Cadmium metabolism and toxicity in rats after long-term subcutaneous administration.
Male Sprague-Dawley rats were given sc injections of Cd at 0.5 mg/kg body weight, 6 d/wk, for 22 wk. Concentrations in the liver, kidney, spleen, heart, testis, and blood were determined every week for 8 wk and at the end of 10, 12, 15, and 22 wk. Daily excretion of Cd and total protein in urine were determined every week in another series of rats given the same dose for up to 25 wk. Hepatic and renal Cd increased linearly for the first several weeks of Cd injection. The Cd concentration in the kidney leveled off at 156 microgram/g wet tissue after 7 wk, whereas hepatic Cd continued to increase for a few more weeks, reached its maximum level (330 microgram/g) at 10 wk, and then declined. Blood Cd showed a steady increase expressed by a logarithmic curve for the first several weeks and a rapid rise in response to the decline of hepatic Cd. Urinary excretion of Cd increased linearly but slightly for several weeks from the beginning of injections. In this period daily excretion of Cd remained less than 1% of the daily Cd dose. From 6 wk the Cd excretion increased rapidly and reached a plateau of about 10 microgram/d (several percent of the daily dose) with a simultaneous increase in urinary excretion of total protein. Urinary excretion of Cd showed a second sharp increase after 10 wk and reached a higher plateau level of 95 microgram/d (about 63% of the daily dose). From these findings the response of the exposed animals could be divided into three stages. The first stage was characterized by a steady increase in hepatic and renal Cd and low-level excretion in the urine. This stage was regarded as a latent period of Cd poisoning. The second stage, which developed between 5 and 7 wk, was characterized by leveling off of Cd accumulation in the kidney and increased excretion of Cd and total protein in the urine. This was an initial toxic stage represented by renal lesions. The third stage was characterized by the second sharp increase in urinary Cd excretion and an elevated level of blood Cd after 10 wk. These responses were related to a decrease in the hepatic capacity for Cd retention as a result of toxic effects of Cd on the liver.
D000818:Animals; D002104:Cadmium / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D007668:Kidney / Q000032:analysis; D008099:Liver / Q000032:analysis; D008168:Lung / Q000032:analysis; D008297:Male; D051381:Rats; D013154:Spleen / Q000032:analysis; D013737:Testis / Q000032:analysis; D013997:Time Factors
D002104:Cadmium