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.