Establishment of a headspace-thermal desorption and gas chromatography-mass spectrometry method (HS-TD-GC-MS) for simultaneous detection of 51 volatile organic compounds in human urine: Application in occupational exposure assessment.

Volatile organic compounds (VOCs) are a group of ubiquitous environment pollutants especially released into the workplace. Assessment of VOCs exposure in occupational populations is therefore a crucial issue for occupational health. However, simultaneous biomonitoring of a variety of VOCs is less studied. In this study, a simple and sensitive method was developed for the simultaneous determination of 51 prototype VOCs in urine by headspace-thermal desorption coupled to gas chromatography-mass spectrometry (HS-TD-GC-MS). The urinary sample was pretreated with only adding 0.50 g of sodium chloride to 2 mL of urine and 51 VOCs should be determined with limits of detection (LODs) between 13.6 ng/L and 24.5 ng/L. The method linearity ranged from 0.005 to 10 µg/L with correlation coefficients (r) of 0.991 to 0.999. The precision for intraday and inter-day, measured by the variation coefficient (CV) at three levels of concentration, was below 15 %, except for 4-isopropyl toluene, dichloromethane, and trichloromethane at low concentration. For medium and high levels, recoveries of all target VOCs were within the standard range, but 1,1-dichloropropene and styrene, which were slightly under 80 % at low levels. In addition, the proposed method has been used to determine urine samples collected in three times (before, during and after working) from 152 workers at four different factories. 41 types of prototype VOCs were detected in workers urine. Significant differences (Kruskal-Wallis chi-squared = 117.18, df = 1, P < 0.05) in the concentration levels of VOCs between the exposed and unexposed groups were observed, but not between the three sampling times (Kruskal-Wallis chi-squared = 3.39, df = 2, P = 0.183). The present study provides an alternative method for biomonitoring and assessing mixed exposures to VOCs in occupational populations.

Assessment of the absorbed dose after exposure to surgical smoke in an operating room.

Surgical smoke produced by electrosurgery contains various chemical substances such as volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). The aim of this study is to investigate airborne concentrations of VOCs and PAHs during electrosurgery in an operating room, in relation to metabolites in urine in order to assess the absorbed dose. A 5-day exposure study was set up in a general surgery operation room including surgeons, scrub assistants and circulation nurses (n = 15). Stationary and personal air sampling for VOCs and PAHs were carried out. Pre-, mid- and end-shift analysis of urinary S-phenylmercapturic acid (SPMA), o-cresol, mandelic acid and 1-hydroxypyrene was performed to assess the internal exposure to respectively benzene, toluene, styrene and PAHs. Several VOCs (styrene, ethyl benzene, benzene and toluene), ranging from 0.7 to 3.27 µg/m3 were detected in the air samples, along with one PAH (naphthalene, ranging from 0.012 to 0.39 µg/m3). There was no significant correlation between air monitoring and urinary biomonitoring. O-cresol levels were increased, especially among assistants and nurses at mid- and end-shift, exceeding current biological exposure indices several times. External and internal exposure for assistants and nurses was substantially more, compared to surgeons. This study confirms the presence of VOCs and PAHs in surgical smoke and shows the presence of their metabolites in urine, but the association is unclear. Urinary biomonitoring shows especially high concentrations of o-cresol.

Urine as a biological modality for colorectal cancer detection.

Introduction: The increasing incidence of colorectal cancer (CRC) in young adults warrants early and preferably noninvasive diagnostic modalities. Although the current stool-based assays have had good performance indicators for CRC detection, the overall poor uptake remains a challenging issue. However, alternative blood and urine markers are emerging.Areas covered: This paper discusses the various urinary biomarkers available for the detection of CRC. The more commonly encountered drawbacks are the small number of studies and the size of the study population. We discuss the role of microRNA and ProstaglandinE2 in CRC detection. The emergence of new, low-cost technologies, specifically in the detection of volatile organic compounds (VOCs), presents a promising future. We postulate possible mechanisms for the origin of these VOCs in urine and their role in carcinogenesis.Expert opinion: Urinary biomarkers provide an alternative option to the stool-based screening tests. MicroRNA and ProstaglandinE2 have shown utility in CRC detection. Evidence so far suggests that VOCs could also be a potential biomarker for the detection of CRC. In addition to its interaction within the colon lumen, this altered 'VOC signature' might also play a role in carcinogenesis. Low-cost technology may enable such diagnostic methods to be utilized at the point of care.

Biomarkers of Exposure among Adult Smokeless Tobacco Users in the Population Assessment of Tobacco and Health Study (Wave 1, 2013-2014).

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.

Simultaneous Assessment of Urinary and Fecal Volatile Organic Compound Analysis in De Novo Pediatric IBD.

Endoscopic evaluation is mandatory in establishing the diagnosis of pediatric inflammatory bowel disease (IBD), but unfortunately carries a high burden on patients. Volatile organic compounds (VOC) have been proposed as alternative, noninvasive diagnostic biomarkers for IBD. The current study aimed to assess and compare the potential of fecal and urinary VOC as diagnostic biomarkers for pediatric IBD in an intention-to-diagnose cohort. In this cohort study, patients aged 4-17 years, referred to the outpatient clinic of a tertiary referral center under suspicion of IBD, were eligible to participate. The diagnosis was established by endoscopic and histopathologic assessment, participants who did not meet the criteria of IBD were allocated to the control group. Participants were instructed to concurrently collect a fecal and urinary sample prior to bowel lavage. Samples were analyzed by means of gas chromatography-ion mobility spectrometry. In total, five ulcerative colitis patients, five Crohn's disease patients, and ten age and gender matched controls were included. A significant difference was demonstrated for both fecal (p-value, area under the curve; 0.038, 0.73) and urinary (0.028, 0.78) VOC profiles between IBD and controls. Analysis of both fecal and urinary VOC behold equal potential as noninvasive biomarkers for pediatric IBD diagnosis.

Assessment of urinary volatile compounds and proteins in the female goat Capra hircus: A pilot study to reveal potential indicators of oestrus.

Urine samples of female goats in pro-oestrus, oestrus and post-oestrus phases were analysed for finding oestrus-specific volatile compounds using gas chromatograph-mass spectrometry (GC-MS), and proteins using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). Fourteen urinary volatile were identified covering all three phases among which four compounds, 1-Tetradecanol, n-Pentadecanol, 3-Methylene tridecane and 2-Ethyl-1-dodecene, were unique to oestrus. Also, oestrus urine contained a 25 kDa protein, which was totally absent in pro-oestrus urine, and less-expressed in post-oestrus urine. This protein revealed to be complement C3 fragment. This pilot study, for the first time, reveals the difference in urinary volatile compounds and proteins in the female goat during the different phases of oestrous cycle. The four unique volatile compounds and a 25 kDa protein that appeared as oestrus-specific in this study warrant further investigation to consider them as urinary biomarkers of oestrus in goats.

Biomonitoring-based exposure assessment of benzene, toluene, ethylbenzene and xylene among workers at petroleum distribution facilities.

Elevated emissions of volatile organic compounds, including benzene, toluene, ethylbenzene, and o, p, and m-xylenes (BTEX), are an occupational health concern at oil transfer stations. This exploratory study investigated personal exposure to BTEX through environmental air and urine samples collected from 50 male workers at a major oil distribution company in Iran. Airborne BTEX exposures were evaluated over 8h periods during work-shift by using personal passive samplers. Urinary BTEX levels were determined using solid-phase microextraction with gas chromatography mass spectrometry for separation and detection. Mean exposure to ambient concentrations of benzene differed by workers' job type: tanker loading workers (5390µg/m3), tank-gauging workers (830µg/m3), drivers (81.9µg/m3), firefighters (71.2µg/m3) and office workers (19.8µg/m3). Exposure across job type was similarly stratified across all personal exposures to BTEX measured in air samples with maximum concentrations found for tanker loading workers. Average exposures concentrations of BTEX measured in urine were 11.83 ppb benzene, 1.87 ppb toluene, 0.43 ppb ethylebenzene, and 3.76 ppb xylene. Personal air exposure to benzene was found to be positively associated with benzene concentrations measured in urine; however, a relationship was not observed to the other BTEX compounds. Urinary exposure profiles are a potentially useful, noninvasive, and rapid method for assessing exposure to benzene in a developing and relatively remote production region.

Assessment of Exposure to VOCs among Pregnant Women in the National Children's Study.

Epidemiologic studies can measure exposure to volatile organic compounds (VOCs) using environmental samples, biomarkers, questionnaires, or observations. These different exposure assessment approaches each have advantages and disadvantages; thus, evaluating relationships is an important consideration. In the National Children's Vanguard Study from 2009 to 2010, participants completed questionnaires and data collectors observed VOC exposure sources and collected urine samples from 488 third trimester pregnant women at in-person study visits. From urine, we simultaneously quantified 28 VOC metabolites of exposure to 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 exposures using ultra high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS) method. Urinary thiocyanate was measured using an ion chromatography coupled with an electrospray ionization tandem mass spectrometry method (IC-ESI/MSMS). We modeled the relationship between urinary VOC metabolite concentrations and sources of VOC exposure. Sources of exposure were assessed by participant report via questionnaire (use of air fresheners, aerosols, paint or varnish, organic solvents, and passive/active smoking) and by observations by a trained data collector (presence of scented products in homes). We found several significant (p < 0.01) relationships between the urinary metabolites of VOCs and sources of VOC exposure. Smoking was positively associated with metabolites of the tobacco constituents acrolein, acrylamide, acrylonitrile, 1,3-butadiene, crotonaldehyde, cyanide, ethylene oxide, N,N-dimethylformamide, propylene oxide, styrene, and xylene. Study location was negatively associated with the toluene metabolite N-acetyl-S-(benzyl)-L-cysteine (BMA), and paint use was positively associated with the xylene metabolites 2-methylhippuric acid (2MHA) and 3-Methylhippuric acid & 4-methylhippuric acid (3MHA + 4MHA). A near-significant (p = 0.06) relationship was observed between acrylamide metabolites and observation of incense.

Analysis of Airborne Biomarkers for Point-of-Care Diagnostics.

Treatable diseases continue to exact a heavy burden worldwide despite powerful advances in treatment. Diagnostics play crucial roles in the detection, management, and ultimate prevention of these diseases by guiding the allocation of precious medical resources. Motivated by globalization and evolving disease, and enabled by advances in molecular pathology, the scientific community has produced an explosion of research on miniaturized integrated biosensor platforms for disease detection. Low-cost, automated tests promise accessibility in low-resource settings by loosening constraints around infrastructure and usability. To address the challenges raised by invasive and intrusive sample collection, researchers are exploring alternative biomarkers in various specimens. Specifically, patient-generated airborne biomarkers suit minimally invasive collection and automated analysis. Disease biomarkers are known to exist in aerosols and volatile compounds in breath, odor, and headspace, media that can be exploited for field-ready diagnostics. This article reviews global disease priorities and the characteristics of low-resource settings. It surveys existing technologies for the analysis of bioaerosols and volatile organic compounds, and emerging technologies that could enable their translation to the point of care. Engineering advances promise to enable appropriate diagnostics by detecting chemical and microbial markers. Nonetheless, further innovation and cost reduction are needed for these technologies to broadly affect global health.

Mouse urinary biomarkers provide signatures of maturation, diet, stress level, and diurnal rhythm.

Body fluids such as urine potentially contain a wealth of information pertaining to age, sex, social and reproductive status, physiologic state, and genotype of the donor. To explore whether urine could encode information regarding environment, physiology, and development, we compared the volatile compositions of mouse urine using solid-phase microextraction and gas chromatography-mass spectrometry (SPME-GC/MS). Specifically, we identified volatile organic compounds (VOCs) in individual urine samples taken from inbred C57BL/6J-H-2(b) mice under several experimental conditions-maturation state, diet, stress, and diurnal rhythms, designed to mimic natural variations. Approximately 1000 peaks (i.e., variables) were identified per comparison and of these many were identified as potential differential biomarkers. Consistent with previous findings, we found groups of compounds that vary significantly and consistently rather than a single unique compound to provide a robust signature. We identified over 49 new predictive compounds, in addition to identifying several published compounds, for maturation state, diet, stress, and time-of-day. We found a considerable degree of overlap in the chemicals identified as (potential) biomarkers for each comparison. Chemometric methods indicate that the strong group-related patterns in VOCs provide sufficient information to identify several parameters of natural variations in this strain of mice including their maturation state, stress level, and diet.