[Six-month chronic toxicity study of miporamicin in rats].

A six-month oral toxicity test of the new macrolide antibiotic miporamicin (MPM) was carried out in male and female rats receiving the compound in feed at concentrations of 1,280, 3,200, 8,000, or 20,000 ppm. The animals were further observed for recovery for 2 months after the completion of the treatment period. 1. No death occurred at any dosage levels throughout the study period. The only notable signs observed were marginal blepharitis and aging-associated changes that were seen occasionally among the treated and control rats. There were no symptomatic changes of particular note. 2. Body weight, feed intake and water consumption data did not reveal any noticeable change. 3. The achieved test compound intake was 69 mg/kg/day for males and 82 mg/kg/day for females in the MPM-1,280 group, 176 mg/kg/day for males and 207 mg/kg/day for females in the MPM-3,200 group, 436 mg/kg/day for males and 519 mg/kg/day for females in the MPM-8,000 group, and 1,080 mg/kg/day for males and 1,280 mg/kg/day for females in the MPM-20,000 group. 4. No changes attributable to these treatments were noted in the hematological examination or serum biochemical tests. 5. Urinalysis disclosed mild changes with respect to urine volume, urinary electrolyte concentration and osmolarity. Animals recovered from all these changes during the recovery phase observation. 6. At gross pathologic examination a dose-related enlargement of the caecum was observed. The change disappeared or diminished following the 2-month recovery phase observation. 7. Organ weight analysis showed a dose-related increase of weight of the caecum. Animals recovered or abated in this respect during the 2-month recovery phase observation. 8. Histopathologic examination revealed no adverse toxicologic changes other than spontaneous or aging-associated ones. 9. No abnormalities were noted in the liver or in the kidneys as examined by electron microscopy. 10. The maximum non-effective level of MPM thus was estimated to be 20,000 ppm at which no organic damage occurred.