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 bridging' is provided, using a subset of the data reported in Part 2 of this supplement (Zenzen et al., 2012) for two conventional lit-end cigarettes (CC) and the Electrically Heated Cigarette Smoking System (EHCSS) series-K6 cigarette. The bridging method provides justified extrapolations of HPHC exposure distributions that cannot be obtained for smoke constituents due to the lack of specific biomarkers of exposure to cigarette smoke constituents in clinical evaluations. Using this modeling approach, exposure reduction is evident when the HPHC exposure distribution curves between the MRTP and the CC users are substantially separated with little or no overlap between the distribution curves.

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 2: Smoke chemistry and in vitro toxicological evaluation using smoking regimens reflecting human puffing behavior

“…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).…”

“…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).…”

Development of Models for the Estimation of Mouth Level Exposure to Aerosol Constituents from a Heat-Not-Burn Tobacco Product Using Mouthpiece Analysis

“…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.…”