The cellular pathology of the kidney is studied in rats following exposure to toxic metals, lead or cadmium. In this phase of the study a series of experiments is being conducted to determine the influence of the toxic metals on essential trace metal metabolism. A number of metabolic parameters and indicators of toxicity are measured. These include cell ultrastructure, toxic and trace metal burden and excretion, changes in metal-binding protein, e.g., metallothionein, and functional changes in the renal tubule. Results to date indicate that lead exposure increases urinary zinc in a dose and exposure length-dependent manner; urinary calcium is increased at the highest lead dose only. Cadmium exposure increases urinary zinc excretion with no effect on urinary calcium. Lead-exposure produces no change in tissue zinc content of most organs with the exception of testes and bone. Calcium content of kidney is normally low, but there is a sudden rise in calcium concentration if kidney lead concentration exceeds 60 Mug/g. A preliminary estimate of a threshold for renal lead toxicity has been determined. Animals injected with cadmium have increased metallothionein content of liver and kidney with liver metallothionein concentration two-fold greater than kidney. The proportion of non-metallothionein bound cadmium in each organ is different with the kidney having the larger fraction. The purpose of these studies is twofold: one is to determine parameters of renal toxicity in response to toxic metal exposure. The second is to determine the influence of dietary essential metal levels on toxicity in organs such as kidney, liver, and bone which preferentially accumulate toxic metals. From these studies the influence of various factors on risk to exposure to toxic metals may be estimated.
