Developmental toxicity during the preimplantation period: embryotoxicity and clastogenic effects of chlorambucil in the rat.
To evaluate the toxicological effects of chemicals on preimplantation mammalian embryos, pregnant rats were treated with chlorambucil (0, 3, 6, and 12 mg/kg IP) on day 1, 2, or 3 of gestation (positive vaginal smear = day 0). Blastocysts were collected on day 4 and evaluated for gross morphology, cell number, and mitotic index. Some females treated on day 3 post coitum were sacrificed on day 20 and fetuses were evaluated for teratogenic effects. On day 4 of gestation a dose-related reduction of cell number/embryo was recorded; this effect was most manifest with treatment on day 3 post coitum. The mitotic index was significantly higher in all treated groups. A dose-related increase in "micronucleus-like bodies" has been observed in treated embryos. A comparison with the micronucleus test in the bone marrow revealed a major sensitivity of the embryonic material. No malformations have been observed in fetuses at term, but their weights were significantly reduced and a dose-related increase of postimplantation loss was recorded in treated females.
D000818:Animals; D001755:Blastocyst / Q000648:ultrastructure; D001853:Bone Marrow / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002699:Chlorambucil / Q000633:toxicity*; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens
D013723:Teratogens; D002699:Chlorambucil