- Apr 2, 2009
- 5,171
- 13,288
- 67
Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 1: Non-clinical and clinical insights
Regulatory Toxicology and Pharmacology
In Press, Uncorrected Proof, Available online 22 August 2012
Matthias K. Schorp, Anthony R. Tricker, Ruth Dempsey
Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
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 3: Eight-day randomized clinical trial in the UK
Regulatory Toxicology and Pharmacology[/URL]
Available online 22 August 2012
Anthony R. Tricker, Adrian J. Stewart, Claire Martin Leroy, Dirk Lindner, Matthias K. Schorp, Ruth Dempsey
Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland
Abstract
A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to nine selected harmful and potentially harmful constituents (HPHC) in cigarette smoke and urinary excretion of mutagenic material in 160 male and female subjects smoking Marlboro cigarettes (6 mg tar, 0.5 mg nicotine, and 7.0 mg CO) at baseline. Subjects were randomized to continue smoking Marlboro cigarettes, or switch to using an electrically heated cigarette smoking system (EHCSS) smoking one of two EHCSS series-K cigarettes, the EHCSS-K6 cigarette (5 mg tar, 0.3 mg nicotine, and 0.6 mg CO) or the EHCSS-K3 cigarette (3 mg tar, 0.2 mg nicotine, and 0.6 mg CO), or switch to smoking Philip Morris One cigarettes (1 mg tar, 0.1 mg nicotine, and 2.0 mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were statistically significant (p ⩽ 0.05) for all determined HPHC including benzene and CO (the primary objectives), and urinary excretion of mutagenic material in the EHCSS-K6 (range −35.5 ± 29.2% to −79.4 ± 14.6% [mean ± standard deviation]), EHCSS-K3 (range −41.2 ± 26.6% to −83.1 ± 9.2%), and PM1 (range −14.6 ± 24.1% to −39.4 ± 17.5%) groups. The largest reductions in exposure occurred in the no-smoking group (range −55.4 ± 45.0% to −100.0 ± 0.0%).
Reduced exposure evaluation of an electrically heated cigarette smoking system. Part 6: 6-day randomized clinical trial of a menthol cigarette in Japan
Regulatory Toxicology and Pharmacology[/URL]
In Press, Uncorrected Proof, Available online 22 August 2012
Anthony R. Tricker, Shigato Kanada, Kohji Takada, Claire Martin Leroy, Dirk Lindner, Matthias K. Schorp, Ruth Dempsey
Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland
Abstract
A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to 12 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke, excretion of mutagenic material in urine, and serum Clara cell 16-kDa protein (CC16) in 102 male and female Japanese subjects who smoked Marlboro Ultra Lights Menthol cigarettes (M4JM; 4 mg tar and 0.3 mg nicotine) at baseline. Subjects were randomized to continue smoking M4JM, or switch to smoking either the electrically heated cigarette smoking system menthol cigarette (EHCSS-K6M; 5 mg tar and 0.3 mg nicotine) or the Lark One menthol cigarette (Lark1M; 1 mg tar and 0.1 mg nicotine), or to no-smoking. The mean decreases from baseline to Day 5/6 were statistically significant (p ⩽ 0.05) for exposure to 10 of 12 cigarette smoke HPHC including the primary endpoint (carbon monoxide) and urinary excretion of mutagenic material in the EHCSS-K6M group (−12.3% to −83.4%). Smaller, but statistically significant reductions (p ⩽ 0.05) occurred in the Lark1M group (−3.3% to −35.2%), with the exception of urinary mutagens. The largest mean reductions (all p ⩽ 0.05) in exposure to cigarette smoke HPHC and excretion of mutagenic material occurred in the no-smoking group (−1.4% to −93.6%). Serum CC16, an indicator of lung epithelial injury, was not significantly different between groups.
Regulatory Toxicology and Pharmacology
In Press, Uncorrected Proof, Available online 22 August 2012
Matthias K. Schorp, Anthony R. Tricker, Ruth Dempsey
Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
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.
http://www.sciencedirect.com/science/article/pii/S0273230012001651
------------------------------------------------------------------------------------------
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
Regulatory Toxicology and Pharmacology
Volker Zenzena, Joerg Diekmanna, Birgit Gerstenberga, Susanne Webera, Sandra Wittkea, Matthias K. Schorpb
Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
Abstract
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.
http://www.sciencedirect.com/science/article/pii/S0273230012001614
------------------------------------------------------------------------------------------
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
Regulatory Toxicology and Pharmacology
Volker Zenzena, Joerg Diekmanna, Birgit Gerstenberga, Susanne Webera, Sandra Wittkea, Matthias K. Schorpb
Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
Abstract
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.
http://www.sciencedirect.com/science/article/pii/S0273230012001614
Reduced exposure evaluation of an electrically heated cigarette smoking system. Part 3: Eight-day randomized clinical trial in the UK
Regulatory Toxicology and Pharmacology[/URL]
Available online 22 August 2012
Anthony R. Tricker, Adrian J. Stewart, Claire Martin Leroy, Dirk Lindner, Matthias K. Schorp, Ruth Dempsey
Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland
Abstract
A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to nine selected harmful and potentially harmful constituents (HPHC) in cigarette smoke and urinary excretion of mutagenic material in 160 male and female subjects smoking Marlboro cigarettes (6 mg tar, 0.5 mg nicotine, and 7.0 mg CO) at baseline. Subjects were randomized to continue smoking Marlboro cigarettes, or switch to using an electrically heated cigarette smoking system (EHCSS) smoking one of two EHCSS series-K cigarettes, the EHCSS-K6 cigarette (5 mg tar, 0.3 mg nicotine, and 0.6 mg CO) or the EHCSS-K3 cigarette (3 mg tar, 0.2 mg nicotine, and 0.6 mg CO), or switch to smoking Philip Morris One cigarettes (1 mg tar, 0.1 mg nicotine, and 2.0 mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were statistically significant (p ⩽ 0.05) for all determined HPHC including benzene and CO (the primary objectives), and urinary excretion of mutagenic material in the EHCSS-K6 (range −35.5 ± 29.2% to −79.4 ± 14.6% [mean ± standard deviation]), EHCSS-K3 (range −41.2 ± 26.6% to −83.1 ± 9.2%), and PM1 (range −14.6 ± 24.1% to −39.4 ± 17.5%) groups. The largest reductions in exposure occurred in the no-smoking group (range −55.4 ± 45.0% to −100.0 ± 0.0%).
http://www.sciencedirect.com/science/article/pii/S0273230012001675
--------------------------------------------------
:
Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 4: Eight-day randomized clinical trial in Korea
Anthony R. Trickera, , , In-Jin Jangb, Claire Martin Leroya, Dirk Lindnera, Ruth Dempseya
a Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
b Clinical Trial Center, Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Republic of Korea
Available online 23 August 2012
Abstract
A randomized, controlled, open-label parallel-group, single-center study to determine biomarkers of exposure to 12 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke and urinary excretion of mutagenic material in 72 male and female Korean subjects smoking Lark One cigarettes (1.0 mg tar, 0.1 mg nicotine, and 1.5 mg CO) at baseline. Subjects were randomized to continue smoking Lark One cigarettes, or switch to an Electrically Heated Cigarette Smoking System (EHCSS) and EHCSS-K3 cigarette (3 mg tar, 0.2 mg nicotine, and 0.6 mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were statistically significant (all p < 0.05) for 10 of 12 HPHC in mainstream cigarette smoke including CO (the primary objective) in the EHCSS-K3 group (range: −1.5% to −74.2%). Exposure to the other determined HPHC was not significantly different. In the Lark One group, the mean exposure to 6 of 12 HPHC in cigarette smoke was significantly (all p < 0.05) decreased; however, exposure to CO was significantly increased. The largest mean reductions in biomarkers of exposure to HPHC occurred in smokers who switched to no-smoking (−3.4% to −98.9%). The mean excretion of mutagenic material was significantly decreased (p < 0.05) in the EHCSS-K3 and no-smoking groups (−31.8% and −45.3%, respectively), and increased in the Lark One group (+31.5%).
http://www.sciencedirect.com/science/article/pii/S0273230012001705
---------------------------------------------
Reduced exposure evaluation of an electrically heated cigarette smoking system. Part 5: 8-Day randomized clinical trial in Japan
Anthony R. Trickera, , , Shigato Kanadab, Kohji Takadac, Claire Martin Leroya, Dirk Lindnera, Matthias K. Schorpa, Ruth Dempseya
a Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
b Osaka Pharmacology Research Clinic (OPHAC), 4-12-11 Kasuga, Suita-shi, Osaka 565-0853, Japan
c Department of Psychology, Teikyo University, 359 Otsuka, Hachioji, Tokyo 192-0395, Japan
Available online 22 August 2012
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 (6 mg tar, 0.5 mg nicotine, and 7.0 mg 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 (5 mg tar, 0.3 mg nicotine, and 0.6 mg CO) or the EHCSS-K3 (3 mg tar, 0.2 mg nicotine, and 0.6 mg CO) cigarette, or switch to smoking Lark One cigarettes (1 mg tar, 0.1 mg nicotine, and 2.0 mg 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%).
http://www.sciencedirect.com/science/article/pii/S0273230012001602
--------------------------------------------------
:
Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 4: Eight-day randomized clinical trial in Korea
Anthony R. Trickera, , , In-Jin Jangb, Claire Martin Leroya, Dirk Lindnera, Ruth Dempseya
a Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
b Clinical Trial Center, Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Republic of Korea
Available online 23 August 2012
Abstract
A randomized, controlled, open-label parallel-group, single-center study to determine biomarkers of exposure to 12 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke and urinary excretion of mutagenic material in 72 male and female Korean subjects smoking Lark One cigarettes (1.0 mg tar, 0.1 mg nicotine, and 1.5 mg CO) at baseline. Subjects were randomized to continue smoking Lark One cigarettes, or switch to an Electrically Heated Cigarette Smoking System (EHCSS) and EHCSS-K3 cigarette (3 mg tar, 0.2 mg nicotine, and 0.6 mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were statistically significant (all p < 0.05) for 10 of 12 HPHC in mainstream cigarette smoke including CO (the primary objective) in the EHCSS-K3 group (range: −1.5% to −74.2%). Exposure to the other determined HPHC was not significantly different. In the Lark One group, the mean exposure to 6 of 12 HPHC in cigarette smoke was significantly (all p < 0.05) decreased; however, exposure to CO was significantly increased. The largest mean reductions in biomarkers of exposure to HPHC occurred in smokers who switched to no-smoking (−3.4% to −98.9%). The mean excretion of mutagenic material was significantly decreased (p < 0.05) in the EHCSS-K3 and no-smoking groups (−31.8% and −45.3%, respectively), and increased in the Lark One group (+31.5%).
http://www.sciencedirect.com/science/article/pii/S0273230012001705
---------------------------------------------
Reduced exposure evaluation of an electrically heated cigarette smoking system. Part 5: 8-Day randomized clinical trial in Japan
Anthony R. Trickera, , , Shigato Kanadab, Kohji Takadac, Claire Martin Leroya, Dirk Lindnera, Matthias K. Schorpa, Ruth Dempseya
a Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
b Osaka Pharmacology Research Clinic (OPHAC), 4-12-11 Kasuga, Suita-shi, Osaka 565-0853, Japan
c Department of Psychology, Teikyo University, 359 Otsuka, Hachioji, Tokyo 192-0395, Japan
Available online 22 August 2012
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 (6 mg tar, 0.5 mg nicotine, and 7.0 mg 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 (5 mg tar, 0.3 mg nicotine, and 0.6 mg CO) or the EHCSS-K3 (3 mg tar, 0.2 mg nicotine, and 0.6 mg CO) cigarette, or switch to smoking Lark One cigarettes (1 mg tar, 0.1 mg nicotine, and 2.0 mg 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%).
http://www.sciencedirect.com/science/article/pii/S0273230012001602
Reduced exposure evaluation of an electrically heated cigarette smoking system. Part 6: 6-day randomized clinical trial of a menthol cigarette in Japan
Regulatory Toxicology and Pharmacology[/URL]
In Press, Uncorrected Proof, Available online 22 August 2012
Anthony R. Tricker, Shigato Kanada, Kohji Takada, Claire Martin Leroy, Dirk Lindner, Matthias K. Schorp, Ruth Dempsey
Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland
Abstract
A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to 12 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke, excretion of mutagenic material in urine, and serum Clara cell 16-kDa protein (CC16) in 102 male and female Japanese subjects who smoked Marlboro Ultra Lights Menthol cigarettes (M4JM; 4 mg tar and 0.3 mg nicotine) at baseline. Subjects were randomized to continue smoking M4JM, or switch to smoking either the electrically heated cigarette smoking system menthol cigarette (EHCSS-K6M; 5 mg tar and 0.3 mg nicotine) or the Lark One menthol cigarette (Lark1M; 1 mg tar and 0.1 mg nicotine), or to no-smoking. The mean decreases from baseline to Day 5/6 were statistically significant (p ⩽ 0.05) for exposure to 10 of 12 cigarette smoke HPHC including the primary endpoint (carbon monoxide) and urinary excretion of mutagenic material in the EHCSS-K6M group (−12.3% to −83.4%). Smaller, but statistically significant reductions (p ⩽ 0.05) occurred in the Lark1M group (−3.3% to −35.2%), with the exception of urinary mutagens. The largest mean reductions (all p ⩽ 0.05) in exposure to cigarette smoke HPHC and excretion of mutagenic material occurred in the no-smoking group (−1.4% to −93.6%). Serum CC16, an indicator of lung epithelial injury, was not significantly different between groups.
http://www.sciencedirect.com/science/article/pii/S027323001200164X
----------------------------------------------------
:
Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 7: A one-month, randomized, ambulatory, controlled clinical study in Poland
Claire Martin Leroya, Katarzyna Jarus-Dziedzicb, Jacek Ancerewicza, Dirk Lindnera, Agnieszka Kuleszab, John Magnettea, ,
a Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
b MTZ Clinical Research Ltd., Pawinskiego 5, 02-106 Warsaw, Poland
Available online 22 August 2012
Abstract
This randomized, open-label, ambulatory, controlled clinical study investigated biomarkers associated with cardiovascular risk and biomarkers of exposure to 10 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke in 316 male and female Polish smokers. Subjects were randomized to continue smoking conventional cigarettes (CC; n = 79) or switch to smoking the Electrically Heated Cigarette Smoking System series-K cigarette (EHCSS-K6; n = 237). Biomarker assessments were performed at several time points during the study at baseline and during the 1-month investigational period. The primary biomarkers were high-sensitivity C-reactive protein and white blood cell counts. No statistically significant differences in the two primary biomarkers were found between the study groups at the end of the study. End-of-study comparisons of secondary biomarkers between study groups indicated an increase in high-density lipoprotein cholesterol, and reductions in red blood cell count, hemoglobin, and hematocrit levels in the EHCSS-K6 group. All biomarkers of exposure to cigarette smoke HPHC were decreased in the EHCSS-K6 group, despite an increase in cigarette consumption, compared to the CC group. There were no apparent differences in any of the safety assessment parameters between the groups, and the overall incidence of study-related adverse events was low.
http://www.sciencedirect.com/science/article/pii/S0273230012001638
--------------------------------------------------------
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
H.-Jörg Urbana, Anthony R. Trickera, Donald E. Leydenb, Natasa Fortea, Volker Zenzenc, Astrid Feuersengerc, Mareike Assinkc, Gerd Kallisch....., Matthias K. Schorpa, ,
a Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
b Hardyville, VA, 23070, USA
c Philip Morris International R&D, Philip Morris Research Laboratories GmbH, Fuggerstrasse 3, 51149 Cologne, Germany
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-hour 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.
http://www.sciencedirect.com/science/article/pii/S0273230012001626
Anyone who obtains the full text copies of these studies, please send to me at smokefree@compuserve.com
----------------------------------------------------
:
Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 7: A one-month, randomized, ambulatory, controlled clinical study in Poland
Claire Martin Leroya, Katarzyna Jarus-Dziedzicb, Jacek Ancerewicza, Dirk Lindnera, Agnieszka Kuleszab, John Magnettea, ,
a Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
b MTZ Clinical Research Ltd., Pawinskiego 5, 02-106 Warsaw, Poland
Available online 22 August 2012
Abstract
This randomized, open-label, ambulatory, controlled clinical study investigated biomarkers associated with cardiovascular risk and biomarkers of exposure to 10 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke in 316 male and female Polish smokers. Subjects were randomized to continue smoking conventional cigarettes (CC; n = 79) or switch to smoking the Electrically Heated Cigarette Smoking System series-K cigarette (EHCSS-K6; n = 237). Biomarker assessments were performed at several time points during the study at baseline and during the 1-month investigational period. The primary biomarkers were high-sensitivity C-reactive protein and white blood cell counts. No statistically significant differences in the two primary biomarkers were found between the study groups at the end of the study. End-of-study comparisons of secondary biomarkers between study groups indicated an increase in high-density lipoprotein cholesterol, and reductions in red blood cell count, hemoglobin, and hematocrit levels in the EHCSS-K6 group. All biomarkers of exposure to cigarette smoke HPHC were decreased in the EHCSS-K6 group, despite an increase in cigarette consumption, compared to the CC group. There were no apparent differences in any of the safety assessment parameters between the groups, and the overall incidence of study-related adverse events was low.
http://www.sciencedirect.com/science/article/pii/S0273230012001638
--------------------------------------------------------
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
H.-Jörg Urbana, Anthony R. Trickera, Donald E. Leydenb, Natasa Fortea, Volker Zenzenc, Astrid Feuersengerc, Mareike Assinkc, Gerd Kallisch....., Matthias K. Schorpa, ,
a Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
b Hardyville, VA, 23070, USA
c Philip Morris International R&D, Philip Morris Research Laboratories GmbH, Fuggerstrasse 3, 51149 Cologne, Germany
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-hour 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.
http://www.sciencedirect.com/science/article/pii/S0273230012001626
Anyone who obtains the full text copies of these studies, please send to me at smokefree@compuserve.com
Last edited:
