Placental transfer and fetal distribution of cadmium and mercury after treatment with dithiocarbamates.

Abstract

The distribution in pregnant C57BL mice (day 18 of gestation) of intravenously administered cadmium (Cd) chloride and mercury (Hg) chloride (0.75 mumol/kg b.w.) was studied, with or without previous dithiocarbamate pretreatment. Diethyldithiocarbamate (DEDTC), disulfiram, or thiram (2 X 1 mmol/kg b.w.) or vehicle (gelatine) alone, were given by gavage 2 h before and immediately after injection of the metals. The mice were sacrificed 4 and 24 h later and subjected to autoradiography or impulse counting of excised organs. All the dithiocarbamates increased the concentration of both Cd and Hg in brain and most other maternal organs. While DEDTC and thiram, in that order, strongly increased Cd concentrations in whole fetuses (around 17-fold at 4 h) and all fetal organs measured, disulfiram caused a decrease in fetal Cd concentrations. For Hg, all the dithiocarbamates substantially decreased fetal levels. Disulfiram, for example, decreased Hg levels by a factor of 5. The 24 h values confirmed those at 4 h both elements, although the differences between control and treatment groups were less pronounced. Although the results suggest the formation of lipid-soluble metal-dithiocarbamate complexes in vivo (e.g., increased concentration in brain), this does not necessarily lead to increased fetal levels of the metals. The increased levels of Cd after thiram and DEDTC pretreatment, however, indicate a risk for higher Cd fetotoxicity. It is likely that Cd is released in fetal cells following metabolism of the dithiocarbamate moiety of the complex.