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  • Title: [Three months oral repeated dose toxicity of T-3761 in beagle dogs].
    Author: Nakagawa S, Nagai A, Nagasawa M, Yoshida K, Iwai N, Sanzen T, Kawamura Y, Kodama T.
    Journal: Jpn J Antibiot; 1995 Jun; 48(6):790-831. PubMed ID: 7666582.
    Abstract:
    A three months oral repeated dose toxicity study was carried out in beagle dogs at dosages of 300, 100, 30 and 10 mg/kg, respectively. The following results were obtained. 1. There was no death of animals during administration at any dose levels. A few to all animals in all T-3761 treated groups complained of pain at the time of extension of limbs. 2. Mild decrease of body weight was observed in 1 of the 10 animals at 300 mg/kg and 1 of the 8 animals at 100 mg/kg, respectively. 3. In urinalysis, crystals which seemed to be the test compound in the urinary sediment, were observed in 5 of the 10 animals at 300 mg/kg and 4 of the 8 animals at 100 mg/kg, respectively. 4. In blood biochemical examination, mild elevation of GPT was observed in 1 of the 10 animals at 300 mg/kg. Increase of A/G ratio was observed in males at 300, 100 and 30 mg/kg, and females at all dose levels. 5. In macroscopic findings at necropsy, blister and erosion were observed at articular cartilage of shoulder, elbow, hip, and/or knee joints in all animals at 300 and 100 mg/kg, 7 of the 8 animals at 30 mg/kg and 1 of the 8 animals at 10 mg/kg. 6. No toxic dose level was less than 10 mg/kg/day in this study.
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