A new potent teratogen in CD rats inducing cleft palate.
The teratogenic potential of cis-1-[4-(p-menthane-8-yloxy)phenyl] [corrected] piperidine (YM9429) was evaluated using CD (SD) rats. YM9429 induced cleft palate and specific skeletal variations including accessory cervical and lumbar ribs or excessive formation of the 7th lumbar vertebra by oral treatment during the organogenetic periods. No visceral or external malformations were induced, and no embryo/fetal mortality or fetal growth retardation was observed. Maternal plasma biochemical examination revealed decreases of cholesterol and phospholipid levels during days 15-17 of pregnancy after the treatment. The results suggest that YM9429 is a potent and specific teratogen inducing cleft palate in CD rats, and the reduced maternal plasma levels of cholesterol and phospholipid during the period of palatine closure are related to the induction of cleft palate.
Shibata
M
M
Yamanouchi Pharmaceutical Co. Ltd., Safety Research Laboratories, Tokyo, Japan.
D000014:Abnormalities, Drug-Induced; D000015:Abnormalities, Multiple / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D002784:Cholesterol / Q000097:blood; D002972:Cleft Palate / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000473:pathology; D008159:Lumbar Vertebrae / Q000002:abnormalities; D010743:Phospholipids / Q000097:blood; D010880:Piperidines / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012272:Ribs / Q000002:abnormalities; D013723:Teratogens / Q000633:toxicity*
D010743:Phospholipids; D010880:Piperidines; D013723:Teratogens; C084611:YM 9429; D002784:Cholesterol