Metabolism of the hair dye component, nitro-p-phenylenediamine, in the rat.

Abstract

The metabolism of nitro-p-phenylenediamine (I), a constituent of hair dyes, was studied following its administration to male rats. Two major metabolites, N4-acetyl-2-nitro-1, 4-diaminobenzene (II) and N1, N4-diacetyl-1, 2, 4-triaminobenzene (IV), were isolated from the urine and identified. However, other N-acetyl regioisomers of II and IV, and the fully N-acetylated metabolite, 1, 2, 4-triacetylaminobenzene, could not be detected by high-pressure liquid chromatography. Further, N4-acetyl-1, 2, 4-triaminobenzene (III), a possible precursor of IV, could also not be detected in the urine.After the administration of the possible intermediates produced through the metabolism of I, the metabolite IV was isolated and identified from the urine of the animals. Based on the results of the present investigation, the hair dye constituent I appears to be metabolized successively to II, III and IV by regioselective N4-acetylation and subsequent nitro reduction, followed by regioselective N1-acetylation, because rats given II or III excreted IV in the urine. Compound I might be also metabolized through an alternative pathway to IV via 1, 2, 4-triaminobenzene (VI) formed by direct nitro reduction, because IV was excreted as a urinary metabolite in rats given VI or its N1-monoacetylated product (III-1). Thus, the metabolism of I appears to proceed through regioselective N-acetylation of the amino groups.