Disposition and toxicity of methylcyclopentadienyl manganese tricarbonyl in the rat.
The disposition and toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT) was studied in Sprague-Dawley rats after subcutaneous administration at a dose of 4 mg/kg. Blood, lung, liver and kidney Mn levels were increased between 1.5 and 96 h after MMT injection, with peak organ levels occurring at 3-6 h. At this time the MMT-derived Mn concentration in lung, liver and kidney averaged 13-, 4- and 4-fold higher, respectively, than in the blood, indicating the accumulation and retention of MMT (or metabolite) in these tissues. Maximal pulmonary toxicity, as assessed by pulmonary lavage protein levels, occurred 24-48 h after injection. Plasma urea and sorbitol dehydrogenase levels were not increased at any time after MMT, suggesting minimal or no hepatic or renal injury. That maximal pulmonary toxicity occurred after peak Mn accumulation, and that the organ-specific toxicity of MMT correlated with its accumulation and retention, suggests a causal relationship between tissue Mn accumulation and MMT-induced toxicity.
D000818:Animals; D008168:Lung / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000378:metabolism; D009942:Organometallic Compounds / Q000378:metabolism* / Q000633:toxicity; D011506:Proteins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D009942:Organometallic Compounds; D011506:Proteins; C009907:2-methylcyclopentadienyl manganese tricarbonyl; D008345:Manganese