The toxicological Evaluation of Tallysomycin s10b -Biosynthettc Tallysomycin Dertvative

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Abstract
Tallysomycin S 10b, a biosynthetic derivative of tallysomycin R, was subjected to intravenous toxicologic studies in mice and dogs. LD.50- and LD 10. values from lethality studies in mice were utilized to establish dose levels for single and five daily dose toxicity studies in mice and dogs. Nephrotoxicity was the most consistent and prominent drug-related alteration in single and multiple dose studies in hoth species and was considered the dose limiting toxicity. Other toxicities included pulmonary toxicity, lymphopenia and necrosis of extremities in mice and dogs and testicular degeneration and focal vacuolation of adrenal cortical cells in the dog. Bleomycin was administered to 2dogs as a reference control agent at a single dose of 270 mg/m2 which was approximately equivalent to the highest tallysomycin S.10b dose of 240 mg/m2 Tallysomycin S10b showed a greater nephrotoxic potential than bleomycin at earlier time periods. However, at termination there was no meaningful difference in the degree of chronic nephrotoxicity. The pulmonary toxicity of both drugs was comparable.