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  • Title: [Toxicological studies on (2''R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic. Its acute toxicity in rats].
    Author: Kurebe M, Sasaki H, Niizato T, Miki M, Kajita T.
    Journal: Jpn J Antibiot; 1986 Jan; 39(1):259-63. PubMed ID: 3702060.
    Abstract:
    (2''R)-4'-O-Tetrahydropyranyladriamycin (THP), a new antitumor antibiotic of anthracycline derivative, was given to Jcl-SD strain rats through intravenous (i.v.), intraperitoneal (i.p.), subcutaneous (s.c.) or oral (p.o.) administration routes and the animals were observed in respect of mortality, clinical signs and body weight for 21 days. Autopsy was done and histopathology on the tissues showing macroscopic abnormality was performed. The results were summarized as follows. Values of LD50 were 18.09 mg/kg i.v., 22.58 mg/kg i.p., 25.39 mg/kg s.c. and above 1,013 mg/kg p.o. for males and 18.07 mg/kg i.v., 20.30 mg/kg i.p., 21.76 mg/kg s.c. and above 1,013 mg/kg p.o. for females. No significant difference was found in LD50 values of different sexes. When higher than lethal dose levels of THP was given to animals, their clinical signs grew worse and weight loss occurred in about 5 days after the administration of the drug. Thereafter, deaths were observed. Macroscopic and microscopic observations on dead and survived rats revealed atrophy of spleen and thymus, whity clouding of spleen capsule, hemorrhage in mucosa of glandular stomach and congestion and hemorrhage in testes. These results suggest that THP shows weaker acute toxicity to rats than doxorubicin does, but the toxic effect of THP is approximately the same as that of other anthracycline derivatives.
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