Dosage-dependent disposition of cadmium administered orally to rats

This study was designed to determine whether the disposition of Cd is dependent on dose. Rats received a single dosage of Cd either orally (1, 10, 100, 1000, or 10,000 micrograms/kg) or intravenously (0.01, 0.1, 10, 100, or 1000 micrograms/kg) and were killed 7 days later to determine concentration of Cd in various organs. When administered intravenously, the concentration of Cd in tissues increased proportionally with dosage and the percentage of dose in each organ remained constant. However, when Cd was administered orally, the concentration of Cd in tissues increased more than the increase in dosage. Moreover, the percentage of the po dosage retained 7 days after administration increased from 0.40% at the 1 microgram/kg dosage to 1.65% at the 100 micrograms/kg and higher dosages. In addition, when administered orally, low dosages of Cd (1 and 10 micrograms/kg) distributed preferentially to the kidney suggesting that Cd may be absorbed as a Cd-metallothionein complex at low dosages. To determine the gastrointestinal absorption of Cd, rats were given an oral dosage of Cd (1 or 10,000 micrograms/kg) and 3 hr later organs were removed to determine Cd content. Concentrations of Cd in tissues increased more than the increase in dosage and the percent of dosage absorbed was dosage-dependent (0.35 and 1% at the 1 and 10,000 micrograms/kg dosages, respectively). At the 1 microgram Cd/kg dosage, approximately 60% of Cd in intestinal cytosol was bound to metallothionein (MT) whereas at the 10,000 micrograms Cd/kg dosage, approximately 50% of the Cd was bound to MT. These results indicate that retention of Cd following oral administration is dosage-dependent and results from increased absorption of Cd at higher dosages.