Lack of methylation of inorganic arsenic in the chimpanzee.
Most mammals methylate inorganic arsenic (As) to methylarsonic acid (MMA) and dimethylarsinic acid, which are rapidly excreted in the urine. Previous studies have shown that, in contrast to humans, all experimental animals excrete very little MMA. With the aim of finding an appropriate animal model for studies on inorganic As metabolism and toxicity, we have investigated the metabolism of As in two male chimpanzees after a single iv dose of [73As]arsenate (5.8 micrograms 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 73As dose was excreted in the urine within 96 hr in a biphasic manner. The second phase of slow urinary excretion was characterized by first-order kinetics with a half-time of about 7 days. Upon ion-exchange chromatography of ultrafiltrated plasma and urine, only inorganic As could be detected, a finding confirmed by thin-layer chromatography. Thus, the results indicate that the chimpanzee, as previously shown for the marmoset monkey, but unlike all other mammals studied so far, including humans, is unable to methylate and detoxify inorganic As.
Vahter
M
M
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Couch
R
R
Nermell
B
B
Nilsson
R
R
D000818:Animals; D001149:Arsenates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001151:Arsenic / Q000378:metabolism*; D020261:Arsenic Poisoning; D001152:Arsenicals / Q000097:blood / Q000652:urine; D002101:Cacodylic Acid / Q000097:blood / Q000633:toxicity / Q000652:urine; D002852:Chromatography, Ion Exchange; D002855:Chromatography, Thin Layer; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D006540:Herbicides / Q000097:blood / Q000633:toxicity / Q000652:urine; D007275:Injections, Intravenous; D008297:Male; D008745:Methylation; D002679:Pan troglodytes / Q000378:metabolism*; D013723:Teratogens / Q000032:analysis / Q000633:toxicity
D001149:Arsenates; D001152:Arsenicals; D006540:Herbicides; D013723:Teratogens; D002101:Cacodylic Acid; C020300:monomethylarsonic acid; D001151:Arsenic