Studies on the embryotoxic risk of drug treatment during the preimplantation period in the mouse.
For risk evaluation of exposure to drugs in early pregnancy the dose-response relationship for embryotoxicity was determined in mice during the preimplantation period using cytotoxic drugs (cyclophosphamide, mitomycin, vinblastine) and therapeutic drugs which are embryotoxic in laboratory animals or in humans during organogenesis (diazepam, doxycycline, phenobarbital, rifamycin, tolbutamide). No malformations but only signs of retardation and a dose related increase in the resorption rate could be detected after treatment with some of the drugs at term even at dose levels close to the maternal LD50 (MLD50). A comparison of the embryolethal dose during the preimplantation period (ELD50) with the MLD50 revealed no risk for the therapeutic drugs, a slight risk for mytomycin and vinblastine and an unusually high risk for cyclophosphamide. The ELD50 for all drugs in this study was higher than the embryotoxic doses during organogenesis which is routinely determined for all drugs. It is concluded that for therapeutic drugs additional testing for embryotoxicity during early pregnancy is not required.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D000970:Antineoplastic Agents / Q000633:toxicity; D001755:Blastocyst / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects; D008297:Male; D051379:Mice; D011247:Pregnancy; D012306:Risk; D013723:Teratogens
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D013723:Teratogens