Inhalation toxicity studies of thimet (phorate) in male Swiss albino mouse, Mus musculus: I. Hepatotoxicity.

Biochemical and histopathological changes in serum and liver of the male Swiss Albino mouse, Mus musculus, exposed subchronically to the recommended field dose of Thimet (6728.5 mg m(-3)) in a whole body inhalation chamber were studied in the second, fourth, sixth, eighth, tenth and twelfth week of exposure. A significant rise in Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) activities were observed throughout the experiment. Alkaline phosphatase (ALP) activity showed a significant rise from the fourth week of exposure until the end of the experiment. The rise in the activities of these enzymes suggested hepatocellular necroinflammatory disease. Total bilirubin level was increased significantly throughout the experiment (indicative of jaundice); however the direct bilirubin level was significantly high in the tenth and twelfth week of exposure and indirect bilirubin showed a significant rise from the fourth week of exposure until the end of the experiment. Changes in bilirubin levels (direct and indirect) suggested both prehepatic and hepatocellular hyperbilirubinaemia. The biochemical changes observed and fatty change in the liver were confirmed by histopathological studies. Liver lesions were present throughout the experimental period. These consisted of mild to severe multifocal cloudy, hydropic and fatty degenerations, with necrosis. After a 30-day recovery period most of the histopathological and biochemical changes except the AST level were almost back to normal. These results suggest the inhalation of Thimet (Phorate) at the recommended field dose could affect the liver of Mus musculus.