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The Teratogenicity of Cyclophosphamide in Mice^{1 ,2}

Department of Pharmacology, Oakdale Toxicology Center, University of Iowa College of Medicine, Iowa City, Iowa 52240

Cyclophosphamide, administered intraperitoneally to time-dated pregnant Swiss Webster mice on gestational Days 9 through 14 in a dosage of 20 mg/kg, resulted in increased numbers of resorptions and a variety of teratogenic effects. Gross examination of fetuses revealed cleft palate, exencephaly, digital defects, and kinky tail. Skeletal anomalies included polydactyly, syndactyly, ectrodactyly, adactyly, fusion of the long bones, curvature of the long bones, and missing ribs. Soft tissue malformations included open eyes, aphakia, microphakia, hydronephrosis, and hydrocephalus. Dosages of 5 and 10 mg/kg resulted in increased resorption and decreased growth rates in a dose-related manner but produced no discernible anomalies. Fetal mortality curves were biphasic, with the highest peak occurring on administration Days 9 and 10 and a second peak on Days 13 and 14.

¹ This research was supported by NIH Grant No. GM-12675.

² A preliminary report of this work was presented at the Sixth Annual Meeting of the Society of Toxicology, Atlanta, Georgia, March 23–25, 1967.

³ USPHS Trainee, NIH Training Grant GM-1308.

Received 7/14/67. Accepted 11/ 4/67.

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