The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 14 , Issue SupplementI
Showing 1-4 articles out of 4 articles from the selected issue
  • Yasushi KURATA, Akihiro HAGIWARA, Seiko TAMANO, Masa-Aki SHIBATA, Hika ...
    1989 Volume 14 Issue SupplementI Pages 1-39
    Published: August 20, 1989
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    The potential tumor-promoting effects of beraprost sodium (TRK-100), stable analogue of prostacyclin (PGI2), were investigated in rats pretreated with N-methyl-N-nitrosourea (MNU) which is a potent initiator of tumor development in a variety of organ or tissues. Male F344 rats were initially given injections of MNU (20 mg/kg b.w. i.p.) twice a week for 3 weeks, and then administered drinking water containing 6, 2, 0.7 or 0.2 ppm of beraprost sodium for the next 29 weeks. For comparison, positive control groups received N-propyl-N-nitrosourea (PNU), which is a carcinogen in hematopoietic system and small intes tine on F344 rat, at the dose of 200, 50 and 12.5 ppm in their drinking water. Appropriate non-treated controls were also included. Numerous tumors were observed in many organs including the hematopoietic system, digestive tract, nervous system, Zymbal's gland (auditory sebaceous glands) and peritoneal mesothelium. However, no tumor-enhancing effects of beraprost sodium were observed. In contrast, the groups treated with PNU demonstrated increased development of tumors in the tongue, forestomach, large intestine and Zymbal's gland. These results thus indicate that beraprost sodium is not capable of modulating the development of MNU-induced tumors.
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  • Sunao MANABE, Seiji SUDO, Kazuo YAMASHITA, Nobuhiro MIYAKOSHI, Naochic ...
    1989 Volume 14 Issue SupplementI Pages 41-55
    Published: August 20, 1989
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Pravastatin sodium was orally administered to cynomolgus monkeys at dosage levels of 50, 200 and 800 mg/kg/day for 7 successive days. Excretions of diarrhea and/or loose stool were observed in the more than 50 mg/kg dose group, but the changes were quite mild. Animals of the 800 mg/kg dose group showed vomiting, diarrhed and/or excretion of soft stool and reduction of cholesterol content in serum. In conclusion, it is estimated that the no effective level is less than 200 mg/kg because no abnormalities were observed except for only very slight excretions of diarrhea and/or loose stool, and that the effective dose is 800 mg/kg in which vomiting was observed.
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  • Sunao MANABE, Seiji SUDO, Kazuo YAMASHITA, Nobuhiro MIYAKOSHI, Naochik ...
    1989 Volume 14 Issue SupplementI Pages 57-83
    Published: August 20, 1989
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Pravastatin sodium was administered orally to cynomolgus monkeys at dosage levels of 50, 100, 200 and 400 mg/kg/day for 5 successive weeks. Five animals of 200 mg/kg and 400 mg/kg dose groups were sacrificed during the study period, because these animals deteriorated in general condition and/or showed remarkable changes in serum biochemical examination. Pathological examination revealed hepatic and/or renal disturbance in these animals. These changes are thought to be the cause of deterioration of general condition or changes in serum biochemical examination. All other animals were terminated at the end of the study period. In the animals of the 100 mg/kg dose group, only one animal showed hepatic and renal disorder similar in nature to the changes in the animals sacrificed during the study period. No animals in the 50 mg/kg dose group showed toxic findings in any examination.
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  • Chitoshi TARUMI, Naochika MATSUNUMA, Nobuhiro MIYAKOSHI, Kazuo YAMASHI ...
    1989 Volume 14 Issue SupplementI Pages 85-101
    Published: August 20, 1989
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Pravastatin sodium was successively given for 104 weeks to beagles orally at doses of 5 and 25mg/kg/day. A decrease in serum cholesterol levels was observed at week 4 and thereafter. No other abnormal findings were obtained in any animals in general conditions, hematological and biochemical examinationd, various function tests, and pathological examinations. The no-effect dose level in beagles receiving pravastatin sbdium orally for 104 weeks is toxicologically estimated to be more than 25mg/kg/day.
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