Teratogenicity of cyclophosphamide in New Zealand white rabbits.
Pregnant rabbit does received daily oral doses of 6.2 or 18.6 mg/kg cyclophosphamide (CP) on days 6-20 of gestation. On day 29, shortly before term, the uterine content was removed by Caesarean section. At the dose of 6.2 mg/kg CP maternal mortality was 2/9 does and at 18.6 mg/kg CP one abortion was recorded. Body weight gain of pregnant females was essentially unaffected by CP treatment. Both doses of CP elicited significant dose-dependent decrease of fetal body, organ (heart, lung, liver, kidney) as well as placental weight. After treatment with 18.6 mg/kg CP, gross examination of fetuses revealed significantly increased incidence of exophthalmos, cleft palate/lip, syndactyly, and brachycardia. Skeletal anomalies and malformations, significantly increased after the higher CP dose, included sternebrae, back-bone and limb defects. Oral administration of CP to rabbits in the dose of 18.6 mg/kg during organogenesis resulted in pronounced embryotoxic and teratogenic changes.
Ujházy
E
E
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Balonová
T
T
Durisová
M
M
Gajdosík
A
A
Jansák
J
J
Molnárová
A
A
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001848:Bone Diseases, Developmental / Q000139:chemically induced; D003338:Corpus Luteum / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011817:Rabbits
D003520:Cyclophosphamide