The metabolism of arsenite and arsenate by the rat.

Differences in distribution and metabolism of arsenite and arsenate were studied in rats and in rat liver and kidney slices and hepatocytes. Five minutes after i.v. administration of 4.8 nmol arsenite or arsenate to male Sprague-Dawley rats, blood levels of arsenic were only 10 percent of the initial dose. Blood arsenic levels then rose: by 4 hours about 67 percent of the initial dose of arsenite and 28 percent of the initial dose of arsenate were in the blood compartment. The predominant form of arsenic in the RBC was dimethylarsinic acid (DMA). Arsenite was rapidly distributed to both liver and kidney; arsenate was rapidly distributed to kidney only. After 4 hours of exposure to arsenite, liver slices had taken up six times more arsenic and kidney slices two times more arsenic than after exposure to arsenate. Isolated hepatocytes took up as much as 20 times more arsenic after arsenite exposure. DMA was found in the medium of the liver slices and hepatocytes exposed to arsenite, but very little DMA was found in the medium of the arsenate-exposed liver slices and hepatocytes. However, five times more DMA was found in the medium of the kidney slices exposed to arsenate than in the medium of the liver slices. Phosphate inhibited uptake and metabolism of arsenate by kidney slices. These studies indicate that inorganic arsenic is rapidly taken up by liver and kidney and methylated. Arsenite is methylated by both organs, whereas arsenate may be methylated by kidney only.