Comparative effects of ten dithiocarbamate and thiuram compounds on tissue distribution and excretion of lead in rats

Abstract

Combined treatment of rats with lead and disulfiram is known to cause increased levels of lead in brain and potentiation of the neurotoxicity of lead. Ten dithiocarbamate and thiuram compounds, including disulfiram, were compared for their efficacies in influencing tissue distribution of a trace dose of intravenously injected lead plus 203Pb in rats. The tested compounds were sodium diethyldithiocarbamate (DEDTC), sodium dimethyldithiocarbamate (DMDTC), tetraethylthiuram disulfide (disulfiram), a complex of zinc and manganese ethylenebisdithiocarbamate (mancozeb), manganese ethylenebisdithiocarbamate (maneb), sodium monomethyldithiocarbamate (metham), zinc propylene bisdithiocarbamate (propineb), tetramethylthiuram disulfide (thiram), zinc ethylenebisdithiocarbamate (zineb), and zinc dimethyldithiocarbamate (ziram). Pronounced effects on tissue distribution of lead were seen after peroral and subcutaneous administration of DEDTC, DMDTC, disulfiram, metham, thiram, and ziram. After peroral administration there was an increased uptake of lead in brain, liver, lung, and spleen and a decreased uptake in femur compared to control rats receiving only lead. Thiram was the most effective compound in enhancing lead uptake in brain, causing a 100-fold increase in 203Pb concentration at 72 hr survival. After subcutaneous administration, metham caused the highest increase in brain concentration of 203Pb. Fecal excretion of lead, which is the main excretory pathway, was decreased after peroral administration of disulfiram, ziram, and thiram to about 20% of the excretion in control rats at 48 hr. Urinary excretion of lead was significantly decreased in all the treated groups except the group treated with zineb. The effects on tissue distribution and excretion can be explained by in vivo formation of lipophilic complexes between lead and these compounds or their metabolites facilitating the transport of lead through cell membranes and the blood-brain barrier. Zineb, maneb, propineb, and mancozeb did not cause similar effects on the tissue distribution of lead. The results of this study show that interactions can occur between lead and DEDTC, DMDTC, disulfiram, metham, thiram, and ziram, resulting in increased levels of lead in brain and probably potentiation of the neurotoxic effects of lead.