CONCURRENT EXPOSURE TO LEAD, CADMIUM, AND ARSENIC - EFFECTS ON TOXICITY AND TISSUE METAL CONCENTRATIONS IN THE RAT

  • 1 January 1981
    • journal article
    • research article
    • Vol. 98  (4) , 463-481
Abstract
Male rats were exposed to dietary Pb (200 ppm), Cd (50 ppm), or As (50 ppm) as arsenate alone or in combination for 10 wk using a 2 .times. 2 .times. 2 factorial design. Cd and As reduced weight gain even when differences in food intake were taken into account and administration of Cd and As depressed weight gain more than did either metal alone. Pb did not adversely affect food consumption or weight gain. Increased RBC [red blood cells] were observed after administration of Pb, Cd or As and more cells were observed when 2 or 3 metals were concomitantly administered. Despite increased numbers of circulating RBC, Hb and hematocrit were reduced, especially with the Pb-Cd combination. Analysis of blood chemistries showed normal ranges for blood urea N, creatinine, cholesterol, Ca, albumin, total protein and bilirubin. Uric acid was increased by Pb only. SGOT [serum glutamic oxaloacetic transaminase] activity was reduced by As alone. Serum alkaline phosphatase was reduced by As or Cd. Combinations of As and Cd did not further reduce the activity of this enzyme. Kidney weight and kidney weight/body weight ratios were increased by Pb alone. Liver weight/body weight ratios were reduced in animals fed Cd. Kidney histology showed predominantly Pb effects: intranuclear inclusion bodies and cloudy swelling. Ultrastructural evaluation of kidneys from Pb-treated animals disclosed nuclear inclusion bodies and mitochondrial swelling. Concurrent administration of Cd reduced total mean bone and kidney Pb levels by 50 and 60%, respectively, and this was associated with decreased kidney intranuclear inclusions. Cd exposure also reduced renal, femur and liver concentrations of Fe by 33, 43 and 63%, respectively, decreased femur Zn by 27% but increased renal Zn by 20%. Administration of As produced mild swelling of tubule cell mitochondria, increased mean total renal Cu to 200% of control and increased liver Fe by 44%. Dietary Pb produced increased urinary excretion of ALA [aminolevulinic acid] and coproporphyrin. Dietary exposure to As increased urinary excretion of uroporphyrin and to a lesser extent coproporphyrin; dietary Cd caused no significant changes in urinary levels of any porphyrins measured. Pb plus As produced an additive effect on coproporphyrin excretion but not that of ALA or uroporphyrin. Interactions between common toxic elements occurred and were characterized by alterations in tissue trace metal levels and toxicity.