title: Safety evaluation of rebaudioside A produced by fermentation.
abstract: The safety of rebaudioside A, produced fermentatively by Yarrowia lipolytica encoding the Stevia rebaudiana metabolic pathway (fermentative Reb A), is based on several elements: first, the safety of steviol glycosides has been extensively evaluated and an acceptable daily intake has been defined; second, the use of Y. lipolytica, an avirulent yeast naturally found in foods and used for multiple applications; and third the high purity of fermentative Reb A and its compliance with internationally defined specifications. A bacterial reverse mutation assay and an in vitro micronucleus test conducted with fermentative Reb A provide evidence for its absence of mutagenicity, clastogenicity and aneugenicity. The oral administration of fermentative Reb A to Sprague-Dawley rats for at least 91 days did not lead to any adverse effects at consumption levels up to 2057 mg/kg bw/day for males and 2023 mg/kg bw/day for females, which were concluded to be the No Observed Adverse Effect Levels. The results were consistent with outcomes of previous studies conducted with plant-derived rebaudioside A, suggesting similar safety profiles for fermentative and plant-derived rebaudioside A. The results of the toxicity studies reported here support the safety of rebaudioside A produced fermentatively from Y. lipolytica, as a general purpose sweetener.
authors.affiliation: DSM Food Specialties B.V., Alexander Fleminglaan 1, 2613 AX, Delft, The Netherlands. Electronic address: melina.rumelhard@dsm.com.
authors.forename: Mélina
authors.initials: M
authors.lastname: Rumelhard
authors.affiliation: WIL Research Laboratories LLC, 1407 George Rd., Ashland, OH, 44805, USA. Electronic address: hiromi.hosako@wilresearch.com.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hosako
authors.affiliation: WIL Research Europe B.V., Hambakenwetering 7, 5231 DD, 's-Hertogenbosch, The Netherlands. Electronic address: irene.eurlings@wilresearch.com.
authors.forename: Irene M J
authors.initials: IM
authors.lastname: Eurlings
authors.affiliation: WIL Research Europe B.V., Hambakenwetering 7, 5231 DD, 's-Hertogenbosch, The Netherlands. Electronic address: walter.westerink@wilresearch.com.
authors.forename: Walter M A
authors.initials: WM
authors.lastname: Westerink
authors.affiliation: WIL Research Laboratories LLC, 310 Millstone Drive, Hillsborough, NC, 27278, USA. Electronic address: lauren.staska@wilresearch.com.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Staska
authors.affiliation: DSM Food Specialties B.V., Alexander Fleminglaan 1, 2613 AX, Delft, The Netherlands. Electronic address: jeanine.wiel-van-de@dsm.com.
authors.forename: Jeanine A G
authors.initials: JA
authors.lastname: van de Wiel
authors.affiliation: DSM Nutritional Products, 45 Waterview Boulevard, Parsippany, NJ, 07054-1298, USA. Electronic address: james.lamarta@dsm.com.
authors.forename: James
authors.initials: J
authors.lastname: La Marta
mesh_terms: D000818:Animals; D045786:Diterpenes, Kaurane / Q000633:toxicity*; D005260:Female; D008297:Male; D015162:Micronucleus Tests; D009154:Mutation; D051381:Rats; D012449:Safety; D059550:Toxicity Tests, Subchronic; D025062:Yarrowia / Q000378:metabolism
chemical_list: D045786:Diterpenes, Kaurane; C025474:rebaudioside A
keywords: Fermentative; Rebaudioside A; Safety evaluation; Steviol glycosides; Yarrowia lipolytica