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ARS Home » Pacific West Area » Logan, Utah » Poisonous Plant Research » Research » Publications at this Location » Publication #322624

Title: Comparative oral dose toxicokinetics of sodium selenite and selenomethionine

Author
item Davis, Thomas - Zane
item TIWARY, ASHEESH - Amgen, Inc
item Stegelmeier, Bryan
item Pfister, James
item Panter, Kip
item HALL, JEFFERY - Utah State University

Submitted to: Journal of Applied Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/21/2016
Publication Date: 12/8/2016
Citation: Davis, T.Z., Tiwary, A.K., Stegelmeier, B.L., Pfister, J.A., Panter, K.E., Hall, J.O. 2017. Comparative oral dose toxicokinetics of sodium selenite and selenomethionine. Journal of Applied Toxicology. 37:231-238. doi: 10.1002/jat.3350.

Interpretive Summary: Selenium (Se) is a physiologically important dietary micronutrient that has been of toxicological concern for many years. Cases of Se deficiency, as well as Se poisoning are encountered in many states within the United States. Selenium is found in plants in many different forms including, selenomethionine (SeMet), Se-methylselenocysteine, selenate as well as several other selenocompounds. Selenium is often added as a feed supplement of which selenite, selenate, and Se yeast are the only approved sources of supplemental Se for livestock in the United States. Accidental Se poisonings of sheep have been reported from overdosing animals with supplemental sodium selenite. Kinetics of Se absorption, distribution and elimination in sheep, using varying intramuscular doses of sodium selenite, has been previously studied and reported. However similar studies describing the oral toxicokinetics of other selenocompounds (selenite and SeMet) in any large animal species are lacking. The purpose of this study was to describe and compare the oral dose toxicokinetics at near lethal doses of commonly used inorganic (selenite) and organic (SeMet) supplemental forms of Se in sheep. The results of this study demonstrate that SeMet has a higher absorption rate, bioavailability, and retention time than sodium selenite. When analyzing serum and whole blood concentrations in cases of Se toxicosis it is important to know the form of Se to which the animal was potentially exposed. In addition, tissue Se concentrations, due to SeMet supplementation, are likely to result in altered interpretation of the Se status of animals, humans or plant tissues in relationship to true nutritional status, as most nutritional studies have utilized inorganic Se studies as the bench marks for interpretation.

Technical Abstract: The toxicokinetics of selenium (Se) absorption, distribution, and elimination were determined in serum and whole blood of lambs that were orally dosed with various doses of Se as sodium selenite (inorganic Se) or selenomethionine (organic Se). Thirty-two lambs were randomly assigned to eight treatment groups, with four animals per group. Selenium was administered at 0, 1, 2, or 3 mg/kg body weight, as either sodium selenite or selenomethionine (SeMet). Two control groups were given similar amounts of sodium chloride or methionine. Blood and serum were collected at predetermined time points for seven days post-dosing. Resulting Se concentrations in both serum and whole blood from SeMet treatment groups were significantly higher than those given equimolar doses of Se as sodium selenite. Se concentrations in serum and whole blood of lambs dosed with SeMet peaked at 1.4 to 1.75 and 1.2 to 1.7 times that of lambs dosed with equimolar doses of sodium selenite. The half-life (t1/2) for absorption, distribution, and elimination of Se in serum ranged from 2.5 to 5.4 h, 8.0 to 16.6 h, and 2.1 to 4.8.d, respectively, depending on the dose and type of Se administered. For the whole blood, the t1/2 for absorption, distribution and elimination ranged from 2.5 to 5.7 h, 8.2 to 14.2 h, and 4.8 to 14.1 d, respectively. Based on the serum and whole blood kinetics, the rate of Se absorption was greater for SeMet than for sodium selenite although rates of absorption for both Se forms decreased with increasing dose. The rates of Se elimination increased with dose. These results demonstrate that different selenocompounds have different toxicokinetics when orally dosed at near lethal dosages.