COMPARISON OF RENAL TOXICITY AFTER LONG-TERM ORAL-ADMINISTRATION OF CADMIUM CHLORIDE AND CADMIUM-METALLOTHIONEIN IN RATS

There is a clear lack of information on the toxicological risk of diet ary intake of cadmium-metallothionein (CdMt). The present study aimed at establishing dose-dependent cadmium (Cd) disposition and to investi gate differences in renal toxicity after long-term dietary exposure to CdMt or cadmium chloride (CdCl2) in rats. Male Wistar rats were fed d iets containing 0.3, 3, 30, or 90 mg Cd/kg either as CdMt or as CdCl2 for 10 months. In rats fed 30 and 90 mg/kg Cd as CdCl2 the Cd concentr ations in intestine, liver, and kidneys were all higher than in rats f ed the same doses in the form of CdMt. The kidney/liver Cd concentrati on ratio was higher with CdMt than with CdCl2. At the lower Cd concent rations (0.3 and 3 mg/kg), no differences in Cd accumulation between C dMt and CdCl2 groups were observed and the kidney/liver Cd ratio was a lso similar. When based on the amount of CdMt per milligram Cd in the tissue, rats fed CdMt and those fed CdCl2 had a similar relative CdMt concentration in liver and kidney. First signs of renal injury, indica ted by an increase of urinary lactate dehydrogenase (LDH) activity, we re seen 4 months after exposure to 90 mg/kg Cd as CdCl2. After 8 and 1 0 months the renal effect of 90 mg/kg Cd as CdCl2 became more pronounc ed and urinary enzyme activities of LDH, N-acetyl-beta-D-glucosaminida se and alkaline phosphatase were all elevated. The only clinical effec t of CdMt at the dose level of 90 mg/kg was a slight increase in urina ry gamma-glutamyl transpeptidase activity at 8 and 10 months. Histopat hological changes (e.g., glomerulonephrosis and basophilic tubules) we re observed after 10 months of exposure in rats fed 30 and 90 mg/kg Cd as CdCl2. Rats fed 90 mg/kg as CdMt also showed slight histomorpholog ical changes, but the effect was less pronounced than that of CdCl2 an d was mainly restricted to the tubules. In conclusion, no difference w as observed in renal disposition between CdMt and CdCl2 after long-ter m exposure to low (less than or equal to 3 mg/kg) dietary doses. Nephr otoxicity was mainly related to the total renal Cd concentration and, in contrast to Cd administered intravenously, not to a difference in s ensitivity between CdMt and CdCl2. Therefore, the health risk of dieta ry intake of Cd at low doses does not seem to differ between CdMt and CdCl2. (C) 1994 Society of Toxicology.