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Regul Toxicol Pharmacol. 2014 Nov;70(2):482-91. doi: 10.1016/j.yrtph.2014.08.003. Epub 2014 Aug 8.

Safety evaluation of the human-identical milk monosaccharide sialic acid (N-acetyl-d-neuraminic acid) in Sprague-Dawley rats.

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Intertek Scientific & Regulatory Consultancy, 2233 Argentia Road, Suite 308, Mississauga, Ontario L5N 2X7, Canada. Electronic address:
Intertek Scientific & Regulatory Consultancy, Room 1036, Building A8, Cody Technology Park, Ively Road, Farnborough, Hampshire GU14 0LX, UK.
BioReliance Corporation, 9630 Medical Center Drive, Rockville, MD 20850, USA.
MPI Research, Inc., 54943 North Main Street, Mattawan, MI 49071-8353, USA.
Nestlé Research Center, Vers-chez-les-Blanc, 1000 Lausanne 26, Switzerland.
Glycom A/S, Diplomvej 373, DK-2800 Kongens Lyngby, Denmark.


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 1895mg/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 1246mg/kgbw/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.


Genotoxicity; Human milk oligosaccharide; Infant formula; N-Acetyl-d-neuraminic acid; Sialic acid; Subchronic toxicity

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