Teratogenicity and embryotoxicity of titanocene dichloride in mice.

The teratogenic and embryotoxic effects of the antitumor agent titanocene dichloride (TDC) were investigated after application of single doses of TDC (30 or 60 mg/kg) to pregnant mice on days 8, 10, 12, 14 or 16 of gestation. The fetuses were removed on day 18 by caesarian section and examined for external, internal and skeletal malformations as well as for toxic phenomena. The most striking result was the occurrence of cleft palate in numerous fetuses (10% of the fetuses, 30 mg/kg; 40-50%, 60 mg/kg) after TDC application on days 10 and 12. Besides the additional appearance of costal malformations in some fetuses, no other malformations were recognizable. On the other hand, the embryotoxic influence of TDC was significant and caused diminution of the number of live fetuses per litter, marked and dose-dependent reduction of mean fetal body weight after TDC application on day 8 through day 16 and distinct retardation of skeletal ossification.