Studies of the mutagenicity and toxicity of benzidine,p-phenylenediamine, and their analogues

Benzidine and p-phenylenediamine are the major mutagenic moieties of azo dyes, and are widely used in many industries. Many azo dyes have been shown to be mutagenic. Some of them are not mutagenic per se, but intestinal and environmental bacteria can convert them into aromatic amines such as benzidine and p-phenylene-diamine. They can then interact with DNA to cause genotoxicity.; Many studies prove that very minor alteration of the chemical structure of aromatic amines might cause major differences in mutagenicity. Chapter I deals with the structure-activity relationships of benzidine and its analogues. The addition of chloro- or nitro-groups to the benzidine increases the mutagenicitiy greatly, while the mutagenicity is significantly decreased when tetramethyl groups are added to benzidine molecule. Some physicochemical parameters such as oxidation potential, energy differences between the Lowest Unoccupied Molecular Orbital (LUMO) and the Highest Occupied Molecular Orbital (HOMO), ionization potential (I.P.), dipole moment ({dollar}mu{dollar}), and pKa were determined for their correlations with mutagenic data. Only pKa is related to the mutagenicity based on the regression model and SAS system.; Benzidine and p-phenylenediamine have been widely used in the manufacture of commercial azo dyes for textile, paper, leather and plastics, and they can be generated from azo dyes through azo reduction by environmental microorganisms. The effect of their discharge from industries to environment was examined (Chapter II). The effect of analogues of benzidine or p-phenylenediamine on the growth of microoragnisms were explored. Moreover, their effects on the growth and nitrogenase activity of Azotobacter vinelandii were tested. Results showed that p-phenylenediamine and its analogues were more harmful to the growth of microorganisms than benzidine and its analogues. The nitrogenase activity of A. vinelandii was suppressed by some p-phenylenediamine analogues. In a series of benzidine analogues, only 4-aminobiphenyl and 3,3{dollar}spprime{dollar}-4,4{dollar}spprime{dollar}-tetraaminobiphenyl were inhibitory to the nitrogenase activity of A. vinelandii.; As an extension of our interest in structure-mutagenicity relationships of p-phenylenediamine, benzidine and their respective analogues, we want to understand the mutagenic specificity of these compounds. Nitro-group containing aromatic amines such as 2-nitro-p-phenylenediamine, 3-nitro-o-phenylenediamine, 4-nitro-ophenylenediamine and 4,4{dollar}spprime{dollar}-dinitro-2-biphenylamine were direct mutagens in TA100. These nitro-group containing compounds were characterized for base-pair mutations by the procedures of Levin and Ames (Chapter III). CG{dollar}to{dollar}TA transition and/or CG{dollar}to{dollar}AT transversion are major types of mutations induced by these nitro-group containing aromatic amines in Salmonella typhimurium TA 100.