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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

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Rostock, 18057 Rostock, Germany

H Weber

Institute of Clinical Chemistry and Pathobiochemistry, University of Rostock, 18057 Rostock, Germany

G Kröning

G Hennighausen

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Rostock, 18057 Rostock, Germany

Di n-butyltin dichloride (DBTC) induced thymus atrophy, bile duct lesions, pancreatitis, and liver lesions in rats. Dependingondose [6and8mg/kgintravenous (i.v.) DBTC] andtime (1–24weeks),thelesionsinpancreasdevelopedto apancreaticfibrosisandthelesionsinlivertolivercirrhosis. 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,thelesionsofbiliopancreaticduct,pancreas,andliver of rats after repeated administration of 4 mg/kg DBTC i.v. at intervals of 3 weeks have been investigated. The histopathologicalchangesofpancreasandliverwereexaminedbylight microscopy1,4,and7daysand2,3,4,6,9,and12weeksafter administration of DBTC. Furthermore, pathobiochemical 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 administration of rats with DBTC (4mg/kgi.v.) atintervals of3weeks induced anacute interstitial pancreatitis and after 9–12 weeks, a pancreatic fibrosis and liver lesions (intrahepatic bile duct hyperplasia, inflammation in periportal tract, and necrosis). In serum, elevated levels of alkaline phosphatase, 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 exposure to organotin at long intervals should be considered.

Key Words: di n-butyltin dichloride • biliopancreatic duct lesions • pancreatitis • pancreatic fibrosis • intrahepatic bile duct hyperplasia

Human & Experimental Toxicology, Vol. 20, No. 8, 386-392 (2001)
DOI: 10.1191/096032701682692964


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