Principles of the Assessment of Food Additives Used in Food for Infants and Toddlers

Main Article Content

Stefania Barmaz Laurence Castle Birgit Dusemund Peter Fürst Christina Kyrkou Agnieszka Mech Alicja Mortensen Ana Maria Rincon Camilla Smeraldi Alexandra Tard Dominique Turck Dina Waalkens-Berendsen Detlef Wölfle Ursula Gundert-Remy

Abstract

Food additives are substances added to food to maintain or improve its safety, freshness, taste, texture, or appearance. Until recently, the assessment of food additives taken up with the normal food was performed only for the population above an age of 12 weeks. With the better knowledge of the physiological specificities in the age group below 12 weeks of age and considering that milk formulae can be the unique dietary source for infants up to 16 weeks, special assessments are performed for food additives already on the market for this age group. This publication explains the background and relevant guidelines for the assessment, including special guidelines for the age group below 16 weeks, and the different sources of information used. The principles followed to assess food additives are described. The requirements for the assessment of food additives used in infants’ food includes testing in special animal models if human data are absent. The amount of food additives the infants are exposed to is estimated based on an exposure assessment. The aim of the assessment is to compare the estimated intake of the FA with milk formulae with safe concentrations taken from clinical studies in infants, special animal models and/or by comparing the exposure by the milk formulae with the content of breast milk whatever is appropriate. Two examples (locust bean gum, lecithin) illustrate the application of the principles. Of special interest is the concentration of impurities in the food additive with a toxic potential, such as lead, arsenic, cadmium, mercury, relevant for all food additives, or glycidyl esters, 3‐monochloropropane diol, erucic acid, and trans-fatty acids, relevant for mono- and diglycerides of fatty acids. The assessment of food additives intended to be used in food for infants below 16 weeks of age revealed that in most cases the maximum permitted regulatory levels of the food additive would result in an exposure which does not raise health concerns, besides lecithins and locust bean gum. However, the content of impurities with a toxic potential at the regulatory permitted levels is of concern for all food additives which indicates the need for lowering those levels.

Keywords: Food additives, infant formula, impurities, safety assessment

Article Details

How to Cite
BARMAZ, Stefania et al. Principles of the Assessment of Food Additives Used in Food for Infants and Toddlers. Medical Research Archives, [S.l.], v. 11, n. 8, aug. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4127>. Date accessed: 12 may 2024. doi: https://doi.org/10.18103/mra.v11i8.4127.
Section
Articles

References

1. Scientific Committee on Food. Opinion of the Scientific Committee on Food on the applicability of the ADI (Acceptable Daily Intak) for food additives to infant (expressed on 17/09/1998). https://food.ec.europa.eu/system/files/2020-12/sci-com_scf_out13_en.pdf
2. World Health Organisation (WHO). Factsheets on food additives. World Health Organisation, Geneva. https://www.who.int/news-room/fact-sheets/detail/food-additives
3. Regulation (EC) No 1333/2008 of the European Parliament and of the Council of 16 December 2008 on food additives (Text with EEA relevance). OJ L 354, 31.12.2008, p. 16–33.
4. Commission Regulation (EU) No 257/2010 of 25 March 2010 setting up a programme for the re-evaluation of approved food additives in accordance with Regulation (EC) No 1333/2008 of the European Parliament and of the Council on food additives (Text with EEA relevance) OJ L 80, 26.3.2010, p. 19–27.
5. World Health Organisation (WHO) Principles for the safety assessment of food additives and contaminants in food. 1987. Environmental Health Criteria no. 70. World Health Organisation, Geneva.
6. Commission of the European Communities. First report of the Scientific Committee for Food on the essential requirements of infant formulae and follow-up milks based on cows’ milk protein (14th series, opinion expressed 27 April 1983).
7. Commission of the European Communities. Opinion on certain additives for use in infant formulae, follow-on formulae and weaning foods. Report of the Scientific Committee for Food (32nd series, opinion expressed 11 December 1992).
8. Commission of the European Communities. Opinion on additives in nutrient preparation for use in infant formulae, follow-on formulae and weaning foods. (40th series, opinion expressed on 7 June 1996)
9. EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V,
Solecki R, Turck D, Bresson J-L, Dusemund B, Gundert-Remy U, Kersting M, Lambre C, Penninks A, Tritscher A, Waalkens-Berendsen I, Woutersen R, Arcella D, Court Marques D, Dorne J-L, Kass GEN and Mortensen A. Guidance on the risk assessment of substances present in food intended for infants below 16 weeks of age. EFSA J. 2017;15(5):4849, 58pp. https://doi.org/10.2903/j.efsa.2017.4849
10. World Health Organisation (WHO). Principles and methods for the risk assessment of chemicals in food. Environmental health criteria, 2009 updated in 2020; 240. https://www.who.int/publications/i/item/9789241572408
11. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Guidance for submission for food additive evaluations. EFSA J. 2012;10(7):2760, 53pp. https://doi.org/10.2903/j.efsa.2012.2760
12. EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, Solecki R, Turck D, Bresson J-L, Dusemund B, Gundert-Remy U, Kersting M, Lambré C, Penninks A, Tritscher A, Waalkens-Berendsen I, Woutersen R, Arcella D, Court Marques D, Dorne J-L, Kass GEN and Mortensen A. Guidance on the risk assessment of substances present in food intended for infants below 16 weeks of age. EFSA J.2017;15(5):4849, 58pp. https://doi.org/10.2903/j.efsa.2017.4849
13. EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen KH, More S, Mortensen A, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Silano V, Solecki R, Turck D, Aerts M, Bodin L, Davis A, Edler L, Gundert-Remy U, Sand S, Slob W, Bottex B, Abrahantes JC, Marques DC, Kass G and Schlatter JR. Update: Guidance on the use of the benchmark dose approach in risk assessment. EFSA J. 2017;15(1):4658, 41pp. https://doi.org/10.2903/j.efsa.2017.4658
14. EFSA Scientific Committee, More SJ, Bampidis V, Benford D, Bragard C, Halldorsson TI, Hernández-Jerez AF, Bennekou SH, Koutsoumanis K, Lambré C, Machera K, Mennes W, Mullins E, Nielsen SS, Schrenk D, Turck D, Younes M, Aerts M, Edler L, Sand S, Wright M, Binaglia M, Bottex B, Cortinas Abrahantes J and Schlatter J. Guidance on the use of the benchmark dose approach in risk assessment. EFSA J. 2022;20(10):7584, 67pp. https://doi.org/10.2903/j.efsa.2022.7584
15. Haber LT, Dourson ML, Allen BC, Hertzberg RC, Parker A, Vincent MJ, Maier A, Boobis AR. Benchmark dose (BMD) modeling: current practice, issues, and challenges. Crit Rev Toxicol. 2018;48(5):387-415. https://doi.org/10.1080/10408444.2018.1430121
16. International Programme on Chemical Safety & IPCS Workshop on Incorporating Uncertainty and Variability into Risk Assessment (‎2000: Berlin, Germany)‎. Chemical-specific adjustment factors for interspecies differences and human variability: guidance document for use of data in dose/concentration-response assessment. 2005. World Health Organization. https://apps.who.int/iris/handle/10665/43294
17. EFSA Scientific Committee. Guidance on selected default values to be used by the EFSA Scientific Committee, Scientific Panels and Units in the absence of actual measured data. EFSA J. 2012;10(3):2579,32pp. https//doi.org:10.2903/j.efsa.2012.2579
18. EFSA Scientific Committee. Scientific Opinion on genotoxicity testing strategies applicable to food and feed safety assessment. EFSA J. 2011;9(9):2379, 69pp. https://doi.org/10.2903/j.efsa.2011.2379
19. EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger M, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Silano V, Solecki R, Turck D, Younes M, Aquilina G, Crebelli R, Gürtler R, Hirsch-Ernst K, Mosesso P, Nielsen E, van Benthem J, Carfì M, Georgiadis N, Maurici D, Parra Morte J and Schlatter J. Clarification of some aspects related to genotoxicity assessment. EFSA J. 2017;15(12):5113,25pp. https://doi.org/10.2903/j.efsa.2017.5113
20. OECD Test Guidelines for Chemicals, Section 4. OECD, Paris. https://www.oecd.org/chemicalsafety/testing/
21. National Toxicology Program – Oral Health Assessment Tool (NTP-OHAT). Handbook for conducting a literature-based health assessment using OHAT approach for systematic review and evidence integration. 2015.
22. Beronius A, Molander L, Rudén C and Hanberg A. Facilitating the use of non-standard in vivo studies in health risk assessment of chemicals: A proposal to improve evaluation criteria and reporting. J Appl Toxicol. 2014; 34:607–617. https://doi.org/10.1002/jat.2991
23. Commission Regulation (EU) No 231/2012 of 9 March 2012 laying down specifications for food additives listed in Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament and of the Council Text with EEA relevance. OJ L 83, 22.3.2012, p. 1–295
24. Larsen JC. Risk assessment of chemicals in European traditional foods. Trends in Food Science & Technology. 2006;17: 471-481. https://doi.org/10.1016/j.tifs.2006.04.007
25. Joint FAO/WHO Expert Committee on Food Additives (JECFA). Safety Evaluation of certain food additives. Seventy-ninth report of the Joint FAO/WHO Expert Committee on food additives. Geneva. 2014. https://www.who.int/publications/i/item/9789241209908
26. Constable A, Mahedavan B, Pressman P, Garthoff JA, Meunier L, Schrenk D, Speijers G, O’Sullivan A, Hayes AW. An integrated approach to the safety assessment of food additives in early life. Toxicology Research and Application. 2017; 1: 1-26. https://doi.org/10.1177/2397847317707370
27. OECD Guideline for the testing of chemicals. Extended one-generation reproductive toxicity (TG 443) adopted 25 June 2018. https://doi.org/10.1787/9789264185371-en
28. Bode G, Clausing P, Gervais F, Loegsted J, Luft J, Nogues V, Sims J and Project R. The utility of the minipig as an animal model in regulatory toxicology. J Pharmacol Toxicol Methods. 2010;62:196–220. https://doi.org/10.1016/j.vascn.2010.05.009
29. Helm RM, Golden C, McMahon M, Thampi P, Badger TM, Nagarajan S. Diet regulates the development of gut-associated lymphoid tissue in neonatal piglets. Neonatology. 2007; 91:248–255. https://doi.org/10.1159/000098523
30. Guilloteau P, Zabielski R, Hammon HM, Metges CC. Nutritional programming of gastrointestinal tract development. Is the pig a good model for man? Nutr Res Rev. 2010; 23:4–22. https://doi.org/10.1017/s0954422410000077
31. Barrow PC. Use of the swine paediatric model. In: Doberman AM,Lewis EM (eds.). Pediatric Non-Clinical Drug Testing: Principles, Requirements, and Practice. John Wiley & Sons Inc, Hoboken, NJ, USA;2012: pp. 213–230.
32. Heinritz SN, Mosenthin R, Weiss E. Use of pigs as a potential model for research into dietary modulation of the human gut microbiota. Nutr Res Rev. 2013;26:191–209. https://doi.org/10.1017/s0954422413000152
33. Odle J, Lin X, Jacobi SK, Kim SW and Stahl CH. The suckling piglet as an agrimedical model for the study of pediatric nutrition and metabolism. Annu Rev Anim Biosci. 2014; 2:419–444. https://doi.org/10.1146/annurev-animal-022513-114158
34. Mudd AT, Dilger RN. Early-life nutrition and neurodevelopment: use of the piglet as a translational model. Adv Nutr. 2017;8:92-104. https://doi.org/10.3945/an.116.013243
35. Farmer C, Quesnel H. Nutritional, hormonal, and environmental effects on colostrum in sows. J. Anim. Sci. 2009; 87:56–65. https://doi.org/10.2527/jas.2008-1203
36. Penninks AH, Van Mierlo GJD, Kuper F, Snel CJ, Ganderup NC, Wolterbeek APM. Juvenile immunodevelopment in minipigs. 2012. In: Doberman AM and Lewis EM (eds.). Pediatric Non-Clinical Drug Testing: Principles, Requirements, and Practice.John Wiley & Sons Inc, Hoboken, NJ, USA: 231–254.
37. Hansen CF, Thymann T, Andersen AD et al. Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs. Am J Physiol. Gastrointest. 2016; 310, G550–G560. https://doi.org/10.1152/ajpgi.00221.2015
38. Van Ginneken C. Gastrointestinal tract. In: McAnulty PA, Dayan AD, Ganderup NC and Hastings KL (eds.). The Minipig in Biomedical Research. CRC Press, Taylor and Francis Group, Boca Raton, FL, USA; 2012: pp. 211–236.
39. Sangild PT, Thymann T, Schmidt M, Stoll B, Burrin DG, Buddington RK. Invited Review: the preterm pig as a model in pediatric gastroenterology. J Anim Sci. 2013; 91:4713–4729. https://doi.org/10.2527/jas.2013-6359
40. McAnulty PA. The kidney. In: McAnulty PA, Dayan AD, Ganderup NC and Hastings KL (eds.). The Minipig in Biomedical Research. CRC Press, Taylor and Francis Group, Boca Raton, FL, USA;2012: 253–262.
41. Preusse C and Tingleff Skaanild M. Minipigs in Absorption, Distribution, Metabolism, and Excretion (ADME) studies. In: McAnulty PA, Dayan AD, Ganderup NC and Hastings KL (eds.). The Minipig in Biomedical Research. CRC Press, Taylor and Francis Group, Boca Raton, FL, USA;2012: 143–158.
42. Haley P. The immune system of pigs: Structure and Function. In: McAnulty PA, Dayan AD, Ganderup NC and Hastings KL (eds.). The Minipig In Biomedical Research. CRC Press, Taylor and Francis Group, Boca Raton, FL, USA;2012: 343–355
43. McAnulty PA, Barrow P, Marsden E. Reproductive system including studies in juvenile mini pigs. In: McAnulty PA, Dayan AD, Ganderup NC and Hastings KL (eds.). The minipig in biomedical research. CRC Press, Taylor and Francis Group, Boca Raton, FL, USA;2012: 263–282.
44. Lind NM, Moustgaard A, Jelsing J, Vajta G, Cumming P and Hansen AK, 2007. The use of pigs in neuroscience: Modeling brain disorders. Neurosci Biobehav Rev. 2007;31:728–751. https://doi.org/10.1016/j.neubiorev.2007.02.003
45. OECD Guideline for the testing of chemicals. Two-generation reproduction toxicity study (TG 416) adopted 22 January 2001.
46. EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings), Younes M, Aquilina G, Castle L, Engel K-H, Fowler P, Frutos Fernandez MJ, Fürst P, Gürtler R, Husøy T, Manco M, Mennes W, Moldeus P, Passamonti S, Shah R, Waalkens-Berendsen I, Wölfle D, Wright M, Dusemund B, Mortensen A, Turck D, Barmaz S, Rincon AM, Smeraldi C, Tard A, Vianello G and Gundert-Remy U, 2020. Opinion on the re-evaluation of starch sodium octenyl succinate (E 1450) as a food additive in foods for infants below 16 weeks of age and the follow-up of its re-evaluation as a food additive for uses in foods for all population groups. EFSA J. 2020;18(8):5874, 60pp. https://doi.org/10.2903/j.efsa.2020.5874
47. EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings), Younes M, Aquilina G, Castle L, Engel K-H, Fowler P, Frutos Fernandez MJ, Fürst P, Gürtler R, Husøy T, Manco M, Mennes W, Moldeus P, Passamonti S, Shah R, Waalkens-Berendsen I, Wölfle D, Wright M, Dusemund B, Mortensen A, Turck D, Barmaz S, Tard A, Vianello G and Gundert-Remy U, 2021. Opinion on the re-evaluation of pectin (E 440i) and amidated pectin (E 440ii) as food additives in foods for infants below 16 weeks of age and follow-up of their re-evaluation as food additives for uses in foods for all population groups. EFSA J. 2021;19(1):6387, 57pp. https://doi.org/10.2903/j.efsa.2021.6387
48. EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings), Younes M, Aquilina G, Castle L, Degen G, Engel K-H, Fowler PJ, Frutos Fernandez MJ, Fürst P, Gürtler R, Husøy T, Manco M, Mennes W, Moldeus P, Passamonti S, Shah R, Waalkens-Berendsen I, Wright M, Wölfle D, Dusemund B, Mortensen A, Turck D, Barmaz S, Mech A, Rincon AM, Tard A, Vianello G and Gundert-Remy U, 2022. Re-evaluation of locust bean gum (E 410) as a food additive in foods for infants below 16 weeks of age and follow-up of its re-evaluation as a food additive for uses in foods for all population groups. EFSA J. 2023;21(2):7775, 70pp. https://doi.org/10.2903/j.efsa.2023.7775
49. Guidelines for reporting outcomes in trial reports. The CONSORT-Outcomes 2022 Extension. Butcher NJ, Monsour A, Mew EJ, Chan AW, Moher D, Mayo-Wilson E, Terwee CB, Chee-A-Tow A, MPH; Baba A, Gavin F, Grimshaw JM, Kelly LE, Saeed L, Thabane L, Askie L, Smith M, Farid-Kapadia M, Williamson PR, Szatmari P, Tugwell P, Golub RM, Monga S, Vohra S, MD; Marlin S, Ungar WJ, Offringa M. JAMA. 2022; 328: 2252-64. https://doi:10.1001/jama.2022.21022
50. Junqueira DR, Zorzela L, Golder S, Loke Y, Gagnier JJ, Julious SA, Li T, Mayo-Wilson E, Pham B, Phillips R, Santaguida P, Scherer RW, Gøtzsche PC, Moher D, Ioannidis JPA, Vohra S; CONSORT Harms Group. J Clin Epidemiol.2023 Apr 22: S0895-356(23)00090-2. https://doi.org/10.1016/j.jclinepi.2023.04.005. Online ahead of print.
51. Jarrold K; Helfer B, Eskander M, Crawley H, Trabulsi J, Caulfield LE, Duffy G, Garcia-Larsen V, Hayward D, Hyde M, Jeffries S, Knip M, Leonardi-Bee J, Loder E, Lodge CJ, Lowe AJ, McGuire W, Osborn D, Przyrembel H, Renfrew MJ, Trumbo P, Warner J, Schneeman B, Boyle RB. Guidance for the conduct and reporting of clinical trials of breast milk substitutes. JAMA Pediatr. 2022; 174: 874-81. https://doi.org10.1001/jamapediatrics.2020.0578
52. EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings), Younes M, Aquilina G, Castle L, Engel K-H, Fowler P, Frutos Fernandez MJ, Fürst P, Gürtler R, Husøy T, Manco M, Mennes W, Moldeus P, Passamonti S, Shah R, Waalkens-Berendsen I, Wölfle D, Wright M, Dusemund B, Mortensen A, Turck D, Barmaz S, Smeraldi C, Tard A, Vianello G, Rincon AM, Gundert-Remy U, 2020. Scientific Opinion on the re-evaluation of ascorbyl palmitate (E 304i) as a food additive in foods for infants below 16 weeks of age and the follow-up of its re-evaluation as a food additive for uses in foods for all population groups. EFSA J. 2020;18(6):6153: 1-37. https://doi.org/10.2903/j.efsa.2020.6153
53. EMA. Committee for Human Medicinal Products.Guideline for good clinical practice E6(R2), 2016. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-good-clinical-practice-e6r2-step-5_en.pdf accessed 19 April 2023
54. Riley DS, Barber MS, Kienle GS, Aronson JK, von Schoen-Angerer T, Tugwell P, Kiene H, Helfand M, Altman DG, Sox H, Werthmann PG, Moher D, Rison RA, Shamseer L, Koch CA, Sun GH, Hanaway P, Sudak NL, Kaszkin-Bettag M, Carpenter JM, Gagnier JJ. CARE guidelines for case reports: explanation and elaboration document. J Clin Epidemiol. 2017; 89: 218-35. https://doi.org/10.1016/j.jclinepi.2017.04.026
55. Fomon SJ. Nutrition of Normal Infants. 1993. Mosby, 488 pp.
56. Fomon SJ, Filer LJ, Thomas LN, Ziegler EE and Leonard MT. Food consumption and growth of normal infants fed milk-based formulas. Acta Paediatr Scand Suppl. 1971: 1–36.
57. Kersting M, Alexy U, Sichert-Hellert W, Manz F and Schoch G. Measured consumption of commercial infant food products in German infants: results from the DONALD study. JPGN. 1998;2: 547–552. https://doi.org/10.1097/00005176-199811000-00011
58. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain). Scientific opinion on the risk for human health related to the presence of 3- and 2-monochloropropandiol (MCPD) and their fatty acids, and glycidyl fatty acids esters in food. EFSA J. 2016; 14 (5): 4426, 159pp. https://doi.org/10.2903/j.efsa.2016.4426
59. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain). Scientific Opinion on the update of the risk assessment on 3-monochloropropane diol and its fatty acid esters. EFSA J. 2018;16(1):5083, 48pp. https://doi.org/10.2903/j.efsa.2018.5083
60. EFSA Panel on Contaminants in the Food Chain (CONTAM), Scientific Opinion on erucic acid in feed and food. EFSA J. 2016;14(11):4593, 173 pp. https//:doi.org/10.2903/j.efsa.2016.4593
61. Commission Regulation (EU) 2023/915 of 25 April 2023 on maximum levels for certain contaminants in food and repealing Regulation (EC) No 1881/2006 (Text with EEA relevance).C/2023/35.OJ L 119, 5.5.2023, p. 103–1572023/915
62. EFSA CONTAM Panel (Panel on Contaminants in the Food Chain. Scientific opinion on Arsenic in food. EFSA J. 2009;7(3):980, 139 pp. https://doi.org/10.2903/j.efsa.2009.980
63. EFSA Scientific Committee, 2012. Guidance on selected default values to be used by the EFSA Scientific Committee, Scientific Panels and Units in the absence of actual measured data. EFSA J. 2012;10(3):2579, 32 pp. https//doi.org/10.2903/j.efsa.2012.2579
64. EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings), Younes M, Aquilina G, Castle L, Engel K-H, Fowler P, Frutos Fernandez MJ, Fürst P, Gürtler R, Husøy T, Mennes W, Moldeus P, Oskarsson A, Shah R, Waalkens-Berendsen I, Wölfle D, Dusemund B, Mortensen A, Turck D, Barmaz S, Smeraldi C, Tard A and Gundert-Remy U. Scientific Opinion on the re-evaluation of acacia gum (E 414) as a food additive in foods for infants below 16 weeks of age and the follow-up of its re-evaluation as a food additive for uses in foods for all population groups. EFSA J. 2019;17(12):5922, 23 pp. https://doi.org/10.2903/j.efsa.2019.5922
65. Cole CR, Grant FK, Swaby-Ellis ED, Smith JL, Jacques A, Northrop-Clewes CA, Caldwell KL, Pfeiffer CM and ZieglerTR. Zinc and iron deficiency and their interrelations in low-income African American and Hispanic children in Atlanta. Am J Clin Nutr. 2010; 91: 1027–1034. https://doi.org/10.3945/ajcn.2009.28089
66. Gozzo S, Oliverio A. Effects of dietary phospholipids and odd-chain fatty acids on the behavioural maturation of mice. Food Chem Toxicology. 1982; 20: 153–157. https://doi.org/10.1016/s0278-6915(82)80240-8
67. Bell JM, Lundberg PK. Effects of a commercial soy lecithin preparation on development of sensorimotor behavior and brain biochemistry in the rat. Dev Psychobiol.1985; 18: 59–66. https://doi.org/10.1002/dev.420180105
68. Bell JM, Slotkin TA. Perinatal dietary supplementation with a commercial soy lecithin preparation: effects on behavior and brain biochemistry in the developing rat. Dev Psychobiol. 1985;18: 383–394. https://doi.org/10.1002/dev.420180504
69. Bell JM, Withmore WL, Cowdery T, Slotkin TA. Perinatal dietary supplementation with a soy lecithin preparation: effects on development of central catecholaminergic neurotransmitter systems. Brain Res Bull. 1986; 17: 189–195. https://doi.org/10.1016/0361-9230(86)90115-2
70. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies). Scientific opinion on Dietary Reference Values for choline. EFSA J. 2016; 14(8):4484, 70 pp. https://doi.org/10.2903/j.efsa.2016.4484
71. EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings), Younes M, Aquilina G, Castle L, Engel K-H, Fowler P, Frutos Fernandez MJ, Fürst P, Gürtler R, Husøy T, Manco M, Mennes W, Moldeus P, Passamonti S, Shah R, Waalkens-Berendsen I, Woelfle D, Wright M, Dusemund B, Mortensen A, Turck D, Barmaz S, Tard A, Vianello G, Gundert-Remy U. Scientific Opinion on the re-evaluation of lecithins (E 322) as a food additive in foods for infants below 16 weeks of age and follow up of its re-evaluation as food additive for uses in foods for all population groups. EFSA J. 2020;18 (11):6266, 37 pp. https://doi.org/10.2903/j.efsa.2020.6266
72. EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings), Younes M, Aquilina G, Castle L, Engel K-H, Fowler P, Frutos Fernandez MJ, Fürst P, Gürtler R, Husøy T, Manco M, Mennes W, Moldeus P, Passamonti S, Shah R, Waalkens-Berendsen I, Wölfle D, Wright M, Dusemund B, Mortensen A, Turck D, Barmaz S, Tard A, Vianello G and Gundert-Remy U. Scientific opinion on the re-evaluation of mono- and diglycerides of fatty acids (E 471) as food additive in foods for infants below 16 weeks of age and follow-up of their re-evaluation as food additives for uses in foods for all population groups. EFSA J. 2021;19(11):6885, 44 pp. https://doi.org/10.2903/j.efsa.2021.6885
73. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain). Scientific opinion on Lead in food. EFSA J. 2010;8(4):1570, 151 pp. https://doi.org/10.2903/j.efsa.2010.1570
74. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain. Scientific opinion on Cadmium in food. EFSA J. 2009;7(10):1351, 199 pp. https://doi.org/10.2903/j.efsa.2009.1351
75. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain), 2012. Scientific Opinion on the risk for public health related to the presence of mercury and methylmercury in food. EFSA J. 2012;10(12):2985,15 pp. https://doi.org/10.2903/j.efsa.2012.2985