Urinary Biomarkers of Exposure to Volatile Organic Compounds from the Population Assessment of Tobacco and Health Study Wave 1 (2013-2014).
ABSTRACT: Volatile organic compounds (VOCs) are ubiquitous in the environment. In the United States (U.S.), tobacco smoke is the major non-occupational source of exposure to many harmful VOCs. Exposure to VOCs can be assessed by measuring their urinary metabolites (VOCMs). The Population Assessment of Tobacco and Health (PATH) Study is a U.S. national longitudinal study of tobacco use in the adult and youth civilian non-institutionalized population. We measured 20 VOCMs in urine specimens from a subsample of adults in Wave 1 (W1) (2013-2014) to characterize VOC exposures among tobacco product users and non-users. We calculated weighted geometric means (GMs) and percentiles of each VOCM for exclusive combustible product users (smokers), exclusive electronic cigarette (e-cigarette) users, exclusive smokeless product users, and tobacco product never users. We produced linear regression models for six VOCMs with sex, age, race, and tobacco user group as predictor variables. Creatinine-ratioed levels of VOCMs from exposure to acrolein, crotonaldehyde, isoprene, acrylonitrile, and 1,3-butadiene were significantly higher in smokers than in never users. Small differences of VOCM levels among exclusive e-cigarette users and smokeless users were observed when compared to never users. Smokers showed higher VOCM concentrations than e-cigarette, smokeless, and never users. Urinary VOC metabolites are useful biomarkers of exposure to harmful VOCs.
Project description:BACKGROUND:Monitoring population-level toxicant exposures from smokeless tobacco (SLT) use is important for assessing population health risks due to product use. In this study, we assessed tobacco biomarkers of exposure (BOE) among SLT users from the Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study. METHODS:Urinary biospecimens were collected from adults ages 18 and older. Biomarkers of nicotine, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), volatile organic compounds (VOC), metals, and inorganic arsenic were analyzed and reported among exclusive current established SLT users in comparison with exclusive current established cigarette smokers, dual SLT and cigarette users, and never tobacco users. RESULTS:In general, SLT users (n = 448) have significantly higher concentrations of BOE to nicotine, TSNAs, and PAHs compared with never tobacco users; significant dose-response relationships between frequency of SLT use and biomarker concentrations were also reported among exclusive SLT daily users. Exclusive SLT daily users have higher geometric mean concentrations of total nicotine equivalent-2 (TNE2) and TSNAs than exclusive cigarette daily smokers. In contrast, geometric mean concentrations of PAHs and VOCs were substantially lower among exclusive SLT daily users than exclusive cigarette daily smokers. CONCLUSIONS:Our study produced a comprehensive assessment of SLT product use and 52 biomarkers of tobacco exposure. Compared with cigarette smokers, SLT users experience greater concentrations of some tobacco toxicants, including nicotine and TSNAs. IMPACT:Our data add information on the risk assessment of exposure to SLT-related toxicants. High levels of harmful constituents in SLT remain a health concern.
Project description:BACKGROUND:How carcinogen exposure varies across users of different, particularly noncigarette, tobacco products remains poorly understood. METHODS:We randomly selected 165 participants of the Golestan Cohort Study from northeastern Iran: 60 never users of any tobacco, 35 exclusive cigarette, 40 exclusive (78% daily) waterpipe, and 30 exclusive smokeless tobacco (nass) users. We measured concentrations of 39 biomarkers of exposure in 4 chemical classes in baseline urine samples: tobacco alkaloids, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC). We also quantified the same biomarkers in a second urine sample, obtained 5 years later, among continuing cigarette smokers and never tobacco users. RESULTS:Nass users had the highest concentrations of tobacco alkaloids. All tobacco users had elevated TSNA concentrations, which correlated with nicotine dose. In both cigarette and waterpipe smokers, PAH and VOC biomarkers were higher than never tobacco users and nass users, and highly correlated with nicotine dose. PAH biomarkers of phenanthrene and pyrene and two VOC metabolites (phenylmercapturic acid and phenylglyoxylic acid) were higher in waterpipe smokers than in all other groups. PAH biomarkers among Golestan never tobacco users were comparable to those in U.S. cigarette smokers. All biomarkers had moderate to good correlations over 5 years, particularly in continuing cigarette smokers. CONCLUSIONS:We observed two patterns of exposure biomarkers that differentiated the use of the combustible products (cigarettes and waterpipe) from the smokeless product. Environmental exposure from nontobacco sources appeared to contribute to the presence of high levels of PAH metabolites in the Golestan Cohort. IMPACT:Most of these biomarkers would be useful for exposure assessment in a longitudinal study.
Project description:BACKGROUND:Cigarette smoking is associated with an increase in cardiovascular disease risk, attributable in part to reactive volatile organic chemicals (VOCs). However, little is known about the extent of VOC exposure due to the use of other tobacco products. METHODS:We recruited 48 healthy, tobacco users in four groups: cigarette, smokeless tobacco, occasional users of first generation e-cigarette and e-cigarette menthol and 12 healthy nontobacco users. After abstaining for 48 h, tobacco users used an assigned product. Urine was collected at baseline followed by five collections over a 3-h period to measure urinary metabolites of VOCs, nicotine, and tobacco alkaloids. RESULTS:Urinary levels of nicotine were ≃2-fold lower in occasional e-cigarette and smokeless tobacco users than in the cigarette smokers; cotinine and 3-hydroxycotinine levels were similar in all groups. Compared with nontobacco users, e-cigarette users had higher levels of urinary metabolites of xylene, cyanide, styrene, ethylbenzene, and benzene at baseline and elevated urinary levels of metabolites of xylene, N,N-dimethylformamide, and acrylonitrile after e-cigarette use. Metabolites of acrolein, crotonaldehyde, and 1,3-butadiene were significantly higher in smokers than in users of other products or nontobacco users. VOC metabolite levels in smokeless tobacco group were comparable to those found in nonusers with the exception of xylene metabolite-2-methylhippuric acid (2MHA), which was almost three fold higher than in nontobacco users. CONCLUSIONS:Smoking results in exposure to a range of VOCs at concentrations higher than those observed with other products, and first generation e-cigarette use is associated with elevated levels of N,N-dimethylformamide and xylene metabolites. IMPLICATIONS:This study shows that occasional users of first generation e-cigarettes have lower levels of nicotine exposure than the users of combustible cigarettes. Compared with combustible cigarettes, e-cigarettes, and smokeless tobacco products deliver lower levels of most VOCs, with the exception of xylene, N,N-dimethylformamide, and acrylonitrile, whose metabolite levels were higher in the urine of e-cigarette users than nontobacco users. Absence of anatabine in the urine of e-cigarette users suggests that measuring urinary levels of this alkaloid may be useful in distinguishing between users of e-cigarettes and combustible cigarettes. However, these results have to be validated in a larger cohortcomprised of users of e-cigarettes of multiple brands.
Project description:Importance:Use of electronic cigarettes (e-cigarettes) is increasing. Measures of exposure to known tobacco-related toxicants among e-cigarette users will inform potential health risks to individual product users. Objectives:To estimate concentrations of tobacco-related toxicants among e-cigarette users and compare these biomarker concentrations with those observed in combustible cigarette users, dual users, and never tobacco users. Design, Setting, and Participants:A population-based, longitudinal cohort study was conducted in the United States in 2013-2014. Cross-sectional analysis was performed between November 4, 2016, and October 5, 2017, of biomarkers of exposure to tobacco-related toxicants collected by the Population Assessment of Tobacco and Health Study. Participants included adults who provided a urine sample and data on tobacco use (N?=?5105). Exposures:The primary exposure was tobacco use, including current exclusive e-cigarette users (n?=?247), current exclusive cigarette smokers (n?=?2411), and users of both products (dual users) (n?=?792) compared with never tobacco users (n?=?1655). Main Outcomes and Measures:Geometric mean concentrations of 50 individual biomarkers from 5 major classes of tobacco product constituents were measured: nicotine, tobacco-specific nitrosamines (TSNAs), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). Results:Of the 5105 participants, most were aged 35 to 54 years (weighted percentage, 38%; 95% CI, 35%-40%), women (60%; 95% CI, 59%-62%), and non-Hispanic white (61%; 95% CI, 58%-64%). Compared with exclusive e-cigarette users, never users had 19% to 81% significantly lower concentrations of biomarkers of exposure to nicotine, TSNAs, some metals (eg, cadmium and lead), and some VOCs (including acrylonitrile). Exclusive e-cigarette users showed 10% to 98% significantly lower concentrations of biomarkers of exposure, including TSNAs, PAHs, most VOCs, and nicotine, compared with exclusive cigarette smokers; concentrations were comparable for metals and 3 VOCs. Exclusive cigarette users showed 10% to 36% lower concentrations of several biomarkers than dual users. Frequency of cigarette use among dual users was positively correlated with nicotine and toxicant exposure. Conclusions and Relevance:Exclusive use of e-cigarettes appears to result in measurable exposure to known tobacco-related toxicants, generally at lower levels than cigarette smoking. Toxicant exposure is greatest among dual users, and frequency of combustible cigarette use is positively correlated with tobacco toxicant concentration. These findings provide evidence that using combusted tobacco cigarettes alone or in combination with e-cigarettes is associated with higher concentrations of potentially harmful tobacco constituents in comparison with using e-cigarettes alone.
Project description:BACKGROUND:Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants formed from incomplete combustion of organic matter; some PAHs are carcinogens. Smoking, diet, and other activities contribute to exposure to PAHs. Exposure data to PAHs among combustible tobacco product users (e.g. cigarette smokers) exist; however, among non-combustible tobacco products users (e.g., e-cigarette users), such data are rather limited. OBJECTIVES:We sought to evaluate exposure to PAHs among participants in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study based on the type of tobacco product (combustible vs non-combustible), and frequency and intensity of product use. METHODS:We quantified seven PAH urinary biomarkers in 11,519 PATH Study participants. From self-reported information, we categorized 8327 participants based on their use of tobacco products as never-tobacco user (never user, n?=?1700), exclusive current established combustible products user (combustible products user, n?=?5767), and exclusive current established non-combustible products user (non-combustible products user, n?=?860). We further classified tobacco users as exclusive cigarette user (cigarette user, n?=?3964), exclusive smokeless product user (SLT user, n?=?509), and exclusive e-cigarette user (e-cigarette user, n?=?280). Last, we categorized frequency of product use (everyday vs some days) and time since use (last hour, within 3?days, over 3?days). We calculated geometric mean (GM) concentrations, and evaluated associations between tobacco product user categories and PAH biomarkers concentrations. RESULTS:Combustible products users had significantly higher GMs of all biomarkers than non-combustible products users and never users; non-combustible products users had significantly higher GMs than never users for four of seven biomarkers. For all biomarkers examined, cigarette users had the highest GMs compared to other tobacco-product users. Interestingly, GMs of 2-hydroxyfluorene, 3-hydroxyfluorene and ?2,3-hydroxyphenanthrene were significantly higher in SLT users than in e-cigarette users; 3-hydroxyfluorene and 1-hydroxypyrene were also significantly higher in e-cigarette and SLT users than in never users. Everyday cigarette and SLT users had significantly higher GMs for most biomarkers than some days' users; cigarette and SLT users who used the product in the last hour had significantly higher GMs of most biomarkers than other occasional cigarette or SLT users respectively. By contrast, everyday e-cigarette users' GMs of most biomarkers did not differ significantly from those in some days' e-cigarette users; we did not observe clear trends by time of last use among e-cigarette users. CONCLUSIONS:Users of tobacco products had higher PAH urinary biomarker concentrations compared to never users, and concentrations differed by type and frequency of tobacco product use.
Project description:BACKGROUND:Assessments supporting smokeless tobacco (SLT) disease risk are generally decades old. Newer epidemiological data may more accurately represent the health risks associated with contemporary US-based SLT products, many of which contain lower levels of hazardous and potentially hazardous chemicals compared to previously available SLT products. METHODS:Data from two longitudinal datasets (National Longitudinal Mortality Study-NLMS, and the National Health Interview Survey-NHIS) were analyzed to determine potential associations between SLT use and/or cigarette smoking and all-cause and disease-specific mortality. Mortality hazard ratios (HR) were estimated using a Cox proportional hazards regression model applied to various groups, including never users of any tobacco or SLT product, and current and former SLT users and/or cigarette smokers. RESULTS:The two datasets yielded consistent findings with similar patterns evident for the specific causes of death measured. All-cause mortality risk for exclusive SLT users was significantly lower than that observed for exclusive cigarette smokers and dual SLT/cigarette users. Similar trends were found for mortality from diseases of the heart, chronic lower respiratory diseases, and malignant neoplasms. Mortality risk for lung cancer in exclusive cigarette smokers was increased by about 12-fold over never-tobacco users but was rarely present in exclusive SLT users in either survey (NHIS, < 5 cases/1,563 observations; NLMS, 3 cases/1,863 observations). While the data in the surveys are limited, SLT use by former cigarette smokers was not associated with an increase in the lung cancer risk HR compared to that by former cigarette smokers who never used SLT. CONCLUSIONS:Emerging epidemiological data provides a new perspective on the health risks of SLT use compared to risks associated with cigarette smoking. HR estimates derived from two current US datasets, which include data on contemporary tobacco products, demonstrate a clear mortality risk differential between modern SLT products and cigarettes. Cigarette smokers had an increased overall mortality risk and risk for several disease-specific causes of death, while SLT users consistently had lower mortality risks.
Project description:INTRODUCTION:Limited research exists about the possible cardiovascular effects of electronic nicotine delivery systems (ENDS). We therefore sought to compare exposure to known or potentially cardiotoxic volatile organic compounds (VOCs) in ENDS users, smokers, and dual users. METHODS:A total of 371 individuals from the Cardiovascular Injury due to Tobacco Use study, a cross-sectional study of healthy participants aged 21-45 years, were categorized as nonusers of tobacco (n = 87), sole ENDS users (n = 17), cigarette smokers (n = 237), and dual users (n = 30) based on 30-day self-reported tobacco product use patterns. Participants provided urine samples for VOC and nicotine metabolite measurement. We assessed associations between tobacco product use and VOC metabolite measures using multivariable-adjusted linear regression models. RESULTS:Mean (SD) age of the population was 32 (±6.8) years, 55% men. Mean urinary cotinine level in nonusers of tobacco was 2.6 ng/mg creatinine, whereas cotinine levels were similar across all tobacco product use categories (851.6-910.9 ng/mg creatinine). In multivariable-adjusted models, sole ENDS users had higher levels of metabolites of acrolein, acrylamide, acrylonitrile, and xylene compared with nonusers of tobacco, but lower levels of most VOC metabolites compared with cigarette smokers or dual users. In direct comparison of cigarettes smokers and dual users, we found lower levels of metabolites of styrene and xylene in dual users. CONCLUSION:Although sole ENDS use may be associated with lower VOC exposure compared to cigarette smoking, further study is required to determine the potential health effects of the higher levels of certain reactive aldehydes, including acrolein, in ENDS users compared with nonusers of tobacco. IMPLICATIONS:ENDS use in conjunction with other tobacco products may not significantly reduce exposure to VOC, but sole use does generally reduce some VOC exposure and warrants more in-depth studies.
Project description:BACKGROUND:The dose-response relationships between number of cigarettes smoked per day (CPD) and health outcomes, such as cancer and heart disease, are well established, but much less is known about the relationships between CPD and biomarkers of exposure. METHODS:We analyzed biomarker data by CPD from more than 2,700 adult daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health Study. Tobacco use categories consisted of exclusive cigarette smokers, dual cigarette and e-cigarette users, and dual cigarette and smokeless tobacco users. RESULTS:Biomarker concentrations consistently increased with CPD for each tobacco user group, although concentrations tended to level off at high smoking levels, such as those at and above 20 CPD. Dual cigarette and e-cigarette users had higher levels of some biomarkers such as Total Nicotine Equivalents-2 (P = 0.0036) than exclusive cigarette smokers, and dual cigarette and smokeless tobacco users had higher levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (P < 0.0001) and N'-nitrosonornicotine (P = 0.0236) than exclusive cigarette smokers. CONCLUSIONS:Among daily smokers, exposure to tobacco toxicants and constituents exhibits a dose-response relationship by number of cigarettes smoked, but the relationship is not necessarily linear in form. Dual users of cigarettes with either e-cigarettes or smokeless tobacco are exposed to higher levels of certain toxicants and carcinogens than exclusive cigarette smokers. IMPACT:Availability of biomarker data by CPD may aid in comparisons between cigarette smoking and use of new and potentially reduced exposure tobacco products, which may result in different levels of constituent and toxicant exposure.
Project description:Introduction:E-cigarette use occurs with tobacco product use in youth. Methods:Using the 2014 National Youth Tobacco Survey (NYTS), we examined past 30-day frequency of cigarette, cigar, smokeless, and e-cigarette use in the context of past 30-day and ever tobacco product use in US middle and high school students (N = 22 007). Frequency of product-specific use was examined by exclusive versus concurrent use with another product in the past 30 days (poly-use). Results:In 2014, the majority (83%) of US middle and high school students had not used tobacco or e-cigarettes in the past 30 days. In the 9.3% of youth reporting any past 30-day e-cigarette use, 63% also reported using a tobacco product; among the 3.3% past 30-day exclusive e-cigarette users, about two-thirds (2.1%) had ever used combustible or non-combustible tobacco products and one-third (1.2%) had not. Few never tobacco users had used e-cigarettes on 10 or more days in the past month (absolute percent < 0.1%). Among past 30-day cigarette and smokeless users, the two highest frequency categories were 1-2 days and daily use; among past 30-day e-cigarette and cigar users, prevalence decreased with increasing frequency of use. The majority of past 30-day cigarette, cigar, smokeless, and e-cigarette users reported poly-use. Conclusions:Prevalence estimates for a single product mask the complex patterns of frequency, temporality, and poly-use in youth. Two-thirds of past 30-day exclusive e-cigarette users have ever used tobacco. Poly-use is the dominant pattern of tobacco and e-cigarette use among US middle and high school students. Implications:Our study highlights the complexity of tobacco use patterns in US middle and high school students. Future studies addressing the full public health impact of movement into or out of combustible tobacco use will require longitudinal data with appropriate measures of tobacco and e-cigarette product-specific use (eg, frequency and intensity), as well as adequate sample size and a sufficient number of waves to determine how use of individual products, like e-cigarettes, impact progression into or out of more stable patterns of tobacco and e-cigarette use.