Disposition and metabolism of p-nitroaniline in the male F-344 rat.
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 mumol/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.
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D005243:Feces / Q000032:analysis; D007700:Kinetics; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000814:Aniline Compounds; C019498:4-nitroaniline