Tobacco-Specific Nitrosamines in the Tobacco and Mainstream Smoke of U.S. Commercial Cigarettes

Abstract

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.S. commercial cigarette brands were measured from November 15, 2011 to January 4, 2012 using a validated, HPLC-MS/MS method. Smoke samples were generated using the International Organization of Standardization (ISO) and Canadian Intense (CI) machine-smoking regimens. NNN and NAT were the most abundant TSNAs in tobacco filler and smoke across all cigarette brands whereas NNK and NAB were present in the least amounts. The average of the ratios for each TSNA in mainstream smoke to filler content is 29% by the CI smoking regimen and 13% for the ISO machine-smoking regimen. The reliability of each TSNA to predict total TSNA amounts in the filler and smoke was examined. NNN, NAT, and NAB have a moderate to high correlation (R2 = 0.61 – 0.98) and all three TSNAs individually predict total TSNAs with minimal difference between measured and predicted total TSNA amounts (error < 7.4%). NNK has weaker correlation (R2 = 0.56 – 0.82) and is a less reliable predictor of total TSNA quantities. Tobacco weight and levels of TSNAs in filler influence TSNA levels in smoke from the CI machine-smoking regimen. 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.

Simultaneous determination of tobacco minor alkaloids and tobacco‐specific nitrosamines in mainstream smoke by dispersive solid‐phase extraction coupled with ultra‐performance liquid chromatography/tandem orbitrap mass spectrometry

“…The reported contents of NNN, NAB and NAT were higher than our study (3.62 ng/cig, 0.40 ng/cig and 6.15 ng/cig), whereas NNK in our study was higher (6.06 ng/cig). The mean contents of NNK, NNN, NAB and NAT in cigarette smoke sold in the United States were 55 ng/cig, 85 ng/cig, 11.7 ng/cig and 80 ng/cig, respectively, under the ISO smoking regimen . The concentrations of tobacco‐specific nitrosamines in cigarette smoke sold in the United States was nine times higher than that in cigarette smoke sold in China, which is consistent with the study of Xiong et al The variation differences in the deliveries of tobacco‐specific nitrosamines of cigarette mainstream smoke could likely result from differences in product characteristics or tobacco types.…”

Mainstream smoke constituents and in vitro toxicity comparative analysis of 3R4F and 1R6F reference cigarettes

“…The lower NNN content observed in the MS of 1R6F cigarettes is also observed in the tobacco blend, with reported values for NNN in 1R6F of 2,131 ng/g [47] or 2,294 ng/g [65] and in 3R4F of 2,636 ng/g [66]. However, this is not the case for NNK, for which the reported values are very similar, with values in 1R6F of 676 ng/g [47] and 675 ng/g [65] and in 3R4F of 679 ng/g [66]. The lower value observed for 1R6F MS NNK yields may be due to a lower transfer from tobacco to smoke of NNK, related to a lower amount of bound NNK in the blend [67,68].…”

“…Those compounds may all be affected by the blend composition [61]; NO content in smoke is primarily determined by the nitrate content in the tobacco blend [61], and NNN and NNK are typically higher in air-cured tobaccos than in flue-cured tobaccos [62], with a tendency for a downward trend in recent years due to the introduction of new agricultural and curing practices [63,64]. The lower NNN content observed in the MS of 1R6F cigarettes is also observed in the tobacco blend, with reported values for NNN in 1R6F of 2,131 ng/g [47] or 2,294 ng/g [65] and in 3R4F of 2,636 ng/g [66]. However, this is not the case for NNK, for which the reported values are very similar, with values in 1R6F of 676 ng/g [47] and 675 ng/g [65] and in 3R4F of 679 ng/g [66].…”

Inhalation Toxicology of Vaping Products and Implications for Pulmonary Health

“…TSNAs are also present in trace amounts in e-cigarette aerosols. TSNAs are among the most important carcinogens in cigarette smoke and are formed during the curing process from nicotine and other tobacco alkaloids [98]. Total levels of TSNAs typically range from 200 to 1600 ng/cigarette [99].…”