Disposition of metals in rats: a comparative study of fecal, urinary, and biliary excretion and tissue distribution of eighteen metals

Fecal (0-4 days), urinary (0-4 days), and biliary (0-2 hr) excretion and tissue distribution of 18 metals were examined in rats after iv administration. Total (fecal + urinary) excretion was relatively rapid (over 50% of dose in 4 days) for cobalt, silver, and manganese; was between 50 and 20% for copper, thallium, bismuth, lead, cesium, gold, zinc, mercury, selenium, and chromium; and was below 20% for arsenic, cadmium, iron methyl mercury, and tin. Feces was the predominant route of excretion for silver, manganese, copper, thallium, lead, zinc, cadmium, iron, and methyl mercury whereas urine was the predominant route of excretion for cobalt, cesium, gold, selenium, and chromium; while both excretion routes were equally important for bismuth, mercury, arsenic, and tin. Biliary excretion seems to be an important determinant for the fecal excretion of silver, arsenic, manganese, copper, selenium, cadmium, lead, bismuth, cobalt, and methyl mercury. Between 45 (silver) and 0.8% (methyl mercury) of the dosages administered of these metals was excreted into bile in 2 hr, and they exhibited high bile/plasma concentration ratios. The biliary excretion of copper, selenium, lead, and chromium did not increase proportionally with dosage, suggesting that the hepatobiliary transport of these metals is saturable. The fraction of dosage excreted into bile was independent of the dosage for silver, arsenic, manganese, bismuth, methyl mercury, mercury, gold, cesium, thallium, and tin, but markedly increased with increase in dosage of cadmium, cobalt, zinc, and iron. The latter phenomenon is probably due to saturation of hepatic (cadmium, zinc) or extrahepatic (iron) metal-binding sites. Comparison of biliary and fecal excretion rates indicates that arsenic and selenium undergo intestinal reabsorption, whereas thallium and zinc enter the feces also by non-biliary routes. Most of the metals reached the highest concentration in liver and kidney. However, there was no direct relationship between the distribution of metals to these excretory organs and their primary route of excretion.