Metallothionein in the extracellular fluids as an index of cadmium toxicity

In rats injected with 5 micron mole CdCl2/kg, 5 days/week, metallothionein was detected in plasma by gel filtration chromatography as early as four weeks. The mean renal concentration of cadmium was 80 microgram/g. The excretion of cadmium in urine at this time was rather low and amounted to 0.01% of the total dose. The amount of metallothionein in plasma, as determined by 109Cd-binding to the 10,000 molecular weight fraction, increased markedly during week 14. Its excretion in urine, however, did not start until about 10 weeks, when the cadmium concentration in kidney approached a mean value of 212 microgram/g. Signs of renal toxicity were evident from glucosuria and proteinuria which became severe during the next four weeks. The excretion of cadmium in urine increased markedly and the majority of it was in the form of metallothionein. It is suggested that the appearance of metallothionein in plasma and urine can be used as specific indices of cadmium poisoning and that the assay of the protein in these fluids may be useful in screening for excessive cadmium exposure.