title: Safety evaluation of Se-methylselenocysteine as nutritional selenium supplement: acute toxicity, genotoxicity and subchronic toxicity.
abstract: The significant toxicity of selenium emphasizes the need to assess the health risk of various selenocompounds as nutritional supplements. Se-methylselenocysteine (SeMC) was recently reported to be more bioactive but the toxicological effects have not been sufficiently characterized. This study aimed to evaluate the safety of SeMC and provide the Acceptable Daily Intake (ADI) for its use in human diet. Our results demonstrated that SeMC, with the Median Lethal Dose (LD50) of 12.6 and 9.26mg/kg BW in female and male mice, was of high potent of health hazard under acute oral exposure, but a battery of tests including Ames test, micronucleus assay and mouse sperm malformation assay suggested that SeMC was not genotoxic. The repeated dose study indicated little systemic toxicity of SeMC at supernutritional levels (0.5, 0.7, 0.9mg/kg BW/day) after 90-day oral exposure. Importantly, the 95% lower confidence value of Benchmark Dose (BMDL) was estimated as 0.34mg/kg BW/day according to the elevated relative liver weight. The ADI for human was established at 3.4μg/kg BW/day. The results suggested greater safety of SeMC as a nutritional selenium supplement, but health risk needs to be further evaluated when SeMC is applied beyond this level to achieve cancer chemoprevention.
authors.affiliation: Key Laboratory of Food Safety Risk Assessment of Ministry of Health, China National Center for Food Safety Risk Assessment, Beijing 100021, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory of Food Safety Risk Assessment of Ministry of Health, China National Center for Food Safety Risk Assessment, Beijing 100021, China. Electronic address: jiaxudong@cfsa.net.cn.
authors.forename: Xudong
authors.initials: X
authors.lastname: Jia
mesh_terms: D000818:Animals; D019587:Dietary Supplements / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009152:Mutagenicity Tests; D019055:No-Observed-Adverse-Effect Level; D017207:Rats, Sprague-Dawley; D012643:Selenium; D017279:Selenocysteine / Q000031:analogs & derivatives* / Q000633:toxicity; D013094:Spermatozoa / Q000187:drug effects / Q000254:growth & development; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic
chemical_list: D017279:Selenocysteine; D012643:Selenium; C002979:selenomethylselenocysteine
keywords: Benchmark dose; Food supplements; Safety evaluation; Se-methylselenocysteine; Selenium