BASAL-METABOLISM OF INTRAPERITONEALLY INJECTED CARRIER-FREE AS-74-LABELED ARSENATE IN RABBITS

The time-dependent occurrence of [As-74]arsenate metabolites in Flemis h Giant rabbits was investigated. As absorbed rapidly, reaching maxima l concentrations in plasma and packed cells after 30 min and 2 hr, res pectively. The [As-74]arsenate in plasma and packed cells was reduced to [As-74]arsenite, to 35 and 50% of the total As-74, respectively. Th e concentration of methylated As species in plasma and packed cells in creased rapidly after 30 min. About 18% of total plasma As-74 maximall y bound to transferrin. Two-thirds of total As-74 in packed cells boun d to hemoglobin. Whereas little or no [As-74]monomethylarsonic acid, o ne of the main As metabolites in humans, could be found in other anima ls, it is present in measurable amounts in the Flemish Giant. Furtherm ore, the plasma clearance rate of As-74 species is lower than that in other rabbits and more similar to that of humans. The tissue As-74 dis tribution varied widely with the highest concentrations in kidneys, li ver, and lungs. As-74 accumulated in bone whereas other tissues and bl ood showed rapid clearance rates. In muscle and heart an important par t of arsenic was associated with components insoluble in phosphate-buf fered isotonic saline. Binding of arsenic to soluble tissue proteins w as most important in the kidneys, liver, and spleen. [As-74]Arsenate m etabolites were detected in all tissues. The relative amounts of [As-7 4]arsenite or [As-74]monomethylarsonic acid seldom exceeded 15% of tot al tissue As-74. The proportion of [As-74]dimethylarsenic acid in the low molecular As-74 fraction increased steadily. Substantial amounts o f [As-74]monomethylarsonic acid were found in the tissues. (C) 1996 So ciety of Toxicology.