LACK OF METHYLATION OF INORGANIC ARSENIC IN THE CHIMPANZEE

Most mammals methylate inorganic arsenic (As) to methylarsonic acid (M MA) and dimethylarsinic acid, which are rapidly excreted in the urine. Previous studies have shown that, in contrast to humans, all experime ntal animals excrete very little MMA. With the aim of finding an appro priate animal model for studies on inorganic As metabolism and toxicit y, we have investigated the metabolism of As in two male chimpanzees a fter a single iv dose of[As-73]arsenate (5.8 mu g As/kg body wt). The initial clearance from plasma was rapid with an apparent half-time of about 1 hr. Urine was found to constitute the major excretory pathway with very little excretion in the feces. About 60% of the administered As-73 dose was excreted in the urine within 96 hr in a biphasic manne r. The second phase of slow urinary excretion was characterized by fir st-order kinetics with a half-time of about 7 days. Upon ion-exchange chromatography of ultrafiltrated plasma and urine, only inorganic As c ould be detected, a finding confirmed by thin-layer chromatography. Th us, the results indicate that the chimpanzee, as previously shown for the marmoset monkey, but unlike all other mammals studied so far, incl uding humans, is unable to methylate and detoxify inorganic As. (C) 19 95 Academic Press, Inc.