Teratogenic response of mice to intraperitoneal administration of hydroxyurea during gestation

A single dose of hydroxyurea, a known teratogen, was administered at 300 mg/kg by intraperitoneal injection to female mice on Day 8, 9, 10, 11, or 12 of gestation. Additional groups of mice received an intraperitoneal dose of sterile water for injection on Day 8, 10, or 12 and served as the negative control. Maternal clinical observation, body weight, body weight gain, food consumption, and gross pathology data indicated no remarkable differences between control and treated groups. Fetal effects noted at cesarean section of the dams included an increased number of early resorptions and a concurrently decreased number of live fetuses in the Day 8, 9, and 12 treatment groups. External, visceral, and skeletal evaluation of fetal specimens revealed varied malformations in the fetuses of all treated groups. The highest percent of malformed fetuses was found in the groups treated with hydroxyurea on Days 8 and 9 of gestation. Urinary system, rib, sternebral, and tail malformations and variations were noted in fetuses dosed on Day 8 while eye and liver malformations and rib variations were noted in fetuses dosed on Day 9. Statistical analysis of the percent of fetuses affected (the number resorbed, plus the number dead, plus the number malformed) indicated a significant increase in these two groups.