Safety evaluation of rebaudioside A produced by fermentation

• Published in: Food and chemical toxicology 2016-03, Vol.89, p.73-84
• Main Authors: Rumelhard, Mélina, Hosako, Hiromi, Eurlings, Irene M.J., Westerink, Walter M.A., Staska, Lauren M., van de Wiel, Jeanine A.G., La Marta, James
• Format: Article
• Language: English
• Subjects: Animals; Diterpenes, Kaurane - toxicity; Female; Fermentative; Male; Micronucleus Tests; Mutation; Rats; Rebaudioside A; Safety; Safety evaluation; Stevia rebaudiana; Steviol glycosides; Toxicity Tests, Subchronic; Yarrowia - metabolism; Yarrowia lipolytica
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2016.01.005

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. •The safety of fermentative rebaudioside A (Reb A) was assessed.•Genotoxicity tests have shown the absence of mutagenicity of fermentative Reb A.•No adverse effects were observed in a 90 day oral toxicity study with fermentative Reb A.•Similar safety profiles were obtained for fermentative and plant-derived rebaudioside A.•The results support the safety of fermentative Reb A, as a general purpose sweetener.