Transplacental passage of titanium after treatment with titanocene dichloride.

The passage of titanium-containing metabolites across the placenta into the embryonal compartment was investigated by analyzing the titanium (Ti) content in embryos/fetuses at various intervals between 1 h and 24 h after treatment of pregnant mice with single doses of the antitumor agent titanocene dichloride (C5H5)2TiCl2 (60 mg/kg) on days 10, 12, 14 or 16 of gestation. The Ti concentration was determined using flameless atomic absorption spectroscopy. After treatment on days 10, 12 or 14, the Ti concentrations were not elevated in comparison to untreated embryos. Only on day 16, i.e. beyond the end of organogenesis, small amounts of Ti were detectable in the fetal compartment 4-24 h after substance application, exceeding the control values by factors ranging between 2 and 3. These results explain the absence of histologic lesions in developing embryonal organs and the lack of multiple teratogenic effects in new-borns after application of therapeutic doses of (C5H5)2TiCl2 to pregnant mice during the embryonal organogenesis.