Nicotine and Its Major Metabolites as Biomarkers of Exposure to Tobacco
Key messages
- Nicotine and its major metabolites are tobacco-specific biomarkers of exposure to tobacco.
- Measuring nicotine and its major metabolites is useful to study how widespread smoking is and how much Canadians are exposed to tobacco products.
Why do we measure exposure to tobacco?
The use of tobacco products and exposure to tobacco smoke is a major risk factor for serious diseases. These diseases include lung cancer and heart disease. Tobacco products are claimed to be responsible for the deaths of over 37,000 Canadians annually.Footnote 7 From a public health point of view, it is important to monitor the use of tobacco products and study how much of the Canadian population is exposed to second-hand smoke. Most surveys on tobacco use and exposure to tobacco smoke are based on self-reports. However, a better indicator of exposure would be to measure the biomarkers of exposure specific to tobacco products and tobacco smoke.
Nicotine and its major metabolites
The use and handling of tobacco products or second-hand exposure to tobacco smoke results in nicotine uptake into the bloodstream. Once nicotine reaches the liver, kidneys and lungs, it is metabolized into several major breakdown products known as cotinine, cotinine-N-glucuronide, nicotine-N-glucuronide, trans-3'-hydroxycotinine and trans-3-hydroxycotinine-O-glucuronide.Footnote 4 These breakdown products (metabolites) as well as nicotine itself are tobacco-specific biomarkers of exposure and can be measured in urine or blood. This information can then be used to determine the extent to which a person has been exposed to tobacco products or tobacco smoke.Footnote 8
Cotinine is one of the most effective biomarkers of exposure to tobacco products and tobacco smoke.Footnote 5 It can be easily measured in urine or bloodFootnote 1Footnote 2 and can be detected in the body for up to four days after exposure to nicotine.Footnote 3Footnote 6 Cotinine is specific to nicotine. It also provides a reliable measurement of exposure to tobacco products and/or tobacco smoke. Recently, measuring cotinine levels was used successfully to validate self-reported smoking status.Footnote 9
How are nicotine and its major metabolites being used?
The Canadian Health Measure Survey (CHMS), a survey by Statistics Canada, examines the exposure of Canadians to a variety of environmental chemicals. Nicotine and its major metabolites are some of the 91 chemicals that the survey measures. Measuring tobacco-specific biomarkers of exposure such as nicotine and its major metabolites through the CHMS willallow researchers to better understand smoking prevalence and the exposure of Canadians to tobacco products and tobacco smoke.
Glossary of Terms
- Metabolism
- The whole range of biochemical processes that occur within an organism. Metabolism consists of build-up and breakdown of substances.
- Metabolite
- The substance, or product, resulting from a metabolic process.
- Specific
- Related in application, or effect, to a particular chemical, structure, or process.
- Toxicant
- Artificially produced poison or poisonous substance.
- Uptake
- Absorption and incorporation of a substance by live tissue.
Footnotes
- Footnote 1
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Brown, K., von Weymarn, L., & Murphy, S. (2005). Identification of N-(hydroxymethyl) norcotinine as a major product of cytochrome P450 2A6, but not cytochrome P450 2A13-catalyzed cotinine metabolism. Chemical Research in Toxicology, 18(12), 1792-98.
- Footnote 2
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Etzel, R.A. (1990). A review of the use of saliva cotinine as a marker of tobacco smoke exposure. Preventive Medicine, 19(2), 190-7.
- Footnote 3
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Florek, E., Piekoszewski, W., & Wrzosek, J. (2003). Relationship between the level and time of exposure to tobacco smoke and urine nicotine and cotinine concentration. Polish Journal of Pharmacology, 55, 97-102.
- Footnote 4
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Hukkanen, J., Pleyton, J., & Benowitz, N.L. (2005). Metabolism and disposition kinetics of nicotine. Pharmacological Reviews, 57(1), 79-115.
- Footnote 5
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Murphy, S.E., Link, C.A., Jensen, J., Le, C., Puumala, S.S., Hecht, S.S., Carmella, S.G., Losey, L., & Hatsukami, D.K. (2004). A comparison of urinary biomarkers of tobacco and carcinogen exposure in smokers. Cancer Epidemiology, Biomarkers and Prevention, 13(10), 1617-23.
- Footnote 6
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Nakajima, M., Yamamoto, T., Nunoya, K., Yokoi, T., Nagashima, K., Inoue, K., Funae, Y., Shimada, N., Kamataki, T., & Kuroiwa, Y. (1996). Role of human cytochrome P4502A6 in C-oxidation of nicotine. Drug Metabolism and Disposition. 24(11), 1212-17.
- Footnote 7
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Rehm. J., Baliunas, D., Brochu, S., Fischer, B., Gnam, W., Patra, J., Popova, S., Sarnocinska-Hart, A., & Taylor, B. (2006). The Costs of Substance Abuse in Canada 2002. Ottawa: Canadian Centre on Substance Abuse.
- Footnote 8
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Wall, M.A., Johnson, J., Jacon, P., & Benowitz, N.L. (1988). Cotinine in the serum, saliva, and urine of nonsmokers, passive smokers, and active smokers. American Journal of Public Health, 78,699-701.
- Footnote 9
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Wong, S.L., Shields, M., Leatherdale, S., Malaison, E., & Hammond, D. (2012). Assessment of validity of self-reported smoking status. Health Reports, Statistics Canada, 23(1), 1-7.