Studies on Poisonous Metals. XVIII. Effects of Several Dithiocarbamates on Tissue Distribution and Excretion of Cadmium in Rats

The effects of various chelating agents, sodium N-benzyl-D-glucamine dithiocarbamate (NBGDTC), sodium N-p-methylbenzyl-D-glucamine dithiocarbamate (NMBGDTC), and sodium N-p-isopropylbenzyl-D-glucamine dithiocarbamate (NPBGDTC), which were newly synthesized, sodium N-methyl-D-glucamine dithiocarbamate (NMGDTC), diethyldithiocarbamate (DEDTC), dihydroxyethyldithiocarbamate (DHEDTC), and dicarboxymethyldithiocarbamate (DCMDTC), on the distribution and excretion of cadmium in rats were compared at 30 min and 24 h following cadmium injection. At 30 min after cadmium administration, these chelating agents all significantly enhanced the biliary excretion of cadmium, and at 24 h after cadmium injection, the chelating agents other than DEDTC and DCMDTC significantly enhanced the biliary excretion of the metal. The effects of NBGDTC, NMBGDTC, and NPBGDTC on the biliary excretion of cadmium were much larger than those of the other chelating agents. The urinary excretion of cadmium was increased by the chelating agents other than DEDTC and NPBGDTC. These chelating agents were effective in mobilizing cadmium from the liver, kidney, and pancreas at 30 min after treatment with cadmium. At both 30 min and 24 h after treatment with cadmium, NBGDTC, NMBGDTC, and NPBGDTC effectively depressed cadmium content in the liver without the mobilization of cadmium to the kidney. The chelating agents other than DEDTC did not result in the redistribution of cadmium to the brain, testes, lung, and heart. These results show that the injection of NBGDTC, NMBGDTC, or NPBGDTC at both 30 min and 24 h after treatment with cadmium can much more effectively mobilize cadmium from the body, mainly through the bile, without redistribution of cadmium to other tissues, such as brain, testes, lung, and heart, when compared with injection of other chelating agents. Furthermore, the pattern of mobilization and excretion of cadmium following treatment with each chelating agent was related to the organic/aqueous partition coefficient of each dithiocarbamate-cadmium complex.