Biomonitoring Summary
Cotinine
CAS No. 486-56-6
Metabolite of nicotine (a component of tobacco smoke)
General Information
Tobacco use is the most important preventable cause of premature morbidity and mortality in the United States. The consequences of smoking and of using smokeless tobacco products are well known and include an increased risk for several types of cancer, emphysema, acute respiratory illness, cardiovascular disease, stroke, and various other disorders (U.S. DHHS, 2006). Persons exposed to secondhand tobacco smoke (SHS) may have adverse health effects that include lung cancer and coronary heart disease; maternal exposure during pregnancy can result in lower birth weight. Children exposed to SHS are at increased risk for sudden infant death syndrome, acute respiratory infections, ear problems, and exacerbated asthma (U.S. DHHS, 2004). The smoke produced by burning tobacco contains at least 250 chemicals that are toxic or carcinogenic, and more than 50 compounds present in SHS are known or reasonably anticipated to be human carcinogens (NTP, 2011).
Cigarettes contain about 1.5% nicotine by weight (Kozlowski et al., 1998), producing roughly 1–2 mg of bioavailable nicotine per cigarette (Benowitz and Jacob, 1994; Hukkanen et al., 2005). Inhaling tobacco smoke from either active or passive (e.g., SHS) smoking is the main source of nicotine exposure for the general population. Up to 90% of the nicotine delivered in tobacco smoke is absorbed rapidly from the lungs into the blood stream (Armitage et al., 1975; Iwase et al., 1991). Mean air concentrations of nicotine in public spaces where smoking was allowed ranged from 0.3 to 30 µg/m3, with higher levels being measured in restaurants and bars. In homes with one or more smokers, mean air concentrations typically ranged from 2 to 14 µg/m3 (NTP, 2011). For adults, the primary sources for SHS exposure have been in workplaces where smoking occurs and in residences shared with one or more smokers. Children are primarily exposed to SHS by parents and caregivers who smoke.
Nicotine can also be absorbed from the gastrointestinal tract and skin by using snuff, chewing tobacco, or chewing gum, nasal sprays, or skin patches that contain nicotine. Workers who harvest tobacco can be exposed to nicotine, even becoming intoxicated as a result of the transdermal absorption of nicotine contained in the plant. The tobacco plant, Nicotiana tabacum, contains nicotine in larger amounts than other nicotine-containing plants, which include potatoes, tomatoes, eggplants, and peppers. Nicotine has been used commercially as an insecticide in its sulfate and alkaloid forms.
Once absorbed, nicotine has a half-life in blood plasma of several hours (Benowitz, 1996). Cotinine, the primary metabolite of nicotine, is currently regarded as the best biomarker of tobacco smoke exposure. Measuring cotinine is preferable to measuring nicotine because cotinine persists longer in the body with a plasma half-life of about 16 hours (Benowitz and Jacob, 1994).However, non-Hispanic blacks metabolize cotinine more slowly than do non-Hispanic whites (Benowitz et al., 1999; Perez-Stable et al., 1998).Cotinine can be measured in serum, urine, saliva, and hair. Nonsmokers exposed to typical levels of SHS have serum cotinine levels of less than 1 ng/mL, with heavy exposure to SHS producing levels in the 1–10 ng/mL range. Active smokers almost always have levels higher than 10 ng/mL and sometimes higher than 500 ng/mL (Hukkanen et al., 2005).
Nicotine stimulates preganglionic cholinergic receptors within peripheral sympathetic autonomic ganglia and at cholinergic sites within the central nervous system. Acute tobacco or nicotine intoxication can produce dizziness, nausea, vomiting, diaphoresis, salivation, diarrhea, variable changes in blood pressure and heart rate, seizures, and death. Nicotine also indirectly causes a release of dopamine in the brain regions that control pleasure and motivation, a process involved in the development of addiction. Symptoms of nicotine withdrawal include irritability, craving, cognitive and sleep disturbances, and increased appetite.
The IARC and the NTP consider tobacco smoke to be a human carcinogen. NIOSH guidelines consider SHS to be a potential occupational carcinogen and recommend that exposure be reduced to the lowest feasible concentration. The Federal Aviation Administration has banned the smoking of tobacco products on both domestic and foreign air carrier flights in the U.S. More information about the effects of smoking and nicotine can be found at https://www.nida.nih.gov/researchreports/nicotine/nicotine.htmlexternal icon.
Biomonitoring Information
Serum cotinine levels reflect recent exposure to nicotine in tobacco smoke. Nonsmoking is usually defined as a serum cotinine level of less than or equal to 10 ng/mL (Pirkle et al., 1996).
The serum cotinine levels in U.S. non-smokers have declined over time, as demonstrated by NHANES 1999-2000 relative to NHANES 2009-2010 (CDC, 2013). Serum cotinine has been measured in many studies of nonsmoking populations, with levels showing similar or slightly higher results (depending on the degree of SHS exposure) than those reported in concurrent NHANES survey periods (CDC 2013; NCI, 1999). Nonsmokers’ exposure to SHS has decreased over time, evidenced by a decline of approximately 70% in geometric mean cotinine serum concentrations and a detection frequency of serum cotinine falling from 88% to 43% from NHANES 1988–1991 to NHANES 1999–2002 (Pirkle et al., 2006). Contributing to the decrease in overall population estimates of serum cotinine is probably the reduced SHS exposure subsequent to greater restrictions of smoking in public places (Pickett et al., 2006; Soliman et al., 2004). During the 1980s and 1990s, the adjusted geometric mean serum cotinine was higher in children aged 4–11 years than in adults among both non-Hispanic blacks and non-Hispanic whites (Pirkle et al., 2006). Non-Hispanic blacks had higher serum cotinine concentrations compared with either non-Hispanic whites or Mexican-Americans. Higher levels of cotinine have previously been reported for non-Hispanic black smokers (Caraballo et al., 1998). Differences in cotinine concentrations among race/ethnicity and age groups may be influenced by pharmacokinetic differences as well as by SHS exposure (Benowitz et al., 1999; Hukkanen et al., 2005; Wilson et al., 2005).
Biomonitoring studies of serum cotinine will help physicians and public health officials determine whether people have been exposed to higher levels of ETS than are found in the general population. Biomonitoring data can also help scientists plan and conduct research about exposure to ETS and about its health effects.
References
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Benowitz NL, Perez-Stable EJ, Fong I, Modin G, Herrera B, Jacob P III. Ethnic differences in N-glucuronidation of nicotine and cotinine. J Pharmacol Exp Ther 1999;291(3):1196-1203.
Caraballo R, Giovino G, Pechacek TF, Mowery PD, Richter PA, Strauss WJ, et al. Racial/ethnic differences in serum cotinine levels among adult U.S. cigarette smokers: the Third National Health and Nutrition Examination Survey, 1988-1991. JAMA 1998;280:135-40.
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