Oral cadmium exposure in mice: toxicokinetics and efficiency of chelating agents.

Abstract

on the acute toxicity of metals have been reviewed by Aaseth,’ B~lman,~~ Catsch and Harm~th-Hoene,~~ Jones,’I4 May and B~lman,’~~ and specifically for cadmium by Andersen6 and Nordberg.’@ In most of the studies, a soluble metal salt as well as a chelator were administered to mice or rats by injection. Thus, the experimental results pertain to effects of chelating agents on absorbed, systemically circulating metal. The purpose of the present review is to identify the best chelation treatment for acute oral cadmium intoxication, as based on earlier published data and the author’s work with oral cadmium intoxication in mice. As mice lack the vomiting reflex, well-defined, accurate oral doses may be administered to these animals, and the resulting toxic effects can be studied in a quantitative manner. Thus, after oral administration of cadmium chloride, dose-related effects were seen with respect to mortality, effects on peristalsis, intestinal absorption, and tissue damage. Further, toxicity after oral administration of cadmium was demonstrated to be due both to local effects toward the epithelia of the gastrointestinal tract and to systemic effects of absorbed cadmium,’”’8 in agreement with published data on oral cadmium intoxications in humans. 32*218 In the following, reported effects of various chelating agents on acute cadmium toxicity are compared to the stabilities of the corresponding complexes taken from the literature available and to other important chemical and biological features of the chelators. Although the present review is restricted to cadmium, the general approach may be applicable also in connection with other metal intoxications.