Metabolism of o-[methyl-14C]toluidine in the F344 rat

Xenobiotica. 1980 Jul-Aug;10(7-8):457-68. doi: 10.3109/00498258009033781.

Abstract

1. Following a single dose (400 mg/kg s.c.) of o-[methyl-14C]toluidine to male F344 rats, 56% of the 14C was recovered in the 24 h urine, 2.3% in the faeces and 1% as exhaled 14CO2. After 48 h, 83.9% of the 14C appeared in the urine, 3.3% in the faeces and 1.4% was exhaled. 2. Ether-extractable urinary metabolites were separated by h.p.l.c. and identified as: o-toluidine (5.1% dose); azoxytoluene (0.2%); o-nitrosotoluene (less than or equal to 0.1%); N-acetyl-o-toluidine (0.2%); N-acetyl-o-aminobenzyl alcohol (0.3%); 4-amino-m-cresol (0.6%); N-acetyl-4-amino-m-cresol (0.3%); anthranilic acid (0.3%) and N-acetylanthranilic acid (0.3%). 3. Acid-conjugated urinary metabolites (51% of dose), separated by paper electrophoresis and by Sephadex LH-20 chromatography, were identified as sulphates of 4-amino-m-cresol (27.8% dose), N-acetyl-4-amino-m-cresol (8.5%), and 2-amino-m-cresol (2.1%), and glucuronides of 4-amino-m-cresol (2.6%), N-acetyl-4-amino-m-cresol (2.8%) and N-acetyl-o-aminobenzyl alcohol. Evidence for a double acid conjugate of 4-amino-m-cresol was also found. 4. These results show that N-acetylation and hydroxylation at the 4 position of o-toluidine are major metabolic pathways in the rat. Minor pathways include hydroxylation at the 6 position, oxidation of the methyl group and oxidation of the amino group. Sulphate conjugates predominate over glucuronides by a ratio of 6:1.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breath Tests
  • Carbon Radioisotopes
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Electrophoresis, Paper
  • Gas Chromatography-Mass Spectrometry
  • Male
  • Rats
  • Rats, Inbred F344
  • Tissue Distribution
  • Toluidines / metabolism*

Substances

  • Carbon Radioisotopes
  • Toluidines
  • 2-toluidine