Comparison of Urine Cotinine and the Tobacco-Specific Nitrosamine Metabolite 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol (NNAL) and Their Ratio to Discriminate Active From Passive Smoking

Abstract

Conclusions:Both urine cotinine and NNAL are sensitive and specific biomarkers for discriminating the source of tobacco smoke exposure. Cotinine is the best overall discriminator when biomarkers are measured while a person has ongoing exposure to tobacco smoke. NNAL because of its long half-life would be particularly useful when there is a delay between exposure and biomarker measurement. The NNAL/cotinine ratio provides similar sensitivity but poorer specificity at discriminating passive versus active smokers when compared with NNAL alone. IntroductionBiomarkers are useful in assessing both active and passive smokers' exposure to tobacco smoke. Self-reported exposure such as cigarettes smoked per day by active smokers and hours per day exposed to secondhand smoke (SHS) in passive smokers is imprecise. Exposure patterns differ significantly from person to person due to differences in how cigarettes are smoked, differences in tobacco products, room ventilation, proximity of smokers to nonsmokers, and many other environmental factors (N. L. Benowitz, 1996).Biomarkers are used to discriminate active from passive smokers in epidemiological studies, population surveillance of tobacco use, and research on the health risks of active and passive smoking. Determination of optimal biomarker cutoff Abstract Objectives: Cotinine is the most widely used biomarker to distinguish active versus passive smoking. However, there is an overlap in cotinine levels when comparing light or occasional smokers versus heavily exposed passive smokers. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. The aim of the study was to determine optimal cutoff points to discriminate active versus passive smokers and to compare sensitivity and specificity for the use of cotinine, NNAL, and the ratio of the NNAL/cotinine in urine.Methods: Cotinine and NNAL were measured in urine of 373 active smokers and 228 passive smokers.Results: Geometric mean cotinine levels were 2.03 ng/ml (interquartile interval: 0.43-8.60) and 1,043 ng/ml (658-2,251) and NNAL levels were 5.80 pg/ml (2.28-15.4) and 165 pg/ml (90.8-360) pg/ml in passive and active smokers, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 vs. 0.16, p < .01). The receiver operating characteristics analysis determined optimal cutoff points to discriminate passive versus active smokers: 31.5 ng/ml for cotinine (sensitivity: 97.1% and specificity: 93.9%), 47.3 pg/ml for NNAL (87.4% and 96.5%), and 0.74 × 10 −3 for NNAL/cotinine ratio (97.3% and 87.3%).

Formaldehyde-induced toxicity in the nasal epithelia of workers of a plastic laminate plant

“…61 The role of smoking habit was investigated in the present study, but a significant influence of tobacco smoking on M 1 dG adducts has been only found in the group of controls, where the generation of DNA damage was linearly correlated to the levels of urinary cotinine, a major proximate metabolite of nicotine, that is oxidized in the liver by the cytochrome P450 2A6 enzyme and distributed in various body fluids. 35 Indeed, although the smoker workers had an increase of cotinine like the controls, the levels of DNA damage in their nasal epithelia were not correlated to the amounts of urinary cotinine. This finding is in agreement with previous studies reporting higher M 1 dG levels in smokers, 22,23,62 but other studies did not report significant differences by smoking status.…”

“…1,46 To estimate the smoking status of the study population, the urinary cotinine was measured by the GC-MS assay, 33,37 since this nicotine metabolite is considered to be a reliable indicator of tobacco smoking. 35 The GC-MS analysis showed that the levels of urinary cotinine were 1064 ± 118 ng ml −1 and 14.18 ± 2.5 ng ml −1 in smokers and non-smokers, respectively, P < 0.001. The concentrations of urinary cotinine ranged from 1.0 to 3306.1 ng ml −1 for the FA workers, and from 0.80 to 1644.4 ng ml −1 for the controls.…”

“…16 M 1 dG adducts have been examined in the nasal epithelial cells using the 32 P-DNA post-labeling technique, 25,[29][30][31][32] whereas the indoor levels of FA have been measured by using passive personal air samplers using the gas-chromatography mass-spectrometry (GC-MS) technique. 23,33,34 The tobacco smoking status has also been estimated by measuring the levels of urinary cotinine, an indicator of tobacco smoke exposure, 35 using the GC-MS assay. 33,36,37 Experimental…”

NIH Electronic Cigarette Workshop: Developing a Research Agenda

“…9,62 The ratio of cotinine to total NNK metabolites (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides) in urine could be a useful biomarker of dual use of combustible tobacco products and e-cigarettes as it is expected to be significantly lower in combustible tobacco product users than in e-cigarette users. 63,64 Total NNN, including its glucuronide, can be measured in urine. Although NNN is expected to be low in e-cigarette users, it can be generated in the body by nitrosation of nornicotine, which is co-extracted with the nicotine from tobacco or can be generated in vivo through nicotine metabolism.…”

Fetal Exposure to Carcinogens With Tobacco Use in Pregnancy: Phase 1 MAW Study Findings

“…12 NNAL, the tobacco-specific carcinogenic metabolite of NNK, has an even longer half-life (10-16 days) and can also be measured in urine. 12,13,15 We sought to enroll a convenience sample of 165 pregnant women (55 smokers, 55 ST [commercial ST and iqmik] users, and 55 non-[tobacco] users) seeking prenatal care at SCF outpatient clinics. Non-users were included as a comparison group.…”