Using biomonitoring as a complementary approach in BTEX exposure assessment in the general population and occupational settings: a systematic review and meta-analysis.

Hazardous organic compounds such as benzene, toluene, ethylbenzene, o-xylene, m-xylene, and p-xylene (known as BTEX) found at work and at home can cause adverse health effects of human beings throughout their lives. Biological monitoring, an exposure assessment method, considers all exposed organic and non-organic compounds. Our goal was to perform a systematic review and a statistical analysis (meta-analysis) of peer-reviewed publications to assess urinary concentrations of BTEX biomarkers in both occupationally-exposed population and the general population. Several major electronic databases, including Scopus, Embase, Medline, Web of Science, and Google scholar (grey literature), were searched for biomonitoring studies of BTEX. Overall, 33 studies met the eligible criteria for the systematic review and six met the full inclusion criteria for meta-analysis. For meta-analysis, we included studies in which unmetabolized BTEX compounds were measured in urine samples. Due to insufficient data, studies that measured BTEX metabolites in urine samples and unmetabolized BTEX compounds in blood samples were excluded from the meta-analysis but were analyzed in the qualitative synthesis. Most studies showed increased urinary concentrations of BTEX in exposed individuals (mainly workers) compared to unexposed individuals. The results showed that the highest total BTEX concentrations were recorded in painters and policemen. This study showed that the undoubted associations between lifestyle and environmental factors and urinary levels of BTEX or its metabolites have not yet been confirmed in current biomonitoring studies. This is attributed to the few studies reported in this research area, the lack of homogeneous information, and the disagreement in the published results of the studies.

Urinary concentrations of BTEX in waterpipe smokers and nonsmokers: Investigating the influence of conventional activities and multiple factors.

The aim of this study was to compare the concentrations of the benzene, toluene, ethylbenzene, and xylene (BTEX) compounds in the urine of smokers and the control group considering the role of age, weight, job, history of waterpipe and cigarette smoking, and driving time. The chemicals in the urine of 99 smokers and 31 nonsmokers were extracted by liquid-liquid extraction method and their concentrations were measured by liquid injection GC/MS. The mean concentration of benzene, toluene, ethylbenzene, m-xylene, o-xylene, p-xylene, and total BTEX in waterpipe smokers were found to be 471.40, 670.90, 127.91, 167.64, 90.62, 46.04, and 1574.50 ng/g. creatinine, respectively. For the waterpipe&cigarette smokers, the concentration of the compounds were 708.00, 959.00, 146.40, 192.50, 93.30, 53.07, and 2152.00 ng/g.creatinine, respectively. For nonsmokers the concentrations of these compounds were 88.12, 140.40, 36.68, 57.29, 31.53, 26.21, and 380.30 ng/g.creatinine, respectively. Driving time, waterpipe smoking and cigarette smoking were positively associated with BTEX concentration (p < 0.05). Fruity tobacco showed higher concentrations of BTEX compared to the regular tobacco, and athlete persons had les urinary BTEX than the non-athletes. There was not significant correlation between the BTEX and age, height, weight, and BMI. High concentrations of BTEX compounds in the urine of waterpipe and cigarette smokers compared to nonsmokers indicate that waterpipe and cigarette can be an important source of exposure to these compounds and the known adverse effects of these compounds, especially carcinogenicity, threaten the health of smokers.

Impact of heat on biological concentrations of toluene and acetone resulting from exposure by inhalation: A pilot study.

Climatic conditions raise new concerns about the potential impact of heat on the absorption and kinetics of certain chemicals. The impact of 3 temperatures (21, 25 and 30 °C WBGT) on the toxicokinetics of toluene and acetone was therefore evaluated in five human subjects during controlled exposures in an inhalation chamber. Biological samples were collected and analyzed by GC-MS/MS. Increases between 4 and 85 % were observed for solvents concentrations in blood (30 vs 21 °C) while decreases in urine samples for acetone and o-cresol were measured at the end of the exposure period (4 h). Mean blood concentrations at 4 h are well correlated with temperature. Results suggest an increased absorption and/or a decreased elimination of volatile chemicals in the presence of heat. Higher increases of blood chemical concentrations were observed in heavier individuals. Further studies should include physiologically based toxicokinetic models to help in better understanding the mechanisms involved and their respective contribution.

Deep eutectic solvent functionalized graphene oxide composite adsorbent for miniaturized pipette-tip solid-phase extraction of toluene and xylene exposure biomarkers in urine prior to their determination with HPLC-UV.

A deep eutectic solvent functionalized graphene oxide composite adsorbent (DFG) was synthesized through reversible-addition fragmentation chain-transfer polymerization. The synthesized DFG had multiple adsorption interactions after covalent modification with a deep eutectic solvent (allyltriethylammonium bromide/ethylene glycol). Adsorption isotherms and kinetics studies of DFG indicate that the adsorption of hippuric acid (HA) and methylhippuric acid (MHA) was monolayer chemical adsorption. The comparison of DFG with commercial adsorbents demonstrates that the adsorption ability of DFG was superior. This was due to the multiple adsorption interactions of DFG for the three analytes (mainly π-interaction, hydrogen bonding, electrostatic adsorption, and hydrophobic interaction). The DFG adsorbent was applied to miniaturized pipette-tip solid-phase extraction (MPT-SPE), followed by high-performance liquid chromatography (HPLC) to determine biomarkers in urine for toluene and xylene exposure. The DFG-MPT-SPE-HPLC method required only 2.00 mg of DFG as adsorbent, 0.50 mL of washing solvent, and 0.40 mL of elution solvent to achieve a wide linear range (0.200-200 µg mL-1), high recoveries (90.9-99.1%), and high precision (RSD ≤ 6.3%). The proposed method was applied to determine HA and MHA in urine samples from occupational workers. Graphical abstract Deep eutectic solvent functionalized graphene oxide composite adsorbent for miniaturized pipette-tip solid-phase extraction of toluene and xylene exposure biomarkers in urine prior to their determination with HPLC-UV.

[Simultaneous determination for metabolites of benzene compounds in urine by high performance liquid chromatography].

Objective: To describe for the determination of contents of metabolites of benzene compounds in urine sample by high performance liquid chromatography. Methods: After acidification with hydrochloric acid, metabolites in urine were first extracted by acetonitrile and isopropanol (V∶V, 9∶1) with excessive sodium chloride, then gradient separated on a C18 column and then determined by DAD detector. Results: There were good linear relationship between peak areas and injection quality in range of 2.00-100 mg/L (r>0.999). The detection limit and quantitative limit of this method were 4.15-70.7 µg/L and 13.8-235 µg/L respectively. The precision for the analysis of urine was1.78%-8.23% (n =6). The average recovery of metabolites was 85.4%-105.5% at thee spiked levels in the range of 2.00-100 mg/L. Conclusion: The accuracy and reproducibility obtained make this method useful for the biological monitoring of occupational exposure to toluene, xylene, styrene and ethylbenzene.

[Determination of seven urinary metabolites of benzene, toluene and xylene by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry].

Objective: To develop a method using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry to determine the urinary metabolites of benzene, toluene and xylene. The selected metabolites are S-phenylmercapturic acid (S-PMA) , trans, trans-muconic acid (t, t-MA) , 8-hydroxy-2 deoxyguanosine (8-OHdG) , hippuric acid (HA) , 2-methylhippuric acid (2-MHA) , 3-methylhippuric acid (3-MHA) and 4-methylhippuric acid (4-MHA) . Methods: The urine sample was pretreated using methanol to precipitate the proteins. HSS T3 chromatographic column was used to separate the metabolites. The mass spectrometric acquisition was carried out using multiple reaction monitoring (MRM) after ionization with ESI source. External standard method was used for quantification. Results: All the standard curves showed good linear relation, and r of the seven metabolites was all above 0.999. The detection limits and quantitative limits of the seven metabolites were 0.01-500 ng/ml and 0.02-1 000 ng/ml (based on the actual dilution ratio) , respectively. The average spiked recoveries of four loadings ranged from 85.8% to 109.9%. The intra-day and inter-day precisions were 0.2%-4.5% and 0.6%-9.5%, respectively. The samples can be kept for at least 14 days at both 4 ℃ and -20 ℃. Conclusion: This method is simple, rapid and highly sensitive with low cost, and its accuracy, precision and stability can meet the daily test requirements. It can be applied for the determination of urinary S-PMA, t, t-MA, 8-OHdG, HA, 2-MHA, 3-MHA and 4-MHA for the occupational population exposed to benzene, toluene and xylene.

Simultaneous determination of 15 BTEX hydroxyl biomarkers in urine by headspace solid-phase microextraction gas chromatography-mass spectrometry.

Benzene (B), toluene (T), ethylbenzene (E), o-, m- and p-xylene (o-, m-, p-X) are ubiquitous and frequently exposed to human throughout the environment. Previously published test methods for phenolic biomarkers are not sensitive enough to be detected in most general population groups and require a lot of labor. A simple and convenient headspace solid-phase microextraction (HS-SPME) gas chromatography-mass spectrometry method was described for the simultaneous determination of 15 hydroxyl biomarkers of BTEX in urine. Hydroxyl biomarkers in urine were vaporized and adsorbed onto a selected fiber after enzyme hydrolysis with ß-glucuronidase/arylsulfatase. The optimal HS-SPME conditions were achieved with an 85-µm-carboxen-polydimethylsiloxane fiber, an extraction temperature of 70 °C, a heating time of 30 min, and a pH of 4.0. The desorption was performed for 1 min at 250 °C. Under the established conditions, the lowest limits of detection were from 0.02 to 0.15 µg/L in 5.0 mL of urine, and the intra- and inter-day relative standard deviations were less than 12.7% at 0.5, 2.0, 50, and 200 µg/L. The calibration curve demonstrated good linearity with greater than r2 = 0.99 in synthetic urine. This method is convenient, simple, environmentally friendly, and amenable to automation.

Direct methyl esterification with 2,2-dimethoxypropane for the simultaneous determination of urinary metabolites of toluene, xylene, styrene, and ethylbenzene by gas chromatography-mass spectrometry.

OBJECTIVES: The purpose of this study was to develop a simple and accurate gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of four urinary metabolites from four organic solvents, that is, hippuric acid (HA) from toluene, methylhippuric acid (MHA) from xylene, and mandelic acid (MA) and phenylglyoxylic acid (PGA) from styrene or ethylbenzene for biological monitoring. METHODS: The four metabolites were directly methyl-esterified with 2,2-dimethoxypropane and analyzed using GC-MS. The proposed method was validated according to the US Food and Drug Administration guidance. The accuracy of the proposed method was confirmed by analyzing a ClinChek® -Control for occupational medicine (RECIPE Chemicals +Instruments GmbH). RESULTS: Calibration curves showed linearity in the concentration range of 10-1000 mg/L for each metabolite, with correlation coefficients >0.999. For each metabolite, the limits of detection and quantification were 3 mg/L and 10 mg/L, respectively. The recovery was 93%-117%, intraday accuracy, expressed as the deviation from the nominal value, was 92.7%-103.0%, and intraday precision, expressed as the relative standard deviation (RSD), was 1.3%-4.7%. Interday accuracy and precision were 93.4%-104.0% and 1.2%-9.5%, respectively. The analytical values of ClinChek obtained using the proposed method were sufficiently accurate. CONCLUSIONS: The proposed method is a simple and accurate which is suitable for routine analyses that could be used for biological monitoring of occupational exposure to four organic solvents.

Lifestyle and occupational factors affecting exposure to BTEX in municipal solid waste composting facility workers.

Composting facilities workers are potentially exposed to different volatile organic compounds (VOCs). This study aims to investigate the potential exposure to benzene, toluene, ethylbenzene and xylenes (BTEX) compounds among workers of composting facilities by measuring un-metabolized BTEX in urine and to investigate the effect that several lifestyle factors (i.e. smoking and residential traffic), using personal protective equipment, and religious practices such as Ramadan fasting can have on the urinary BTEX concentrations. We assessed concentrations of BTEX in the urine of a composting facility workers. Samples were collected in May 2018. Overall, 25 workers chosen as the exposed group and 20 inhabitants living close to the composting facility as a control group. The urine samples were collected from studied subjects. Identification and quantification of un-metabolized BTEX was performed using a headspace gas chromatography-mass spectrometry (GC-MS). Detailed information of participants was gathered by a comprehensive questionnaire. The geometric mean levels of urinary benzene, toluene, ethylbenzene, m­p xylene, and o­xylene in the exposed subjects were 1.27, 2.12, 0.54, 1.22 and 1.51 µg/L, respectively; 1.4 to 3.7-time higher than values in control group (p < 0.05). Post-shift levels were significantly higher than pre-shift for all chemicals (p < 0.05). Smoking habits, exposure to environmental tobacco smoke, and Ramadan fasting predicted urinary BTEX levels. Personal protective equipment which included a simple N95 mask did not protected workers from BTEX emissions. Composting facilities represent a significant source BTEX emissions and exposure for staff. More effective protective strategies are required to minimize exposure and related occupational hazards.

Niveles urinarios de ácido trans, trans mucónico y orto cresol en una población infanto-juvenil residente en Ciudad Autónoma de Buenos Aires y Conurbano Bonaerense / Urinary levels of trans, trans muconic and ortho cresol in an infant-juvenile population resident in the Autonomous City of Buenos Aires and the Conurbano of Buenos Aires

Introducción: la exposición crónica al benceno y tolueno produce alteraciones sobre la médula ósea y el sistema nervioso central, entre otros. En orina, el ácido trans, trans mucónico (t, t-MA) es uno de los biomarcadores de exposición al benceno y el o-cresol (oCre) al tolueno. Objetivo: analizar los resultados de los niveles de t, t-MA y oCre urinarios en una población infanto-juvenil residente en Ciudad Autónoma de Buenos Aires y Conurbano Bonaerense potencialmente expuesta a benceno y tolueno ambiental. Materiales y métodos: se realizó un estudio retrospectivo de los resultados de t, t-MA y oCre urinarios. Las muestras de orina ingresaron al laboratorio con solicitud de t, t-MA (n=1519) y oCre (n=1447) durante el período 2011-2017 (rango etario entre 0 a 19 años). El t, t-MA se cuantificó por UFLC con detector de arreglo de diodos y el oCre por CG con detector de ionización por llama. Resultados: la edad promedio de los pacientes fue de 4,8 años y la mediana 4,6 años.Las concentraciones de t, t-MA urinario fueron: menor de 50 μg/l (44,8%); entre 50-500 μg/l (52,1%) y mayores de 500 μg/l (3,1%). Expresadas por gramo de creatinina: entre 15-163 μg/g creatinina (60,4%) y mayores de 163 μg/g creatinina (39,6%). El límite de cuantificación de t, t-MA fue de 50 μg/l. Las concentraciones de oCre urinario fueron: menor de 0,20 mg/l (97,7%) y entre 0,20-0,50 mg/l (2,3%) y mayor de 0,50 mg/l (0%). Expresadas por gramo de creatinina: menor de 0,30 mg/g creatinina en el 0,8% y mayores de 0,30 mg/g creatinina en el 1,5%. El límite de cuantificación de oCre fue de 0,20 mg/l. Conclusiones: los resultados del trabajo podrían indicar una contaminación ambiental persistente, en especial en el Conurbano Bonaerense, donde debería continuarse el monitoreo de algunas zonas. Pero, por otro lado, es de vital importancia tener en cuenta los factores de confusión, tales como la dieta, la exposición al humo de tabaco ambiental (fumador pasivo) y la tasa de excreción renal que llevarían a una sobre-estimación de los resultados y a una incorrecta toma de decisiones.

Introduction: Chronic exposure to benzene and toluene produces alterations in the bone marrow and the central nervous system, among other effects. In urine, trans, trans muconic acid (t, t-MA) is one of the biomarkers of exposure to benzene and o-cresol (oCre), to toluene. Objective: To analyze the results of urinary t, t-MA and oCre levels in an infant-juvenile population resident in the Autonomous City of Buenos Aires and the Conurbano Bonaerense, potentially exposed to environmental benzene and toluene. Materials and methods: A retrospective study of urinary t, t-MA and oCre results was performed. The urine samples entered the laboratory with the request of t, t-MA (n = 1519) and oCre (n = 1447) during the period 2011- 2017. The age range of the population was between 0 and 19 years. The t, t-MA was quantified by UFLC with diode array detector and the oCre by GC with flame ionization detector. Results: The average age of the patients was 4.8 years and the median age was 4.6 years. The urinary concentrations of t, t-MA were: below 50 μg/l (44.8%); between 50-500 μg/l (52.1%) and above 500 μg/l (3.1%). Expressed per gram of creatinine: between 15-163 μg/g creatinine (60.4%) and greater 163 μg/g creatinine (39.6%). The limit of quantification of t, t-MA was 50 μg/l. The urinary oCre concentrations were: less than 0.20 mg/l (97.7%) and between 0.20-0.50 mg/l (2.3%). Expressed per gram of creatinine: less than 0.30 mg/g creatinine in 0.8% and greater than 0.30 mg/g creatinine in 1.5%. The limit of quantification of oCre was 0.20mg/l. Conclusions: The results of the study could indicate persistent environmental contamination, especially in the Conurbano Bonaerense, where monitoring of some areas should be continued. However, it is of vital importance to take into account the confounding factors, such as diet, exposure to environmental tobacco smoke (passive smoking) and the rate of renal excretion, which would lead to an over-estimation of the results and to incorrect decision-making.

Urinary metabolites of volatile organic compounds of infants in the neonatal intensive care unit.

BackgroundPreterm infants (PTI) in the NICU are often placed in incubators that may increase their exposure to volatile organic chemicals (VOCs). To determine whether PTI in incubators have higher urinary concentrations of VOC metabolites compared with infants in cribs.MethodsUrine from 40 PTI in incubators and 40 infants in cribs was collected and analyzed for 28 urinary VOC biomarkers. Differences in metabolite concentrations between the two groups were compared.ResultsTwenty two of the VOC metabolites were detected in at least one urine sample. All urine samples tested had measurable levels of six VOC metabolites. Biomarkers for acrolein, acrylonitrile, carbon disulfide, cyanide, N-dimethylformamide, ethylbenzene, ethylene oxide, propylene oxide, styrene, toluene/benzyl alcohol, vinyl chloride, and xylene were higher in the incubator group. The geometric means of five VOC metabolites were 2-fold higher than those reported for NHANES children 6-11 years of age in one or both of the groups with benzyl mercapturic acid being 7-fold and 12-fold greater than NHANES in the crib and incubator group, respectively.ConclusionAll infants were exposed to VOCs. PTI in incubators have a different VOC exposure profile compared with infants in cribs. The health implications associated with these exposures require further study.

Use of urinary biomarkers to characterize occupational exposure to BTEX in healthcare waste autoclave operators.

Urinary benzene, toluene, ethylbenzene, and xylenes (BTEX) can be used as a reliable biomarker of exposure to these pollutants. This study was aimed to investigate the urinary BTEX concentration in operators of healthcare waste (HCW) autoclaves. This cross-sectional study was conducted in selected hospitals in Tehran, Iran between April and June 2017. Twenty operators (as the case group) and twenty control subjects were enrolled in the study. Personal urine samples were collected at the beginning and end of the work shift. Urinary BTEX were measured by a headspace gas chromatography-mass spectrometry (GC/MS). A detailed questionnaire was used to gather information from subjects. Results showed that the median of urinary benzene, toluene, ethylbenzene, m-p xylene, and o-xylene levels in the exposed group were 3.26, 3.36, 0.84, 3.94 and 4.48 µg/L, respectively. With the exception of ethylbenzene, subjects in the exposed group had significantly higher urinary BTEX levels than control group (p < 0.05). Urinary BTEX concentrations in the exposed case group were 2.5-fold higher than in the control group. There was a significant relationship between the amount of generated waste per day and the urinary BTEX in the exposed group. Smoking status and type of autoclave used were also identified as predictors of urinary BTEX concentrations. The healthcare waste treatment autoclaves can be considered as a significant BTEX exposure source for operators working with these treatment facilities. The appropriate personal protection equipment and control measures capable in reducing BTEX exposure should be provided to HCW workers to reduce their exposures to BTEX.

Design of a calix[4]arene-functionalized metal-organic framework probe for highly sensitive and selective monitor of hippuric acid for indexing toluene exposure.

In the present work, a novel metal-organic framework (MOF) fluorescent probe was prepared by post-synthetic modification of MIL-53-NH2(Al) with carboxylatocalix[4]arene (CC[4]A). The introduced CC[4]A could not only enhance the fluorescence performance and the recognition ability of the probe, but also sustain the high stability under UV light and moisture conditions. A method based on the as-synthesized CC[4]A@MIL-53-NH2(Al) probe was established for sensing hippuric acid. The detection limit was determined to be as low as 3.7 µg mL-1. Over the concentration range of 0.005-3 mg mL-1, the calibration curve was obtained with a satisfactory linearity (R2 = 0.993). The method was successfully used for rapid and highly selective direct monitor of hippuric acid in human urine. The sensor had great potential to be used as a simple diagnostic tool for hippuric acid in human urine which is regarded as a biological index of toluene exposure.

Ion-pair-based hollow-fiber liquid-phase microextraction combined with high-performance liquid chromatography for the simultaneous determination of urinary benzene, toluene, and styrene metabolites.

In the current study, a novel technique for extraction and determination of trans,trans-muconic acid, hippuric acid, and mandelic acid was developed by means of ion-pair-based hollow fiber liquid-phase microextraction in the three-phase mode. Important factors affecting the extraction efficiency of the method were investigated and optimized. These metabolites were extracted from 10 mL of the source phase into a supported liquid membrane containing 1-octanol and 10% w/v of Aliquat 336 as the ionic carrier followed by high-performance liquid chromatography analysis. The organic phase immobilized in the pores of a hollow fiber was back-extracted into 24 µL of a solution containing 3.0 mol/L sodium chloride placed inside the lumen of the fiber. A very high preconcentration of 212- to 440-fold, limit of detection of 0.1-7 µg/L, and relative recovery of 87-95% were obtained under the optimized conditions of this method. The relative standard deviation values for within-day and between-day precisions were calculated at 2.9-8.5 and 4.3-11.2%, respectively. The method was successfully applied to urine samples from volunteers at different work environments. The results demonstrated that the method can be used as a sensitive and effective technique for the determination of the metabolites in urine.

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.

Toluene and methylethylketone: effect of combined exposure on their metabolism in rat.

1. Multiple exposures are ubiquitous in industrial environments. In this article, we highlight the risks faced by workers and complete the data available on the metabolic impact of a common mixture: toluene (TOL) and methylethylketone (MEK). 2. Rats were exposed by inhalation under controlled conditions either to each solvent individually, or to mixtures of the two. How the interaction between the two solvents affected their fate in the blood and brain, their main relevant urinary metabolites (o-cresol, benzylmercapturic acid for TOL and 2,3-butanediols for MEK) and their hepatic metabolism were investigated. 3. Although the cytochrome P450 concentration was unchanged, and the activities of CYP1A2 and CYP2E1 isoforms were not additively or synergistically induced by co-exposure, TOL metabolism was inhibited by the presence of MEK (and vice versa). Depending on the relative proportions of each compound in the mixture, this sometimes resulted in a large increase in blood and brain concentrations. Apart from extreme cases (unbalanced mixtures), the amount of o-cresol and benzylmercapturic acid (and to a lesser extent 2,3-butanediols) excreted were proportional to the blood solvent concentrations. 4. In a co-exposure context, ortho-cresol and benzylmercapturic acid can be used as urinary biomarkers in biomonitoring for employees to relatively accurately assess TOL exposure.

Spatial characteristics of urinary BTEX concentrations in the general population.

Benzene, toluene, ethylbenzene, o-, m-, and p-xylenes (BTEX) are ubiquitous outdoor and indoor air pollutants associated with both environmental and health effects. The objective of this exploratory study was to determine the magnitude and variability of urinary BTEX levels among residents of two areas located in the same city (Nicosia, Cyprus). The two areas differed with respect to their proximity to an industrial cluster and an intercity-highway. First morning urine voids were collected during a random campaign from selected households in the two urban areas (n = 48). Urinary BTEX measurements were obtained using headspace solid phase micro extraction coupled with gas chromatography-mass spectrometry. The majority of participants were females (65%) and non-smokers (85%) with a mean age of 49 years. Median urinary BTEX levels were: 118 ng L-1, 124 ng L-1, 9 ng L-1, 29 ng L-1 and 28 ng L-1 for benzene, toluene, ethylbenzene, (p + m)-xylene and o-xylene, respectively. With the exception of benzene, participants from area 2 (closer to the industrial cluster and an intercity road than area 1) had significantly (p < 0.05) higher urinary BTEX levels than those from area 1 (regression analysis). The residence location (in area 2) was the sole significant (p < 0.05) predictor of urinary BTEX levels after adjusting for sex, smoking, age, body mass index, and educational level. This observational study showed differences in BTEX exposures between two urban areas of the same city. This baseline BTEX dataset may prove useful for future activities of natural gas extraction and handling nearby urban settings.

Diazepam influences urinary bioindicator of occupational toluene exposure.

In the present study, we investigated the influence of diazepam (DZP) on the excretion of TOL by examining their urinary metabolites, hippuric acid (HA) and ortho-cresol (o-C). Male Wistar rats were exposed to TOL (20ppm) in a nose-only exposure chamber (6h/day, 5days/week for 6 weeks) with simultaneous administration of DZP (10mg/kg/day). Urinary o-C levels were determined by GC-MS, while HA, creatinine (CR), DZP and its metabolite, nordiazepam, were analysed by HPLC-DAD. The results of a Mann-Whitney U test showed that DZP influenced the urinary excretion of o-C (p<0.05). This pioneering study revealed that there was an interaction between DZP and TOL, probably by the inhibition of the CYP isoforms (CYP2B6, CYP2C8, CYP2E1, and CYP1A2) involved in the oxidative metabolism of the solvent. This is relevant information to be considered in the biomonitoring of occupational toluene exposure.

Evaluation and modeling of the impact of coexposures to VOC mixtures on urinary biomarkers.

CONTEXT: Urinary biomarkers are widely used among biomonitoring studies because of their ease of collection and nonintrusiveness. Chloroform and TEX (i.e., toluene, ethylbenzene, and m-xylene) are chemicals that are often found together because of common use. Although interactions occurring among TEX are well-known, no information exists on possible kinetic interactions between these chemicals and chloroform at the level of parent compound or urinary biomarkers. OBJECTIVE: The objective of this study was therefore to study the possible interactions between these compounds in human volunteers with special emphasis on the potential impact on urinary biomarkers. MATERIALS AND METHODS: Five male volunteers were exposed by inhalation for 6 h to single, binary, and quaternary mixtures that included chloroform. Exhaled air and blood samples were collected and analyzed for parent compound concentrations. Urinary biomarkers (o-cresol, mandelic, and m-methylhippuric acids) were quantified in urine samples. Published PBPK model for chloroform was used, and a Vmax of 3.4 mg/h/kg was optimized to provide a better fit with blood data. Adapted PBPK models from our previous study were used for parent compounds and urinary biomarkers for TEX. RESULTS: Binary exposures with chloroform resulted in no significant interactions. Experimental data for quaternary mixture exposures were well predicted by PBPK models using published description of competitive inhibition among TEX components. However, no significant interactions were observed at levels used in this study. CONCLUSION: PBPK models for urinary biomarkers proved to be a good tool in quantifying exposure to VOC.

Simultaneous determination of benzene, toluene, ethylbenzene, and xylene metabolites in human urine using electromembrane extraction combined with liquid chromatography and tandem mass spectrometry.

For the first time, electromembrane extraction combined with liquid chromatography and tandem mass spectrometry was applied for the determination of urinary benzene, toluene, ethylbenzene, and xylene metabolites. S-Phenylmercapturic acid, hippuric acid, phenylglyoxylic acid, and methylhippuric acid isomers were extracted from human urine through a supported liquid membrane consisting of 1-octanol into an alkaline acceptor solution filling the inside of a hollow fiber by application of an electric field. Various extraction factors were investigated and optimized using response surface methodology, the statistical method. The optimum conditions were established to be 300 V applied voltage, 15 min extraction time, 1500 rpm stirring speed, and 5 mM ammonium acetate (pH 10.2) acceptor solution. The method was validated with respect to selectivity, linearity, accuracy, precision, limit of detection, limit of quantification, recovery, and reproducibility. The results showed good linearity (r(2) > 0.995), precision, and accuracy. The extract recoveries were 52.8-79.0%. Finally, we applied this method to real samples and successfully measured benzene, toluene, ethylbenzene, and xylene metabolites.