Mike Dixon

The Retention of Tobacco Smoke Constituents in the Human Respiratory Tract

Measurements on the retention of cigarette smoke constituents in the human respiratory tract have been undertake for more than 100 years. The first studies on nicotine retention were begun by Lehmann in Germany in 1903 and published in 1908. The first studies on the retention of smoke particulate matter were published by Baumbereger in the United States in 1923. Since those early publications, many studies have been undertaken, more or less continuously. This article is a review of the work that has been done over the last 100 years, including a large number of unpublished studies undertaken by British American Tobacco in Southampton, UK. The techniques used have evolved over the years and there is a certain amount of variation in the data. However, the general trends in the results are reassuringly consistent. The bulk of the studies indicate that, on average, 60 to 80% of the mainstream smoke particulate matter is retained in the lungs after inhalation. For nicotine, carbon monoxide, nitric oxide, and aldehydes the total retentions are of the order of 90–100, 55–65, 100, and approximately 90%, respectively, during cigarette smoke inhalation. For most smoke constituents the retentions in the mouth only are considerably smaller than in the whole respiratory tract. The lung retention values for smoke particulate matter are dependent on the depth of inhalation, hold time in the lungs, exhalation volume, and other factors. However, the degree of nicotine retention following inhalation is not markedly influenced by changes in respiratory parameters. Furthermore, the percentage retentions for smoke particulate matter and nicotine are smaller for nonsmoking subjects exposed to environmental tobacco smoke than with active smoking. The smoke retentions are related to properties of the smoke aerosol particles and gases and their behavior as they travel through the respiratory tract. This includes particle growth in the respiratory tract and evaporation of gases out of the particles, and relevant aspects of these processes are also reviewed.

Validation of methods for determining consumer smoked cigarette yields from cigarette filter analysis

Abstract Methods based on the analyses of cigarette filters have been used to estimate ‘tar’ and nicotine yields to smokers. These methods rely on the measurement of filtration efficiencies (FEs). However FEs may be influenced by both cigarette design features e.g., type of filter and levels of filter ventilation, and human smoking behaviour factors such as puff flow-rates and cigarette butt lengths. Two filter analysis methods are considered in our study. One is based on the analysis of whole filters using average values of FEs obtained from a range of machine smoking regimes. The other, a ‘part filter’ method, analyses a 10 mm section from the mouth end of the filter where the FE remains relatively constant irrespective of puff flow rates and butt lengths. Human puffing behaviour records were obtained from 10 smokers, each smoking six commercial cigarettes ranging from 1 mg to 12 mg ‘tar’ yields [International Standard (ISO) values]. These records were used to drive a human smoke duplicator and the resulting ‘tar’ and nicotine yields obtained from duplication were compared with the estimates obtained from ‘whole’ and ‘part filter’ analysis. The results indicated that whilst both filter methods gave good correlations with nicotine and ‘tar’ yields obtained from smoke duplication, the ‘part filter’ method was less susceptible to the effect of nicotine condensation and changes in FEs and hence gave a more accurate assessment of yields than the ‘whole filter’ method.

A study to evaluate the effect on Mouth Level Exposure and biomarkers of exposure estimates of cigarette smoke exposure following a forced switch to a lower ISO tar yield cigarette

A forced switch to a lower ISO tar yield cigarette was used in a clinical study, conducted in Germany, that compared two methods of estimating exposure to cigarette smoke. Pre- and post-switch estimates of Mouth Level Exposure (MLE) to nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene and acrolein were obtained by chemical analysis of spent cigarette filters for nicotine content. Similarly, pre- and post-switch estimates of uptake of these smoke constituents were achieved by analysis of corresponding urinary biomarkers of exposure (BoE): total nicotine equivalents; total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL); total 1-hydroxypyrene (1-OHP), and 3-hydroxypropyl-mercapturic acid (3-HPMA), plus the nicotine metabolite cotinine, in plasma and saliva. Three hundred healthy volunteers were recruited comprising 100 smokers of each of 9-10 and 4-6 mg ISO tar yield cigarettes and 50 smokers of 1-2mg ISO tar yield cigarettes and 50 non-smokers. Fifty smokers of each of the 9-10 and 4-6 mg ISO tar yield cigarettes took part in the switching aspects of this study whilst the remaining smokers formed non-switching control groups who smoked their usual ISO tar yield cigarette throughout the study. After 5 days, all subjects were admitted into a clinic where baseline measures of MLE and BoE were obtained. The 10mg switching group was then switched to the 4 mg ISO tar yield cigarette and the 4 mg ISO tar yield switching group switched to the 1mg cigarette. Subjects returned home for 12 days, continuing to smoke the supplied cigarettes before being readmitted into the clinic where samples were collected for MLE and BoE analysis. Changes in daily exposure estimates were determined on a group and individual basis for both methods. The pre- to post-switch directional changes in MLEs and their corresponding BoEs were generally consistent and the MLE/BoE relationship maintained. Switching to a lower yield cigarette generally resulted in reductions in exposure with the resultant exposure level being similar to that seen in regular smokers of the lower yield cigarette.

A survey of mouth level exposure to cigarette smoke in the United States.

Smoke yields determined by a machine-based smoking method cannot adequately predict exposures experienced by human smokers. In this work, a filter analysis technique which addresses this fundamental limitation was used to measure mouth level exposures (MLE) to tar and nicotine in 1330 smokers of 26 brand-styles of US cigarettes covering a wide range of machine-generated yields. Despite the high degree of variability observed among individual smokers, MLEs were significantly correlated with machine-derived tar and nicotine yields (r=0.423 for nicotine MLE/cigarette; r=0.493 for tar MLE/cigarette; p<0.001 for both). Mean tar and nicotine MLE was higher for males than for females. Mean MLE across races was generally similar. Menthol cigarettes tended toward lower MLE than non-menthol cigarettes and King-Size cigarettes (≈ 83 mm) tended toward lower MLE than 100s cigarettes (≈ 100 mm), though those trends were not statistically significant. There were good agreements between MLEs measured in a group of 159 subjects smoking their usual cigarette brand-style on two separate occasions and between two independent groups of subjects smoking the same brand-styles. The results indicated that the filter analysis method used had sufficient precision to show similarity among groups.

Relationship between cigarette format and mouth-level exposure to tar and nicotine in smokers of Russian king-size cigarettes

Differences in length and circumference of cigarettes may influence smoker behaviour and exposure to smoke constituents. Superslim king-size (KSSS) cigarettes (17mm circumference versus 25mm circumference of conventional king-size [KS] cigarettes), have gained popularity in several countries, including Russia. Some smoke constituents are lower in machine-smoked KSSS versus KS cigarettes, but few data exist on actual exposure in smokers. We investigated mouth-level exposure (MLE) to tar and nicotine in Russian smokers of KSSS versus KS cigarettes and measured smoke constituents under machine-smoking conditions. MLE to tar was similar for smokers of 1mg ISO tar yield products, but lower for smokers of 4mg and 7mg KSSS versus KS cigarettes. MLE to nicotine was lower in smokers of 4mg KSSS versus KS cigarettes, but not for other tar bands. No gender differences were observed for nicotine or tar MLE. Under International Organization for Standardization, Health Canada Intense and Massachusetts regimes, KSSS cigarettes tended to yield less carbon monoxide, acetaldehyde, nitric oxide, acrylonitrile, benzene, 1,3-butadiene and tobacco-specific nitrosamines, but more formaldehyde, than KS cigarettes. In summary, differences in MLE were observed between cigarette formats, but not systematically across pack tar bands.

Tobacco industry research on smoking and cigarette toxicity.

Michael Dixon and Stewart Massey (April 22, p 1317) criticise our review of internal research by British American Tobacco (BAT) and Imperial Tobacco Limited (ITL) on smoking behaviour and product design. They dispute the notion that BAT and ITL have exploited the international testing standards for cigarette emission. Our paper describes internal documents which suggest that BAT designed products to maximise the discrepancy between: (a) the tar and nicotine numbers under standardised testing and (b) the levels that could be delivered to consumers. Moreover, the documents we reviewed indicate that this strategy was kept secret from consumers and regulators. Dixon and Massey seem to suggest that this was “fair game” because regulators acknowledged certain limitations of the testing regimen when it was introduced. Their argument would be more compelling had their companies not also marketed these brands as lowtar alternatives for health-concerned smokers and had they not attached misleading descriptors such as “light” and “mild” to brands that generated low machine readings. Indeed, BAT product scientists worked closely with the marketing department to develop such synergies. Dixon and Massey also suggest that the industry has previously disclosed much of the research we describe in our paper. Even if all of the information in our review had been previously disclosed, it still warrants alarm among consumers and regulators. However, to suggest that the industry has been forthright about their product research and strategy is simply not credible. Tobacco manufacturers have a track record of publishing only those research fi ndings that either obscure or undermine scientifi c questions with public-health implications. Additionally, our paper cites a memo from Alan Heard, a senior BAT scientist, to S R Massey. Heard writes: “Instinctively I question the idea of publishing papers in relation to smoking behaviour...I think it is unwise to publish any fi ndings of our studies on smoking behaviour on any smoking products.” Dixon and Massey also reject the suggestion that BAT and ITL have designed “elastic” cigarettes. The term “elastic” is not our invention; rather, it is drawn from the BAT documents we reviewed. Our paper may or may not include the best examples of product elasticity; however, statements made by senior BAT employees leave no question as to the reality of “elastic” cigarette designs.