Chemical research in toxicology
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Chem. Res. Toxicol. · Aug 2017
Carboxylate Counteranions in Electronic Cigarette Liquids: Influence on Nicotine Emissions.
The wide pH range reported for electronic cigarette (ECIG) liquids indicates that nicotine may be present in one or more chemical forms. The nicotine form affects the bioavailability and delivery of nicotine from inhaled products. Protonated nicotine is normally associated with counteranions in tobacco products. ⋯ This study also shows that the identity of the counteranion has no effect on total nicotine emission from ECIG in agreement with previous reports on tobacco cigarettes. However, the partitioning of aerosolized nicotine into NicH+ and Nic is anion-dependent even when the parent liquid pH is held constant. These results indicate that the anions found in a given ECIG product may influence the nicotine delivery profile to the user by enriching aerosols with free-base nicotine as in the case of polycarboxylic acids such as citric acid.
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Chem. Res. Toxicol. · Aug 2017
A Model To Estimate the Sources of Tobacco-Specific Nitrosamines in Cigarette Smoke.
Tobacco-specific nitrosamines (TSNAs) are one of the most extensively and continually studied classes of compounds found in tobacco and cigarette smoke.1-5 The TSNAs N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) have been characterized by the US Food and Drug Administration (FDA) as harmful and potentially harmful constituents in tobacco products,6 and cigarette manufacturers report their levels in cigarette tobacco filler and cigarette smoke to the FDA. NNN and NNK are classified by IARC as carcinogenic to humans.7 TSNAs transfer from tobacco to smoke by evaporation driven by heat and the flow of gases down the cigarette rod. Other TSNA sources in smoke include pyrorelease, where room temperature-unextractable TSNAs are released by smoking, and pyrosynthesis, where TSNAs are formed by reactions during smoking. ⋯ For commercial blended cigarettes, NNN pyrogeneration appears to be unimportant, but NNK pyrogeneration contributes roughly 30-70% of NNK in smoke with the greater contribution at lower tobacco NNK levels. This means there is an opportunity to significantly reduce smoke NNK by up to 70% if pyrogeneration can be decreased or eliminated, perhaps by finding a way to grow and cure tobacco with reduced matrix-bound NNK. For burley research cigarettes, pyrogeneration may account for 90% or more of both NNN and NNK in smoke.
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Chem. Res. Toxicol. · Feb 2017
Tobacco-Specific Nitrosamines in the Tobacco and Mainstream Smoke of U.S. Commercial Cigarettes.
Tobacco-specific nitrosamines (TSNAs) are N-nitroso-derivatives of pyridine-alkaloids (e.g., nicotine) present in tobacco and cigarette smoke. Two TSNAs, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are included on the Food and Drug Administration's list of harmful and potentially harmful constituents (HPHCs) in tobacco products and tobacco. The amounts of four TSNAs (NNK, NNN, N-nitrosoanabasine (NAB), and N'-nitrosoanatabine (NAT)) in the tobacco and mainstream smoke from 50 U. ⋯ In contrast, filter ventilation is a major determinant of levels of TSNAs in smoke by the ISO machine-smoking regimen. Comparative analysis demonstrates substantial variability in TSNA amounts in tobacco filler and mainstream smoke yields under ISO and CI machine-smoking regimens among U. S. commercial cigarette brands.
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Chem. Res. Toxicol. · Oct 2016
Comparative StudyChemical Composition of Aerosol from an E-Cigarette: A Quantitative Comparison with Cigarette Smoke.
There is interest in the relative toxicities of emissions from electronic cigarettes and tobacco cigarettes. Lists of cigarette smoke priority toxicants have been developed to focus regulatory initiatives. However, a comprehensive assessment of e-cigarette chemical emissions including all tobacco smoke Harmful and Potentially Harmful Constituents, and additional toxic species reportedly present in e-cigarette emissions, is lacking. ⋯ Thus, the aerosol from the e-cigarette is compositionally less complex than cigarette smoke and contains significantly lower levels of toxicants. These data demonstrate that e-cigarettes can be developed that offer the potential for substantially reduced exposure to cigarette toxicants. Further studies are required to establish whether the potential lower consumer exposure to these toxicants will result in tangible public health benefits.
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Chem. Res. Toxicol. · Aug 2016
Rethinking Drugs from Chemistry to Therapeutic Opportunities: Pixantrone beyond Anthracyclines.
Pixantrone (6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione) has been approved by the European Medicines Agency for the treatment of refractory or relapsed non-Hodgkin's lymphoma (NHL). It is popularly referred to as a novel aza-anthracenedione, and as such it is grouped with anthracycline-like drugs. Preclinical development of pixantrone was in fact tailored to retain the same antitumor activity as that of anthracyclines or other anthracenediones while also avoiding cardiotoxicity that dose-limits clinical use of anthracycline-like drugs. ⋯ For example, pixantrone causes mis-segregation of genomic material in cancer cells and inhibits formation of toxic anthracycline metabolites in cardiac cells. Understanding the differences between pixantrone and anthracyclines or mitoxantrone may help one to appreciate how it worked in the phase 3 study that led to its approval in Europe and how it might work in many more patients in everyday clinical practice, were it properly perceived as a drug with its own characteristics and therapeutic potential. The road is rocky but not a dead-end.