Carcinogenicity of an oxidation product of p-phenylenediamine

Abstract

para-Phenylenediamine (p-PD), a widely used aromatic amine in the preparation of commercial oxidative-type hair dyes, has been previously demonstrated to have neither mutagenic activity to Salmonella typhimurium nor carcinogenic activity in rats and mice. In this study, the mutagenicity of p-PD after an oxidation by hydrogen peroxide towards S. typhimurium TA98 and its carcinogenicity in Wistar rats were examined both by topical application to the shaved skin and by s.c. injection. The oxidation product was found to be strongly mutagenic to the bacterial tester strain in the presence of rat liver S-9 fraction. Interestingly, in female rats, both topical application and s.c. injection for 18 months of oxidized p-PD could induce a statistically significant incidence of mammary gland tumors (greater than 50%, P less than 0.05). In addition, uterine tumors and soft tissue tumors of both malignant and benign types were also significantly induced (43% and 57%, P less than 0.05) in the s.c. injection group. On the other hand, tumors of mammary gland and soft tissue were not observed in male rats under similar experimental conditions. However, tumors of other organs including liver, kidney, adrenal gland, thyroid gland, urinary bladder and lung were occasionally observed in male rats of both groups and might be related to the p-PD treatment.