Safety evaluation of a mixture of the human-identical milk oligosaccharides 2′-fucosyllactose and difucosyllactose. (October 2018)

• Record Type: Journal Article
• Authors: Phipps, Kirt R.; Baldwin, Nigel; Lynch, Barry; Flaxmer, Jessica; Šoltésová, Alica; Gilby, Ben; Mikš, Marta H.; Röhrig, Christoph H.
• Is Part Of: Food and chemical toxicology. Volume 120(2018)
• Page Start: 552
• Page End: 565
• Publication Date: 2018-10
• Subjects: 2′-fucosyllactose -- Difucosyllactose -- Lactodifucotetraose -- Human-identical milk oligosaccharide -- Infant formula -- Safety; 2-AA 2-aminoanthracene -- 2′-FL 2′-fucosyllactose -- 2′-FL/DFL 2′-fucosyllactose/difucosyllactose mixture -- 2-NF 2-nitroflourine -- 4-NQO 4-nitroquinoline-1-oxide -- 9-AA 9-aminocacridine -- AAALAC Assessment and Accreditation of Laboratory Animal Care -- ANOVA analysis of variance -- ARRIVE Animal Research: Reporting of In Vivo Experiments -- AST aspartate aminotransferase -- BaP benzo[a]pyrene -- bw body weight -- CBPI cytokinesis block proliferative index -- DFL difucosyllactose -- EMA European Medicines Agency -- EPA United States Environmental Protection Agency -- FDA United States Food and Drug Administration -- FOS fructooligosaccharide -- Fuc fucose -- Gal galactose -- GD gestation day -- Glc Glucose -- GLP Good Laboratory Practice -- GRAS Generally Recognized as Safe -- HCD historical control data -- HiMO human-identical milk oligosaccharide -- HMO human milk oligosaccharide -- IF infant formula -- LD lactation day -- LDFT lactodifucotetraose -- LNnT lacto-N-neotetraose -- LUC large unstained cells -- MCH mean cell hemoglobin -- MCHC mean cell hemoglobin concentration -- MCV mean cell volume -- MoE margin of exposure -- NOAEL no-observed-adverse-effect-level -- OECD Organisation for Economic Co-operation and Development -- PND postnatal day -- PT prothrombin time -- RBC red blood cell count -- RDW red cell distribution width -- S9 S9 microsomal fraction -- UK United Kingdom -- U.S. United States -- WBC white blood cell count; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.07.054
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Human milk oligosaccharides (HMOs) are endogenous indigestible carbohydrates representing the largest compositional difference between human breastmilk and infant formula (IF). Two major HMOs in human breastmilk are 2′-fucosyllactose (2′-FL) and difucosyllactose (DFL); commercial IF can be supplemented with manufactured structurally identical versions of HMOs [known as human-identical milk oligosaccharides (HiMOs)] to better replicate the composition of human milk. As 2′-FL and DFL are always found together in human milk, a mixture of these HiMOs (2′-FL/DFL) has been proposed for use in IF and as a food ingredient. Safety assessment of 2′-FL/DFL included conduct of in vitro genotoxicity tests and a subchronic oral toxicity study. In the subchronic study, 2′-FL/DFL (8:1 ratio) was administered to neonatal rats at doses up to 5000 mg/kg body weight (bw)/day, once daily for 90 days, followed by a 4-week recovery period. A concurrent reference control group received 5000 mg/kg bw/day of an oligosaccharide already used in IF (fructooligosaccharide), for direct comparison with the high-dose 2′-FL/DFL group. No evidence of genotoxicity was observed. In the absence of compound-related adverse effects in the 90-day study, 5000 mg/kg bw/day was established as the no-observed-adverse-effect-level. These results support the use of 2′-FL/DFL in IF and as a food ingredient. Highlights: Human milk oligosaccharides 2′-fucosyllactose (2′-FL) and difucosyllactose (DFL) are always found together in human milk. Potential genotoxicity and subchronic toxicity of a mixture of manufactured 2′-FL and DFL (2′-FL/DFL) was assessed. 2′-FL/DFL was non-genotoxic in a series of in vitro tests. No treatment-related adverse effects were seen at doses up to 5000 mg/kg body weight/day in a 90-day study in neonatal rats. These results support the safe use of 2′-FL/DFL in infant formula and as a food ingredient.