Determination of benzene and its metabolites: application in biological monitoring of environmental and occupational exposure to benzene.
ABSTRACT Methods for the biological monitoring of benzene and its metabolites in exhaled air, blood and urine are reviewed. Analysis of benzene in breath can be carried out by using an exhaled-air collection tube and direct analysis by GC or GC-MS; however, this technique is less reliable when compared to analysis using blood or urine. For the determination of non-metabolized benzene in blood and urine, GC head-space analysis is recommended. Phenol, the major metabolite of benzene can be monitored by either HPLC or GC methods. However, urinary phenol has proved to be a poor biomarker for low-level benzene exposure. Recent studies have shown that trans,trans-muconic acid, a minor metabolite of benzene can be determined using HPLC with UV detection. This biomarker can be used for detection of low-level benzene exposure. Urinary S-phenylmercapturic acid is another sensitive biomarker for benzene, but it can be detected only by GC-MS. Hydroquinone, catechol and 1,2,4-benzenetriol can be measured using HPLC with either ultraviolet or fluorimetric detection. Nevertheless, their use for low-level assessment requires further studies. Eventually, for the assessment of health risks caused by benzene, biological-exposure reference values need to be established before they can be widely used in a field setting.
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Article: NGAL-Siderocalin in kidney disease.[show abstract] [hide abstract]
ABSTRACT: Kidney damage induces the expression of a myriad of proteins in the serum and in the urine. The function of these proteins in the sequence of damage and repair is now being studied in genetic models and by novel imaging techniques. One of the most intensely expressed proteins is lipocalin2, also called NGAL or Siderocalin. While this protein has been best studied by clinical scientists, only a few labs study its underlying metabolism and function in tissue damage. Structure-function studies, imaging studies and clinical studies have revealed that NGAL-Siderocalin is an endogenous antimicrobial with iron scavenging activity. This review discusses the "iron problem" of kidney damage, the tight linkage between kidney damage and NGAL-Siderocalin expression and the potential roles that NGAL-Siderocalin may serve in the defense of the urogenital system. This article is part of a Special Issue entitled: Cell Biology of Metals.Biochimica et Biophysica Acta 06/2012; 1823(9):1451-8. · 4.66 Impact Factor
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ABSTRACT: We have developed a gas chromatography-mass spectrometry method for analysis of benzene (BZ) metabolites in human urine and blood. Here we describe peripheral blood concentrations of hydroquinone (HQ(1)) and catechol (CAT(2)) in total, protein-bound, and unbound (free) forms obtained from BZ-exposed factory workers and controls. Total and unbound metabolites were directly measured in independent experiments, while bound forms were calculated as [total]-[unbound]. In this subset of a larger study, breathing zone benzene, toluene, and xylene were measured for the duration of a workshift, and end-shift blood samples taken from 143 subjects and controls. Potential lifestyle and environmental influences were assessed by questionnaire and bioassay, and single nucleotide polymorphisms in xenobiotic metabolizing enzymes NQO1, MPO, CYP2E1, and GSTT1 were also analyzed for potential contribution to differences in blood metabolite concentration. Total CAT, bound CAT, total HQ, and bound HQ correlated well with benzene exposure, while unbound CAT and HQ displayed no correlation. Nearly all of the metabolites found in blood were bound to protein (CAT 96-99+%, HQ 78-92+%), and when the ratio of bound to unbound metabolites were compared in subsets of exposed workers, the increase in blood metabolite concentration was nearly all due to an increase in the protein-bound molecule. These findings suggest that a threshold for conjugation does not exist within the exposure spectrum studied (0.01-78.8 mg/m(3)). This method demonstrates the feasibility of analyzing benzene metabolites in human blood, and should allow for further investigation of the health effects of benzene and its metabolites.Chemico-biological interactions 12/2009; 184(1-2):182-8. · 2.46 Impact Factor
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ABSTRACT: Abstract A framework of "Common Criteria" (i.e. a series of questions) has been developed to inform the use and evaluation of biomonitoring data in the context of human exposure and risk assessment. The data-rich chemical benzene was selected for use in a case study to assess whether refinement of the Common Criteria framework was necessary, and to gain additional perspective on approaches for integrating biomonitoring data into a risk-based context. The available data for benzene satisfied most of the Common Criteria and allowed for a risk-based evaluation of the benzene biomonitoring data. In general, biomarker (blood benzene, urinary benzene and urinary S-phenylmercapturic acid) central tendency (i.e. mean, median and geometric mean) concentrations for non-smokers are at or below the predicted blood or urine concentrations that would correspond to exposure at the US Environmental Protection Agency reference concentration (30 µg/m(3)), but greater than blood or urine concentrations relating to the air concentration at the 1 × 10(-5) excess cancer risk (2.9 µg/m(3)). Smokers clearly have higher levels of benzene exposure, and biomarker levels of benzene for non-smokers are generally consistent with ambient air monitoring results. While some biomarkers of benzene are specific indicators of exposure, the interpretation of benzene biomonitoring levels in a health-risk context are complicated by issues associated with short half-lives and gaps in knowledge regarding the relationship between the biomarkers and subsequent toxic effects.Critical Reviews in Toxicology 02/2013; 43(2):119-53. · 6.25 Impact Factor