Inorganic Arsenicals. The metabolism of inorganic arsenic has been extensively studied in humans and
animals, and is diagrammed in Figure 3-7. Two basic processes are involved: (1) reduction/oxidation
reactions that interconvert As(III) and As(V), and (2) methylation reactions, which convert arsenite to
MMA and DMA. The resulting series of reactions results in the reduction of inorganic arsenate to
arsenite (if necessary), methylation to MMA(V), reduction to MMA(III), and methylation to DMA(V).
These processes appear to be similar whether exposure is by the inhalation, oral, or parenteral route. The
human body has the ability to change inorganic arsenic to organic forms (i.e., by methylation) that are
more readily excreted in urine. In addition, inorganic arsenic is also directly excreted in the urine. It is
estimated that by means of these two processes, >75% of the absorbed arsenic dose is excreted in the
urine (Marcus and Rispin 1988), although this may vary with the dose and exposure duration. This
mechanism is thought to have an upper-dose limit which, when overwhelmed, results in a higher
incidence of arsenic toxicity. This is supported by a case report of an individual who died 3 days after
ingesting 8 g of arsenic trioxide (about 3 g of arsenic) (Benramdane et al. 1999a). Only 20% of the total
arsenic in all tissues analyzed was methylated (14% MMA, 6% DMA), while 78% remained as arsenite
and 2% as arsenate