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The use of traditional nicotine delivery products such as tobacco has long been linked to detrimental health effects. However, little work to date has focused on the emerging market of aerosolized nicotine delivery known as electronic nicotine delivery systems (ENDS) or electronic cigarettes, and their potential for new effects on human health. Challenges studying these devices include heterogeneity in the formulation of the common components of most available ENDS, including nicotine and a carrier (commonly composed of propylene glycol and vegetable glycerin, or PG/VG). In the present study, we report on experiments interrogating the effects of major identified components in e‐cigarettes. Specifically, the potential concomitant effects of nicotine and common carrier ingredients in commercial "vape" products are explored in vitro to inform the potential health effects on the craniofacial skeleton through novel vectors as compared to traditional tobacco products. MC3T3‐E1 murine pre‐osteoblast cells were cultured in vitro with clinically relevant liquid concentrations of nicotine, propylene glycol (PG), vegetable glycerin (VG), Nicotine+PG/VG, and the vape liquid of a commercial product (Juul). Cells were treated acutely for 24 h and RNA‐Seq was utilized to determine segregating alteration in mRNA signaling. Influential gene targets identified with sparse partial least squares discriminant analysis (sPLS‐DA) implemented in mixOmics were assessed using the PANTHER Classification system for molecular functions, biological processes, cellular components, and pathways of effect. Additional endpoint functional analyses were used to confirm cell cycle changes. The initial excitatory concentration (EC50) studied defined a target concentration of carrier PG/VG liquid that altered the cell cycle of the calvarial cells. Initial sPLS‐DA analysis demonstrated the segregation of nicotine and non‐nicotine exposures utilized in our in vitro modeling. Pathway analysis suggests a strong influence of nicotine exposures on cellular processes including metabolic processes and response to stimuli including autophagic flux. Further interrogation of the individual treatment conditions demonstrated segregation by treatment modality (Control, Nicotine, Carrier (PG+VG), Nicotine+PG/VG) along three dimensions best characterized by: latent variable 1 (PLSDA‐1) showing strong segregation based on nicotine influence on cellular processes associated with cellular adhesion to collagen, osteoblast differentiation, and calcium binding and metabolism; latent variable 2 (PLSDA‐2) showing strong segregation of influence based on PG+VG and Control influence on cell migration, survival, and cycle regulation; and latent variable 3 (PLSDA‐3) showing strong segregation based on Nicotine and Control exposure influence on cell activity and growth and developmental processes. Further, gene co‐expression network analysis implicates targets of the major pathway genes associated with bone growth and development, particularly craniofacial (FGF, Notch, TGFβ, WNT) and analysis of active subnetwork pathways found these additionally overrepresented in the Juul exposure relative to Nicotine+PG/VG. Finally, experimentation confirmed alterations in cell count, and increased evidence of cell stress (markers of autophagy), but no alteration in apoptosis. These data suggest concomitant treatment with Nicotine+PG/VG drives alterations in pre‐osteoblast cell cycle signaling, specifically transcriptomic targets related to cell cycle and potentially cell stress. Although we suspected cell stress and well as cytotoxic effects of Nicotine+PG/VG, no great influence on apoptotic factors was observed. Further RNA‐Seq analysis allowed for the direct interrogation of molecular targets of major pathways involved in bone and craniofacial development, each demonstrating segregation (altered signaling) due to e‐cigarette‐type exposure. These data have implications directed toward ENDS formulation as synergistic effects of Nicotine+PG/VG are evidenced here. Thus, future research will continue to interrogate how varied formulation of Nicotine+PG/VG affects overall cell functions in multiple vital systems. [ABSTRACT FROM AUTHOR]

It has been demonstrated that propylene glycol (PG), vegetable glycerin (VG), and flavoring chemicals can thermally degrade to form carbonyls during vaping, but less is known about carbonyl emissions produced by transformation of flavoring chemicals and the interactive effects among e-liquid constituents. This study characterized carbonyl composition and levels in vaping emissions of PG-VG (e-liquid base solvents) and four e-liquid formulations flavored with trans-2-hexenol, benzyl alcohol, l-(-)-menthol, or linalool. Utilizing gas chromatography (GC)- and liquid chromatography (LC)-mass spectrometry (MS) methods, 14 carbonyls were identified and quantified. PG-VG emitted highest levels of formaldehyde, acetaldehyde, and acrolein. However, flavored e-liquids contributed to the production of a wider variety of carbonyls, with some carbonyls directly corresponding to the oxidation of alcohol moieties in flavoring compounds (e.g., trans-2-hexenol and benzyl alcohol transformed into trans-2-hexenal and benzaldehyde, respectively). Detections of formaldehyde-GSH and trans-2-hexenal-GSH adducts signify interactions of carbonyls with biological nucleophiles. The global reactivity descriptors (I, A, μ, η, and ω) and condensed Fukui parameters (fk0, fk-, fk+, and dual-descriptor) were computed to elucidate site reactivities of selected simple and α,β-unsaturated carbonyls found in vaping emissions. Overall, this study highlights carbonyl emissions and reactivities and their potential health risk effects associated with vaping.

Oral cavity is the first site to encounter e-cigarette (EC) or tobacco smoke. Increased gingival pigmentation can lead to aesthetic concerns and hinder successful outcomes of gingival depigmentation procedures as well as lead to color alterations in patients with dental restorations. While the effects of tobacco smoke and nicotine in increasing pigmentation in the gingiva of the smoker have been well-documented, the effects of EC on pigmentation have not been explored. Due to large variations in e-liquids from different sources, this study focused on the effects of EC liquid base constituents, propylene glycol (PG) and vegetable glycerin (VG), which are a universal constituent of all e-liquids. Effects of PG and VG solutions mixed at different ratios (0/100, 20/80, 55/45, 80/20, and 100/0 % v/v) were examined using primary human melanocytes obtained from neonatal foreskin; this cell model is representative of the physiological model of gingival melanocytes and has been used in our previous study. Results showed significant concentration-dependent cytotoxicity for all groups, although mixtures with higher PG content showed higher cytotoxicity to cells as compared to those with VG. Melanogenesis was robustly activated by PG-containing mixtures with the greatest effect obtained for 80/20 PG/VG mixture as compared to other ratios, while VG by itself did not activate melanogenesis. The activation of melanin synthesis within cells was not correlated to intracellular tyrosinase activity as that was suppressed by PG at higher ratios. Morphological changes of a multidendritic phenotype were observed in cells exposed to all PG/VG mixtures, with markedly greater effects for groups with higher PG content. Taken together, the results of this pilot study demonstrate for the first time that EC base constituents possess the capacity to significantly activate melanogenesis in human melanocytes at nontoxic concentrations, with the dominant effect obtained at a PG/VG ratio of 80/20, indicative of a nonlinear response with increasing concentrations of PG. Moreover, further studies to address the impact of PG/VG with the addition of nicotine and the effects of different EC flavors are underway. Future studies to elucidate mechanisms of increased pigmentation as well as further investigate effects in melanocytes with the presence of other oral cell types and other components of the oral microenvironment such as saliva and bacterial flora are warranted. This research emphasizes the need to reconsider the regulation of EC base constituents PG and VG as different ratios of these compounds can cause differential effects.

Abstract We investigated the effects of vegetable glycerin (VG), a main e-cigarette constituent, on endotoxin-induced acute lung injury (ALI). Mice received intratracheal administration of 30% VG in phosphate buffered saline (PBS) vehicle or only PBS (control) for 4 days. On Day 5, mice received an intratracheal instillation of lipopolysaccharide (LPS) (LPS group and VG + LPS group) or PBS (VG group and control group). Lung histopathology, expression of chemokine receptors, and regulatory signaling were analyzed 24 h after the Day 5 treatment. VG significantly increased ALI-associated histopathological and fibrotic changes in both the VG group and LPS-induced ALI mice (VG + LPS group). Immunohistochemistry (IHC) and western blot analyses revealed that VG administration resulted in upregulation of neutrophil markers [lymphocyte antigen 6 complex locus G6D (Ly6G) and myeloperoxidase (MPO)] as well as upregulation of the expression of transforming growth factor-β (TGF-β), a central mediator of fibrogenesis, in the lungs of both VG and VG + LPS groups. VG enhanced the expression of adhesion molecules [very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1)] and increased activation of p38 mitogen-activated protein kinase (p38 MAPK) to prompt neutrophil recruitment in the lungs of mice with ALI. Intraperitoneal administration of a p38 inhibitor attenuated these histopathological changes significantly as well as VG-induced upregulation in expression of Ly6G, MPO, VLA-4, VCAM-1, TGF-β, and collagen-1 in mice with ALI. In conclusion, VG enhances neutrophil chemotaxis and fibrosis and it amplifies the inflammatory response associated with LPS-induced ALI in the lungs via enhancement of p38 MAPK activity.

Oral cavity is the first site to encounter e-cigarette (EC) or tobacco smoke. Increased gingival pigmentation can lead to aesthetic concerns and hinder successful outcomes of gingival depigmentation procedures as well as lead to color alterations in patients with dental restorations. While the effects of tobacco smoke and nicotine in increasing pigmentation in the gingiva of the smoker have been well-documented, the effects of EC on pigmentation have not been explored. Due to large variations in e-liquids from different sources, this study focused on the effects of EC liquid base constituents, propylene glycol (PG) and vegetable glycerin (VG), which are a universal constituent of all e-liquids. Effects of PG and VG solutions mixed at different ratios (0/100, 20/80, 55/45, 80/20, and 100/0 % v/v) were examined using primary human melanocytes obtained from neonatal foreskin; this cell model is representative of the physiological model of gingival melanocytes and has been used in our previous study. Results showed significant concentration-dependent cytotoxicity for all groups, although mixtures with higher PG content showed higher cytotoxicity to cells as compared to those with VG. Melanogenesis was robustly activated by PG-containing mixtures with the greatest effect obtained for 80/20 PG/VG mixture as compared to other ratios, while VG by itself did not activate melanogenesis. The activation of melanin synthesis within cells was not correlated to intracellular tyrosinase activity as that was suppressed by PG at higher ratios. Morphological changes of a multidendritic phenotype were observed in cells exposed to all PG/VG mixtures, with markedly greater effects for groups with higher PG content. Taken together, the results of this pilot study demonstrate for the first time that EC base constituents possess the capacity to significantly activate melanogenesis in human melanocytes at nontoxic concentrations, with the dominant effect obtained at a PG/VG ratio of 80/20, indicative of a nonlinear response with increasing concentrations of PG. Moreover, further studies to address the impact of PG/VG with the addition of nicotine and the effects of different EC flavors are underway. Future studies to elucidate mechanisms of increased pigmentation as well as further investigate effects in melanocytes with the presence of other oral cell types and other components of the oral microenvironment such as saliva and bacterial flora are warranted. This research emphasizes the need to reconsider the regulation of EC base constituents PG and VG as different ratios of these compounds can cause differential effects. [ABSTRACT FROM AUTHOR]

We investigated the effects of vegetable glycerin (VG), a main e-cigarette constituent, on endotoxin-induced acute lung injury (ALI). Mice received intratracheal administration of 30% VG in phosphate buffered saline (PBS) vehicle or only PBS (control) for 4 days. On Day 5, mice received an intratracheal instillation of lipopolysaccharide (LPS) (LPS group and VG + LPS group) or PBS (VG group and control group). Lung histopathology, expression of chemokine receptors, and regulatory signaling were analyzed 24 h after the Day 5 treatment. VG significantly increased ALI-associated histopathological and fibrotic changes in both the VG group and LPS-induced ALI mice (VG + LPS group). Immunohistochemistry (IHC) and western blot analyses revealed that VG administration resulted in upregulation of neutrophil markers [lymphocyte antigen 6 complex locus G6D (Ly6G) and myeloperoxidase (MPO)] as well as upregulation of the expression of transforming growth factor-β (TGF-β), a central mediator of fibrogenesis, in the lungs of both VG and VG + LPS groups. VG enhanced the expression of adhesion molecules [very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1)] and increased activation of p38 mitogen-activated protein kinase (p38 MAPK) to prompt neutrophil recruitment in the lungs of mice with ALI. Intraperitoneal administration of a p38 inhibitor attenuated these histopathological changes significantly as well as VG-induced upregulation in expression of Ly6G, MPO, VLA-4, VCAM-1, TGF-β, and collagen-1 in mice with ALI. In conclusion, VG enhances neutrophil chemotaxis and fibrosis and it amplifies the inflammatory response associated with LPS-induced ALI in the lungs via enhancement of p38 MAPK activity. [ABSTRACT FROM AUTHOR]

BackgroundAs thousands of electronic cigarette (e-cigarette) refill fluids continue to be formulated and distributed, there is a growing need to understand the cytotoxicity of the flavouring chemicals and solvents used in these products to ensure they are safe. The purpose of this study was to compare the cytotoxicity of e-cigarette refill fluids/solvents and their corresponding aerosols using in vitro cultured cells.MethodsE-cigarette refill fluids and do-it-yourself products were screened in liquid and aerosol form for cytotoxicity using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The sensitivity of human pulmonary fibroblasts, lung epithelial cells (A549) and human embryonic stem cells to liquids and aerosols was compared. Aerosols were produced using Johnson Creek's Vea cartomizer style e-cigarette.ResultsA hierarchy of potency was established for the aerosolised products. Our data show that (1) e-cigarette aerosols can produce cytotoxic effects in cultured cells, (2) four patterns of cytotoxicity were found when comparing refill fluids and their corresponding aerosols, (3) fluids accurately predicted aerosol cytotoxicity 74% of the time, (4) stem cells were often more sensitive to aerosols than differentiated cells and (5) 91% of the aerosols made from refill fluids containing only glycerin were cytotoxic, even when produced at a low voltage.ConclusionsOur data show that various flavours/brands of e-cigarette refill fluids and their aerosols are cytotoxic and demonstrate the need for further evaluation of e-cigarette products to better understand their potential health effects.

Vegetable glycerin (VG) and propylene glycol (PG) serve as delivery vehicles for nicotine and flavorings in most e-cigarette (e-cig) liquids. Here, we investigated whether VG e-cig aerosols, in the absence of nicotine and flavors, impact parameters of mucociliary function in human volunteers, a large animal model (sheep), and air-liquid interface (ALI) cultures of primary human bronchial epithelial cells (HBECs). We found that VG-containing (VG or PG/VG), but not sole PG-containing, e-cig aerosols reduced the activity of nasal cystic fibrosis transmembrane conductance regulator (CFTR) in human volunteers who vaped for seven days. Markers of inflammation, including interleukin-6 (IL6), interleukin-8 (IL8) and matrix metalloproteinase-9 (MMP9) mRNAs, as well as MMP-9 activity and mucin 5AC (MUC5AC) expression levels, were also elevated in nasal samples from volunteers who vaped VG-containing e-liquids. In sheep, exposures to VG e-cig aerosols for five days increased mucus concentrations and MMP-9 activity in tracheal secretions and plasma levels of transforming growth factor-beta 1 (TGF-β1). In vitro exposure of HBECs to VG e-cig aerosols for five days decreased ciliary beating and increased mucus concentrations. VG e-cig aerosols also reduced CFTR function in HBECs, mechanistically by reducing membrane fluidity. Although VG e-cig aerosols did not increase MMP9 mRNA expression, expression levels of IL6, IL8, TGFB1, and MUC5AC mRNAs were significantly increased in HBECs after seven days of exposure. Thus, VG e-cig aerosols can potentially cause harm in the airway by inducing inflammation and ion channel dysfunction with consequent mucus hyperconcentration. [ABSTRACT FROM AUTHOR]

This comprehensive review deals with the multifaceted aspects of electronic cigarettes (e-cigarettes), examining their composition, health implications, regulatory challenges, and market dynamics. E-cigarettes, also known as vaping devices, function by warming a solution of liquid containing flavors, nicotine, and various other compounds to produce an aerosol for users to inhale. This review underscores the evolution and widespread adoption of e-cigarettes since their introduction in 2003, highlighting their appeal as alternatives to traditional tobacco smoking. The essential parts of e-cigarettes are the battery, heating element, e-liquid (or e-juice), and mouthpiece. Propylene glycol and vegetable glycerin are common ingredients in e-liquids, along with nicotine and other flavors. Concerns over the health impacts of e-cigarettes have grown, particularly in light of incidents like the e-cigarette or vaping-associated lung injury outbreak in 2019 linked to vaping-associated lung injuries. Evidence suggests that while e-cigarettes may pose fewer risks than conventional cigarettes, they are not without health consequences, including potential respiratory and cardiovascular effects. Regulatory efforts worldwide have struggled to keep pace with the rapid evolution of e-cigarettes, exacerbated by their diverse flavors and marketing strategies that appeal to youth. The review discusses global regulatory responses, including bans and restrictions, to curb youth uptake and address public health concerns. Furthermore, the rise of a black market for e-cigarettes poses additional challenges to effective regulation and tobacco control efforts. In conclusion, while e-cigarettes offer potential harm reduction benefits for adult smokers seeking alternatives to traditional tobacco products, their widespread availability and evolving landscape necessitate vigilant regulatory oversight to protect public health, especially among youth. Future research should continue to explore the long-term health impacts and efficacy of e-cigarettes as smoking elimination aids, informing evidence-based policies and interventions., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ghuman et al.)

Vegetable glycerin (VG) and propylene glycol (PG) serve as delivery vehicles for nicotine and flavorings in most e-cigarette (e-cig) liquids. Here, we investigated whether VG e-cig aerosols, in the absence of nicotine and flavors, impact parameters of mucociliary function in human volunteers, a large animal model (sheep), and air-liquid interface (ALI) cultures of primary human bronchial epithelial cells (HBECs). We found that VG-containing (VG or PG/VG), but not sole PG-containing, e-cig aerosols reduced the activity of nasal cystic fibrosis transmembrane conductance regulator (CFTR) in human volunteers who vaped for seven days. Markers of inflammation, including interleukin-6 (IL6), interleukin-8 (IL8) and matrix metalloproteinase-9 (MMP9) mRNAs, as well as MMP-9 activity and mucin 5AC (MUC5AC) expression levels, were also elevated in nasal samples from volunteers who vaped VG-containing e-liquids. In sheep, exposures to VG e-cig aerosols for five days increased mucus concentrations and MMP-9 activity in tracheal secretions and plasma levels of transforming growth factor-beta 1 (TGF-β1). In vitro exposure of HBECs to VG e-cig aerosols for five days decreased ciliary beating and increased mucus concentrations. VG e-cig aerosols also reduced CFTR function in HBECs, mechanistically by reducing membrane fluidity. Although VG e-cig aerosols did not increase MMP9 mRNA expression, expression levels of IL6, IL8, TGFB1, and MUC5AC mRNAs were significantly increased in HBECs after seven days of exposure. Thus, VG e-cig aerosols can potentially cause harm in the airway by inducing inflammation and ion channel dysfunction with consequent mucus hyperconcentration.

Propylene glycol (PG) and vegetable glycerin (VG) are common ingredients used in the preparation of various products, and notably in e-cigarette liquids. In this work, we investigated the generation of light gases from the pyrolysis of PG, VG and their mixtures. ReaxFF-MD was used to study the elementary reactions involved in the pyrolysis of PG/VG mixtures of 50/50 and 30/70 percent by volume. Main reactions included dehydration, dehydrogenation and C-C bond cleavage. In addition, we focused on the elementary reactions that form the light gases: C 2 hydrocarbons, CO, CO 2 , and H 2. Kinetic rates of PG and VG decomposition, and the Arrhenius parameters, were calculated, with errors as low as 1% with respect to pure PG and VG kinetic rate constants. Furthermore, experimental results were obtained by conducting pyrolysis experiments on PG, VG and their mixtures, in a continuous flow tube reactor at reaction temperatures ranging between 550°C and 850°C. The main gas products were predominantly CO, CH 4 , C 2 H 4 , in addition to C 2 H 6 , C 2 H 2 , H 2 , and CO 2. Gas product concentrations increased with temperature except for ethane, which underwent further decomposition, as expected from the elementary reactions. Liquid mixtures proved to produce more products due to reactions taking place between the different pyrolysis products obtained from PG and VG, as shown by ReaxFF-MD simulations. • Pyrolysis of PG/VG mixtures were studied using MD simulations and experiments. • Elementary reactions in ReaxFF-MD gave methane, C2 hydrocarbons, CO, CO 2 and H 2 • CO, CH 4 , and C 2 H 4 were the most significant products during experiments. • C 2 H 6 , C 2 H 2 , H 2 , and CO 2 were detected but at low concentrations. • Kinetic rates of PG/VG mixtures decompositions were comparable to pure liquids. [ABSTRACT FROM AUTHOR]

AimsTo measure the systemic retention of nicotine, propylene glycol (PG) and vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics.DesignE-cigarette users recruited over the internet participated in a 1-day research ward study. Subjects took 15 puffs from their usual brand of e-cigarette. Exhaled breath was trapped in gas-washing bottles and blood was sampled before and several times after use.SettingSan Francisco, California, USA.ParticipantsThirteen healthy, experienced adult e-cigarette users (six females and seven males).MeasurementsPlasma nicotine was analyzed by gas chromatography-mass spectrometry (GC-MS/MS) and nicotine, VG and PG in e-liquids and gas traps were analyzed by LC-MS/MS. Heart rate changes and subjective effects were assessed.FindingsE-cigarettes delivered an average of 1.33 (0.87-1.79) mg [mean and 95% confidence interval (CI)] of nicotine, and 93.8% of the inhaled dose, 1.22 (0.80-1.66) was systemically retained. Average maximum plasma nicotine concentration (Cmax ) was 8.4 (5.4-11.5) ng/ml and time of maximal concentration (Tmax ) was 2-5 minutes. One participant had Tmax of 30 minutes. 84.4% and 91.7% of VG and PG, respectively, was systemically retained. Heart rate increased by an average of 8.0 beats per minute after 5 minutes. Withdrawal and urge to smoke decreased and the e-cigarettes were described as satisfying.ConclusionsE-cigarettes can deliver levels of nicotine that are comparable to or higher than typical tobacco cigarettes, with similar systemic retention. Although the average maximum plasma nicotine concentration in experienced e-cigarette users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential.

Objectives: Electronic cigarette (ECIG)-generated aerosol contains particulate matter with a diameter less than 2.5 microns (PM2.5). Particles of this size may be injurious to the health of those who inhale them. Few studies have assessed the relationship between ECIG aerosol PM2.5 and ECIG liquid ingredients or ECIG device power. Methods: Two studies were conducted in which participants generated aerosols with ECIGs. In one, ECIG liquids contained various vegetable glycerin/propylene glycol ratios; in the other, ECIG devices varied by electrical power output. Results: Results indicate that, in general, PM2.5 increases as the ratio of vegetable glycerin to propylene glycol increases, or as device power increases. Conclusions: Regulating ECIG PM2.5 emissions to protect non-users requires an understanding of all the factors that influence these emissions. [ABSTRACT FROM AUTHOR]

Information on the effects of propylene glycol (PG) and vegetable glycerin (VG) and on cytotoxicity and subsequent activation of the biological mediators is limited in periodontal diseases. This study analyzes the effect of unflavored PG/VG alone or in combination with nicotine on gingival epithelial cells. The cells were exposed to different PG/VG (± nicotine) concentrations for 24 h and cytotoxicity was evaluated by calorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromid assay. The expressions of interleukin (IL)-6, IL-8, and matrix metalloproteinases (MMPs)-9 were measured using an enzyme-linked immunosorbent assay and a western blotting. Stimulation with PG/VG mixtures reduced cell viability compared to nonexposed controls (p < 0.05). Adding PG/VG increased the levels of IL-6, IL-8, and MMP-9, and the amount of PG had more biological impact compared to the VG amount. The nicotine augmented this effect compared to its nicotine-free counterparts. In western blotting result, MMP-9 was clearly activated in almost all samples. These findings suggest that the main constituents PG/VG are cytotoxic and able to induce biological response in gingival cells in vitro. Despite being advertised as less harmful than conventional cigarettes, electronic cigarette liquid pose certain risks on periodontal cells. Awareness about the effects of electronic cigarettes on periodontal diseases must be increased. [ABSTRACT FROM AUTHOR]

It has been demonstrated that propylene glycol (PG), vegetable glycerin (VG), and flavoring chemicals can thermally degrade to form carbonyls during vaping, but less is known about carbonyl emissions produced by transformation of flavoring chemicals and the interactive effects among e-liquid constituents. This study characterized carbonyl composition and levels in vaping emissions of PG-VG (e-liquid base solvents) and four e-liquid formulations flavored with trans-2-hexenol, benzyl alcohol, l-(-)-menthol, or linalool. Utilizing gas chromatography (GC)- and liquid chromatography (LC)-mass spectrometry (MS) methods, 14 carbonyls were identified and quantified. PG-VG emitted highest levels of formaldehyde, acetaldehyde, and acrolein. However, flavored e-liquids contributed to the production of a wider variety of carbonyls, with some carbonyls directly corresponding to the oxidation of alcohol moieties in flavoring compounds (e.g., trans-2-hexenol and benzyl alcohol transformed into trans-2-hexenal and benzaldehyde, respectively). Detections of formaldehyde-GSH and trans-2-hexenal-GSH adducts signify interactions of carbonyls with biological nucleophiles. The global reactivity descriptors (I, A, μ, η, and ω) and condensed Fukui parameters (fk0, fk−, fk+, and dual-descriptor) were computed to elucidate site reactivities of selected simple and α,β-unsaturated carbonyls found in vaping emissions. Overall, this study highlights carbonyl emissions and reactivities and their potential health risk effects associated with vaping.

Objectives: We evaluated urine propylene glycol (PG) and vegetable glycerin (VG) as potential markers for discriminating e-cigarette (ECIG) users and non-users and verifying ECIG abstinence. Methods: We analyzed urine samples from 51 ECIG users (collected pre-/post-12-hour ECIG abstinence), and 50 controls (nicotine/tobacco non-users) urine cotinine, PG, and VG concentration. Results: Of 42 ECIG users with pre-abstinence urine cotinine indicating nicotine use, mean (SD) urine cotinine concentration was 1053.7 ng/ml (874.5) and for controls was 1.93 ng/ml (0.4); after abstinence, ECIG users' mean cotinine decreased to 615.4 ng/ml (753.0). For ECIG users, mean urine PG pre-abstinence was 25.6 mcg/ml (20.0) and was 9.8 mcg/ml (13.5) for controls; after abstinence, ECIG users' mean urine PG decreased to 9.7 mcg/ml (15.0; ps < .05). For ECIG users, mean urine VG pre-abstinence was 7.5 mcg/ml (7.1) and was 13.2 mcg/ml (25.0) for controls; after abstinence, ECIG users' mean VG decreased to 5.0 mcg/ml (4.4; ps < .05). Conclusions: ECIG users' mean urine PG was greater than controls and decreased after 12-hour ECIG abstinence suggesting urine PG may be useful for discriminating ECIG users from non-users and verifying short-term abstinence. [ABSTRACT FROM AUTHOR]

Rationale: Electronic nicotine delivery systems (ENDS or e-cigarettes) share salient features of combustible smoking, such as inhalation and exhalation behaviors, and evidence indicates that first- and second-generation ENDS generalize as smoking cues. The present study examined whether newer, tank-based third-generation ENDS ("mods") also evoke smoking urges, and whether enhancing the visibility of exhaled aerosol clouds—by increasing the e-liquid vegetable glycerin (VG) content—strengthens the cue salience of ENDS. Objectives: The objective was to assess the role of exhaled aerosol clouds on ENDS cue potency using a standardized laboratory paradigm designed to mimic real-world exposures. Methods: Using a mixed design, young adult smokers (n = 50; mean age 26.5 years; ≥ 5 cigarettes/day) observed a study confederate drinking bottled water (control cue) and vaping an ENDS mod containing e-liquid with either high (73%) or low (0%) VG. Participants completed the Brief Questionnaire on Smoking Urges (BQSU) and visual analog scales (VAS) assessing cigarette and e-cigarette desire pre- and post-cue exposure. Results: Increasing the e-liquid content of VG enhanced the size and visibility of the exhaled aerosol clouds and evoked a greater increase in smoking desire and a more sustained increase in e-cigarette desire relative to the low VG cue. Both cues elicited increases in smoking urges. These results remained after controlling for sex, prior ENDS experience, recent smoking behavior, and menthol preference. Conclusions: Observation of tank-based ENDS use generalizes as a smoking cue and its cue salience is strengthened by increasing the e-liquid content of VG to enhance the visibility of the exhaled aerosol cloud. [ABSTRACT FROM AUTHOR]

Background Electronic cigarettes (ECIGs) are a class of tobacco products that produce different effects (e.g., nicotine delivery), depending on the device, liquid, and behavioral factors. However, the influence of the two primary ECIG liquid solvents, propylene glycol (PG) and vegetable glycerin (VG), on ECIG acute effects is unknown. Methods Thirty ECIG-experienced, ≥12-h nicotine- abstinent participants completed four conditions consisting of two ECIG-use bouts (10 puffs, 30 s interpuff-interval) differing only by liquid PG:VG ratio (2PG:98VG, 20PG:80VG, 55PG:45VG, 100PG). Device power (7.3 W) and liquid nicotine concentration (18 mg/ml) remained constant. Nicotine delivery, subjective effects, heart rate (HR), and puff topography were assessed. Results In the 100PG condition, participants took shorter and smaller puffs but obtained significantly more nicotine relative to the two VG-based conditions. Total nicotine exposure (i.e., area under the curve) was also significantly higher during use of the two PG-based liquids. However, participants reported that the 100 PG liquid was significantly less “pleasant” and “satisfying” relative to the other liquids (all p s < .05). Increases in HR and decreases in abstinence symptoms (e.g., “craving”) did not differ across conditions. Conclusions PG:VG ratio influenced nicotine delivery, some subjective effects, and puff topography. Lower overall product satisfaction associated with the 100PG liquid suggests factors other than nicotine delivery (e.g., aerosol visibility) may play a role in maintaining ECIG use. Regulating ECIG acute effects such as nicotine delivery and subjective effects may require simultaneous attention to liquid PG:VG ratio as well as device, liquid, and behavioral factors known to influence these outcomes. [ABSTRACT FROM AUTHOR]

Introduction The power output of e-cigarettes varies considerably, as does the composition of liquids used with these products. Most e-cigarette liquids contain two primary solvents: propylene glycol (PG) and vegetable glycerin (VG). The primary aim of this study was to examine the extent to which PG and VG composition and device power interact with each other to influence e-cigarette nicotine emissions. Methods Aerosols were generated using a 2nd generation e-cigarette and an automatic smoking machine. Nicotine was measured in aerosols, via gas chromatography, produced from three solutions containing pure PG, pure VG, or a mixture of both solvents (50:50) across three different power settings (4.3, 6.7, and 9.6 W). Results At the lowest power setting, nicotine yield increased significantly as more PG was added to the solution. However, as device power was increased, differences in nicotine yield across liquids became less pronounced. At the highest power setting (9.6 W), nicotine yields did not differ across the three liquids examined. Conclusions The present study demonstrated that the extent to which e-cigarette liquid PG and VG composition influences nicotine emissions is dependent on device power. Thus, device power may influence e-cigarette nicotine emissions to a greater degree relative to solvent concentrations. [ABSTRACT FROM AUTHOR]

An analytical method was developed for the parallel quantitation of nicotine (Nic) and two key solvents (propylene glycol (PG) and vegetable glycerin (VG)) in e-cigarette (EC) liquids before vaping and from aerosols after vaping. For analysis of the EC refill solutions, the samples were diluted by a factor of about 100 in methanol. The aerosol samples generated by a modified international puffing protocol were initially collected on Cambridge filter pads and extracted with methanol. Both types of samples were analyzed by a gas chromatography-flame ionization detector (GC-FID) together with the mass change tracking (MCT) procedure introduced in our earlier study. The recovery of all three target components (Nic/PG/VG) in both EC liquid and aerosol samples was assessed after spiking Nic at four different concentrations (2, 5, 10, and 20 mg g − 1 ) in the e-solutions (prepared in the laboratory at three different PG:VG mass ratios of 10:0, 5:5, and 0:10). The method recoveries of Nic, PG, and VG in the e-liquid samples were 96.0 ± 1.0, 96.0 ± 1.2, and 101.4 ± 6.9%, respectively, while those in the aerosol samples were slightly lower at 94.7 ± 5.6, 85.5 ± 3.0, and 91.4 ± 15.7%, respectively. The amounts of VG and Nic in the e-liquid had a significant influence on the emission factors of PG, VG, and Nic. The detection limit values (ng) were 0.36 (Nic), 0.72 (PG), and 8.15 (VG) for the liquid samples and 0.51 (Nic), 0.96 (PG), and 3.99 (VG) for the aerosol samples. Overall, this method was reliable enough to determine each target in both liquid and aerosol samples. [ABSTRACT FROM AUTHOR]

• A scaled-model experimental setup of electronic cigarette was designed and built. • Average vaporization rate is linearly and positively correlated with heating power. • Effective thermal efficiency for PG was relatively higher than that of VG. Due to the limitations of encapsulation structure and small size, it is difficult to measure the atomization temperatures of electronic cigarettes. In order to explore the thermodynamic characteristics of electronic cigarettes more conveniently, we designed and built a scaled-model experimental setup based on similarity theory. The scaled-model experiment provided a new idea for the temperature measurements of electronic cigarettes. The thermodynamic natures of propylene glycol (PG) and vegetable glycerin (VG) were analyzed from the view of thermophysical parameters. Under the same heating power and puffing topography condition, the temperature rising rate of VG was higher than that of PG at the later heating stage. The average vaporization rate and effective thermal efficiency of PG were relatively larger than those of VG. The effective thermal efficiency and average vaporization rate of PG and VG were linearly and positively correlated with the heating power in the range of 2∼10 W. [ABSTRACT FROM AUTHOR]

• The major components in liquid and aerosol samples of E-cigarettes were analyzed. • The measured nicotine contents were 1.2 times higher than those provided by the manufacturers. • The consumption rate of PG and nicotine decreased with the increasing voltage from 3.4 to 4.8 V. • The amounts of PG/VG generated from E-cigarettes are much larger than other comparable products. Generally, the liquid used in electronic cigarettes (E-cigarettes), which is also called E-liquid, is composed of propylene glycol (PG), vegetable glycerin (VG), and nicotine, with many other miscellaneous ingredients. E-liquid is consumed mainly in the form of aerosol via inhalation by the e-cigarette user. The amount and composition of the aerosol generated during its consumption depend on various factors. In this study, the three major constituents (PG, VG, and nicotine) of E-cigarettes were analyzed in both liquid and aerosol samples from 50 commercial products. Their concentrations in the liquid (and aerosol at 3.4 V) samples were 538 (4 6 7), 482 (4 4 9), and 8.75 mg g−1 (7.91 mg g−1), respectively. The nicotine levels in the E-liquids measured in this study were normally 1.2 times greater than those specified by the manufacturers. Furthermore, the amount of liquid consumed increased proportionally as the voltage of the E- cigarette increased. The consumption rate of VG increased as the voltage of the E-cigarette increased, whereas that of PG and nicotine decreased. The results of our study confirm that the amounts of PG and VG generated through the use of E-cigarettes are noticeably larger than those from other tobacco products (such as traditional tobaccos and heat-not-burn products), although no such trend was evident in case of nicotine. [ABSTRACT FROM AUTHOR]