The effects of cobalt sulfate administered to pregnant C57BI mice, OFA-SD rats, and New Zealand rabbits was studied on fetal and postnatal offspring. Cobalt concentration in the maternal blood was increased in proportion to the administered doses. Cobalt crossed the placenta and appeared in the fetal blood and amniotic fluid. Regardless of the administered dose of cobalt sulfate, cobalt concentration in the blood peaked 2 h after administration. Cobalt produced dose-dependent maternal toxicity and was found to be embryotoxic in all three species, as evidenced by elevated frequency of fetuses with body weight or skeletal retardation and embryolethality. Cobalt increased the frequency of major anomalies significantly in mice and rats, with anomalies of the eyes, kidneys, skull, spine, and sternum in mice, and anomalies of the urogenital system in rats. Cobalt sulfate was not teratogenic in rabbits. Intra-amnial administration of cobalt sulfate produced a dose-dependent increase of the frequency of dead fetuses, and weight retardation of the live fetuses. The direct cytotoxic effect probably plays a role in the embryotoxic and teratogenic effects of cobalt. The postnatal examinations revealed a decrease of the perinatal index in the treated group. The body weight of the pups in the treated group was lower during wk 1 of life, but no difference was found between the control and treated by the end of wk 2. Eye opening was completed in the usual time period in both groups, while time of appearance of the teeth, descending of the testes, shaping of ears, and development of hearing was delayed in the treated group. The development of muscle strength and of the locomotor system was delayed. All the functions studied (forward movement, swimming, righting reflex) normalized by postnatal d 21, with the exception of muscle strength. It was concluded that cobalt sulfate exposure decreases the perinatal viability of the fetuses, but the functions of the surviving fetuses with perinatal retardation become compensated by postnatal wk 2-3. The development of fetuses is undisturbed thereafter.

No abstract

Carbon disulfide exerted adverse effects on the structure or hemodynamics of the cardiovascular system, and whether ethanol exposure modifies the cardiovascular effect of carbon disulfide, was examined. Male Sprague-Dawley rats were used in the study. Animals in the control and ethanol groups drank water containing 5% sugar, or 10% ethanol in addition to 5% sugar, respectively, for 14 wk. Sepatare animals inhaled 700 mg/m3 of carbon disulfide for 6 h daily. Carbon disulfide treatment did not affect the food and fluid consumption of the animals, while this gas decreased body mass gain. CS2 increased arterial blood pressure and cardiac index, decreased their cardiac output, the fraction of the cardiac output, and blood flow for the kidneys and the lungs, and increased the relative heart, liver, and kidneys mass and the vascular resistance of the brain, lungs, and kidneys. Ethanol decreased the food and fluid consumption and body mass gain of the animals, the fraction of the cardiac output for the kidneys, and the vascular resistance of the liver, while it increased the blood flow of the brain and liver. Simultaneous administration of carbon disulfide and ethanol decreased the heart rate and increased the QRS duration. Significant interaction was found between the effect in case of heart rate, PQ distance, and QRS duration; carbon disulfide significantly increased the minimal-moderate effect of ethanol on all three parameters. With histological examinations no pathologic alterations were found in the organs studied. It was concluded that the early hemodynamic changes produced by carbon disulfide may play a significant role in the pathomechanism of the effects of the substance (hypertension, damage to the myocardium and kidneys). On the other hand, a potentiating interaction of carbon disulfide was expected with the effects of ethanol, at the administered concentration and dose in the study.

Daily indium chloride doses of control (0) or 200 mg/kg were administered orally to pregnant Sprague-Dawley (SD) rats by gavage, on d 6-15 of gestation. On d 16 of gestation hemodynamic tests were performed; Arterial blood pressure, cardiac output (CO), and volume organ blood flow were determined with radioactive microspheres using the reference sample method (McDevitt & Nies, 1976). Indium chloride increased the cardiac index (CI), but did not change arterial blood pressure and total peripheral resistance (TPR). Indium decreased the organ fractions of the cardiac output to kidneys, ovaries, uterus, and placenta, while those to brain, lungs, and liver were not affected. In the placenta the blood flow was reduced significantly while the vascular resistance increased. The blood flow and vascular resistance did not change in the rest of the organs studied. The changes in arterial blood pressure, CO, Cl, TPR, organ fraction of cardiac output, blood flow, and vascular resistance in most of the organs displayed normal responsiveness to noradrenaline (NA) infusion. The reduction of uterine and placenta fractions and placental blood flow, produced by NA infusion were significantly greater in control than in the indium-treated group. Data indicate that the hemodynamic changes induced by indium are detrimental to the fetus. Indium chloride exposure modifies the maternal effect of noradrenaline such that there is maternal survival at the expense of fetal mortality.

Daily indium chloride doses of control (0) or 400 mg/kg were administered orally to pregnant Sprague-Dawley (SD) rats by gavage, on d 20 of gestation. Indium concentration was determined in the maternal and fetal blood, livers, kidneys, skulls, and femurs by atomic absorption spectrometry. Further groups of pregnant rats were treated with control (0) or 400 mg/kg indium chloride orally, during the whole gestation period. The fetuses were examined on d 21 of gestation, using histological and histochemical methods. Four hours after the administration indium concentration was found to be significant in the blood, liver, and kidneys of the dams. Twenty-four hours later it increased in the blood but not in the liver and kidney. Fetal indium concentrations were 40-50% of the maternal levels due to a barrier of the placenta. In the skull and the femur, indium was already detectable at 4 h after the administration, and by the end of 24 h, metal concentration was several times higher than that at 4 h, indicating accumulation. Furthermore, it was found that the birefringency of collagen detectable by picrosirius red staining in polarized light around the chondrocytes disappeared and became irregular. In the matrix of the epiphyseal cartilage, the regular, birefringent network demonstrable by Rivanol reaction became irregular and hardly recognizable. In the cytoplasm of the chondrocytes, the diffuse, evenly distributed positive Ricinus communis agglutinin reaction became irregular or disappeared. Similar but much weaker changes were observed with concanavalin A and wheat germ agglutinin stainings. It was concluded that the missing femur and micromelia diagnosed by alizarin staining is the consequence of a specific toxic effect of indium that inhibits chondrogenic ossification. No similar histochemical changes were observed in the bones of the skull developing by desmogenic ossification, despite the presence of indium. Data indicate that the mechanisms of the effects of indium causing retardation and/or malformation differ in the bones developing through desmogenic or chondrogenic ossification.