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.     

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.     

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.     

Pharmacokinetics of nicotine in rats after multiple-cigarette smoke exposure

The pharmacokinetics of nicotine and its major metabolites was evaluated in male rats after multiple-cigarette smoke exposure. A smoke-exposure apparatus was used to deliver cigarette smoke to the exposure chamber. The rats were exposed to smoke from a single cigarette every 8 hr for 14 days and to the smoke of a cigarette spiked with radiolabeled nicotine on the 15th day. Blood and urine samples were collected at timed intervals during the 10-min smoke-exposure period of the last cigarette and up to 48 hr thereafter. Nicotine, cotinine, and other polar metabolites were separated by thin-layer chromatography and quantified by liquid scintillation counting. The data were analyzed by computer fitting, and the derived pharmacokinetic parameters were compared to those observed after a single iv injection of nicotine and after a single-cigarette smoke exposure. The results indicated that the amount of nicotine absorbed from multiple-cigarette smoke was approximately 10-fold greater than that absorbed from a single cigarette. Also, unlike the single-cigarette smoke exposure experiment, nicotine plasma levels did not decay monotonically but increased after the 5th hr, and high plasma concentrations persisted for 30 hr. The rate and extent of the formation of cotinine, the major metabolite of nicotine, were decreased as compared with their values following a single-cigarette smoke exposure. It was concluded that nicotine or a constituent of tobacco smoke inhibits the formation of cotinine and may affect the biotransformation of other metabolites. Urinary excretion tended to support the conclusions that the pharmacokinetic parameters of nicotine and its metabolites were altered upon multiple as compared to single dose exposure.     

Time course of nicotine and cotinine incorporation into samples of nonsmokers' beard hair following a single dose of nicotine polacrilex

Hair nicotine and cotinine have been proposed as longer-term markers of exposure to secondhand smoke. In this study, we evaluated the rate and extent of nicotine and cotinine deposition into beard hair among six male nonsmokers following a single exposure to 4 mg of nicotine in Nicorette(?) (nicotine polacrilex) gum. We collected beard hair samples daily for 12 days following exposure and urine samples for 6 days after exposure. Using liquid chromatographic-tandem mass spectrometric analysis, we found that both nicotine and cotinine could be detected in beard samples within 24 h of the exposure and reached a maximum of about 71 pg nicotine and 47 pg cotinine/mg hair, respectively, within 1-2 days, followed by a gradual decline. Compared to beard hair concentrations, nicotine, cotinine, and hydroxycotinine were excreted in urine at much higher levels and also peaked on the day after exposure (mean ± SD urine cotinine = 300 ± 183 ng/mL). Our results confirmed that both nicotine and cotinine can be measured in beard hair samples following a single dose of nicotine. However, both the time-course and extent of deposition of these analytes in beard hair in this study differed from the results reported previously from a similar evaluation.     

Selective hair analysis of nicotine by molecular imprinted solid-phase extraction: an application for evaluating tobacco smoke exposure.

A method using a molecularly imprinted polymer (MIP) as the selective sorbent for solid-phase extraction (SPE) has been developed. Its application to the assay of hairy nicotine level among smokers and non-smokers with high-performance liquid chromatography (HPLC) and evaluation of exposures to the environmental tobacco smoke (ETS) were validated. The MIP was synthesized using nicotine as the template molecule and methacrylic acid (MAA) as the functional monomer. This MIP-SPE method provided inherent selectivity and a sensitive response to nicotine with a detection limit of 0.2 ng/ml hair at a signal-to-noise ratio of 3:1 and the limit of quantification was 0.5 ng/ml. The linearity was assessed in the range of 0.5-80 ng/ml hair, with a coefficient (r(2)) greater than 0.987. The amounts of nicotine determined in smokers and non-smokers hair were in the range of 5.1-69.5 ng/mg hair and 0.50-9.3 ng/mg hair, respectively. The reported measures of ETS exposure were significantly associated with hairy nicotine levels. This assay of nicotine in hair using MISPE provided a very selective and reliable method for the evaluation of the exposure to tobacco smoke.     

Secondhand smoke and nicotine exposure: a brief review

Secondhand tobacco smoke exposure is linked to a number of adverse health outcomes. This paper reviews published studies examining nicotine levels related to exposure to secondhand tobacco smoke. Twenty-two field studies measuring biological levels of nicotine associated with secondhand tobacco smoke exposure were evaluated. Positive associations between self-reported and/or objective measures of secondhand tobacco smoke exposure and concentrations of nicotine and/or biomarkers of nicotine in the body were frequently reported. Two studies indicated that nicotine exposure from secondhand tobacco smoke can engender plasma nicotine concentrations that are equivalent to levels produced by tobacco smoking and that are associated with nicotine-induced changes in behavior. Future research should examine whether nicotine exposure from secondhand tobacco smoke has functional effects on neurobiological and behavioral processes associated with tobacco use.     

Comparison of the effects of e-cigarette vapor and cigarette smoke on indoor air quality

Context: Electronic cigarettes (e-cigarettes) have earned considerable attention recently as an alternative to smoking tobacco, but uncertainties about their impact on health and indoor air quality have resulted in proposals for bans on indoor e-cigarette use.

Objective: To assess potential health impacts relating to the use of e-cigarettes, a series of studies were conducted using e-cigarettes and standard tobacco cigarettes.

Methods and materials: Four different high nicotine e-liquids were vaporized in two sets of experiments by generic 2-piece e-cigarettes to collect emissions and assess indoor air concentrations of common tobacco smoke by products. Tobacco cigarette smoke tests were conducted for comparison.

Results: Comparisons of pollutant concentrations were made between e-cigarette vapor and tobacco smoke samples. Pollutants included VOCs, carbonyls, PAHs, nicotine, TSNAs, and glycols. From these results, risk analyses were conducted based on dilution into a 40 m³ room and standard toxicological data. Non-cancer risk analysis revealed “No Significant Risk” of harm to human health for vapor samples from e-liquids (A-D). In contrast, for tobacco smoke most findings markedly exceeded risk limits indicating a condition of “Significant Risk” of harm to human health. With regard to cancer risk analysis, no vapor sample from e-liquids A-D exceeded the risk limit for either children or adults. The tobacco smoke sample approached the risk limits for adult exposure.

Conclusions: For all byproducts measured, electronic cigarettes produce very small exposures relative to tobacco cigarettes. The study indicates no apparent risk to human health from e-cigarette emissions based on the compounds analyzed.     

Toxicological considerations on the use of propylene glycol as a humectant in cigarettes

Propylene glycol (PG) is a humectant commonly used in cigarettes. Previous toxicological examinations of the effects on the addition of PG to tobacco used mixtures with several other flavoring agents. In the present work, toxicological comparisons were made of experimental cigarettes containing no added PG against otherwise similar cigarettes with three different amounts of PG added to the tobacco. The main toxicological comparison was a sub-chronic inhalation study with mainstream smoke in Sprague–Dawley rats (exposures of 150 mg/m³ of total particulate matter, 6 h exposure per day, for 90 consecutive days). The target PG concentrations in the tobacco of the four cigarette types were 0, 4, 7 and 10%. Additional studies with mainstream smoke were bacterial mutagenicity (5 Salmonella strains, both with and without metabolic activation, particulate phase only), cytotoxicity of both particulate and gas/vapor phases (using the neutral red uptake assay), and analytical chemistry (41 analytes). The graded inclusion of PG into experimental cigarettes resulted in increases in the smoke concentrations of propylene oxide, at very low concentrations. Broadly similar responses were seen across the four cigarette types, and the responses were similar to those previously described in the scientific literature. The addition of PG to experimental cigarettes reduced concentrations of some smoke components (e.g. nicotine), but had minimal effects on the biological responses. Most of the changes produced in the 90-days of exposure were resolved in a 42-day post-inhalation period.     

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.     

Selenium in Mainstream and Sidestream Smoke of Cigarettes Containing Fly Ash-Grown Tobacco

ABSTRACT

The quantities of selenium, tar and nicotine present in mainstream (MS) and sidestream (SS) smoke of machine-smoked cigarettes was studied. The cigarettes were prepared from tobacco purposely cultured on fly ash-amended soil so as to increase its selenium concentration. Selenium concentration was found to be the same in the gaseous phase of both MS and SS smoke, but its concentration was significantly higher (p < 0.05) in the particulate matter of the MS smoke. Tar was higher in MS smoke and nicotine in SS smoke. Factors affecting selenium concentrations in tobacco and its possible environmental significance are discussed.     

Tobacco smoke exposure induces nicotine dependence in rats

Rationale

Tobacco smoke contains nicotine and many other compounds that act in concert on the brain reward system. Therefore, animal models are needed that allow the investigation of chronic exposure to the full spectrum of tobacco smoke constituents.

Objectives

The aim of these studies was to investigate if exposure to tobacco smoke leads to nicotine dependence in rats.

Methods

The intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Somatic signs were recorded from a checklist of nicotine abstinence signs. Nicotine self-administration sessions were conducted to investigate if tobacco smoke exposure affects the motivation to self-administer nicotine. Nicotinic receptor autoradiography was used to investigate if exposure to tobacco smoke affects central α7 nicotinic acetylcholine receptor (nAChR) and non-α7 nAChR levels (primarily α4β2 nAChRs).

Results

The nAChR antagonist mecamylamine dose-dependently elevated the brain reward thresholds of the rats exposed to tobacco smoke and did not affect the brain reward thresholds of the untreated control rats. Furthermore, mecamylamine induced more somatic withdrawal signs in the smoke-exposed rats than in the control rats. Nicotine self-administration was decreased 1 day after the last tobacco smoke exposure sessions and was returned to control levels 5 days later. Tobacco smoke exposure increased the α7 nAChR density in the CA2/3 area and the stratum oriens and increased the non-α7 nAChR density in the dentate gyrus.

Conclusion

Tobacco smoke exposure leads to nicotine dependence as indicated by precipitated affective and somatic withdrawal signs and induces an upregulation of nAChRs in the hippocampus.     

The possible role of ammonia toxicity on the exposure, deposition, retention, and the bioavailability of nicotine during smoking

A complete and rigorous review is presented of the possible effect(s) of ammonia on the exposure, deposition and retention of nicotine during smoking and the bioavailability of nicotine to the smoker. There are no toxicological data in humans regarding ammonia exposure within the context of tobacco smoke. Extrapolation from occupational exposure of ammonia to smoking in humans suggests minimal, non-toxicological effects, if any. No direct study has examined the effect of the ammonia on the total rate or amount of nicotine reaching the arterial bloodstream or brains of smokers. Machine-smoking methods have been reported which accurately quantify >99% of the nicotine in mainstream (MS) smoke for a wide variety of commercial and test cigarettes, including a series of experimental cigarettes having a range in MS smoke ammonia yields using the US Federal Trade Commission (FTC) protocol. However, the actual exposure of nicotine to smokers depends on their own smoking behavior. The nicotine ring system is relatively thermally stable. Protonated nicotine forms nicotine which evaporates before the nicotine ring system decomposes. The experimental data indicate that neither nicotine transfer from tobacco to MS smoke nor nicotine bioavailability to the smoker increases with an increase in any of the following properties: tobacco soluble ammonia, MS smoke ammonia, “tobacco pH” or “smoke pH” at levels found in commercial cigarettes. Gas phase nicotine deposits primarily in the mouth and upper respiratory tract. To the extent that ammonia increases the deposition of nicotine in the buccal cavity and upper respiratory tract during smoking, the total rate and amount of nicotine into the arterial bloodstream and to the central nervous system will decrease. Charged nicotine analogues are actively transported in a number of tissues. This active transport system appears to be insensitive to pH and the form of nicotine in the biological milieu, suggesting that protonated nicotine may be a substrate for active transport. Neither “smoke pH” of commercial cigarettes nor “smoke pH_eff” nor the fraction of non-protonated nicotine in tobacco smoke particulate matter are useful, practical smoke parameters for providing understanding or predictability of nicotine bioavailability to smokers. Greater than 95% of both ammonia and nicotine are in the gas phase of environmental tobacco, and both are likely to deposit in the buccal cavity and upper respiratory tract following 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.     

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.     

Repeated pre-exposure to tobacco smoke potentiates subsequent locomotor responses to nicotine and tobacco smoke but not amphetamine in adult rats

These studies investigated if pre-exposure to tobacco smoke affects the locomotor response to tobacco smoke, nicotine, and amphetamine in adult rats. The rats were habituated to an open field for 3-4 days and then exposed to tobacco smoke for 2 h/day for 13-14 days. The effect of exposure to tobacco smoke on locomotor activity was investigated after 1, 7, and 14 days of smoke exposure and after one 2-hour exposure session that followed a 3-week off period. The effects of tobacco smoke on the locomotor responses to nicotine (0.04 and 0.4 mg/kg, base) and amphetamine (0.1 and 0.5 mg/kg) were investigated on day 14, one day after the last smoke exposure session. The locomotor response to tobacco smoke was increased after 7 and 14 days of smoke exposure and after one exposure session after the 3-week off-period. The acute administration of the high dose of nicotine (0.4 mg/kg) led to a brief period of hypoactivity that was followed by a period of hyperactivity. Pre-exposure to tobacco smoke attenuated the nicotine-induced hypoactivity and potentiated the nicotine-induced hyperactivity. The low dose of nicotine (0.04 mg/kg) did not affect locomotor activity in the control rats but increased the total distance traveled in the tobacco smoke exposed rats. Exposure to tobacco smoke did not affect the locomotor response to amphetamine. These findings indicate that exposure to tobacco smoke leads to tolerance to the depressant effects of nicotine and potentiates the stimulant effects of nicotine and tobacco smoke.     

Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke

Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm to public health caused by tobacco smoking by offering smokers a less harmful means of receiving nicotine. As e-cigarettes are a relatively new phenomenon, there are limited scientific data on the longer-term health effects of their use. This study describes a robust in vitro method for assessing the cytotoxic response of e-cigarette aerosols that can be effectively compared with conventional cigarette smoke. This was measured using the regulatory accepted Neutral Red Uptake assay modified for air–liquid interface (ALI) exposures. An exposure system, comprising a smoking machine, traditionally used for in vitro tobacco smoke exposure assessments, was adapted for use with e-cigarettes to expose human lung epithelial cells at the ALI. Dosimetric analysis methods using real-time quartz crystal microbalances for mass, and post-exposure chemical analysis for nicotine, were employed to detect/distinguish aerosol dilutions from a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity than 3R4F cigarette smoke based on matched EC₅₀ values at different dilutions (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1?μg/cm²) and nicotine (0.89 vs. 0.27?μg/cm²), respectively. Test doses where cigarette smoke and e-cigarette aerosol cytotoxicity were observed are comparable with calculated daily doses in consumers. Such experiments could form the basis of a larger package of work including chemical analyses, in vitro toxicology tests and clinical studies, to help assess the safety of current and next generation nicotine and tobacco products.     

Validation of a liquid chromatography-tandem mass spectrometry method for the detection of nicotine biomarkers in hair and an evaluation of wash procedures for removal of environmental nicotine

The aim of this exploratory study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the quantification of nicotine, eight nicotine metabolites, and two minor tobacco alkaloids in fortified analyte-free hair and subsequently apply this method to hair samples collected from active smokers. An additional aim of the study was to include an evaluation of different wash procedures for the effective removal of environmentally deposited nicotine from tobacco smoke. An apparatus was designed for the purpose of exposing analyte-free hair to environmental tobacco smoke in order to deposit nicotine onto the hair surface. A shampoo/water wash procedure was identified as the most effective means of removing nicotine. This wash procedure was utilized for a comparison of washed and unwashed heavy smoker hair samples. Analytes and corresponding deuterated internal standards were extracted using a cation-exchange solid-phase cartridge. LC-MS-MS was carried out using an Acquity? UPLC(?) system (Waters) and a Quattro Premier XE? triple quadrupole MS (Waters) operated in electrospray positive ionization mode, with multiple reaction monitoring data acquisition. The developed method was applied to hair samples collected from heavy smokers (n = 3) and low-level smokers (n = 3) collected through IRB-approved protocols. Nicotine, cotinine, and nornicotine were quantified in both the washed and unwashed hair samples collected from three heavy smokers, whereas 3-hydroxycotinine was quantified in only one unwashed sample and nicotine-1'-oxide in the washed and unwashed hair samples from two heavy smokers. In contrast, nicotine-1'-oxide was quantified in one of the three low-level smoker samples; nicotine was quantified in the other two low-level smoker samples. No other analytes were detected in the hair of the three low-level smokers.     

Relationship between the level and time of exposure to tobacco smoke and urine nicotine and cotinine concentration

The study attempts to evaluate whether it is possible to determine time and level of exposure of rats to tobacco smoke based on nicotine and cotinine content in urine. The animals were exposed to tobacco smoke by inhalation in a specially designed experimental chambers. The exposure to three different tobacco smoke levels (500, 1000 and 1500 mg CO/m3 of air) lasted 6 h per day, for one, three and five days. Nicotine and cotinine concentrations were measured in daily urine using high performance liquid chromatography procedure developed by the authors. It has been shown that cotinine but not nicotine can be used as a biomarker of time and extent of exposure to tobacco smoke.     

Effects of developmental nicotine exposure in rats on decision-making in adulthood

Exposure to tobacco smoke during pregnancy is associated with a range of adverse outcomes in offspring, including cognitive deficits and increased incidence of attention deficit-hyperactivity disorder, but there is a considerable controversy with regard to the causal role of tobacco smoke in these outcomes. To determine whether developmental exposure to the primary psychoactive ingredient in tobacco smoke, nicotine, may cause long-lasting behavioral alterations analogous to those in attention deficit-hyperactivity disorder, male Sprague-Dawley rats underwent a chronic neonatal nicotine administration regimen, which models third-trimester human exposure. Male rat pups were administered nicotine (6 mg/kg/day) by oral gastric intubation on postnatal days 1-7. In adulthood, rats were tested in two decision-making tasks (risky decision-making and delay discounting) as well as in free-operant responding for food reward and the elevated plus maze. Chronic neonatal nicotine attenuated weight gain during nicotine exposure, but there were no effects on performance in the decision-making task, and only a modest decrease in arm entries in the elevated plus maze in one subgroup of rats. These data are consistent with previous findings that developmental nicotine exposure has no effect on delay discounting, and they extend these findings to risky decision-making as well. They further suggest that at least some neurocognitive alterations associated with prenatal tobacco smoke exposure in humans may be due to genetic or other environmental factors, including non-nicotine components of tobacco smoke.