Structural requirements for chelate antidotes for acute cadmium intoxication

Abstract

Twenty-one chelating agents have been examined to determine their relative efficacy as antidotes for acute cadmium chloride intoxication when administered 20 min after the injection of cadmium chloride. In agreement with earlier studies in which cadmium salt and antidote were administered simultaneously, the most effective antidotes were the polyamino-polycarboxylates, such as DTPA, EDTA and EGTA, administered as their calcium or zinc complexes. In the case of DTPA, the administration of the compound as its zinc chelate provided no improvement in the survival rate over the calcium chelate. ZnDTPA and CaDTPA are, by a significant margin, the most effective antidotes. The efficacy of these compounds as antidotes is dependent both on the stability constants of the cadmium complexes and the toxicity of the cadmium complexes which are formed. For chelating agents of the EDTA type a very close correlation was observed between the log stability constant value of the cadmium complex and the survival ratio obtained. The correlation does not appear to extend to other structural types of antidotes under the conditions used by us. The conditions used in these studies were sufficiently severe to show that chelating agents may be effective antidotes for low level acute cadmium intoxication and yet not show any antidote activity in the procedure given here because of the inherent toxicity of the cadmium chelates themselves.