Acute studies to investigate the mechanism of action of caffeine as a teratogen in mice.
1 In Charles River CD1 mice, a single dose of 100 mg kg-1 caffeine injected intraperitoneally on day 14 of pregnancy caused a low incidence of cleft palate in the fetuses. 2 Single oral doses of caffeine of 200 and 300 mg kg-1 but not 100 mg kg-1 on day 14, caused cleft palate in some of the fetuses, but was clearly toxic to the dams. 3 Oral doses of caffeine up to 300 mg kg-1 on day 14 of pregnancy did not reduce utero-placental blood flow, placental transfer function, or amniotic fluid volume. 4 An oral dose of 100 mg kg-1 caffeine induced a marked stimulation of adrenocortical secretion producing plasma corticosterone levels of 1248 +/- 129 microgram per 100 ml by 2 h and with elevated levels persisting more than 8 h. 5 It is suggested that the elevated plasma corticosterone is the cause of the cleft palate induced in mice by caffeine. Since corticosterone is a known cleft palate inducer in mice but not in man these results do not predict a hazard from normal caffeine consumption in man.
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000302:Adrenal Cortex / Q000187:drug effects; D000653:Amniotic Fluid / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000633:toxicity*; D002972:Cleft Palate / Q000139:chemically induced; D003345:Corticosterone / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D010920:Placenta / Q000098:blood supply; D011247:Pregnancy; D012039:Regional Blood Flow / Q000187:drug effects
D002110:Caffeine; D003345:Corticosterone