Synthesis and mutagenicity of 3,3'-dihalogenated benzidines

3,3'-Difluorobenzidine (F2Bz), and 3,3'-dibromobenzidine (Br2Bz) were synthesized and compared with 3,3'-dichlorobenzidine (Cl2Bz) for ability to revert Salmonella typhimurium. The relative mutagenicities in all systems are Cl2Bz approximately equal to Br2Bz greater than F2Bz greater than Bz. F2Bz, Cl2Bz, and Br2Bz are direct-acting mutagens towards S. typhimurium strain TA98. The acetylase-deficient derivative TA98/1,8-DNP6 displays no resistance to induction of mutagenesis by these compounds, in the absence of mammalian activation. With addition of hamster hepatic S-9 activation the mutagenicity of these compounds increases greatly. TA98/1,8-DNP6 shows some resistance to this mutagenicity. Multiple mechanisms must exist for the genotoxicity of 3,3'-dihalogenated benzidines.