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Nasal Cavity Carcinogens: Possible Routes of Metabolic Activation
Published in D. V. M. Gerd Reznik, Sherman F. Stinson, Nasal Tumors in Animals and Man, 2017
Stephen S. Hecht, Andre Castonguay, Dietrich Hoffmann
Identification of the urinary metabolites of Fischer 344 rats treated with NNK showed that this tobacco-specific N-nitrosamine was metabolized by α-carbon hydroxylation (Figure 5). The three intermediates myosmine (13), 4-hydroxy-l-(3-pyridyl)-l-butanone (14), and 4-oxo-4-(3-pyridyl)butanal (8) were observed in vitro and were not detected in urine extracts.71 Further oxidation and/or reduction of (8) and (14) in vivo resulted in the formation of the urinary metabolites diol (17), keto acid (15), and hydroxy acid (16).
Comparison of the content of tobacco alkaloids and tobacco-specific nitrosamines in ‘heat-not-burn’ tobacco products before and after aerosol generation
Published in Inhalation Toxicology, 2018
Won Tae Jeong, Hyun Ki Cho, Hyung Ryeol Lee, Ki Hoon Song, Heung Bin Lim
Nicotine is generally the most abundant alkaloid in tobacco leaves, but tobacco alkaloids such as nornicotine, anatabine, anabasine, cotinine, and myosmine coexist in trace amounts (Matsushima et al., 2014; Tassew & Chandravanshi, 2015). In our study result, four alkaloids (nicotine, nornicotine, anatabine, and anabasine) in all of HTP cigarettes were significantly decreased after aerosol generation. We regarded first this reduced amount as a potential amount of inhalation that could be inhaled by smokers. Nicotine and other alkaloids are released from tobacco heated above 140 °C (Rowell & Tarran, 2015). Because the HTP heating range is between 200 °C and 350 °C, alkaloids in the sample can be seen as emissions due to the conversion of aerosols (Forster et al., 2018). Myosmine, in particular, has been reported to undergo less conversion to aerosols than other alkaloids (Liu et al., 2017). As a difference in the two regimes (ISO and HCI), four alkaloids showed more reduction in samples smoked under the HCI regime. HCI regime can detect more chemical components of aerosols in conventional tobacco and HTP because the parameters of the smoking machine, such as puff volume, puff frequency, and puff duration, are higher than ISO (Purkis et al., 2012). These results show that smoking according to an HCI regime was associated with a larger decrease in TAs in our results.
Effect of E-Cigarette aerosol exposure on airway inflammation in a murine model of asthma
Published in Inhalation Toxicology, 2020
Huda R. Taha, Nour A. Al-Sawalha, Karem H. Alzoubi, Omar F. Khabour
Electronic cigarettes (E-Cigs), also known as electronic nicotine delivery devices, are battery powered devices that heat a liquid to produce an aerosol that is inhaled by the user (Leigh et al. 2016; Larcombe et al. 2017). The E-Cigs liquid commonly contains humectants, a flavoring agent and a variable concentration of nicotine (Morean et al. 2016). E-Cigs are a new smoking method that was introduced to market in early 2000s, and became a trend, especially among adolescent and young adults (Grana et al. 2014). The prevalence of E-Cig use is rapidly increasing, rising from 0.3% in 2010, to 6.8% in 2013, 7.4% in 2015, and 8.5% in 2017 in USA (Levy et al. 2019). Although E-Cigs are portrayed as a safer alternative to tobacco smoking and are extensively marketed as an effective method for smoking cessation, there is a lot of debates about their safety (Grana et al. 2014). Three toxic metals were identified in E-Cig vapor; chromium, nickel, and lead (Williams et al. 2013). Further, E-Cig cartridge solution contains toxic nitrosamines and diethylene glycol as well as noxious alkaloids, including anabasine and myosmine (Lim and Kim 2014). Propylene glycol and glycerol, the most commonly utilized humectants in E-Cig liquids, when heated and aerosolized, cause irritation to eyes and respiratory system (Grana et al. 2014; Hahn et al. 2014). E-Cig users reported a twofold increase in respiratory symptoms including cough, phlegm, and bronchitis and until 2019, seven deaths were attributable to E-Cig use (Gotts et al. 2019). Osei et al. (2019) reported an increased odds of asthma among E-Cigs users who never smoked cigarettes. However, both short- and long-term health consequences of E-Cig remain largely unexplored, especially in asthma patients, because of the relative novelty of this product. Therefore, the aim of the current study was to evaluate the effect of E-Cig aerosol exposure on airway inflammation, inflammatory mediators, and matrix metalloproteinase in an allergen-driven murine model of asthma.
Nicotine forms: why and how do they matter in nicotine delivery from electronic cigarettes?
Published in Expert Opinion on Drug Delivery, 2020
Vinit V Gholap, Leon Kosmider, Laleh Golshahi, Matthew S Halquist
While the cigarettes use among middle school and high school students has dropped significantly (from 4.3% in 2011 to 2.3% in 2019 for middle school and from 15.8% in 2011 to 5.8% in 2019 for high school students), the e-cigarette use among them has increased dramatically so as to reverse the progress toward reducing overall tobacco use [10]. With more than 5 million middle and high school students having used e-cigarettes in the United States, it is important to address the concerns of nicotine addiction in youth [11]. Consideration should be given to nicotine delivery and the factors affecting it. Several studies have identified the factors which can affect the nicotine delivery, either alone or in combination. These interlinked factors include the nicotine concentration, ratio of propylene glycol (PG) and vegetable glycerin (VG), type of e-cigarette device, battery power, puffing profile and flavors [12–17]. As stated earlier [1], the unregulated nicotine levels in e-liquids can expose users to high nicotine levels. Additionally, Kosmider et al. [12] found out that the nicotine delivery increased with higher PG content at low power settings. Baassiri et al. [13] also found out that decreasing the PG/VG ratio decreases the nicotine delivery. Furthermore, DeVito et al. [15] has summarized multiple studies [18–21 in their review article which shows that higher powers of advanced e-cigarettes can increase the amount of nicotine aerosolized and increase nicotine delivery. Flavors also play an important role in the choice and addiction of e-cigarettes, especially in youth population [15]. In the study carried out by Helen et al. [17] flavors were found to affect the nicotine delivery through change in puffing behavior as well as e-liquid pH. Some authors [22,23] have also studied the stability of nicotine in e-liquids over time as nicotine can undergo degradation to form products such as nicotine-N-oxide, cotinine, and myosmine. Based on these stability studies, the nicotine breakdown products were not found to be more than 2% of nicotine content of e-liquids. Thus, stability may not act as major factor affecting nicotine delivery.