Methods to assess potential reduced exposure products

University of Minnesota Cancer Center, Minneapolis, MN 55414, USA.
Nicotine & Tobacco Research (Impact Factor: 3.3). 01/2006; 7(6):827-44. DOI: 10.1080/14622200500266015
Source: PubMed


The availability of tobacco products purported to reduce toxin exposure or potentially reduce health risks necessitates the development of methods and identification of biomarkers that can be used to assess these products. These assessments occur on multiple levels and stages, from identifying constituents in the tobacco products and smoke, to human exposure and health effects trials, to postmarketing surveillance. A conference of multidisciplinary experts was convened to present and discuss methods and biomarkers to assess these products and to consider the infrastructure necessary to facilitate the evaluation process. Although no currently available set of measures was thought to be sufficient for determining the relative health risk of potential reduced exposure products, this paper provides a blueprint for future research toward this end.


Available from: Deirdre (Dee) Lawrence Kittner
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    • "Data from this study are expected to contribute to the development and long-term assessment of tobacco products with reduced contents of harmful substances following their introduction on to the market, as part of post-marketing surveillance programmes [16,17,28,29]. In the next few years, new methods to analyse biomarkers of exposure to tobacco products are expected to be available. "
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    ABSTRACT: Long-term studies of smokers who switch to lower nicotine yield cigarettes have been identified by the World Health Organization Study Group TobReg and the US Food and Drug Administration as one key area where new knowledge is required to guide science based regulation. The limited number of long-term switching studies have concluded that smokers who switch to lower nicotine yield cigarettes show evidence of partial compensation. Since the European Union tobacco product directive of 2001 introduced tar and nicotine yield ceilings, there has been no long-term observational switching study. To address the limitations of previous studies where smokers were forced switched for relatively short durations, we plan to undertake a long-term study of spontaneous switching which is appropriately powered and includes non-switchers as a control group.Methods/design: Healthy adult smokers aged 21-64 years will be enrolled into this 5-year non-residential, multicentre study across 10 cities in Germany. They will be assessed at 10 timepoints with 6 month intervals during which inclusion criteria will be reassessed and spent cigarette filter tips, saliva and 24 h urine samples will be collected. These samples will be used to determine average daily cigarette consumption, estimate mouth-level exposure to tar and nicotine and measure selected biomarkers of exposure, respectively. Spontaneous changes in subjects' preferred cigarette products and any consequent change in tar or nicotine yield will be monitored. Subjects will be required to complete questionnaires on quality of life, smoking behaviours, smoking-related sensory attributes and recent life changes. The planned study is anticipated to contribute to understanding smokers' behaviours and their consequent exposure to smoke constituents. It will also allow assessment of compensatory changes in their behaviour following spontaneous switching of cigarette product smoked. Data from this study are expected to provide insights into study design and conduct for non-clinical assessment of smokers' exposure as part of post marketing surveillance programmes.Trial registration: Current Controlled Trials Database reference ISRCTN95019245.
    BMC Public Health 04/2014; 14(1):348. DOI:10.1186/1471-2458-14-348 · 2.26 Impact Factor
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    • "A series of clinical studies have been performed which were designed to measure exposure to selected HPHC in a highly controlled environment over a period of several days (Parts 3–6; Tricker et al., 2012a,b,c,d). Such studies are considered appropriate to examine human exposure occurring under natural conditions (Hatsukami et al., 2005). To investigate whether such studies represent realworld patterns of product use, we also investigated biomarkers of exposure and effect in smokers for a one month period under conditions of actual use (Part 7; Martin Leroy et al., 2012). "
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    ABSTRACT: The following series of papers presents an extensive assessment of the Electrically Heated Cigarette Smoking System EHCSS series-K cigarette vs. conventional lit-end cigarettes (CC) as an example for an extended testing strategy for evaluation of reduced exposure. The EHCSS produces smoke through electrical heating of tobacco. The EHCSS series-K heater was designed for exclusive use with EHCSS cigarettes, and cannot be used to smoke (CC). Compared to the University of Kentucky Reference Research cigarette 2R4F and a series of commercial CC, mainstream cigarette smoke of both the non-menthol and menthol-flavored EHCSS cigarettes showed a reduced delivery of a series of selected harmful and potentially harmful constituents (HPHC), mutagenic activity determined using the Salmonella typhimurium Reverse Mutation (Ames) assay, and cytotoxicity in the Neutral Red Uptake Assay. Clinical evaluations confirmed reduced exposure to HPHC and excretion of mutagenic material under controlled clinical conditions. Reductions in HPHC exposure were confirmed in a real-world ambulatory clinical study. Potential biomarkers of cardiovascular risk were also reduced under real-world ambulatory conditions. A modeling approach, 'nicotine bridging', was developed based on the determination of nicotine exposure in clinical evaluations which indicated that exposure to HPHC for which biomarkers of exposure do not exist would also be reduced.
    Regulatory Toxicology and Pharmacology 08/2012; 64(2). DOI:10.1016/j.yrtph.2012.08.008 · 2.03 Impact Factor
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    • "The study was designed to examine changes in selected tobacco-specific and tobacco-related biomarkers of exposure to HPHC known to be present in the gas–vapor phase (1,3-butadiene, acrolein, benzene, CO, and crotonaldehyde ) and the particulate phase (2-naphthylamine, 4-aminobi- phenyl, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK], acrylamide, nicotine, pyrene, and o-toluidine) of mainstream cigarette smoke. The use of suitable biomarkers of exposure to these HPHC offers one potential method to assess whether differences in exposure to cigarette smoke HPHC has occurred in smokers switching from one cigarette to another (Shields, 2002; Hecht, 2003; Hatsukami et al., 2005). Excretion of mutagenic material in urine was also measured. "
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    ABSTRACT: A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to twelve selected harmful and potentially harmful constituents (HPHCs) in cigarette smoke and urinary excretion of mutagenic material in 128 male and female Japanese subjects smoking Marlboro cigarettes (6mg tar, 0.5mg nicotine, and 7.0mg CO) at baseline. Subjects were randomized to continue smoking Marlboro cigarettes, or switch to the Electrically Heated Cigarette Smoking System (EHCSS) and smoke either the EHCSS-K6 (5mg tar, 0.3mg nicotine, and 0.6mg CO) or the EHCSS-K3 (3mg tar, 0.2mg nicotine, and 0.6mg CO) cigarette, or switch to smoking Lark One cigarettes (1mg tar, 0.1mg nicotine, and 2.0mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were statistically significant (p⩽0.05) for all cigarette smoke HPHC including CO (the primary objective) and excretion of mutagenic material in the EHCSS-K6 (range: -14.6% to -75.6%) and EHCSS-K3 (range: -9.8% to -73.0%) groups. Statistically significant reductions (all p⩽0.05) in exposure to ten cigarette smoke HPHC (range: -5.9% to -34.6%), but not urinary mutagenicity, were observed in the Lark One group. The largest mean reductions in exposure to HPHC (all p⩽0.01 level) occurred in the no-smoking group (range: -13.7% to -97.6%).
    Regulatory Toxicology and Pharmacology 08/2012; 64(2). DOI:10.1016/j.yrtph.2012.08.003 · 2.03 Impact Factor
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