In utero exposure to itraconazole during different gestational periods of rats

The present study aimed to investigate the teratogenic and genotoxic effects of itraconazole administered orally to pregnant rats on gestation days 1-7 (implantation), 8-14 (organogenesis) and 14-20 (fetal developmental period) at doses 75, 100 or 150 mg/kg b.wt. The results indicated that itraconazole had embryolethal effect when administered at a dose of 150 mg/kg b.wt throughout implantation and organogenesis periods as well as at 100 mg/kg b.wt during implantation period. Itraconazole elevated the teratogenicity when administrated at a dose of 100 mg/kg b.wt during organogenesis period, the most prominent abnormalities were abdominal hernia, protruding tongue, exencephaly, incompletely ossified, unossified or missing skull bones (mostly frontal, parietal and interparietal), abnormal vertebrae and fused and supernumerary ribs. However, minimal adverse effects were observed at doses given during the fetal developmental period. Itraconazole increased DNA damage of fetal osteocytes via significant increase in the measured comet parameters in all the treated groups, indicating that itraconazole severely affects fetal genetic material.