title: Developmental toxicity during the preimplantation period: embryotoxicity and clastogenic effects of chlorambucil in the rat.
abstract: 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.
mesh_terms: 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
chemical_list: D013723:Teratogens; D002699:Chlorambucil