Environmental tobacco smoke at home and in public places prior to smoking ban enforcement: Assessment by hair analysis in a population of young adult students

Despite inititatives to reduce tobacco consumption, smoking remains a primary cause of death for both smokers and nonsmokers exposed to environmental tobacco smoke (ETS). The characteristics of some specific groups can make them more exposed to ETS or limit the benefit of prevention measures. This study investigated determinants of ETS in a population of young adult students, considered at higher risk of exposure due to their specific lifestyle. This cross-sectional study involved 90 students aged 20 ± 1.7 years, from the University of Luxembourg, prior to the smoking ban enforcement in public places in the country. Participants reported their tobacco consumption and exposure to ETS at home and/or in public places, and provided a hair sample analyzed for nicotine and cotinine. Nicotine and cotinine were significantly higher in smokers than in nonsmokers' hair in general (median: 2.6 vs. 0.9 ng/mg and 87.1 vs. 22.5 pg/mg respectively). However, nonsmokers exposed to ETS at home and in public places had comparable concentrations to smokers (nic = 2.2 ng/mg; cot = 56.2 pg/mg), whereas unexposed nonsmokers presented significantly lower values (nic = 0.4 ng/mg, cot = 8.5 pg/mg). Nonsmokers exposed to ETS only at home presented higher values than nonsmokers only exposed in public places (nic: 1.3 vs. 0.8 ng/mg, cot: 70.4 vs. 15.0 pg/mg). The study shows the widespread exposure to ETS in this population, the importance of exposure assessment, and the relevance of hair analysis for this purpose. Results suggest that ETS can lead to equivalent exposure to active smoking and that exposure at home can highly contribute to ETS, which is not solved by smoking ban in public places.     

Low level saliva cotinine determination and its application as a biomarker for environmental tobacco smoke exposure.

1. The determination of personal exposures to environmental tobacco smoke (ETS) and respirable suspended particles (RSP) for housewives, and fixed site monitoring of their homes, have been undertaken by these authors throughout Europe, South East Asia and Australia. Median 24 h time weighted average (TWA) concentrations for ETS particles and nicotine were found to be significantly higher for housewives living in smoking households compared with those living in nonsmoking households. For Europe, median TWA concentrations of 4.1 and <0.26 microg/ml for ETS particles and 0.63 and < 0.08 microg/m3 for nicotine were found for housewives living in smoking and nonsmoking households respectively. 2. In addition to the measurement of RSP, ETS particles and nicotine, saliva cotinine concentrations were determined using a radioimmunoassay method with a limit of quantitation of 1 ng/ml. Median saliva cotinine concentrations of 1.4 and <1 ng/ml were determined for European housewives living in smoking and nonsmoking households respectively, which reflected the poor limit of quantitation of this methodology. A chromatographic method utilising tandem mass-spectrometric detection was developed and validated for the determination of both cotinine and 3-hydroxycotinine, two of the main metabolites of nicotine, with lower limits of quantitation of 0.05 and 0.10 ng/ml respectively. This method was applied to samples collected from subjects with a known ETS exposure history and median cotinine concentrations of <0.05 ng/ml for self-reported unexposed nonsmokers, 0.65 ng/ml for nonsmokers reporting some ETS exposure and 1.28 ng/ml for nonsmokers living with smokers were found. 3. In conclusion, the measurement of RSP and ETS concentrations derived from personal or fixed site monitors for housewives may provide some indication of potential exposures to dependent children. The recent development and application of a highly sensitive assay for the determination of cotinine in saliva has provided evidence to suggest that concentrations determined at sub-nanogram levels may be used as a biomarker for ETS exposure. This improved methodology, coupled with non-invasive sampling for saliva, may be of significance when considering the application of cotinine as a biomarker for ETS exposure in children.     

Reference values for hair cotinine as a biomarker of active and passive smoking in women of reproductive age, pregnant women, children, and neonates: systematic review and meta-analysis

Exposure to environmental tobacco smoke (ETS) is most often estimated using questionnaires, but they are unreliable. Biomarkers can provide valid information on ETS exposure, the preferred biomarker being cotinine. However, no reference range of hair cotinine exists to distinguish among active, passive, and unexposed nonsmokers. This study identifies cutoffs to validate cotinine as a marker for exposure to ETS. Data were obtained from six databases (four US, one Canada, one France). Active smoking and exposure to ETS were measured in the hair of women of reproductive age, pregnant women, their children, and neonates. Subjects were classified into active smokers, passively exposed to ETS, and unexposed nonsmokers. A total of 1746 cases were available for analysis. For active smokers, mean hair cotinine concentrations (95% confidence interval) were 2.3 to 3.1 ng/mg for nonpregnant women and 1.5 to 1.9 ng/mg for pregnant women. In the group of passive smokers, mean hair cotinine concentrations were 0.5 to 0.7 ng/mg for nonpregnant women, 0.04 to 0.09 ng/mg for pregnant women, 0.9 to 1.1 for children, and 1.2 to 1.7 for neonates. Among unexposed nonsmokers, mean hair cotinine was 0.2 to 0.4 ng/mg in nonpregnant women, 0.06 to 0.09 ng/mg in pregnant women, and 0.3 to 0.4 ng/mg in children. Cutoff values for hair cotinine were established to distinguish active smokers from passive or unexposed (0.8 ng/mg for nonpregnant women and 0.2 ng/mg for pregnant women). A cutoff value of 0.2 ng/mg was accurate in discriminating between exposed children and unexposed. These new values should facilitate clinical diagnosis of active and passive exposure to tobacco smoke. Such diagnosis is critical in pregnancy and in a large number of tobacco-induced medical conditions.     

Increased β-amyloid deposition in Tg-SWDI transgenic mouse brain following in vivo lead exposure

The present methodology was developed to simultaneously assess chronic exposure to PAHs and to tobacco from the analysis of one hair specimen per examined individual. The method is a two step extraction of twelve mono-hydroxy-PAHs and of nicotine, and their separate analysis by optimized methods using gas chromatography-negative chemical ionization-mass spectrometry. After method validation and assessment of the hair decontamination procedure, 105 hair specimens from smokers and non-smokers were analyzed. All the hair samples tested positive for nicotine. Median concentration was 10.7ng/mg for smokers and 0.5ng/mg for non-smokers. 70% of the samples tested positive for OH-PAHs. The most common one was 2-naphthol (61%) and its concentration was significantly higher in smokers than in non-smokers (median: 111 vs 70pmol/g, p=0.006). 2-OH-benzo(c)phenanthrene and 6-OH-chrysene were only detected once in a non-smoker's hair. The concentration of the sum of all PAH-metabolites ranged from 24 to 67190pmol/g (median: 118pmol/g). Only six samples tested positive for more than two different metabolites. The simultaneous detection of nicotine and OH-PAHs in hair is possible and provides reliable results. This represents a useful tool for the accurate biomonitoring of chronic exposure to PAH and correct identification of the sources of exposure.     

Turkish coffeehouse kahvehane is an important tobacco smoke exposure area in Turkey

This study was undertaken to investigate the extent of environmental tobacco smoke (ETS) exposure in coffeehouses, as these are commonly frequented public places in Turkey. From 86 coffeehouses in the 3 districts, 59 coffeehouse workers and 35 hospital staff members (as a control group) were evaluated. Participants answered a questionnaire about demographics, working characteristics, smoking behavior, and ETS exposure during their daily life lives. The amount of nicotine in hair was determined by using gas chromatography/mass spectrometry (GC/MS). The mean hair nicotine level of the nonsmoker and smoker coffeehouse workers were 23.2 +/- 12.3 microg/g and 62.5 +/- 49.8 microg/g, respectively. Among the hospital staff, mean hair nicotine levels were 4.5 +/- 6 microg/g in nonsmokers and 30.6 +/- 14 microg/g in smokers. Working in coffeehouses has a marked effect on hair nicotine levels and potential adverse health effects.     

Correlation between urinary nicotine, cotinine and self-reported smoking status among educated young adults

The objective of this study was to correlate, differentiate and validate the self-reported smoking status of educated young adults with urinary biomarkers (i.e. nicotine and cotinine). Freshmen students were recruited on voluntary basis. They filled-up self-administered questionnaire and their urine samples were collected for analysis. The urinary nicotine (UN) and cotinine (UC) were measured by gas chromatograph-mass spectrometry. Smokers, non-smokers and ex-smokers were found to be both significantly correlated and different in their UN and UC levels. UC level of 25ng/ml was the optimal cut-off to differentiate smokers from non-smokers. Using this cut-off value, the prevalence of smoking among the students was found to be higher (15.4%) than the self-reported data (14.3%). UC is useful in validating individual recent smoking history and the cut-off could serve as a marker for assessing the clinical impact of smoking and environmental tobacco smoke (ETS) exposure on human health.     

Psychophysiological reactivity to environmental tobacco smoke on smokers and non-smokers

Environmental tobacco smoke (ETS) is an air pollutant with a relevant impact on public health. In addition, ETS is a significant stimulus that may elicit different responses depending on previous experience and current status regarding smoking. Exposure to cigarette cues has been shown to be a reliable method for inducing subjective and physiological responses. However, the role of ETS as a stimulus has not received, to date, enough attention in the research literature. This study aimed to analyse both the autonomic and subjective responses of smokers and non-smokers to exposure to ETS. To that end, 41 non-smokers and 57 smokers were exposed to ETS, in a controlled laboratory setting. We measured the subjective perception of smoke, unpleasantness, heart rate and skin conductance to compare the reactions of smokers and non-smokers to ETS. Additionally, subjective tobacco craving after exposure was assessed for current smokers. We found different psychophysiological responses to ETS exposure for smokers and non-smokers. Smokers showed a generalised increase in autonomic activity, significantly greater than that of non-smokers. In addition, heart rate increase during exposure to ETS was positively correlated with subjective craving. Our data suggested that ETS was an important stimulus and acted as a relevant cue for smokers; it induced both psychophysiological reactions and subjective craving. Hence, this kind of stimulus within the cue-reactivity research paradigm may be useful for studying the effect of ETS on smokers' reactions, craving, quitting attempts, or relapse probabilities.     

Interindividual Differences in Hair Uptake of Air Nicotine and Significance of Cigarette Counting for Estimation of Environmental Tobacco Smoke Exposure

Abstract: Hair from 80 male subjects, smokers and non-smokers, was exposed continously in a dynamic exposure chamber to constant nicotine vapour concentrations of 20, 200 or 2000 μg/m³ for 72 hr. Subgroups of high and low nicotine adsorbing hair were also exposed intermittantly to environmental tobacco smoke for 8 months. Air and hair concentrations of nicotine were determined by gas chromatography/mass spectrometry. The chamber experiments demonstrated a hair nicotine uptake which followed a second order relation to the applied concentrations of nicotine, y=–0.00018x²+0.715x+1.13, r²=0.99999. The function and the experimental points showed linearity up to an air nicotine vapour concentration of about 200 μg/m³ covering the most relevant range of environmental exposure. An approximately 7- and 2-fold interindividual variation was observed in the hair uptake rate constant of nicotine vapour for the investigated material within the 10 to 90 and 25 to 75% percentiles, respectively. The factors causing this variation were not identified. It was shown that subject age, hair diameter and hair content of eumelanin were without correlation to the rate constants of hair nicotine uptake. The exposure of subgroups of hair to environmental tobacco smoke showed similar uptake profiles of nicotine as that experienced with exposure to pure nicotine vapour, supporting the relevance of controlled chamber nicotine vapour exposures as a relevant tool for the evaluation of hair nicotine uptake from a more complex environmental situation. Standardized measurements of air nicotine vapour and particulate concentrations in a modern office during 8 hr periodical smoking periods, showed that the number of cigarettes smoked was a poor indicator for the estimation of individual exposure to environmental tobacco smoke constituents. Hair nicotine measurements so far seem to be superior to other suggested methodologies for estimation of environmental tobacco smoke exposure, but further studies should be initiated to identify factors determining the rate constant of hair nicotine uptake.     

High performance liquid chromatographic determination of nicotine and cotinine in plasma and nicotine and cotinine, simultaneously, in urine

Three analytical procedures were developed to determine nicotine in plasma, cotinine in plasma and, simultaneously, nicotine and cotinine in urine. After liquid or solid-phase extraction, the purified aqueous phase is injected into a high performance liquid chromatograph equipped with an ultra-violet detector using a CN Spheri-5 micron cartridge-column with an inner diameter of 4.6 mm and a length of 10 or 22 cm. The limit of quantitation for nicotine in plasma was around 8 to 15 ng/ml, that of cotinine in plasma around 50 ng/ml and that of nicotine and cotinine in urine around 170 ng/ml and 70 ng/ml, respectively. The limit of detection of nicotine in plasma was around 1 ng/ml and that of nicotine and cotinine in urine around 20 ng/ml and 10 ng/ml, respectively. The passive exposure to cigarette smoke by non-smokers and the "resting levels" of nicotine in plasma and urine of smokers were studied. The analytical methods were set up to study the pharmacokinetics and bioavailability of nicotine in healthy volunteers following single and repeated administrations of different doses of transdermal nicotine systems.     

Hair nicotine/cotinine concentrations as a method of monitoring exposure to tobacco smoke among infants and adults

In this pilot study, we examined the validity and usefulness of hair nicotine-cotinine evaluation as a biomarker of monitoring exposure to tobacco. Head hair samples were collected from 22 infants (<2 years of age) and 44 adults with different exposures to tobacco (through either active or passive smoking) and analyzed by liquid chromatography-mass spectrometry (LC-MS) for nicotine and cotinine. Hair samples were divided into three groups, infants, passive smoker adults and active smoker adults, and into eight subgroups according to the degree of exposure. The limit of quantification (LOQ) was 0.1 ng/mg for nicotine and 0.05 ng/mg for cotinine. Mean recovery was 69.15% for nicotine and 72.08% for cotinine. The within- and between-day precision for cotinine and nicotine was calculated at different concentrations. Moreover, hair nicotine and cotinine concentrations were highly correlated among adult active smokers (R (2) = 0.710, p < 0.001), among adult nonsmokers exposed to secondhand smoke (SHS; R (2) = 0.729, p < 0.001) and among infants (R (2) = 0.538, p = 0.01). Among the infants exposed to SHS from both parents the noted correlations were even stronger (R (2) = 0.835, p = 0.02). The above results identify the use of hair samples as an effective method for assessing exposure to tobacco, with a high association between nicotine and cotinine especially among infants heavily exposed to SHS.     

Behavioral effects of nicotine exposure from secondhand tobacco smoke among bar and restaurant workers

This study explores the behavioral effects of nicotine exposure from secondhand tobacco smoke (SHS) on bar and restaurant workers. Baseline data were obtained from a longitudinal study of 105 bar and restaurant workers. Hair nicotine, self-reported SHS exposure, smoking status, symptoms of nicotine exposure after being exposed to a smoky environment, and nicotine dependence were assessed. Nonsmokers reporting four or more symptoms of nicotine exposure had higher hair nicotine levels than those reporting less than four symptoms. Nonsmokers with higher hair nicotine levels were 2.2 times more likely to report 4 or more behavioral symptoms. Self-reported secondhand tobacco smoke exposure and hair nicotine were not predictive of nicotine dependence among smokers. Nicotine exposure from secondhand tobacco smoke may have important behavioral outcomes in nonsmokers. This study provides further evidence for the importance of prohibiting smoking in hospitality venues to protect the health of workers.     

Comparison of the behavioral effects of cigarette smoke and pure nicotine in rats

Animal models of tobacco dependence typically rely on parenteral administration of pure nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. The primary goal of this study was to validate methods for administering cigarette smoke to rats using exposure conditions that were clinically relevant and also produced brain nicotine levels similar to those produced by behaviorally active doses of pure nicotine. A secondary goal was to begin examining the behavioral effects of smoke. Nose-only exposure (NOE) to smoke for 10-45 min or whole-body exposure (WBE) to smoke for 1-4 h produced serum nicotine concentrations similar to those in smokers (14-55 ng/ml), without excessive carbon monoxide exposure. Daily nicotine (0.1 mg/kg, s.c.) induced locomotor sensitization whereas 45-min NOE producing brain nicotine levels within the same range did not. Nicotine 0.125 mg/kg s.c. reversed withdrawal from a chronic nicotine infusion as measured by elevations in intracranial self-stimulation thresholds whereas 4-h WBE producing similar brain nicotine levels did not. These data demonstrate the feasibility of delivering cigarette smoke to rats at clinically relevant doses, and provide preliminary evidence that the behavioral effects of nicotine delivered in smoke may differ from those of pure nicotine.     

Accumulation of Nicotine in Human Hair during Long-Term Controlled Exposure to a Low Concentration of Nicotine Vapour

Abstract: Hair from 5 subjects were exposed in dynamic exposure chambers to air nicotine vapour for 72 hr or 12 months at concentrations of 200 or 5μg/m³, respectively. Nicotine in the chamber air and human hair was determined by GC/ MS. A linear accumulation of nicotine in hair was found with time for all hairs during the long-term, low concentration exposure, with individual hair nicotine uptake rate constants ranging from 0.70 to 3.75×10^?3 m³/gxhr. The corresponding hair nicotine uptake rate constants during short-term, high concentration exposure, were significantly higher, ranging from 1.35 to 15.11×10^?3 m³/gxhr, showing, however, a highly significant linear correlation with the individual long-term exposure rate constants, r²=0.9961. It is indicated that long-term hair nicotine uptake rate constants calculated from controlled exposure experiments with pure nicotine vapour are adequate for estimation of individual long-term hair accumulation of nicotine from environmental tobacco smoke even at variable and intermittent exposure. Although higher than the long-term uptake rate constants, the short-term uptake rate constants seem well fitted for a differentiation between different types of hair in their ability to adsorb nicotine also during long-term exposures. The short-term uptake rate constants might also be useful parameters for establishing a reliable cut-off limit in the hair concentration of nicotine between smokers and non-smokers which otherwise seems to be overlapping.     

Threshold doses for nicotine discrimination in smokers and non-smokers

RATIONALE: Tobacco use during initial experimentation often involves modest nicotine exposure, escalating to larger doses and more frequent exposure with the onset of tobacco dependence. Threshold doses for nicotine discrimination therefore may differ between naive and experienced tobacco users. OBJECTIVES: We determined the lowest (threshold) dose of nasal spray nicotine that smokers and non-smokers could reliably discriminate from placebo spray. METHODS: Male and female smokers (n=18) and non-smokers (n=17) were initially trained to discriminate 20 microg/kg from placebo before proceeding to threshold determination sessions, which involved discrimination of progressively lower doses below 20 microg/kg ("descending order" subgroup) or higher doses above 1 microg/kg ("ascending order" subgroup). Threshold was determined by the lowest dose reliably discriminated from placebo (correct on > or =80% of testing trials) and by failure to discriminate the next lowest dose. RESULTS: Threshold doses for nicotine discrimination were low and not different between smokers and non-smokers (median thresholds of 3 versus 2 microg/kg and approximate blood levels of 2.6 versus 1.6 ng/ml, respectively). Thresholds were similar between descending and ascending order subgroups. Several subjective responses differentiated threshold dose from the dose just below threshold, particularly in non-smokers. CONCLUSIONS: Threshold doses for nasal spray nicotine discrimination in humans are low, well below the typical nicotine delivery of most cigarette brands, and may not change after long-term smoking exposure.     

DNA damage and repair capacity by comet assay in lymphocytes of white-collar active smokers and passive smokers (non- and ex-smokers) at workplace

The comet assay has been widely used to quantify DNA damage in isolated lymphocytes from subjects exposed to several environmental or occupational substances, especially for estimation of oxidative damage in the DNA, which is well-known to be induced by tobacco smoke. Passive smoking or environmental tobacco smoke (ETS) has been included among those substances that cause cancer with sufficient evidence in humans. In this study, we analyzed, by the alkaline version of comet assay, the lymphocyte DNA damage of white-collar active smokers and non- and ex-smokers exposed to ETS at the workplace. We investigated basal DNA damage, DNA oxidation by formamidopyrimidine glycosylase (Fpg), the repair capacity H2O2-induced DNA damage by kinetics studies and lymphocyte GSH levels, the major intracellular defense against exogenous oxidative stress imposed by cigarette smoking. Our results indicated high basal DNA damage with clear significant correlations with urinary nicotine and cotinine, number of cigarettes/day, and an inverse significant correlation with GSH cellular content in active smokers. Significant Fpg-sensitive sites were found in smokers (> 85%), considerably high but not significant in passive non- and ex-smokers (> 51% and 37%, respectively). The DNA repair capacity had seriously decreased in non-smokers > smokers > ex-smokers, while the same damage was repaired in a short time in never smokers.     

Development and Characterization of an Elisa for Cotinine in Biological Fluids

Abstract

Cotinine is a major metabolite of nicotine and serves as an important biomarker of tobacco smoke exposure. To monitor exposure to tobacco smoke or nicotine, a sensitive enzyme-linked immunosorbent assay (ELISA) for cotinine was developed. The test had an 1–50 of between 0.5 and 1.0 ng/ml for cotinine and about 500-fold less affinity for nicotine. Few matrix effects were not detectable in human saliva, although relatively small matrix effects (1–50 for cotinine, 2.8 ng/ml) were observed in human serum and urine. The test accurately measured the levels of cotinine in NI5T standards in freeze-dried human urine derivative material (r = .9999) indicating its reliability for measurement of cotinine. The test readily detected low levels (5–500 nglml) of cotinine in human saliva and serum samples. Also, the levels of cotinine in plasma and urine samples from smoke-exposed mice and rats could be rapidly analyzed for cotinine. This ELISA is therefore a sensitive and accurate test for the determination of cotinine in plasma, serum, saliva, and urine samples from humans and animals, and can be successfully used for monitoring and quantifying exposure to tobacco smoke or nicotine.     

Absorption of nicotine from a cigarette that does not burn tobacco

Ten smokers participated in a study to compare the absorption of nicotine from the smoke aerosol of a new cigarette that heats, but does not burn tobacco (test) with a cigarette that burns tobacco (reference). The average plasma nicotine concentrations obtained by the 7th test cigarette (13 ng/ml) and 7th reference cigarette (24 ng/ml) were proportional to the nicotine yielded by the two cigarettes as determined under Federal Trade Commission machine-smoking conditions. These data demonstrate that the smoke aerosol obtained by smoking a cigarette which heats tobacco produces plasma profiles of nicotine that are similar to the profiles obtained from smoking a cigarette that burns tobacco.     

Urinary mutagenicity after controlled exposure to environmental tobacco smoke (ETS)

20 non-smokers on a defined diet low in polycyclic aromatic hydrocarbons (PAH) were exposed to environmental tobacco smoke (ETS) in an unventilated room for 8 h. The urinary mutagenicity in the 24-h urine samples as tested with the Salmonella (TA98) microsome assay did not significantly increase after exposure to either 10 ppm CO or 20-25 ppm CO. We conclude that exposure of non-smokers to ETS does not lead to an increase in their urinary mutagenicity, provided the exposure conditions are within a realistic range.     

Nicotine in hair of bar and restaurant workers

AIM: To measure the relation between workplace smoking policies and exposures to Environmental Tobacco Smoke (ETS) of workers in bars and restaurants. METHODS: 114 workers in Wellington and Auckland were questioned about sources of exposure to ETS and smoking habits, and details of the smoke-free policy in their work place were recorded. A hair sample was collected from each participant and tested for nicotine. RESULTS: Among non-smoking workers, hair nicotine levels varied strongly according to the smoke free policy at their place of work (Kruskall-Wallis, chi2 = 26.38, p < 0.0001). Those working in 100% smoke free restaurants had much lower levels than staff working in bars with no restrictions on smoking, and levels were intermediate for staff working in places with a partial smoking ban. These findings were not changed when adjustments were made for other sources of ETS exposure. Hair nicotine levels among nonsmokers working in places with no restriction on smoking were similar to hair nicotine levels of active smokers. CONCLUSION: The present New Zealand Smoke Free Environment Act does not protect workers in the hospitality industry from exposure to ETS. The findings from this study highlight the substantial levels of exposure of bar and restaurant staff from patrons' smoking.     

Preadolescent tobacco smoke exposure leads to acute nicotine dependence but does not affect the rewarding effects of nicotine or nicotine withdrawal in adulthood in rats

Epidemiological studies indicate that parental smoking increases the risk for smoking in children. However, the underlying mechanisms by which parental smoking increases the risk for smoking are not known. The aim of these studies was to investigate if preadolescent tobacco smoke exposure, postnatal days 21-35, affects the rewarding effects of nicotine and nicotine withdrawal in adult rats. The rewarding effects of nicotine were investigated with the conditioned place preference procedure. Nicotine withdrawal was investigated with the conditioned place aversion procedure and intracranial self-stimulation (ICSS). Elevations in brain reward thresholds in the ICSS paradigm reflect a dysphoric state. Plasma nicotine and cotinine levels in the preadolescent rats immediately after smoke exposure were 188 ng/ml and 716 ng/ml, respectively. Preadolescent tobacco smoke exposure led to the development of nicotine dependence as indicated by an increased number of mecamylamine-precipitated somatic withdrawal signs in the preadolescent tobacco smoke exposed rats compared to the control rats. Nicotine induced a similar place preference in adult rats that had been exposed to tobacco smoke or air during preadolescence. Furthermore, mecamylamine induced place aversion in nicotine dependent rats but there was no effect of preadolescent tobacco smoke exposure. Finally, preadolescent tobacco smoke exposure did not affect the elevations in brain reward thresholds associated with precipitated or spontaneous nicotine withdrawal. These studies indicate that passive exposure to tobacco smoke during preadolescence leads to the development of nicotine dependence but preadolescent tobacco smoke exposure does not seem to affect the rewarding effects of nicotine or nicotine withdrawal in adulthood.