Patricia Richter

Epidemiology of menthol cigarette use

Approximately one-fourth of all cigarettes sold in the United States are mentholated. An understanding of the consequences, patterns, and correlates of menthol cigarette use can guide the development and implementation of strategies to reduce smoking prevalence and smoking-attributable morbidity and mortality. This paper summarizes the literature on the health effects of mentholated cigarettes and describes various patterns of use as indicated by consumption and survey data from the United States and other nations. The epidemiological literature on menthol cigarettes and cancer risk is inconclusive regarding whether these cigarettes confer a risk for cancer above that of nonmentholated varieties. Available data indicate that mentholated cigarettes are at least as dangerous as their nonmentholated counterparts. In addition, because mentholation improves the taste of cigarettes for a substantial segment of the smoking population and appears to mask disease symptoms, this additive may facilitate initiation or inhibit quitting. Menthol market share is high in the Philippines (60%), Cameroon (35%-40%), Hong Kong (26%), the United States (26%), and Singapore (22%). Newport has become the leading menthol brand in the United States. Surveys from four nations indicate that menthol use among adult smokers is more common among females than males. Among U.S. smokers, 68.9% of Blacks, 29.2% of Hispanics, and 22.4% of Whites reported smoking a mentholated variety. Research is needed to better explain factors that may influence menthol preference, such as marketing, risk perceptions, brand formulation, and taste preferences. Such research would guide the development of potentially more effective programs and policies.

Global surveillance of oral tobacco products: total nicotine, unionised nicotine and tobacco-specific N-nitrosamines

Objective Oral tobacco products contain nicotine and carcinogenic tobacco-specific N-nitrosamines (TSNAs) that can be absorbed through the oral mucosa. The aim of this study was to determine typical pH ranges and concentrations of total nicotine, unionised nicotine (the most readily absorbed form) and five TSNAs in selected oral tobacco products distributed globally. Methods A total of 53 oral tobacco products from 5 World Health Organisation (WHO) regions were analysed for total nicotine and TSNAs, including 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), using gas chromatography or liquid chromatography with mass spectrometric detection. Unionised nicotine concentrations were calculated using product pH and total nicotine concentrations. Fourier transform infrared spectroscopy was used to help categorise or characterise some products. Results Total nicotine content varied from 0.16 to 34.1 mg/g product, whereas, the calculated unionised nicotine ranged from 0.05 to 31.0 mg/g product; a 620-fold range of variation. Products ranged from pH 5.2 to 10.1, which translates to 0.2% to 99.1% of nicotine being in the unionised form. Some products have very high pH and correspondingly high unionised nicotine (eg, gul powder, chimó, toombak) and/or high TSNA (eg, toombak, zarda, khaini) concentrations. The concentrations of TSNAs spanned five orders of magnitude with concentrations of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) ranging from 4.5 to 516 000 ng/g product. Conclusions These data have important implications for risk assessment because they show that very different exposure risks may be posed through the use of these chemically diverse oral tobacco products. Because of the wide chemical variation, oral tobacco products should not be categorised together when considering the public health implications of their use.

Tobacco Smoke Exposure and Levels of Urinary Metals in the U.S. Youth and Adult Population: The National Health and Nutrition Examination Survey (NHANES) 1999–2004

We assessed 12 urine metals in tobacco smoke-exposed and not exposed National Health and Nutrition Examination Survey participants. Our analysis included age, race/ethnicity, and poverty status. Gender and racial/ethnic differences in cadmium and lead and creatinine-adjusted and unadjusted data for group comparisons are presented. Smokers’ had higher cadmium, lead, antimony, and barium levels than nonsmokers. Highest lead levels were in the youngest subjects. Lead levels among adults with high second-hand smoke exposure equaled smokers. Older smokers had cadmium levels signaling the potential for cadmium-related toxicity. Given the potential toxicity of metals, our findings complement existing research on exposure to chemicals in tobacco smoke.

Surveillance of moist snuff: total nicotine, moisture, pH, un-ionized nicotine, and tobacco-specific nitrosamines

In 2005, approximately 2.3% of U.S. adults used smokeless tobacco. Moist snuff leads all types of smokeless tobacco in revenues and marketing expenditures. The U.S. Surgeon General has concluded that smokeless tobacco use can lead to nicotine addiction. The National Toxicology Program of the National Institutes of Health has classified smokeless tobacco as a human carcinogen. Tobacco-specific nitrosamines (TSNAs) are potent carcinogens in smokeless tobacco products, and the pH of the product influences the content of un-ionized nicotine which is the form of nicotine most rapidly absorbed in the mouth. The Centers for Disease Control and Prevention analyzed 40 top-selling brands of moist snuff to measure nicotine, moisture, pH, un-ionized nicotine, and TSNAs, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The study findings indicate that moist snuff brands varied widely in content of rapidly absorbed, addictive un-ionized nicotine (500-fold range) and of carcinogenic TSNAs (18-fold range). Product characteristics such as packaging and moisture content appeared to be correlated with concentrations of un-ionized nicotine, and flavor characteristics of low-priced brands may correlate with TSNA concentrations. These findings warrant further study in light of (a) the marketing of smokeless tobacco for use in places where smoking is prohibited, (b) the promotion of smokeless tobacco as a harm-reduction product, and (c) the ever-expanding number of highly flavored smokeless varieties brought to the market.

Determination of tar, nicotine, and carbon monoxide yields in the mainstream smoke of selected international cigarettes

Objective: Survey of nicotine, tar, and carbon monoxide (CO) smoke deliveries from 77 cigarette brands purchased in 35 countries was conducted using a standardised machine smoking method. The goal of this study was to determine regional variations and differences in the tar, nicotine, and CO smoke yields of a cigarette brand manufactured by a leading transnational corporation and of non-US locally popular cigarette brands. Design: The majority of the cigarettes were purchased in each of the participating countries by delegate members of the World Health Organization and forwarded to the Centers for Disease Control and Prevention for analysis. Smoke deliveries were determined using a standardised smoking machine method and subsequent gravimetric and gas chromatography analysis. Results: The smoke deliveries varied widely. Mainstream smoke deliveries varied from 6.8 to 21.6 mg tar/cigarette, 0.5 to 1.6 mg nicotine/cigarette, and 5.9 to 17.4 mg CO/cigarette. In addition to the smoke deliveries, the cigarettes were examined to determine physical parameters such as filter composition, length, and ventilation levels. Conclusion: Analysis of the smoke deliveries suggested that cigarettes from the Eastern Mediterranean, Southeast Asia, and Western Pacific WHO regions tended to have higher tar, nicotine, and CO smoke deliveries than did brands from the European, American, or African WHO regions surveyed.

Tobacco-related disease mortality among men who switched from cigarettes to spit tobacco

Background: Although several epidemiological studies have examined the mortality among users of spit tobacco, none have compared mortality of former cigarette smokers who substitute spit tobacco for cigarette smoking (“switchers”) and smokers who quit using tobacco entirely. Methods: A cohort of 116 395 men were identified as switchers (n = 4443) or cigarette smokers who quit using tobacco entirely (n = 111 952) when enrolled in the ongoing US American Cancer Society Cancer Prevention Study II. From 1982 to 31 December 2002, 44 374 of these men died. The mortality hazard ratios (HR) of tobacco-related diseases, including lung cancer, coronary heart disease, stroke and chronic obstructive pulmonary disease, were estimated using Cox proportional hazards regression modelling adjusted for age and other demographic variables, as well as variables associated with smoking history, including number of years smoked, number of cigarettes smoked and age at quitting. Results: After 20 years of follow-up, switchers had a higher rate of death from any cause (HR 1.08, 95% confidence interval (CI) 1.01 to 1.15), lung cancer (HR 1.46, 95% CI 1.24 to 1.73), coronary heart disease (HR 1.13, 95% CI 1.00 to 1.29) and stroke (HR 1.24, 95% CI 1.01 to 1.53) than those who quit using tobacco entirely. Conclusion: The risks of dying from major tobacco-related diseases were higher among former cigarette smokers who switched to spit tobacco after they stopped smoking than among those who quit using tobacco entirely.

Small-group discussions on menthol cigarettes: listening to adult African American smokers in Atlanta, Georgia.

Objective. In 2002, the First Conference on Menthol Cigarettes brought together researchers from diverse backgrounds to summarize what is known about menthol cigarettes and the people who smoke them, and to identify areas of needed research on menthol cigarettes. Since the conference, PubMed reports 24 articles, including the conference proceedings, on menthol cigarettes and African Americans. Many of the articles address epidemiological or biomedical topics. While there has been some focus on social influences and marketing issues, more research and a greater focus on this topic are needed. Design. To stimulate research on a population disproportionately burdened by the health effects of smoking, we conducted small-group discussions in 2005 with adult African American smokers in Atlanta, Georgia. Each group discussion focused on a different topic: smoking behavior and preferences, perceptions of social influences, health effects and perceived harmfulness of menthol, quitting menthol cigarette smoking, or the influence of marketing and advertising of menthol cigarettes. Results. Themes emerged from the discussions: (1) emulation of black culture by white youth and racial integration of neighborhoods and communities may have modified the perception that African Americans smoke menthol cigarettes and whites smoke non-menthol cigarettes; (2) non-menthol cigarette smokers were thought to be ‘hardcore’ smokers with less interest in quitting; (3) switching to non-menthol cigarettes was discussed as a way of quitting cigarettes for habitual menthol smokers; and, (4) smoking menthol cigarettes was thought to lead to fewer negative health effects. Conclusion. Some topics suggested by the participants warrant further investigation. More research is needed to assess the pervasiveness of these beliefs and their potential utility for smoking cessation interventions.

Unintentional Child Poisonings Through Ingestion of Conventional and Novel Tobacco Products

OBJECTIVE: This study examines child poisonings resulting from ingestion of tobacco products throughout the nation and assesses the potential toxicity of novel smokeless tobacco products, which are of concern with their discreet form, candy-like appearance, and added flavorings that may be attractive to young children. METHODS: Data representing all single-substance, accidental poisonings resulting from ingestion of tobacco products by children <6 years of age, reported to poison control centers, were examined. Age association with ingestion of smokeless tobacco versus other tobacco products was tested through logistic regression. Total nicotine content, pH, and un-ionized nicotine level were determined, and the latter was compared with values for moist snuff and cigarettes. RESULTS: A total of 13705 tobacco product ingestion cases were reported, >70% of which involved infants <1 year of age. Smokeless tobacco products were the second most common tobacco products ingested by children, after cigarettes, and represented an increasing proportion of tobacco ingestions with each year of age from 0 to 5 years (odds ratio: 1.94 [95% confidence interval: 1.86–2.03]). A novel, dissolvable, smokeless tobacco product with discreet form, candy-like appearance, and added flavorings was found to contain an average of 0.83 mg of nicotine per pellet, with an average pH of 7.9, which resulted in an average of 42% of the nicotine in the un-ionized form. CONCLUSION: In light of the novelty and potential harm of dissolvable nicotine products, public health authorities are advised to study these products to determine the appropriate regulatory approach.

Effects of 10 Cigarette Smoke Condensates on Primary Human Airway Epithelial Cells by Comparative Gene and Cytokine Expression Studies

Cigarettes vary in tobacco blend, filter ventilation, additives, and other physical and chemical properties, but little is known regarding potential differences in toxicity to a smokers airway epithelia. We compared changes in gene expression and cytokine production in primary normal human bronchial epithelial cells following treatment for 18 h with cigarette smoke condensates (CSCs) prepared from five commercial and four research cigarettes, at doses of approximately 4 microg/ml nicotine. Nine of the CSCs were produced under a standard International Organization for Standardization smoking machine regimen and one was produced by a more intense smoking machine regimen. Isolated messenger RNA (mRNA) was analyzed by microarray hybridization, and media was analyzed for secreted cytokines and chemokines. Twenty-one genes were differentially expressed by at least 9 of the 10 CSCs by more than twofold, including genes encoding detoxifying and antioxidant proteins. Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and NAD(P)H dehydrogenase, quinone 1 (NQO-1) were selected for validation with quantitative real-time PCR (qRT-PCR) and Western blot analyses. NQO-1 expression determined with microarrays, qRT-PCR, and Western blotting differed among the CSC types, with good correlation among the different assays. CYP1A1 mRNA levels varied substantially, but there was little correlation with the protein levels. For each CSC, the three most induced and three most repressed genes were identified. These genes may be useful as markers of exposure to that particular cigarette type. Furthermore, differences in interleukin-8 secretion were observed. These studies lay the foundation for future investigations to analyze differences in the responses of in vivo systems to tobacco products marketed with claims of reduced exposure or reduced harm.

Mutagenicity of 11 cigarette smoke condensates in two versions of the mouse lymphoma assay

Cigarette smoke condensate (CSC) is genotoxic in nearly all assays in which it has been tested. In this study, we investigated the mutagenicity of 11 CSCs using the microwell and soft-agar versions of the mouse lymphoma assay (MLA). These CSCs were prepared from commercial or experimental cigarettes, 10 of them were produced using International Organisation for Standardisation (ISO) conditions and one CSC was generated using intense Massachusetts Department of Public Health (MDPH) conditions. In the presence of rat liver S9, the L5178Y/Tk(+/-) mouse lymphoma cells were treated with 11 CSCs at different concentrations (25-200 μg/ml) for 4 h. All CSCs resulted in dose-dependent increases of both cytotoxicity and mutagenicity in both versions of the MLA. The mutagenic potencies of the CSCs were calculated as mutant frequency per microgram CSC from the slope of the linear regression of the dose-response curves and showed no correlations with the tar yield of the cigarette or nicotine concentrations of the CSCs. Comparing two CSCs produced from the same commercial cigarettes using two different smoking conditions, the one generated under ISO conditions was more mutagenic than the other generated under intense conditions on a per microgram CSC basis. We also examined the loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11 for the mutants induced by 11 CSCs. The most common type of mutation observed was LOH with chromosome damage spanning less than ∼34 Mbp. These results indicate that the MLA identifies different genotoxic potencies among a variety of CSCs and that the results from both versions of the assay are comparable.