RELATIONSHIP BETWEEN THE DEVELOPMENT OF HEPATORENAL TOXICITY AND CADMIUM ACCUMULATION IN RATS GIVEN MINIMUM TO LARGE AMOUNTS OF CADMIUM CHLORIDE IN THE LONG-TERM - PRELIMINARY-STUDY

We wished to clarify the relationship between the sensitivity to induc e hepato-renal toxicity and the level of cadmium (Cd) in the organs of rats exposed to minimum to large amounts of cadmium chloride (CdCl2). For this purpose, groups of female Sprague-Dawley (SD) rats, each con sisting of 24 animals, were fed diet containing CdCl2 at concentration s of 0, 8, 40, 200, and 600 ppm for 2, 4, and 8 months from 5 weeks of age. All surviving rats given 600 ppm Cd were killed at 3 months beca use of deterioration of their general condition. Animals of this group showed anemia and decreased hematopoiesis in the bone marrow, in addi tion to reduction of cancellous bone in their femurs. Hepatotoxicity w as observed after 2 months in the groups treated with greater than or equal to 200 ppm: By 4 months, the rats in the 600 ppm group had devel oped periportal liver cell necrosis. Renal toxicity characterized by d egeneration of proximal tubular epithelia was apparent in the groups t reated with greater than or equal to 200 ppm from 2 months, becoming m ore prominent in the high-dose rats at 4 months. Hepatic accumulation of Cd increased linearly with the duration of treatment. In contrast, the concentration of Cd in the renal cortex of rats treated with 600 p pm reached a plateau level of similar to 250 mu g/g within the first 2 months, The renal concentration of Cd in the 200 ppm group when renal toxic lesions were first detected at 2 months ranged from 104 to 244 mu g/g. No renal lesions were observed in the 40 ppm group after 8 mon ths, despite the presence of 91-183 mu g/g of Cd in the kidneys. The r esults thus suggest that renal toxicity would not be induced by treatm ent with minimum amounts of CdCl2 for periods longer than 8 months, al though accumulation of Cd might gradually progress. A further 2-year f eeding study of CdCl2 and Cd-polluted rice is now in progress.