Rationale Nicotine uptake during smoking was estimated by either analyzing the metabolites of nicotine in various body fluids or by analyzing filters from smoked cigarettes. However, no comparison of the filter analysis method with body fluid analysis methods has been published. Objectives Correlate nicotine uptake estimates between filter analysis, salivary cotinine, and urinary excretion of selected nicotine metabolites to determine the suitability of these methods in estimating nicotine absorption in smokers of filtered cigarettes. Materials and methods A 5-day clinical study was conducted with 74 smokers who smoked 1-19 mg Federal Trade Commission tar cigarettes, using their own brands ad libitum. Filters were analyzed to estimate the daily mouth exposure of nicotine. Twenty-four-hour urine samples were collected and analyzed for nicotine, cotinine, and 3′-hydroxycotinine plus their glucuronide conjugates. Saliva samples were collected daily for cotinine analysis.Results Each method correlated significantly (p<0.01) with the other two. The best correlation was between the mouth exposure of nicotine, as estimated by filter analysis, and urinary nicotine plus metabolites. Multiple regression analysis implies that saliva cotinine and urinary output are dependent on nicotine mouth exposure for multiple days. Creatinine normalization of the urinary metabolites degrades the correlation with mouth exposure. Conclusions The filter analysis method was shown to correlate with more traditional methods of estimating nicotine uptake. However, because filter analysis is less complicated and intrusive, subjects can collect samples easily and unsupervised. This should enable improvements in study compliance and future study designs.

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. [Beitr. Tabakforsch. Int. 22 (2006) 176-184] ZUSAMMENFASSUNG Zur Abschätzung der Kondensat-und Nikotinaufnahme durch Raucher können Methoden verwendet werden, die auf Analysen von Zigarettenfiltern beruhen. Diesen Methoden liegt die Messung der Filtrationseffizienz (FE) zu Grunde. Die Filtrationseffizienz kann jedoch sowohl durch das Zigarettendesign, wie zum Beispiel Filtertyp und Grad der Filterventilation, als auch durch Faktoren des menschlichen Rauchverhaltens, wie die Flussrate während eines Zuges und die Stummellänge, beeinflusst werden. In unserer Untersuchung wurden zwei Filteranalysemethoden berücks-ichtigt. Die eine Methode basiert auf der Analyse der ganzen Filter. Hierbei werden Durchschnittswerte der FE verwendet, die unter verschiedenen maschinellen Abrauchbedingungen ermittelt wurden. Bei der anderen, einer "Teil-Filter" Methode, wird ein 10 mm großes Stück vom mundseitigen Ende des Filters untersucht. In diesem Bereich bleibt die FE, unabhängig von den Flussraten während des Zuges und der Stummellänge, relativ konstant. Die Werte des menschlichen Rauchverhaltens stammen von 10 Rauchern, die jeweils sechs handelsübliche Zigaretten mit Kondensatgehalten von 1 bis 12 mg (Methode der Internationalen Organisation für Normung, ISO) rauchten. Mit diesen Parametern wurde ein Rauch-Duplikator betrieben und die ermittelten Kondensat-und Nikotinwerte wurden mit den Schätzungen verglichen, die mit der Gesamt-und der Teil-Filter Methode ermittelt wurden. Diese Ergebnisse zeigen, dass beide Filteranalysemethoden eine gute Korrelation mit den aus dem Rauch-D...

No abstract

In this study, a comparison between the chemical composition of the particulate-phase of exhaled smoke and that of smoke generated with a smoking machine has been performed. For this purpose, eight human subjects smoked a common Lights (10.6 mg ‘tar’/cig) commercial cigarette and the exhaled particulate-phase smoke from three cigarettes was collected on Cambridge pads for each smoker. The smoke collection from the human subjects was vacuum assisted. The cigarette butts from the smokers were collected and analyzed for nicotine. The machine smoking was performed with a Borgwaldt RM20 CSR smoking machine working under conditions recommended by the U.S. Federal Trade Commission (FTC). The nicotine levels for the cigarette butts from the smokers were used to normalize the level of exhaled smoke condensate to that of the FTC smoking conditions. The smoke condensates from exhaled smoke as well as that from the machine smoking were analyzed by a gas chromatographic technique with mass spectral peak identification. The retention efficiency for 160 compounds was calculated from the ratio of the compound peak areas in the exhaled smoke (normalized by the corresponding butt nicotine level) vs. the areas of the corresponding peaks from the chromatogram of the smoke generated by the smoking machine. In the calculation of the results, it was assumed that the composition of mainstream smoke remains practically constant at different smoking regimes. All compounds found in the machine-generated smoke were also present in the exhaled smoke, but at different levels. About one third of the compounds were retained more than 66% by the smoker. Another third of the compounds were retained between 33% and 66%, and the rest of the compounds were retained very little from the mainstream particulate-phase of the cigarette smoke. The compounds retained more than 66% were in general compounds with lower molecular weight and with higher water solubility, which eluted first from a 5% phenyl dimethyl-polysiloxane (DB-5MS) chromatographic column. The compounds retained less than 33% from smoke were those with higher molecular weights and boiling points, which had longer elution times from the chromatographic column. These compounds consisted mainly of long-chain hydrocarbons (saturated or squalene type) and phytosterol-type compounds. The compounds retained between 33% and 66% had intermediate chromatographic retention times. No attempt was made to evaluate or identify new compounds formed in the exhaled smoke. The results were obtained from a limited number of subjects, but among these the retentions for individual compounds did not show large differences, indicating that the retention process is not very different for the subjects evaluated. An attempt was made to verify whether or not the retention of compounds by the smoker is analogous to a distribution process. Only weak correlations were obtained between the human retention and octanol/water partition coefficients or between the human retention and the chromatographic retention times of individual compounds.

SUMMARYThe analysis of spent filters from human-smoked (HS) cigarettes has been used to estimate cigarette yields for over three decades. Until recently, the whole filter was used for estimation; however a part-filter method has been shown to improve the accuracy of estimated HS yields. The partfilter method uses only the mouth-end portion of the filter, downstream of the ventilation holes, for analysis. In this portion, the filtration efficiency is relatively constant irrespective of typical puff flow rates of humans and also minimizes butt length effects (e.g. nicotine condensation) on filtration efficiency. Therefore, the estimations of HS cigarette yields are more robust to human smoking conditions than previous whole-filter methods. British American Tobacco has adopted this method to obtain better understanding of how smokers actually use their products in their everyday environment. This can give information to help understand approaches to harm reduction. Since adopting this method, modifications and quality control features have been added to improve the accuracy of the estimation. This paper will describe in detail the methodology currently in use, along with sources of error, storage studies, quality control, repeatability and reproducibility. [Beitr. Tabakforsch. Int. 23 (2009) 232-243]

Methodologies have been developed, described and demonstrated that convert mouth exposure estimates of cigarette smoke constituents to dose by accounting for smoke spilled from the mouth prior to inhalation (mouth-spill (MS)) and the respiratory retention (RR) during the inhalation cycle. The methodologies are applicable to just about any chemical compound in cigarette smoke that can be measured analytically and can be used with ambulatory population studies. Conversion of exposure to dose improves the relevancy for risk assessment paradigms. Except for urinary nicotine plus metabolites, biomarkers generally do not provide quantitative exposure or dose estimates. In addition, many smoke constituents have no reliable biomarkers. We describe methods to estimate the RR of chemical compounds in smoke based on their vapor pressure (VP) and to estimate the MS for a given subject. Data from two clinical studies were used to demonstrate dose estimation for 13 compounds, of which only 3 have urinary biomarkers. Compounds with VP > 10−5 Pa generally have RRs of 88% or greater, which do not vary appreciably with inhalation volume (IV). Compounds with VP < 10−7 Pa generally have RRs dependent on IV and lung exposure time. For MS, mean subject values from both studies were slightly greater than 30%. For constituents with urinary biomarkers, correlations with the calculated dose were significantly improved over correlations with mouth exposure. Of toxicological importance is that the dose correlations provide an estimate of the metabolic conversion of a constituent to its respective biomarker.

SummaryThe vapor pressure of nicotine has been reported for unprotonated nicotine and for nicotine-water solutions. Yet no published values exist for nicotine in any commercially relevant matrix or for protonated forms (e.g., tobacco, smoke, electronic cigarette solutions, nicotine replacement products, nicotine salts). Therefore a methodology was developed to measure nicotine activity (defined as the vapor pressure from a matrix divided by the vapor pressure of pure nicotine). The headspace concentration of nicotine was measured for pure nicotine and tobacco stored at 23, 30, and 40 °C which allowed for conversion to vapor pressure and nicotine activity and for the estimation of enthalpy of vaporization. Burley, Flue-cured, Oriental, and cigarette blends were tested. Experiments were conducted with pure nicotine initially until the storage and sampling techniques were validated by comparison with previously published values. We found that the nicotine activity from tobacco was less than 1% with Burley > Flue-cured > Oriental. At 23 °C the nicotine vapor pressure averaged by tobacco type was 0.45 mPa for Oriental tobacco, 1.8 mPa for Flue-cured, 13 mPa for Burley while pure nicotine was 2.95 Pa. In general, the nicotine activity increased as the (calculated) unprotonated nicotine concentration increased. The nicotine enthalpy of vaporization from tobacco ranged from 77 kJ/mol to 92 kJ/mol with no obvious trends with regard to tobacco origin, type, stalk position or even the wide range of nicotine activity. The mean value for all tobacco types was 86.7 kJ/mol with a relative standard deviation of 6.5% indicating that this was an intrinsic property of the nicotine form in tobacco rather than the specific tobacco properties. This value was about 30 kJ/mol greater than that of pure nicotine and is similar to the energy needed to remove a proton from monoprotonated nicotine.

No abstract