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.

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.

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.

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.

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.

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.

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.

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.

Biomass fuels and coke plants are important sources of human exposure to polycyclic aromatic hydrocarbons, benzene and toluene.

Large amounts of carcinogenic polycyclic aromatic hydrocarbons (PAHs), benzene and toluene (BT) might be emitted from incomplete combustion reactions in both coal tar factories and biomass fuels in rural China. The health effects arising from exposure to PAHs and BT are a concern for residents of rural areas close to coal tar plants. To assess the environmental risk and major exposure sources, 100 coke plant workers and 25 farmers in Qujing, China were recruited. The levels of 10 mono-hydroxylated PAHs (OH-PAHs), four BT metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the urine collected from the subjects were measured. The 8-OHdG levels in the urine were determined to evaluate the oxidative DNA damage induced by the PAHs and BT. The results showed that the levels of the OH-PAHs, particularly those of 1-hydroxynathalene and 1-hydroxypyrene, in the farmers were 1-7 times higher than those in the workers. The concentrations of the BT metabolites were comparable between the workers and farmers. Although the exact work location within a coke oven plant might affect the levels of the OH-PAHs, one-way ANOVA revealed no significant differences for either the OH-PAHs levels or the BT concentrations among the three groups working at different work sites. The geometric mean concentration (9.17 µg/g creatinine) of 8-OHdG was significantly higher in the farmers than in the plant workers (6.27 µg/g creatinine). The levels of 8-OHdG did not correlate with the total concentrations of OH-PAHs and the total levels of BT metabolites. Incompletely combusted biomass fuels might be the major exposure source, contributing more PAHs and BT to the local residents of Qujing. The estimated daily intakes (EDIs) of naphthalene and fluorene for all of the workers and most of the farmers were below the reference doses (RfDs) recommended by the U.S. Environmental Protection Agency (EPA), except for the pyrene levels in two farmers. However, the EDIs of benzene in the workers and local farmers ranged from 590 to 7239 µg/day, and these levels were 2- to 30-fold higher than the RfDs recommended by the EPA. Biomass fuel combustion and industrial activities related to coal tar were the major sources of the PAH and BT exposure in the local residents. Using biomass fuels for household cooking and heating explains the higher exposure levels observed in the farmers relative to the workers at the nearby coal tar-related industrial facility.

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.

Rapid determination of hippuric acid as an exposure biomarker of toluene using a colorimetric assay and comparison with high-performance liquid chromatography.

Occupational exposure to toluene is associated with health risks that require reliable monitoring methods. Hippuric acid (HA), a urinary metabolite of toluene, serves as a valuable biomarker for such exposure. Colorimetric methods for the quantitative determination of HA have gained prominence due to their simplicity, cost-effectiveness, and suitability for field application. In the present study, a simple colorimetric technique was optimized for the determination of HA in the urine sample, and compared with a usual HPLC technique. The central composite design (CCD) was applied to examine the effective parameters on the colorimetric determination of HA. The calibration curve for HA was established within the concentration range of 6 to 100 mg L-1 with R2 = 0.97. The detection limit (LOD) and quantification limit (LOQ) were determined to be 1.8 mg L-1 and 6 mg L-1 respectively. The relative standard deviation (RSD%) was less than 5%, and the recovery% (R%) was 90.5-100.1. The overall results showed good agreement between the colorimetric and HPLC results. There was a significant relationship between the results obtained from HPLC and colorimetric methods especially for higher concentration levels of HA (≥ 500 mg/g creatinine). In conclusion, our optimized colorimetric method is a simple, cost-effective, and rapid method for determination of HA in occupational exposure, which is comparable with the HPLC technique.

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.

Biomarkers of exposure to aromatic hydrocarbons and methyl tert-butyl ether in petrol station workers.

This cross-sectional study was aimed at reconstructing the exposure to gasoline in 102 petrol station attendants by environmental and biological monitoring of benzene, toluene, ethylbenzene and xylene (BTEX) and biomonitoring of methyl tert-butyl ether (MTBE). Airborne BTEX were higher for manual refuelers than self-service assistants and were highly correlated with each other. Significant relationships were found between airborne BTX and the corresponding urinary solvents (U-BTX) and beween airborne B and urinary MTBE (U-MTBE). Smokers eliminated higher values of U-B, trans,trans-muconic (t,t-MA) and S-phenylmercapturic (S-PMA) acids but not U-MTBE. All these biomarkers were, however, significantly raised during the shift, independently from smoking. Linear regression confirmed that occupational exposure was a main predictor of U-MTBE, U-B and S-PMA values, both the latter confounded by smoking habits. The study supports the usefulness of biomonitoring even at low exposure levels.

Applicability of urinary benzene to biological monitoring of occupational and environmental exposure to very low benzene concentrations.

OBJECTIVE: To verify whether urinary benzene is an applicable biomarker of occupational exposure to very low concentrations of benzene, considering the influence of cigarette smoke and benzene-toluene co-exposure. MATERIALS AND METHODS: 23 filling station attendants with occupational exposure to benzene and 31 controls were analyzed. Occupational and environmental exposure was monitored and t,t-muconic acid (t,t-MA), S-phenylmercapturic acid (SPMA), urinary benzene and creatinine in the urine samples were tested. RESULTS: Occupational exposure to benzene and toluene was significantly higher in the filling station attendants than in the controls, whereas t,t-MA, SPMA and urinary benzene were not different in the two groups. Instead, the smoker group showed significantly higher values for the above biomarkers than the non-smoker group, each of which included both exposed workers and controls. SPMA was dependent on airborne benzene and cigarette smoking, and urinary benzene only on cigarette smoking, while t,t-MA was not dependent on either of these variables. CONCLUSIONS: At very low concentrations of occupational exposure to benzene, urinary benzene is less valid than SPMA as a biomarker, even if both are strongly influenced by smoking habit. Abstention from smoking should therefore be recommended for at least two hours before urine collection.

[Lesser validity of urinary benzene than S-phenylmercapturic acid for measuring occupational and environmental exposure to very low concentrations of benzene]. / Minore validità del benzene urinario rispetto all'acido S-fenilmercapturico nel rilevare l'esposizione occupazionale ed ambientale a concentrazioni molto basse di benzene.

AIM: To study the validity of urinary benzene as a biomarker of low and very low exposure to this toxicant, as compared with t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (SPMA), also taking into account the influence of cigarette smoking and co-exposure to toluene on the urinary excretion of benzene. MATERIALS AND METHODS: The results obtained in two different studies were compared: in the first, workers occupationally exposed to low concentrations of benzene (18 fuel tanker drivers and 23 filling station attendants) were compared with 31 controls and in the second, workers exposed to very low concentrations of benzene (the same 23 filling station attendants) were compared with the 31 controls. Exposure to airborne benzene and toluene was monitored with passive personal samplers (Radiello). Then the urine collected at the end of the work shift was analyzed for t,t-MA, SPMA and urinary benzene. All participants also filled out a questionnaire about their lifestyle habits. RESULTS: There were no differences among the three groups in terms of age and smoking habit. Occupational exposure to benzene and toluene and the urinary concentrations of t,t-MA, SPMA and urinary benzene were higher in the fuel tanker drivers than the filling station attendants and higher in the latter than in the controls. Cigarette smoking was found to be associated with urinary excretion of t,t-MA, SPMA and urinary benzene at both low and very low exposure to benzene. The biomarkers t,t-MA, SPMA and urinary benzene were almost always correlated, for both low and very low exposure to benzene. Notably, for low exposure to benzene a dependency relation was found with the levels of t,t-MA, SPMA and urinary benzene on both cigarette smoking and airborne benzene, whereas for very low exposure to benzene there was a dependency relation of SPMA on cigarette smoking and airborne benzene, of urinary benzene only on cigarette smoking and of t,t-MA on none of the variables considered. CONCLUSIONS: For occupational exposure to low concentrations of benzene, urinary benzene and SPMA showed a comparable validity, while for exposure to very low concentrations of this toxicant the validity of SPMA was confirmed while urinary benzene was found to be less useful. Cigarette smoking was the main factor conditioning the excretion of all the biomarkers of benzene in conditions of both low and very low exposure to the toxicant, so for the analysis of occupational exposure to benzene it is best to recommend abstention from smoking at least in the hours immediately before urine collection.

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.

Identification of NTBC metabolites in urine from patients with hereditary tyrosinemia type 1 using two different mass spectrometric platforms: triple stage quadrupole and LTQ-Orbitrap.

The objective of our work was to identify known and unknown metabolites of the drug NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione) in urine from patients during the treatment of hereditary tyrosinemia type 1 (HT-1) disease, a severe inborn error of tyrosine metabolism. Two different mass spectrometric techniques, a triple stage quadrupole and an LTQ-Orbitrap (Fourier transform mass spectrometry (FTMS)), were used for the identification and the structural elucidation of the detected metabolites. Initially, the mass spectrometric (MS) approach consisted of the precursor ion scan detection of the selected product ions, followed by the corresponding collision-induced dissociation (CID) fragmentation analysis (MS(2)) for the targeted selected reaction monitoring (SRM) mode. Subsequently, accurate and high-resolution full scan and MS/MS measurements were performed on the possible metabolites using the LTQ-Orbitrap. Final confirmation of the identified metabolites was achieved by measuring commercially supplied or laboratory-synthesized standards. Altogether six metabolites, including NTBC itself, were extracted, detected and identified. In addition, two new NTBC metabolites were unambiguously identified as amino acid conjugates, namely glycine-NTBC and beta-alanine-NTBC. These identifications were based on their characteristics of chromatographic retention times, protonated molecular ions, elemental compositions, product ions (using CID and higher-energy C-trap dissociation (HCD) techniques) and synthesized references. The applied MS strategy, based on two different MS platforms (LC/MS/MS and FTMS), allowed the rapid identification analysis of the drug metabolites from human extracts and could be used for pharmaceutical research and drug development.