102.

Engstroem B, Norin H, Jawait M, Ingman F. Influence of different cadmium-EDTA complexes on distribution and toxicity of cadmium in mice after oral or parenteral administration. Acta Pharmacol. Toxicol. 1980; 46(3):219-234. (CA) [The distribution and toxicity of Cd were investigated in mice after giving the metal alone or with EDT by various routes and also to study Cd binding with metallothioneins and other proteins of kidney and liver. The toxicity of the metal was mainly dependent on the stability of its complexes with Cd which in turn were the function of physiol. conditions. For example, low toxicity of Cd + EDTA (molar ratio 1:4) was because of a strong 1:1 complex and relatively low availability of Cd. The difference in the toxicity following Cd + EDTA (1:0.4) following different routes of administration probably reflected the changes in the stability of the Cd2-EDTA complex due to changes in pH and competition with other metal binding sites. A decreased toxicity of the metal after Cd-EDTA s.c. administration was attributed to its rapid elimination (~45% of the initial dose). In contrast to oral gavage, a slightly increased toxicity of Cd was obsd. after direct infusion of 1:0.4 Cd-EDTA soln. into the stomach or duodenum. A higher accumulation of Cd in the liver and kidney was seen compared to when Cd was given alone. Gel filtration studies were made on the liver and kidney to elucidate the manifestation of Cd toxicity in relation to the accumulation and binding of Cd. Increased toxicity seen following the administration of EDTA in the presence of excess Cd is due to the formation of a weak 2:1 Cd2-EDTA complex. Thus, during Cd poisoning, it is important to ascertain that the EDTA dose always exceeds that of the toxic metal.]

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