Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 5: 8-Day randomized clinical trial in Japan

Regulatory Toxicology and Pharmacology

Volumn 64, Issue SUPPL. 2, 2012, Pages

  Tricker, Anthony R ^a   Kanada, Shigeto ^b   Takada, Kohji ^c   Leroy, Claire Martin ^a   Lindner, Dirk ^a   Schorp, Matthias K ^a   Dempsey, Ruth ^a  

^a PHILIP MORRIS PRODUCTS S A   (Switzerland)

^b Osaka Pharmacology Research Clinic (OPHAC)   (Japan)

^c TEIKYO UNIVERSITY   (Japan)

Author keywords

Biomarkers of exposure; Cigarettes; Constituent; EHCSS; Electrically Heated Cigarette Smoking; Harmful and potentially harmful; HPHC; Smoking; System

Indexed keywords

1 HYDROXYPYRENE; 1,3 BUTADIENE; 2 METHYLANILINE; 2 NAPHTHYLAMINE; 3 HYDROXY 1 METHYLPROPYLMERCAPTURIC ACID; 3 HYDROXYMETHYLPROPYLMERCAPTURIC ACID; 4 (METHYLNITROSAMINO) 1 (3 PYRIDYL) 1 BUTANOL; 4 (METHYLNITROSAMINO) 1 (3 PYRIDYL) 1 BUTANONE; 4 BIPHENYLAMINE; ACROLEIN; BENZENE; BIOLOGICAL MARKER; CARBON MONOXIDE; CARBOXYHEMOGLOBIN; COTININE; CROTONALDEHYDE; MONOHYDROXYBUTENYLMERCAPTURIC ACID; MUTAGENIC AGENT; NICOTINE; PYRENE; TAR; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CHEMICAL COMPOSITION; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; ELECTRICAL EQUIPMENT; ELECTRICALLY HEATED CIGARETTE SMOKING SYSTEM; FEMALE; HEMOGLOBIN BLOOD LEVEL; HUMAN; HUMAN EXPERIMENT; JAPAN; MALE; POPULATION EXPOSURE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RISK ASSESSMENT; SMOKING; SMOKING HABIT; URINARY EXCRETION;

ADULT; BIOLOGICAL MARKERS; CARBOXYHEMOGLOBIN; ELECTRICITY; FEMALE; HOT TEMPERATURE; HUMANS; INHALATION EXPOSURE; JAPAN; MALE; MIDDLE AGED; SMOKING; TIME FACTORS; TOBACCO; TOBACCO PRODUCTS; TOBACCO SMOKE POLLUTION; YOUNG ADULT;

EID: 84868340004     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2012.08.003     Document Type: Article

References (48)

1. Benowitz N.L. Pharmacologic aspects of cigarette smoking and nicotine addiction. New Engl. J. Med. 1988, 319:1318-1330.
2. Benowitz N.L., Jacob P., Fong I., Gupta S. Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine. J. Pharmacol. Exp. Ther. 1994, 268:296-303.
3. Buchhalter A.R., Eissenberg T. Preliminary evaluation of a novel smoking system: effects on subjective and physiological measures and on smoking behavior. Nicotine Tob. Res. 2000, 2:39-43.
4. Buchhalter A.R., Schrinel L., Eissenberg T. Withdrawal-suppressing effects of a novel smoking system: comparison with own brand, not own brand, and a de-nicotinized cigarette. Nicotine Tob. Res. 2001, 3:111-118.
5. Carmella S.G., Han S., Fristad A., Yang Y., Hecht S.S. Analysis of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in human urine. Cancer Epidemiol. Biomarkers Prev. 2003, 11:1257-1261.
6. Deyton L., Sharfstein J., Hamburg M. Tobacco product regulation: a public health approach. New Engl. J. Med. 2010, 362:1753-1756.
7. Einistö P., Nohmi T., Watanabe M., Ishidate M. Sensitivity of Salmonella typhimurium YG1024 to urine mutagenicity caused by cigarette smoking. Mutat. Res. 1990, 245:87-92.
8. Family Smoking Prevention and Tobacco Control Act (FSPTCA), 2009. Public Law No. 111-31 (June 22, 2009).
9. Food and Drug Administration, 2001. Guidance for Industry. Bioanalytical Method Validation. Available from: (accessed 23.04.2009). http://www.fda.gov/cder/guidance/4252fnl.pdf.
10. Food and Drug Administration, 2012a. FDA's Guidance for Industry " Modified Risk Tobacco Products Applications" Request for Comments Docket No. FDA-2012-D-0071. Available at: (accessed May 23, 2012). http://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation/ucm297750.htm.
11. Frost-Pineda K., Zedler B.K., Oliveri D., Feng S., Liang Q., Roethig H.J. Short-term clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers. Regul. Toxicol. Pharmacol. 2008, 52:104-110.
12. Frost-Pineda K., Zedler B.K., Oliveri D., Liang Q., Feng S., Roethig H.J. 12-Week clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers. Regul. Toxicol. Pharmacol. 2008, 52:111-117.
13. Hatsukami D.K., Gorvino G.A., Eissenberg T., Clark P.I., Lawrence D., Leichow S. Methods to assess potential reduced exposure products. Nicotine Tob. Res. 2005, 7:827-844.
14. Heatherton T.F., Kozlowski L.T., Frecker R.C., Fagerström K.-O. The Fagerström Test for nicotine dependence: a revision of the Fagerström Tolerance Questionnaire. Br. J. Addict. 1991, 86:1119-1127.
15. Hecht S.S. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat. Rev. Cancer 2003, 3:733-744.
16. Hecht S.S., McIntee E.J., Wang M. New DNA adducts of crotonaldehyde and acetaldehyde. Toxicology 2001, 166:31-36.
17. Hughes J.R., Keely J.P. The effect of a novel smoking system - accord - on ongoing smoking and toxin exposure. Nicotine Tob. Res. 2004, 6:1021-1027.
18. Institute of Medicine Scientific Standards for Studies on Modified Risk Tobacco Products 2012, The National Academy Press, Washington, DC.
19. International Organization for Standardization Tobacco and Tobacco Products - Atmosphere for Conditioning and Testing. ISO 3402 1991, International Organization for Standardization, Geneva.
20. International Organization for Standardization Cigarettes - Determination of Carbon Monoxide in the Vapour Phase of Cigarette Smoke - NDIR method. ISO 8454 1995, International Organization for Standardization, Geneva. second ed.
21. International Organization for Standardization Routine Analytical Cigarette-Smoking Machine - Definitions and Standard Conditions. Standard 3308 2000, International Organization for Standardization, Geneva. fourth ed.
22. International Organization for Standardization Cigarettes - Determination of Total and Nicotine-Free Dry Particulate Matter Using a Routine Analytical Smoking Machine. ISO Standard 4387 2000, International Organization of Standardization, Geneva. third ed.
23. International Organization for Standardization Cigarettes - Determination of Nicotine in Smoke Condensates - Gas Chromatographic Method. ISO Standard 10315 2000, International Organization for Standardization, Geneva. second ed.
24. Lindner D., Smith S., Martin Leroy C., Tricker A.R. Comparison of exposure to selected cigarette smoke constituents in adult smokers and nonsmokers in a European, multicenter, observational study. Cancer Epidemiol. Biomarkers Prev. 2011, 20(7):1524-1536.
25. Martin Leroy C., Jarus-Dziedzic K., Ancerewicz J., Lindner D., Kulesza A., Magnette J. Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 7: A one-month, randomized, controlled clinical study in Poland. Regul. Toxicol. Pharmacol. 2012, 64(Suppl. 1):S74-S84.
26. Mascher D.G., Mascher H.J., Scherer G., Schmid E.R. High-performance liquid chromatographic-tandem mass spectrometric determination of 3-hydroxypropylmercapturic acid in human urine. J. Chromatogr. B Biomed. Sci. Appl. 2001, 750:163-169.
27. Medeiros A.M., Bird M.G., Witz G. Potential biomarkers of benzene exposure. J. Toxicol. Environ. Health 1997, 51:519-539.
28. Ministry of Health, Labour and Welfare, Japan, 2004. MHLW Ordinance No. 172, Dec 21, 2004.
29. Ministry of Health, Labour and Welfare, Japan, 2008. Annual Health, Labour and Welfare Report 2007-2008. Available from: (accessed 08.04.2009). http://www.mhlw.go.jp/english/wp/wp-hw2/index.html.
30. Pojer R., Whitfield J.B., Poulos V., Eckhard I.F., Richmond R., Hensley W.J. Carboxyhemoglobin, cotinine, and thiocyanate assay compared for distinguishing smokers from non-smokers. Clin. Chem. 1984, 30:1377-1380.
31. Riedel K., Scherer G., Engl J., Hagedorn H.-W., Tricker A.R. Determination of three carcinogenic aromatic amines in urine of smokers and nonsmokers. J. Anal. Toxicol. 2006, 30:187-195.
32. Roethig H.J., Kinser R.D., Lau R.W., Walk R.-A., Wang N. Short-term exposure evaluation of adult smokers switching from conventional to first-generation electrically heated cigarettes during controlled smoking. J. Clin. Pharmacol. 2005, 45:133-145.
33. Roethig H.J., Zedler B.K., Kinser R.D., Feng S., Nelson B.L., Liang Q. Short-term clinical exposure evaluation of a second generation electrically heated cigarette smoking system. J. Clin. Pharmacol. 2007, 47:518-530.
34. Scherer G. Smoking behaviour and compensation: a review of the literature. Psychopharmacology (Berl) 1999, 145:1-20.
35. Scherer G., Urban M., Hagedorn H.-W., Feng S., Kinser R.D., Sarkar M., Liang Q., Roethig H.J. Determination of two mercapturic acids related to crotonaldehyde in human urine: influence of smoking. Hum. Exp. Toxicol. 2007, 26:37-47.
36. Schorp M.K., Tricker A.R., Dempsey R. Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 1: Non-clinical and clinical insights. Regul. Toxicol. Pharmacol. 2012, 64(Suppl. 1):S1-S10.
37. Shields P.G. Tobacco smoking, harm reduction, and biomarkers. J. Natl. Cancer Inst. 2002, 94:1435-1444.
38. Smith C.J., Karnes S.C., Davies R.A., Livingston S.D., Bombick B.R., Avalos J.T., Morgan W.T., Doolittle D.J. Human urine mutagenicity study comparing cigarettes which burn or primarily heat tobacco. Mutat. Res. 1996, 361:1-9.
39. Stevens J.F., Maier C.S. Acrolein: sources, metabolism, and biomolecular interaction relevant to human and disease. Mol. Nutr. Food Res. 2008, 52:7-25.
40. Strickland P., Kang D., Sithisarankul P. Polycyclic aromatic hydrocarbon metabolites in urine as biomarkers of exposure and effect. Environ. Health Perspect. 1996, 104(Suppl. 5):927-932.
41. Tricker A.R., Stewart A.J., Martin Leroy C., Lindner D., Schorp M.K., Dempsey R. Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 3: 8-day randomized clinical trial in the UK. Regul. Toxicol. Pharmacol. 2012, 64(Suppl. 1):S35-S44.
42. Tricker A.R., Jang I.-J., Martin Leroy C., Lindner D., Dempsey R. Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 4: 8-day randomized clinical trial in Korea. Regul. Toxicol. Pharmacol. 2012, 64(Suppl. 1):S45-S53.
43. Tricker A.R., Kanada S., Takada K., Martin Leroy C., Lindner D., Schorp M.K., Dempsey R. Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 6: 6-day randomized clinical trial of a menthol cigarette in Japan. Regul. Toxicol. Pharmacol. 2012, 64(Suppl. 1):S64-S73.
44. Urban M., Kavvadias D., Riedel K., Scherer G., Tricker A.R. Urinary mercapturic acids and a hemoglobin adduct for the dosimetry of acrylamide exposure in smokers and nonsmokers. Inhal. Toxicol. 2006, 18:831-839.
45. US Department of Health and Human Services, 2010. A Report of the Surgeon General: How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking Attributable Disease. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health.
46. van Sittert N.J., Mergens H.J., Watson W.P., Boogaard P.J. Biomarkers of exposure to 1,3-butadiene as a basis for cancer risk assessment. Toxicol. Sci. 2000, 56:189-202.
47. Werley M.S., Freelin S.A., Wrenn S.E., Gerstenberg B., Roemer E., Schramke H., Van Miert E., Vanscheeuwijck P., Weber S., Coggins C.R.E. Smoke chemistry, in vitro and in vivo toxicology evaluations of the electrically heated cigarette smoking system series K. Regul. Toxicol. Pharmacol. 2008, 52:122-139.
48. Zenzen V., Diekmann J., Gerstenberg B., Weber S., Wittke S., Schorp M.K. 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. Regul. Toxicol. Pharmacol. 2012, 64(Suppl. 1):S11-S34.