Menthol, the only cigarette additive that is actively marketed by manufacturers, is particularly favored by youth and ethnic/racial minorities. There is growing evidence that menthol cigarettes are starter products for youth, impede cessation, increase relapse following cessation and undermine social justice by the incessant targeted marketing of these products to communities of color. Tying menthol cigarette use to increased risk of tobacco-related diseases has been difficult. Generally, epidemiologic studies that have been used to try to make that connection have been inconclusive, whereas laboratory-based studies have been hampered by the inability to get established menthol or non-menthol smokers to use the opposite cigarette style for the extended periods necessary to compare classic measures of toxicity, and results obtained have been mixed. A major reason for this may lie with the commercial cigarettes that were used in these tests. Because cigarettes are so highly engineered, there are likely many differences between menthol and non-menthol cigarettes other than menthol levels. The investigators'previous work has resulted in some intriguing contrasts in menthol and non-menthol cigarettes, but it cannot be known if the differences were the result of the effects of mentholation alone, or the many other possible differences in the properties of commercial cigarettes. To adequately study the effect of mentholation of cigarettes, we need to test cigarettes that differ only in menthol content. The specific aims of this research are to determine the acute effects of smoking cigarettes that are equivalent except for levels of menthol. The over-all goal is to establish methods for testing which are valid without requiring prolonged periods of exposure and compliance with long-duration protocols. We will therefore characterize a set of cigarettes that are the same except for variation in menthol levels. The cigarettes are a commercial non-menthol cigarette that is mentholated at a low level and a high level, and Camel Crush, a non-menthol cigarette with a small menthol pellet in the filter which, when crushed, releases menthol into the filter. Chemical characterization of the cigarettes will be followed by real-time human toxicity measurements in a within-subjects design, to assess human exposure to select smoke-related toxins/carcinogens. Finally, to generate subject-specific smoke emissions and estimate uptake of smoke- related toxins/carcinogens, a smoking machine will be programmed to smoke the test cigarettes, and smoke emissions of each of the test cigarettes will be compared. PUBLIC HEALTH RELEVANCE: This work has public health implications because, although African Americans smoke fewer cigarettes per day and tend to begin smoking later in life than do Euro-Americans, their smoking-related mortality from diseases associated with tobacco use is higher. The majority of African American smokers prefer smoking mentholated cigarettes compared to Euro-Americans smokers, and the preference for menthol cigarettes is even higher among younger smokers. Use of menthol cigarettes has been implicated as a cause of this disease disparity, but evidence from traditional epidemiologic and other studies has been weak. This study will determine if mentholation alone results in differences in smoking patterns, smoke emissions, biomarkers of exposure, and/or uptake of select toxins/carcinogens.