TOXICITY STUDIES OF TE-031 (A-56268) IV SUBACUTE TOXICITY IN RATS

• Published in: CHEMOTHERAPY Vol. 36; no. Supplement3; pp. 289 - 310
• Main Authors: OHSHIMA, TAKASHI, WATANABE, TAKASHI, NAKAMURA, ISAMU, KIMURA, MASAAKI, TSUCHIDA, TAKESHI, NAKANE, SADAO
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1988
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.36.Supplement3_289

TE-031 (A-56268), a new macrolide antibiotic, was administered orally to Wistar rats at doses of 12.5, 50, 200 and 800 mg/kg/day for 28 days to determine the subacute toxicity of the drug and recovery in the 28-day withdrawal period. The results are as follows. 1. No drug-related change except increased caecum weight were observed in the 50 mg/kg group. 2. Animals in the 200 mg/kg group, revealed elevation of GOT and GPT levels, increased liver and caecum weight, necrosis of hepatocytes and increased multinucleated hepatocytes. 3. In addition to the above changes, piloerection, nose- bleed and reduction in spontaneous activity were observed, and 31 deaths (13 males and 18 females) occurred during the treatment. Animals in the 800 mg/kg group showed decreased body weight gain accompanying decreased food consumption, increased incidence of occult blood, slight anemic changes, increased total cholesterol and phospholipid values, and decreased total protein value. In the 800 mg/kg group, pathological examination showed discoloration of liver, kidney and adrenal gland, swelling and increased fatty deposition in cortical tubular epithelia, atrophic changes in lymphatic tissues and genital organs, and swelling of adrenal cortical cells. 4. Effects of TE-031 were observed at dose leves of 200 mg/kg or more and these changes generally regressed or normalized in the recovery test. In our study, the no-effect dose of TE-031 was considered to be 50 mg/kg.