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arsenic metabolites. Factors considered are methodological aspects; genetic polymorphism; age, sex, and recreational habits; effects of dose; and individual variation.

Methodological Aspects

The efficiency of arsenic methylation is often evaluated by the relative distribution  of metabolites  of inorganic  arsenic  (inorganic  arsenic, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)) in the urine. However, the relative amounts of arsenic metabolites in the urine might not reflect the actual methylation efficiency in the body (i.e., the fraction of the absorbed dose that is methylated), because the methylated metabolites are excreted in the urine more quickly than inorganic arsenic (Buchet et al. 1981a). Given that inorganic arsenic, especially As(III), is the main form of arsenic interacting with tissues (Buchet et al. 1981a; Vahter and Marafante 1983; Bogdan et al. 1994), a decrease in tissue methylation would result in more arsenic being retained in the body (Marafante and Vahter 1984; Marafante et al. 1985).

Ideally, the evaluation of the in vivo methylation of arsenic in humans would be based on the assessment of urinary excretion of MMA and DMA in relationship to the absorbed dose. That assessment is not easily done, because the exact amounts of arsenic inhaled or ingested with drinking water and food, as well as the fraction absorbed, are seldom known. However, a few experimental studies on human volunteers have specified the administered dose and form of arsenic. In a study by Tam et al. (1979), six males ingested 74 As-labeled arsenate (about 0.01 µg of arsenic, greater than 90% As(V), per person), and the excretion of 74 As was followed for 5 days. Results indicate that approximately 58 % of the dose was excreted within that time. In another study, two subjects ingesting 200 µg of As(V) (1 L of bottled water each) excreted about 66% of the dose over 7 days following ingestion (Johnson and Farmer 1991). Taken together, the results of these experimental studies indicate that the proportion of DMA in the urine (relative to U-Asmet) is associated with the urinary excretion of DMA (% of ingested dose), as well as the total urinary excretion of metabolites of inorganic arsenic (U-Asmet), in percentage of the given dose. Similar results were reported in studies of human volunteers exposed to arsenite (Crecelius 1977; Buchet et al. 1981a,b), but the variation was considerable. Thus, on a group basis, a low proportion of DMA in urine (relative to U-Asmet) indicates that the rate of methylation is low and that the overall rate of excretion of arsenic metabolites (in percentage of dose) is low. This would lead to more inorganic arsenic being retained in



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