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.
"Similarly, benzene in expired breath has not proven to be a reliable biomarker for assessing benzene exposure. Breath sampling, transportation and storage considerations, contamination, adsorption, losses, and lack of standardized methods, among other factors, have thus far precluded a reliable application of this biomarker on a broad scale (Hays et al., 2012; Ong & Lee, 1994). SPMA is considered to be the most specific metabolite of benzene. "
[Show abstract][Hide abstract] 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.
"Benzene is also used in rubber, lubricants, detergents and pesticides. The most important causes of exposure for general population are vehicle exhaust and cigarette fumes (Brief et al., 1980; Ong and Lee, 1994; Wallace et al., 1997). "
[Show abstract][Hide abstract] ABSTRACT: Benzene is a common element of environmental pollution. Although this substance is not recognized as a teratogenic agent, it is not known whether prenatal exposure to benzene may induce neurobehavioral changes in the progeny. Benzene 0.1mg/kg was injected subcutaneously (s.c.) acutely at day 15 of gestation into pregnant female rats of the Sprague-Dawley strain and neurotoxicity of the substance was studied in pups and male adult animals of the same progeny. No change was found in total number of neonates, body weight and eye opening time between benzene-exposed animals and controls. No malformations were observed. At birth, neonatal reflexes (cliff aversion, forelimb placing, bar holding, forelimb grasping, startle) were scored in benzene-exposed pups and their percent appearance was found to be anticipated (more benzene-exposed pups exhibited reflexes each day) in comparison to that of control animals. Also, the completion (maximum appearance, i.e. 100% of the brood was found to exhibit each reflex) of neonatal reflexes in benzene-exposed animals preceded that of controls. Starting 2 months after birth, cognitive and motor performance was assessed only in male animals of the prenatally benzene-exposed progeny. The overall evaluation of motor activity in benzene-exposed animals in the open-field test revealed reduced ambulation in these rats as compared to control animals. Acquisition of active avoidance responses in the shuttle-box test, as assessed by the number of conditioned avoidance responses and the percent of learners, was impaired in benzene-exposed rats as compared to control animals. Prenatal exposure to benzene was also followed by reduced retention latency in a step-through passive avoidance task in two retention tests. These results suggest that acute exposure to benzene during gestational organogenesis may cause long-lasting changes in motor behavior and cognitive processes. This may be relevant for the assessment of benzene toxic profile for the progeny of pregnant subjects, although teratogenic effects are not observed.
"In the current study, both free and conjugated phenol, based on acid hydrolyzation, were observed, while only free trans, trans-muconic acid and conjugated hydroquinone and catechol were measured following the low exposures. Phenol, hydroquinone and catechol have been reported excreted primarily as sulfate and glucuronide conjugates, which are released by acid hydrolysis (Sabourin et al., 1989; Ong et al., 1994; Valentine et al., 1996; Medeiros et al., 1997), while free trans,trans-muconic acid is the common form of this metabolite previously reported (Bechtold et al., 1991). The predominance of conjugated hydroquinone and catechol and only free trans,trans-muconic acid measured here agrees with previously reported analyses following occupational studies. "
[Show abstract][Hide abstract] ABSTRACT: The use of stable, isotopically labeled compounds in controlled exposure experiments at environmentally relevant levels allows for the distinguishing of urinary metabolites associated with known exposure from background levels generally present in the urine. Exposures of volunteers to (13)C-benzene for 2 h at 40+/-10 p.p.b. were conducted after obtaining informed consent, and urinary phenol, catechol, hydroquinone and trans,trans- muconic acid were measured. Each isotopically labeled urinary metabolite was determined in the presence of significantly higher concentrations of the unlabeled metabolite. Following exposure, free and acid hydrolyzed phenol, acid hydrolyzed catechol and hydroquinone, and free trans,trans-muconic acid were determined by GC/MS. The percentage of trans,trans-muconic acid excreted was higher than reported following exposure at occupational levels. The use of isotopically labeled compounds has the potential to investigate the metabolism of common environmental contaminants for validation of toxicokinetic models and improve risk extrapolation from high concentration occupational exposures and animal studies to environmentally relevant pollutant levels.
Journal of Exposure Analysis and Environmental Epidemiology 10/2003; 13(5):393-402. DOI:10.1038/sj.jea.7500285 · 2.72 Impact Factor
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