Metabolism of derivatives of toluene. 5. The fate of the xylenols in the rabbit, with further observations on the metabolism of the xylenes

Abstract

The metabolism of 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-xylen-l-ols in the rabbit follow essentially similar metabolic paths, 8-16% being excreted as ethereal sulfate and 50-72% as ether glucuronide. 1-3% is excreted unconjugated. Small amts. of the xylenols were isolated by direct extraction of the metabolic urines and characterized as carbanilates. Crystalline glucuronides were isolated as metabolites of all 6 isomers. Evidence was obtained by means of paper chromatography of the excretion of small amts. of phenolic and reducing metabolites of the xylenols. 2,5-Dihydroxy-l,3-dimethyl-benzene was identified as a metabolite of both 2,6- and 3,5-xylen-l-ols. The xylenes give rise to non-acidic phenol, 0.1-0.3% being excreted free and 2-4% conjugated. 2,5-Xylen-1-ol was isolated from p-xylene urine and characterized as its carbanilate.