Estimating smokers' mouth-level exposure to select mainstream smoke constituents from discarded cigarette filter butts.

INTRODUCTION: Standardized machine smoking measurements are poor predictors of exposure. We have refined a method using the solanesol deposited in discarded cigarette butts as a marker for estimating deliveries of mainstream smoke constituents. Developing a fast and accurate method for measuring solanesol in cigarette filters to assess tobacco smoke intake could provide a way to assess how people smoke under natural conditions. We have developed and validated a new, lower-cost, high-throughput method to measure the solanesol content in discarded cigarette filter butts and correlated these measurements with mainstream smoke deliveries of nicotine and tobacco-specific nitrosamines (TSNAs). METHODS: Cigarettes were machine smoked under a variety of conditions to cover a wide range of nicotine deliveries and solanesol levels in the spent cigarette filter. Following machine smoking, a 1-cm portion of filter material, measured from the mouth end, was removed from the cigarette butts for analysis. Although an isotopically labeled solanesol analog is currently not commercially available, we achieved excellent quantitative results using a structurally similar compound, geranylgeraniol, as an internal standard (IS). After spiking with IS and solvent extracted, solanesol extracts were then analyzed using liquid chromatography coupled with a single-quadrupole mass analyzer. Analysis was carried out using manual preparation as well as a high-throughput 48-well format using automated liquid handlers. RESULTS: Recoveries of solanesol from cigarette butts exceeded 95% with excellent precision and exhibited excellent linearity for both preparation methods. In addition, we show that the mouth-level exposure for both nicotine and TSNAs may be estimated by their relation to the solanesol retained in the cigarette filter. DISCUSSION: We believe that this method provides excellent versatility and throughput for the estimation of mouth-level exposure to a wide range of toxins in cigarette smoke under naturalistic conditions. In addition, this method allows a far more accurate measure of exposure both from a single cigarette as well as from daily smoking.

Effect of differing levels of tobacco-specific nitrosamines in cigarette smoke on the levels of biomarkers in smokers.

BACKGROUND: Smokers are exposed to significant doses of carcinogens, including tobacco-specific nitrosamines (TSNA). Previous studies have shown significant global differences in the levels of TSNAs in cigarette smoke because of the variation in tobacco blending and curing practices around the world. METHODS: Mouth-level exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) measured in cigarette butts and urinary concentrations of its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were examined among 126 daily smokers in four countries over a 24-hour study period. RESULTS: As mouth-level exposure of NNK increased, the urinary NNAL increased even after adjustment for other covariates (beta = 0.46, P = 0.004). The relationship between mouth-level exposure to nicotine and its salivary metabolite, cotinine, was not statistically significant (beta = 0.29, P = 0.057), likely because of the very limited range of differences in mouth-level nicotine exposure in this population. CONCLUSIONS: We have shown a direct association between the 24-hour mouth-level exposure of NNK resulting from cigarette smoking and the concentration of its primary metabolite, NNAL, in the urine of smokers. Internal dose concentrations of urinary NNAL are significantly lower in smokers in countries that have lower TSNA levels in cigarettes such as Canada and Australia in contrast to countries that have high levels of these carcinogens in cigarettes, such as the United States. IMPACT: Lowering the levels of NNK in the mainstream smoke of cigarettes through the use of specific tobacco types and known curing practices can significantly affect the exposure of smokers to this known carcinogen.

Tobacco-specific nitrosamines in tobacco from U.S. brand and non-U.S. brand cigarettes.

Tobacco-specific nitrosamines (TSNAs) are one of the major classes of carcinogens found in tobacco products. As part of collaborative efforts to reduce tobacco use and resulting disease, the U.S. Centers for Disease Control and Prevention (CDC) carried out a two-phase investigation into the worldwide variation of the levels of TSNAs in cigarette tobacco. In the first phase, representatives of the World Health Organization (WHO) purchased cigarettes; scientists from the CDC subsequently measured the levels of TSNAs in tobacco from 21 different countries. Although the data collected from this initial survey suggested that globally marketed U.S.-brand cigarettes typically had higher TSNA levels than locally popular non-U.S. cigarettes in many countries, the number of samples limited the statistical power of the study. To improve statistical power and to ensure adequate sampling, the CDC conducted a second survey of 14 countries. In addition to the United States, the CDC selected the world's 10 most populous countries and three additional countries, so that at least two countries from each of the six WHO regions were represented. For each country, the CDC compared 15 packs of Marlboro cigarettes, which is the world's most popular brand of cigarettes, with 15 packs of a locally popular non-U.S. brand in the study country. Marlboro cigarettes purchased in 11/13 foreign countries had significantly higher tobacco TSNA levels than the locally popular non-U.S. brands purchased in the same country. The findings suggest that TSNA levels in tobacco can be substantially reduced in some cigarettes.