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CORESTA Congress, Kyoto, 2004, SS 08

Dose-response relationships for biomarkers of selected tobacco smoke constituents

MARINER D.C.; St. CHARLES F.K.; KRAUTTER G.; McEWAN M.; APPLETON S.
British American Tobacco, Group R&D, Southampton, UK

Biomarkers have been used to assess exposure to cigarette smoke, both in smokers and non-smokers. Metabolites of nicotine have received most attention, but more recently, reports have been published relating to exposure to other smoke constituents. These reports often describe differences between smokers and non-smokers or smokers of high and low 'tar' products or between levels of consumption (cigarettes per day). While these reports may indicate the presence of dose-response type relationships between levels of exposure and biomarkers they are not well defined. A study has been conducted with 75 smokers of 1-17 mg tar products (FTC). The subjects stayed in a clinic for 5 days during which time they were allowed to smoke their own brand of cigarette whenever they wished. The filters from smoked cigarettes were analysed and estimates of daily mouth intake of nicotine were derived. Five 24-hour urine samples were collected which were analysed for metabolites of acrolein, benzene, 1,3-butadiene, nicotine, NNK and pyrene. Dietary influences were minimised through the consumption of a bland diet. To derive an estimate of the dose of each smoke constituent the subjects received, the most represented cigarette brands were analysed at FTC and Massachusetts intense regimes for mainstream yields of the smoke constituents of interest. Estimates of the actual human deliveries of the smoke constituents were then obtained by interpolation between the two standardised regimes, using the nicotine deliveries estimated from filter analysis and the nicotine yields measured at the standard regimes. An estimate of daily intake was then calculated from these estimated deliveries and daily cigarette consumption. This was then compared with the amounts of the smoke constituent and/or metabolites found in the urine samples. The results demonstrate a range of correlations between the estimated amounts of smoke constituents taken in by the subjects and the amounts excreted in urine. Whilst it is recognised that there are limitations with this approach due to the uncertainties associated with the process of intake estimation it considered indicative of the applicability of the various biomarkers to the assessment of smoke exposure in consumers.