Mechanism of diethyldithiocarbamate, dihydroxyethyldithiocarbamate, and dicarboxymethyldithiocarbamate action of distribution and excretion of cadmium

Diethyldithiocarbamate (DEDC), dihydroxyethyldithiocarbamate (DHDC), and dicarboxymethyldithiocarbamate (DCDC) were assessed for their relative efficacies in mobilizing metallothionein-bound cadmium (Cd) from selected organs and tissues of mice and in promoting Cd excretion. The DHDC was effective but less so than DEDC in mobilizing Cd from liver, kidney and spleen. However, while DEDC effected a redistribution of Cd which resulted in higher levels in lungs, testes, heart, and brain, DHDC after 13 injections reduced the levels of Cd in all four of these organs. The DCDC analog did not alter the Cd load of any organ. Bone Cd content was most effectively reduced by DEDC; DCDC was somewhat less active, and DCDC was without effect. Skin Cd burden was enhanced markedly after treatment with DEDC but was reduced by treatment with DHDC or DCDC. Treatment with DEDC increased the muscle Cd content about 250 percent over control values; treatment with DHDC reduced it significantly, while DCDC was without effect. Both DEDC and DHDC reduced the whole body Cd burden, but DCDC was ineffective. The initial rate of fecal excretion of Cd was much greater following DHDC treatment than after DEDC treatment, while DCDC did not promote excretion to any detectable extent. The pattern of mobilization, redistribution, and excretion of Cd following treatment with each chelator was related to the organic/aqueous partition coefficient of each dithiocarbamate-Cd complex.