Urinary t,t-muconic acid as an indicator of exposure to benzene.

Abstract

A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit ( < 0 1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5-0 mg/l as a non-corrected value) was higher than the 97'5%-tile values for the non-exposed (1-4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene.Benzene, an established human leukaemogen,' is an important material in the chemical industry, and it is also known to be present in petrol2 and in petroleum distillate solvents of low boiling point.3 Accordingly, efforts have been made to identify exposure markers, preferably in urine, which are sensitive enough to detect benzene exposure at or below 10 ppm. 45 The present report is an extension of three previous studies on the biological monitoring of exposure to benzene by means of urine analysis for metabolites such as phenol,5 catechol, and quinol,6 and on the effects of combined exposure to toluene.' A time and work saving method of urine analysis for t,t-muconic acid (MA) has been developed and successfully used for the biological monitoring of workers exposed to 6-7 ppm benzene. Materials and methods WORKERS STUDIED AND URINE COLLECTIONThose who participated in this study were 152 workers exposed to benzene (64 men exposed up to 92 ppm, 88 women up to 210 ppm), 55 male workers exposed to a mixture of benzene (up to 1 6 ppm) and toluene (up to 114 ppm), and 213 non-exposed workers (113 men, 100 women) in factories in China. The jobs of the Accepted 2 February 1988 exposed workers have been described previously8; the benzene workers were mostly shoemakers whereas the workers with mixed exposure were predominantly painters. The urine samples were collected at 1500 in the second half of a working week, when the concentrations of benzene metabolites in urine are expected to reach a maximum.9 URINE ANALYSIS FOR t,t-MA The high performance liquid chromatographic (HPLC) method of Karim et all' for t,t-MA was simplified for urine analysis as follows: an aliquot of urine sample, kept frozen and thawed immediately before analysis, was well mixed with an equal volume of methanol. The mixture was spun at 3000 rpm for 10 minutes to remove precipitates as in urinary hippuric acid determination." The supernatant layer (5 to 10 pl per injection) was introduced into a HPLC (Hitachi Model 635) equipped with a Spherisorb ODS 5 im colu...

Urinary Phenylmercapturic Acid as a Marker of Occupational Exposure to Benzene.

“…Thus, the present survey not only supports the opinion that PMA is a good biomarker of benzene exposure 8,9,[15][16][17][18][19] , but has demonstrated that PMA is useful even under the condition of co-exposure to other aromatics and most probably to other solvents in general. The latter observation suggests that, as a benzene exposure marker, PMA is superior to mono-to tri-hydroxylated benzenes [phenol 27) , quinol 27) and catechol 27) , 1,2,4-benzenetriol 11) ] and t,t-muconic acid 13) , because the excretion of these urinary benzene metabolites other than PMA are all known to be suppressed by coexposure to other aromatics. For example, urinary excretion of phenolic metabolites were suppressed by 33 to 60% 11) , and it was as large as 74% in case of t,t-muconic acid 13) , when metabolite excretion of by workers exposed to benzene and toluene together was compared with the excretion of those exposed to benzene only.…”

“…Benzene exposure in cokeries in the iron and steel industry is also known 8,9) . This study group has been studying on urinary biomarkers of occupational exposure to benzene such as catechol 10) , quinol 10) , 1,2,4-benzenetriol 11,12) as well as t,t-muconic acid 13) in addition to a traditional marker of phenol 14) . Urinary phenylmercapturic acid (PMA; N-acetyl-S-phenyl-L-cysteine), a N-acetylcysteine conjugate of benzene, has also been evaluated as a marker of exposure to low-level benzene 8,9,[15][16][17][18][19][20] , but the analytical methods employed are rather complex, e.g., requiring derivatization or clean-up through columns before instrumental analysis [21][22][23][24][25] such as gas chromatography-mass spectrometry 15) or liquid chromatography-mass spectrometry 26) , and application of the methods to routine occupational health services appear to be not practical.…”

Biological monitoring of occupational exposure to low levels of benzene.

“…Methods based on its urinary metabolites, such as phenol and the newly proposed trans, trans-muconic acid (4,5), are nonspecific because these compounds are also generated from sources other than benzene. S-phenylmercapturi c acid in urine is reported to be useful in monitoring exposures even below benzene concentrations of I cm 3 • m-3 (6).…”

Avaliação dos métodos analíticos para a determinação de metabólitos do benzeno como potenciais biomarcadores de exposição humana ao benzeno no ar

“…Além do hábito de fumar 80 e a ingestão de ácido sórbico 51,52 , a co-exposição ao tolueno também interfere na avaliação da exposição ao benzeno 60,81,82 . Há suspeitas que hidrocarbonetos policíclicos aromáticos (HPAs) também interfiram nesta avaliação 56 .…”