Metabolism and disposition of 2-methoxy-4-nitroaniline in male and female Harlan Sprague Dawley rats and B6C3F1/N mice

Xenobiotica. 2012 Dec;42(12):1213-24. doi: 10.3109/00498254.2012.697211. Epub 2012 Jun 23.

Abstract

The disposition of 2-Methoxy-4-nitroaniline (MNA) was investigated in male and female Harlan Sprague Dawley rats and B6C3F(1)/N mice following oral, intravenous, and dermal exposure to [(14)C]MNA at 2, 15, or 150 mg/kg. Clearance of MNA was investigated in male and female rat, mouse, and human hepatocytes. MNA was cleared slowly in hepatocytes from rat (t(1/2) = 152-424 min) and human (t(1/2) = 118-403 min) but faster in mouse (t(1/2)= 70-106 min). MNA was well-absorbed in rats and mice following oral administration and eliminated chiefly in urine (rats, 75-79%; mice, 55-68%) 72 h post dosing. Less than 1% of the radioactivity remained in tissues at 72 h. MNA was poorly absorbed following dermal application in rats (5.5%) and mice (10%) over 24 h. The major pathway of metabolism of MNA was via hydroxylation of the phenyl ring to form 6-hydroxy MNA; major metabolites detected were sulfate and glucuronide conjugates of 6-hydroxy MNA. Following oral administration, the percent of total radioactivity bound in tissues bound was highest in liver (43%) and red blood cells (30%), whereas the radioactivity bound to DNA was highest in cecum (160 pmol/mg DNA).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aniline Compounds / administration & dosage
  • Aniline Compounds / metabolism*
  • Aniline Compounds / pharmacokinetics*
  • Aniline Compounds / urine
  • Animals
  • Bile / metabolism
  • Carbon Radioisotopes / administration & dosage
  • Chromatography, High Pressure Liquid
  • DNA / metabolism
  • Drug Administration Routes
  • Female
  • Hepatocytes / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Metabolic Networks and Pathways
  • Metabolome
  • Metabolomics
  • Mice
  • Nitro Compounds / administration & dosage
  • Nitro Compounds / metabolism*
  • Nitro Compounds / pharmacokinetics*
  • Nitro Compounds / urine
  • Radioactivity
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics*
  • Tissue Distribution / drug effects

Substances

  • Aniline Compounds
  • Carbon Radioisotopes
  • Nitro Compounds
  • DNA
  • 2-methoxy-4-nitroaniline