Disposition and metabolism of 2-bromo-4,6-dinitroaniline in the male F344 rat

Abstract

The disposition of [ ¹⁴ C]‐2‐bromo‐4,6‐dinitroaniline (BDNA) was studied in male F344 rats following oral or intravenous (iv) administration. The gastrointestinal absorption of BDNA was nearly complete and was not affected by dose in the range (10–100 μmol/kg body weight) studied. Following either oral or iv administration, BDNA was rapidly distributed throughout the tissues and showed no marked affinity for any particular tissue. Clearance of [ ¹⁴ C]BDNA‐derived radioactivity from various tissues was rapid and was best described by two‐component decay curves. The whole‐body half‐life of BDNA was approximately 7 h. Within 72 h, clearance of [ ¹⁴ C]BDNA‐derived radioactivity from the body was 98% complete. [ ¹⁴ C]BDNA was rapidly cleared by metabolism to 13 metabolites, which were excreted in urine (62%) and feces (33%). Most (66%,) of the urinary radioactivity was excreted in the form of sulfate conjugates of two metabolites of BDNA; excretion of unmetabolized BDNA was minimal (less than 2%J. Biliary excretion of [ ¹⁴ C]BDNA was significant; however, some of this BDNA‐derived radioactivity underwent enterohepatic circulation and was subsequently excreted in urine. Results of this study indicate that, if metabolism is a detoxification process, the rapid metabolism and excretion of this compound should minimize the likelihood of chronic toxicity from repeated exposure to BDNA beyond that predicted by data from acute or short‐term exposures.