In Vitro high-throughput toxicological assessment of E-cigarette flavors on human bronchial epithelial cells and the potential involvement of TRPA1 in cinnamon flavor-induced toxicity.

Electronic cigarettes (ECs) are considered a less hazardous alternative to tobacco smoking but are not harmless. Growing concerns about the safety profiles of flavors in e-liquids underpin the need for this study. Here, we screened 53 nicotine-free flavored e-liquids (across 15 flavor categories) across a 3-point concentration range (0.25%, 0.5%, and 1% v/v) in a high-throughput fashion in human bronchial epithelial (HBEC-3KT) submerged cell cultures to identify 'toxic hits' using in vitro endpoint assays comprising cell count, cell viability, and lactate dehydrogenase (LDH). We observed significant, dose-dependent adverse effects only with cinnamon, vanilla tobacco, and hazelnut e-liquids compared to media-only and PG/VG vehicle controls. Hence, we further analyzed these three flavors for their effects on HBEC-3KT proliferation, mitochondrial health, and oxidative stress. A significant decrease in cell proliferation after 36 h was observed for each e-liquid toxic hit compared to media-only and PG/VG controls. Hazelnut (at all concentrations) and vanilla tobacco (1%) increased cytoplasmic reactive oxygen species generation compared to media-only and PG/VG controls. Conversely, all three flavors at 0.5% and 1% significantly decreased mitochondrial membrane potential compared to PG/VG and media-only controls. Chemical analysis revealed that all three flavors contained volatile organic compounds. We hypothesized that the cytotoxicity of cinnamon might be mediated via TRPA1; however, TRPA1 antagonist AP-18 (10 µM) did not mitigate these effects, and cinnamon significantly increased TRPA1 transcript levels. Therefore, pathways mediating cinnamon's cytotoxicity warrant further investigations. This study could inform public health authorities on the relative health risks assessment following exposure to EC flavor ingredients.

Vaping Dose, Device Type, and E-Liquid Flavor are Determinants of DNA Damage in Electronic Cigarette Users.

INTRODUCTION: Despite the widespread use of electronic cigarettes, the long-term health consequences of vaping are largely unknown. AIMS AND METHODS: We investigated the DNA-damaging effects of vaping as compared to smoking in healthy adults, including "exclusive" vapers (never smokers), cigarette smokers only, and nonusers, matched for age, gender, and race (N = 72). Following biochemical verification of vaping or smoking status, we quantified DNA damage in oral epithelial cells of our study subjects, using a long-amplicon quantitative polymerase chain reaction assay. RESULTS: We detected significantly increased levels of DNA damage in both vapers and smokers as compared to nonusers (p = .005 and p = .020, respectively). While the mean levels of DNA damage did not differ significantly between vapers and smokers (p = .522), damage levels increased dose-dependently, from light users to heavy users, in both vapers and smokers as compared to nonusers. Among vapers, pod users followed by mod users, and those who used sweet-, mint or menthol-, and fruit-flavored e-liquids, respectively, showed the highest levels of DNA damage. The nicotine content of e-liquid was not a predictor of DNA damage in vapers. CONCLUSIONS: This is the first demonstration of a dose-dependent formation of DNA damage in vapers who had never smoked cigarettes. Our data support a role for product characteristics, specifically device type and e-liquid flavor, in the induction of DNA damage in vapers. Given the popularity of pod and mod devices and the preferability of sweet-, mint or menthol-, and fruit-flavored e-liquids by both adult- and youth vapers, our findings can have significant implications for public health and tobacco products regulation. IMPLICATIONS: We demonstrate a dose-dependent formation of DNA damage in oral cells from vapers who had never smoked tobacco cigarettes as well as exclusive cigarette smokers. Device type and e-liquid flavor determine the extent of DNA damage detected in vapers. Users of pod devices followed by mod users, and those who use sweet-, mint or menthol-, and fruit-flavored e-liquids, respectively, show the highest levels of DNA damage when compared to nonusers. Given the popularity of pod and mod devices and the preferability of these same flavors of e-liquid by both adult- and youth vapers, our findings can have significant implications for public health and tobacco products regulation.

Effect of menthol/mint-flavored pods on young JUUL E-cigarette users' subjective experience, puffing behavior, and nicotine exposure: A pilot study.

BACKGROUND: Recent regulations have banned all flavors except menthol/mint and classic tobacco from pod-based e-cigarette devices such as JUUL. However, menthol/mint flavor can present a potential risk given its increasing popularity among young people in the US and its puffing and nicotine-enhancing properties. This study examines the impact of menthol/mint flavor manipulation on users' puffing behavior, subjective experience, and nicotine exposure among young people. METHODS: JUUL users (n = 33, 18-24 years) attended two 60-min ad libitum e-cigarette use sessions (menthol/mint flavor vs. classic tobacco flavor) in a cross-over design. Puff topography and plasma nicotine concentration were measured, and participants completed subjective experience questionnaires. RESULTS: Following the use of the menthol/mint-flavored pod, increases were observed in measures of satisfaction, pleasurable/interest to use, willingness to use again, enjoyment, urge to vape, product appeal, taste, and concentration (p < .05 for all). For example, compared to the classic tobacco flavor, participants experienced significantly more satisfaction of the product (4.24 vs. 3.09; p = .001) and sensation enjoyment of the product (3.55 vs. 2.48; p = .002) when using the menthol/mint flavor. While means of the plasma nicotine boost and puff parameters were lower in the classic tobacco condition compared to the menthol/mint flavor condition, no statistical significance was observed between the two conditions (p > .05 for all). CONCLUSIONS: Results of this pilot study suggest that menthol/mint-flavor increases e-cigarette users' subjective experience significantly. Regulating menthol/mint flavor is a potentially promising strategy to curb e-cigarette use among young people.

FDA Aims to Ban Menthol in Cigarettes.

The FDA has proposed a ban on menthol flavoring in cigarettes. If enacted, the prohibition would increase smoking cessation rates and decrease first-time tobacco use, in turn drastically reducing smoking-related cancer deaths.

Flavour chemicals, synthetic coolants and pulegone in popular mint-flavoured and menthol-flavoured e-cigarettes.

BACKGROUND: The Food and Drug Administration (FDA) has recently banned flavours from pod-style electronic cigarettes (e-cigarettes), except for menthol and tobacco. JUUL customers have quickly discovered that flavoured disposable e-cigarettes from other manufacturers, such as Puff, are readily available. Our goal was to compare flavour chemicals, synthetic coolants and pulegone in mint-flavoured/menthol-flavoured e-cigarettes from JUUL and Puff, evaluate the cytotoxicity of the coolants and perform a cancer risk assessment for pulegone, which is present in both JUUL pods and disposable Puff products. METHODS: Identification and quantification of chemicals were performed using gas chromatography/mass spectrometry. Cytotoxicity of the coolants was evaluated with BEAS-2B cells using the MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cancer risk of pulegone was calculated using the margin of exposure (MOE). RESULTS: Menthol was the dominant flavour chemical (>1 mg/mL) in all products from both manufacturers. Minor flavour chemicals (<1 mg/mL) differed in the JUUL and Puff fluids and may produce flavour accents. The concentrations of WS-3 and WS-23 were higher in Puff than in JUUL. WS-23 was cytotoxic in the MTT assay at concentrations 90 times lower than concentrations in Puff fluids. The risk of cancer (MOE<10 000) was greater for mint than for menthol products and greater for Puff than for JUUL. CONCLUSIONS: Switching from flavoured JUUL to Puff e-cigarettes may expose users to increased harm due to the higher levels of WS-23 and pulegone in Puff products. Cancer risk may be reduced in e-cigarettes by using pure menthol rather than mint oils to produce minty-flavoured e-cigarette products.

Patch Testing to Carvone: North American Contact Dermatitis Group Experience, 2009 to 2018.

BACKGROUND/OBJECTIVES: Carvone, a flavoring agent, may cause allergic contact dermatitis. This study summarizes patch test reactions to carvone in patients tested by the North American Contact Dermatitis Group, 2009 to 2018. METHODS: This was a retrospective analysis of patients positive to carvone (5% petrolatum). Demographics were compared with those of patients who were negative. Other analyses included reaction strength, clinical relevance, coreactivity with other fragrance/flavor allergens, and exposure sources. RESULTS: Of 24,124 patients tested to carvone, 188 (0.78%) were positive. As compared with carvone-negative patients, carvone-positive patients were significantly more likely older than 40 years (P = 0.0284). Women (76.1%) and/or facial involvement (33.0%) were common in the carvone-positive group but not statistically different from carvone-negative patients; 73.3% (n = 138) of the reactions were currently relevant. Relevant sources were personal care products (46.3%, n = 87) and food (14.3%, n = 27). Coreactivity with other fragrance/flavor markers was present in 60.6% of carvone-positive patients, most commonly fragrance mix I (34.6%), balsam of Peru (24.5%), and cinnamic aldehyde (15.4%). CONCLUSIONS: Ten-year prevalence of carvone sensitivity was 0.78%. Most carvone-positive patients were female, were older than 40 years, and/or had facial dermatitis. Personal care products were the most common source. Two-fifths of carvone reactions would have been missed by relying on other fragrance/flavoring allergens.

E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos.

Environmental teratogens such as smoking are known risk factors for developmental disorders such as cleft palate. While smoking rates have declined, a new type of smoking, called vaping is on the rise. Vaping is the use of e-cigarettes to vaporize and inhale an e-liquid containing nicotine and food-like flavors. There is the potential that, like smoking, vaping could also pose a danger to the developing human. Rather than waiting for epidemiological and mammalian studies, we have turned to an aquatic developmental model, Xenopus laevis, to more quickly assess whether e-liquids contain teratogens that could lead to craniofacial malformations. Xenopus, like zebrafish, has the benefit of being a well-established developmental model and has also been effective in predicting whether a chemical could be a teratogen. We have determined that embryonic exposure to dessert flavored e-liquids can cause craniofacial abnormalities, including an orofacial cleft in Xenopus. To better understand the underlying mechanisms contributing to these defects, transcriptomic analysis of the facial tissues of embryos exposed to a representative dessert flavored e-liquid vapor extract was performed. Analysis of differentially expressed genes in these embryos revealed several genes associated with retinoic acid metabolism or the signaling pathway. Consistently, retinoic acid receptor inhibition phenocopied the craniofacial defects as those embryos exposed to the vapor extract of the e-liquid. Such malformations also correlated with a group of common differentially expressed genes, two of which are associated with midface birth defects in humans. Further, e-liquid exposure sensitized embryos to forming craniofacial malformations when they already had depressed retinoic acid signaling. Moreover, 13-cis-retinoic acid treatment could significantly reduce the e-liquid induced malformation in the midface. Such results suggest the possibility of an interaction between retinoic acid signaling and e-liquid exposure. One of the most popular and concentrated flavoring chemicals in dessert flavored e-liquids is vanillin. Xenopus embryos exposed to this chemical closely resembled embryos exposed to dessert-like e-liquids and a retinoic acid receptor antagonist. In summary, we determined that e-liquid chemicals, in particular vanillin, can cause craniofacial defects potentially by dysregulating retinoic acid signaling. This work warrants the evaluation of vanillin and other such flavoring additives in e-liquids on mammalian development.

Factors Associated With the Use of a Salt Substitute in Rural China.

Importance: Lowering sodium intake reduces blood pressure and may reduce the risk of cardiovascular diseases. The use of reduced-sodium salt (a salt substitute) may achieve sodium reduction, but its effectiveness may be associated with the context of its use. Objective: To identify factors associated with the use of salt substitutes in rural populations in China within the Salt Substitute and Stroke Study, a large-scale cluster randomized trial. Design, Setting, and Participants: This sequential mixed-methods qualitative evaluation, conducted from July 2 to August 28, 2018, in rural communities across 3 provinces in China, included a quantitative survey, collection of 24-hour urine samples, and face-to-face interviews. A random subsample of trial participants, selected from the 3 provinces, completed the quantitative survey (n = 1170) and provided urine samples (n = 1025). Interview respondents were purposively selected from the intervention group based on their different ranges of urinary sodium excretion levels. Statistical analysis was performed from September 18, 2018, to February 22, 2019. Exposures: The intervention group of the Salt Substitute and Stroke Study was provided with the free salt substitute while the control group continued to use regular salt. Main Outcomes and Measures: Knowledge, attitudes, and behaviors regarding the use of the salt substitute were measured using quantitative surveys, and urinary sodium levels were measured using 24-hour urine samples. Contextual factors were explored through semistructured interviews and integrated findings from surveys and interviews. Results: A total of 1170 individuals participated in the quantitative survey. Among the 1025 participants with successful urine samples, the mean (SD) age was 67.4 (7.5) years, and 502 (49.0%) were female. The estimated salt intake of participants who believed that high salt intake was good for health was higher; however, it was not significantly different (0.84 g/d [95% CI, -0.04 to 1.72 g/d]) from those who believed that high salt intake was bad for health. Thirty individuals participated in the qualitative interviews (18 women [60.0%]; mean [SD] age, 70.3 [6.0] years). Quantitative and qualitative data indicated high acceptability of and adherence to the salt substitute. Contextual factors negatively associated with the use of the salt substitute included a lack of knowledge about the benefits associated with salt reduction and consumption of high-sodium pickled foods. In addition, reduced antihypertensive medication was reported by a few participants using the salt substitute. Conclusions and Relevance: This study suggests that lack of comprehensive understanding of sodium reduction and salt substitutes and habitual consumption of high-sodium foods (such as pickled foods) were the main barriers to the use of salt substitutes to reduce sodium intake. These factors should be considered in future population-based, sodium-reduction interventions.

Evaluación semicuantitativa de los microelementos del esmalte en un modelo de obesidad inducido por glutamato monosódico en ratas / Semi-quantitative evaluation of enamel microelements in an obesity model induced by monosodium glutamate in rats

RESUMEN: En la actualidad, existen múltiples modelos experimentales de obesidad, unos de ellos es la utilización de glutamato monosódico (GMS), un potenciador del sabor ampliamente utilizado en industria alimentaria. Este GMS ha sido relacionado con obesidad, diabetes, insulino resistencia, así como en alteraciones en múltiples órganos, tales como testículos, riñón e hígado, entre otros. Ha sido reportado el efecto del GMS en estructuras orales, tales como las glándulas salivales, alterando su morfología y función. La relación del efecto del GMS frente a tejidos dentarios no ha sido reportada, siendo esto relevantes debido a la información que proporciona a disciplinas tales como arqueología científica, identificación forense, paleoecología y odontología. El objetivo del estudio fue observar la modificación de los elementos en la superficie dental, en un modelo de obesidad inducida por GMS, en ratas. Se utilizaron 12 ratas neonatas Sprague Dawley machos, divididas en dos grupos según exposición a GMS (Grupo Control y Grupo GMS 1: 4 mg/g peso de GMS, 5 dosis, mantenidas 16 semanas. Fue calculado el índice de masa corporal (IMC) e Índice de Lee, además de ser analizados el porcentaje de masa de los elementos C, O, Na, P, Ca, Fe y K en la superficie dental, mediante análisis semicuantitativo. Los resultados indican que GMS indujo obesidad en las ratas, así como alteraciones en los porcentajes de masa de los elementos en la superficie dental, evidenciándose disminución de Ca, P y O, además de aumentos en C y Fe. Según reportes previos, la obesidad inducida por GMS, causa alteraciones en secreción y composición salival, elemento íntimamente relacionado con la composición del esmalte, lo que vendría a explicar nuestros resultados. Entender la composición superficial del esmalte superficial podría ayudarnos a comprender de mejor manera la relación entre caries dentaria y obesidad.

SUMMARY: Monosodium glutamate (MSG) is a flavor enhancer widely used in the food industry. It has been associated with obesity, diabetes, insulin resistance, as well as alterations in multiple organs, such as testicles, kidney, liver, among others. While its effect on oral structures such as the salivary glands has been reported, the impact on dental tissues has not been described. Since this information is also relevant in fields such as forensic identification, palaeoecology and dentistry, the objective of the study was to observe alterations on the tooth surface in a model of obesity in rats induced by MSG. Twelve neonate male Sprague Dawley rats were used, divided into two groups according to MSG exposure (Control Group and MSG1 Group: 4 mg / g weight of MSG, 5 doses were maintained for 16 weeks. Body mass index (BMI) and Lee's index as well as mass percentage of elements C, O, Na, P, Ca, Fe and K on the tooth surface were evaluated by semi-quantitative analysis. In addition to increases in C and Fe, results indicate that MSG induced obesity and alterations in the percentages of mass on the tooth surface in rats, showing a decrease in Ca, P and O, According to previous reports, MSG induced obesity causes alterations in secretion and salivary composition, an aspect closely related to enamel composition, thus explaining our results. Enhanced knowledge of enamel surface composition may help improve our understanding of the relationship between dental caries and obesity.

Characteristics of e-Cigarette Use Behaviors Among US Youth, 2020.

Importance: Comprehensive surveillance of e-cigarette use behaviors among youth is important for informing strategies to address this public health epidemic. Objective: To characterize e-cigarette use behaviors among US youth in 2020. Design, Setting, and Participants: The 2020 National Youth Tobacco Survey, a nationally representative, cross-sectional, school-based survey of middle school (grades 6-8) and high school (grades 9-12) students, was conducted from January 16, 2020, to March 16, 2020. A total of 14 531 students from 180 schools participated in the 2020 survey, yielding a corresponding student-level participation rate of 87.4% and school-level participation rate of 49.9%. The overall response rate, a product of the school-level and student-level participation rates, was 43.6%. Exposures: Current (past 30-day) e-cigarette use. Main Outcomes and Measures: Self-reported current e-cigarette use behaviors (frequency of use, usual e-cigarette brand, and access source) by school level and flavored e-cigarette use and flavor types among current e-cigarette users by school level and device type. Prevalence estimates were weighted to account for the complex survey design. Results: Overall, 14 531 students completed the survey, including 7330 female students and 7133 male students with self-reported grade level and sex. In 2020, 19.6% (95% CI, 17.2%-22.2%) of high school students and 4.7% (95% CI, 3.6%-6.0%) of middle school students reported current e-cigarette use. Among them, 38.9% (95% CI, 35.2%-42.6%) of high school users and 20.0% (95% CI, 16.0%-24.8%) of middle school users reported e-cigarette use on 20 to 30 days within the past 30 days. Among current users, JUUL was the most commonly reported usual brand (high school: 25.4%; 95% CI, 18.8%-33.4%; middle school: 35.1%; 95% CI, 27.9%-43.1%). Among current users, the most common source of obtaining e-cigarettes was from a friend (high school: 57.1%; 95% CI, 52.6%-61.4%; middle school: 58.9%; 95% CI, 51.4%-66.1%). Among current users, 84.7% (95% CI, 82.2%-86.9%) of high school students and 73.9% (95% CI, 66.9%-79.8%) of middle school students reported flavored e-cigarette use. Fruit-flavored e-cigarettes were the most commonly reported flavor among current exclusive e-cigarette users of prefilled pods or cartridges (67.3%; 95% CI, 60.9%-73.0%), disposable e-cigarettes (85.8%; 95% CI, 79.8%-90.3%), and tank-based devices (82.7%; 95% CI, 68.9%-91.1%), followed by mint-flavored e-cigarettes. Conclusions and Relevance: These results suggest that although current e-cigarette use decreased during 2019 to 2020, overall prevalence, frequent use, and flavored e-cigarette use remained high. Continued actions are warranted to prevent and reduce e-cigarette use among US youth.

4-Phenylselanyl-7-chloroquinoline attenuates hepatic injury triggered by neonatal exposure to monosodium glutamate in rats.

AIMS: Obesity is associated with a spectrum of hepatic abnormalities that can be experimentally induced by injections of monosodium glutamate (MSG) in neonatal rodents. We investigated the protective actions of the repeated therapy with 4-phenylselenyl-7-chloroquinoline (4-PSQ), a quinoline derivative containing selenium, on damage to the liver triggered by early postnatal administration of MSG in male Wistar rats. MAIN METHODS: Neonatal rats received MSG (4 g/kg, subcutaneous route) or saline (1 ml/kg) from 5 to 14 postnatal day (PND) to induce obesity with consequent damages in the liver. 4-PSQ treatment (5 mg/kg) or canola oil (1 ml/kg) was administered from 60 to 76 PND by the intragastric route. On 76 PND, animals were anesthetized for blood and liver collection. Plasma markers of hepatic function, hepatic lipoperoxidation levels and histology analysis of liver tissue were assessed. KEY FINDINGS: Our data revealed that treatment with 4-PSQ reverted the increase in plasma transaminases activities observed in MSG rats. Treatment with 4-PSQ reduced plasma lactate levels in obese rats. In the liver, MSG elevated the content of lipoperoxidation which was reverted by 4-PSQ administrations. Lastly, 4-PSQ therapy attenuated the histological alterations induced by MSG. SIGNIFICANCE: Together, the results indicate a hepatoprotective action of repeated treatment with 4-PSQ in obese rats.

An updated overview of e-cigarette impact on human health.

The electronic cigarette (e-cigarette), for many considered as a safe alternative to conventional cigarettes, has revolutionised the tobacco industry in the last decades. In e-cigarettes, tobacco combustion is replaced by e-liquid heating, leading some manufacturers to propose that e-cigarettes have less harmful respiratory effects than tobacco consumption. Other innovative features such as the adjustment of nicotine content and the choice of pleasant flavours have won over many users. Nevertheless, the safety of e-cigarette consumption and its potential as a smoking cessation method remain controversial due to limited evidence. Moreover, it has been reported that the heating process itself can lead to the formation of new decomposition compounds of questionable toxicity. Numerous in vivo and in vitro studies have been performed to better understand the impact of these new inhalable compounds on human health. Results of toxicological analyses suggest that e-cigarettes can be safer than conventional cigarettes, although harmful effects from short-term e-cigarette use have been described. Worryingly, the potential long-term effects of e-cigarette consumption have been scarcely investigated. In this review, we take stock of the main findings in this field and their consequences for human health including coronavirus disease 2019 (COVID-19).

Assessment of changes in the liver of pregnant female rats and their fetuses following monosodium glutamate administration.

Monosodium glutamate (MSG) is a common flavor enhancer and stabilizer for ready-made or packaged foods. This research investigated the impact of MSG on the maternal and fetal liver. The present study was carried out on sixteen mature female Albino rats and eight male rats of reproductive age. The control group was dissected on day 20 of gestation. MSG group was administrated MSG daily at a dosage of 1 g/5 mL/kg body weight from day 0 to day 20 of gestation. The liver function and lipid profile of the control and treated mothers were investigated in the blood sera. The levels of nitric oxide (NO), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), and reduced glutathione (GSH) activities in the liver homogenate of maternal and fetal tissue were assayed, in addition to histopathological, histochemical and immunohistochemical studies were done to the liver tissue. The activities of liver functions and lipid profile significantly altered in the treated mothers with MSG. MSG significantly reduced the SOD and reduced GSH activities in addition to the elevated TNF-α and NO in liver tissue of pregnant mothers and their fetuses. Severe histopathological alterations were observed in both maternal and fetal liver tissues of MSG-treated groups. Moreover, histochemical observations showed a reduction of total polysaccharides in the liver of pregnant rats and fetuses. A significant increase in the percentage area of positive immunoreaction for caspase 3 was observed in the liver of treated rats with MSG compared to the liver of the control. The liver of fetuses treated with MSG revealed an alteration like their mother. This study showed that during the gestational period MSG exposure resulted in several biochemical, histological, and histochemical changes in the maternal and fetal liver tissues which emphasize the toxic effect of MSG.

Risk assessment of inhaled diacetyl from electronic cigarette use among teens and adults.

Diacetyl (C4H6O2) is a toxicant commonly found in electronic cigarettes (e-Cigs) as a flavoring component and an enhancer of e-juices. Lung injury in current and former workers in popcorn manufacturing suggests a possible association with diacetyl inhalation exposure. Although the number of e-Cig users continues to rise steadily among the teens and adults, the potential risk of pulmonary disease has not been characterized. A systematic review of the open literature identified bronchiolitis obliterans-a pathological inflammation resulting in fibrosis of the bronchioles leading to an irreversible limitation to airflow in lungs-as the primary outcome of diacetyl exposures. Following the deterministic United States National Research Council/Environmental Protection Agency's risk assessment framework, that consists of four key steps: hazard identification, dose-response assessment, exposure assessment and risk characterization, we estimated noncarcinogenic (systemic) risks using a Hazard Quotient (HQ) approach upon exposure to diacetyl among teens and adults who use e-Cigs. Based on the NIOSH Benchmark Dose (BMD; 0.0175 mg/kg-day) and modelled Average Daily Doses (ADDs; range 0.11-5.2 mg/kg-day), we estimated 12 different HQ values-a measure of non-carcinogenic risk for diacetyl inhalation exposures-all of which were greater than 1 (range 6.2875-297.1429), suggesting a significantly higher non-carcinogenic risk from diacetyl exposures among the teens and adults who use e-Cigs. These results underscore the need to regulate e-Cigs to protect teens and adults from diacetyl exposures and risk of developing lung injuries, including bronchiolitis obliterans.

Recent updates on biomarkers of exposure and systemic toxicity in e-cigarette users and EVALI.

Electronic nicotine delivery systems (ENDS), or e-cigarettes, are emerging tobacco products that produce aerosols by heating e-liquids, which most often consist of propylene glycol and vegetable glycerin along with various flavoring compounds, bypassing the combustion that occurs in the use of traditional tobacco cigarettes. These products have seen a drastic increase in popularity in recent years both as smoking cessation devices as well as among younger generations, due in large part to the widespread perception among consumers that e-cigs are significantly less harmful to health than traditional tobacco cigarettes. Due to the novelty of ENDS as well as their rapidly increasing use, research into biomarkers of e-cig exposure and toxicity have lagged behind their popularity, leaving important questions about their potential toxicity unanswered. Research into potential biomarkers of acute and chronic e-cig use, and e-cigarette- or vaping-associated lung injury is necessary for informing both clinical and regulatory decision-making. We aim to provide an updated review of recent research into potential circulating, genomic, transcriptomic, and epigenetic biomarkers of exposure to and toxicity of e-cigs. We additionally highlight research areas that warrant additional study to gain a better understanding of health risks associated with ENDS use, as well as to provide validation of existing data and methods for measuring and analyzing e-cig-associated biomarkers in human and animal biofluids, tissues, and cells. This review also highlights ongoing efforts within the WNY Center for Research on Flavored Tobacco for research into novel biomarkers in extracellular vesicles that may be associated with short- and long-term ENDS use.

Biological Toxicity of the Compositions in Electronic-Cigarette on Cardiovascular System.

Using electronic cigarette (e-cig) among youth is becoming a critical public health crisis in the USA. However, the biological impacts of the e-cig on multiple organ systems, especially in the cardiovascular system, are largely unknown. Unlike conventional tobacco, e-cig combines various chemical ingredients including nicotine and other add-on non-nicotine chemicals, such as the solvents (propylene glycol and/or vegetable glycerin) and flavoring chemicals, which dramatically increases the diversity of the potential implications. The recent outbreak of e-cig vaping-related tragic deaths in youth and multiple hospitalized patients raised a question on the safety of e-cig use and led to an urgent need for the knowledge of the health risk of the e-cig compositions. Therefore, in the review, we summarized the latest findings from both human and animal studies on the potential cardiovascular toxicological effects of e-cig on the cardiovascular system in terms of the systemic physiological implications and the cellular and molecular mechanisms involved.