Edward B. Sanders

A model that distinguishes the pyrolysis of d-glucose, d-fructose, and sucrose from that of cellulose. Application to the understanding of cigarette smoke formation

Abstract A literature review is presented on the pyrolysis chemistry of mono-, di- and polysaccharides, with emphasis on d -glucose, d -fructose, sucrose and cellulose. A model, consisting of nine factors, is proposed to explain the pyrolysis product distributions observed. Product profiles depend on experimental conditions, particularly pyrolysis temperatures and residence times and the presence of other substances, e.g. acids, bases and salts. At higher temperatures, polynuclear aromatic hydrocarbons (PAHs) are the predominant condensed-phase products from carbohydrates. At lower temperatures, pyrolysis of pure cellulose generally favors 1,6-anhydro-β- d -glucopyranose (levoglucosan) formation as well as low molecular weight oxygenated products, e.g. glycolaldehyde. Cellulose pyrolysis also yields other products, including furans. Pyrolysis of d -glucose, d -fructose, and sucrose appears to favor furan production rather than anhydrosugars and low molecular weight carbonyl compounds. Furans distill rapidly from the pyrolysis zone rather than degrade. For reducing sugars, the ability to react from their acyclic isomers to form cyclic five-membered rings, i.e. furan precursors, may be a significant controlling factor. Multiple pathways to products are likely in all these pyrolyses. These pyrolysis studies provide parallels to mainstream (MS) cigarette smoke precursor–product relationships.

Meta-analysis of the relation between European and American smokeless tobacco and oral cancer

BackgroundSmokeless tobacco is often referred to as a major contributor to oral cancer. In some regions, especially Southeast Asia, the risk is difficult to quantify due to the variety of products, compositions (including non-tobacco ingredients) and usage practices involved. In Western populations, the evidence of an increased risk in smokeless tobacco users seems unclear, previous reviews having reached somewhat differing conclusions. We report a detailed quantitative review of the evidence in American and European smokeless tobacco users, and compare our findings with previous reviews and meta-analyses.MethodsFollowing literature review a meta-analysis was conducted of 32 epidemiological studies published between 1920 and 2005 including tests for homogeneity and publication bias.ResultsBased on 38 heterogeneous study-specific estimates of the odds ratio or relative risk for smokeless tobacco use, the random-effects estimate was 1.87 (95% confidence interval 1.40–2.48). The increase was mainly evident in studies conducted before 1980. No increase was seen in studies in Scandinavia. Restricting attention to the seven estimates adjusted for smoking and alcohol eliminated both heterogeneity and excess risk (1.02; 0.82–1.28). Estimates also varied by sex (higher in females) and by study design (higher in case-control studies with hospital controls) but more clearly in studies where estimates were unadjusted, even for age. The pattern of estimates suggests some publication bias. Based on limited data specific to never smokers, the random-effects estimate was 1.94 (0.88–4.28), the eight individual estimates being heterogeneous and based on few exposed cases.ConclusionSmokeless tobacco, as used in America or Europe, carries at most a minor increased risk of oral cancer. However, elevated risks in specific populations or from specific products cannot definitely be excluded.

Does Increased Cigarette Consumption Nullify Any Reduction in Lung Cancer Risk Associated with Low-Tar Filter Cigarettes?

Epidemiological data suggest that smoking filter and lower tar cigarettes is associated with less lung cancer risk than is smoking plain and higher tar cigarettes. A recent National Cancer Institute monograph claimed these apparent benefits of lower delivery products may be illusory if relative risks are adjusted for daily consumption, and switching leads to “compensation” for reduced nicotine intake by increasing numbers of cigarettes smoked. To investigate this, we compared relative risks unadjusted and adjusted for daily cigarette consumption. Overall estimates of the filter/plain relative risk, using random-effects meta-analysis, were 0.61 (95% confidence interval 0.54 to 0.70) for unadjusted data and 0.66 (0.58 to 0.76) for adjusted data. The lower tar/higher tar relative risk was estimated as 0.60 (0.45 to 0.81) for unadjusted data and 0.73 (0.64 to 0.83) for adjusted data. The risk reductions were clearly seen regardless of gender, study location, period, or design, and when only studies providing both unadjusted and adjusted estimates were considered. Whether or not relative risk estimates are adjusted for cigarette consumption is not crucial to the conclusion of a clear advantage to filter cigarettes and tar reduction. Data on “compensation” for amount smoked were reviewed and any increase following switching to reduced-tar-yield cigarettes was shown to be quite small. Other biases in the epidemiology are also discussed, and we conclude that the apparent advantage to reduced-tar-delivery products is real and likely to be a marked underestimate of the reduction in lung cancer risk from lifetime smoking of low-tar cigarettes.

Does use of flue-cured rather than blended cigarettes affect international variation in mortality from lung cancer and COPD?

We compared risk of lung cancer and chronic obstructive pulmonary disease (COPD) associated with flue-cured and blended cigarettes. Mortality and smoking data were collected for 1971–2000 by sex, age, and period for three countries with a mainly flue-cured market and four with a blended market. Epidemiological relative risk estimates for current and ex smoking were summarized. Smoking statistics and mortality were compared between flue-cured cigarette and blended cigarette countries. Unadjusted mortality rates were generally lower in blended cigarette countries early on, with the difference diminishing or reversing by the 1990s. Differences by cigarette type were rarely significant, due to variations, particularly for COPD, between countries within cigarette type. Current smoking prevalence was generally lower in blended cigarette countries in 1971–1975, with the difference reducing over time. Differences by type were never significant, with blended cigarette countries varying markedly. Ex-smoking increased over time and was lower for blended cigarette countries, generally not significantly. Consumption per smoker was somewhat lower for blended cigarette countries. Relative risk estimates for smoking, derived mainly from U.S. and UK studies, varied little by cigarette type. Conclusions based on estimated smoking-related excess mortality were similar to those based on unadjusted mortality rates. There was little indication of any difference between flue-cured and blended cigarettes on risk of lung cancer or COPD. Our approach could have detected differences of about 40% for male lung cancer, or twofold differences for females or for COPD, had they existed. Between-country differences in rates of two major diseases predominantly caused by smoking cannot materially be explained by whether the countries use flue-cured or blended cigarettes.

The ability of the FTC method to quantify nicotine as a function of ammonia in mainstream smoke

Abstract Whether ammonia-forming ingredients added to tobacco and ammonia in smoke affect the ability of the Cambridge filter pad to trap nicotine in the Federal Trade Commission (FTC) method was examined. Three commercial cigarettes, two industry reference cigarettes, and four specially designed test cigarettes were used in this study to represent cigarettes with different construction and mainstream (MS) smoke yield characteristics. One of the commercial cigarettes, a US 1998 Marlboro Lights¯ King Size cigarette, was used as a control cigarette for the four experimental test cigarettes. The test cigarettes differed from the control cigarette as follows: first, a reduction in ammonia-forming ingredients added to the reconstituted tobaccos; second, no ammonia-forming ingredients added to the reconstituted tobacco; third, no ingredients at all added to the reconstituted tobaccos; and fourth, no ingredients at all added to the entire tobacco blend. An XAD-4 tube was placed downstream of the standard Cambridge filter pad in the FTC method to trap the gas-vapor phase nicotine for subsequent analysis. The Cambridge filter pad used in the FTC method was determined to provide greater than 99% trapping efficiency for MS smoke nicotine from cigarettes with widely different soluble ammonia levels in filler and MS smoke ammonia yields.

Occupational acrylonitrile exposure and lung cancer: a meta-analysis.

The present work summarizes the currently available published studies on lung cancer and occupational acrylonitrile exposure. Meta-analytic methods were used to estimate the overall risk. To adjust for the healthy worker effect, rate ratio estimates based on regression analyses and ratios of standard mortality ratios were aggregated. Overall effect estimates were 0.95 (95% CI 0.86 to 1.06) and 1.25 (95% CI 1.10 to 1.43) before and after adjustment for the healthy worker effect, respectively. Therefore, a 25% increase in lung cancer risk attributable to occupational acrylonitrile exposure is suggested. Possible contribution of smoking confounding the increased risk cannot be fully excluded.

Uses and analyses of curtin-hammett/winstein-holness systems involving second order reactions

Abstract The Curtin-Hammett (C-H) principle and the Winstein-Holness (W-H) equation approximate the product ratio and overall rate constant of reaction for systems involving a starting material which exists in two forms, each of which reacts via first-order kinetics to give a different product. The C-H/W-H approximations are valid when the rates of isomer interconversion are significantly faster than the rates of product formation. The present treatment encompasses non-first-order reactions to product. A numerical predictor-corrector technique is used to show (1) that relative reagent concentration can affect both the product ratio and the observed rates of product formation; (2) that the absolute concentration of reagent and substrate can affect the kinetics; and (3) that factors (1) and (2) above can affect the validity of the C-H/W-H approximations for non-first-order C-H/W-H schemes.

Does the use of ingredients added to tobacco increase cigarette addictiveness?: a detailed analysis.

The possibility that ingredients added to tobacco contribute to the addictiveness of cigarette smoking was evaluated by comparing cessation rates of smokers of traditional blended cigarettes to those of smokers of flue-cured cigarettes. Such a comparison is a valid means of assessing cigarette ingredients as traditional blended cigarettes contain ingredients (>20), whereas flue-cured cigarettes contain no or very few ingredients. Separate analysis of 108 treatment groups and 108 control groups from randomized clinical trials of nicotine replacement therapy (NRT) were performed by multiple logistic regressions. The results of these analyses demonstrated slightly higher quit rates for smokers of blended cigarettes (OR = 1.90, 95% CI 1.70–2.13 and OR = 1.32, 95% CI 1.14–1.53 for treatment and control groups, respectively). The control groups were also investigated using classification tree analysis from which no difference in quit rates were observed for smokers of either type of cigarette. Further analyses showed that studies that utilized a high level of psychological support in conjunction with NRT produced at least a two-fold increase in quit rates compared to studies that utilized a low level of psychological support. It was also demonstrated that there is a large difference when results were reported by sustained abstinence compared to point prevalence. Additional meta-analyses found the pooled OR for NRT treatment to be in exact agreement with a recent review that assessed the effectiveness of NRT. Overall these results strongly suggest that ingredients used in the manufacture of traditional blended cigarettes do not increase the inherent addictiveness of cigarettes.

Review of biomarkers to assess the effects of switching from cigarettes to modified risk tobacco products

Abstract Context: One approach to reducing the harm caused by cigarette smoking, at both individual and population level, is to develop, assess and commercialize modified risk alternatives that adult smokers can switch to. Studies to demonstrate the exposure and risk reduction potential of such products generally involve the measuring of biomarkers, of both exposure and effect, sampled in various biological matrices. Objective: In this review, we detail the pros and cons for using several biomarkers as indicators of effects of changing from conventional cigarettes to modified risk products. Materials and methods: English language publications between 2008 and 2017 were retrieved from PubMed using the same search criteria for each of the 25 assessed biomarkers. Nine exclusion criteria were applied to exclude non-relevant publications. Results: A total of 8876 articles were retrieved (of which 7476 were excluded according to the exclusion criteria). The literature indicates that not all assessed biomarkers return to baseline levels following smoking cessation during the study periods but that nine had potential for use in medium to long-term studies. Discussion and conclusion: In clinical studies, it is important to choose biomarkers that show the biological effect of cessation within the duration of the study.

Menthol Cigarettes, Time to First Cigarette, and Smoking Cessation

Summary The goal of the present work is to determine if menthol and non-menthol cigarette smokers differ with respect to time to first cigarette (TTFC) and successful smoking cessation via a meta-analysis of published results. For 13 independent estimates, menthol smokers were slightly but statistically significantly more likely to exhibit TTFC ≤ 5 min (random-effects odds ratio (OR) = 1.12; 95% confidence interval (CI), 1.04–1.21), while 17 independent estimates provided a non-significant difference for TTFC ≤ 30 min (random-effects OR = 1.06; 95% CI, 0.96–1.16). For cessation studies, meta-analysis of 30 published estimates indicated a decreased likelihood for menthol cigarette smokers to quit (random-effects OR = 0.87; 95% CI, 0.80–0.96). There was no difference between cessation rates for Caucasian menthol and non-menthol cigarette smokers, but the results support that African American menthol cigarette smokers find it more difficult to quit. Adjustment of cessation for socioeconomic status eliminated any statistically significant advantage for smoking cessation in non-menthol smokers. In conclusion, these results suggest that the observed differences in cessation rates between menthol and non-menthol cigarette smokers are likely explained by differences in socioeconomic status and also suggest that TTFC may not be a robust predictor of successful smoking cessation.