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Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2969-77. doi: 10.1158/1055-9965.EPI-10-0711. Epub 2010 Sep 10.

Urine concentrations of a tobacco-specific nitrosamine carcinogen in the U.S. population from secondhand smoke exposure.

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  • 1Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.



The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its reduction product in the body, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are potent pulmonary carcinogens. We have measured total NNAL in the U.S. population of tobacco users and nonsmokers exposed to secondhand smoke.


We measured total urinary NNAL (free NNAL plus its glucuronides following hydrolysis) by using a sensitive and specific high-performance liquid chromatography/tandem mass spectrometry method. We calculated the percentage above the limit of detection, the 50th through 95th percentiles, and in some cases, geometric means for groups classified by age, gender, and race/ethnicity.


Total urinary NNAL was measureable at or above its limit of detection (0.6 pg/mL) in 55% of the study participants, including 41% of nonsmokers. The population distribution of urinary NNAL included smoker and nonsmoker regions similar to the bimodal distribution of serum cotinine, and serum cotinine and total urinary NNAL were strongly correlated (r = 0.92; P < 0.001). Among nonsmokers, children had significantly higher concentrations of NNAL than did adults with the age of ≥20 years (P < 0.001).


Among National Health and Nutrition Examination Survey participants, total NNAL was found at measurable levels in the urine of 41% of nonsmokers and in 87.5% of those with substantial secondhand-smoke exposure (with serum cotinine concentrations of 0.1-10 ng/mL). Children with the age of 6 to 11 years had the highest NNAL concentrations among all nonsmokers.


We describe for the first time the distribution of total urinary NNAL in the entire U.S. population, including smokers and nonsmokers. NNAL was detected in 41% of all nonsmokers.

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