Relation of dosage and time of administration of diphenylhydantoin to its teratogenic effect in mice

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Abstract
Diphenylhydantoin was teratogenic and caused prenatal death in Swiss‐Webster mice. Most deaths resulted after single treatment on days 10, 11, 12, 14, and 15. Fetal body weight was significantly reduced in a dose‐related manner after single treatment on days 9 to 15. Single injections of diphenylhydantoin produced open eye, ectrodactyly, cleft lip, cleft palate, hydronephrosis, and internal hydrocephalus. Skeletal defects noted were incomplete ossification of sternebrae or cervical centra, unfused sternebrae, and fused vertebrae. Long bones were shortened in a day‐ and dosage‐dependent fashion. Mortality, teratogenesis, and effect on fetal growth were day‐ and dosage‐dependent as was the spectrum of anomalies produced.

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