TOXICITY STUDIES ON TE-031 (A-56268) IX CHRONIC TOXICITY IN RATS

• Published in: CHEMOTHERAPY Vol. 36; no. Supplement3; pp. 311 - 333
• Main Authors: OHSHIMA, TAKASHI, YAGI, KENICHI, KASAI, AKIRA, IWAMATSU, YUKO, KIMURA, MASAAKI, NAKANE, SADAO
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1988
• DOI: 10.11250/chemotherapy1953.36.Supplement3_311
• ISSN: 0009-3165

TE-031 (A-56268), a new macrolide antibiotic, was administered orally to Wistar rats at doses of 1.6, 8, 40 and 200 mg/kg/day for 6 months to determine the chronic toxicity of the drug and recovery in the 2- month withdrawal period. The results are as follows. 1. No deaths occurred during the treatment and increased caecum weight was seen in all except the 40 mg/kg group. No other changes were observed in the 8 mg/kg or less groups. 2. In the 40 mg/kg group, salivation was sporadically seen and elevation of GPT levels was noted. Pathological examination revealed increased multinucleated hepatocytes, necrosis of hepatocytes and increased small round cell infiltration. 3. In addition to the above changes, animals in the 200 mg/kg group showed a slight decrease in body weight gain, increased sodium and decreased potassium values in urine, slight anemic changes, elevation of GPT and Al- P levels, decreased lipid and albumin levels. Pathological examination showed increase in liver, spleen and adrenal gland weight, and hepatotoxicity (in the 200 mg/kg group) was marked in comparison with the 40 mg/kg group. 4. The effects of TE- 031 were observed at dose levels of 40 mg/kg or more. These changes generally regressed or normalized in the recovery test. The no-effect dose of TE-031 was considered to be 8 mg/kg in the present study.