ANALYSIS AND EVALUATION OF TRANS,TRANS-MUCONIC ACID AS A BIOMARKER FOR BENZENE EXPOSURE

Benzene is an important industrial chemical and, due to its occurrence in mineral oil and its formation in many combustion processes, a wide spread environmental pollutant. Since benzene is hematoxic and has bee n classified as a human carcinogen, monitoring and control of benzene exposure is of importance. Although trans,trans-muconic acid (ttMA) wa s identified as a urinary metabolite of benzene at the beginning of th is century, only recently has its application as a biomarker for occup ational and environmental benzene exposure been investigated. The rang e of metabolic conversion of benzene to ttMA is about 2-25% and depend ent on the benzene exposure level, simultaneous exposure to toluene, a nd probably also to genetic factors. For the quantitation of ttMA in u rine, HPLC methods using UV and diode array detection as well as GC me thods combined with MS or FID detection have been described. Sample pr etreatment for both HPLC and GC analysis comprises centrifugation and enrichment by solid-phase extraction on anion-exchange sorbents. Descr ibed derivatization procedures prior to GC analysis include reaction w ith N,O-bis(trimethysilyl)acetamide, N,O-bis (trimethylsilyl)trifluoro acetamide, pentafluorobenzyl bromide and borontrifluoride-methanol. Re ported limits of detection for HPLC methods range from 0.1 to 0.003 mg l-(1), whereas those reported for GC methods are 0.03-0.01 mg l(-1). Due to its higher specificity, GC methods appear to be more suitable f or determination of low urinary ttMA levels caused by environmental ex posure to benzene. In studies with occupational exposure to benzene (> 0.1 ppm), good correlations between urinary ttMA excretion and benzene levels in breathing air are observed. From the reported regressions f or these variables, mean excretion rates of ttMA of 1.9 mg g(-1) creat inine or 2.5 mg l(-1) at an exposure dose of 1 ppm over 8 h can be cal culated. The smoking-related increase in urinary ttMA excretion report ed in twelve studies ranged from 0.022 to 0.2 mg g(-1) creatinine. Onl y a few studies have investigated the effect of exposure to environmen tal levels of benzene (<0.01 ppm) on urinary ttMA excretion. A trend f or slightly increased ttMA levels in subjects living in areas with hig h automobile traffic density was observed, whereas exposure to environ mental tobacco smoke did not significantly increase the urinary ttMA e xcretion. It is concluded that urinary ttMA is a suitable biomarker fo r benzene exposure at occupational levels as low as 0.1 ppm. Biomonito ring of exposure to environmental benzene levels (<0.01 ppm) using uri nary ttMA appears to be possible only if the ingestion of dietary sorb ic acid, another precursor to urinary ttMA, is taken into account. (C) 1998 Elsevier Science B.V. All rights reserved.