[Safety evaluation of micronomicin. I. Subacute and chronic toxicity in dogs]

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara by Nara et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Toxicological studies of MCR in dogs were carried out by intravenous injection for safety evaluation. 1. Study on subacute toxicity: Beagle dogs were injected intravenously with MCR at the dose levels of 4, 10, 25, 63 mg/kg and 100 mg/kg for 30 days. 2. Study on chronic toxicity: Beagle dogs were injected intravenously with MCR at the dose levels of 1.6, 4 mg/kg and 10 mg/kg for 180 days. The results of the studies are as follows: 1. In the subacute toxicity study, animals died at the dose level of 100g/kg (3 out of 6 animals). Main changes observed were renal disorders and ataxia which showed a close similarity to those seen during intramuscular toxicity studies in dogs. The renal histological disorders occurred at the dose levels of 10 mg/kg and over, but they were slight at the dose levels of 10 mg/kg and 25 mg/kg. Ataxia was observed at the dose levels of 63 mg/kg and over, but its grade was slight at the dose level of 63 mg/kg. 2. In the chronic toxicity study, animals did not die at any dose. Renal disorders occurred; they were almost similar to those observed in the subacute toxicity study and were slight at the dose level of 10 mg/kg. Ataxia was not observed at any dose. 3. The maximum safety dose was equal to in the subacute toxicity and chronic toxicity study (4 mg/kg). Therefore, cumulative toxicity by intravenous injection seemed very slight.