RESUMEN
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 (less than 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.
Asunto(s)
Benceno/metabolismo , Ácidos Grasos Insaturados/orina , Ácido Sórbico/orina , Contaminantes Ocupacionales del Aire/análisis , Benceno/farmacología , Cromatografía Líquida de Alta Presión , Vestuario , Exposición a Riesgos Ambientales , Femenino , Humanos , Masculino , Pintura , Ácido Sórbico/análogos & derivados , Tolueno/metabolismo , Tolueno/farmacologíaRESUMEN
A sensitive h.p.l.c. method is described which separated urinary metabolites from benzene-treated male CD-1 mice. Phenol, trans,trans-muconic acid and quinol in the 48 h urine accounted, respectively, for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the orally administered single dose of benzene (880, 440 and 220 mg/kg body wt.). Catechol occurred in trace amounts. Ascorbic acid was used to adjust urine pH and increase the extraction efficiency of metabolites, especially muconic acid. It allowed an accurate estimation of quinol by preventing its auto-oxidation. trans,trans-Muconic acid was identified and was unique to benzene as none was detected in urine of mice dosed orally with phenol, catechol or quinol (250, 150 and 200 mg/kg, respectively). The potential existence of a toxic benzene metabolite in the form of an aldehyde precursor of muconic acid in vivo is discussed.