Dose-Response Relationships for the Metabolism and Urinary Excretion of Arsenicals in Humans

摘要

Two population-based studies of the metabolism and fate of arsenic were performed in individuals who chronically consumed drinking water that contains inorganic arsenic. The first study examined the relationship between the intensity of exposure to inorganic arsenic in drinking water and the urinary excretion of the methylated metabolites, methyl arsenic and dimethyl arsenic. The output of methyl and dimethyl arsenic in urine was found to be relatively constant throughout the day and over a 5-day period. Over a wide range of exposure to inorganic arsenic in drinking water (8-620 μg/l), neither the amount nor percentage of total arsenic in urine that was present as methyl or dimethyl arsenic declined. That is, capacities to methylate inorganic arsenic and to excrete its metabolites in urine were not exceeded over this exposure range. Percentages of the total arsenic in urine that were accounted for by each methylated metabolite varied among individuals. Inter-individual variation could arise from polymorphisms in the enzyme that methylates arsenicals. Further characterization of the enzymology of arsenic methylation in humans will be required to identify sources of interindividual variation. The second study was a pilot study of arsenic and selenium status in chronically exposed individuals. Selenium modifies the distribution, metabolism, retention, and toxicity of inorganic arsenic in many experimental systems; however, few data are available on arsenic and selenium interactions in humans. Although the concentrations of arsenic in blood and urine were correlated, the concentrations of selenium in blood and urine were not. This difference may reflect homeostatic control of selenium metabolism and the absence of such control for arsenic metabolism. When expressed on the basis of body mass, the concentrations of arsenic and selenium in blood, but not in urine, were significantly correlated. Body mass has previously been identified as potential confounder of the analysis of dose-response relationships in individuals chronically exposed to inorganic arsenic.