Urine cotinine underestimates exposure to the tobacco-derived lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in passive compared with active smokers.

OBJECTIVES Cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are widely used biomarkers for tobacco-derived nicotine and the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. The discrepancy between cotinine levels in relation to disease risk comparing active versus passive smoking suggests a nonlinear tobacco smoke dose-response and/or that cotinine is not providing an accurate measure of exposure to the toxic constituents of secondhand tobacco smoke. METHODS Cotinine and NNAL were measured in the urine of 373 active smokers and 228 passive smokers. RESULTS Average cotinine levels were 1,155 (interquartile range, 703-2,715) for active smokers and 1.82 (0.45-7.33) ng/mg creatinine for passive smokers. Average NNAL levels were 183 (103-393) and 5.19 (2.04-11.6) pg/mg creatinine, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 × 10(3) versus 0.16 × 10(3), P < 0.0001). CONCLUSIONS Passive smoking is associated with a much higher ratio of NNAL/cotinine in the urine compared with active smoking. IMPACT Cotinine measurement leads to an underestimation of exposure to the carcinogen NNK from secondhand smoke when compared with active smoking.