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Disposition and metabolism ofp-nitroaniline in the male F-344 rat

Fundamental and Applied Toxicology
Publication Date
DOI: 10.1016/0272-0590(84)90207-0
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Abstract The disposition of p-[ 14C]nitroaniline (PNA) was studied in male F-344 rats following oral and/or intravenous (iv) administration. The gastrointestinal absorption of PNA was near complete and was not affected by dose in the range studied (2–100 μmol/kg). Following either oral or iv administration, PNA was rapidly distributed throughout the tissues and showed no marked affinity for any particular tissue. The clearance of [ 14C]PNA-derived radioactivity from various tissues was rapid and followed a two-component decay curve. The whole body half-life of PNA was approximately 1 hr. Within 3 days clearance of PNA-derived radioactivity from the body was almost complete. [ 14C]PNA was rapidly cleared by metabolism to nine metabolites which were excreted primarily in the urine and to a lesser extent in feces. Most (56%) of the urinary radioactivity was in the form of sulfate conjugates of two metabolites of PNA; the excretion of unmetabolized PNA was minimal (less than 3%). Biliary excretion of [ 14C]PNA was significant, however, much of this PNA-derived radioactivity underwent enterohepatic circulation and was subsequently excreted in urine. The results of this study indicate that, if metabolism is a detoxification process, the rapid metabolism and excretion of this compound minimize the likelihood of significant toxicity from repeated exposure to PNA beyond that predicted by data from acute or short-term exposures.

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