Teratogenic effects of carboplatin, an oncostatic drug, administered during the early organogenetic period in rats.
In the preceding study, no teratological effects against rat fetuses were observed when carboplatin, an oncostatic platinum coordination complex, was dosed to their dams from days 7 to 17 of gestation at a dose level of 4 mg/kg/day. However, there are a few reports which show the teratogenic action of carboplatin injected from days 6 to 15 of pregnancy at a dose level of 6 mg/kg/day. In the present study, carboplatin was administered intravenously to pregnant female Crj: CD (Sprague-Dawley) rats from days 6 to 9 or 7 to 10 of gestation at a dose level of 6 mg/kg/day in order to know the teratogenicity of this drug. Carboplatin were highly embryolethal in dams when dosed from days 6 to 9 of gestation, but not in animals when injected from days 7 to 10 of pregnancy. Carboplatin also produced external, internal and skeletal anomalies in fetuses such as gastroschisis, dilatation of cerebral ventricles, cleft sternum, fused ribs, malformed thoracic vertebra when administered from days 6 to 9 of gestation, but not in conceptuses when dosed from days 7 to 10 of pregnancy. However, the delayed ossification which was ascribed to the fetal growth retardation was observed in rats treated with this drug during both administration periods. These results suggest that carboplatin is embryotoxic, inducing intrauterine death and congenital malformations in rats, when injected during the early stages of gestation including day 6 of pregnancy.
Kai
S
S
Drug Safety Research Department, Bristol-Myers Research Institute, Ltd. Aichi, Japan.
Kohmura
H
H
Ishikawa
K
K
Makihara
Y
Y
Ohta
S
S
Kawano
S
S
Takahashi
N
N
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities; D016190:Carboplatin; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D008297:Male; D009944:Organoplatinum Compounds / Q000633:toxicity*; D010012:Osteogenesis / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016190:Carboplatin