Influence of Different Cd‐EDTA Complexes on Distribution and Toxicity of Cadmium in Mice after Oral or Parenteral Administration
Authors: Engström Birgitta , Norin Harald , Jawaid Mohammad , Ingman Folke 
Published: July 2010

AbstractThe distribution and toxicity of cadmium in mice was investigated after single exposure to CdCl2(labelled with109Cd) alone or in combination with EDTA (ethylenediaminetetraacetic acid) in Cd: EDTA molar ratios of 1:0.4 or 1:4, respectively, by different routes of exposure: I.Subcutaneous injection. The mortality rate observed (during a period of three weeks) in the groups of mice exposed to either Cd alone (3.2 mg=0.028 mmol Cd/kg b.wt.)or Cd in combination with EDTA was 60% and 0%, respectively. Furthermore a marked decrease of the whole‐body activity of109Cd was seen during the first 24 hours following exposure to Cd and EDTA (about 80% in the Cd + EDTA 1:4‐group and about 45% in the 1:0.4‐group, compared to only about 4% in the Cd‐group). Cd given alone or simultaneously with an excess of EDTA was bound similarly to different proteins in liver and kidneys, 5 hours after exposure (i.e. mainly bound to low molecular weight proteins) whereas relatively more of the Cd administered in the Cd + EDTA (1:0.4)‐solution was bound to high molecular weight proteins, as studied by gel‐filtration. II.Direct infusion into the stomach or the duodenum (under anaesthesia). About 10% of the administered Cd‐dose (60 mg=0.53 mmol Cd/kg b.wt.) was absorbed in the mice exposed to Cd alone (which was about 4 times more than what was seen after oral exposure via stomachtube, see below), resulting in a 100% mortality in these mice within 96 hours after exposure. After administration of 1:0.4‐solution the concentrations of cadmium in liver and kidneys (1 hour after exposure) were about twice as high as in the Cd‐exposed mice. However, cadmium given simultaneously with EDTA in the (1:4)‐ solution was not toxic. Five hours after exposure to Cd alone most cadmium was bound to high molecular weight proteins in liver and kidneys, while almost all Cd in the liver of mice exposed simultaneously to Cd and EDTA was bound to low molecular weight proteins, which indicates that cadmium is more rapidly absorbed from the gastrointestinal tract in the presence of EDTA. III.Oral exposure. Cadmium was found to be more toxic when administered alone (60 = 0.53 mmol Cd/kg b.wt.) than together with either concentrations of EDTA as shown by a higher mortality in the Cd‐exposed mice (75%) compared to the Cd + EDTA‐exposed animals (0%). Most Cd was bound to high molecular weight proteins in liver and kidneys in the Cd‐exposed mice (5 hours after exposure) while mice given Cd + EDTA had part of the cadmium also bound to low molecular weight proteins in the livers. No difference in the distribution of Cd among renal proteins were seen between mice from the various exposure groups. The complex formation of Cd (II) and EDTA in the present solutions was studied by a potentiometric method. Apart from the formation of a 1:1 Cd‐EDTA complex a binuclear Cd2‐EDTA complex was formed (accounting for about 35% of the total mol percent distribution of complexes) in the solution where an exess of cadmium with respect to EDTA was present. The results from the present studies show that administration of cadmium in a 2: 1‐complex with EDTA may lead to an increased toxicity of the metal under certain physiological conditions. The difference in toxicity of cadmium following exposure to the Cd2‐EDTA complex by different routes of exposure probably reflects changes in the stability of this complex due to variations in pH and to competition with other metal‐binding ligandsin vivo.