Disposition, toxicity, and intestinal absorption of cobaltous chloride in male Fischer 344 rats

The absorption and disposition of inorganic cobalt salts after oral adminis tration have not been well characterized. The objectives of this study were to compare in vivo results with cobalt transport through the in vitro ever ted small intestine and to relate the disposition results to a biochemical indicator of cobalt toxicity. Cobalt chloride was given to male Fischer 344 rats orally at 33.3 mg Co(II)/kg or intravenously at 4.16 mg Co(II)/kg. By 36 h, 74.5% of the oral dose was eliminated in the feces. The liver, kidne y, and heart accumulated cobalt to the greatest extent. Following the singl e oral dose, the blood cobalt concentration-time curve was triphasic, peake d at 3.2 h, and had an absorptive half-life of 0.9 h, an elimination phase half-life of 3.9 h, and a terminal elimination half-life of 22.9 h. Followi ng intravenous administration, 10.1% of the dose was excreted in the feces, indicating that cobalt can be secreted in the bile. Following a single int ravenous injection, the concentration-time curve displayed three segments. The first segment, which occurred during the first 4 h, had a rapid half-li fe of 1.3 h. The second phase, from 4 to IZ h, demonstrated a slower cleara nce rate with a half-life of 4.3 h. The final and slowest phase, from 12 to 36 h, had a half-life of 19 h. Intestinal jejunal ring experiments indicat ed that cobalt transport has both active and passive components; however, c obalt transport through the in vitro rat everted duodenum indicated that co balt transport had almost exclusively passive components with facilitated d iffusion. The finding that uptake was saturable may explain the small exten t of absorption following oral dosing. Heme oxygenase studies following sub cutaneous and intravenous administration resulted in an increase in activit y (twofold) over controls, while oral administration did not. We concluded that the extent of cobalt absorption across the gastrointestinal tract is i ncomplete, and that the concentration administered and the route of exposur e may determine its systemic toxicity.