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      Thermal reaction products and formation pathways of two monoterpenes under in situ thermal desorption conditions that mimic vaping coil temperatures

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      Scientific Reports
      Nature Publishing Group UK
      Environmental sciences, Chemistry

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          Abstract

          Vaping has become more popular and different brands and types of vaping devices have rapidly emerged. However, little is known about the potential health risks of human inhalation exposures to the volatile chemicals in the vapour, which includes both directly vaporised components of vaping liquid and their reaction products formed during vaping processes. This study investigated reaction products of two monoterpenes (α-pinene and terpinolene) that are used as flavouring agents in vaping liquids with a focus on the identification of reaction products and their formation pathways. The thermal desorption was conducted under an in situ condition that is in the range of heating coil temperature in vaping by thermally desorbing the chemicals at a temperature range of 100–300 °C. Additional clean air was introduced during the thermal desorption. 36 and 29 reaction products were identified from α-pinene and terpinolene, respectively, at a relative concentration of 0.01% and greater in the desorbed mixture. 3-Carene was the dominant reaction product of α-pinene, while reaction products of terpinolene was dominated by p-isopropenyltoluene. Several reaction pathways including ring opening, allylic oxidation, cyclo-etherification, Wagner–Meerwein rearrangement, epoxidation, cleavage and removal of partial structure, and dehydration were involved in the formation of various reaction products. These pathways and resulting relative concentrations of residual parent compound and reaction products were influenced by both temperature and amount of air present during thermal desorption. The study results demonstrate possible existence of reaction products from thermally labile chemicals like monoterpenes in vaping aerosols and can help inform policies regulating vaping devices and products to protect public health.

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          Tobacco Use Among Middle and High School Students — United States, 2011–2014

          Tobacco use and addiction most often begin during youth and young adulthood (1,2). Youth use of tobacco in any form is unsafe (1). To determine the prevalence and trends of current (past 30-day) use of nine tobacco products (cigarettes, cigars, smokeless tobacco, e-cigarettes, hookahs, tobacco pipes, snus, dissolvable tobacco, and bidis) among U.S. middle (grades 6–8) and high school (grades 9–12) students, CDC and the Food and Drug Administration (FDA) analyzed data from the 2011–2014 National Youth Tobacco Surveys (NYTS). In 2014, e-cigarettes were the most commonly used tobacco product among middle (3.9%) and high (13.4%) school students. Between 2011 and 2014, statistically significant increases were observed among these students for current use of both e-cigarettes and hookahs (p<0.05), while decreases were observed for current use of more traditional products, such as cigarettes and cigars, resulting in no change in overall tobacco use. Consequently, 4.6 million middle and high school students continue to be exposed to harmful tobacco product constituents, including nicotine. Nicotine exposure during adolescence, a critical window for brain development, might have lasting adverse consequences for brain development (1), causes addiction (3), and might lead to sustained tobacco use. For this reason, comprehensive and sustained strategies are needed to prevent and reduce the use of all tobacco products among youths in the United States. NYTS is a cross-sectional, school-based, self-administered, pencil-and-paper questionnaire administered to U.S. middle and high school students. Information is collected on tobacco control outcome indicators to monitor the impact of comprehensive tobacco control policies and strategies (4) and inform FDA’s regulatory actions (5). A three-stage cluster sampling procedure was used to generate a nationally representative sample of U.S. students who attend public and private schools in grades 6–12. This report includes data from 4 years of NYTS (2011–2014), using an updated definition of current tobacco use that excludes kreteks (sometimes referred to as clove cigarettes).* Of 258 schools selected for the 2014 NYTS, 207 (80.2%) participated, with a sample of 22,007 (91.4%) among 24,084 eligible students; the overall response rate was 73.3%. Sample sizes and overall response rates for 2011, 2012, and 2013 were 18,866 (72.7%), 24,658 (73.6%), and 18,406 (67.8%), respectively. Participants were asked about current (past 30-day) use of cigarettes, cigars (defined as cigars, cigarillos, or little cigars), smokeless tobacco (defined as chewing tobacco, snuff, or dip), e-cigarettes,† hookahs,§ tobacco pipes (pipes),¶ snus, dissolvable tobacco (dissolvables), and bidis. Current use for each product was defined as using a product on ≥1 day during the past 30 days. Tobacco use was categorized as “any tobacco product use,” defined as use of one or more tobacco products and “≥2 tobacco product use,” defined as use of two or more tobacco products. Data were weighted to account for the complex survey design and adjusted for nonresponse; national prevalence estimates with 95% confidence intervals and population estimates rounded down to the nearest 10,000 were computed. Estimates for current use in 2014 are presented for any tobacco use, use of ≥2 tobacco products, and use of each tobacco product, by selected demographics for each school level (high and middle). Orthogonal polynomials were used with logistic regression analysis to examine trends from 2011 to 2014 in any tobacco use, use of ≥2 tobacco products, and use of each tobacco product by school level, controlling for grade, race/ethnicity, and sex and simultaneously assessing for linear and nonlinear trends.** A p-value <0.05 was considered statistically significant. SAS-Callable SUDAAN was used for analysis. In 2014, a total of 24.6% of high school students reported current use of a tobacco product, including 12.7% who reported current use of ≥2 tobacco products. Among all high school students, e-cigarettes (13.4%) were the most common tobacco products used, followed by hookahs (9.4%), cigarettes (9.2%), cigars (8.2%), smokeless tobacco (5.5%), snus (1.9%), pipes (1.5%), bidis (0.9%), and dissolvables (0.6%) (Table). Among high school non-Hispanic whites, Hispanics,†† and persons of non-Hispanic other races, e-cigarettes were the most used product, whereas among non-Hispanic blacks, cigars were used most commonly. Current use of any tobacco and ≥2 tobacco products among middle school students was 7.7% and 3.1%, respectively. E-cigarettes (3.9%) were the tobacco product used most commonly by middle school students, followed by hookahs (2.5%), cigarettes (2.5%), cigars (1.9%), smokeless tobacco (1.6%), pipes (0.6%), bidis (0.5%), snus (0.5%), and dissolvables (0.3%). From 2011 to 2014, statistically significant nonlinear increases were observed among high school students for current e-cigarette (1.5% to 13.4%) and hookah (4.1% to 9.4%) use (Figure 1). Statistically significant linear decreases were observed for current cigarette (15.8% to 9.2%) and snus (2.9% to 1.9%) use. Statistically significant nonlinear decreases were observed for current cigar (11.6% to 8.2%), pipe (4.0% to 1.5%), and bidi (2.0% to 0.9%) use. Current use of any tobacco product (24.2% to 24.6%) and use of ≥2 tobacco products (12.5% to 12.7%) did not change significantly from 2011 to 2014. Among middle school students, similar trends were observed during 2011–2014 (Figure 2). A statistically significant linear decrease was observed only in middle school students currently using ≥2 tobacco products (3.8% to 3.1%). In 2014, an estimated 4.6 million middle and high school students currently used any tobacco product, of which an estimated 2.2 million students currently used ≥2 tobacco products. Of current tobacco users, 2.4 million used e-cigarettes and 1.6 million used hookahs. The largest increase in current e-cigarette use occurred from 2013 to 2014. Current e-cigarette use tripled from 2013 (660,000 [4.5%]) to 2014 (2 million [13.4%]) among high school students (Figure 1); and among middle school students, prevalence increased by a similar magnitude, from 1.1% (120,000) to 3.9% (450,000) (Figure 2). From 2013 to 2014, substantial increases also were observed for current hookah use, with prevalence almost doubling for high school students from 5.2% (770,000) to 9.4% (1.3 million) and for middle school students from 1.1% (120,000) to 2.5% (280,000) over this period. Discussion From 2011 to 2014, substantial increases were observed in current e-cigarette and hookah use among middle and high school students, resulting in an overall estimated total of 2.4 million e-cigarette youth users and an estimated 1.6 million hookah youth users in 2014. Statistically significant decreases occurred in the use of cigarettes, cigars, tobacco pipes, bidis, and snus. The increases in current use of e-cigarettes and hookahs offset the decreases in current use of other tobacco products, resulting in no change in overall current tobacco use among middle and high school students. In 2014, one in four high school students and one in 13 middle school students used one or more tobacco products in the last 30 days. In 2014, for the first time in NYTS, current e-cigarette use surpassed current use of every other tobacco product, including cigarettes. These findings are subject to at least three limitations. First, data were collected only from youths who attended either public or private schools and might not be generalizable to all middle and high school-aged youth. Second, current tobacco use was estimated by including students who reported using at least one of the nine tobacco products asked in the survey but might have had missing responses to any of the other eight tobacco products; missing responses were considered as nonuse, which might have resulted in underestimated results. Finally, changes between 2013 and 2014 in the wording and placement of questions about the use of e-cigarettes, hookahs, and tobacco pipes might have had an impact on reported use of these products. Despite these limitations, overall prevalence estimates are similar to the findings of other nationally representative youth surveys (6,7). Tobacco prevention and control strategies, including increasing tobacco product prices, adopting comprehensive smoke-free laws, and implementation of national public education media campaigns, might have influenced the reduction of cigarette smoking in youths (2). However, the lack of decline in overall tobacco use from 2011 to 2014 is concerning and indicates that an estimated 4.6 million youths continue to be exposed to harmful constituents, including nicotine, present in tobacco products (Table). Youth use of tobacco in any form, whether it be combustible, noncombustible, or electronic, is unsafe (1); regardless of mode of delivery, nicotine exposure during adolescence, a critical time for brain development, might have lasting adverse consequences for brain development (1), causes addiction (3), and might lead to sustained use of tobacco products. Rapid changes in use of traditional and emerging tobacco products among youths underscore the importance of enhanced surveillance of all tobacco use. What is already known on this topic? Tobacco use and addiction most often begins during youth and young adulthood. Youth use of tobacco in any form is unsafe and might have lasting adverse consequences on their developing brains. What is added by this report? In 2014, an estimated 4.6 million youths, including 3.7 million high school and 900,000 middle school students, reported current use (use on one or more days in the past 30 days) of any tobacco product. From 2011 to 2014, statistically significant increases were observed in e-cigarette and hookah use among high school and middle school students, while statistically significant decreases were observed in the use of cigarettes, cigars, tobacco pipes, bidis, and snus. The increases in current use of e-cigarettes and hookahs offset the decreases in other tobacco products, resulting in no change in overall current tobacco use among youths. What are the implications for public health practice? In 2014, nearly one in four high school students and one in 13 middle school students reported current use of any tobacco product. Because the use of emerging tobacco products (e-cigarettes and hookahs) is on the rise among middle and high school students, it is critical that comprehensive tobacco control and prevention strategies for youths should address all tobacco products and not just cigarettes. Sustained efforts to implement proven tobacco control policies and strategies are necessary to prevent youth use of all tobacco products. In April 2014, FDA issued a proposed rule to deem all products made or derived from tobacco subject to FDA jurisdiction, and the agency is reviewing public comments on the proposed rule (8). Regulation of the manufacturing, distribution, and marketing of tobacco products coupled with full implementation of comprehensive tobacco control and prevention strategies at CDC-recommended funding levels could reduce youth tobacco use and initiation (1,2,9). Because use of emerging tobacco products (e-cigarettes and hookahs) is increasing among middle and high school students, it is critical that comprehensive tobacco control and prevention strategies for youths should address all tobacco products and not just cigarettes.
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            Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

            The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.
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              Intentions to smoke cigarettes among never-smoking US middle and high school electronic cigarette users: National Youth Tobacco Survey, 2011-2013.

              Electronic cigarette (e-cigarette) use is increasing rapidly, and the impact on youth is unknown. We assessed associations between e-cigarette use and smoking intentions among US youth who had never smoked conventional cigarettes.
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                Author and article information

                Contributors
                jiping.zhu@hc-sc.gc.ca
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                8 December 2023
                8 December 2023
                2023
                : 13
                : 21650
                Affiliations
                Exposure and Biomonitoring Division, Environmental Health Science and Research Bureau, Health Canada, ( https://ror.org/05p8nb362) Ottawa, Canada
                Author information
                http://orcid.org/0000-0001-9154-5978
                http://orcid.org/0000-0003-1917-7343
                Article
                49174
                10.1038/s41598-023-49174-2
                10709557
                38066090
                afbbf8af-d631-463e-b999-f242c5912369
                © Crown 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 October 2023
                : 5 December 2023
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                © Springer Nature Limited 2023

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                environmental sciences,chemistry
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                environmental sciences, chemistry

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