trans,trans-Muconic acid, a reliable biological indicator for the detection of individual benzene exposure down to the ppm level

Abstract

trans,trans-Muconic acid (2,4-hexadienedioic acid) (t,t-MA) is a minor benzene metabolite which can be used as a biological indicator for benzene exposure. The purpose of the study was to evaluate the limits of use of t,t-MA for detection and quantification of occupational exposures to benzene, particularly on an individual scale, phenol being used as the metabolite of reference. A simple and sensitive method previously described by the authors was carried out to analyse t,t-MA in 105 end-of-shift urinary samples from 23 workers exposed to benzene used as an extraction solvent for "concretes" recovery in the perfume industry. Good correlations were found between atmospheric benzene and both metabolites (uncorrected or corrected for creatinine) or between the metabolites themselves, with correlation coefficients from 0.81 to 0.91 (P < 0.0001). Correlation- coefficients were not improved after correction for creatinine. The overall individual benzene exposure range, median, and arithmetic mean were respectively 0.1-75, 4.5, and 9.0 ppm with corresponding t,t-MA excretion of 0.1-47.9, 5.2 and 8.9 mg/l (uncorrected) and phenol excretion of 1.4-298, 30.9, and 42.2 mg/l (uncorrected). In the control group (145 determinations for t,t-MA and 76 for phenol from 79 individuals) the range, median, and arithmetic mean were respectively < 0.04-0.66, 0.08, and 0.13 mg/l (uncorrected t,t-MA) and 1.5-42.0, 9.85 and 11.3 mg/l (uncorrected phenol). t,t-MA was far more specific than phenol and could be easily and practically used to estimate with a given probability the upper or lower corresponding benzene concentrations down to around the ppm level.(ABSTRACT TRUNCATED AT 250 WORDS)

Suitability of S-Phenyl Mercapturic Acid and trans-trans-Muconic Acid as Biomarkers for Exposure to Low Concentrations of Benzene

“…Relatively high background values of tt-MA in individuals without exposure to benzene have repeatedly been reported (8,13,15,16). This background is partly due to compounds in the urine that coelute with tt-MA in the HPLC analysis.…”

“…The method for determining tt-MA as described by Ducos and co-workers (7,8) gave irreproducible results with some brands of quaternary ammonium exchange columns because the recovery of tt-MA from these columns appeared dependent on the pH of the urine samples. This problem could be solved by adjusting the pH of the samples to a pH of 7 to 10 with sodium hydroxide prior to extraction.…”

“…For the determination of tt-MA, the method by Ducos et al (7,8) was modified because the recovery of tt-MA appeared to be dependent on the urinary pH with some brands of the quaternary ammonium ion exchange resin (SAX columns) used. Alkalization of the samples to pH 7 to 10 prior to extraction gave optimum recoveries, which were invariably over 95% (10).…”

“…This S-PMA test was validated in 12 separate studies in various chemical manufacturing plants, oil refineries, and natural gas production installations and proved a reliable and sensitive biomarker capable of measuring 8-hr TWA benzene exposures of 0.3 ppm and higher (6). In the past few years, the method by Inoue and coworkers for assessment of tt-MA has also been modified by several investigators, and a sensitivity as low as 1 ppm (8-hr TWA) has been reported (7)(8)(9). The determination of S-PMA requires gas chromatography-mass spectrometry (GC-MS), whereas the determination of tt-MA is based on high performance liquid chromatography (HPLC) analysis, which is in general more readily available in a laboratory and easier to operate.…”

Avaliação da exposição ocupacional ao benzeno em trabalhadores frentistas e analistas de combustíveis utilizando o Teste Cometa como biomarcador de genotoxicidade

“…No Grupo II, os valores encontrados de AttM urinário são similares a valores reportados na literatura, que foram de <0,01-0,66 mg/g de creatinina 28,39,40 , considerando os diversos fatores que influenciam a concentração do AttM na urina, como tabagismo, o consumo de ácido sórbico e seus sais presentes em alguns alimentos, álcool, além de fatores individuais. Para diminuir os fatores de confusão, foram excluídos deste estudo os indivíduos fumantes e um questionário detalhado foi aplicado em ambos os grupos.…”