【Animal Modeling】-Discussion on the mode of administration of cyclophosphamide in rabbit embryo-fetal developmental toxicity test

  Objective: To investigate the effects of different administration routes and doses of cyclophosphamide on the embryos and fetuses of pregnant rabbits, so as to determine the best administration method for inducing fetal malformation in rabbits.

  Methods: Pregnant rabbits were divided into normal saline control group C, intravenous injection Y1 group (15 mg/kg), subcutaneous low-dose Y2 group (20 mg/kg) and subcutaneous high-dose Y3 group (30 mg/kg). All groups were administered according to the corresponding route from GD10 to 13 (GD0 on the day of conception). GD28 dissection, check the number of corpus luteum, number of implantation, weight of conjoined uterus, fetus absorption rate; take fetus, check fetus sex, body length, tail length, number of live fetuses, number of stillbirths, and perform appearance deformity, visceral deformity and skeleton as required Deformity check.

  Results: The fetuses of pregnant rabbits in the cyclophosphamide intravenous injection group and subcutaneous injection low-dose group were all deformed. were 20.51% and 47.83%. In the high-dose subcutaneous injection group, the incidence of resorption was 100%.

  CONCLUSION: Subcutaneous injection of cyclophosphamide 20 mg/kg at GD10-13 in pregnant rabbits can be used as a positive administration method in the developmental test of rabbit embryo-fetal toxicity. The method has the advantages of short administration cycle, convenient operation, less fetuses absorbed, and high fetal malformation rate, which can provide a basis for colleagues to select a suitable rabbit embryo-fetal developmental toxicity positive model.