Subchronic oral toxicity studies of Se-methylselenocysteine, an organoselenium compound for breast cancer prevention. Food Chem Toxicol

Life Sciences Group, IIT Research Institute, Chicago, IL 60616, USA.
Food and Chemical Toxicology (Impact Factor: 2.9). 03/2008; 46(3):1068-78. DOI: 10.1016/j.fct.2007.11.001
Source: PubMed


Se-methylselenocysteine (MSC) is an organoselenium compound being developed for breast cancer chemoprevention. To characterize MSC toxicity, CD rats received daily gavage doses of 0, 0.5, 1.0, or 2.0 mg/kg/day (0, 3, 6, or 12 mg/m(2)/day), and beagle dogs received daily gavage doses of 0, 0.15, 0.3, or 0.6 mg/kg/day (0, 3, 6, or 12 mg/m(2)/day) for 28 days. In rats, MSC induced dose-related hepatomegaly in both sexes; mild anemia, thrombocytopenia, and elevated liver enzymes were observed in high dose females only. Microscopic pathology included hepatocellular degeneration (high dose males, all doses in females); arrested spermatogenesis (high dose males); and atrophy of corpora lutea (middle and high dose females). In dogs, MSC induced mild anemia in middle and high dose males, and in high dose females. Toxicologically significant microscopic lesions in dogs were seen only in the liver (peliosis and vacuolar degeneration in high dose males, midzonal necrosis in males in all dose groups). Based on liver pathology seen in female rats in all dose groups, the no observed adverse effect level (NOAEL) for MSC in rats is <0.5mg/kg/day. Based on alterations in hematology parameters and liver morphology in male dogs in all dose groups, the NOAEL for MSC in dogs is <0.15 mg/kg/day.

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    • "Se was first discovered in 1817 in the form of a reddish precipitate, an elemental form of Se (Zhang, 2009). Elemental Se was originally considered to biologically inert in upregulating selenoenzymes and consequently most work has focused on organic forms such as selenomethionine and Se-methylselenocysteine, and on inorganic sodium selenate and selenite (Weekley and Harris, 2013; Schrauzer, 2000; Johnson et al., 2008). Materials at nanometer dimensions or with nanostructures almost invariably exhibit new properties different from those of either bulk materials or isolated atoms. "
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    • "SeMSC is considered to be one of the most effective Se compounds for chemoprevention, but unfortunately its systemic toxicities are high as well.112–114 Zhang et al111 have demonstrated that SeMSC and Nano-Se have equal bioavailability at nutritional doses. "
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    • "The toxicity of this species of Se is probably at least as high as other forms; toxicity to rats occurred at doses >0.5 mg/kg BW (Johnson et al., 2008). Typically, the maximum tolerable level of Se for sheep and cattle is given as 5 mg/kg diet dry matter (NRC, 2005). "
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