Comparison of the toxic effects of dehydroheliotridine and heliotrine in pregnant rats and their embryos.
Female hooded rats were injected intraperitoneally on the 14th day of pregnancy with dehydroheliotridine (DHH), a pyrrolic metabolite of pyrrolizidine alkaloids, at 30 to 90 mg/kg, or with the alkaloid heliotrine at 200 mg/kg and the effects on the embryos were evaluated on the 20th day. DHH was both growth-retarding and teratogenic. A dose of 40 mg DHH/kg approximated 200 mg heliotrine/kg in its effects on embryos, the principal abnormalities being skeletal, including retarded ossification, distorted ribs and long bones, cleft palate and feet defects. At higher dose rates growth almost ceased in many tissues and although more than 60 per cent. of the embryos were alive they would not have survived birth. All were very immature and had multiple skeletal and visceral defects. The effects observed in the liver were anomalous in that the embryonic parenchyma showed little response to the anti-mitotic activity of DHH.
D000014:Abnormalities, Drug-Induced / Q000196:embryology*; D000818:Animals; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005317:Fetal Growth Retardation / Q000139:chemically induced; D005865:Gestational Age; D016686:Monocrotaline / Q000031:analogs & derivatives*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011763:Pyrrolizidine Alkaloids / Q000378:metabolism / Q000633:toxicity*; D051381:Rats
D011763:Pyrrolizidine Alkaloids; D016686:Monocrotaline; C007241:dehydroretronecine; C010178:heliotrine