title: Toxicological evaluation of ethanolic extract from Stevia rebaudiana Bertoni leaves: Genotoxicity and subchronic oral toxicity.
abstract: Stevia rebaudiana Bertoni leaves have a long history of use as an abundant source of sweetener. The aqueous extract of stevia leaves and the predominant constitutes steviol glycosides have been intensively investigated. However, rare studies provided toxicological evaluation of bioactive components in the polar extract regarding their safety on human health. This study aimed to evaluate the toxicity of ethanolic extract of Stevia rebaudiana Bertoni leaves through a battery of in vitro and in vivo tests. Negative results were unanimously obtained from bacterial reverse mutation assay, mouse bone marrow micronucleus assay and mouse sperm malformation assay. Oral administration at dietary levels of 1.04%, 2.08% and 3.12% for 90 days did not induce significant behavioral, hematological, clinical, or histopathological changes in rats. Significant reduction of cholesterol, total protein and albumin was observed in female animals only at high dose level. The results demonstrated that Stevia rebaudiana Bertoni leaves ethanolic extract, which is rich in isochlorogenic acids, does not possess adverse effects through oral administration in this study. Our data provided supportive evidence for the safety of Stevia rebaudiana Bertoni leaves that may potentially be used in functional foods as well as nutritional supplements beyond sweetner.
authors.affiliation: Key Laboratory of Food Safety Risk Assessment of Ministry of Health, National Center for Food Safety Risk Assessment, Beijing 100021, China.
authors.forename: Qiannan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Food Safety Risk Assessment of Ministry of Health, 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, National Center for Food Safety Risk Assessment, Beijing 100021, China.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Food Safety Risk Assessment of Ministry of Health, National Center for Food Safety Risk Assessment, Beijing 100021, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Food Safety Risk Assessment of Ministry of Health, 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; D045786:Diterpenes, Kaurane / Q000633:toxicity; D009152:Mutagenicity Tests / Q000379:methods*; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity*; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D036625:Stevia / Q000737:chemistry*; D013549:Sweetening Agents / Q000633:toxicity; D059550:Toxicity Tests, Subchronic / Q000379:methods*
chemical_list: D045786:Diterpenes, Kaurane; D010936:Plant Extracts; D013549:Sweetening Agents
keywords: Ethanolic extract; Genotoxicity; Safety evaluation; Stevia rebaudiana Bertoni; Subchronic toxicity