Choice of chelating antidotes for acute cadmium intoxication∗

During acute oral intoxication by cadmium compounds, gastrointestinal epithelial damage contributes to immediate toxicity. However, secondary systemic toxicity may develop due to intestinal uptake of cadmium. This review presents an evaluation of the effects of chelators on the acute toxicity of cadmium after parenteral or oral exposure and on the intestinal uptake of cadmium. This review shows: Chelating agents may affect the acute toxicity of cadmium in a variety of ways depending on the exposure route for cadmium and administration route for the chelator. With regard to survival, systemic toxicity of absorbed cadmium is of major importance, as intraperitoneal administration of chelators could eliminate or reduce mortality due to orally administered cadmium chloride. Lipophilicity of chelators and their cadmium complexes may result in extensively augmented intestinal uptake. However, hydrophilic chelators may efficiently reduce the intestinal cadmium uptake. For hydrophilic chelators, the stability of the cadmium complex is an important determining factor of efficacy. The optimal oral antidote towards orally administered cadmium are the BAL analogs, especially DMSA, while the optimal intraperitoneal antidotes towards orally or intraperitoneally administered cadmium are the higher members of the polyaminopolycarboxylate family, especially TTHA. When administered simultaneously (DMSA orally and TTHA intraperitoneally), these chelators synergistically reduce the whole‐body retention of cadmium. In conclusion, chelation treatment in acute oral cadmium intoxication should first prevent/reduce intestinal damage and uptake by rapid oral administration of a chelating antidote and then alleviate systemic toxicity due to absorbed cadmium and enhance renal/biliary cadmium excretion by parenteral administration of a chelating antidote.