Route-dependent pharmacokinetics, distribution, and placental permeability of organic and inorganic selenium in hamsters.
Inorganic selenium (Se) salts (selenite and selenate oxyanions) and the organic selenoamino acids (selenomethionine and seleniferous grains) are teratogenic and embryolethal in domestic and wild birds. Selenium bioaccumulation has been held responsible for reproductive failure among waterfowl at the Kesterson Reservoir (California), the Ouray and Stewart Lake Wildlife Refuges (Utah), and the Carson Sink (Nevada). Anecdotal field and controlled laboratory reports have implicated Se exposure in mammalian embryotoxicity (including human), but developmental toxicity studies in hamsters failed to demonstrate an adverse response, except at maternally toxic doses (Ferm et al., Reprod. Toxicol., in press). Uptake, distribution, and elimination of Se after a single bolus equimolar dose (60 mumol/kg) of selenate or selenomethionine by oral or intravenous administration were compared using day 8 pregnant hamsters. Intravenous selenate was eliminated ten times more rapidly from maternal plasma than oral selenate, but concentrated in liver, kidney, and placenta to the same degree. Intravenous (iv) L-selenomethionine achieved lower maximum circulating total [Se], but it was eliminated more slowly than iv selenate. Larger areas under the plasma and peripheral tissue [Se]:time curve (AUC) after oral or parenteral selenomethionine than after equimolar selenate were consistent with previous studies in rodents and in humans. Embryonic [Se] plateaued at 3 nmol/g after selenate, but embryonic [Se] after selenomethionine continued to accumulate (80 nmol/g) as gestation progressed. The lack of a teratogenic response in hamsters at doses of either selenate or selenomethionine less than those associated with maternal intoxication cannot be attributed to lack of Se accumulation in early embryonic and placental tissue.
Willhite
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Department of Health Services, State of California, Berkeley 94704.
Ferm
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VH
Zeise
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D000818:Animals; D001682:Biological Availability; D006224:Cricetinae; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D008431:Maternal-Fetal Exchange; D008647:Mesocricetus; D010539:Permeability; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012643:Selenium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013723:Teratogens / Q000493:pharmacokinetics; D014018:Tissue Distribution
D013723:Teratogens; D012643:Selenium