Abstract
The effects of acute parenteral, repeated parenteral and dietary administration of cadmium chloride have been investigated in the male rat. A release of kidney enzymes into the urine occurred during the development of cadmium-induced renal damage, and provided a useful criterion of toxicity in further studies. Cadmium accumulation in liver and kidney was associated with increases in the concentrations of zinc and copper in these tissues. Dietary cadmium exposure depleted the renal and hepatic content of iron. Repeated parenteral administration of cadmium had a similar effect but only in the kidney, and produced an excessive loss of trace metals into the urine, which may have exacerbated the disturbances in their metabolism. Changes in the plasma concentration of trace metals depended upon the route of administration and dosage of cadmium. A single injection of cadmium chloride increased the concentration of copper in plasma but decreased that of zinc and iron, while repeated injections increased the concentrations of both zinc and copper, and decreased iron. Long term dietary administration of cadmium chloride raised plasma copper but decreased both zinc and iron. The administration of high doses of zinc sulphate altered the tissue disposition of cadmium. The possibility that zinc may prevent some of the toxic effects of cadmium was investigated, but zinc itself induced changes in the homeostasis of essential metals. Cadmium-treated rats showed changes in calcium homeostasis which were suggestive of an impaired absorption, and the accumulation of trace metals in the femur was inhibited. These changes were independent of the development of kidney damage. The dietary administration of cadmium also decreased the activity of femur alkaline phosphatase. This effect was prevented by dietary zinc supplementation. The effectiveness of a variety of chelating agents to mobilise and promote the excretion of cadmium was compared. Some lipophilic derivatives of diethylenetriaminepentaacetic acid were very effective when administered after acute cadmium exposure, but no compounds significantly decreased the body burden of cadmium in animals which had accumulated the metal in tissues.