Toxic effects of methylcyclopentadienyl manganese tricarbonyl (MMT) in rats: Role of metabolism

The toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT) has been investigated in relation to its in vivo biotransformation in the rat. The LD₅₀ dose of MMT was found to be 50 mg/kg for oral administration and 23 mg/kg for ip administration. Death appeared to be caused by severe pulmonary hemorrhagic edema. Histological studies of MMT-treated animals revealed pathologic changes in lungs, liver, and kidney. Phenobarbital pretreatment protected rats from the lethal effects of 2.5 times the LD₅₀ dose of MMT, it shifted the site of tissue injury from the lungs to the liver, and it caused a doubling of the rate of biliary excretion of MMT metabolites. The possibility is discussed that MMT per se is toxic without bioactivation, and that the protective effect of phenobarbital pretreatment is due to a first-pass effect preventing toxic concentrations of orally administered MMT from reaching the systemic circulation.