Metabolism of derivatives of toluene. 1. The metabolism of acetotoluidides in the rabbit

Abstract

O-Acetotoluidide is partly oxidized in the rabbit to anthranilic (6%) and acetylanthranilic (1%) acids; a considerable part of the remainder appears to be converted to 6-amino-m-cresol, which was isolated. This latter compound is probably excreted as its N-acetyl deriv. conjugated with glucuronic acid and sulfate. The extent of sulfate conjugation corresponds to 32% of the dose. The metabolism of m-acetotoluidide is similar to that of the o-isomer; 25% is oxidized to the corresponding N-acetamidobenzoic acid, and the only other metabolite detected was 5-amino-o-cresol which was isolated. This is probably excreted as its N-acetyl deriv. conjugated with glucuronic acid and sulfate; 10% of the dose is excreted as an ethereal sulfate. p-Acetotolui-dide is virtually completely oxidized to p-acetamidobenzoic acid, 10% being excreted as ester glucuronide. There is no conjugation with sulfuric acid, o- and m-acetotoluidides cause an abnormally high excretion of reducing material in urine. The reason for this has not been determined.