Teratogenic effects of diphenyl diselenide in Wistar rats

Diphenyl diselenide is an organoselenium compound with potential therapeutic use. The present study evaluates the effects of single maternal subcutaneous injection of 50 and 100 mg/kg diphenyl diselenide [(PhSe)2] at gestational days (GD) 6, 10 or 17 in Wistar rats. The highest dose of (PhSe)2 was also administered at GD 7-12. External and internal fetal soft-tissue examination was performed at GD 20. No mortality was observed in fetuses or dams at any (PhSe)2 treatment group. Neither did exposure to (PhSe)2 cause significant changes to fetal body weight, organ weight, or fetal size when administered at GD 6-8, 10-12 or 17. Exposure to 100 mg/kg (PhSe)2 at GD 9 produced significant changes in fetal biometry (crown-rump (CR) length) and body weight. No significant increase in the proportion of fetuses with external visible abnormalities was observed in groups exposed to (PhSe)2. Skeletal anomalies were observed in fetuses in the GD 9-11 treatment groups and included incomplete ossification of cranial bones, misshapen and incomplete ossification of sternebrae, reduced sternebrae number, wavy and extra ribs, incomplete ossification of fore and hindpaw bones and incomplete ossification of sacral and caudal bones. We conclude that maternal administration of (PhSe)2 during GD 7-12 led to increased incidences of these skeletal variations or anomalies, but did not cause externally visible malformations in rat fetuses.