Smoking Behavior and Exposure: Results of a Menthol Cigarette Cross-over Study.

OBJECTIVE: Our objective was to improve understanding of the differences in use behavior and exposure when smoking menthol and non-menthol cigarettes using a 2-part cross-over design. METHODS: Adult daily smokers were assigned randomly to alternate between 2 weeks of exclusively smoking a menthol test cigarette or a non-menthol test cigarette. Urine and saliva were collected for biomarker measurements; carbon monoxide (CO) was measured, and participants smoked test cigarettes through a CreSS® smoking topography device during 3 clinic visits. Participants turned in their cigarette butts from the test periods for determination of mouth level nicotine and completed subjective questionnaires related to the test cigarettes. RESULTS: Regardless of cigarette preference, participants had higher salivary cotinine when smoking the non-menthol test cigarette, but there were no significant differences detected in urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol between the 2 test cigarettes. Mouth level nicotine, puff volume, and puff duration were significantly higher when smoking the menthol brand. Both menthol and non-menthol smokers reported significantly lower enjoyment and satisfaction scores for test cigarettes compared with their brand of choice. CONCLUSIONS: Our results suggest that mentholation has an effect on measures of smoking behavior and that mouth level nicotine is a useful indicator of between-brand smoke exposure.

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.

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.

Development of a method to assess cigarette smoke intake.

Tar and nicotine deliveries of cigarettes measured using current standardized smoking machine protocols provide poor estimates of smoke exposure. The characteristics of human smoking behavior vary considerably and differ from the rigid parameters used with current standardized smoking machine protocols. Current alternatives, including measurement of biomarkers, are invasive, time-dependent, and can be too expensive to be used as mechanisms for carrying out large-scale investigations required to help determine the influence of cigarette design on smoking behaviors. To obtain more reasonable estimates of mainstream smoke exposure, we developed a method to quantitatively measure solanesol, a naturally occurring component in tobacco that is deposited during smoking in the cigarette filter butt. Quantification of solanesol extracted from the filters using liquid chromatography and tandem mass spectrometry is efficient, rapid, and extremely reliable. We found that the amount of solanesol deposited in a cigarette filter is related to the mainstream smoke deliveries of tar and nicotine under a variety of smoking conditions. In addition, the amount of solanesol trapped in the filter remains stable at least 4 weeks after smoking. Measuring solanesol in cigarette filters as an exposure marker provides a noninvasive means to obtain reasonable estimates of mainstream tar and nicotine smoke deliveries under a wide variety of smoking conditions.

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.