Repeated administration of a mild acute toxic dose of di-n-butyltin dichloride at intervals of 3 weeks induces severe lesions in pancreas and liver of rats

Di-n-butyltin dichloride (DBTC) induced thymus atrophy, bile duct lesions, pancreatitis, and liver lesions in rats. Depending on dose [ 6 and 8 mg/kg intravenous (i.v.) DBTC I and time (1-24 weeks), the lesions in pancreas de veloped to a pancreatic fibrosis and the lesions in liver to liver cirrhosi s. A single i.v. administration of 4 mg/kg DBTC induces a mild interstitial pancreatitis after 2-4 days followed by a restitutio ad integrum after 21- 28 days. In the present study, the lesions of biliopancreatic duct, pancrea s, and liver of rats after repeated administration of 4 mg/kg DBTC Lv. at i ntervals of 3 weeks have been investigated. The histopathological changes o f pancreas and liver were examined by light microscopy 1, 4, and 7 days and 2,3,4,6,9, and 12 weeks after administration of DBTC. Furthermore, pathobi ochemical parameters of pancreatitis (amylase and lipase activity in serum) , liver lesions (alkaline phosphatase activity and bilirubin in serum), and of fibrosis (hyaluronic acid in serum) were studied. Repeated administrati on of rats with DBTC (4 mg/kg i.v.) at intervals of 3 weeks induced an acut e interstitial pancreatitis and after 9 - 12 weeks, a pancreatic fibrosis a nd liver lesions (intrahepatic bile duct hyperplasia, inflammation in perip ortal tract, and necrosis). In serum, elevated levels of alkaline phosphata se, bilirubin, and hyaluronic acid were found. This study demonstrates that the organotin compound induces toxic effects on pancreas and liver of rats by repeated administration of lower doses at long intervals. The risk of e xposure to organotin at long intervals should be considered.