Safety of 2′-O-fucosyllactose as a novel food ingredient pursuant to Regulation (EC) No 258/97

EFSA Journal

Volumn 13, Issue 7, 2015, Pages

[No Author Info available]

Author keywords

2 O fucosyllactose, 2 FL; novel food ingredient; safety; synthetic oligosaccharide

Indexed keywords

EID: 85070592713     PISSN: None     EISSN: 18314732     Source Type: Journal    
DOI: 10.2903/j.efsa.2015.4184     Document Type: Article

References (72)

1. Albrecht S, Lane JA, Marino K, Al Busadah KA, Carrington SD, Hickey RM and Rudd PM, 2014. A comparative study of free oligosaccharides in the milk of domestic animals. British Journal of Nutrition, 111, 1313–1328.
2. Aldredge DL, Geronimo MR, Hua S, Nwosu CC, Lebrilla CB and Barile D, 2013. Annotation and structural elucidation of bovine milk oligosaccharides and determination of novel fucosylated structures. Glycobiology, 23, 664–676.
3. Asakuma S, Urashima T, Akahori M, Obayashi H, Nakamura T, Kimura K, Watanabe Y, Arai I and Sanai Y, 2008. Variation of major neutral oligosaccharides levels in human colostrum. European Journal of Clinical Nutrition, 62, 488–494.
4. Asakuma S, Hatakeyama E, Urashima T, Yoshida E, Katayama T, Yamamoto K, Kumagai H, Ashida H, Hirose J and Kitaoka M, 2011. Physiology of consumption of human milk oligosaccharides by infant gut-associated bifidobacteria. Journal of Biological Chemistry, 286, 34583–34592.
5. Bali V, Panesar PS, Bera MB and Panesar R, 2015. Fructo-oligosaccharides: production, purification and potential applications. Critical Reviews in Food Science and Nutrition, 55, 1475–1490.
6. Bao Y, Chen C and Newburg DS, 2013. Quantification of neutral human milk oligosaccharides by graphitic carbon high-performance liquid chromatography with tandem mass spectrometry. Analytical Biochemistry, 433, 28–35.
7. Barrow P, 2007. Toxicology Testing for Products Intended for Pediatric Populations. In: Nonclinical drug safety assessment: practical considerations for successful registration. Eds Sietsema WK and Schwen R. FDA News, Washington, DC, USA, 411–440.
8. Bode L, 2012. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology, 22, 1147–1162.
9. Brand-Miller JC, McVeagh P, McNeil Y and Gillard B, 1995. Human milk oligosaccharides are not digested and absorbed in the small intestine of young infants. Proceedings of the Nutrition Society of Australia, 19, 44.
10. Brand-Miller JC, McVeagh P, McNeil Y and Messer M, 1998. Digestion of human milk oligosaccharides by healthy infants evaluated by the lactulose hydrogen breath test. Journal of Pediatrics, 133, 95–98.
11. Castanys-Munoz E, Martin MJ and Prieto PA, 2013. 2′-Fucosyllactose: an abundant, genetically determined soluble glycan present in human milk. Nutrition Reviews, 71, 773–789.
12. Chaturvedi P, Warren CD, Ruiz-Palacios GM, Pickering LK and Newburg DS, 1997. Milk oligosaccharide profiles by reversed-phase HPLC of their perbenzoylated derivatives. Analytical Biochemistry, 251, 89–97.
13. Chaturvedi P, Warren CD, Altaye M, Morrow AL, Ruiz-Palacios G, Pickering LK and Newburg DS, 2001a. Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. Glycobiology, 11, 365–372.
14. Chaturvedi P, Warren CD, Buescher CR, Pickering LK and Newburg DS, 2001b. Survival of human milk oligosaccharides in the intestine of infants. Advances in Experimental Medicine and Biology, 501, 315–323.
15. Coppa GV, Pierani P, Zampini L, Carloni I, Carlucci A and Gabrielli O, 1999. Oligosaccharides in human milk during different phases of lactation. Acta Paediatrica, supplement, 88, 89–94.
16. Coppa GV, Pierani P, Zampini L, Bruni S, Carloni I and Gabrielli O, 2001. Characterization of oligosaccharides in milk and faeces of breast-fed infants by high-performance anion-exchange chromatography. Advances in Experimental Medicine and Biology, 501, 307–314.
17. Coppa GV, Gabrielli O, Zampini L, Galeazzi T, Ficcadenti A, Padella L, Santoro L, Soldi S, Carlucci A, Bertino E and Morelli L, 2011. Oligosaccharides in 4 different milk groups, Bifidobacteria, and Ruminococcus obeum. Journal of Pediatric Gastroenterology and Nutrition, 53, 80–87.
18. Coulet M, Phothirath P, Allais L and Schilter B, 2014. Pre-clinical safety evaluation of the synthetic human milk, nature-identical, oligosaccharide 2′-O-fucosyllactose (2′FL). Regulatory Toxicology and Pharmacology, 68, 59–69.
19. Coussement P and Franck A, 2001. Inulin and oligofructose. In: Handbook of dietary fibre. Food science and technology, Volume 113). Eds Cho SS and Dreher ML. New York (NY):Marcel Dekker/Boca Raton (FL): CRC Press, 721–736.
20. Davies PS, Wells JC and Lucas A, 1994. Adjusting milk intake for body size in early infancy. Early Human Development, 36, 61–67.
21. Dotz V, Rudloff S, Blank D, Lochnit G, Geyer R and Kunz C, 2014. 13C-labeled oligosaccharides in breastfed infants' urine: individual-, structure- and time-dependent differences in the excretion. Glycobiology, 24, 185–194.
22. EFSA (European Food Safety Authority), 2012. Food Additives Intake Model (FAIM) Template - Version 1.0 - December 2012. EFSA - FIP Unit - FAIM - Instructions for use. http://www.efsa.europa.eu/en/search.htm?search=FAIM&text=FAIM.
23. EFSA AFC Panel (EFSA Panel on Food additives, flavourings, processing aids and materials in contact with food), 2006. Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to 2,2-bis(4-hydroxyphenyl)propane. The EFSA Journal, 428, 1–75.
24. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the essential composition of infant and follow-on formulae. EFSA Journal 2014;12(7):3760, 106 pp. doi:10.2903/j.efsa.2014.3760.
25. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2015. Scientific opinion on the safety of lacto-N-neotetraose as a novel food ingredient pursuant to Regulation (EC) No 258/97. EFSA Journal 2015;13(7):4183, 32 pp. doi:10.2903/j.efsa.2015.4183.
26. EMA (European Medicines Agency), 2014. Determination of health based exposure limits. Calculation of a Permitted Daily Exposure (PDE). In: Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities. (EMA/CHMP/ CVMP/ SWP/169430/2012). Committee for Medicinal Products for Human Use (CHMP), Committee for Medicinal Products for Veterinary Use (CVMP), p. 4. Available online: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/11/WC500177735.pdf.
27. Engfer MB, Stahl B, Finke B, Sawatzki G and Daniel H, 2000. Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. American Journal of Clinical Nutrition, 71, 1589–1596.
28. Erney RM, Malone WT, Skelding MB, Marcon AA, Kleman-Leyer KM, O'Ryan ML, Ruiz-Palacios G, Hilty MD, Pickering LK and Prieto PA, 2000. Variability of human milk neutral oligosaccharides in a diverse population. Journal of Pediatric Gastroenterology and Nutrition, 30, 181–192.
29. Erney R, Hilty M, Pickering L, Ruiz-Palacios G and Prieto P, 2001. Human milk oligosaccharides: a novel method provides insight into human genetics. Advances in Experimental Medicine and Biology, 501, 285–297.
30. Gabrielli O, Zampini L, Galeazzi T, Padella L, Santoro L, Peila C, Giuliani F, Bertino E, Fabris C and Coppa GV, 2011. Preterm milk oligosaccharides during the first month of lactation. Pediatrics, 128, e1520–1531.
31. Galeotti F, Coppa GV, Zampini L, Maccari F, Galeazzi T, Padella L, Santoro L, Gabrielli O and Volpi N, 2012. On-line high-performance liquid chromatography-fluorescence detection-electrospray ionization-mass spectrometry profiling of human milk oligosaccharides derivatized with 2-aminoacridone. Analytical Biochemistry, 430, 97–104.
32. Galeotti F, Coppa GV, Zampini L, Maccari F, Galeazzi T, Padella L, Santoro L, Gabrielli O and Volpi N, 2014. Capillary electrophoresis separation of human milk neutral and acidic oligosaccharides derivatized with 2-aminoacridone. Electrophoresis, 35, 811–818.
33. Gnoth MJ, Kunz C, Kinne-Saffran E and Rudloff S, 2000. Human milk oligosaccharides are minimally digested in vitro. Journal of Nutrition, 130, 3014–3020.
34. Gnoth MJ, Rudloff S, Kunz C and Kinne RK, 2001. Investigations of the in vitro transport of human milk oligosaccharides by a Caco-2 monolayer using a novel high performance liquid chromatography-mass spectrometry technique. Journal of Biological Chemistry, 276, 34363–34370.
35. Havenaar R and Van Dokkum W, 2001. Lactulose: a review on effects, clinical results, and safety aspects in relation to its influence on the colonic environment. Food Science and Technology, 113, 179–194.
36. Heaney RP, 2013. Dairy intake, dietary adequacy, and lactose intolerance. Advances in Nutrition, 4, 151–156.
37. Hester SN, Hustead DS, Mackey AD, Singhal A and Marriage BJ, 2012. Is the macronutrient intake of formula-fed infants greater than breast-fed infants in early infancy? Journal of Nutrition and Metabolism, 2012, 891201.
38. Hong Q, Ruhaak LR, Totten SM, Smilowitz JT, German JB and Lebrilla CB, 2014. Label-free absolute quantitation of oligosaccharides using multiple reaction monitoring. Analytical Chemistry, 86, 2640–2647.
39. ICH (International Conference on Harmonisation), 2011. ICH harmonised tripartite guideline. Impurities: guideline for residual solvents: Q3C(R5). Current step 4 version, dated 4 February 2011, parent guideline dated 17 July 1997. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland. Available online: www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3C/Step4/Q3C_R5_Step4.pdf.
40. Ishizuka Y, Nemoto T, Fujiwara M, Fujita KI and Nakanishi H, 1999. Three-dimensional structure of fucosyllactoses in an aqueous solution. Journal of Carbohydrate Chemistry, 18, 523–533.
41. Kunz C and Rudloff S, 1993. Biological functions of oligosaccharides in human milk. Acta Paediatrica, 82, 903–912.
42. Leo F, Asakuma S, Fukuda K, Senda A and Urashima T, 2010. Determination of sialyl and neutral oligosaccharide levels in transition and mature milks of Samoan women, using anthranilic derivatization followed by reverse phase high performance liquid chromatography. Bioscience, Biotechnology, and Biochemistry, 74, 298–303.
43. Mattar R, De Campos Mazo DF and Carrilho FJ, 2012. Lactose intolerance: diagnosis, genetic, and clinical factors. Clinical and Experimental Gastroenterology, 5, 113–121.
44. Meyrand M, Dallas DC, Caillat H, Bouvier F, Martin P and Barile D, 2013. Comparison of milk oligosaccharides between goats with and without the genetic ability to synthesize alpha-casein. Small Ruminant Research, 113, 411–420.
45. Morrow AL, Ruiz-Palacios GM, Altaye M, Jiang X, Guerrero ML, Meinzen-Derr JK, Farkas T, Chaturvedi P, Pickering LK and Newburg DS, 2004. Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants. Journal of Pediatrics, 145, 297–303.
46. Musumeci M, Simpore J, D'Agata A, Sotgiu S and Musumeci S, 2006. Oligosaccharides in colostrum of Italian and Burkinabe women. Journal of Pediatric Gastroenterology and Nutrition, 43, 372–378.
47. Nakhla T, Fu D, Zopf D, Brodsky NL and Hurt H, 1999. Neutral oligosaccharide content of preterm human milk. British Journal of Nutrition, 82, 361–367.
48. NatCen Social Research, Medical Research Council, Resource Centre for Human Nutrition Research, Medical Research Council, Epidemiology and Medical Care Unit, University of Newcastle upon Tyne, Institute for Ageing and Health, and Human Nutrition Research Centre, 2013. Diet and Nutrition Survey of Infants and Young Children (DNSIYC) 2011 [computer file]. (SN 7263), Prepared by London, Engl., National Centre for Social Research (NatCen) / Cambridge, UK, Medical Research Council (MRC), Human Nutrition Research / Cambridge, UK, MRC Epidemiology Unit / Cambridge, UK, MRC Epidemiology Unit / Human Nutrition Research Centre (HNRC), Newcastle University for Department of Health / London, UK, Food Standards Agency (FSA) and Distributed by Colchester, UK, UK Data Archive. Available online: http://esds.ac.uk/doi/?sn=7263 [Last modified date: 16 May 2013; open full catalogue record].
49. Newburg DS, 2013. Glycobiology of human milk. Biochemistry, 78, 771–785.
50. Obermeier S, Rudloff S, Pohlentz G, Lentze MJ and Kunz C, 1999. Secretion of 13C-labelled oligosaccharides into human milk and infant's urine after an oral 13C-galactose load. Isotopes in Environmental and Health Studies, 35, 119–125.
51. OECD (Organisation for Economic Co-operation and Development), 1997a. Test No. 471: Bacterial reverse mutation test. In: OECD guidelines for the testing of chemicals, Section 4: Health effects, 11 pp.
52. OECD (Organisation for Economic Co-operation and Development), 1997b. Test No. 476: In vitro mammalian cell gene mutation test. In: OECD guidelines for the testing of chemicals, Section 4: Health effects, 10 pp.
53. OECD (Organisation for Economic Co-operation and Development), 1998a. Test No. 408: Repeated dose 90-day oral toxicity study in rodents. In: OECD guidelines for the testing of chemicals, Section 4: Health effects, 10 pp.
54. OECD, (Organisation for Economic Co-operation and Development), 1998b. OECD Principles of good laboratory practice (as revised in 1997). OECD series on principles of good laboratory practice and compliance monitoring, number 1, ENV/MC/CHEM(98)17, 41 pp.
55. OECD (Organisation for Economic Co-operation and Development), 2014. Test No. 487: In vitro mammalian cell micronucleus test. In: OECD guidelines for the testing of chemicals, Section 4: Health effects, 23 pp.
56. Rudloff S and Kunz C, 2012. Milk oligosaccharides and metabolism in infants. Advances in Nutrition, 3, 398S–405S.
57. Rudloff S, Obermeier S, Borsch C, Pohlentz G, Hartmann R, Brosicke H, Lentze MJ and Kunz C, 2006. Incorporation of orally applied 13C-galactose into milk lactose and oligosaccharides. Glycobiology, 16, 477–487.
58. Rudloff S, Pohlentz G, Borsch C, Lentze MJ and Kunz C, 2012. Urinary excretion of in vivo 13C-labelled milk oligosaccharides in breastfed infants. British Journal of Nutrition, 107, 957–963.
59. Smilowitz JT, O'Sullivan A, Barile D, German JB, Lonnerdal B and Slupsky CM, 2013. The human milk metabolome reveals diverse oligosaccharide profiles. Journal of Nutrition, 143, 1709–1718.
60. Sumiyoshi W, Urashima T, Nakamura T, Arai I, Saito T, Tsumura N, Wang B, Brand-Miller J, Watanabe Y and Kimura K, 2003. Determination of each neutral oligosaccharide in the milk of Japanese women during the course of lactation. British Journal of Nutrition, 89, 61–69.
61. Tao N, DePeters EJ, German JB, Grimm R and Lebrilla CB, 2009. Variations in bovine milk oligosaccharides during early and middle lactation stages analyzed by high-performance liquid chromatography-chip/mass spectrometry. Journal of Dairy Science, 92, 2991–3001.
62. Tao N, Ochonicky KL, German JB, Donovan SM and Lebrilla CB, 2010. Structural determination and daily variations of porcine milk oligosaccharides. Journal of Agricultural and Food Chemistry, 58, 4653–4659.
63. Thurl S, Henker J, Siegel M, Tovar K and Sawatzki G, 1997. Detection of four human milk groups with respect to Lewis blood group dependent oligosaccharides. Glycoconjugate Journal, 14, 795–799.
64. Thurl S, Munzert M, Henker J, Boehm G, Muller-Werner B, Jelinek J and Stahl B, 2010. Variation of human milk oligosaccharides in relation to milk groups and lactational periods. British Journal of Nutrition, 104, 1261–1271.
65. Torres DPM, Gonçalves MDPF, Teixeira JA and Rodrigues LR, 2010. Galactooligosaccharides: production, properties, applications, and significance as prebiotics. Comprehensive Reviews in Food Science and Food Safety, 9, 438–454.
66. UKDA (UK Data Archive), 2012. National Diet and Nutrition Survey, 2008–2010 [computer file], 3rd edition. (SN: 6533), Colchester, Essex, UK Data Archive (UK) [distributor]. Available online: http://dx.doi.org/10.5255/UKDA-SN-6533–2.
67. Unpublished study report, 2015a. Dated 27 February 2015. Wil Research Europe B.V., s'Hertogenbosch, The Netherlands. Study Title: ‘An in vitro micronucleus assay with 2’-O-fucosyllactose in cultured peripheral human lymphocytes' (Project 507397).
68. Unpublished study report, 2015b. Dated: 25 February 2015. Study Title: ‘Clinical safety of a new infant starter formula containing 2 human milk oligosaccharides (HMOs), Part 1′ (Study number 11.26.INF).
69. Unpublished study report, 2015c. Dated: 1 June 2015. Study Title: ‘The effects of human-milk-oligosaccharides on the faecal microbiota and on gastrointestinal symptoms in healthy adult volunteers’ (Study number 2014–1).
70. Unpublished study report, 2015d. Dated: 3 June 2015. Study title: ‘Stool microbiota and metabolic signature in infants at 3 months of age who were fed a starter infant formula supplemented with 2’FL and LNnT’ (Study number 11.26INF).
71. Urashima T, Bubb WA, Messer M, Tsuji Y and Taneda Y, 1994. Studies of the neutral trisaccharides of goat (Capra hircus) colostrum and of the one- and two-dimensional 1H and 13C NMR spectra of 6′-N-acetylglucosaminyllactose. Carbohydrate Research, 262, 173–184.
72. WHO (World Health Organisation), 2014. WHO Child Growth Standards. Geneva, Switz., WHO Multicentre Growth Reference Study Group, World Health Organization (WHO). Available online: http://www.who.int/childgrowth/standards/weight_for_age/en/index.html.