Effects of maternal age on teratogenicity of di-n-butyltin diacetate in rats.
The present study was designed to assess changes in the teratogenic potency of di-n-butyltin diacetate (DBTA) with increasing maternal age in rats. Pregnant Wistar rats of 3, 7.5 or 12 months were treated orally with DBTA at 0, 7.5, 10, 15 or 22 mg/kg on day 8 of gestation. Cesarean sections were performed on day 20 of gestation. Maternal age had greater impact on litter size in the 7.5- and 12-month dams than the 3-month dams. The death of most of the fetuses of the 12-month dams made it difficult to evaluate the teratogenic potency of DBTA. In 3-month groups, fetuses with external malformation, such as cleft mandible, cleft lower lip, ankyloglossia and/or schistoglossia, which are malformations typical of DBTA, were observed at 15 and 22 mg/kg, while similar malformations were observed in 7.5-month groups at doses of 10 mg/kg and above. At 15 and 22 mg/kg, the incidences of these malformations in 7.5-month groups were similar to these from 3-month groups. In our previous studies, however, single DBTA-treatment at 10 mg/kg on day 8 of gestation has not produced such malformations from 3-month dams. The results suggest that the teratogenic potency of DBTA in 7.5-month dams may be greater than in 3-month dams.
Noda
T
T
Osaka City Institute of Public Health and Environmental Sciences, 8-34 Tojo-cho Tennoji, Osaka, 543-0026, Japan. noda23@nara-i.net
Yamano
T
T
Shimizu
M
M
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008423:Maternal Age; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D009947:Organotin Compounds / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity*; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
D009947:Organotin Compounds; D013723:Teratogens; C004924:dibutyltin diacetate