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 Nov 1;64(2 Suppl):S11-34. doi: 10.1016/j.yrtph.2012.08.004. Epub 2012 Aug 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BALB 3T3 Cells
  • Behavior
  • Biomarkers / analysis
  • Biomarkers / urine
  • Carbon Monoxide / chemistry
  • Carbon Monoxide / toxicity
  • Cell Survival / drug effects
  • Data Interpretation, Statistical
  • Electricity
  • Hot Temperature
  • Humans
  • Inhalation Exposure / adverse effects
  • Inhalation Exposure / analysis
  • Inhalation Exposure / prevention & control*
  • Mice
  • Models, Psychological
  • Mutagenicity Tests
  • Nicotine / chemistry
  • Nicotine / toxicity
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics
  • Smoking / adverse effects*
  • Smoking / psychology
  • Tars / chemistry
  • Tars / toxicity
  • Tobacco Products / analysis*
  • Tobacco Products / toxicity
  • Tobacco Smoke Pollution / adverse effects
  • Tobacco Smoke Pollution / analysis
  • Tobacco Smoke Pollution / prevention & control*
  • Tobacco* / chemistry
  • Tobacco* / toxicity


  • Biomarkers
  • Tars
  • Tobacco Smoke Pollution
  • tobacco tar
  • Nicotine
  • Carbon Monoxide