Embryotoxic and teratogenic effects of indium chloride in rats and rabbits

Daily indium chloride doses of control (0), 50, 100, 200, or 400 mg/kg were administered orally to Sprague-Dawley rats by gavage, on d 6-15 of gestati on, and daily metal doses of control (0), 50, 100, or 200 mg/kg were admini stered to New Zealand rabbits on d 6-20 of gestation. Further groups of pre gnant rats were treated with control (0) or 400 mg/kg indium chloride orall y on one of d 8, 9, 10, 11, 12, 13, 14, or 15 of gestation. The dams and fe tuses were examined on d 21 (rats) and 30 (rabbits) of gestation, using sta ndard teratological methods. Indium concentration was determined in the mat ernal and fetal blood, as well as in the amniotic fluid by atomic absorptio n spectrometry. Indium was found to cross the placenta and appeared in feta l blood in proportion to the metal concentration of the maternal blood. In the amniotic fluid indium concentrations remained below the detection limit . In rats, indium chloride produced dose-dependent maternal toxic effects, with a dose of 400 mg/kg inducing embryotoxicity (embryolethality) and tera togenicity. Doses of 200 and 100 mg/kg were embryotoxic (retarding) and ter atogenic, causing skeletal and visceral anomalies in addition to external a nomalies (rudimentary or missing tail, syndactylia, clubfoot, exencephalia) in rats. In rabbits, 200 mg/kg indium chloride was lethal for the dams and the embryos (some of the animals died, and the number of abortions and ful l resorptions increased). This dose was found to be teratogenic (caused gro ss renal anomalies) and increased the frequency of fetuses with skeletal re tardation. In rats, the effects of indium chloride causing fetal retardatio n was found to be independent of exposure time. The teratogenic effects wer e the highest on d 11 and 12 of gestation, when indium chloride caused gros s external malformations. Data suggest that the teratogenic effects of indi um chloride can be attributed primarily to a direct cytotoxic action of ind ium resulting from placental transfer, but the effect is not a selective on e, as it appears only in the presence of maternal toxic effects.