Page 9: Guidelines for Canadian Drinking Water Quality: Guideline Technical Document – Selenium
Part II. Science and Technical Considerations (continued)
Very little quantitative information is available on the absorption of selenium compounds through the lungs or skin. Oral absorption via the intestine is the major route of uptake of selenium into the body (Thiry et al., 2012). In laboratory animals and humans, most organic (selenomethionine and selenocysteine) and inorganic (selenite and selenate) forms of selenium are readily absorbed along the ileum and duodenum (Patterson and Levander, 1997; Fairweather-Tate et al., 2010; U.S. EPA, 2010). The form of the element, the amount of selenium in the body and the presence of certain amino acids and sulphur compounds or heavy metals such as mercury in the gut influence the absorption rate (Patterson and Levander, 1997; IPCS, 2006). Elemental selenium and selenosulphide species are poorly absorbed (U.S. EPA, 1991a). Organic selenium is subject to active transport, whereas selenite undergoes passive diffusion in the gut. Selenate is absorbed through the small intestine via the sodium-dependent transporter of sulphate.
In a kinetic comparison study, two 150 µg doses of selenomethionine or selenite were given to healthy American adults with normal plasma selenium concentrations (80-160 µg/L). The absorption of selenomethionine was 97%, whereas that of selenite was around 60% (Wastney et al., 2011). The results of this study were confirmed in another interventional study in the United States (Burk et al., 2006). Selenomethionine increased plasma selenium levels twice as efficiently as selenite at the same doses (200, 400 or 600 µg). Oral absorption of selenite given as a single dose of 81.7 µg has been measured at higher levels (89%) in healthy males (Martin et al., 1988). The composition of the diet was thought to influence absorption.
Oral ingestion of 1700 mg of selenite in humans generated a plasma concentration of selenium of 2.7 mg/L 3 hours after ingestion (generally, blood concentrations are 0.060-0.150 mg/L) (Gasmi et al., 1997).
Selenite is poorly absorbed in ruminants because of the reducing environment of the rumen (Wright and Bell, 1966; Gunter et al., 2003). In general, organic compounds are better absorbed in ruminants and are converted to selenoproteins (Gunter et al., 2003). Selenate and selenite added at 0.3 mg/kg of dry food were absorbed in equal amounts by sheep, cattle and horses, and both induced an increase in blood selenium concentration (Podoll et al., 1992).
Inhalation of selenium-containing aerosols that are not soluble in water have been reported in occupational exposures, such as workers in copper smelters or selenium rectifier plants (U.S. EPA, 2010), but it will not be considered further, as it is not relevant to drinking water. Dermal absorption did not occur in mice or humans exposed to selenium sulphide or selenomethionine (ATSDR, 2003).
Once in the bloodstream, selenium is distributed throughout the body. Most of the absorbed portion of selenite, selenomethionine and selenocysteine is transported to organs with a high rate of selenoprotein synthesis: liver, muscle, brain and, to a lesser extent, testis and kidneys (Deagen et al., 1987; Willhite et al., 1992; Thiry et al., 2012). The remaining selenium stays in plasma or enters the lymphatic tissues before being distributed to other organs (Wastney et al., 2011).
Selenium compounds are transported in the blood to various organs by albumin and other proteins containing sulphydryl groups, such as low-density lipoproteins, selenoprotein P and glutathione peroxidase (IARC, 1975; Schrauzer, 2000; Thiry et al., 2012).
Radioactively marked selenite or selenomethionine given orally to rats for 4 weeks were both found to be distributed to all tissues analysed, with the highest proportion in the muscles and liver (Beilstein and Whanger, 1988). Erythrocytes, spleen, lung and muscles exhibited an increased glutathione peroxidase activity, demonstrating that selenium was distributed to these tissues and used to synthesize this enzyme. Liver, kidney and heart were the organs containing the highest selenium concentrations after exposure of sheep and swine to high concentrations via ingestion and intravenous injection (Blodgett and Bevill, 1987).
Selenium is metabolized mainly to the intermediate selenide before entering other metabolism routes. Selenate, selenite and selenocysteine directly follow reduction reaction pathways to form selenide, whereas selenomethionine is either incorporated non-specifically into methionine-containing proteins or converted by the enzyme selenocysteine-β-lyase to elemental selenium, which can be reduced to selenide in the body (Esaki et al., 1982; Fairweather-Tate et al., 2010; Wastney et al., 2011). When selenium is present at high concentrations, selenide is methylated and excreted, but when it is present at low or normal levels, it is used in selenoprotein synthesis via incorporation into the amino acid cysteine (Suzuki, 2005; Suzuki et al., 2005; Gromadzińska et al., 2008; Wastney et al., 2011).
Organic selenium induces higher concentrations of selenium in serum and liver compared with inorganic selenium at equivalent doses, as well as a higher response in blood glutathione peroxidase activity, supportive of its higher incorporation into selenoproteins (Kim and Mahan, 2001; Wastney et al., 2011).
In a trial in which selenium was administered to 120 Chinese volunteers at amounts up to 75 µg/day for 20 weeks, both organic (selenomethionine) and inorganic selenium (selenite) increased glutathione peroxidase activity and blood selenium concentrations. The organic form induced maximal enzyme activity at a lower dose (37 µg/day) than did selenite (66 µg/day) (Xia et al., 2005). Another trial in which 90 µg selenite or 100 µg selenomethionine was administered to human volunteers for 17 weeks in New Zealand showed similar results (Thomson et al., 1982). In animals, similar results were obtained in six female rhesus monkeys exposed to selenite in the diet at concentrations of 0.25-0.5 µg/mL for 11 months (Butler et al., 1990).
At high doses (higher than suggested nutritional requirements), selenomethionine and methylselenocysteine are metabolized by methioninase and β-lyases, respectively. These pathways generate methylselenol, which can react with glutathione, as selenite does (Zhang and Spallholz, 2011). Methylselenol is believed to be the cornerstone of the anticarcinogenicity mode of action for selenium (Sanmartin et al., 2008). It can be oxidized to methylseleninic acid.
The kidney is the main organ of selenium excretion (Zachara et al., 2001). In experimental animals and humans, selenium is excreted mainly through the urine, followed by faeces and breath, with proportions varying with the intake (Lopez et al., 1969; Martin et al., 1988). The total intake of selenium determines the extent of methylation and demethylation, which regulate the amount excreted (Thiry et al., 2012). Oral or intravenous doses of selenite given to healthy men both resulted in high urinary and, to a lesser extent, faecal excretion (Martin et al., 1988). At low and normal levels, monomethylselenium and selenosugars represent the major excretion compounds in the urine, whereas the amount of the exhaled trimethylselenium compound increases with dose (ATSDR, 2003; Francesconi and Pannier, 2004; U.S. EPA, 2010).
Selenite has a shorter half-life in the body in comparison with selenomethionine (Patterson and Levander, 1997), because selenomethionine is an amino acid, which is recycled by the body (Swanson et al., 1991; Wastney et al., 2011). The half-life in the body is 252 days for selenomethionine and 102 days for selenite (Schrauzer, 2000).
Mice injected with 2.25 µg selenite excreted the excess selenium in faeces and urine mainly in the chemical form of 1β-methylselenol-N-acetyl-D-galactosamine (selenosugar) (Suzuki et al., 2010). The selenosugar was the main compound excreted in urine when rats were given water containing selenite at concentrations up to 1 µg/mL ad libitum for 7 days, whereas the excretion of monomethylselenium and trimethylselenium increased at selenite concentrations above 2 µg/mL (Suzuki, 2005; Suzuki et al., 2005; Thiry et al., 2012). Rats exposed to high doses of selenite excrete trimethylselenium in the urine and faeces and exhale dimethylselenide in the breath (Suzuki, 2005; Zhang and Spallholz, 2011).
The methylation of selenide generates dimethylselenide or trimethylselenium, which are excreted; this is considered to be a detoxification process (Gailer et al., 2002). When selenite was given orally to humans at a dose considered to be within the normal range (81.7 µg), trimethylselenium accounted for only 2.2% of total selenium in the urine (other metabolites were not detailed by the authors) (Martin et al., 1988). In another study, 300 µg selenite was administered orally to one man. Dimethylselenide was the only selenium compound exhaled, and its concentration spiked 1.5 hours after administration. After 10 days, the exhalation route accounted for 11% of total excretion, whereas urine accounted for 18%. Another maximum peak in blood selenium concentration was observed after 20 hours, suggestive of the existence of another, slower pathway (Kremer et al., 2005).
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