Phenazine derivatives as the mutagenic reaction product from o- or m-phenylenediamine derivatives with hydrogen peroxide.
8 Kinds of o- and m-phenylenediamine (PD) derivatives, which are used as oxidative-type hair dyes, were treated with hydrogen peroxide (H2O2). Both before and after H2O2 treatment, their mutagenicity was tested by using Salmonella typhimurium TA98 in the presence or absence of a mammalian metabolic activation system (S9 mix). After H2O2 treatment, the mutagenic potencies of p-nitro-o-phenylenediamine, 3,4-diaminotoluene, p-nitro-m-phenylenediamine and 2,4-diaminophenol did not vary or slightly increased in comparison with those of the starting materials. The mutagenicity of o-PD, p-chloro-o-phenylenediamine (p-Cl-o-PD), m-PD and 2,4-diaminoanisole (p-OMe-m-PD) was enhanced remarkably by treatment with H2O2 and all the oxidation products required metabolic activation by S9 mix for their mutagenesis. In a gas chromatography/mass spectrometric study, 2,3-diaminophenazine and 2,7-diaminophenazine were identified with authentic samples in o-PD and m-PD oxidation mixture, respectively. The oxidation mixture obtained from p-Cl-o-PD and p-OMe-m-PD was separated into several fractions by repeated column chromatography. Brownish yellow crystals were isolated from oxidized p-Cl-o-PD and the structure of the compound was determined to be 2,3-diamino-7-chlorophenazine from physicochemical and chemical evidence. Two reddish yellow crystals, obtained from oxidized p-OMe-m-PD, were 2,7-diamino-3,8-dimethoxyphenazine and 2,7-diamino-3-methoxyphenazine. The number of revertants induced by 1 nmole of phenazines detected from oxidized PD derivatives was as follows; 2,3-diaminophenazine: 349 rev.; 2,3-diamino-7-chlorophenazine; 406 rev.: 2,7-diaminophenazine: 12 110 rev.; 2,7-diamino-3,8-dimethoxyphenazine: 4229 rev.; 2,7-diamino-3-methoxyphenazine: 24 640 rev. in S. typhimurium TA98 strain with 25 microliters S9 per plate.
Watanabe
T
T
Kyoto Pharmaceutical University, Japan.
Hirayama
T
T
Fukui
S
S
D000818:Animals; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D006202:Hair Dyes / Q000633:toxicity*; D006203:Hair Preparations / Q000633:toxicity*; D006861:Hydrogen Peroxide; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics; D010084:Oxidation-Reduction; D010619:Phenazines / Q000493:pharmacokinetics / Q000633:toxicity*; D010655:Phenylenediamines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000235:genetics
D006202:Hair Dyes; D006203:Hair Preparations; D009153:Mutagens; D010619:Phenazines; D010655:Phenylenediamines; D006861:Hydrogen Peroxide