Association between urinary BTEX metabolites and dyslexic odds among school-aged children.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are ubiquitous in the environment, and all of them can cause neurotoxicity. However, the association between BTEX exposure and dyslexia, a disorder with language network-related regions in left hemisphere affected, remains unclear. We aimed to assess the relationship between BTEX exposure and dyslexic odds among school-aged children. A case-control study, including 355 dyslexics and 390 controls from three cities in China, was conducted. Six BTEX metabolites were measured in their urine samples. Logistic regression model was used to explore the association between the BTEX metabolites and the dyslexic odds. Urinary trans,trans-muconic acid (MU: a metabolite of benzene) was significantly associated with an increased dyslexic odds [odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.01, 1.50], and the adjusted OR of the dyslexic odds in the third tertile was 1.72 (95% CI: 1.06, 2.77) compared to that in the lowest tertile regarding urinary MU concentration. Furthermore, the association between urinary MU level and the dyslexic odds was more pronounced among children from low-income families based on stratified analyses. Urinary metabolite levels of toluene, ethylbenzene, and xylene were not found to be associated with the dyslexic odds. In summary, elevated MU concentrations may be associated with an increased dyslexic odds. We should take measures to reduce MU related exposure among children, particularly those with low family income.

Associations of personal urinary volatile organic compounds and lung function in children.

BACKGROUND: We investigated the correlation between urine VOC metabolites and airway function in children exposed to anthropogenic volatile organic compounds (VOCs), notable pollutants impacting respiratory health. METHODS: Out of 157 respondents, 141 completed skin prick tests, spirometry, IOS, and provided urine samples following the International Study of Asthma and Allergies in Childhood (ISAAC)-related questions. Allergic sensitization was assessed through skin prick tests, and airway functions were evaluated using spirometry and impulse oscillometry (IOS). Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) was recorded and FEV1/FVC ratio was calculated. Airway mechanics parameters including respiratory resistance at 5 Hz (Rrs5) mean respiratory resistance between 5 Hz and 20 Hz (Rrs5-20), were also recorded. Urine concentrations of metabolites of benzene, ethylbenzene, toluene, xylene, styrene, formaldehyde, carbon-disulfide were analyzed by gas chromatography/tandem mass spectroscopy. RESULTS: The median age at study participation was 7.1 (SD 0.3) years. Muconic acid (benzene metabolites) and o-methyl-hippuric acid (xylene metabolites) above medians were associated with a significant increase in Rrs5 (muconic acid: aß = 0.150, p = .002; o-methyl-hippuric acid: aß = 0.143, p = .023) and a decrease in FEV1/FVC (o-methyl-hippuric acid: aß = 0.054, p = .028) compared to those below median. No associations were observed for Rrs5-20 and FEV1 between the groups categorized as above and below the median (all parameter p values > .05). CONCLUSIONS: Elevated levels of benzene and xylene metabolites were associated with a significant increase in Rrs5 and a decrease in FEV1/FVC, related to increased resistance and restrictive lung conditions compared to individuals with concentrations below the median.

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.

[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.

A needle trap device packed with MIL-100(Fe) metal organic frameworks for efficient headspace sampling and analysis of urinary BTEXs.

The aim of this study was to develop a new method for the determination of benzene, toluene, ethylbenzene and xylene isomers (BTEXs) in urine samples. In this method, MIL-100(Fe)@Fe3 O4 @SiO2 metal-organic framework was synthesized, characterized and packed inside a needle trap device (NTD) as a sorbent for headspace extraction of unmetabolized BTEXs from urine samples followed by gas chromatography (GC) analysis. The GC device was equipped with a flame ionization detector (FID). The results showed that the optimal extraction time, extraction temperature and salt content were 60 min, 30°C and 5%, respectively. Also, the optimal desorption time and temperature were determined to be 1 min and 250°C, respectively. The limits of detection and quantification of the analytes of interest were in the ranges 0.0001-0.0005 and 0.0003-0.0014 µg ml-1 , respectively. The intra- and inter-day repeatability were <7.6%. The accuracy of the measurements in urine samples was in the range 7.1-11.4%. The results also demonstrated that the proposed NTD offered various advantages such as having high sensitivity and being inexpensive, reusable, user friendly, environmentally friendly and compatible for use with the GC device. Therefore, it can be efficiently used as a MIL-NTD for the extraction and analysis of unmetabolized BTEXs from urine samples.

Evaluation of immunological, inflammatory, and oxidative stress biomarkers in gasoline station attendants.

BACKGROUND: Gasoline is a complex mixture of saturated and unsaturated hydrocarbons, in which aromatic compounds, such as BTX (benzene, toluene, and xylene) feature as the main constituents. Simultaneous exposure to these aromatic hydrocarbons causes a significant impact on benzene toxicity. In order to detect early alterations caused in gasoline station attendants exposed to BTX compounds, immunological, inflammatory, and oxidative stress biomarkers were evaluated. METHODS: A total of 66 male subjects participated in this study. The gasoline station attendants (GSA) group consisted of 38 gasoline station attendants from Rio Grande do Sul, Brazil. The non-exposed group consisted of 28 subjects who were non-smokers and who had no history of occupational exposure. Environmental and biological monitoring of BTX exposure was performed using blood and urine. RESULTS: The GSA group showed increased BTX concentrations in relation to the non-exposed group (p < 0.001). The GSA group showed elevated protein carbonyl (PCO) levels and pro-inflammatory cytokines, decreased expression of CD80 and CD86 in monocytes, and reduced glutathione S-transferase (GST) activity compared to the non-exposed group (p < 0.05). BTX levels and trans,trans-muconic acid levels were positively correlated with pro-inflammatory cytokines and negatively correlated with interleukin-10 contents (p < 0.001). Increased levels of pro-inflammatory cytokines were accompanied by increased PCO contents and decreased GST activity (p < 0.001). Furthermore, according to the multiple linear regression analysis, benzene exposure was the only factor that significantly contributed to the increased pro-inflammatory cytokines (p < 0.05). CONCLUSIONS: Taken together, these findings show the influence of exposure to BTX compounds, especially benzene, on the immunological, inflammatory, and oxidative stress biomarkers evaluated. Furthermore, the data suggest the relationship among the evaluated biomarkers of effect, which could contribute to providing early signs of damage to biomolecules in subjects occupationally exposed to BTX compounds.

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.

Ethylbenzene and styrene exposure in the United States based on urinary mandelic acid and phenylglyoxylic acid: NHANES 2005-2006 and 2011-2012.

Ethylbenzene and styrene are air toxicants with widespread nonoccupational exposure sources, including tobacco smoke and diet. Ethylbenzene and styrene (EB/S) exposure was quantified from their common metabolites measured in spot urine samples obtained from participants (≥6 years old) in the 2005-2006 and 2011-2012 cycles of the National Health and Nutrition Examination Survey (NHANES; N = 4690). EB/S metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured using ultra-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). MA and PGA were detected in 98.9% and 90.6% of tested urine specimens, respectively. Exclusive smokers had 2-fold and 1.6-fold higher median urinary MA and PGA, respectively, compared with non-users. Sampleweighted regression analysis among exclusive smokers showed that smoking 0.5 pack cigarettes per day significantly increased MA (+97.9 µg/L) and PGA (+69.3 µg/L), controlling for potential confounders. In comparison, exposure from the median daily dietary intake of grain products increased MA by 1.95 µg/L and was not associated with statistically significant changes in urinary PGA levels. Conversely, consuming vegetables and fruit was associated with decreased MA and PGA. These results confirm tobacco smoke as a major source of ethylbenzene and styrene exposure for the general U.S. population.

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.

Biological monitoring of occupational ethylbenzene exposure by means of urinalysis for un-metabolized ethylbenzene.

This study aimed to examine quantitative relation between ethylbenzene (EB) in air (EB-A) and un-metabolized EB in urine (EB-U) for biological monitoring of occupational EB exposure by urinalysis for EB. In total, 49 men in furniture production factories participated in the study. Time-weighted average EB-A was monitored by diffusive sampling. Urinalysis for EB was conducted by head-space gas-chromatography with end-of-shift samples. Data were subjected to regression analysis for statistical evaluation. A geometric mean (GM) and the maximum (Max) EB-A levels were 2.1 and 45.5 ppm, respectively. A GM and the Max for EB-U (observed values) were 4.6 and 38.7 µg/l. A significant linear correlation was observed. The regression equation was Y=3.1+0.73X where X is EB-A (ppm) and Y is EB-U (µg/l) (r=0.91, p<0.01). The significant correlation between EB-A and EB-U coupled with a small intercept suggests that biological monitoring of occupational EB exposure is possible by analysis for un-metabolized EB in end-of-shift urine samples. Further validation studies (including those on applicability to women) are envisaged. The feasibility should be examined for biological monitoring and the applicability of the equation among the workers exposed to EB at low levels.

Exposure to bisphenol A, chlorophenols, benzophenones, and parabens in relation to reproductive hormones in healthy women: A chemical mixture approach.

BACKGROUND: Little is known about the associations of bisphenol A, chlorophenols, benzophenones, and parabens with reproductive hormone levels in women. Our goal was to evaluate the associations between repeated measures of these chemicals and their mixtures with reproductive hormones in women. METHODS: Longitudinal urine samples from healthy, premenopausal women (n = 143 with 3-5 urine samples each) were measured for bisphenol A, five chlorophenols (2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol, triclosan), two ultraviolet (UV) filters (benzophenone-1, benzophenone-3), and eight parabens and their metabolites (benzyl, butyl, ethyl, heptyl, methyl, propyl, 4-hydroxybenzoic acid (4-HB), 3,4-dihydroxybenzoic acid (3,4-DHB)) over two menstrual cycles. Estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in blood up to 8 times each menstrual cycle. Linear mixed models were used for both single and multi-chemical exposures estimated using principal component analysis. Four factors were identified including: paraben; paraben metabolites and BPA, phenols, and UV filters. Models were adjusted for creatinine, age, race, and body mass index and weighted with inverse probability of exposure weights to account for time varying confounding. RESULTS: In single-chemical models, 3,4-DHB was associated with estradiol (0.06 (95% confidence interval (CI): 0.001, 0.12)), 2-4-DCP with increased progesterone 0.14 (0.06, 0.21) and decreased FSH -0.08 (-0.11, -0.04), and 4-HB was associated with increased FSH 0.07 (0.01, 0.13). In multi-chemical models, all factors were associated with increased progesterone (beta coefficient range: 0.15 for UV filter factor to 0.32 for paraben factor). The paraben factor and the paraben metabolite and BPA factor were associated with increased estradiol [0.21 (0.15, 0.28); 0.12 (0.07, 0.18)]. The phenol and UV filter factors were associated with decreased estradiol, FSH, and LH. The UV filter factor showed the strongest inverse association with estradiol -0.16 (-0.22, -0.10), FSH -0.12 (-0.17, -0.07), and LH -0.17 (-0.23, -0.10). CONCLUSION: Mixtures of phenols were associated with changes in reproductive hormones. Such changes could contribute to adverse health in women but additional research is necessary.

Further examination of log Pow-based procedures to estimate biological occupational exposure limits.

OBJECTIVES: To test the reliability of the procedures (described in a previous article) for estimation of biological occupational exposure limits (BOELs). METHODS: Data on four organic solvents (styrene, ethyl benzene, isopropyl alcohol and tetrachloroethylene) were obtained from recent publications and added to previously cited data for 10 organic solvents. Regression analysis was used for statistical evaluation. RESULTS AND DISCUSSION: The previously reported results obtained using 10 solvents were reproduced by the analysis with 14 solvents. Repeated randomized division of the 14 sets into two subgroups of equal size followed by statistical comparisons did not show a significant difference between two regression lines. This reproducibility suggests that the procedures used to estimate BOELs may be applicable across many solvents, and this may be of particular benefit for protecting the health of workers who work with skin-penetrating solvents.

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.

Advanced data mining approaches in the assessment of urinary concentrations of bisphenols, chlorophenols, parabens and benzophenones in Brazilian children and their association to DNA damage.

Human exposure to endocrine disrupting chemicals (EDCs) has received considerable attention over the last three decades. However, little is known about the influence of co-exposure to multiple EDCs on effect-biomarkers such as oxidative stress in Brazilian children. In this study, concentrations of 40 EDCs were determined in urine samples collected from 300 Brazilian children of ages 6-14 years and data were analyzed by advanced data mining techniques. Oxidative DNA damage was evaluated from the urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8OHDG). Fourteen EDCs, including bisphenol A (BPA), methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), 3,4-dihydroxy benzoic acid (3,4-DHB), methyl-protocatechuic acid (OH-MeP), ethyl-protocatechuic acid (OH-EtP), triclosan (TCS), triclocarban (TCC), 2-hydroxy-4-methoxybenzophenone (BP3), 2,4-dihydroxybenzophenone (BP1), bisphenol A bis(2,3-dihydroxypropyl) glycidyl ether (BADGE·2H2O), 2,4-dichlorophenol (2,4-DCP), and 2,5-dichlorophenol (2,5-DCP) were found in >50% of the urine samples analyzed. The highest geometric mean concentrations were found for MeP (43.1 ng/mL), PrP (3.12 ng/mL), 3,4-DHB (42.2 ng/mL), TCS (8.26 ng/mL), BP3 (3.71 ng/mL), and BP1 (4.85 ng/mL), and exposures to most of which were associated with personal care product (PCP) use. Statistically significant associations were found between urinary concentrations of 8OHDG and BPA, MeP, 3,4-DHB, OH-MeP, OH-EtP, TCS, BP3, 2,4-DCP, and 2,5-DCP. After clustering the data on the basis of i) 14 EDCs (exposure levels), ii) demography (age, gender and geographic location), and iii) 8OHDG (effect), two distinct clusters of samples were identified. 8OHDG concentration was the most critical parameter that differentiated the two clusters, followed by OH-EtP. When 8OHDG was removed from the dataset, predictability of exposure variables increased in the order of: OH-EtP > OH-MeP > 3,4-DHB > BPA > 2,4-DCP > MeP > TCS > EtP > BP1 > 2,5-DCP. Our results showed that co-exposure to OH-EtP, OH-MeP, 3,4-DHB, BPA, 2,4-DCP, MeP, TCS, EtP, BP1, and 2,5-DCP was associated with DNA damage in children. This is the first study to report exposure of Brazilian children to a wide range of EDCs and the data mining approach further strengthened our findings of chemical co-exposures and biomarkers of effect.

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.

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.

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.

Exposure to BTEX and Ethers in Petrol Station Attendants and Proposal of Biological Exposure Equivalents for Urinary Benzene and MTBE.

OBJECTIVE: To assess exposure to benzene (BEN) and other aromatic compounds (toluene, ethylbenzene, m+p-xylene, o-xylene) (BTEX), methyl tert-butyl ether (MTBE), and ethyl tert-butyl ether (ETBE) in petrol station workers using air sampling and biological monitoring and to propose biological equivalents to occupational limit values. METHODS: Eighty-nine petrol station workers and 90 control subjects were investigated. Personal exposure to airborne BTEX and ethers was assessed during a mid-week shift; urine samples were collected at the beginning of the work week, prior to and at the end of air sampling. RESULTS: Petrol station workers had median airborne exposures to benzene and MTBE of 59 and 408 µg m(-3), respectively, with urinary benzene (BEN-U) and MTBE (MTBE-U) of 339 and 780 ng l(-1), respectively. Concentrations in petrol station workers were higher than in control subjects. There were significant positive correlations between airborne exposure and the corresponding biological marker, with Pearson's correlation coefficient (r) values of 0.437 and 0.865 for benzene and MTBE, respectively. There was also a strong correlation between airborne benzene and urinary MTBE (r = 0.835). Multiple linear regression analysis showed that the urinary levels of benzene were influenced by personal airborne exposure, urinary creatinine, and tobacco smoking [determination coefficient (R(2)) 0.572], while MTBE-U was influenced only by personal exposure (R(2) = 0.741). CONCLUSIONS: BEN-U and MTBE-U are sensitive and specific biomarkers of low occupational exposures. We propose using BEN-U as biomarker of exposure to benzene in nonsmokers and suggest 1457 ng l(-1) in end shift urine samples as biological exposure equivalent to the EU occupational limit value of 1 p.p.m.; for both smokers and nonsmokers, MTBE-U may be proposed as a surrogate biomarker of benzene exposure, with a biological exposure equivalent of 22 µg l(-1) in end shift samples. For MTBE exposure, we suggest the use of MTBE-U with a biological exposure equivalent of 22 µg l(-1) corresponding to the occupational limit value of 50 p.p.m.

Evaluation of Urinary Btex, Nicotine, and Cotinine as Biomarkers of Airborne Pollutants in Nonsmokers and Smokers.

Benzene, toluene, ethylbenzene, and isomeric xylenes (BTEX) are by-products of tobacco smoke and traffic emissions. The aim of this study was to determine the contribution of cigarette smoking to urinary levels of BTEX present in humans. Nicotine and cotinine, biomarkers of exposure to tobacco smoke, as well as BTEX, were measured in urine of smokers (n = 70) and nonsmokers (n = 65) using headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry (GC-MS). In smokers, a significant correlation was found between urinary BTEX levels and nicotine and cotinine. In addition, significant regression models with nicotine and cotinine as predictors showed that BTEX in smokers' urine was predominantly derived from exposure to tobacco smoke. In nonsmokers a weak correlation between BTEX and nicotine and cotinine was found in urine. Further, there was a lack of significant contribution of BTEX to urinary nicotine and cotinine concentrations in nonsmokers. Thus, it was presumed that vehicle exhaust was the main source of exposure to BTEX in nonsmokers.