CHRONIC TOXICITY OF DICYCLOPENTADIENYLIRON (FERROCENE) IN DOGS

Daily oral administration of dicyclopentadienyliron (ferrocene) at dosages of 30, 100, and 300 mg/kg for 6 months and 1000 mg/kg for 3 months produced hemosiderosis with an unusually high, dose-related accumulation of iron in dogs. A decrease in hemoglobin, packed cell volume, and erythrocyte count occurred within 4 weeks in dogs receiving 300 mg/kg. Dosages of 300 and 1000 mg/kg resulted in cirrhosis, which was considered to be an effect of the hydrocarbon moiety. At the end of the 6-month period of compound administration, testicular hypoplasia was found in dogs that received a ferrocene dosage of 100 or 300 mg/kg or oral ferrous sulfate dosages of 150 or 500 mg/kg. No other evidence of latent effects of massive chronic iron overload was observed in dogs that were kept for 12-26 months after the 6-month treatment period. The ferrocene-induced hepatic iron overload was reduced after the removal of large quantities of iron by repeated venesection resulting in mobilization of storage iron for hemoglobin synthesis. © 1969.