Assessing exposure to tobacco-specific carcinogen NNK using its urinary metabolite NNAL measured in US population: 2011-2012

J Expo Sci Environ Epidemiol. May-Jun 2016;26(3):249-56. doi: 10.1038/jes.2014.88. Epub 2015 Jan 7.


Carcinogenic tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are found only in tobacco and derived products. Food and Drug Administration of the United States (US FDA) lists NNK as one of the 93 harmful and potentially harmful constituents (HPHCs) found in tobacco products and tobacco smoke. The aim of this study was to use the urinary concentration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major metabolite of NNK, to quantitatively estimate exposure to NNK in the US general population. In 2011-2012, the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) collected urine and serum samples from a representative sample of US residents. We used a serum cotinine cutoff of 10 ng/ml with combination of questionnaire data to select non-users from cigarette users and used self-reported data to determine different tobacco product user groups. We estimated the absorbed total daily dose of NNK using a probabilistic method based on a two-compartment model. The geometric mean (GM) for the daily dose of NNK among smokers aged 12-16 years was significantly higher than that for non-users at the same age stage exposed to second-hand smoke (SHS) (P<0.001). Among those exposed to SHS, the GM for daily dose of NNK in young children (6-11 years) was nearly three times of those for adults in the age range 21-59 years. Among cigarette users, non-Hispanic Whites had the highest NNK daily dose and Mexican Americans had the lowest levels. Exclusive snuff or chewing product users had significantly higher daily dose of NNK than did cigarette smokers. Our study found that the maximum daily dose of NNK for children aged from 6 to 11 years and that for a significant percentage of cigarette users, chewing product and snuff users were higher than an estimated provisional "reference" risk level.

MeSH terms

  • Carcinogens / toxicity*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Nitrosamines / toxicity*
  • Nitrosamines / urine*
  • Pyridines / urine*
  • Surveys and Questionnaires
  • Tobacco / chemistry*
  • United States


  • Carcinogens
  • Nitrosamines
  • Pyridines
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol