Abstract
Single oral doses ranging from 20 to 960 mg/kg of procarbazine were given to pregnant SD-JCL rats on any one day between day 3 and day 14 of gestation (sperm day = day 0). The rats were sacrificed at term and their fetuses examined for external, visceral and skeletal anomalies. The results were summarized as follows. 1. In general, susceptibility of embryos to the lethal action of procarbazine decreased as development proceeded. However, fetal mortality in rats treated on day 7 was higher than that on day 6. 2. Term fetuses exhibited gross external malformations such as microcephaly, micrognathia, cleft palate, anal atresia, shortening or curvature of the tail, hypoplastic digits, reduction deformities of the limb and generalized edema. The microcephaly was complicated with hydrocephaly and produced by treatment on day 8 to day 14. Micrognathia, cleft palate, shortening or curvature of the tail and hypoplastic digits were detected in fetuses treated on day 10 or later. The critical period for reduction deformities of the limb was between day 11 and day 14. 3. Visceral examination revealed enlargement and deformation of the brain ventricles, anophthalmos and microphthalmos, and lower position of the ovary or higher position of the testis. Eye anomalies were observed in fetuses treated before day 9. The critical period for the enlargement of the lateral ventricles extended over all days of administration. After day 10 of gestation, the treatment induced enlargement of the lateral ventricles complicated with enlargement of the third ventricle or atrophy in a posterior part of the cerebrum. 4. Skeletal I malformations were observed in the skull and facial bones, vertebrae, ribs, clavicle, scapula, ossa coxae and limb bones. The vertebral anomalies, which were detected in the cervical and thoracic segments at lower doses, involved all vertebral segments at higher doses. Deformities in the clavicle, scapula and ossa coxae, together with malformed limb bones, were found in fetuses treated after day 10. Hindlirnb bones, especially the fibula, were more susceptible to procarbazine than forelimb bones.
