The Metabolism of C4-labeled Ethylenediamine- Tetraacetic Acid in the Rat*

Interest in ethylenediaminetetraacetic acid (EDTA) arises from its ability to combine with metal ions to form water-soluble chelates. Several important biological applications have been made of this property. The material has been shown to be effective (a) in mobilizing radioactive elements such as Pu, Am, and Y from the skeleton (1, 2), (b) as a valuable therapeutic agent in the treatment of poisoning by heavy metals such as lead’ (3) and mercury,2 and (c) for hastening the elimination of Cu in Wilson’s disease.3 For this type of application, the agent presents a unique advantage in that the toxic effects resulting from the release of free metal ions (i.e., Pb++) into the blood stream, as often occurs in previous methods of treatment, are circumvented, since the metal is mobilized as a non-ionizable complex. By virtue of its strong calcium-binding capacity, EDTA is finding extensive use as an anticoagulant in blood drawn for transfusions and for the preparation of plasma fractions (44). In addition, EDTA and its chelates have been found useful in situations in which close control of metal ion concentration is essential; i.e., in investigations of the metabolic effects of trace metals (7, S), in the study of calcium metabolism (9, lo), and in the study of the blood clotting mechanism (1 l), etc. In view of the increasing importance of EDTA in biology and in anticipation of its increasing use in humans, a study of the metabolism of the material was undertaken. The study was carried out by using the calcium chelate because this is the form commonly employed in the treatment of heavy metal poisoning. The work was greatly facilitated by the availability of ethylenediaminetetra-2-(C414-acetic) acid prepared by Murray and Ronxio (12).