Volatile Organic Compounds In Blood Research Articles

Recent Advancements in Method Development and Exposure Assessment for 45 Blood VOCs Analyzed by Headspace SPME GC-MS

For over three decades our laboratory has been developing and improving methods for quantifying toxic volatile organic compounds (VOCs) in blood in support of numerous national and regional studies, including nine National Health and Nutrition Examination Survey (NHANES) cycles. Absorption of VOCs most commonly occurs through inhalation, as 100% of blood circulates to the lungs for exchange with alveolar gas. The high blood:gas partition ratios of most VOCs favor preconcentration in the blood, but blood VOC equilibration with tissues and organs is what influences VOC elimination half-life. As such, VOC analysis in blood is best-suited for compounds that are stable in the body by offering a direct measure of VOC burden experienced by tissues and organs.The current analysis method uses headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS). Important to the success of this method is the use of isotopically labeled analogs specific to every compound to compensate for competition effects in the headspace and SPME fiber, as well as adsorption and volatilization losses. The combination of these techniques has enabled us to simultaneously quantify a broad array of VOCs (boiling points from 32 to 204 °C) in the low parts-per-trillion (ng/L) range from a 3-mL blood sample.This presentation will include an overview of the blood VOC method and describe recent improvements to achieve accuracy and precision of < 15% for nonpolar compounds (e.g., alkanes) and within 5% for most of the other VOCs. We will also describe noteworthy blood VOC trends in the United States and reveal new analytes that are to be included in future studies and NHANES cycles. In addition to individual VOC trends, we will describe recent work comparing relative VOC levels among participants using artificial neural networks as a means to objectively distinguish exposure between different VOC sources within a large population.

Blood Volatile Organic Compounds Related to Oxidative Stress as Potential Biomarkers for Huntington’s disease (P1.327)

Blood Volatile Organic Compounds Related to Oxidative Stress as Potential Biomarkers for Huntington’s disease (P1.327)

232 Toxic Compounds in Burn Patients with Smoke Inhalation Injury

Current advanced analytical methods allow for the detection of volatile organic compounds (VOC) levels in blood and enable exploration of VOCs and their potential effects. National Health and Nutrition Examination Survey (NHANES) released data in the public domain for 33 analytes of blood VOC levels for a sample representative of the U.S. population for years 2007–2008. The goal of this study was to use data from NHANES 2007–2008 to evaluate the variability in concentration levels of selected VOC analytes (known toxicants in cigarettes) between the general U.S. population and burn victims with smoke inhalation. After IRB approval, blood samples were obtained from burn victims with smoke inhalation injury at our institution from 2008 to present. NHANES data was used for control comparisons. Subjects in the NHANES dataset were matched to subjects in the burn victim dataset based on age, gender and race in a 1:1 ratio (n=23 per group). The analysis focus was placed on seven biomarkers: benzene (VBZ), toluene (VTO), ethylbenzene (VEB), m-/p-xylene (VXY), o-xylene (VOX), styrene (VST), and 2-5-dimethylfuran (2DF) - all of which are well-known toxicants in tobacco smoke. 1,2-dichloroethane (V2A) is not associated with tobacco smoke but was included as a burn victim positive control. . SAS version 9.4 proc ttest was used for univariate analysis of log transformed values of the seven analytes of interest. Cigarette smokers identified by questionnaire were found to have significantly higher blood VOC levels for the seven smoke biomarkers than non-smokers in NHANES data. However, no significant statistical difference was found in blood VOC levels between smokers and nonsmokers among burn victims. Nevertheless, among the matched data, burn victims with smoke inhalation were found to have statistically significantly higher blood VOC levels for: VBZ (p 0.0258), VOX (p 0.0006), VST (p 0.0010), and positive control V2A (<.0001) than NHANES smokers. Although not statically significant, burn victims with smoke inhalation were also found to have higher blood VOC levels than NHANES smokers for VTO, VEB and VXY. The data presented here add to the knowledge about exposure of VOCs among house-fire burn victims with smoke inhalation injury. The most significant finding of this study was that smoke inhalation from house-fire was associated with relatively higher levels of VOC toxicants when compared to cigarette smokers of the U.S. general population. Further investigation is warranted to determine if there is a correlation of elevated VOCs and clinical prognosis. Identification of VOCs that may exacerbate smoke inhalation injury may help develop more sensitive diagnostic tools to help determine severity and/or outcome of an individual’s smoke inhalation injury.

Predictors of blood volatile organic compound levels in Gulf coast residents.

To address concerns among Gulf Coast residents about ongoing exposures to volatile organic compounds, including benzene, toluene, ethylbenzene, o-xylene, and m-/p- xylene (BTEX), we characterized current blood levels and identified predictors of BTEX among Gulf state residents.We collected questionnaire data on recent exposures and measured blood BTEX levels in a convenience sample of 718 Gulf residents. Because BTEX is rapidly cleared from the body, blood levels represent recent exposures in the past 24 hours. We compared participants’ levels of blood BTEX to a nationally representative sample. Among nonsmokers we assessed predictors of blood BTEX levels using linear regression, and predicted the risk of elevated BTEX levels using modified Poisson regression.Blood BTEX levels in Gulf residents were similar to national levels. Among nonsmokers, sex and reporting recent smoky/chemical odors predicted blood BTEX. The change in log benzene was −0.26 (95% CI: −0.47, −0.04) and 0.72 (0.02, 1.42) for women and those who reported odors, respectively. Season, time spent away from home, and self-reported residential proximity to Superfund sites (within a half mile) were statistically associated with benzene only, however mean concentration was nearly an order of magnitude below that of cigarette smokers.Among these Gulf residents, smoking was the primary contributor to blood BTEX levels, but other factors were also relevant.

Detection rates, trends in and factors affecting observed levels of selected volatile organic compounds in blood among US adolescents and adults

Data from National Health and Nutrition Examination Survey were analyzed to evaluate detection rates, trend in and factors affecting the observed levels of 1,4-dichlorobenzene, benzene, ethylbenzene, o-xylene, styrene, toluene, and m/p-xylene among US adolescents and adults over 2005–2012. Over 2005–20102, among adolescents, detection rates declined by more than 50% for benzene, ethylbenzene, and o-xylene, and among adults, detection rates declined by more than 50% for ethylbenzene and o-xylene and by a little less than 50% for benzene. Among adults, adjusted levels of 1, 4-dichlorobenzene, benzene, ethylbenzene, o-xylene, toluene, and m/p-xylene decreased by 13.7%, 17.1%, 20%, 17.7%, 23.2%, and 18.7% respectively for every two-year survey cycle. Among adolescents, percentage decline in the levels of 1, 4-dichlorobenzene, benzene, ethylbenzene, o-xylene, styrene, toluene, and m/p-xylene was 15.2%, 21.4%, 19.3%, 16.1%, 47.8%, and 17.7% respectively for every two year survey period. The ratio of adjusted geometric means for adult smokers as compared to adult nonsmokers was 10.7 for benzene, 3.5 for ethylbenzene, 2.0 for o-xylene, 3.4 for styrene, 3.5 for toluene, and 2.2 for m/p-xylene. Among adolescents, gender did not affect the adjusted levels of any of the seven VOCs, and the order in which adjusted levels for 1, 4-dichlorobenzene by race/ethnicity was observed was: non-Hispanic white (0.038ng/mL)<Mexican American (0.102ng/mL)<non-Hispanic black (0.178ng/mL) and most of the pairwise comparisons were statistically significantly different (p<=0.02) but race/ethnicity did not affect the adjusted levels for benzene, ethylbenzene, o-xylene, styrene, toluene, and m/p-xylene. For benzene, males had lower levels of adjusted geometric means (AGM) than females (0.021 vs. 0.025ng/mL). For adults, gender did not affect the adjusted levels of 1, 4-dicholorobenzene, ethylbenzene, o-xylene, styrene, toluene, and m/p-xylene.

Associations between blood BTEXS concentrations and hematologic parameters among adult residents of the U.S. Gulf States

BackgroundStudies of workers exposed to benzene at average air concentrations below one part per million suggest that benzene, a known hematotoxin, causes hematopoietic damage even at low exposure levels. However, evidence of such effects outside of occupational settings and for other volatile organic compounds (VOCs) is limited. ObjectiveTo investigate associations between ambient exposures to five VOCs, including benzene, and hematologic parameters among adult residents of the U.S. Gulf Coast. Materials and methodsBlood concentrations of selected VOCs were measured in a sample of adult participants in the Gulf Long-term Follow-up Study (GuLF STUDY) during 2012 and 2013. Complete blood counts with differentials were also performed on a subset of participants (n=406). We used these data together with detailed questionnaire data to estimate adjusted associations between blood BTEXS (benzene, toluene, ethylbenzene, o-xylene, m/p-xylene, and styrene) concentrations and hematologic parameters using generalized linear models. ResultsWe observed inverse associations between blood benzene concentrations and hemoglobin concentration and mean corpuscular hemoglobin concentration, and a positive association with red cell distribution width among tobacco smoke-unexposed participants (n=146). Among tobacco smoke-exposed participants (n=247), we observed positive associations between blood VOC concentrations and several hematologic parameters, including increased white blood cell and platelet counts, suggestive of hematopoietic stimulation typically associated with tobacco smoke exposure. Most associations were stronger for benzene than for the other VOCs. ConclusionsOur results suggest that ambient exposure to BTEXS, particularly benzene, may be associated with hematologic effects, including decreased hemoglobin concentration, mean corpuscular hemoglobin concentration, and increased red cell distribution width.

Thermal desorption comprehensive two-dimensional gas chromatography coupled to variable-energy electron ionization time-of-flight mass spectrometry for monitoring subtle changes in volatile organic compound profiles of human blood

Blood is a matrix with high potential for forensic investigations and human rescue. Its volatile signature can be used in search exercises to locate injured or deceased individuals. Little is known, however, about the volatile organic compound (VOC) profile of blood, except that it is complex and varies while blood ages. In the present study, we used thermal desorption (TD) and comprehensive two-dimensional gas chromatography (GCxGC) coupled to variable-energy electron ionization time-of-flight mass spectrometry (TOFMS) to monitor VOC signatures of human blood. A highly complex reference standard (Century Mix) containing 108 compounds of various chemical functionalities and several homologue series of compounds was used for the purpose of transposing our previously developed cryogenically modulated GCxGC-TOFMS methods into the use of a reverse fill/flush (RFF) flow modulator. The average peak width at half height was 340ms and the average tailing factor was 1.16. Light VOCs (down to C4) were effectively flow modulated and exhibited minimal breakthrough over a large dynamic range spanning four orders of magnitude. Mass spectrometric detection was performed using electron impact ionization (EI) carried out at 70eV and lower energies (12, 14, and 16eV). The use of variable-energy (ve) EI allowed mass spectra to be produced with less fragmentation and an increased presence of structurally significant ions and the molecular ion. This provided additional confidence in peak assignments, especially for closely eluting isomers often observed in the profiling of the headspace of blood. Variable-energy EI TD-GCxGC-TOFMS blood data sets were statistically processed using principal component analyses (PCA) and hierarchical cluster analyses (HCA). These techniques demonstrated that the effect of aging was greater than the inter-individual variation on the blood VOC profile. The combination of retention indices, low and high EI MS spectra served as a strong basis to gain more confidence in analytical identification by excluding identities proposed by mass spectral databases (70eV) for compounds contributing to the separation of blood of different ages.

Volatile Organic Compounds in Blood as Biomarkers of Exposure to JP-8 Jet Fuel Among US Air Force Personnel.

This study aimed to evaluate blood volatile organic compound (VOC) levels as biomarkers of occupational jet propulsion fuel 8 (JP-8) exposure while controlling for smoking. Among 69 Air Force personnel, post-shift blood samples were analyzed for components of JP-8, including ethylbenzene, toluene, o-xylene, and m/p-xylene, and for the smoking biomarker, 2,5-dimethylfuran. JP-8 exposure was characterized based on self-report and measured work shift levels of total hydrocarbons in personal air. Multivariate regression was used to evaluate the relationship between JP-8 exposure and post-shift blood VOCs while controlling for potential confounding from smoking. Blood VOC concentrations were higher among US Air Force personnel who reported JP-8 exposure and work shift smoking. Breathing zone total hydrocarbons was a significant predictor of VOC blood levels, after controlling for smoking. These findings support the use of blood VOCs as a biomarker of occupational JP-8 exposure.

A method for quantification of volatile organic compounds in blood by SPME-GC-MS/MS with broader application: From non-occupational exposure population to exposure studies.

Humans are continuously exposed to volatile organic compounds (VOCs) as these chemicals are ubiquitously present in most indoor and outdoor environments. In order to assess recent exposure to VOCs for population-based studies, VOCs are measured in the blood of participants. This work describes an improved method to detect 12 VOCs by head-space solid-phase microextraction gas chromatography coupled with isotope-dilution mass spectrometry in selected reaction monitoring mode (SPME-GC-MS/MS). This method was applied to the analysis of trihalomethanes, styrene, trichloroethylene, tetrachloroethylene and BTEX (benzene, toluene, ethylbenzene, m-xylene, p-xylene, o-xylene) in a population-based biomonitoring study (Canadian Health Measures Survey). The method showed good linearity (>0.990) in the range of 0.010-10μg/L and detection limits between 0.007 and 0.027μg/L, precision better than 25% and good accuracy (±25%) based on proficiency testing materials. Quality Control data among runs over a 7 month period showed %RSD between 14 and 25% at low levels (∼0.03μg/L) and between 9 and 23% at high levels (∼0.4μg/L). The method was modified to analyze samples from a pharmacokinetic study in which 5 healthy volunteers were exposed to single, binary and quaternary mixtures of CTEX (chloroform, ethylbenzene, toluene and m-xylene), thus the expected concentration in blood was 1 order of magnitude higher than those found in the general population. The method was modified by reducing the sample size (from 3g to 0.5g) and increasing the upper limit of the concentration range to 395μg/L. Good linearity was found in the range of 0.13-395μg/L for toluene and ethylbenzene and 0.20-609μg/L for m/p-xylene. Quality control data among runs over the period of the study (n=13) were found to vary between 7 and 25%.

Sa1075 Volatile Organic Compounds in Blood for Non-Invasive Diagnosis of Barrett's Esophagus - A Pilot Study

modalities were included in this analysis. Patients who stopped EET and started surveillance prior to CE-IM were excluded. Complete eradication of intestinal metaplasia (CE-IM) was defined as having an endoscopy with no visible columnar lined epithelium in the tubular esophagus and biopsies of the neo-squamous mucosa showing no intestinal metaplasia. Patients were considered to have achieved CE-IM if they had done so with 2cm were less likely to achieve CE-IM compared to those with C extents ≤2cm (64.3% vs. 73.5%, p=0.027). Patients with M extents of > 3cm were less likely to achieve CE-IM compared to those with M extents ≤3cm (61.2% vs. 88.4%, p<0.001). Conclusions: Results of this multi-center effectiveness trial show that pre-treatment Barrett's esophagus extent as measured by the Prague criteria is associated with the rate of achieving CE-IM with endoscopic eradication therapy. This was true for both the C and M extents of disease. This study provides the first validation of the Prague criteria with clinically relevant outcomes in the management of patients with Barrett's esophagus.

Effects of exposure to mixed volatile organic compounds on the neurobehavioral test performance in a cross-sectional study of US adults

While the environmental exposure to multiple volatile organic compounds (VOCs) is ubiquitous, its neurobehavioral effects are not well understood. We assessed the associations between short-term exposure to VOC mixtures and neurobehavioral test performances on 497 participants in the Third National Health and Nutrition Examination Survey, using quantile and ordinary least squares regression models. We grouped 10 blood VOCs into 3 mixtures based on the principal component analysis, where Mix1 included benzene, toluene, ethylbenzene, m-/p-xylene, o-xylene, and styrene; Mix2 included chloroform and tetrachloroethene; and Mix3 included 1,1,1-trichloroethane and 1,4-dichlorobenzene. We found a general lack of significant adverse effects with exceptions limited to those with the worst performance (i.e. the top 10 percent) in the simple reaction time test, suggesting that these people were potentially more susceptible to impacts of VOC mixtures. However, further research is needed to clarify the neurobehavioral effects of chronic low-level exposure to VOC mixtures among the general population.

Blood Volatile Organic Compounds as Potential Biomarkers for Amyotrophic Lateral Sclerosis: an Animal Study in the SOD1 G93A Mouse

Amyotrophic lateral sclerosis (ALS) is a rapid progressive motor neuron disease. Currently, there are no specific or reliable biomarkers for the diagnosis of this disease, and there are no effective medical treatments. The early diagnosis and treatment of this disease has the potential to prolong the survival of ALS patients, but typically, approximately 1 year passes between the onset of symptoms and the diagnosis of this disease. Therefore, there is an urgent need to find specific biomarkers to enable early diagnosis and therapeutic intervention in this disease. Analyzing the volatile organic compounds (VOCs) present in the blood and exhaled breath is a useful and convenient approach for investigating potential biomarkers. In this study, we examined the VOCs present in blood samples from copper zinc superoxide dismutase 1 (SOD1) glycine to alanine mutation at position 93 (G93A) mice to determine whether a specific biomarker pattern exists in these transgenic mice. Blood samples from ALS mice and their age-matched littermates were analyzed using gas chromatography-mass spectrometry. A total of 12 independent compounds associated with oxidative stress were identified at the early stage of disease. The data show that there is a specific pattern of blood VOCs in ALS mice that could potentially be used as biomarkers that could improve the diagnosis of this disease. Furthermore, these compounds could also potentially be used to monitor the response to neuroprotective agents and to help us better understand the underlying mechanisms of ALS.

Comparison of blood volatile organic compound levels in residents of Calcasieu and Lafayette Parishes, LA, with US reference ranges

Agency for Toxic Substances and Disease Registry conducted a study to evaluate body burden levels of volatile organic compounds (VOCs) among residents of highly industrialized Calcasieu Parish, LA, USA, in 2002. Blood VOC levels in a representative sample of participants in Calcasieu Parish were compared with a similar group of participants in the less-industrialized Lafayette Parish. Participants' ages ranged from 15 to 91 years, 46% were men, and 89% were Caucasian. VOC levels in these two populations were also compared at the national levels. Solid-phase microextraction coupled with gas chromatography mass spectrometry was used to measure levels of 30 VOCs in blood samples collected from 283 self-described non-smoking study participants. Of the 30 VOCs, 6 had quantifiable levels in at least 25% of the blood samples analyzed. The frequency of detection was >95% for benzene and m-/p-xylene, >60% for 1,4-dichlorbenzene and toluene, 27% for ethylbenzene, and 39% for styrene. Calcasieu and Lafayette Parish participants had similar distributions for six VOCs in key percentiles and geometric means. When compared with a representative sampling of the 1999-2000 US general population, no significant differences were found between the parish data and the US general population.

Blood volatile compounds as biomarkers for colorectal cancer

Many recent studies have focused on the connection between the composition of specific volatile organic compounds (VOCs) in exhaled breath and various forms of cancer. However, the composition of exhaled breath is affected by many factors, such as lung disease, smoking, and diet. VOCs are released into the bloodstream before they are exhaled; therefore, the analysis of VOCs in blood will provide more accurate results than the analysis of VOCs in exhaled breath. Blood were collected from 16 colorectal cancer patients and 20 healthy controls, then solid phase microextraction–chromatography–mass spectrometry (SPME-GC-MS) was used to analysis the exhaled volatile organic compounds (VOCs). The statistical methods principal component analysis (PCA) and partial least-squares discriminant analysis (PLSDA) were performed to deal with the final dates. Three metabolic biomarkers were found at significantly lower levels in the group of CRC patients than in the normal control group (P < 0.01): phenyl methylcarbamate, ethylhexanol, and 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne. In addition, significantly higher levels of 1,1,4,4-tetramethyl-2,5-dimethylene-cyclohexane were found in the group of CRC patients than in the normal control group (P < 0.05). Compared with healthy individuals, patients with colorectal adenocarcinoma exhibited a distinct blood metabolic profile with respect to VOCs. The analysis of blood VOCs appears to have potential clinical applications for CRC screening.

Simultaneous analysis of 28 urinary VOC metabolites using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS)

Volatile organic compounds (VOCs) are ubiquitous in the environment, originating from many different natural and anthropogenic sources, including tobacco smoke. Long-term exposure to certain VOCs may increase the risk for cancer, birth defects, and neurocognitive impairment. Therefore, VOC exposure is an area of significant public health concern. Urinary VOC metabolites are useful biomarkers for assessing VOC exposure because of non-invasiveness of sampling and longer physiological half-lives of urinary metabolites compared with VOCs in blood and breath. We developed a method using reversed-phase ultra high performance liquid chromatography (UPLC) coupled with electrospray ionization tandem mass spectrometry (ESI/MSMS) to simultaneously quantify 28 urinary VOC metabolites as biomarkers of exposure. We describe a method that monitors metabolites of acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, 1,3-butadiene, carbon-disulfide, crotonaldehyde, cyanide, N,N-dimethylformamide, ethylbenzene, ethylene oxide, propylene oxide, styrene, tetrachloroethylene, toluene, trichloroethylene, vinyl chloride and xylene. The method is accurate (mean accuracy for spiked matrix ranged from 84 to104%), sensitive (limit of detection ranged from 0.5 to 20ngmL−1) and precise (the relative standard deviations ranged from 2.5 to 11%). We applied this method to urine samples collected from 1203 non-smokers and 347 smokers and demonstrated that smokers have significantly elevated levels of tobacco-related biomarkers compared to non-smokers. We found significant (p<0.0001) correlations between serum cotinine and most of the tobacco-related biomarkers measured. These findings confirm that this method can effectively quantify urinary VOC metabolites in a population exposed to volatile organics.

Blood/air distribution of volatile organic compounds (VOCs) in a nationally representative sample

Volatile organic compounds (VOCs) in human blood are an effective biomarker of environmental exposure and are closely linked to health outcomes. Unlike VOC concentrations in air, which are routinely collected, blood VOC data are not as readily available. This study aims to develop the quantitative relationship between air and blood VOCs by deriving population-based blood/air distribution coefficients (popKs) of ten common VOCs in the general U.S. population. Air and human blood samples were collected from 364 adults aged 20–59years in 1999–2000 National Health and Nutrition Examination Survey (NHANES). Determinants of popKs were identified using weighted multivariate regression models. In the non-smoking population, median popKs ranged from 3.1 to 77.3, comparable to values obtained in the laboratory. PopKs decreased with increasing airborne VOC concentrations. Smoking elevated popKs by 1.5–3.5 times for aromatic compounds, but did not affect the popKs for methyl tert-butyl ether (MTBE) or chlorinated compounds. Drinking water concentration was a modifier of MTBE's popK. Age, gender, body composition, nor ethnicity affected popKs. PopKs were predictable using linear models with air concentration as the independent variable for both adults and children. This is the first study to estimate blood/air distribution coefficients using simultaneous environmental and biological monitoring on a national population sample. This study was also the first to determine the blood/air distribution coefficient of p-dichlorobenzene, a compound frequently found in indoor environments. These results have applications in exposure assessment, pharmacokinetic analysis, physiologically-based pharmacokinetic (PBPK) modeling, and uncertainty analysis.

Headspace In-Tube Extraction Gas Chromatography-Mass Spectrometry for the Analysis of Hydroxylic Methyl-Derivatized and Volatile Organic Compounds in Blood and Urine

A novel headspace in-tube extraction gas chromatography-mass spectrometry (ITEX-GC-MS) approach was developed for broad-scale analysis of low molecular weight organic compounds in blood and/or urine. One sample was analyzed following in-vial derivatization with dimethyl sulfate for ethylene glycol (EG), glycolic acid (GA), formic acid (FA), other hydroxylic compounds, and another sample for underivatized volatile organic compounds. Tenax adsorbent resin was used in the microtrap, and a porous layer, open tubular GC capillary column was used for separation. MS was operated in the full-scan mode, identification was based on the Automated Mass Spectral Deconvolution and Identification System, and quantification was based on extracted ions. The limits of quantification for EG, GA, and FA in blood were 10, 50, and 30 mg/L, respectively, and the expanded uncertainties of measurement were 20%, 16%, and 14%, respectively. The procedure allowed for the first time the inclusion of EG and GA as their methyl derivatives within a quantitative HS analysis. The ITEX method described here was more sensitive for analysis of volatile organic compounds than the corresponding static headspace analysis as demonstrated for 11 representative compounds.

Unmetabolized VOCs in urine as biomarkers of low level occupational exposure

To compare the usefulness of determining unchanged forms of volatile organic compounds (VOCs), namely toluene (TOL), ethylbenzene (EB) and xylene (XYL), in urine with the effectiveness of the already used biomarkers of occupational exposure. Surveys were conducted in two workplaces (paint factory and footwear factory). In total, 65 subjects participated in the study. Air samples were collected using individual samplers during work shift. Urine and blood samples were collected at the end of work shift. Urine samples were analyzed for unchanged compounds and selected metabolites, while blood samples were tested for unchanged compounds. VOCs in blood and urine were determined by solid phase microextraction gas chromatography (SPME-GC-MS). In the paint factory, the geometric mean (GM) concentrations of VOCs in the air ranged as follows: 0.2-4.7 mg/m(3) for TOL, 0.4-40.9 mg/m(3) for EB and 0.1-122.6 mg/m(3) for XYL. In the footwear factory, the GM concentration of TOL in the air amounted to 105.4 mg/m(3). A significant correlation (p < 0.05) was observed between VOCs in blood, urine and air. The regression analyses performed for paint factory workers showed that TOL-U and TOL-B were better biomarkers of exposure (r = 0.72 and r = 0.81) than benzoic acid (r = 0.12) or o-cresol (r = 0.55). The findings of the study point out that the concentration of unchanged VOCs in urine can be a reliable biological indicator of low level occupational exposure to these compounds.

Mass spectrometric investigations to obtain the first direct comparisons of endogenous breath and blood volatile organic compound concentrations in healthy volunteers

Volatile organic compounds (VOCs) in breath could be clinically useful for the early detection and diagnosis of diseases, physiological disorders and therapeutic monitoring. However, it is crucial to compare the reliability and precision of breath measurements with those from blood if endogenous VOCs on breath are to be used as biomarkers. Few studies have been undertaken to investigate this, none of which relate to endogenous VOCs in freely breathing subjects. Here we establish the reliability and precision of breath measurements to determine endogenous VOC concentrations in comparison to blood measurements in order to assess the viability of using breath measurements for potential diagnostic and screening purposes. Acetone and isoprene concentration levels in the breath, radial arterial blood and peripheral venous blood and in vivo arterial blood/breath ratios for freely breathing subjects have been determined using mass spectrometric techniques. Mean (range) breath concentrations in parts per billion by volume are 1090 (515–2335) for acetone and 465 (308–702) for isoprene. The mean (range) blood concentrations are: for acetone in radial arterial blood 26 (10–73) μmol/l and in peripheral venous blood 18 (9–39) μmol/l; for isoprene in radial arterial blood 6.8 (3.7–11) μmol/l and in peripheral venous blood 14 (5.5–30) μmol/l. Arterial blood/breath ratios mean (range) are 580 (320–860) for acetone and 0.38 (0.19–0.58) for isoprene. An important finding is that the coefficients of repeatability as a percentage of mean are less than 30% in breath but greater than 70% in blood. This study suggests that breath VOC measurements could provide a more consistent measure for investigating underlying physiological function or pathology than single blood measurements.

Relationships between levels of volatile organic compounds in air and blood from the general population

The relationships between levels of volatile organic compounds (VOCs) in blood and air have not been well characterized in the general population where exposure concentrations are generally at parts per billion levels. This study investigates relationships between the levels of nine VOCs, namely, benzene, chloroform, 1,4-dichlorobenzene, ethylbenzene, methyl tert-butyl ether (MTBE), tetrachloroethene, toluene, and m-/p- and o-xylene, in blood and air from a stratified random sample of the general US population. We used data collected from 354 participants, including 89 smokers and 265 nonsmokers, aged 20-59 years, who provided samples of blood and air in the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Demographic and physiological characteristics were obtained from self-reported information; smoking status was determined from levels of serum cotinine. Multiple linear regression models were used to investigate the relationships between VOC levels in air and blood, while adjusting for effects of smoking and demographic factors. Although levels of VOCs in blood were positively correlated with the corresponding air levels, the strength of association (R(2)) varied from 0.02 (ethylbenzene) to 0.68 (1,4-DCB). Also the blood-air relationships of benzene, toluene, ethylbenzene, and the xylenes (BTEX) were influenced by smoking, exposure-smoking interactions, and by gender, age, and BMI, whereas those of the other VOCs were not. Interestingly, the particular exposure-smoking interaction for benzene was different from those for toluene, ethylbenzene, and the xylenes. Whereas smokers retained more benzene in their blood at increasing exposure levels, they retained less toluene, ethylbenzene, and xylenes at increasing exposure levels. Investigators should consider interaction effects of exposure levels and smoking when exploring the blood-air relationships of the BTEX compounds in the general population.