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

Autor: Mathews, James M., Zhan, Qiao, Etheridge, Amy S., Patel, Purvi R., Black, Sherry R., Banks, Troy T., Fennell, Timothy R., Snyder, Rodney W., Burgess, Jason P., Warren, Stephen D., Surh, Inok, Waidyanatha, Suramya
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Zdroj: Xenobiotica; Dec2012, Vol. 42 Issue 12, p1213-1224, 12p
Abstrakt: abstract 1. 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. 2. 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). 3. 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. 4. 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. 5. 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). [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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