The acute toxicity and teratogenicity of cadmium in the pregnant rat

Until the 16th day of gestation the intravenous LD50 of Cd2+ in the pregnant Wistar-Porton rat is higher, but not significantly different from that (1.8 mg Cd2+ per kg body weight) in nulliparous females. At 20 days it is 1.1 mg Cd2+ kg per body weight. This decrease is related to the rapid increase in weight of the conceptuses in late gestation and to the retention of most of the dose in the maternal compartment. If the dose is based on body weight at conception, the LD50 for the 20-day pregnant rat (1.6 mg Cd2+ per kg body weight) and non-gravid female do not differ significantly. Nevertheless, after the same Cd2+ dose, hepatic and renal Cd2+ concentrations are less in the pregnant than in the non-pregnant animal. The Cd2+ concentrations, therefore, do not determine the liver and kidney damage, which is restricted to the pregnant rat. Placentae also accumulate Cd2+ and placental haemorrhage follows the injection of the appropriate Cd2+ LD50 on day 12-20 of gestation. In those animals that die between 16 and 30 h after dosing, haemorrhage and death appear to be correlated. Renal damage, therefore, probably results from haemorrhagic shock. It is not dependent on the transfer of protein-bound Cd2+ from the necrotic placentae to the kidney. Between the 8th and 15th day of gestation, Cd2+ (1.25 mg per kg body weight) is highly teratogenic. Hydrocephalus is the most frequent abnormality when the dose is given between the 8th and 12th day. Other malformations include eye defects, gastroschiasis and umbilical hernia.