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 Nov 1;64(2 Suppl):S64-73. doi: 10.1016/j.yrtph.2012.08.007. Epub 2012 Aug 23.


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 (M4J(M); 4 mg tar and 0.3mg nicotine) at baseline. Subjects were randomized to continue smoking M4J(M), or switch to smoking either the Electrically Heated Cigarette Smoking System menthol cigarette (EHCSS-K6(M); 5mg tar and 0.3mg nicotine) or the Lark One menthol cigarette (Lark1(M); 1mg tar and 0.1mg 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-K6(M) group (-12.3% to -83.4%). Smaller, but statistically significant reductions (p ≤ 0.05) occurred in the Lark1(M) 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / urine
  • Carboxyhemoglobin / analysis
  • Electricity
  • Female
  • Hot Temperature
  • Humans
  • Inhalation Exposure / adverse effects*
  • Inhalation Exposure / analysis
  • Japan
  • Male
  • Middle Aged
  • Smoking / adverse effects
  • Smoking / blood*
  • Smoking / urine*
  • Time Factors
  • Tobacco / chemistry
  • Tobacco / metabolism*
  • Tobacco / toxicity
  • Tobacco Products / analysis*
  • Tobacco Products / toxicity
  • Tobacco Smoke Pollution / adverse effects
  • Tobacco Smoke Pollution / analysis*
  • Tobacco Smoke Pollution / prevention & control
  • Young Adult


  • Biomarkers
  • Tobacco Smoke Pollution
  • Carboxyhemoglobin