Alterations in Tissue Pb Distribution and Hematopoietic Indices During Advanced Age

The inevitable degenerative processes accompanying advanced age suggest that senescent organisms might exhibit differences in toxicokinetics or an altered manifestation of toxic effects. This hypothesis was tested in the present experiment which compared tissue distribution and hematopoietic indices in groups of adult (8 months) and old male Fischer-344 rats (16 months) exposed to concentrations of 0, 250 or 500 ppm lead (Pb) acetate in drinking water for 7 months. A group of young (weanling) rats was included as a partial comparison. Blood lead (PbB), zinc protoporphyrin (ZPP) and urinary delta-aminolevulinic acid levels were determined after both 3 and 7 months of exposure. Organ weights, tissue Pb concentrations and urinary excretion of Pb, calcium, copper, and zinc were examined after 7 months of exposure. Tissue Pb distribution was markedly altered in old rats: bone and kidney Pb were reduced; liver Pb was substantially increased, even though PbB levels in adult and old rats were comparable at both measurement intervals, as was urinary Pb excretion at 7 months. Pb-induced elevation of ZPPs exhibited differential changes between 3 and 7 months: values in adults declined while levels in old rats increased or remained unchanged. These findings show that the responses of adult rats to Pb do not predict those of older rats and indicate the need for further characterization and elaboration of mechanisms of toxic effects with advanced age.