Comparative effects of diethyldithiocarbamate, dimercaptosuccinate, and diethylenetriaminepentaacetate on organ distribution and excretion of cadmium

Diethyldithiocarbamate (DDTC), dimercaptosuccinate (DMSA), and diethylenetriaminepentaacetate (DTPA) were compared for their relative efficacies at equimolar doses in promoting mobilization of metallothionein-bound cadmium (Cd) from its sites of deposition several weeks after i.p. injection of a sublethal dose of Cd containing 109Cd. Routes and rates of excretion were also determined. The most rapid and extensive reduction of renal, hepatic, and splenic Cd was obtained with DDTC. Concurrently, however, DDTC caused moderate increases in lung, testicular, and heart Cd burdens, and increased the brain burden about ten-fold. Only renal and testicular levels of Cd were reduced by DTPA, and it was much less effective than DDTC in lowering the renal levels. No reduction of Cd levels in any organ was attained with DMSA treatment. Excretion of Cd following DDTC treatment was exclusively by the fecal route; DTPA promoted both urinary and fecal excretion, but the total amount excreted by both routes was considerably less than that observed following DDTC treatment. It was concluded that the effectiveness of a chelator in promoting mobilization and excretion of metallothionein-bound Cd cannot be predicted on the basis of its effectiveness in protecting mice against a lethal dose of Cd when given immediately after Cd and prior to induction of metallothionein synthesis. The possibility is discussed that the greater effectiveness of DDTC may be due to an interaction with nascent metallothionein rather than to chelation of Cd.