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Abstract
1. The disposition and metabolism of 2,4-dinitroaniline was studied in male F-344 rats following oral and i.v. administration. Gastrointestinal absorption was near complete and was not affected by dose (10–90 μmol/kg). Following either oral or i.v. administration, dinitroaniline was rapidly distributed throughout the tissues and showed no marked affinity for any particular tissue.
2. 14C-dinitroaniline was readily cleared by metabolism to at least nine metabolites; radioactivity was excreted primarily in urine (70% dose) and to a lesser extent in faeces (25–30% dose). Clearance of radioactivity from the body was near complete in 3 days.
3. As the whole-body half-life of dinitroaniline derived radioactivity in the rat was <3 h and there was no evidence for saturation of any mechanism of absorption, distribution, metabolism or excretion in the dose range studied, 2,4-dinitroaniline appears to have little potential for bioaccumulation in animal tissues.
4. Analysis of urine and bile detected nine metabolites of 2,4-dinitroaniline. The major metabolite was excreted in urine as a sulphate conjugate and in bile as a glucuronide. This metabolite was characterized by combined h.p.l.c./mass spectrometry as 2,4-dinitrophenylhydroxylamine.