Antimony in drinking-water
Background document for development of WHO Guidelines for Drinking-water Quality
Kinetics and metabolism in laboratory animals and humans
The solubility of ATO in synthetic gastric juice has been shown to be 20 mg/litre after 24 h (DuPont, 2001). However, studies on absorption indicate that it is relatively low. Even in soluble forms, antimony is not readily absorbed from the gastrointestinal tract, irrespective of the valence state (Felicetti et al., 1974). Absorption rates between 5% and 20% have been observed in animals (Moskalev, 1959; Waitz et al., 1965; Van Bruwaene, 1982). Examination of four persons after involuntary acute intoxication with APT revealed an absorption rate of 5% (Iffland & Bösche, 1987; Lauwers et al., 1990).
In experimental animals, after absorption, antimony is bound to the red blood cells (Molokhia & Smith, 1969; Felicetti et al., 1974; Gerber et al., 1982; Dieter et al., 1991) and then transported mainly to the spleen, liver and bone (Casals, 1972) and to some extent into skin and hair (Felicetti et al., 1974; Berman et al., 1988). It is unknown to what extent inorganic and organic antimony(V) may be reduced to antimony(III) in vivo. Antimony(III) in the form of antimony trihydroxide (Sb(OH)3) can easily pass through cell membranes due to its lack of electrical charge. This seems to be the reason for its longer elimination half-time (94 h vs. 24 h) compared with antimony(V) (Stemmer, 1976; Gebel, 1997).
Although there appear to be few data available on the in vivo reduction of antimony(V) to antimony(III), it appears that conditions under which this may occur are not the normal physiological conditions found in cells and tissues. Only special conditions of low pH may facilitate the change, and, under normal circumstances, the bulk of any ingested antimony(V) will not be reduced. However, this may occur to a small extent, and the view expressed recently (Frezard et al., 2001; Shaked-Mishan et al., 2001) is that this reduction may be important for the antileishmanial activity of meglumine antimoniate, reduction of antimony(V) to toxic antimony(III) occurring in specific organelles of the leishmania species.
Sb(OH)3, like As(OH)3, readily reacts with thiol groups. Both trivalent metal species accumulate in vitro in cultured mammalian cells and seem to exert mutually additive or sub-additive toxicity in combined incubation (Felicetti et al., 1974; Buchet et al., 1980; Bailly et al., 1991; Gebel, 1997, 1998; Schaumlöffel & Gebel, 1998). Elimination of antimony(III) and arsenic(III) from cells follows the same ATP-dependent mechanisms and explains the cross-resistance between both trivalent elements in bacterial and mammalian cells (Rosen et al., 1988; Mukhopadhyay et al., 1996; Wang et al., 1996).
Antimony is not an essential element in plants or animals (Fowler & Goering, 1991).