Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 1: Non-clinical and clinical insights

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.

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

“…Both M6J and Lark1 contain a carbon filter, which is typical for the Japanese market. The ISO tar, nicotine and carbon monoxide yields (International Organization for Standardization, 1991Standardization, , 1995aStandardization, ,b, 2000a obtained on a linear smoking machine are presented in Schorp et al (2012).…”

“…The puff count for the EHCSS was restricted to 8 puffs (Werley et al, 2008). Using a linear smoking machine a higher 'tar' delivery is obtained under ISO conditions (International Organization for Standardization, 2000b) as reported by Schorp et al (2012).…”

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).…”

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 7: A one-month, randomized, ambulatory, controlled clinical study in Poland

“…Very similar to that reported in the current study in which smokers of the EHCSS-K increased mean consumption from 25 CPD at baseline while smoking own-brand cigarettes to 38 CPD when smoking EHCSS-K6 (Table 4), while no significant change in cigarette consumption occurred in smokers who continued to smoker their own brand of CC (25 CPD). Providing EHCSS cigarettes Table 5 Summary of overall high sensitivity C-reactive protein (hs-CRP) concentrations at baseline and end of study, and change from baseline to end of study by study group (PP population free-of-charge cannot solely explain the increase in cigarette consumption in the EHCSS group which could also be due to the reduced number of eight puffs the subjects could obtain using the EHCSS (Werley et al, 2008;Schorp et al, 2012), while users of CC average 12-13 puffs per cigarette (Perkins et al, 2012).…”

“…An automated enzyme-linked immunosorbent assay (ELISA) system (Immunomat™ BASE Plus; Serion Immundiagnostica GmbH, D-97076 Würzburg, Germany) with commercial ELISA kits was used to determine interleukin-6 (IL-6) (Ref. Tobacco-specific and tobacco-related biomarkers of exposure (Hecht, 2003;Lindner et al, 2011;Schorp et al, 2012) were determined for the following HPHC (Table 2) using methods validated according to the FDA criteria (Food and Drug Administration, 2001). These included nicotine and five metabolites (expressed as nicotine equivalents: Neq) as a biomarker of exposure for nicotine (Benowitz et al, 1994), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide conjugates (total NNAL) for NNK (Carmella et al, 2003), monohydroxybutenyl mercapturic acid (MHBMA) for 1,3-butadiene (van Sittert et al, 2000), 3-hydroxypropyl mercapturic acid (3-HPMA) for acrolein (Mascher et al, 2001), S-phenyl mercapturic acid (S-PMA) for benzene (Medeiros et al, 1997), and 1-hydroxypyrene and its sulfate and glucuronide conjugates (total 1-OHP) for pyrene (Strickland et al, 1996).…”