Subacute toxicity of several ring-substituted dialkylanilines in the rat

Aniline, o-toluidine, 2,4-dimethylaniline, 2,6-dimethylaniline, 2,6-diethylaniline, 2,6-methylethylaniline, 2,6-diisopropylaniline, and methylene-bis-2,6-diisopropylaniline were administered to male Fischer 344 rats daily for 5, 10 or 20 days. Histopathologic evaluation of selected tissues revealed splenic congestion, increased hematopoiesis and hemosiderosis, and bone marrow hyperplasia in aniline- and o-toluidine-treated animals. These changes, characteristics consistent with enhanced erythrocytic destruction, were not observed in any of the dialkylaniline-treated animals. Hepatoxicity, characterized by biliary hyperplasia, periacinar vacuolar degeneration, hepatocytic cloudy swelling and periacinar necrosis, was observed in methylene-bis-2,6-diisopropyl-, aniline- and 2,4-dimethylaniline-treated animals. Multifocal discrete areas of necrosis were also observed in livers of animals treated with the latter compound. There were no histopathologic changes which could be attributed to any of the alkylanilines studied in kidney, esophagus, trachea, thyroid, parathyroid or urinary bladder.