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

Regulatory Toxicology and Pharmacology

Volumn 70, Issue 2, 2014, Pages 482-491

  Choi, Sharon S H ^a   Baldwin, Nigel ^b   Wagner, Valentine O ^c   Roy, Shambhu ^c   Rose, Jennifer ^d   Thorsrud, Bjorn A ^d   Phothirath, Phoukham ^e   Röhrig, Christoph H ^f  

^a Intertek Scientific and Regulatory Consultancy   (Canada)

^b QinetiQ   (United Kingdom)

^c BioReliance Corporation   (United States)

^d MPI RESEARCH   (United States)

^e NESTLÉ RESEARCH CENTER   (Switzerland)

^f Glycom A S   (Denmark)

Author keywords

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

Indexed keywords

N ACETYLNEURAMINIC ACID; MONOSACCHARIDE; NEURAMINIC ACID DERIVATIVE;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DEVELOPMENT; FEMALE; GENOTOXICITY; GROWTH; IN VITRO STUDY; MALE; MATERNAL NUTRITION; MICRONUCLEUS TEST; MILK; MUTAGENICITY; NONHUMAN; PROGENY; RAT; REPRODUCTION; SAFETY; SPRAGUE DAWLEY RAT; URINALYSIS; ANIMAL; ARTIFICIAL MILK; BREAST MILK; CHEMICAL SAFETY; HUMAN; INFANT; METABOLISM; MUTAGEN TESTING; PROCEDURES;

RATTUS;

ANIMALS; CHEMICAL SAFETY; FEMALE; HUMANS; INFANT; INFANT FORMULA; MALE; MILK, HUMAN; MONOSACCHARIDES; MUTAGENICITY TESTS; N-ACETYLNEURAMINIC ACID; NEURAMINIC ACIDS; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84907462641     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2014.08.003     Document Type: Article

References (59)

1. Ames B.N., McCann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the salmonella/mammalian-microsome mutagenicity test. Mutat. Res. 1975, 31:347-363.
2. Angata T., Varki A. Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem. Rev. 2002, 102:439-469.
3. Ankier S.I. New hot plate tests to quantify anti-nociceptive and narcotic antagonist activities. Eur. J. Pharmacol. 1974, 27:1-4.
4. Blix G., Svennerholm L., Werner I. The isolation of chondrosamine from gangliosides and from submaxillary mucin. Acta Chem. Scand. 1952, 6:358-362.
5. Blix F.G., Gottschalk A., Klenk E. Proposed nomenclature in the field of neuraminic and sialic acids. Nature 1957, 179:1088.
6. Burns R.A., Wibert G.J., Diersen-Schade D.A., Kelly C.M. Evaluation of single-cell sources of docosahexaenoic acid and arachidonic acid: 3-month rat oral safety study with an in utero phase. Food Chem. Toxicol. 1999, 37:23-36.
7. Carlson S.E. N-Acetylneuraminic acid concentrations in human milk oligosaccharides and glycoproteins during lactation. Am. J. Clin. Nutr. 1985, 41:720-726.
8. Casterton P.L., Curry L.L., Lina B.A., Wolterbeek A.P., Kruger C.L. 90-Day feeding and genotoxicity studies on a refined arachidonic acid-rich oil. Food Chem. Toxicol. 2009, 47:2407-2418.
9. Davies L.R., Varki A. Why is N-glycolylneuraminic acid rare in the vertebrate brain?. Top. Curr. Chem. 2013, (Advance Publication - March 8, 2013) [Epub ahead of print].
10. Dickson J.J., Messer M. Intestinal neuraminidase activity of suckling rats and other mammals. Relationship to the sialic acid content of milk. Biochem. J. 1978, 170:407-413.
11. Edwards P.M., Parker V.H. A simple, sensitive, and objective method for early assessment of acrylamide neuropathy in rats. Toxicol. Appl. Pharmacol. 1977, 40:589-591.
12. EFSA, 2011. EFSA Scientific Committee. Scientific opinion on genotoxicity testing strategies applicable to food and feed safety assessment (Question no. EFSA-Q-2009-00782, adopted on 13 September 2011 by European Food Safety Authority). EFSA J. 9 (2379), 68. doi:10.2903/j.efsa.2011.2379. http://www.efsa.europa.eu/en/efsajournal/pub/2379.htm.
13. Fedorova-Dahms I., Marone P.A., Bauter M., Ryan A.S. Safety evaluation of DHA-rich algal oil from Schizochytrium sp. Food Chem. Toxicol. 2011, 49:3310-3318.
14. Fenech M., Morley A.A. Cytokinesis-block micronucleus method in human lymphocytes: effect of in-vivo ageing and low dose X-irradiation. Mutat. Res. 1986, 161:193-198.
15. Galeotti F., Coppa G.I.V., Zampini L., Maccari F., Galeazzi T., Padella L., Santoro L., Gabrielli O., Volpi N. On-line high-performance liquid chromatography-fluorescence detection-electrospray ionization-mass spectrometry profiling of human milk oligosaccharides derivatized with 2-aminoacridone. Anal. Biochem. 2012, 430:97-104.
16. Ghaderi D., Taylor R.E., Padler-Karavani V., Diaz S., Varki A. Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins. Nat. Biotechnol. 2010, 28:863-867.
17. Hayakawa K., De Felice C., Watanabe T., Tanaka T., Iinuma K., Nihei K., Higuchi S., Ezoe T., Hibi I., Kurosawa K. Determination of free N-acetylneuraminic acid in human body fluids by high-performance liquid chromatography with fluorimetric detection. J. Chromatogr. 1993, 620:25-31.
18. Hayakawa T., Aki I., Varki A., Satta Y., Takahata N. Fixation of the human-specific CMP-N-acetylneuraminic acid hydroxylase pseudogene and implications of haplotype diversity for human evolution. Genetics 2006, 172:1139-1146.
19. Hempenius R.A., Lina B.A., Haggitt R.C. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats. Food Chem. Toxicol. 2000, 38:127-139.
20. Hester S.N., Hustead D.S., Mackey A.D., Singhal A., Marriage B.J. Is the macronutrient intake of formula-fed infants greater than breast-fed infants in early infancy?. J. Nutr. Metab. 2012, 2012:891201. 10.1155/2012/891201.
21. ICH, 1996. Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals: S2A. Geneva, Switz. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceutical for Human Use (ICH), Geneva, Switz. ICH Harmonised Tripartite Guideline.
22. ICH, 1997. Genotoxicity: A Standard Battery For Genotoxicity Testing of Pharmaceuticals: Current Step 4 Version Dated July 16, 1997. S2B. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceutical for Human Use (ICH), Geneva, Switz. ICH Harmonised Tripartite Guideline.
23. ICH, 2009. Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals: Current Step 4 Version Dated 11 June 2009. M3(R2). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceutical for Human Use (ICH), Geneva, Switz. ICH Harmonised Tripartite Guideline. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplinary/M3_R2/Step4/M3_R2__Guideline.pdf.
24. ILAR Guide for the Care and Use of Laboratory Animals 2011, National Academy Press, Washington, (National Research Council (NRC), Institute of Laboratory Animal Resources (ILAR), Commission on Life Sciences). http://www.nap.edu/catalog.php?record_id=12910, eighth ed.
25. Klenk E., Langerbeins H., Schumann E. Über die Verteilung der Neuraminsäure im Gehirn (Mit einer Mikromethode zur quantitativen Bestimmung der Substanz im Nervengewebe). Hoppe-Seyler Z. Physiol. Chem. 1941, 270:20185-20193.
26. Lina B.A., Wolterbeek A.P., Suwa Y., Fujikawa S., Ishikura Y., Tsuda S., Dohnalek M. Subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonate-enriched triglyceride oil (SUNTGA40S) in rats. Food Chem. Toxicol. 2006, 44:326-335.
27. Maron D.M., Ames B.N. Revised methods for the salmonella mutagenicity test. Mutat. Res. 1983, 113:173-215.
28. Martín-Sosa S., Martín M.J., García-Pardo L.A., Hueso P. Distribution of sialic acids in the milk of Spanish mothers of full term infants during lactation. J. Pediatr. Gastroenterol. Nutr. 2004, 39:499-503.
29. McNaught A.D. Nomenclature of carbohydrates (IUPAC Recommendations 1996). Pure Appl. Chem. 1996, 68:1919-2008.
30. Meyer O.A., Tilson H.A., Byrd W.C., Riley M.T. A method for the routine assessment of fore - and hindlimb grip strength of rats and mice. Neurobehav. Toxicol. 1979, 1:233-236.
31. Moser V.C., Ross J.F. US EPA/AIHC Training Video and Reference Manual for a Functional Observational Battery 1996, US Environmental Protection Agency (EPA), Washington (DC).
32. Moser V.C., McCormick J.P., Creason J.P., MacPhail R.C. Comparison of chlordimeform and carbaryl using a functional observational battery. Fundam. Appl. Toxicol. 1988, 11:189-206.
33. Muchmore E.A. Developmental sialic acid modifications in rat organs. Glycobiology 1992, 2:337-343.
34. Nöhle U., Schauer R. Uptake, metabolism and excretion of orally and intravenously administered, (14)C-and (3)H labeled N-acetylneuraminic acid mixture in the mouse and rat. Hoppe Seylers Z. Physiol. Chem. 1981, 362:1495-1506.
35. OECD, 1997. Bacterial reverse mutation test. In: OECD Guidelines for the Testing of Chemicals. Organisation for Economic Co-operation and Development (OECD). Paris, France. OECD Guideline No. 471. (adopted 21.07.1997). http://www.oecd-ilibrary.org/environment/test-no-471-bacterial-reverse-mutation-test_9789264071247-en;jsessionid=1ijgh8o34k0qd.delta.
36. OECD, 1998a. OECD Series on principles of good laboratory practice and compliance monitoring. Number 1. Organization for Economic Co-operation and Development (OECD). http://search.oecd.org/officialdocuments/displaydocumentpdf/?cote=env/mc/chem(98)17%26doclanguage=en.
37. OECD, 1998b. Repeated dose 90-day oral toxicity study in rodents. In: OECD Guidelines for the Testing of Chemicals. Organisation for Economic Co-operation and Development (OECD). Paris, France. OECD Guideline No. 408. (adopted 21.09.1998). http://www.oecd-ilibrary.org/environment/test-no-408-repeated-dose-90-day-oral-toxicity-study-in-rodents_9789264070707-en;jsessionid=1m6bvwspup322.delta.
38. OECD, 2010. In vitro mammalian cell micronucleus test. In: OECD Guidelines for the Testing of Chemicals. Organisation for Economic Co-operation and Development (OECD). Paris, France. OECD Guideline No. 487. (adopted 22.07.2010). http://www.oecd-ilibrary.org/environment/test-no-487-in-vitro-mammalian-cell-micronucleus-test_9789264091016-en.
39. Oriquat G.A., Saleem T.H., Abdullah S.T., Soliman G.T., Yousef R.S., Hameed A.M.A., Salim M.L. Soluble CD14, sialic acid and l-fucose in breast milk and their role in increasing the immunity of breast-fed infants. Am. J. Biochem. Biotech. 2011, 7:21-28.
40. Padler-Karavani V., Varki A. Potential impact of the non-human sialic acid N-glycolylneuraminic acid on transplant rejection risk. Xenotransplantation 2011, 18:1-5.
41. Papadopoulos N.M. Determination of neuraminic acid in cerebral tissues. Anal. Biochem. 1960, 1:486-490.
42. Puente R., Garcia-Pardo L.A., Rueda R., Gil A., Hueso P. Seasonal variations in the concentration of gangliosides and sialic acids in milk from different mammalian species. Int. Dairy J. 1996, 6:315-322.
43. Rueda R., Puente R., Hueso P., Maldonado J., Gil A. New data on content and distribution of gangliosides in human milk. Biol. Chem. Hoppe-Seyler 1995, 376:723-727.
44. Sabharwal H., Sjöblad S., Lundblad A. Sialylated oligosaccharides in human milk and feces of preterm, full-term, and weaning infants. J. Pediatr. Gastroenterol. Nutr. 1991, 12:480-484.
45. Sakai F., Ikeuchi Y., Urashima T., Fujihara M., Ohtsuki K., Yanahira S. Effects of feeding sialyllactose and galactosylated N-acetylneuraminic acid on swimming learning ability and brain lipid composition in adult rats. J. Appl. Glycosci. 2006, 53:249-254.
46. Samraj A., Läubli H., Varki N., Varki A. Involvement of a non-human sialic acid in human cancer. Front. Oncol. 2014, 4:33.
47. Schauer R. Sialic acids: fascinating sugars in higher animals and man. Zoology 2004, 107:49-64.
48. Scobie L., Padler-Karavani V., Le Bas-Bernardet S., Crossan C., Blaha J., Matouskova M., Hector R.D., Cozzi E., Vanhove B., Charreau B., Blancho G., Bourdais L., Tallacchini M., Ribes J.M., Yu H., Chen X., Kracikova J., Broz L., Hejnar J., Vesely P., Takeuchi Y., Varki A., Soulillou J.P. Long-term IgG response to porcine Neu5Gc antigens without transmission of PERV in burn patients treated with porcine skin xenografts. J. Immunol. 2013, 191:2907-2915.
49. Sprenger N., Duncan P.I. Sialic acid utilization. Adv. Nutr. 2012, 3:392S-397S.
50. Thurl S., Mueller-Werner B., Sawatzki G. Quantification of individual oligosaccharide compounds from human milk using high-pH anion-exchange chromatography. Anal. Biochem. 1996, 235:202-206.
51. US FDA, 2003. IV.C.4a. Subchronic toxicity studies with rodents. In: Toxicological Principles for the Safety Assessment of Food Ingredients: Redbook 2000. US Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Silver Spring (MD). (November 2003) (updated to July, 2007). http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGRASPackaging/ucm078345.htm.
52. US FDA, 2013. Part 58 - Good laboratory practice for nonclinical laboratory studies. In: US Code of Federal Regulations (CFR). Title 21: Food and Drugs (US Food and Drug Administration). US Food and Drug Administration (US FDA), US Government Printing Office (GPO), Washington (DC). http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=58.
53. Varki A. Uniquely human evolution of sialic acid genetics and biology [In Light of Evolution IV: The Human Conditions Sackler Colloquium]. Proc. Natl. Acad. Sci. U.S.A. 2010, 107(Suppl. 2):8939-8946.
54. Wang B., Brand-Miller J.C., McNeil Y., McVeagh P. Sialic acid concentration of brain gangliosides: variation among eight mammalian species. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 1998, 119:435-439.
55. Wang B., Brand-Miller J., McVeagh P., Petocz P. Concentration and distribution of sialic acid in human milk and infant formulas. Am. J. Clin. Nutr. 2001, 74:510-515.
56. Wang B., Yu B., Karim M., Hu H., Sun Y., McGreevy P., Petocz P., Held S., Brand-Miller J. Dietary sialic acid supplementation improves learning and memory in piglets. Am. J. Clin. Nutr. 2007, 85:561-569.
57. WHO 2009, WHO Multicentre Growth Reference Study Group, World Health Organization (WHO), Geneva, Switz. http://www.who.int/childgrowth/standards/weight_for_age/en/index.html.
58. Wiederschain G.Y., Newburg D.S. Glycoconjugate stability in human milk: glycosidase activities and sugar release. J. Nutr. Biochem. 2001, 12:559-564.
59. Witt W., von Nicolai H., Zilliken F. Uptake and distribution of orally applied N-acetyl-((14)C)neuraminosyl-lactose and N-acetyl-((14)C)neuraminic acid in the organs of newborn rats. Nutr. Metab. 1979, 23:51-61.