Importance of exposure to gaseous and particulate phase components of tobacco smoke in active and passive smokers

Summary The uptake of tobacco smoke constituents from gaseous and particulate phases of mainstream smoke (MS), inhaled by smokers, and of environmental tobacco smoke (ETS), breathed in by non-smokers, was investigated in two experimental studies. Tobacco smoke uptake was quantified by measuring carboxyhemoglobin (COHb), nicotine and cotinine in plasma and urine and the data obtained were correlated with urinary excretion of thioethers and of mutagenic activity. An increase in all biochemical parameters was observed in smokers inhaling the complete MS of 24 cigarettes during 8 h, whereas only an increase in COHb and, to a minor degree, in urinary thioethers was found after smoking the gas phase of MS under similar conditions. Exposure of non-smokers to the gaseous phase of ETS or to whole ETS at similar high concentrations for 8 h led to identical increases in COM, plasma nicotine and cotinine as well as urinary excretion of nicotine and thioethers which were much lower than in smokers. Urinary mutagenicity was not found to be elevated under either ETS exposure condition. As shown by our results, the biomarkers most frequently used for uptake of tobacco smoke (nicotine and cotinine) indicate on the one hand the exposure to particulate phase constituents in smoking but on the other hand the exposure to gaseous phase constituents in passive smoking. Particle exposure during passive smoking seems to be low and a biomarker which indicates ETS particle exposure is as yet not available. These findings emphasize that risk extrapolations from active smoking to passive smoking which are based on cigarette equivalents or the use of one biomarker (e.g. cotinine) might be misleading.     

Biochemical validation of self-reported exposure to environmental tobacco smoke

Biochemical validation of reported exposure to environmental tobacco smoke (ETS) lends credibility to epidemiological studies investigating the association of passive inhalation of smoke to respiratory disease or lung cancer. In the current study, a series of questions regarding ETS exposure was self-administered to nonsmokers and self-reported intensity of exposure was compared with cotinine levels in urine samples obtained on site. The target population of this study was a group of municipal workers who reported exposure in a domestic setting and/or in the workplace. When asked if they were exposed to ETS on social occasions, both males and females who responded positively had higher urinary cotinine levels (P less than 0.02) than those who gave a negative response. Mean urinary cotinine concentrations were found to be elevated in both men and women who reported that they lived with a smoker. Cotinine levels in the urine of those reporting exposure were over twice as high as those in the urine of respondents who denied having been exposed. ETS exposure in the home was the greatest contributor to increased urinary cotinine levels in both men and women. Among individuals who were exposed at work only, the reported degree of exposure agreed well with the mean urinary cotinine values. Those findings emphasize that the validation of exposure status with a biomarker is an essential prerequisite for epidemiological studies investigating passive smoking.     

Maternal tobacco smoke exposure and persistent pulmonary hypertension of the newborn.

We propose that in utero exposure to tobacco smoke products places a newborn at risk for persistent pulmonary hypertension of the newborn (PPHN). To test this hypothesis, infants with PPHN were identified. Healthy newborns of similar ethnicity were identified as a comparison group. Cord blood cotinine concentrations and maternal questionnaires were obtained. The number of women exposed to tobacco smoke in each group ascertained by questionnaire was borderline significantly different (38.7% vs. 20.5%; p = 0.080). However, more PPHN infants had detectable cotinine in their cord blood (64.5% vs. 28.2%; p = 0.002), and the median cotinine concentrations were significantly higher (5.2 ng/ml vs. 2 ng/ml; p = 0.051) than the comparison infants. Among infants delivered to nonsmoking women, more PPHN infants had detectable cotinine (50% vs. 19%; p = 0.015), and the cotinine concentrations were higher (3.5 ng/ml vs. 1.65 ng/ml; p = 0.022) than the comparison group. We conclude that active and passive smoking during pregnancy is a risk factor for PPHN. Therefore, we recommend that pregnant women cease smoking and avoid environmental tobacco smoke. Key words. cotinine, newborns, passive, persistent pulmonary hypertension, smoking, tobacco smoke pollution.     

Cord serum cotinine as a biomarker of fetal exposure to cigarette smoke at the end of pregnancy

This study investigated the association between biomarkers of fetal exposure to cigarette smoke at the end of pregnancy, cotinine in cord serum and in maternal and newborn urine samples, and quantitative measurement of smoking intake and exposure evaluated by maternal self-reported questionnaire. Study subjects were 429 mothers and their newborns from a hospital in Barcelona, Spain. A questionnaire including smoking habits was completed in the third trimester of pregnancy and on the day of delivery. Cotinine concentration in cord serum was associated with daily exposure to nicotine in nonsmokers and with daily nicotine intake in smokers. The geometric mean of cotinine concentration in cord serum statistically discriminated between newborns from nonexposed and exposed nonsmoking mothers, and between these two classes and smokers, and furthermore was able to differentiate levels of exposure to tobacco smoke and levels of intake stratified in tertiles. Urinary cotinine levels in newborns from nonsmoking mothers exposed to more than 4 mg nicotine daily were statistically different from levels in two other categories of exposure. Cotinine concentration in urine from newborns and from mothers did not differentiate between exposure and nonexposure to environmental tobacco smoke (ETS) in nonsmoking mothers. Cord serum cotinine appeared to be the most adequate biomarker of fetal exposure to smoking at the end of pregnancy, distinguishing not only active smoking from passive smoking, but also exposure to ETS from nonexposure.     

Cotinine and N-(2-hydroxyethyl)valine as markers of passive exposure to tobacco smoke in children

Large segments of populations, including children, are exposed to environmental tobacco smoke (ETS), a risk factor for lung cancer and heart, circulatory and respiratory diseases. Recently, ETS was classified as a class A carcinogen by USEPA, as carcinogenic to humans by IARC (group 1) and by the National Toxicology Program of the US National Institutes of Health. Cotinine, a product of the metabolism of nicotine, is measurable in urine and, correlates strictly and directly to ETS exposure, therefore representing a well-known internal dose marker. Another marker of active tobacco smoking is the N-(2-hydroxyethyl) valine (HOEtVal) which results from the reaction between ethylene oxide (EtO) and the N-terminal valine of hemoglobin. The aim of this study was the evaluations of ETS markers, namely urinary cotinine and HOEtVal measured in blood in 100 children with ages ranging between 3 and 13 years. Experimental findings show that cotinine, as a specific internal dose marker, and HOEtVal, as a nonspecific biological effective dose marker, both depend on the passive exposure to ETS as well as on the active habit of smoking.     

Restrictive workplace smoking policies: impact on nonsmokers' tobacco exposure.

The health consequences of exposure to environmental tobacco smoke (ETS) are well documented. Although nonsmokers are generally aware of the health risks of ETS exposure, the majority of nonsmokers are regularly exposed. The most common source of exposure is the workplace. Restrictive workplace smoking policies are being used as a primary means of reducing ETS exposure. However, few studies have focused on the relation between workplace policy and ETS exposure. We performed two studies which examined the relationship between smoking policy, self-reported ETS exposure, and salivary cotinine concentrations. Study I, a pilot study, focused on a workplace-based sample of 106 volunteers; Study 2 examined exposure among 881 nonsmokers in workplace settings. In both studies, more restrictive workplace smoking policies were associated with a lower proportion of nonsmoking volunteers with detectable salivary cotinine. In Study 2, the larger study, the only other variable found to be significantly related to cotinine detection was the presence of smokers in the home. These results suggest that restrictive workplace smoking policies may reduce employees' overall ETS exposure.     

Environmental tobacco smoke exposure in children: parental perception of smokiness at home and other factors associated with urinary cotinine in preschool children

Parental smoking behavior at home and sociodemographic variables may influence exposure to environmental tobacco smoke (ETS) in children. A sample of 115 preschool children aged 3-6 years was enrolled in this study. ETS exposure was evaluated through a questionnaire about parents' smoking behavior and determinations of urinary cotinine -- a biomarker of exposure -- in children. Bivariate and multiple regression analyses were used to evaluate the association between the smoking behavior of each parent at home, sociodemographic factors and cotinine levels in children. The parental perception of smokiness in the home was significantly associated with urinary cotinine in children (r-partial coefficient=0.324; P<0.002). The father's education, mother's smoking status, and day of the week when urine was sampled (Tuesday) were also independently associated with levels of cotinine. These four variables explained 26.4% of the variance in the cotinine levels of children. In designing educational programs to reduce passive smoking among children, it is necessary to take into account those factors related with cotinine levels in children. Our results support the influence of the mothers' smoking status, the fathers' educational level, and the day of the week of sampling on cotinine in children. The perception of parents (smokers and nonsmokers) about the smokiness in the home could also be a useful indicator of the cotinine in children exposed to environmental tobacco smoke in the household.     

Relationship between environmental tobacco smoke and urinary cotinine levels in passive smokers at their residence

Studies of the health effects of environmental tobacco smoke (ETS) using measured air concentrations are subject to bias. Cotinine, a nicotine metabolite detected in urine, has been recommended as a quantitative measure of nicotine intake and thus as a marker for ETS exposure in humans. The aim of this study was to correlate home indoor ETS levels with passive smokers' urinary cotinine levels. The urinary cotinine concentrations of 57 non-smoking women who spend >19 h a day at home and the nicotine levels in their living room air were measured over a period of 24 h. Nicotine and urinary cotinine levels were analyzed using GC/MS and HPLC/UV, respectively. In addition, information was collected regarding the smoking habits of the subjects' families. A significant correlation was found between the nicotine levels in indoor air and the urinary cotinine to creatinine ratio of the passive smokers. The smoking habits of the subjects' family members were also correlated to the urinary cotinine levels of the passive smokers.     

Cotinine, thioether, and glucuronide excretion among active and passive bidi smokers in India

The authors examined biomarkers for environmental tobacco smoke exposure (ETS) from bidis (Indian cigarettes) among male smokers, their nonsmoking female family members (passive smokers), and an unexposed control group (N = 66). The 3 parameters used to determine the magnitude of exposure were cotinine (a tobacco-specific alkaloid indicating nicotine exposure) and thioethers and glucuronides (indicators of electrophilic burden). Urinary excretion of cotinine was significantly higher among active smokers (4.30 +/- 1.18), compared with passive smokers (wives = 1.76 +/- 0.50; daughters = 0.50 +/- 0.26). Similar trends were noted for thioethers and glucuronides. The authors found that cotinine and glucuronide levels were correlated significantly with exposure to ETS among both active and passive bidi smokers.     

Validation of a five-question survey to assess a child's exposure to environmental tobacco smoke

PURPOSE: To study the potentially adverse health effects of environmental tobacco smoke (ETS) exposure in young children, a short five-question survey was developed to identify routine exposure to ETS in a large epidemiological study. METHODS: The survey is administered to parents of a healthy cohort of children starting at age 3 months. To validate the survey, urinary cotinine levels were measured on 50 children from this cohort who were selected based on ETS exposure as reported in the survey: 24 with no exposure and 26 with exposure. Cotinine was adjusted for creatinine. RESULTS: Overall, children with some form of reported ETS exposure had urinary cotinine levels 7.5 times higher than those who were not exposed. Analysis of variance shows that mean levels of log transformed cotinine in children whose parent(s) smoke in the home, parent(s) who smoke but not in the home, and non-smoking parents are 137.13, 75.60, and 43.28 respectively (p = 0.0009), indicating decreasing levels of cotinine as reported exposure decreases. Using a cut-point of 30 ng/mg of cotinine to differentiate unexposed and exposed to ETS, we found 80% agreement with our survey. A Spearman's ranked correlation coefficient of 0.62 indicates a direct relationship between cotinine and an ETS exposure intensity score (p < 0.0001).CONCLUSIONS: These results suggest that the 5-question survey reflects the child's exposure to passive smoke and that the survey is sensitive to varying levels of exposure.     

A review of the use of saliva cotinine as a marker of tobacco smoke exposure

Cotinine, the major metabolite of nicotine, is a useful marker of exposure to tobacco smoke. It can be measured in plasma, urine, or saliva. However, distinguishing between active and passive smoking on the basis of a cotinine measurement may be difficult. In order to evaluate the relationship between saliva cotinine concentration and self-reported tobacco smoke exposure in both active and passive smokers, an English-language literature search using MEDLINE was conducted (1973-1989), and the bibliographies of identified articles were reviewed. Of 43 originally identified articles, only 22 met the criteria for inclusion. Specific information regarding population studied, reported tobacco smoke exposure, method of measurement, and cotinine concentrations was assessed. Passive smokers usually have cotinine concentrations in saliva below 5 ng/ml, but heavy passive exposure can result in levels greater than or equal to 10 ng/ml. Levels between 10 and 100 ng/ml may result from infrequent active smoking or regular active smoking with low nicotine intake. Levels greater than 100 ng/ml are probably the result of regular active smoking. Four categorizations of tobacco smoke exposure are suggested on the basis of saliva cotinine concentrations.     

Lifetime environmental exposure to tobacco smoke and primary lung cancer of non-smoking Taiwanese women

BACKGROUND: For a female population with a high lung cancer mortality rate, such as Taiwanese women, who smoke relatively rarely, but live in an environment with high male smoking prevalence, the risk and population burden of lung cancer due to environmental tobacco smoke (ETS) are relatively important. METHODS: An age-matched case-control study was designed to investigate the effects of cumulative environmental exposure to tobacco smoke during childhood and adult life on lung cancer risk among non-smoking women in Taiwan. Information on passive smoking from all possible sources and life periods were obtained from interviews with 268 and 445 lifetime non-smoking cases and controls. Conditional logistic regression and synergism 'S' index were applied to the data to assess the independent and joint effects of passive smoking in different life stages while controlling for possible confounding variables. RESULTS: Risks of contracting lung cancer among women near-distantly exposed to the highest level of ETS in childhood (>20 smoker-years) and in adult life (>40 smoker-years) were 1.8-fold (95% CI: 1.2-2.9) and 2.2-fold (95% CI: 1.4-3.7) higher than that among women being never exposed to ETS, and the two variables accounted for about 37% of tumours in this non-smoking female population. Children were found to be more susceptible to ETS than adults and such early exposure was found to modify the effect of subsequent tobacco smoke exposure in adult life based on an additive interaction model. CONCLUSIONS: Environmental tobacco smoke exposure occurring in childhood potentiates the effect of high doses of exposure in adult life in determining the development of lung cancer. Smoking prohibition would be expected to protect about 37% of non-smoking Taiwanese women against lung cancer.     

Passive smoking by self report and serum cotinine and the prevalence of respiratory and coronary heart disease in the Scottish heart health study.

STUDY OBJECTIVE--To explore the relationship between self reported environmental tobacco smoke exposure (or passive smoking), the serum cotinine concentration, and evidence of respiratory or coronary disease in men and women who have never smoked. DESIGN--Cross sectional random population survey identifying disease markers and relating them to measures of passive smoking. Disease markers were previous medical diagnoses, response to standard symptom questionnaires, and electrocardiographic signs. SETTING--Samples of men and women aged 40-59 years drawn from general practitioner lists in 22 local government districts of Scotland, between 1984 and 1986. PARTICIPANTS--A total of 786 men and 1492 women who reported never having smoked tobacco, and who had serum cotinine concentrations below 17.5 ng/ml, the cut off point for smoking "deceivers", took part. RESULTS--Fewer than one third of never smokers reported no recent exposure to environmental tobacco smoke and the same proportion had no detectable cotinine. Women had lower cotinine values than men but reported more exposure to smoke. The correlation between the measures of exposure was poor. Self-reported exposure showed strong, statistically significant, dose response relationships with respiratory symptoms and with the coronary disease markers. These relationships were weak or absent for serum cotinine, except for diagnosed coronary heart disease. Here the dose response gradient was as strong as that for self report, with an odds ratio of 2.7 (95% CI 1.3, 5.6) for the highest v the lowest exposure group, adjusted for age, housing tenure, total cholesterol, and blood pressure, and not explained by fibrinogen. CONCLUSIONS--The validity of different measures of tobacco smoke exposure needs further investigation. The gradient of diagnosed coronary heart disease with both self reported exposure and serum cotinine was, however, surprisingly strong, statistically significant, and unexplained by other factors. These findings reinforce current policies to limit passive tobacco smoke exposure.     

Environmental tobacco smoke and risk of spontaneous abortion

BACKGROUND: Studies of exposure to environmental tobacco smoke (ETS) and risk of spontaneous abortion are limited to a few studies of self-reported exposure, and the results have been inconsistent. The aim of this study was to investigate risk of early spontaneous abortion related to ETS and active smoking as defined by plasma cotinine levels. METHODS: We conducted a population-based case-control study in Uppsala County, Sweden, between January 1996 and December 1998. Cases were 463 women with spontaneous abortion at 6 to 12 completed weeks of gestation, and controls were 864 pregnant women matched to cases according to the week of gestation. Exposure status was defined by plasma cotinine concentrations: nonexposed, <0.1 ng/mL; ETS-exposed, 0.1-15 ng/mL; and exposed to active smoking, >15 ng/mL. Multivariable analysis was used to estimate the relative risk of spontaneous abortion associated with exposure to ETS and active smoking. RESULTS: Nineteen percent of controls and 24% of cases were classified as having been exposed to ETS. Compared with nonexposed women, risk of spontaneous abortion was increased among both ETS-exposed women (adjusted odds ratio = 1.67; 95% confidence interval = 1.17-2.38) and active smokers (2.11; 1.36-3.27). We could not show a differential effect of exposure to ETS or active smoking between normal and abnormal fetal karyotype abortions. CONCLUSIONS: Nonsmoking pregnant women exposed to ETS may be at increased risk of spontaneous abortion. Given the high prevalence of ETS exposure, the public health consequences of passive smoking regarding early fetal loss may be substantial.     

Nicotine and cotinine in adults' urine: The German Environmental Survey 1998

In 1998, the German Environmental Survey (GerES III) recruited approximately 5000 adults between the ages of 18 and 69 years. The study population for these analyses consisted of 1580 smokers (34% of the total population) and 3126 nonsmokers. Nicotine and cotinine concentrations in urine were determined by HPLC methods with UV-detection and corrected for creatinine. Nicotine and cotinine concentrations differed between smokers and nonsmokers by factors of 10-100. The multiple linear regression models used for the analyses of nicotine detection in the urine of smokers explained 43.2% and 42.3% of the total volume-specific and creatinine-specific variances, respectively. Cigarette smoking was the major factor responsible for 41% of the total variance. The explained variances of the cotinine results were larger, 51.0% and 49.3% of the total variance were volume-specific and creatinine-specific, respectively. More than 20% of nonsmokers in GerES III were exposed to environmental tobacco smoke at home, at work or in other places. The logistic regression analysis approach used for the group of nonsmokers showed the greatest effects for those exposed to tobacco smoke at home (adjusted OR varied between 4 and 6). These results were seen for nicotine as well as for cotinine excretion. Exposure to tobacco smoke in the workplace doubled the risk for the detection of nicotine and cotinine in urine. When other risk factors such as age, sex, social status, community size, season of urine collection, and the consumption of food containing nicotine such as potatoes, cabbage, tea were included, the effect estimates for tobacco smoke exposure remained unchanged. A new federal bill to diminish environmental tobacco smoke (ETS) exposure in the workplace was recently passed in Germany, but protection of nonsmokers from smoking family members at home needs more attention.     

Neonatal hair nicotine levels and fetal exposure to paternal smoking at home

Exposure to environmental tobacco smoke (ETS) is a major risk to human health, and the home is the greatest single source of ETS for children. The authors investigated fetal exposure to paternal smoking at home during pregnancy. Korean families were included as trios of fathers, mothers, and neonates identified in 2005-2007. Sixty-three trios were finally enrolled in this study after exclusion of those in which the mother was a smoker or was regularly exposed to ETS at places other than the home. Nicotine and cotinine concentrations in hair were measured by using liquid chromatography-tandem mass spectrometry to determine long-term exposure to ETS. The difference between neonatal nicotine concentrations in the smoker and nonsmoker groups was not statistically significant. However, in the indoor-smoker group, neonatal nicotine concentrations were significantly higher than in the outdoor and nonsmoker groups (P < 0.05). Furthermore, neonatal nicotine concentrations in the outdoor-smoker group were not different from those in the nonsmoker group. These findings indicate that paternal smoking inside the home leads to significant fetal and maternal exposure to ETS and may subsequently affect fetal health. Conversely, findings show that paternal smoking outside the home prevents the mother and her fetus from being exposed to ETS.     

Environmental tobacco smoke exposure among pregnant women: impact on fetal biometry at 20–24 weeks of gestation and newborn child’s birth weight

Aim While there are sufficient data regarding the negative effect of exposure to the constituents of tobacco smoke on newborn infants birth weights, it is still unclear whether this effect may originate in early pregnancy. The aim of the present study was to evaluate the impact of exposure to tobacco smoke components in early pregnancy (20–24 weeks) on fetal biometry.Methods The study population comprised 183 women consecutively enrolled at 20–24 weeks of pregnancy at the two antenatal care units. Ultrasound biometric measurements of fetal bi-parietal diameter (BPD), abdominal circumference (AC) and femur length (FL) were performed at the time of enrolment. Serum cotinine concentration was determined at 20–24 weeks of gestation by gas chromatography with mass spectrometry detector (GC/MS) to assess environmental tobacco smoke (ETS) exposure during the previous evening and the morning of the same day (blood collection at 1200–1300 h). ETS exposure (passive smoking) was assumed to occur when the level of serum cotinine ranged from 2–10 ng/ml.Results In a multiple regression model for bi-parietal diameter (BPD), after adjustment for pregnancy duration at the time of ultrasound examination, fetal gender, and maternal pre-pregnancy weight, a statistically significant negative association was found between the BPD and serum cotinine concentration. A similar association was identified for subjects with serum cotinine concentrations below 10 ng/ml (corresponding to passive smoking) (P=0.06). After controlling for pregnancy duration, maternal pre-pregnancy weight and infants gender, we found that serum cotinine levels at 20–24 weeks of gestation was inversely associated with infant birth weight (P=0.004). For the subjects with serum cotinine levels below 10 ng/ml, a borderline association (P=0.09) with infant birth weight was found.Conclusions Maternal exposure to tobacco smoke in early pregnancy, as measured by serum cotinine concentrations at 20–24 weeks of gestation, adversely affects fetal BPD. Preventive measures need to be undertaken to encourage pregnant women to stop smoking and avoid passive exposure to tobacco smoke from the very beginning of pregnancy.     

Assessment of environmental tobacco smoke exposure in children with asthmatic symptoms by questionnaire and cotinine concentrations in plasma, saliva, and urine

To validate a detailed questionnaire for assessment of environmental tobacco smoke (ETS) exposure by the biomarker cotinine in various media, a population-based study in the urban area of Malm?, Sweden was performed in children aged 8-13 years with and without asthmatic symptoms. There were strong correlations between urinary and saliva cotinine concentrations and also, though to a lesser extent, between these media and plasma. Even a detailed questionnaire gave only a rough picture of the ETS exposure, as indicated by the biomarkers. In a multivariate model, the most significant questionnaire-derived predictor of the cotinine levels was the maternal smoking habits; other questionnaire variables gave only a minimal explained variance. Children with a history of asthmatic symptoms had statistically significantly lower median cotinine levels in urine and saliva compared to referent children, most likely because of the antismoking information to their parents. This should be considered in epidemiological studies of ETS risks.     

Is the hair nicotine level a more accurate biomarker of environmental tobacco smoke exposure than urine cotinine?

STUDY OBJECTIVE: The aim of this study was to compare the two biomarkers of exposure to environmental tobacco smoke (ETS); urine cotinine and hair nicotine, using questionnaires as the standard. DESIGN: A cross sectional study of children consecutively admitted to hospital for lower respiratory illnesses during the period of the study. SETTINGS: Three regional hospitals in the larger Wellington area, New Zealand. PARTICIPANTS: Children aged 3-27 months and admitted to the above hospitals during August 1997 to October 1998. A total of 322 children provided 297 hair samples and 158 urine samples. MAIN RESULTS: Hair nicotine levels were better able to discriminate the groups of children according to their household's smoking habits at home (no smokers, smoke only outside the home, smoke inside the house) than urine cotinine (Kruskall-Wallis; chi(2)=142.14, and chi(2)=49.5, respectively (p<0.0001)). Furthermore, hair nicotine levels were more strongly correlated with number of smokers in the house, and the number of cigarettes smoked by parents and other members of the child's households. Hair nicotine was better related to the questionnaire variables of smoking in a multivariate regression model (r(2)=0.55) than urine cotinine (r(2)=0.31). CONCLUSIONS: In this group of young children, hair nicotine was a more precise biomarker of exposure to ETS than urine cotinine levels, using questionnaire reports as the reference. Both biomarkers indicate that smoking outside the house limits ETS exposure of children but does not eliminate it.     

Personal exposure to environmental tobacco smoke: salivary cotinine, airborne nicotine, and nonsmoker misclassification.

A large study was conducted to assess exposure to environmental tobacco smoke (ETS) in a geographically dispersed study population using personal breathing zone air sampling and salivary cotinine levels. Approximately 100 self-reported nonsmoking subjects in each of 16 metropolitan areas were recruited for this investigation. Cumulative distributions of salivary cotinine levels for subjects in smoking and nonsmoking homes and workplaces exhibited a general trend of decreasing salivary cotinine levels with decreasing time spent in smoking environments. Median salivary cotinine levels for the four experimental cells in the study (product of smoking and nonsmoking home and workplaces) were comparable to those reported for a large national study of serum levels of cotinine (Third National Health and Nutrition Examination Survey, NHANES III), when the latter was corrected for expected differences between serum and saliva concentrations. However, the most highly exposed group in this study had a median salivary cotinine concentration approximately a factor of 2 greater than that of the comparable group in the NHANES III study. Misclassification rates, both simple (for self-reported nonsmokers) and complex (self-reported lifetime never smokers), were near the median of those reported for other studies. Estimated misclassification rates for self-reported lifetime never-smoking females are sufficiently high (2.95% using a discrimination level of 106 ng/ml) that, if used in the Environmental Protection Agency (EPA) risk assessment related to ETS and lung cancer, would place the lower 90% confidence interval (CI) for relative risk at nearly 1.00, i.e., no statistically significant increased risk. For the 263 most highly exposed subjects in the study whose self-reported nonsmoking status was accurate, the correlation between airborne exposure to nicotine and average salivary cotinine is so small, on an individual basis, that it makes the relationship useless for estimating exposure on a quantitative basis. When subjects are grouped according to likely categories of nicotine exposure, correlation between group median airborne nicotine exposure and salivary cotinine level increases dramatically. The comparison improves for the most highly exposed subjects, suggesting that such quantitative comparisons are useful for only those subjects who are exposed to the higher levels of ETS. However, airborne nicotine exposure for most of the subjects does not account for estimated systemic levels of nicotine, based on salivary cotinine levels.