Urine nicotine metabolite concentrations in relation to plasma cotinine during low-level nicotine exposure

Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, San Francisco General Hospital Medical Center, University of California, San Francisco, Box 1220, San Francisco, CA 94143-1220, USA.
Nicotine & Tobacco Research (Impact Factor: 3.3). 07/2009; 11(8):954-60. DOI: 10.1093/ntr/ntp092
Source: PubMed


Plasma or saliva cotinine concentrations are used widely as biomarkers of secondhand smoke (SHS) exposure and have been associated with the risk of SHS-related disease. Concentrations of cotinine and other nicotine metabolites are considerably higher in urine than in plasma or saliva, making chemical analysis easier. In addition, urine is often more convenient to collect in some SHS exposure studies. The optimal use of nicotine metabolites in urine, singly or in combination, with or without correction for urine creatinine concentration, to estimate plasma cotinine concentration with low-level nicotine exposure has not been determined.
We dosed 36 nonsmokers with 100, 200, or 400 microg deuterium-labeled nicotine (simulating exposure to SHS) by mouth daily for 5 days and then measured plasma and urine cotinine and metabolites at various intervals over 24 hr.
A plasma cotinine concentration of 1 ng/ml corresponds on average to a daily intake of 100 microg nicotine. Cotinine concentrations in urine averaged four to five times those in plasma. Correction of urine cotinine for creatinine concentration improved the correlation between urine and plasma cotinine. Measuring multiple cotinine metabolites in urine did not improve the correlation with plasma cotinine, compared with the use of urine cotinine alone.
Measurement of urine cotinine corrected for creatinine concentration appears to be the best predictor of plasma cotinine.

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    • "In addition to the characterization of external exposure, the determination of the body burden of the target substances or their urinary metabolites is an accurate method of obtaining important information to use in a risk assessment (Angerer et al., 2011). We focused predominantly on nicotine and its transformation products, cotinine and trans-3- hydroxycotinine, as well as on tobacco-related nitrosamines, all of which are specific biomarkers of tobacco smoke exposure in humans (Benowitz et al., 2009). The determination of the content of mercapturic acids in urine is also a good indication of the absorbed internal dose of a carcinogen, because mercapturic acids are metabolites of the highly reactive components of tobacco smoke (Schettgen et al., 2008). "
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    ABSTRACT: Waterpipe (WP) smoking is growing as an alternative to cigarette smoking, especially in younger age groups. E-cigarette use has also increased in recent years. A majority of smokers mistakenly believe that WP smoking is a social entertainment practice that leads to more social behavior and relaxation and that this type of smoking is safe or less harmful and less addictive than cigarette smoking. In reality, WP smokers are exposed to hundreds of toxic substances that include known carcinogens. High exposures to carbon monoxide and nicotine are major health threats. Persons exposed to secondhand WP smoke are also at risk. There is growing evidence that WP smoke causes adverse effects on the pulmonary and cardiovascular systems and is responsible for cancer.
    Atmospheric Environment 04/2015; 106:429-441. DOI:10.1016/j.atmosenv.2014.08.030 · 3.28 Impact Factor
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    • "Dietary intake of nicotine from food like fruits and vegetables is possible but likely to be negligible [8]. Urinary cotinine, especially when corrected for creatinine concentration, is highly correlated with plasma cotinine [9]. "
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    ABSTRACT: Cotinine levels provide a valid measure of exposure to environmental tobacco smoke (ETS). The goal of this study was to examine exposure to tobacco smoke among smoking and nonsmoking Israeli adults and to identify differences in ETS exposure among nonsmokers by socio-demographic factors. We analyzed urinary cotinine data from the first Israeli Human Biomonitoring Study conducted in 2011. In-person questionnaires included data on socio-demographic and active smoking status. Cotinine levels were measured using a gas chromatography-mass spectrometry procedure. We calculated creatinine-adjusted urinary cotinine geometric means (GM) among smokers and nonsmokers, and by socio-demographic, smoking habits and dietary factors. We analyzed associations, in a univariable and multivariable analysis, between socio-demographic variables and proportions of urinary cotinine >=1 mug/l (Limit of Quantification = LOQ) or >=4 mug/l. Cotinine levels were significantly higher among 91 smokers (GM = 89.7 mug/g creatinine; 95% confidence interval [CI]: 47.4-169.6) than among 148 nonsmokers (GM = 1.3; 1.1-1.7). Among exclusive waterpipe smokers, cotinine levels were relatively high (GM = 53.4; 95% CI 12.3-232.7). ETS exposure was widespread as 62.2% of nonsmokers had levels >= LOQ, and was higher in males (75.8%) than in females (52.3%). In a multivariable model, urinary cotinine >= LOQ was higher in males (Prevalence ratio [PR] = 1.30; 95% CI: 1.02-1.64, p = 0.032) and in those with lower educational status (PR = 1.58; 1.04-2.38, p = 0.031) and decreased with age (PR = 0.99; 0.98-1.00, p = 0.020, per one additional year). There were no significant differences by ethnicity, residence type or country of birth. Our findings indicate widespread ETS exposure in the nonsmoking Israeli adult population, especially among males, and younger and less educated participants. These findings demonstrate the importance of human biomonitoring, were instrumental in expanding smoke-free legislation implemented in Israel on July 2012 and will serve as a baseline to measure the impact of the new legislation.
    BMC Public Health 12/2013; 13(1):1241. DOI:10.1186/1471-2458-13-1241 · 2.26 Impact Factor
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    • "Repace and Lowrey (1993) derived a urine cotinine U to plasma cotinine P ratio of U/P = 6.5 (n = 19). Benowitz et al. (2009) "
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    ABSTRACT: We estimated the impact of a smoke-free workplace bylaw on non-smoking bar workers' health in Ontario, Canada. We measured bar workers' urine cotinine before (n = 99) and after (n = 91) a 2004 smoke-free workplace bylaw. Using pharmacokinetic and epidemiological models, we estimated workers' fine-particle (PM 2.5) air pollution exposure and mortality risks from workplace secondhand smoke (SHS). Workers' pre-law geometric mean cotinine was 10.3 ng/ml; post-law dose declined 70% to 3.10 ng/ml and reported work hours of exposure by 90%. Pre-law, 97% of workers' doses exceeded the 90th percentile for Canadians of working age. Pre-law-estimated 8-h average workplace PM 2.5 exposure from SHS was 419 ug/m3 or 'Very Poor' air quality, while outdoor PM 2.5 levels averaged 7 ug/m3 , 'Very Good' air quality by Canadian Air Quality Standards. We estimated that the bar workers' annual mortality rate from workplace SHS exposure was 102 deaths per 100 000 persons. This was 2.4 times the occupational disease fatality rate for all Ontario workers. We estimated that half to two-thirds of the 10 620 Ontario bar workers were non-smokers. Accordingly, Ontario's smoke-free law saved an estimated 5–7 non-smoking bar workers' lives annually, valued at CA $50 million to $68 million (US $49 million to $66 million). Practical Implications Worker's cotinine measurements can be compared with population databases to assess an occupational group's dose of secondhand smoke relative to the general population. Cotinine can be used to estimate secondhand smoke air pollution exposures and risks for workers and evaluate the efficacy of smoke-free workplace laws in terms of lives and social costs saved. Although Canadian bars are now smoke-free, substantial exposure persists on bar patios, and in many other countries, indoor air in bars remains polluted with secondhand smoke.
    Indoor Air 04/2013; 23(2):93-104. DOI:10.1111/ina.12004 · 4.90 Impact Factor
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