Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5856786 | Regulatory Toxicology and Pharmacology | 2014 | 10 Pages |
Abstract
N-Acetyl-d-neuraminic acid (Neu5Ac) is the predominant form of sialic acid (Sia) in humans, while other mammals express Sia as a mixture with N-glycolyl-d-neuraminic acid (Neu5Gc). Neu5Ac occurs in highest levels in the brain and in breast milk, and is therefore, coined a human-specific milk monosaccharide, and is thought to play an important nutritional role in the developing infant. Synthesized human-identical milk monosaccharide (HiMM) Neu5Ac is proposed for use in infant formulas to better simulate the free saccharides present in human breast milk. As part of the safety evaluation of HiMM Neu5Ac, a subchronic dietary toxicity study preceded by an in utero phase was conducted in Sprague-Dawley rats. Neu5Ac was without maternal toxicity or compound-related adverse effects on female reproduction and on the general growth and development of offspring at a maternal dietary level of up to 2%, equivalent to a dose of 1895 mg/kg body weight (bw)/day. During the subchronic phase, no compound-related adverse effects were observed in first generation rats at dietary levels of up to 2% (highest level tested), corresponding to doses of 974 and 1246 mg/kg bw/day in males and females, respectively. Neu5Ac also was non-genotoxic in a series of in vitro genotoxicity/mutagenicity tests. These results support the safe use of Neu5Ac both in infant formula and as a food ingredient at levels equivalent to those found naturally in human breast milk.
Keywords
N-Acetyl-D-neuraminic acidGLPNOAEL2-NFSIA9-AAMMSFOBOECD2-aminoanthraceneNaN3Neu5AcNeu5GcPND2-AA2-nitrofluorene9-AminoacridineUS FDAArachidonic aciddocosahexaenoic acidSialic acidshuman milk oligosaccharideFunctional observational batteryGood Laboratory PracticeARADHAgestation daypost-natal dayOrganisation for Economic Co-operation and Developmentsodium azideSubchronic toxicityGenotoxicitySialic acidInfant formulamethyl methanesulfonateICHfirst generationno-observed-adverse-effect levelParentalbody weightinternational conference on harmonization of technical requirements for registration of pharmaceuticals for human use
Related Topics
Life Sciences
Environmental Science
Health, Toxicology and Mutagenesis
Authors
Sharon S.H. Choi, Nigel Baldwin, Valentine O. III, Shambhu Roy, Jennifer Rose, Bjorn A. Thorsrud, Phoukham Phothirath, Christoph H. Röhrig,