title: Safety evaluation of the human-identical milk monosaccharide sialic acid (N-acetyl-d-neuraminic acid) in Sprague-Dawley rats.
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 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.
authors.affiliation: Intertek Scientific & Regulatory Consultancy, 2233 Argentia Road, Suite 308, Mississauga, Ontario L5N 2X7, Canada. Electronic address: sharon.choi@intertek.com.
authors.forename: Sharon S H
authors.initials: SS
authors.lastname: Choi
authors.affiliation: Intertek Scientific & Regulatory Consultancy, Room 1036, Building A8, Cody Technology Park, Ively Road, Farnborough, Hampshire GU14 0LX, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Baldwin
authors.affiliation: BioReliance Corporation, 9630 Medical Center Drive, Rockville, MD 20850, USA.
authors.forename: Valentine O
authors.initials: VO
authors.lastname: Wagner
authors.affiliation: BioReliance Corporation, 9630 Medical Center Drive, Rockville, MD 20850, USA.
authors.forename: Shambhu
authors.initials: S
authors.lastname: Roy
authors.affiliation: MPI Research, Inc., 54943 North Main Street, Mattawan, MI 49071-8353, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rose
authors.affiliation: MPI Research, Inc., 54943 North Main Street, Mattawan, MI 49071-8353, USA.
authors.forename: Bjorn A
authors.initials: BA
authors.lastname: Thorsrud
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, 1000 Lausanne 26, Switzerland.
authors.forename: Phoukham
authors.initials: P
authors.lastname: Phothirath
authors.affiliation: Glycom A/S, Diplomvej 373, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Röhrig
mesh_terms: D000818:Animals; D062067:Chemical Safety / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D041943:Infant Formula / Q000378:metabolism*; D008297:Male; D008895:Milk, Human / Q000378:metabolism*; D009005:Monosaccharides / Q000009:adverse effects*; D009152:Mutagenicity Tests / Q000379:methods; D019158:N-Acetylneuraminic Acid / Q000009:adverse effects*; D009438:Neuraminic Acids / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009005:Monosaccharides; D009438:Neuraminic Acids; D019158:N-Acetylneuraminic Acid
keywords: Genotoxicity; Human milk oligosaccharide; Infant formula; N-Acetyl-d-neuraminic acid; Sialic acid; Subchronic toxicity