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

Abstract

The disposition of 2-Methoxy-4-nitroaniline (MNA) was investigated in male and female Harlan Sprague Dawley rats and B6C3F1/N mice following oral, intravenous, and dermal exposure to [14C]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 (t1/2 = 152–424 min) and human (t1/2 = 118–403 min) but faster in mouse (t1/2= 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).