Page 9: Guidelines for Canadian Drinking Water Quality: Guideline Technical Document – Arsenic
Although the results of available studies indicate that arsenic may be an essential element for several animal species (e.g., goats, minipigs, rats, chicks), there is no evidence that it is essential for humans. A Technical Panel on Arsenic convened by the U.S. EPA was "not aware of case reports describing an arsenic requirement for humans, nor of experimental or epidemiologic-type studies designed to determine whether arsenic is essential." After reviewing the available data, the Technical Panel concluded that "if arsenic is a required nutrient for humans, current environmental arsenic exposures are not known to produce human arsenic deficiency" (U.S. EPA, 1988).
Ingested elemental arsenic is poorly absorbed and largely eliminated unchanged. Arsenic oxides are readily absorbed (>80%) from the gastrointestinal tract (Fowler et al., 1979) and, to a lesser extent, through the lungs and skin (Wickström, 1972). On the basis of faecal recovery experiments in human volunteers, soluble As(III) and As(V) and organic arsenic are well absorbed; As(III) tends to accumulate in tissues, but As(V) and organic arsenic are rapidly and almost completely eliminated via the kidneys (Bertolero et al., 1987). Both organic and inorganic arsenic are not well absorbed by the skin. Dermal exposure is reported to be of minor importance compared with ingestion. The National Research Council (U.S. NRC, 1999) and the Agency for Toxic Substances and Disease Registry (ATSDR, 2000) reviewed the available information on dermal absorption of arsenic and indicated that systemic absorption of arsenic via the skin is sufficiently low that this route of exposure is unlikely to be of concern to health.
Following ingestion, inorganic arsenic appears rapidly in the circulation, where it binds primarily to haemoglobin (Axelson, 1980); within 24 hours, it is found mainly in the liver, kidneys, lungs, spleen, and skin (Wickström, 1972). Skin, bone, and muscle represent the major storage organs. The accumulation of arsenic in skin is probably related to the abundance of proteins containing sulphydryl groups, with which arsenic readily reacts (Fowler et al., 1979). In humans, inorganic arsenic does not appear to cross the blood-brain barrier; however, transplacental transfer of arsenic in both humans (Gibson and Gage, 1982) and mice (Hood et al., 1987) has been reported.
Pathways for the conversion of one form of arsenic to another have been proposed (U.S. NRC, 2001). Methylation of inorganic arsenic is thought to occur following the reduction of pentavalent arsenic to trivalent arsenic. Methylation of this trivalent form of arsenic is then believed to result from the oxidative addition of a methyl group from S-adenosylmethionine by a methyl transferase. Sequential reduction and methylation of arsenic compounds result in the creation of pentavalent monomethylarsinic acid (MMAV) and dimethylarsinic acid (DMAV), as well as the trivalent monomethylarsinous acid (MMAIII) and dimethylarsinous acid (DMAIII) (U.S. NRC, 2001).
There appear to be two main processes, with different rates, for the elimination of ingested trivalent arsenic (As(III)) from the body (Lovell and Farmer, 1985). The first is the rapid urinary excretion of inorganic arsenic in both the trivalent and pentavalent forms (close to 90% of the total urinary arsenic over the first 12-hour period). The second involves the sequential methylation of As(III) in the liver to the organic forms MMAIII, DMAIII, MMAV, and DMAV (Buchet and Lauwerys, 1985; Lovell and Farmer, 1985). Excretion of the methylated compounds commences approximately 5 hours after ingestion but reaches its maximum level 2-3 days later. Less important routes of elimination of inorganic arsenic include skin, hair, nails, and sweat (ICRP, 1975; Kurttio et al., 1999). The half-life of inorganic arsenic in humans is estimated to be between 2 and 40 days (Pomroy et al., 1980).
The results of a study in which inorganic arsenic (125, 250, 500, or 1000 µg NaAsO2) was administered orally once a day for 5 consecutive days to four volunteers indicate that the arsenic methylation capacity is progressively saturated when daily intake exceeds 0.5 mg (Buchet et al., 1981a); it does not, however, appear to be completely saturated even for daily doses as high as 1 mg. Studies with human volunteers indicate that most ingested organic arsenic is rapidly excreted unchanged (>80% of the dose within 4 days) (Buchet et al., 1981b; Luten et al., 1982; Tam et al., 1982).
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