Joni Jensen

New and traditional smokeless tobacco: comparison of toxicant and carcinogen levels

Declining cigarette use and spreading bans on smoking in public places in the United States are encouraging the U.S. cigarette industry to turn to another tobacco category, smokeless tobacco products. Currently, a number of new brands are being test marketed, including Taboka, Marlboro Snus, Camel Snus, and Skoal Dry. We report here levels of tobacco-specific nitrosamines (TSNAs), alkaloids, anions, polycyclic aromatic hydrocarbons (PAH), and volatile aldehydes in these products, and compare them to the most popular traditional moist snuff brands. Total TSNAs averaged 1.97 microg/g dry weight tobacco in Taboka, Marlboro Snus, and Camel Snus, 4.54 microg/g tobacco in Skoal Dry, and 7.42 microg/g tobacco in traditional brands. The amounts of unprotonated nicotine averaged 0.961 mg/g tobacco in Taboka, Marlboro Snus, and Skoal Dry, 7.22 mg/g tobacco in Camel Snus, and 7.57 mg/g tobacco in traditional brands. Levels of minor tobacco alkaloids were relatively high in Taboka, Marlboro Snus, and Skoal Dry, as compared to other products analyzed here. Levels of nitrite and nitrate in new U.S. smokeless tobacco products and the Swedish snus General were lower than those in the other products. Remarkably high levels of chloride and some PAH were observed in the traditional moist snuff. Crotonaldehyde levels were about five times higher in Taboka and Marlboro Snus than in traditional products. The large variation in the levels of some toxicants and carcinogens analyzed here indicates that more effort is required from the U.S. tobacco industry to further reduce their amounts in new and traditional smokeless tobacco products.

Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation

AIMS To examine the effects of reduced nicotine cigarettes on smoking behavior, toxicant exposure, dependence and abstinence. DESIGN Randomized, parallel arm, semi-blinded study. Setting University of Minnesota Tobacco Use Research Center. INTERVENTIONS Six weeks of: (i) 0.05 mg nicotine yield cigarettes; (ii) 0.3 mg nicotine yield cigarettes; or (iii) 4 mg nicotine lozenge; 6 weeks of follow-up. Measurements Compensatory smoking behavior, biomarkers of exposure, tobacco dependence, tobacco withdrawal and abstinence rate. FINDINGS Unlike the 0.3 mg cigarettes, 0.05 mg cigarettes were not associated with compensatory smoking behaviors. Furthermore, the 0.05 mg cigarettes and nicotine lozenge were associated with reduced carcinogen exposure, nicotine dependence and product withdrawal scores. The 0.05 mg cigarette was associated with greater relief of withdrawal from usual brand cigarettes than the nicotine lozenge. The 0.05 mg cigarette led to a significantly higher rate of cessation than the 0.3 mg cigarette and a similar rate as nicotine lozenge. CONCLUSION The 0.05 mg nicotine yield cigarettes may be a tobacco product that can facilitate cessation; however, future research is clearly needed to support these preliminary findings.

Characterization of tobacco withdrawal symptoms: transdermal nicotine reduces hunger and weight gain

Abstract The accurate assessment of both tobacco withdrawal and the impact of the nicotine patch on withdrawal may be compromised by attrition of subjects, or by subjects smoking during withdrawal. To reduce these occurrences, 211 participants were provided with intensive cessation counseling while trying to quit smoking with either nicotine (21 mg) or placebo transdermal patches. Subject attrition was low, with 80.5% of participants continuing through the 5-week study period. Abstinence rates were also high over this period (75% and 61% in active and placebo groups, respectively). In this multisite, double-blind trial, withdrawal severity was assessed using a nine-item daily self-report questionnaire, and abstinence was confirmed via CO monitoring. Abrupt smoking cessation increased multiple tobacco withdrawal symptoms/signs including craving for cigarettes, irritability, anxiety, appetite, sleep disruption, difficulty concentrating, restlessness, depression, and impatience. Treatment with transdermal nicotine reduced craving for cigarettes, anxiety, irritability, and appetite, as well as weight gain (1.85 versus 2.88 kg mean gain over 4 weeks in active and placebo groups, respectively).

Tobacco-specific nitrosamines in new tobacco products.

New tobacco products, designed to attract consumers who are concerned about the health effects of tobacco, have been appearing on the market. Objective evaluation of these products requires, as a first step, data on their potentially toxic constituents. Tobacco-specific nitrosamines (TSNAs) are an important class of carcinogens in tobacco products, but virtually no data were available on their levels in these products. In the present study, we analyzed several new products-Ariva, Stonewall, Exalt, Revel, Smokey Mountain, and Quest-for TSNAs and compared their TSNA levels with those in nicotine replacement products and conventional smokeless tobacco and cigarette brands. TSNAs were not detected in Smokey Mountain, which is a tobacco-free snuff product. The lowest levels among the new products containing tobacco were in Ariva and Stonewall (0.26-0.28 microg/g wet weight of product). The highest levels in the new products were found in Exalt (3.3 microg/g tobacco), whereas Revel and Quest had intermediate amounts. Only trace amounts were found in nicotine replacement products, and conventional brands had levels consistent with those reported in the literature. These results demonstrate that TSNA levels in new tobacco products range from relatively low to comparable with those found in some conventional brands.

Similar uptake of lung carcinogens by smokers of regular, light, and ultralight cigarettes

Cigarette design has changed markedly over the past 60 years and sales-weighed levels of tar and nicotine have decreased. Currently, cigarettes are classified as regular (>14.5 mg tar), light (>6.5-14.5 mg tar), and ultralight (≤6.5 mg tar), based on a Federal Trade Commission–specified machine-smoking protocol. Epidemiologic studies suggest that there is no difference in lung cancer risk among people who smoke light or ultralight cigarettes compared with regular cigarettes, but the uptake of lung carcinogens in smokers of these types of cigarettes has never been reported. We recruited 175 smokers, who filled out a tobacco use questionnaire in which their current brand was identified as regular, light, or ultralight. Urine samples were collected and analyzed for 1-hydroxypyrene (1-HOP), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides) and total cotinine (cotinine plus its glucuronides). 1-HOP and total NNAL are biomarkers of uptake of polycyclic aromatic hydrocarbons and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, lung carcinogens in cigarette smoke. Total cotinine is a biomarker of nicotine uptake. There were no statistically significant differences in urinary levels of 1-HOP, total NNAL, and total cotinine in smokers of regular, light, and ultralight cigarettes, whether the results were expressed per mg urinary creatinine, per mL of urine, or per mg creatinine divided by cigarettes per day. Levels of machine measured tar were available for the cigarettes smoked by 149 of the subjects. There was no correlation between levels of tar and any of the biomarkers. These results indicate that lung carcinogen and nicotine uptake, as measured by urinary 1-HOP, total NNAL, and total cotinine is the same in smokers of regular, light, and ultralight cigarettes. The results are consistent with epidemiologic studies that show no difference in lung cancer risk in smokers of these cigarettes.

Randomized Trial of Reduced-Nicotine Standards for Cigarettes

BACKGROUND The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. METHODS We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. RESULTS A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. CONCLUSIONS In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875.).

Effects of Smoking Cessation on Eight Urinary Tobacco Carcinogen and Toxicant Biomarkers

We determined the persistence at various times (3, 7, 14, 21, 28, 42, and 56 days) of eight tobacco smoke carcinogen and toxicant biomarkers in the urine of 17 smokers who stopped smoking. The biomarkers were 1-hydroxy-2-(N-acetylcysteinyl)-3-butene (1) and 1-(N-acetylcysteinyl)-2-hydroxy-3-butene (2) [collectively called MHBMA for monohydroxybutyl mercapturic acid] and 1,2-dihydroxy-4-(N-acetylcysteinyl)butane (3) [DHBMA for dihydroxybutyl mercapturic acid], metabolites of 1,3-butadiene; 1-(N-acetylcysteinyl)-propan-3-ol (4, HPMA for 3-hydroxypropyl mercapturic acid), a metabolite of acrolein; 2-(N-acetylcysteinyl)butan-4-ol (5, HBMA for 4-hydroxybut-2-yl mercapturic acid), a metabolite of crotonaldehyde; (N-acetylcysteinyl)benzene (6, SPMA for S-phenyl mercapturic acid), a metabolite of benzene; (N-acetylcysteinyl)ethanol (7, HEMA for 2-hydroxyethyl mercapturic acid), a metabolite of ethylene oxide; 1-hydroxypyrene (8) and its glucuronides (1-HOP), metabolites of pyrene; and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (9) and its glucuronides (total NNAL), a biomarker of exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These biomarkers represent some of the major carcinogens and toxicants in cigarette smoke: 1,3-butadiene, acrolein, crotonaldehyde, benzene, ethylene oxide, polycyclic aromatic hydrocarbons (PAH), and NNK. With the exception of DHBMA, levels of which did not change after cessation of smoking, all other biomarkers decreased significantly after 3 days of cessation (P < 0.001). The decreases in MHBMA, HPMA, HBMA, SPMA, and HEMA were rapid, nearly reaching their ultimate levels (81-91% reduction) after 3 days. The decrease in total NNAL was gradual, reaching 92% after 42 days, while reduction in 1-HOP was variable among subjects to about 50% of baseline. Since DHBMA did not change upon smoking cessation, there appear to be sources of this metabolite other than 1,3-butadiene. The results of this study demonstrate that the tobacco smoke carcinogen/toxicant biomarkers MHBMA, HPMA, HBMA, SPMA, HEMA, 1-HOP, and NNAL are related to smoking and are good indicators of the impact of smoking on human exposure to 1,3-butadiene, acrolein, crotonaldehyde, benzene, ethylene oxide, PAH, and NNK.

Measuring dependence in smokeless tobacco users.

Two scales based on the Fagerstrom Tolerance Questionnaire were developed to measure dependence in smokeless tobacco users. The total score for both scales correlated positively with saliva cotinine levels in subjects, and several individual items produced equally positive correlations. Regression analyses yielded two subsets of three items from each scale that predicted cotinine level. Reports of using smokeless tobacco within 30 min of waking served as a predictor in both models. For the purposes of measuring smokeless tobacco dependence, attention should be given to individual items correlated with saliva cotinine levels that could be used to determine the direction of cessation efforts. Future research should also develop additional items specific to the use of snuff or chewing tobacco and eliminate questions not contributing to the overall scale.

Efficacy of Nicotine Patch in Smokers With a History of Alcoholism

BACKGROUND Smokers with a history of alcohol dependence may have more difficulty quitting, might relapse to alcohol use, and might especially benefit from nicotine replacement therapy for smoking cessation. METHODS One hundred fifteen smokers with a history of alcohol dependence (median of 5 years previously) were randomly assigned to either a 21-mg nicotine patch or placebo in a trial designed to be as similar as possible to a prior study that examined smokers with no history of alcoholism. Both studies were of heavy smokers with similar levels of nicotine dependence; thus, any differences in trials would be due to a history of alcohol problems per se. RESULTS In the current trial, adjusted prolonged smoking abstinence in those with a history of alcohol dependence was higher in the active than the placebo group at end-of-treatment (28% vs. 11%; odds ratio, 3.2; p = 0.04) and at 6-month follow-up (24% vs. 6%; odds ratio, 4.9; p = 0.02). Among subjects not lost to follow-up, none reported drinking problems or increases in craving for alcohol. Smoking abstinence was not lower and the odds ratio for nicotine patch therapy was not greater in smokers with a history of alcohol dependence than in smokers with no such history. CONCLUSIONS Heavy smokers with a history of alcoholism benefit from nicotine patch treatment. A history of alcohol problems after a period of stable sobriety does not appear to influence smoking outcomes or response to nicotine replacement. Although no smokers relapsed to alcohol use, a trial that follows up all subjects is needed to verify this.

Analysis of 23 polycyclic aromatic hydrocarbons in smokeless tobacco by gas chromatography-mass spectrometry

Smokeless tobacco contains 28 known carcinogens and causes precancerous oral lesions and oral and pancreatic cancer. A recent study conducted by our research team identified eight different polycyclic aromatic hydrocarbons (PAHs) in U.S. moist snuff, encouraging further investigations of this group of toxicants and carcinogens in smokeless tobacco products. In this study, we developed a gas chromatography-mass spectrometry method that allows simultaneous analysis of 23 various PAHs in smokeless tobacco after a simple two-step extraction and purification procedure. The method produced coefficients of variation under 10% for most PAHs. The limits of quantitation for different PAHs varied between 0.3 and 11 ng/g tobacco, starting with a 300 mg sample. The recovery of the stable isotope-labeled internal standards averaged 87%. The method was applied to analysis of 23 moist snuff samples that included various flavors of the most popular U.S. moist snuff brands, as well as 17 samples representing the currently marketed brands of spit-free tobacco pouches, a relatively new type of smokeless tobacco. The sum of all detected PAHs in conventional moist snuff averaged 11.6 (+/-3.7) microg/g dry weight; 20% of this amount was comprised of carcinogenic PAHs. The levels of PAHs in new spit-free tobacco products were much lower than those in moist snuff; the sum of all detected PAHs averaged 1.3 (+/-0.28) microg/g dry weight. Our findings render PAHs one of the most prevalent groups of carcinogens in smokeless tobacco. Urgent measures are required from the U.S. tobacco industry to modify manufacturing processes so that the levels of these toxicants and carcinogens in U.S. moist snuff are greatly reduced.