Metabolism of 74As-labeled trivalent and pentavalent inorganic arsenic in mice

Man is exposed to different forms of arsenic in the environment but differences in metabolism and toxicity are poorly understood. The differences in metabolism between pentavalent and trivalent inorganic arsenic in mice following single oral administration of ⁷⁴As-labeled arsenate or arsenite (0.4 and 4 mg As/kg body wt) was studied. Valence state of the administered arsenic was strictly controlled, which has not always been the case in previous studies. In mice given the high dose, whole body retention was two to three times higher after exposure to As(III) compared to As(V). Retention was also dose dependent. Five weeks after administration, high dose/low dose retention ratios were 6 and 11 for As(V) and As(III). Differences found in most organs studied (blood, kidney, liver, bile, brain, skeleton, and skin) were most obvious in liver and bile with concentrations 2 to 10 times higher in the As(III) groups. Red cell/plasma ratios were 2–3 for As(III) and close to unity for As(V). It is suggested that the observed differences between As(V) and As(III) are due to differences in degree of methylation and subsequent elimination primarily via the kidneys.