Effect of toluene and xylenes on liver glutathione and their urinary excretion as mercapturic acids in the rat.
Administration of toluene and xylenes to rats caused a decrease in liver glutathione concentration. The effect was most pronounced after the administration of o-xylene. 26% of the initial glutathione level was found three hours after treatment with o-xylene (4.0 mmoles/kg). No in vitro conjugation of o-xylene with glutathione was observed, neither spontaneously nor in the presence of 105,000 g supernatant from rat liver homogenate, containing glutathione S-transferases. Thus, a metabolite of o-xylene, which is not formed during incubation with 105,000 g supernatant, reacts with glutathione. A thioether was isolated from urine of rats given o-xylene; the compound was identified as o-methylbenzyl mercapturic acid by GC-MS and NMR. Chromatographic evidence was found for the presence of benzyl mercapturic acid in the urine of toluene-treated rats. The amounts of mercapturic acids excreted in the urine after administration of toluene, p-xylene, m-xylene, and o-xylene were 0.4-0.7,0.6,1.3, and 10-21% of the dose, respectively. These results demonstrate the involvement of a thusfar unknown pathway in the biotransformation of toluene and xylenes.
D000111:Acetylcysteine / Q000652:urine*; D000818:Animals; D001711:Biotransformation; D005978:Glutathione / Q000378:metabolism* / Q000652:urine; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D013440:Sulfides / Q000652:urine; D014050:Toluene / Q000633:toxicity* / Q000652:urine; D014992:Xylenes / Q000633:toxicity* / Q000652:urine
D013440:Sulfides; D014992:Xylenes; D014050:Toluene; D005978:Glutathione; D000111:Acetylcysteine