Abstract

The mechanism whereby ethylenediaminetetraacetate (EDTA) acts to increase the excretion of lead was studied. All experiments were conducted on rats which received lead, 7 mg/kg, containing Pb²¹⁰. The administration of EDTA resulted in marked removal of lead from the bone. This effect was terminated by the end of the period of EDTA infusion. Depletion of the lead burden of soft tissues continued well past the termination of EDTA infusion. Excretion of mobilized lead occurred mainly during the period of EDTA infusion. EDTA had no effect on the ultrafilterability of lead in whole cell suspensions of liver and kidney. The refractoriness of whole cell suspensions to the chelating effect of EDTA was not due to failure of EDTA to penetrate into cells. The efflux of lead from isolated perfused livers was characterized by two first-order rates, one of which was rapid (T_1/2 = 0.2-1.1 hr) and the other slow (T_1/2 = 34-183 hr). EDTA had no effect on the efflux. Changing the blood in the perfusion reservoir markedly accelerated efflux. Perfusion with nonrecirculating blood or electrolyte solution also generally caused a marked increase in efflux, independent of the presence or absence of EDTA. It is concluded that the effect of EDTA is mainly, if not altogether, on the lead deposited in bone and that the reduction in the lead content of soft tissues is the result of secondary redistribution to the bone.