Search Results (28)

Electronic cigarette (ECIG) liquids are marketed with labeled nicotine concentrations and propylene glycol (PG) to vegetable glycerin (VG) ratios, yet quality control inconsistencies may alter vaping emissions. We quantified discrepancies between labeled and measured chemical content and evaluated how these differences affect emissions of particulate matter with an aerodynamic diameter of 2.5 µm or smaller (PM_2.5). Flavor-free liquids (n = 20) spanning nicotine labels of 0, 9, 18, and 48 mg/mL and PG content from 0% to 80% were purchased. Nuclear magnetic resonance spectroscopy measured nicotine, PG, and VG. Aerosols were generated using a standardized device in a controlled exposure chamber. PM_2.5 was measured using a pDR-1500 and SMPS/APS, with gravimetric correction factors calculated. Labeling inaccuracies were widespread: “nicotine-free” liquids contained 0.1 to 0.4 mg/mL nicotine, and labeled nicotine deviated by up to ±30%. PG/VG ratios were frequently incorrect; 70% of samples contained higher VG than labeled, including “100% VG” products with about 10% PG. Higher VG consistently increased PM_2.5 mass, while nicotine had a minimal effect. The pDR overestimated mass, whereas SMPS/APS underestimated due to volatilization losses. Overall, inaccurate ECIG liquid labeling can alter measured PM_2.5 emissions under controlled conditions. Full article

Background and Objectives: The rising popularity of new-generation electronic cigarettes (e-cig) like JUUL necessitates a better understanding of their impact on respiratory and other body systems, as the effects of JUUL’s components remain unclear. This study aimed to investigate the effects of JUUL components on ion channels and airway surface liquid (ASL) height in human bronchial epithelial cells (HBECs). Furthermore, the cytotoxic effects of these components were investigated in human embryonic kidney 293T (HEK293T) cells. Materials and Methods: The components tested included nicotine salt (NicSalt), benzoic acid (BA), sodium hydrogen tartrate (NaTar), propylene glycol/vegetable glycerin (PG/VG), freebase nicotine (FBNic) and nicotine salt+benzoic acid (NicSalt+BA). Each component was prepared at 100 µM, and HBECs were exposed for 24 h to measure ASL height, short-circuit current (I_sc), and transepithelial electrical resistance (TEER). Results: Initial exposure (0 h) to these substances did not significantly alter ASL height. However, after 2 h, FBNic-treated HBECs exhibited a significant reduction in ASL height compared to NicSalt and other tested substances, with the most pronounced decrease observed at the 6th hour. This effect persisted over prolonged exposure, suggesting a cumulative impact on airway hydration and epithelial function. Additionally, adenosine administration did not induce a significant increase in ASL height. NicSalt, BA, and FBNic were found to disrupt ion balance in HBECs, affecting ion channels and ASL homeostasis while significantly decreasing TEER. In terms of cytotoxicity, NicSalt, and benzoic acid demonstrated minimal cytotoxicity at low concentrations, whereas FBNic showed significantly higher cytotoxicity at moderate levels. Conclusions: In conclusion, this study highlights that e-cigarette components can disrupt airway surface liquid homeostasis by affecting ion channel activity, compromise epithelial barrier integrity by reducing transepithelial electrical resistance, and emphasize the importance of their cytotoxic effects. Full article

Background: Acute and chronic sinusitis significantly impact patients’ quality of life. Effective drug delivery to paranasal sinuses is crucial for treating these conditions. However, medications from conventional devices like nasal drops, sprays, and nebulized mists often fail to penetrate the small ostia and reach the sinuses. This study aims to assess the effectiveness of e-vape-generated aerosols entering and filling paranasal sinus cavities, particularly the maxillary sinus. Methods: The aerosol droplets were generated using an electronic vaporizer (e-vape) and were composed solely of vegetable glycerin (VG) and propylene glycol (PG). Patient-specific, transparent nose-sinus models, including one with post-uncinectomy surgery, were used to evaluate the effectiveness of these e-vape-generated VG-PG aerosols in entering the sinuses under unidirectional and bidirectional airflow conditions. Visualizations from various nasal model views and lighting conditions were recorded. Particle size distribution measurements of the e-vape aerosol were conducted using a laser diffraction particle size analyzer. Results: E-vape-generated VG-PG droplets effectively enter paranasal sinuses under specific administration conditions. E-vape aerosol droplet size measurements revealed a mean particle size ranging from 2.895 to 3.359 μm, with a median particle size (D50) averaging 2.963 μm. The speed of aerosol entering the paranasal sinuses is directly proportional to the ostia size; larger ostia result in faster sinus entry. A continuous moderate flow is necessary to gradually fill the paranasal sinus cavities. The aerosol entry into sinuses was observed at 2 L/min and decreased with increasing flow rate. The mechanisms of aerosol entry involve maintaining a positive pressure gradient across the ostial canal, a non-equilibrium transverse pressure distribution, and a two-way flow through the ostium. Gravitational forces and recirculation currents further enhance the deposition of e-vape aerosols. Comparative tests showed that traditional delivery devices exhibited limited penetration into paranasal sinuses. Conclusions: This study demonstrated that e-vape-generated aerosols could serve as a vehicle for delivering active pharmaceutical ingredients (APIs) directly to the paranasal sinuses, improving treatment outcomes. Full article

The objective of this study is to investigate the potential mutagenic effects of the exposure of mice to aerosols produced from the component liquids of an electronic nicotine delivery system (ENDS). The use of electronic cigarettes (e-cigs) and ENDSs has increased tremendously over the past two decades. From what we know to date, ENDSs contain much lower levels of known carcinogens than tobacco smoke. While conventional tobacco smoke is a well-established mutagen, little is known about the mutagenicity of ENDS aerosols. Here, we report the mutagenic effects of a 3-month whole body exposure of C57 lacI mice (BigBlue^TM) to filtered air (AIR) or ENDS aerosols in several tissues. Aerosols were generated from a 50/50 vegetable glycerin (VG)/propylene glycol (PG) mixture with and without nicotine. The results revealed that in the lung, bladder urothelial tissue, and tongue, mutagenesis was significantly greater in the VG/PG/nicotine group than in the AIR group. In all organs except the bladder, mutagenesis in the VG/PG only group was similar to those exposed to AIR. In the bladder, mutagenesis in the VG/PG group was elevated compared to that in the AIR group. In the liver, mutagenesis was modestly elevated in the VG/PG/nicotine group, but the elevation failed to reach statistical significance. Overall, there were no consistent differences in mutagenesis between the sexes. The results of this study suggest that exposure to e-cig aerosols containing nicotine represents a risk factor for carcinogenesis in several organ systems, and exposure to VG/PG alone may be a risk factor for bladder cancer. Full article

The use of E-cigarettes, often considered a safer alternative to traditional smoking, has been associated with high rates of cellular toxicity, genetic alterations, and inflammation. Neuroinflammatory impacts of cigarette smoking during pregnancy have been associated with increased risks of adverse childhood health outcomes; however, it is still relatively unknown if the same propensity is conferred on offspring by maternal vaping during gestation. Results from our previous mouse inhalation studies suggest such a connection. In this earlier study, pregnant C57BL/6 mice were exposed daily to inhaled E-cig aerosols (i.e., propylene glycol and vegetable glycerin, [PG/VG]), with or without nicotine (16 mg/mL) by whole-body inhalation throughout gestation (3 h/d; 5 d/week; total ~3-week) and continuing postnatally from post-natal day (PND) 4–21. As neuroinflammation is involved in the dysregulation of glucose homeostasis and weight gain, this study aimed to explore genes associated with these pathways in 1-mo.-old offspring (equivalent in humans to 12–18 years of age). Results in the offspring demonstrated a significant increase in glucose metabolism protein levels in both treatment groups compared to filtered air controls. Gene expression analysis in the hypothalamus of 1 mo. old offspring exposed perinatally to E-cig aerosols, with and without nicotine, revealed significantly increased gene expression changes in multiple genes associated with neuroinflammation. In a second proof-of-principal parallel study employing the same experimental design, we shifted our focus to the hippocampus of the postpartum mothers. We targeted the mRNA levels of several neurotrophic factors (NTFs) indicative of neuroinflammation. While there were suggestive changes in mRNA expression in this study, levels failed to reach statistical significance. These studies highlight the need for ongoing research on E-cig-induced alterations in neuroinflammatory pathways. Full article

Heated Tobacco Products (HTPs) purport to reduce exposure to tobacco-related toxicants compared to combustible cigarettes. This cross-sectional study examined the content of nicotine, two humectants (propylene glycol (PG) and vegetable glycerin (VG)), and four tobacco-specific nitrosamines (TSNAs: NNN, NNK, NAT, and NAB) in the tobacco filler of a popular HTP brand (IQOS). Non-menthol and menthol IQOS sticks were purchased from nine countries between 2017 and 2020 and were classified into two versions (“Bold” and “Light”) using Philip Morris’s flavor descriptors. The average nicotine concentration was 4.7 ± 0.5 mg/stick, and the highest nicotine concentration was found in products from Japan (5.1 ± 0.2 mg/stick). VG was the dominant humectant found in all sticks, with an average concentration of (31.5 ± 2.3 mg/stick). NNN, NNK, and NAT were substantially higher in the “Bold” sticks than the “Light” sticks. Significant differences between countries for TSNAs were also observed: the NAT and NAB contents were the highest in the “Light” products from Canada (192.5 ± 24.1 and 22.9 ± 1.0 ng/stick, respectively); the NNK concentration was the highest in the “Bold” products from Poland (64.8 ± 7.9 ng/stick); and the highest NNN concentrations were observed in the “Bold” products from South Africa (488.9 ± 26.7 ng/stick). As NNN and NNK are known human carcinogens, and as humectants like PG and VG can degrade into toxic carbonyl compounds upon heating, monitoring the concentration of these chemicals in HTPs is important for protecting users’ health and ensuring compliance with regulations. Full article

Tobacco smoking remains one of the leading causes of premature death worldwide. Electronic Nicotine Delivery Systems (ENDSs) are proposed as a tool for smoking cessation. In the last few years, a growing number of different types of ENDSs were launched onto the market. Despite the manufacturing differences, ENDSs can be classified as “liquid e-cigarettes” (e-cigs) equipped with an atomizer that vaporizes a liquid composed of vegetable glycerin (VG), polypropylene glycol (PG), and nicotine, with the possible addition of flavorings; otherwise, the “heated tobacco products” (HTPs) heat tobacco sticks through contact with an electronic heating metal element. The presence of some metals in the heating systems, as well as in solder joints, involves the possibility that heavy metal ions can move from these components to the liquid, or they can be adsorbed into the tobacco stick from the heating blade in the case of HTPs. Recent evidence has indicated the presence of heavy metals in the refill liquids and in the mainstream such as arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), copper (Cu), and lead (Pb). The present review discusses the toxicological aspects associated with the exposition of heavy metals by consumption from ENDSs, focusing on metal carcinogenesis risk. Full article

Early detection and timely intervention play a vital role in the effective management of Alzheimer’s disease. Currently, the diagnostic accuracy for Alzheimer’s disease based on a single blood biomarker is relatively low, and the combined use of multiple blood biomarkers can greatly improve diagnostic accuracy. Herein, we report a printed electrochemical biosensor based on vertical graphene (VG) modified with gold nanoparticles (VG@nanoAu) for the simultaneous detection of four Alzheimer’s disease blood biomarkers. The printed electrochemical electrode array was constructed by laser etching and inkjet printing. Then gold nanoparticles were modified onto the working electrode surface via electrodeposition to further improve the sensitivity of the sensor. In addition, the entire printed electrochemical sensing system incorporates an electrochemical micro-workstation and a smartphone. The customized electrochemical micro-workstation incorporates four electro-chemical control chips, enabling the sensor to simultaneously analyze four biomarkers. Consequently, the printed electrochemical sensing system exhibits excellent analytical performance due to the large surface area, biocompatibility, and good conductivity of VG@nanoAu. The detection limit of the sensing system for Aβ40, Aβ42, T-tau, and P-tau181 was 0.072, 0.089, 0.071, and 0.051 pg/mL, respectively, which meets the detection requirements of Alzheimer’s disease blood biomarkers. The printed electrochemical sensing system also exhibits good specificity and stability. This work has great value and promising prospects for early Alzheimer’s disease diagnosis using blood biomarkers. Full article

Despite claims of safety or harm reduction for electronic cigarettes (E-cig) use (also known as vaping), emerging evidence indicates that E-cigs are not likely safe, or necessarily safer than traditional cigarettes, when considering the user’s risk of developing vascular dysfunction/disease. E-cigs are different from regular cigarettes in that E-cig devices are highly customizable, and users can change the e-liquid composition (such as the base solution, flavors, and nicotine level). Since the effects of E-cigs on the microvascular responses in skeletal muscle are poorly understood, we used intravital microscopy with an acute (one-time 10 puff) exposure paradigm to evaluate the individual components of e-liquid on vascular tone and endothelial function in the arterioles of the gluteus maximus muscle of anesthetized C57Bl/6 mice. Consistent with the molecular responses seen with endothelial cells, we found that the peripheral vasoconstriction response was similar between mice exposed to E-cig aerosol or cigarette smoke (i.e., 3R4F reference cigarette); this response was not nicotine dependent, and endothelial cell-mediated vasodilation was not altered within this acute exposure paradigm. We also report that, regardless of the base solution component [i.e., vegetable glycerin (VG)-only or propylene glycol (PG)-only], the vasoconstriction responses were the same in mice with inhalation exposure to 3R4F cigarette smoke or E-cig aerosol. Key findings from this work reveal that some component other than nicotine, in inhaled smoke or aerosol, is responsible for triggering peripheral vasoconstriction in skeletal muscle, and that regardless of one’s preference for an E-cig base solution composition (i.e., ratio of VG-to-PG), the acute physiological response to blood vessels appears to be the same. The data suggest that vaping is not likely to be ‘safer’ than smoking towards blood vessels and can be expected to produce and/or result in the same adverse vascular health outcomes associated with smoking cigarettes. Full article

The E-cigarette has been promoted as an alternative nicotine delivery device with potentially fewer toxicant emissions. The objective of this review is to summarize the current knowledge on the particle size distribution (PSD) of e-cigarette emissions and to analyze the knowledge gaps between existing particle size measurements and the vision toward harm reduction from e-cigarette use. Here, we focus on firstly describing the physical parameters used to characterize PSD, followed by comparing particle size measurement approaches, investigating the factors that impact the PSD of e-cigarette mainstream aerosols, and conclude by linking size distribution to the respiratory dosimetry by demonstrating the modeling results of particle deposition in the respiratory tract. This review calls for a harmonized testing protocol to conduct inter-comparisons and further understand e-cigarette particle sizes. Among the influencing factors investigated, puff topography, operation power, flavorings, PG/VG ratio, and nicotine strength impose a substantial impact on the PSD, but the underlying mechanisms have not yet been fully investigated. The effects brought by the type of device refill and nicotine are yet inconclusive due to lack of evidence. Coil aging has no significant impact on the PSD of e-cigarette aerosols within the coil lifetime. Lastly, while computational models of particle deposition have been adopted to profile the deposition of e-cigarette mainstream emissions, existing models have limited applicability and generality when dealing with e-cigarette aerosols that have high volatility and hygroscopicity, which can dynamically evaporate or grow during the transport process. Additionally, the size-dependent chemical composition (e.g., nicotine and harmful and potentially harmful constituents) of e-cigarette aerosols is unknown, impeding the understanding of the health effects of e-cigarette use. Therefore, it is essential for future studies to bridge these knowledge gaps and unveil the mechanisms determining PSD and respiratory deposition. Full article

The use of e-cigarettes (ECs) has become increasingly popular worldwide, even though scientific results have not established their safety. Diacetyl (DA) and acetylpropionyl (AP), which can be present in ECs, are linked with lung diseases. Ethyl maltol (EM)—the most commonly used flavoring agent—can be present in toxic concentrations. Until now, there is no methodology for the determination of nicotine, propylene glycol (PG), vegetable glycerin (VG), EM, DA, and acetylpropionyl in e-liquids that can be used as a quality control procedure. Herein, gas chromatography coupled with mass spectrometry (GC-MS) was applied for the development of analytical methodologies for these substances. Two GC-MS methodologies were developed and fully validated, fulfilling the standards for the integration in a routine quality control procedure by manufacturers. As proof of applicability, the methodology was applied for the analysis of several e-liquids. Differences were observed between the labeled and the experimental levels of PG, VG, and nicotine. Three samples contained EM at higher concentrations compared to the other samples, while only one contained DA. These validated methodologies can be used for the quality control analysis of EC liquid samples regarding nicotine, PG, and VG amounts, as well as for the measurement of the EM. Full article

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. Full article

Propylene glycol (PG) and glycerin (G) are the most widely used humectants in electronic nicotine delivery system (ENDS) devices. Carbonyls are present in aerosols produced when ENDS devices heat PG and G. Whether aerosolized PG and G are innocuous to the lungs has not been established. Here, we determined the chemical profiles of ENDS aerosols containing three humectant ratios (30/70, 50/50 and 70/30, PG/VG), for three flavors (strawberry, vanilla and Catalan cream) containing either 12 or 18 mg/mL of nicotine. Additionally, we examined the in vitro toxicity of the strawberry- and vanilla-flavored ENDS aerosol in human lung epithelial cells (BEAS-2B) exposed at the air-liquid interface for 1 h. For strawberry- and vanilla-flavored aerosols produced by a 3rd-generation ENDS device with the same PG/G ratio, the e-liquid nicotine content of 12 and 18 mg/mL did not transfer to the aerosol with substantial differences in concentrations. Our data also indicate the presence of carbonyls in all three flavored e-cig aerosols analyzed, with levels exceeding 1 µg/puff for acetone, butyraldehyde, and acetaldehyde, in strawberry-, vanilla, and Catalan cream-flavored e-cig aerosols, respectively. Furthermore, closed-system ENDS of the fourth generation emitted trace levels of carbonyls in the aerosols (<0.3 µg/puff), while open-system tank-style ENDS of the third generation produced elevated levels of harmful chemicals, including acrolein (>1 µg/puff), formaldehyde (>5 µg/puff), and m- & p-tolualdehyde (>4 µg/puff). Moreover, under non-cytotoxic conditions, BEAS-2B cells exposed to strawberry-flavored aerosols exhibited significantly increased reactive oxygen and nitric oxide species (ROS/NOS) levels in cell media compared to air controls, while vanilla-flavored ENDS aerosols up-regulated the expression of pro-inflammatory and oxidative stress markers. Our data suggest (a) that ENDS aerosol chemical composition will vary based upon the presence and concentration of the initial e-liquid ingredients, with a pronounced impact of the flavoring components; and (b) short-term exposures to flavored ENDS aerosols may impair lung cells’ redox signaling in a flavor-specific manner. Full article

Flavoring chemicals in electronic nicotine delivery systems have been shown to cause cellular inflammation; meanwhile, the effects of fruit and tobacco flavors on lung inflammation by nose-only exposures to mice are relatively unknown. We hypothesized that exposure to flavored e-cigarettes would cause lung inflammation in C57BL/6 J mice. The mice were exposed to air, propylene glycol/vegetable glycerin, and flavored e-liquids: Apple, Cherry, Strawberry, Wintergreen, and Smooth & Mild Tobacco, one hour per day for three days. Quantification of flavoring chemicals by proton nuclear magnetic resonance spectroscopy (¹H NMR), differential cell counts by flow cytometry, pro-inflammatory cytokines/chemokines by ELISA, and matrix metalloproteinase levels by western blot were performed. Exposure to PG/VG increased neutrophil cell count in lung bronchoalveolar lavage fluid (BALF). KC and IL6 levels were increased by PG/VG exposure and female mice exposed to Cherry flavored e-cigarettes, in lung homogenate. Mice exposed to PG/VG, Apple, Cherry, and Wintergreen increased MMP2 levels. Our results revealed flavor- and sex-based e-cigarette effects in female mice exposed to cherry-flavored e-liquids and male mice exposed to tobacco-flavored e-liquids, namely, increased lung inflammation. Full article

Alzheimer’s disease (AD) is a long-term neurodegenerative disease that poses a serious threat to human life and health. It is very important to develop a portable quantitative device for AD diagnosis and personal healthcare. Herein, we develop a portable electrochemical sensing platform for the point-of-care detection of AD biomarkers in the blood. Such a portable platform integrates nanoAu-modified vertical graphene (VG@Au) into a working electrode, which can significantly improve sensitivity and reduce detection limit due to the large specific surface, excellent electrical conductivity, high stability, and good biocompatibility. The tau protein, as an important factor in the course of AD, is selected as a key AD biomarker. The results show that the linear range of this sensing platform is 0.1 pg/mL to 1 ng/mL, with a detection limit of 0.034 pg/mL (S/N = 3), indicating that this portable sensing platform meets the demand for the detection of the tau protein in the blood. This work offers great potential for AD diagnosis and personal healthcare. Full article