would search for other e-cigarette products/liquids to replace their current liquids, but using other tobacco products (e.g., cigarettes) may be less likely. Conclusions: If nicotine concentrations were decreased in e-cigarette liquids, e-cigarette users may attempt to purchase different e-cigarette products or modify their products to achieve desired effects.

Effect of Electronic Cigarette Liquid pH on Retention of 11C-Nicotine in a Respiratory Tract Model.

Based on our preliminary 11C-nicotine positron emission tomography (PET) imaging studies in humans, we speculated that greater deposition of nicotine in the respiratory tract from electronic cigarettes compared to combustible cigarettes could result from the alkaline pH of typical aerosol-producing electronic cigarette liquids (e-liquids). To address this hypothesis, we assessed the effect of e-liquid pH on the retention of nicotine in vitro using 11C-nicotine, PET, and a human respiratory tract model of nicotine deposition. A single 2-second 35-mL puff was delivered to a human respiratory tract cast from a 2.8-Ohm cartomizer at 4.1 volts. Immediately after the puff, a 2-second 700-mL air wash-in volume was administered. E-liquids (glycerol and propylene glycol 50/50 vol/vol) containing 24 mg/mL nicotine were mixed with 11C-nicotine. Deposition (retention) of nicotine was assessed using a GE Discovery MI DR PET/CT scanner. Eight e-liquids with different pH values (range 5.3-9.6) were investigated. All experiments were performed at room temperature and at a relative humidity of 70%-80%. Retention of nicotine in the respiratory tract cast was pH dependent and the pH-sensitive component of the retention was well described by a sigmoid curve. In total, 50% of the maximal pH-dependent effect was observed at pH 8.0, which is close to the pKa2 of nicotine. The retention of nicotine in the respiratory tract conducting airways is dependent on the e-liquid pH. Lowering the e-liquid pH reduces retention of nicotine. Nonetheless, reduction of the pH below 7 has little effect, consistent with the pKa2 of protonated nicotine. Similar to combustible cigarettes, the retention of nicotine in the human respiratory tract from consumption of electronic cigarettes may have some health consequences and affect nicotine dependence. Here we demonstrated that the retention of nicotine in the respiratory tract is dependent on the e-liquid pH, and lowering pH reduces retention of nicotine in conducting airways of the respiratory tract. Therefore, e-cigarettes with low pH values would result in reduced respiratory tract nicotine exposure and faster delivery of nicotine to the central nervous system (CNS). The latter can be associated with e-cigarette abuse liability and the effectiveness of e-cigarettes as substitutes for combustible cigarettes.

A Wide Range of Flavoring-Carrier Fluid Adducts Form in E-Cigarette Liquids.

A range of flavoring molecules are used in electronic cigarette liquids (e-liquids), some of which have been shown to form cyclic acetal adducts with e-liquid solvent components propylene glycol (PG) and vegetable glycerine (VG). The objective of this study was to identify the range of flavoring molecules which form adducts in e-liquid products. Common e-liquid flavoring molecules (N = 36) from a range of chemical class groups were exposed to PG, VG, or methanol and analyzed by GC-MS over a time frame of 4 weeks to identify possible reaction products. Adduct formation was observed, with 14 of the flavoring molecules reacting with methanol, 10 reacting with PG, and 10 reacting with VG. Furfural PG and VG acetals, valeraldehyde PG and VG acetals, veretraldehyde PG and VG acetals, p-anisaldehyde PG and VG acetals, and piperonal VG acetal were confirmed for the first time. Adducts formed by reaction with ketone-containing flavoring molecules were also observed for the first time. The presence of these acetals was confirmed in 32% of commercial e-liquid products analyzed (N = 142). This study has established a range of flavoring molecules which are able to react with solvent components PG and VG in e-liquids under standard storage conditions. These newly identified adducts need to be further assessed to determine their toxicological safety.

Effects of E-Cigarette Liquid Ratios on the Gravimetric Filter Correction Factors and Real-Time Measurements.

Electronic cigarettes (ECIGs) generate high concentrations of particulate matter (PM), impacting the air quality inhaled by humans through secondhand exposure. ECIG liquids are available commercially and some users create their own "do-it-yourself" liquids, and these liquids often vary in the amounts of their chemical ingredients, including propylene glycol (PG) and vegetable glycerin (VG). Previous studies have quantified PM concentrations in ECIG aerosol generated from liquids containing different PG/VG ratios. However, the effects of these ratios on aerosol instrument filter correction factors needed to measure PM concentrations accurately have not been assessed. Thus, ECIG aerosol filter correction factors for multiple aerosol instruments (SMPS + APS, MiniWRAS, pDR, and SidePak) were determined for five different PG/VG ratios 1) 0PG/100VG, 2) 15PG/85VG, 3) 50PG/50VG, 4) 72PG/28VG, and 5) 90PG/10VG and two different PM sizes, PM1 (1 μm and smaller) and PM2.5 (2.5 μm and smaller). ECIG aerosols were generated inside a controlled exposure chamber using a diaphragm pump and a refillable ECIG device for all the ratios. In addition, the aerosol size distribution and mass median diameter were measured for all five ECIG ratios. PM2.5 correction factors (5-7.6) for ratios 1, 2, 3, and 4 were similar for the SMPS + APS combined data, and ratios 1, 2, 3 were similar for the MiniWRAS (~2), pDR (~0.5), and SidePak (~0.24). These data suggest different correction factors may need to be developed for aerosol generated from ECIGs with high PG content. The higher correction factor values for the 90PG/10VG ratio may have resulted from greater PG volatility relative to VG and sensor losses. The correction factors (ratios 1-4) for PM2.5 were SMPS + APS data (4.96-7.62), MiniWRAS (2.02-3.64), pDR (0.50-1.07), and SidePak (0.22-0.40). These data can help improve ECIG aerosol measurement accuracy for different ECIG mixture ratios.

Electronic cigarettes with different nicotine concentrations in unflavoured liquid induce oxidative stress

Background/Aim: Nicotine content and flavour in electronic cigarette (e-cig) liquids have been demonstrated to cause oxidative stress in acute exposure. However, the chronic effects of using unflavoured and with or without nicotine in e-cigs liquid have not been evaluated. This in vivo study aims to investigate the chronic effect of e-cig exposure with unflavoured liquids at different nicotine concentrations on oxidative stress. Methods: The 24 male Wistar rats were divided into four groups of six each. Normal, as a control group. Nic 0, Nic 6 and Nic 12 groups were exposed to unflavoured e-cig liquid for eight weeks with different nicotine concentrations: 0, 6 and 12 mg/mL, respectively. E-cig exposure in rats was conducted using an exposure instrument adjusted to real-life exposure to humans. Oxidative stress markers, including plasma, liver and lung malondialdehyde (MDA) and superoxide dismutase (SOD), as well as plasma catalase (Cat) and glutathione peroxidase (GPx) were assessed at the end of the study. Results: Unflavoured e-cig liquids induced oxidative stress in a nicotine concentration-dependent manner, in which the nicotine content of 12 mg/mL demonstrated the greatest response. There was a significant increase in plasma, liver and lung MDA and concurrently decreased plasma and selected organs SOD, as well as plasma Cat and GPx in all nicotine concentration exposed groups compared to the Normal group. Conclusions: Chronic unflavoured liquids in e-cig exposure at different nicotine concentrations induced oxidative stress, potentially leading to various oxidative stress-induced diseases.

The degree of nicotine dependence among users of different tobacco and nicotine products in Madinah City, Saudi Arabia.

Nicotine addiction has many consequences. The World Health Organization has classified nicotine dependence as a disorder of substance use. This study aimed to assess the dependence in users of different tobacco and/or nicotine-containing products (TNPs). This analytical, cross-sectional study involved 211 TNP users in Madinah, Saudi Arabia. The data was collected using a self-administered questionnaire that consisted of two main sections. The first section included sociodemographic domain, TNP status domain, and the Stages of Change model domain. The second section of the instrument included the ABOUT dependence construct comprising 12 items. Independent t-test, analysis of variance, and correlation analysis were used to assess the relationship between the study variables. Most users of TNPs exclusively used tobacco cigarettes (53.1%). Total dependence score was significantly associated with gender, marital status, age group, monthly income, nicotine concentration in electronic cigarettes (e-cigarettes) liquid, and the number of cigarettes smoked per day (P < 0.05). Total dependence score was correlated with the duration of TNP usage (r = 0.24, P < 0.001), Switching attempts to another TNP (r = 0.16, P = 0.020), attempts of quitting TNPs (r = 0.25, P < 0.001), and willingness to quit (r = -0.37, P < 0.001). Dependence was associated with gender, marital status, age group, monthly income, nicotine concentration in e-cigarette liquid, and the number of cigarettes smoked per day. It was also associated with duration of TNP usage, Switching attempts to another TNP, attempts of quitting TNPs and the willingness to quit.

Chemical analysis of electronic cigarette liquids (e-liquids) and direct nicotine quantitation using surface-assisted flowing atmospheric-pressure afterglow desorption/ionization mass spectrometry (SA-FAPA-MS).

Ambient desorption/ionization mass spectrometry (ADI-MS) has been widely used for direct analysis of real samples without sample preparation or separation. Studies on the quantification of low molecular weight compounds in complex matrices with ADI-MS remain scarce. In this paper, we report the application of surface-assisted flowing atmospheric-pressure afterglow mass spectrometry (SA-FAPA-MS) for fast qualitative screening of electronic cigarette liquid (e-liquids) ingredients and direct quantification of nicotine. The quantification approach is rapid, uses a deuterated D4-nicotine standard spike, and does not require a preceding chromatography step or other methods to remove the complex sample matrix. Selected e-liquids were directly applied on thin-layer chromatography (TLC) plate surfaces (normal phase (NP) silica, reversed phase (RP) modified silica, cyano (CN) modified silica, and dimethyl (RP2) modified silica) after dilution and internal standard spiking. The plates served purely as sample carriers and no analyte separation was performed. Promising qualitative results were obtained, demonstrating the ability to detect nicotine alkaloids using this approach and the ability to differentiate e-liquids based on their flavor variations. In addition, dimethyl- (RP2-) and cyano-modified (CN-) silica surfaces were selected for quantification based on performance results of previous studies. It was shown that results were in high accordance with high-performance liquid chromatography (HPLC) experiments with lowest deviations <3% on dimethyl surfaces. Additional quantitative experiments including a certified reference material achieved equally satisfying results with lowest deviations of -1.1% from the certified nicotine content. For nicotine, detection limits down to the fmol range (96 fmol on CN and 20 fmol on RP2) were obtained. A detailed comparison of glass surfaces with functionalized surfaces showed that the functionalized surfaces were superior in terms of sample application reproducibility, mass spectra quality, sensitivity, and information density. Thus, functionalized thin-layer surfaces are considered promising tools for both qualitative and quantitative ADI-MS analysis of complex samples.

Impact of tobacco flavoring on oral nicotine consumption in C57BL/6J mice

BackgroundThe continued use of flavors in tobacco products has been a prominent factor in their popularity, yet little is known regarding their role in nicotine dependence. This study aimed to investigate the impact of tobacco flavoring on oral nicotine consumption in mice using the two-bottle choice (2BC) test and assessed the potential impact of age and sex in their interactions. MethodsAdolescent and adult male and female C57BL/6J mice were used. First, voluntary consumption of tobacco flavor concentrate from a commercial electronic cigarette liquid vendor (Avail Vapor LLC) was measured; then, the effects of tobacco flavoring in combination with nicotine were examined. In one approach, tobacco flavor concentration was kept constant while nicotine concentration varied, and in the second, nicotine was kept constant while the tobacco flavor concentration varied. ResultsOverall, tobacco flavoring decreased oral nicotine consumption in mice, and its effects were sex- and age-dependent. Although females consumed the tobacco-flavored solution at a slightly higher rate than males, male mice were more sensitive to the effects of the combination (nicotine + tobacco). Furthermore, adolescent mice showed a starker reduction in nicotine consumption in the presence of tobacco flavoring compared to adult mice. This attenuation was most likely due to a basal aversion to the tobacco flavoring itself, thus, creating a negative synergistic effect with nicotine. ConclusionsTobacco flavoring increases aversion to nicotine in the 2BC test in C57BL6J mice, suggesting that some flavors may diminish rather than enhance oral nicotine consumption in rodents.

Electronic cigarette users’ reactions and responses to a hypothetical ban of flavoured electronic cigarette liquids

BackgroundRegulations have been proposed to limit e-cigarette flavours, but limited research has examined potential impacts of such policies. This study examined adult e-cigarette users’ reactions to a hypothetical e-cigarette flavour...

Absence of Relevant Thermal Conversion of Cannabidiol to Tetrahydrocannabinol in E-Cigarette Vapor and Low-Tetrahydrocannabinol Cannabis Smoke.

Introduction:Recent research claimed that CBD in commercial electronic cigarette (e-cigarette) liquids can be converted into psychotropic amounts of Δ9-THC. This study aims to validate this claim using a realistic e-cigarette setup. In addition, this study also investigates if such a conversion may occur during smoking of CBD-rich cannabis joints.Materials and Methods:Two different CBD liquids were vaporized using two different e-cigarette models, one of which was operated at extreme energy settings (0.2 Ω and 200 W). The smoke of six CBD joints was collected using a rotary smoking machine according to ISO 4387:2019. Analyses were conducted using nuclear magnetic resonance spectrometry as well as liquid chromatography tandem mass spectrometry.Results:For the condensed e-cigarette liquids, no increase in THC concentration could be observed. For the CBD joints, no THC formation was provable. The recovered THC concentrations were ranging between 1% and 48% (0.034 and 0.73 mg) of the THC amount initially contained in the joints before smoking.Conclusions:Using realistic conditions of consumer exposure, relevant conversion of CBD to THC appears to not be occurring. The health risk of CBD liquids for e-cigarettes, as well as low-THC cannabis intended for smoking, can be assessed by concentrations in the source material without the need to consider significant changes in psychotropic compounds during use by consumers.

Electronic Cigarette Nicotine Flux, Nicotine Yield, and Particulate Matter Emissions: Impact of Device and Liquid Heterogeneity.

Electronic cigarettes (ECIGs) heat a nicotine-containing liquid to produce an inhalable aerosol. ECIG power (wattage) and liquid nicotine concentration are two factors that predict nicotine emission rate ("flux"). These factors can vary greatly across devices and users. The purpose of this study was to examine ECIG device and liquid heterogeneity in "real world" settings and the association with predicted nicotine flux, nicotine yield, and total particulate matter (TPM) emissions. Past 30-day ECIG users (n = 84; mean age = 23.8 years [SD = 9.6]) reported device and liquid characteristics. Device power was measured via multimeter, device display screens, or obtained via labeling. Liquid nicotine concentration was obtained via labeling or through chemical analysis. Predicted nicotine flux, nicotine yield, and TPM associated with 10 4-second puffs were calculated for participants' primary devices. Participants' primary devices were box mods (42.9%), disposable vapes (20.2%), and pod mods (36.9%). Most participants (65.5%) reported not knowing their primary device wattage. Rebuildable/box mods had the greatest power range (11.1-120.0 W); pod mod power also varied considerably (4.1-21.7 W). Unlike device wattage, most participants (95.2%) reported knowing their liquid nicotine concentration, which ranged from 3.0 to 86.9 mg/ml (M = 36.0, SD = 29.3). Predicted nicotine flux varied greatly across products (range =12.0-160.1 μg/s, M = 85.6 μg/s, SD = 34.3). Box mods had the greatest variability in wattage and predicted nicotine flux, nicotine yield, and TPM yield. ECIG device and liquid heterogeneity influence nicotine and other toxicant emissions. Better measurement of ECIG device and liquid characteristics is needed to understand nicotine and toxicant emissions and to inform regulatory policy. ECIG device and liquid heterogeneity cause great variability in nicotine flux and toxicants emitted. These data demonstrate the need to examine device and liquid characteristics to develop empirically informed, health-promoting regulatory policies. Policies may include setting product standards such that ECIG products cannot (1) have nicotine fluxes much greater than that of a cigarette to decrease the risk of dependence, (2) have nicotine fluxes that are very low and thus would have minimal appeal to cigarette smokers and may serve as starter products for youth or nontobacco users, and (3) emit large amounts of particulate matter and other toxicants.

Composition of aerosols from thermal degradation of flavors used in ENDS and tobacco products

Aim: The cardiovascular toxicity of unheated and heated flavorants and their products as commonly present in electronic cigarette liquids (e-liquids) was evaluated previously in vitro. Based on the results of in vitro assays, cinnamaldehyde, eugenol, menthol, and vanillin were selected to conduct a detailed chemical analysis of the aerosol generated following heating of each compound both at 250 and 750 °C. Materials and Methods: Each flavoring was heated in a drop-tube furnace within a quartz tube. The combustion atmosphere was captured using different methods to enable analysis of 308 formed compounds. Volatile organic compounds (VOCs) were captured with an evacuated Summa canister and assayed via gas chromatography interfaced with mass spectrometry (GC–MS). Carbonyls (aldehydes and ketones) were captured using a 2,4-dinitrophenylhydrazine (DNPH) cartridge and assayed via a high-performance liquid chromatography-ultra-violet (HPLC-UV) assay. Polyaromatic hydrocarbons (PAHs) were captured using an XAD cartridge and filter, and extracts were assayed using GC–MS/MS. Polar compounds were assayed after derivatization of the XAD/filter extracts and analyzed via GC–MS. Conclusion: At higher temperature, both cinnamaldehyde and menthol combustion significantly increased formaldehyde and acetaldehyde levels. At higher temperature, cinnamaldehyde, eugenol, and menthol resulted in increased benzene concentrations. At low temperature, all four compounds led to higher levels of benzoic acid. These data show that products of thermal degradation of common flavorant compounds vary by flavorant and by temperature and include a wide variety of harmful and potentially harmful constituents (HPHCs).

Using the BMD Approach to Derive Acceptable Daily Intakes of Cannabidiol (CBD) and Tetrahydrocannabinol (THC) Relevant to Electronic Cigarette Liquids.

In the past 60 years, Cannabis sativa L. has been an object of increasing interest because of the psychotropic effects of some of its constituents. These effects mainly arise from the cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC). C. sativa species also synthesize and accumulate the non-psychotropic compound cannabidiol (CBD). Due to their therapeutic potential, both cannabinoids are an object of medical research and drug development. More recently, CBD has received increasing interest as an ingredient in electronic cigarette liquids (e-liquids). This trend may have been reinforced by health and disease-related claims, often based on clinical studies, which are used to advertise CBD. CBD liquids may be based on full-spectrum hemp extracts, CBD isolates, or synthetic CBD, all of which may contain some residual levels of Δ9-THC from either natural content (in the extracts) or from possible degradation of CBD to Δ9-THC, which may occur during storage. There is uncertainty about safety regarding the consumption of CBD (and Δ9-THC) in e-liquids. The aim of this publication was to present an approach for a toxicological risk assessment of CBD and Δ9-THC relevant to e-liquids by using the benchmark dose (BMD) approach. Before an analysis to estimate a reference dose (RfD) for both cannabinoids, a systematic review of dose-response data was conducted. The data obtained were analyzed using the BMD approach to derive a benchmark dose lower confidence limit (BMDL). The BMDL was used as a point of departure to estimate the RfD. No adequate human data suitable for dose-response modeling were identified. Based on animal data, the RfD values for the most sensitive endpoints were selected. For CBD, an RfD for acute exposure of 1 mg/kg body weight (bw) was estimated. For Δ9-THC, an acute RfD was found to be 0.006 mg/kg bw. Additionally, the RfD for chronic exposure to CBD was estimated to be 4 mg/kg bw per day. The respective endpoints for CBD were a reduction in norepinephrine turnover and a reduction in uterus weight. The endpoint for Δ9-THC was a change in blood pressure. Because of the limited availability and quality of dose-response data, it cannot be excluded that the estimated RfD values might be afflicted with considerable uncertainties. Therefore, it is recommended to conduct further research on dose-response data, preferably from human studies.

Electronic cigarette liquids impair metabolic cooperation and alter proteomic profiles in V79 cells

BackgroundAlthough still considered a safer alternative to classical cigarettes, growing body of work points to harmful effects of electronic cigarettes (e-cigarettes) affecting a range of cellular processes. The biological effect of e-cigarettes needs to be investigated in more detail considering their widespread use.MethodsIn this study, we treated V79 lung fibroblasts with sub-cytotoxic concentration of e-cigarette liquids, with and without nicotine. Mutagenicity was evaluated by HPRT assay, genotoxicity by comet assay and the effect on cellular communication by metabolic cooperation assay. Additionally, comprehensive proteome analysis was performed via high resolution, parallel accumulation serial fragmentation-PASEF mass spectrometry.ResultsE-cigarette liquid concentration used in this study showed no mutagenic or genotoxic effect, however it negatively impacted metabolic cooperation between V79 cells. Both e-cigarette liquids induced significant depletion in total number of proteins and impairment of mitochondrial function in treated cells. The focal adhesion proteins were upregulated, which is in accordance with the results of metabolic cooperation assay. Increased presence of posttranslational modifications (PTMs), including carbonylation and direct oxidative modifications, was observed. Data are available via ProteomeXchange with identifier PXD032071.ConclusionsOur study revealed impairment of metabolic cooperation as well as significant proteome and PTMs alterations in V79 cells treated with e-cigarette liquid warranting future studies on e-cigarettes health impact.