p‐phenylenediamine dihydrochloride: Comparative disposition in male and female rats and mice

Abstract

The absorption, distribution, metabolism, and excretion of p‐phenylenediamine (PDA) was studied in both sexes of F344 rats and B6C3F₁ mice. Absorption of PDA from the gastrointestinal tract was nearly complete in both species, and tissue distribution and excretion were not affected by the route of administration or dose in the range studied. The highest PDA‐derived radioactivity was present in muscle, skin, and liver in both species at all time points examined. Both sexes of either species cleared radioactivity from all tissues rapidly, so that in 24 h only 10–15% of the total dose administered was still present in the animal body. Clearance of PDA‐derived radioactivity was primarily through urine (68–86%) and secondarily through feces (10–19%). Over 95% of the radioactivity excreted in urine of both species was in the form of metabolites. The major metabolites in male and female rat urine were qualitatively and quantitatively similar, while major quantitative differences were observed between urinary metabolites of male and female mice. Variability in urinary metabolites was observed between the two species. Supplementary experiments have shown that PDA and/or metabolites do not bind covalently to hepatic DNA. However, PDA‐derived radioactivity was found to bind with hepatic protein of both sexes of each species.