Reproductive and Developmental Toxicity Studies of Amrubicin Hydrochloride(SM-5887) (3)-Teratogenicity Study in Rabbits.
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Accession number;99A0241094
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| Title;Reproductive and Developmental Toxicity Studies of Amrubicin Hydrochloride(SM-5887) (3)-Teratogenicity Study in Rabbits. |
| Author;
HIGUCHI TOSHIHIRO
(Sumitomo Chemical Co., Ltd.)
UTSUMI TOORU
(Sumitomo Chemical Co., Ltd.)
TAKABA KATSUMI
(Sumitomo Chemical Co., Ltd.)
KODA AKIRA
(Sumitomo Chemical Co., Ltd.)
KATO TERUSHIGE
(Sumitomo Chemical Co., Ltd.)
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Journal Title;Japanese Pharmacology & Therapeutics
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Journal Code:Z0947A
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ISSN:0386-3603
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VOL.27;NO.Suppl.1;PAGE.S.461-S.472(1999)
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| Figure&Table&Reference;FIG.3, TBL.5, REF.10 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Amrubicin hydrochloride(SM-5887) was administered intravenously to pregnant rabbits(JW-NIBS) at the dosages of 0.15, 0.3 and 0.6mg/kg daily during the period of fetal organogenesis to examine its effects on dams and embryos/fetuses. 1) One dam was found dead in the 0.6mg/kg group. Three dams in the 0.6mg/kg group and one dam in the 0.3mg/kg group had abortions. 2) Maternal body weight gain was decreased in the 0.6mg/kg group late in the treatment period. Food consumption was not affected by treatment at any dosage level. 3) No treatment-related effect on dams was observed at necropsy. Necropsy of the dam found dead in the 0.6mg/kg group revealed hemorrhagic changes in heart, lung, digestive tract, subcutis and uterus. 4) Embryofetal death rate was increased in the 0.6mg/kg group, resulting in a decreased number of live fetuses. 5) No treatment-related abnormality was observed on external examination of live fetuses. Incidences of skeletal variations such as 13th ribs were increased in groups with dosages of 0.3mg/kg or higher. Fetuses in the 0.6mg/kg group had malformations in the axial skeleton including the cranial bones and malformations in the cardiovascular system. SM-5887 administration thus resulted in maternal death and decreased maternal body weight gain at 0.6mg/kg and abortions at 0.3mg/kg and higher dosages. The maternal no observed adverse effect level was therefore considered to be 0.15mg/kg. Embryofetal deaths and fetal abnormalities in the axial skeleton, cranial bones and cardiovascular system were observed at 0.6mg/kg and 13th ribs at 0.3mg/kg and higher dosages. The developmental no observed adverse effect level was therefore also considered to be 0.15mg/kg. (author abst.) |
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