Toxicity and distribution of cadmium administered to rats at sublethal doses

Abstract

Male Sprague-Dawley rats were given a single oral dose of [109Cd]cadmium chloride (0, 25, 50, 100, and 150 mg of Cd/kg), and plasma glucose, blood hemoglobin, hematocrit, hepatic cytochrome P-450 concentrations, aniline hydroxylase activity, and hexobarbital oxidase activity were measured 2 and 14 days after dosing. The plasma glucose, blood hemoglobin, and hematocrit values observed were the same in all rats. Hepatic cytochrome P-450 and aniline hydroxylase activity were also the same in all rats, however, the hexobarbital oxidase activity was lower in the rats receiving the higher doses. Testicular function measured 14 days after dosing was decreased in male rats given the higher doses of Cd (100 and 150 mg of Cd/kg). Systolic blood pressure, heart rate, body weight, urine, protein excretion, and motor activity were measured daily for 14 days after dosing. The systolic blood pressure and heart rate remained unchanged in dosed and control rats. The rats given the higher doses showed a decrease in body weight during the first 3–4 days; thereafter, all rats had the same growth rate as controls. Urine flow and protein excretion of dosed rats were approximately one-half the value of control rats for 2 days but the same thereafter. Daily motor activity for the first 2–3 days was lower in the dosed rats (50, 100, 150 mg of Cd/kg) than the control rats. The tissue concentration of cadmium after 2 days was highest in the liver, which contained most of the body burden of Cd, followed by intestine, kidney, pancreas, spleen, heart, lung, testes, muscle, brain, blood, and plasma. After 2 weeks most tissue concentrations decreased 50% with some exceptions, notably the liver, which remained unchanged at higher doses, and the kidney, which showed up to a three- to four-fold increase. The concentration of metallothionein in the liver was increased at 2 days and was approximately the same after 14 days. In contrast, the concentration of metallothionein in the kidney at 2 days was unchanged but at 14 days had increased. It appears that the redistribution of cadmium to the kidney with time is due to the longer time period required for the increase of metallothionein levels in the kidney.