Comparison of Exposure to Selected Cigarette Smoke Constituents in Adult Smokers and Nonsmokers in a European, Multicenter, Observational Study

Abstract

Background: This multicenter, observational study was conducted in three European countries (Germany, Switzerland, and the United Kingdom) to determine the exposure of adult cigarette smokers and nonsmokers to selected cigarette smoke constituents: 1,3-butadiene, 2-naphthylamine, 4-aminobiphenyl, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrolein, benzene, carbon monoxide, nicotine, pyrene, and o-toluidine.Methods: Smokers were grouped by tar category (TC) according to the tar yield of their regular cigarette brand: TC1: 4 mg tar, TC2: 5-7 mg tar, and TC3: !8 mg tar [to the legal tar yield ceiling in the respective countries (10 or 12 mg tar)]. Levels of biomarkers of exposure to the aforementioned cigarette smoke constituents were compared between smokers and nonsmokers, and within smokers across tar categories.Results: The full population consisted of 1,631 subjects (1,223 smokers and 408 nonsmokers). Biomarkers of exposure were analyzed for 1,558 subjects (valid case population) as follows: 1,159 smokers (TC1: n ¼ 402, TC2: n ¼ 379, TC3: n ¼ 378), and 399 nonsmokers. Exposure levels were higher in smokers than nonsmokers and increased with increasing tar yield and cigarette consumption. An association of tar category and exposure level was observed for all smoke constituents, except pyrene, 4-aminobiphenyl, and o-toluidine, whereas only NNK exposure was different in all three tar categories.Conclusions: Smoking status and, among smokers, daily cigarette consumption and tar yield were observed to affect biomarker of exposure levels.Impact: This research provides a comprehensive evaluation of smoke constituent exposure of adult cigarette smokers and nonsmokers in three European countries. Cancer Epidemiol Biomarkers Prev; 20(7); 1524-36. '2011 AACR.

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 8: Nicotine bridging – Estimating smoke constituent exposure by their relationships to both nicotine levels in mainstream cigarette smoke and in smokers

“…Nicotine uptake was expressed as excretion of nicotine equivalents in 24 h urine (Neq; the calculated molar sum of the concentrations of nicotine, cotinine, trans-3 0 -hydroxycotinine, and their respective glucuronide conjugates). Nicotine uptake, expressed as 24 h urine excretion of Neq, was also determined in a European population of smokers from the UK, Germany, and Switzerland (Lindner et al, 2011). Smokers were randomized according to different cigarette ISO tar categories (TC): TC1 (1-4 mg ISO tar; N = 409), TC2 (5-7 mg ISO tar, N = 399), and TC3 (8-12 mg ISO tar, N = 387).…”

“…Nicotine is mainly present (>99%) in the particulate phase of the MS smoke aerosol (Seeman et al, 2004), and the nicotine dose obtained from a cigarette is subject to substantial inter-and intra-individual differences in smoking behavior (Scherer et al, 2007;Lindner et al, 2011). Smoking a cigarette can be described by distinct physical processes: Puffing, mouth hold, inhalation, and exhalation (Bernstein, 2004).…”

“…However, because no single smoking machine regimen will adequately reflect human smoking behavior (Institute of Medicine 2001; Baker, 2002;Borgerding and Klus, 2005; World Health Organization Study Group on Tobacco Product Regulation, 2007Regulation, , 2008, only poor correlations exist between smoke nicotine yields determined using machinesmoking protocols and nicotine-derived biomarker of exposure estimates in smokers (Russell et al, 1980;Rickert and Robinson, 1981;Benowitz and Jacob, 1984;Gori and Lynch, 1985;Diding, 1987;Andersson et al, 1997;Byrd et al, 1998;Jarvis et al, 2001;Ueda et al, 2002;Scherer et al, 2007;Mendes et al, 2009;Lindner et al, 2011). Consequently, the U.S. Federal Trade Commission (FTC) has officially rescinded its guidance for reported smoking machine tar and nicotine yields (Federal Trade Commission, 2008b), while increased interest has occurred within the tobacco control community to develop alternative protocols which better reflect smoker exposure to harmful and potentially harmful constituents (HPHC) (World Health Organization Study Group on Tobacco Product Regulation, 2004Hammond et al, 2006Hammond et al, , 2007Marian et al, 2009).…”

“…This concept is used to evaluate HPHC-to-nicotine and in vitro toxicity-to-nicotine relationships for 2 conventional cigarettes (Marlboro, Philip Morris One) (M6UK, PM1) and the EHCSS-K6 smoked according to ISO and 15 different machine-smoking regimens to reflect 'human puffing behavior' Zenzen et al, 2012). Human smoking behavior was determined using nicotine uptake distributions derived from nicotine metabolite excretion data obtained in two clinical studies Lindner et al, 2011). The two approaches are then combined ('nicotine bridging') to model HPHC uptake proportional to nicotine uptake distributions as a means of assessment of exposure to HPHC for which biomarkers of exposure are not available (Urban and Schorp, 2006).…”

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 5: 8-Day randomized clinical trial in Japan

“…Tobacco-specific and tobacco-related biomarkers of exposure (Hecht, 2003;Lindner et al, 2011;Schorp et al, 2012) were determined for the following HPHC: (i) tobacco-specific biomarkers of exposure were determined for nicotine (Benowitz et al, 1994) and NNK (Carmella et al, 2003), and (ii) tobacco-related biomarkers of exposure were selected for 1,3-butadiene (van Sittert et al, 2000), 2-naphthylamine , 4-aminobiphenyl , acrolein (Mascher et al, 2001), acrylamide (Urban et al, 2006), benzene (Medeiros et al, 1997), crotonaldehyde (Scherer et al, 2007), pyrene (Strickland et al, 1996), and o-toluidine . All biomarkers were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using methods validated according to Food and Drug Administration criteria (Food and Drug Administration, 2001).…”