[Subacute toxicity study of miporamicin in rats by twenty-eight-day administration in feed].
A 28-day oral dosage test of miporamicin (MPM), a new macrolide antibiotic, was performed to assess its toxicologic potential in groups of male and female rats receiving the compound in feed. Five graded dosage levels of 0, 3,200, 8,000, 20,000, and 50,000 ppm were employed for treatment with MPM in feed and the treatment period was followed by a 28-day recovery phase observation period. 1. No deaths occurred throughout the course of the experiment. Animals receiving 50,000 ppm developed signs: ruffled hair coat and emaciation, which disappeared following withdrawal of the drug. 2. The MPM-50,000 group displayed depression of weight gain and decrease of feed and water intake during the treatment period. During the posttreatment recovery phase observation period the animals showed recovery in weight gain rate as well as in feed and water intake. 3. The achieved compound dosage was 273 mg/kg/day in males and 288 mg/kg/day in females in the MPM-3,200 group, 721 and 773 mg/kg/day respectively in the MPM-8,000 group, 1,738 and 1,856 mg/kg/day in the MPM-20,000 group, and 3,405 and 3,611 mg/kg/day in the MPM-50,000 group. 4. Hematological examinations revealed low values for RBC, WBC, hematocrit and hemoglobin concentration and decreased platelet counts in the MPM-50,000 group, which were considered to be due to the decreased feed intake. These changes disappeared or abated following withdrawal. 5. Of various serum biochemical parameters assessed, total protein, albumin, glucose and triglycerides showed lowered values in the MPM-50,000 group. All these changes were considered to be attributable to the decreased feed intake. During the ensuing recovery phase observation period, all these parameters showed restoration or abatement in parallel with the recovery in feed intake. 6. Urine analysis disclosed decrease of urine volume, lowered electrolyte concentration and elevation of urine osmolarity in the MPM-20,000 and the MPM-50,000 groups. These changes were considered to be secondary to cecal enlargement which is commonly seen with antibiotic medication, or to the decreased feed and water intake. Following drug withdrawal, all these changes disappeared with the recovery in feed and water intake and abatement of cecal hyperplasia. 7. At terminal necropsy, diminution of body fat and atrophy of the spleen and thymus that correlated with emaciation were noted in the MPM-50,000 group. Dose-related enlargement of the caecum was also noted in the treated groups. All these changes disappeared or abated following withdrawal.(ABSTRACT TRUNCATED AT 400 WORDS)
Motoyama
K
K
Toxicological Research Laboratories, Toyo Jozo Co., Ltd.
Sumi
A
A
Miura
M
M
Yano
J
J
Morino
T
T
Matsumoto
K
K
Yamamoto
H
H
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D001769:Blood; D001772:Blood Cell Count / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004032:Diet; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D018942:Macrolides; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014556:Urine / Q000032:analysis
D000900:Anti-Bacterial Agents; D018942:Macrolides; C063027:mirosamicin