Studies on the toxic interaction between monensin and tiamulin in rats: Toxicity and pathology

The characteristics of the toxic interaction between monensin and tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxic ity study was performed in Phase I, when the effects of monensin and tiamul in were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 1 20, and 200 mg/kg body weight, respectively). In Phase II, the two compound s were administered simultaneously to study the toxic interaction (monensin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 and 50 mg/kg. Tiamulin was well tolerated up t o the dose of 200 mg/kg. After combined administration, signs of toxicity w ere seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect and vacuolar degeneration of the skeletal muscles in th e animals given 50 mg/kg. Both compounds exerted a toxic effect on the live r in high doses. After simultaneous administration of the two compounds, th ere was a mild effect on the liver (females only), hydropic degeneration of the myocardium and vacuolar degeneration of the skeletal muscles. The alte ration seen in the skeletal muscles was more marked than that seen after th e administration of 50 mg/kg monensin alone.