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were topically applied to human skin or the skin of rhesus monkeys showed that about 2-6% of the applied arsenic was absorbed in 24 hr (Wester et al. 1993). Similar in vitro studies using dorsal skin of mice showed a much higher absorption; 30% of the applied dose of radiolabeled arsenate in aqueous solution (100-200 ng/L) was absorbed in 24 hr (Rahman et al. 1994). A large percentage, on average 60-90 %, of the absorbed arsenic was retained in the skin. That result indicates that inorganic arsenic can bind externally to skin and hair. Rapid binding of 74 As to the skin and epithelium of the upper gastrointestinal tract in the marmoset fetus has also been observed 8 hr after maternal exposure to 74As-arsenite (Lindgren et al. 1984). Taken together, those results indicate a low degree of systemic absorption of arsenic via the skin. Some further information on the skin absorption of arsenic in humans may be obtained from a study in Fairbanks, Alaska, where arsenic was found in home water at 345 µg/L (Harrington et al. 1978). One group of people who drank bottled water only but used the arsenic-rich water for other purposes had about the same low concentrations of the sum of arsenic metabolites in urine (average 43 µg/L) as people with less than 50 µg/L in their home water (average 38 µg/L in urine), indicating a low degree of skin absorption. However, the hair arsenic concentrations were clearly elevated in the group drinking bottled water (5.7 µg/g compared with 0.43 µg/g in the low-arsenic-water group), suggesting that arsenic is bound externally to hair and probably also to skin during washing with arsenic-rich water.

Biotransformation

In this section, arsenate reduction and arsenite methylation are described. Species differences are reviewed, as are other factors influencing the metabolism of arsenic. Variations in arsenic methylation in humans are reviewed in more detail in Chapter 7.

Arsenate Reduction and Arsenite Methylation

In humans and in most experimental animals, inorganic arsenic is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Compared with inorganic arsenic, the methylated metabolites are less reactive with tissue constituents, less acutely toxic, less cytotoxic, and more readily excreted in the urine (Buchet et al. 198 1a; Vahter and Marafante 1983; Vahter et al. 1984; Yamauchi and Yamamura 1984; Marafante et al. 1987; Moore et al. 1997; Rasmussen and Menzel, 1997; Concha et al. 1998a; Hughes and



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