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Bernert JT, Pirkle JL, Xia Y, Jain RB, Ashley DL, Sampson EJ. Urine concentrations of a tobacco-specific nitrosamine carcinogen in the U.S. population from secondhand smoke exposure. Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2969-77.


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

Methods: 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 LOD, the 50th through 95th percentiles, and in some cases geometric means for groups classified by age, gender and race/ethnicity.

Results: 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 aged ≥20 years (p < 0.001).

Conclusions: Among NHANES participants, total NNAL was found at measurable levels in the urine of 41% of nonsmokers, and in 87.5% of those with substantial SHS exposure (with serum cotinine concentrations of 0.1 to 10 ng/mL). Children aged 6–11 years had the highest NNAL concentrations among all nonsmokers.

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

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