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
Abstract:A modeling approach termed 'nicotine bridging' is presented to estimate exposure to mainstream smoke constituents. The method is based on: (1) determination of harmful and potentially harmful constituents (HPHC) and in vitro toxicity parameter-to-nicotine regressions obtained using multiple machine-smoking protocols, (2) nicotine uptake distributions determined from 24-h excretion of nicotine metabolites in a clinical study, and (3) modeled HPHC uptake distributions using steps 1 and 2. An example of 'nicotine… Show more
“…TPM, tar, and 32 of the 49 HPHC measured as well as 5 toxicity parameters were used for regression analyses. The intercept, slope, and coefficient of determination (r 2 ) of these regressions are reported by Urban et al (2012). Criteria for selecting HPHC and toxicological effects for regression analyses were the availability of mean values P LOQ for at least 4 smoking protocols and the calculability of the regressions with nicotine for the EHCSS-K6, the M6UK, and the PM1.…”
“…3-10. The intercept, slope, and coefficient of determination (r 2 ) for the cigarettes used for the 'nicotine bridging method' are reported in Urban et al (2012).…”
“…Using the current testing strategy , three versions of EHCSS series-K cigarettes have been investigated in pre-clinical studies presented in this publication, in clinical trials (Martin Leroy et al, 2012;Tricker et al, 2012a,b,c,d), and in a modeling approach termed 'nicotine bridging' (Urban et al, 2012). This paper presents the analytical chemistry, cytotoxicity, and bacterial mutagenicity results for the EHCSS series-K and commercial conventional lit-end cigarettes (CC) smoked under ISO smoking conditions (International Organization for Standardization, 2000a), as well as under a variety of smoking regimens reflecting human puffing behavior (HPB) conditions (Table 1).…”
Section: Introductionmentioning
confidence: 99%
“…This extended testing strategy for evaluation of reduced exposure enables a rigorous examination of the relative product performance and represents one necessary step in reduced exposure substantiation in a translational fashion -from 'product' to 'smoker' to 'population'. The investigation of the impact of different puffing intensities on the delivery of HPHC, and in particular their relationship to nicotine, allows for a better understanding of the product performance in real life situations, i.e., different puffing intensities and smoke intake, and enables predictions of exposure based on measured nicotine uptake distributions in smokers (Urban et al, 2012).…”
Chemical analysis of up to 49 harmful and potentially harmful constituents (HPHC) in mainstream smoke, in vitro cytotoxicity of the particulate and gas/vapor phase of mainstream smoke determined in the Neutral Red Uptake assay, and in vitro bacterial mutagenicity of the particulate phase determined in the Salmonella typhimurium Reverse Mutation (Ames) assay are reported for three Electrically Heated Cigarette Smoking System (EHCSS) series-K cigarettes, the University of Kentucky Reference Cigarette 2R4F, and a number of comparator commercial conventional lit-end cigarettes (CC) under ISO machine-smoking conditions and a total of 25 additional smoking regimens reflecting 'human puffing behavior' (HPB). The smoking machines were set to deliver nicotine yields for the EHCSS and comparator CC derived from the 10th percentile to the 90th percentile of nicotine uptake distributions in smokers determined in two clinical studies. Duplication of the smoking intensity 'per cigarette' on a smoking machine may provide an insight into product performance that is directly relevant to obtaining scientific evidence for reduced exposure substantiation based on mainstream cigarette smoke HPHC-to-nicotine regressions. The reported data support an overall evaluation of reduced exposure to HPHC and biological activity.
“…TPM, tar, and 32 of the 49 HPHC measured as well as 5 toxicity parameters were used for regression analyses. The intercept, slope, and coefficient of determination (r 2 ) of these regressions are reported by Urban et al (2012). Criteria for selecting HPHC and toxicological effects for regression analyses were the availability of mean values P LOQ for at least 4 smoking protocols and the calculability of the regressions with nicotine for the EHCSS-K6, the M6UK, and the PM1.…”
“…3-10. The intercept, slope, and coefficient of determination (r 2 ) for the cigarettes used for the 'nicotine bridging method' are reported in Urban et al (2012).…”
“…Using the current testing strategy , three versions of EHCSS series-K cigarettes have been investigated in pre-clinical studies presented in this publication, in clinical trials (Martin Leroy et al, 2012;Tricker et al, 2012a,b,c,d), and in a modeling approach termed 'nicotine bridging' (Urban et al, 2012). This paper presents the analytical chemistry, cytotoxicity, and bacterial mutagenicity results for the EHCSS series-K and commercial conventional lit-end cigarettes (CC) smoked under ISO smoking conditions (International Organization for Standardization, 2000a), as well as under a variety of smoking regimens reflecting human puffing behavior (HPB) conditions (Table 1).…”
Section: Introductionmentioning
confidence: 99%
“…This extended testing strategy for evaluation of reduced exposure enables a rigorous examination of the relative product performance and represents one necessary step in reduced exposure substantiation in a translational fashion -from 'product' to 'smoker' to 'population'. The investigation of the impact of different puffing intensities on the delivery of HPHC, and in particular their relationship to nicotine, allows for a better understanding of the product performance in real life situations, i.e., different puffing intensities and smoke intake, and enables predictions of exposure based on measured nicotine uptake distributions in smokers (Urban et al, 2012).…”
Chemical analysis of up to 49 harmful and potentially harmful constituents (HPHC) in mainstream smoke, in vitro cytotoxicity of the particulate and gas/vapor phase of mainstream smoke determined in the Neutral Red Uptake assay, and in vitro bacterial mutagenicity of the particulate phase determined in the Salmonella typhimurium Reverse Mutation (Ames) assay are reported for three Electrically Heated Cigarette Smoking System (EHCSS) series-K cigarettes, the University of Kentucky Reference Cigarette 2R4F, and a number of comparator commercial conventional lit-end cigarettes (CC) under ISO machine-smoking conditions and a total of 25 additional smoking regimens reflecting 'human puffing behavior' (HPB). The smoking machines were set to deliver nicotine yields for the EHCSS and comparator CC derived from the 10th percentile to the 90th percentile of nicotine uptake distributions in smokers determined in two clinical studies. Duplication of the smoking intensity 'per cigarette' on a smoking machine may provide an insight into product performance that is directly relevant to obtaining scientific evidence for reduced exposure substantiation based on mainstream cigarette smoke HPHC-to-nicotine regressions. The reported data support an overall evaluation of reduced exposure to HPHC and biological activity.
“…Thus, presumably, the nicotine content in filters and the corresponding relationship with HPHC yields would be affected. This assumption relies on regression models reported by URBAN et al (12) between smoke constituents and nicotine smoke yields measured in both cigarettes and the Electrically Heated Cigarette Smoking System (EHCSS). Here, linear models were used for the cigarettes whereas log-linear models were preferred for 15 out of 33 constituents measured in EHCSS aerosol.…”
SUMMARYPhilip Morris International has developed a heat-not-burn tobacco heating system (THS 2.2) that produces an aerosol without combustion. Adult smokers are anticipated to use the product with differing behaviors, such as puffing volume or puffing frequency, therefore it was important to find an easy way to study how users are exposed to the aerosol constituents. Thus, the intended outcome of this study was to propose and assess a simple approach for the estimation of THS users' exposure to harmful and potentially harmful constituents (HPHCs). THS operates using tobacco sticks (HeatSticks) that include a mouthpiece and a tobacco plug which, when heated, generates an aerosol. The analysis of nicotine retained in the mouthpiece of the HeatSticks during use was identified as a potential approach to estimate users' mouth level exposure (MLE) to HPHCs. Consequently, the following study was conducted with the objectives 1.) to assess the correlation between the quantity of retained nicotine in the mouthpiece (Nicotine MP) of the HeatSticks and the nicotine delivered in the aerosol of machine-smoked products, 2.) to verify the practical range for Nicotine MP based on the analysis of used HeatSticks left by THS users, and 3.) to develop models describing the relationship between Nicotine MP and specific aerosol constituents measured in the aerosol of machine-smoked products. The regular non-mentholated HeatSticks variant was machine-smoked under various smoking regimens to cover the range of anticipated human puffing behaviors. The suitability of this practical range of machine-smoking conditions was verified by collecting used HeatSticks from two different trials conducted with THS users. The determined Nicotine MP distribution indicated that the machinesmoked regimens encompassed the range observed for users. Multiple Linear Regression (MLR) combined with a stepwise approach was used for selecting models describing the relationship between Nicotine MP and specific aerosol constituents. The stepwise approach interactively explores which amongst various tested predictors provides a good fit. The developed models showed good adjusted coefficients of determination (i.e., R 2 adj. $ 0.75) for 28 out of the 43 investigated HPHCs. Previously published studies showed that actual MLE can be estimated from cigarette filter analysis. This study demonstrated that the analysis of nicotine in THS mouthpiece (filter section) corresponded to an estimation of the upper limits of MLE, in line with maximum possible usage conditions. [Beitr. Tabakforsch. Int. 27 (2017) 42-64]
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