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

Regul Toxicol Pharmacol. 2012 Nov 1;64(2 Suppl):S85-97. doi: 10.1016/j.yrtph.2012.08.005. Epub 2012 Aug 23.


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-h 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.

Publication types

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

MeSH terms

  • Biomarkers / blood
  • Biomarkers / urine
  • Carbon Monoxide / metabolism
  • Carbon Monoxide / toxicity
  • Electricity
  • Hot Temperature
  • Humans
  • Inhalation Exposure / adverse effects*
  • Inhalation Exposure / analysis
  • Models, Biological
  • Mutagenicity Tests
  • Nicotine / analysis
  • Nicotine / blood
  • Nicotine / metabolism*
  • Nicotine / urine
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics
  • Smoking / adverse effects
  • Smoking / blood*
  • Smoking / urine*
  • Tars / metabolism
  • Tars / toxicity
  • 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


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