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http://dx.doi.org/10.9721/KJFST.2020.52.5.546

Usage- and daily intake-based cytotoxicity study of frequently used natural food additives in South Korea  

Yu, Jin (Division of Applied Food System, Major of Food Science & Technology, Seoul Women's University)
Kim, Ye-Hyun (Division of Applied Food System, Major of Food Science & Technology, Seoul Women's University)
Choi, Soo-Jin (Division of Applied Food System, Major of Food Science & Technology, Seoul Women's University)
Publication Information
Korean Journal of Food Science and Technology / v.52, no.5, 2020 , pp. 546-554 More about this Journal
Abstract
Natural food additives have recently attracted attention as alternatives to synthetic additives. However, little information is available regarding their potential toxicity. In this study, we evaluated ten different natural food additives that are widely used in commercial foods in South Korea based on their actual usage level and daily intake. The results showed that none of the tested natural additives exhibited cytotoxicity in terms of inhibition of cell proliferation/viability and lactate dehydrogenase leakage. Additionally, the tested natural food additives did not generate intracellular reactive oxygen species (ROS), whereas they significantly decreased intracellular ROS levels produced by hydrogen peroxide. Moreover, none of the tested natural additives affected cell proliferation and viability in 2D and 3D intestinal epithelium models. Taken together, the ten natural food additives did not exhibit cytotoxicity in their actual usage levels. These findings can be used to further assess the toxicity of natural food additives.
Keywords
natural food additives; cytotoxicity; actual usage level; daily intake;
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1 Xi L, Qian Z, Du P, Fu J. Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats. Phytomedicine 14: 633-636 (2007)   DOI
2 Yoon JA, Yu KW, Shin SH, Cho HY. Activation of intestinal immune system by an orally administered methanol extract from pine needles. J. Korean Soc. Food Sci. Nutr. 39: 356-362 (2010)   DOI
3 Yu J, Hwang JS, Oh MS, Lee S, Choi SJ. Antioxidant activity of ethanol extracts from common and tartary buckwheat milling fractions. Korean J. Food Sci. Technol. 50: 549-554 (2018)   DOI
4 Clifford T, Constantinou CM, Keane KM, West DJ, Howatson G, Stevenson EJ. The plasma bioavailability of nitrate and betanin from Beta vulgaris rubra in humans. Eur. J. Nutr. 56: 1245-1254 (2017)   DOI
5 Singla RK, Bhat GV. Crocin: an overview. Indo Glob. J. Pharm. 1: 281-286 (2011)
6 Wu X, Pittman HE, Prior RL. Pelargonidin is absorbed and metabolized differently than cyanidin after marionberry consumption in pigs. J. Nutr. 134: 2603-2610 (2004)   DOI
7 Food and Drug Administration (FDA). CFR-Code of Federal Regulations Title 21. Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=170.3. Accessed Aug. 4, 2020
8 de Araujo RFF, Martins DBG, Borba MACSM. Oxidative Stress and Disease. pp. 185-199. In: A Master Regulator of Oxidative Stress -The Transcription Factor Nrf2. Morales-Gonzalez JA, Morales-Gonzalez A, Madrigal-Santillan EO (ed). IntechOpen, London, UK (2016)
9 des Rieux A, Fievez V, Theate I, Mast J, Preat V, Schneider YJ. An improved in vitro model of human intestinal follicle-associated epithelium to study nanoparticle transport by M cells. Eur. J. Pharm. Sci. 30: 380-391 (2007)   DOI
10 Edmondson R, Broglie JJ, Adcock AF, Yang L. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev. Techn. 12: 207-218 (2014)   DOI
11 Fernandes I, de Freitas V, Mateus N. Anthocyanins and human health: how gastric absorption may influence acute human physiology. Nutr. Aging 2: 1-14 (2014)   DOI
12 Fukuoka A, Yoshimoto T. Barrier dysfunction in the nasal allergy. Allergol. Int. 67: 18-23 (2018)   DOI
13 Gamboa JM, Leong KW. In vitro and in vivo models for the study of oral delivery of nanoparticles. Adv. Drug Deliver. Rev. 65: 800-810 (2013)   DOI
14 Korea Health Industry Development Institute (KHIDI). National Food & Nutrition Statistics. Available from: https://www.khidi.or.kr/kps/dhraStat/result1?menuId=MENU01652&year=2017. Accessed Jul. 23, 2019
15 Korea Health Industry Development Institute (KHIDI). National Food & Nutrition Statistics. Available from: https://www.khidi.or.kr/kps/dhraStat/result1?menuId=MENU01652&gubun=age1&year=2018. Accessed Aug. 5, 2020
16 Kim IH. The status of Korean food additive production usage and foreign countries. J. Korean Soc. Food Sci. Nutr. 19: 519-529 (1990)
17 BCC research. The global market for food additives. Available from: https://www.bccresearch.com/market-research/food-and-beverage/food-additives-market.html. Accessed Aug. 4, 2020
18 Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol. Pharm. 4: 807-818 (2007)   DOI
19 Bae SH, Yu J, Lee TG, Choi SJ. Protein matrix-ZnO nanoparticle interactions affect protein conformation, but may not be biological responses. Int. J. Mol. Sci. 19: 1-15 (2018)   DOI
20 Baek HH. International management trend of food additives. Food Sci. Ind. 49: 2-10 (2016)
21 Datta K, Sinha S, Chattopadhyay P. Reactive oxygen species in health and disease. Natl. Med. J. India 13: 304-310 (2000)
22 Cho MH, Niles A, Huang R, Inglese J, Austin CP, Riss T, Xia M. A bioluminescent cytotoxicity assay for assessment of membrane integrity using a proteolytic biomarker. Toxicol. In Vitro 22: 1099-1106 (2008)   DOI
23 Choi YJ. Food and tar color. Food Sci. Ind. 49: 62-69 (2016)
24 da Silva DVT, Baiao DS, Silva FO, Alves G, Perrone D, Aguila EMD, Paschoalin VMF. Betanin, a natural food additive: stability, bioavailability, antioxidant and preservative ability assessments. Molecules 24: 1-15 (2019)   DOI
25 Kim IS, Yoo GC. The comparative study on cell cytotoxicity of H2O2 and grapefruit seed extract. J. Korean Ophthalmic Opt. Soc. 9: 173-180 (2004)
26 Kim CY. Inhibition of interleukin-$1{\alpha}$-induced intestinal epithelial tight junction permeability by curcumin treatment in Caco-2 cells. J. Life Sci. 26: 1082-1087 (2016)   DOI
27 Kim SH, Kim IW, Lee HY, Chae IH, Kim MA, Kim HS, Kim CH, Sohn DW, Oh BH, Lee MM, Park YB, Choi YS, Lee YW. The effect of naringin on the lysophosphatidylcholine-induced proliferation of vascular smooth muscle cells. Korean Circ. J. 32: 61-70 (2002)   DOI
28 Kim TK, Ku Sk, Kim YB, Jeon KH, Choi YS. Substitution and technology trend of synthetic additives in processed meat industry: nitrite and phosphate. Food Sci. Anim. Resour. Indu. 6: 98-108 (2017)
29 Lee HH, Jeong JY, Park JM. Analysis of research trend in natural food additives. Food Sci. Ind. 49: 82-93 (2016)
30 Li Y, Zhang ZY, Zhang JL. Determination of hydroxysafflor yellow A in rat plasma and tissues by high-performance liquid chromatography after oral administration of safflower extract or safflor yellow. Biomed. Chromatogr. 21: 326-334 (2007)   DOI
31 Lim JC, Bae CS, Jeong SY, Boo HO, Hwang SJ, Lim SK, Park MJ, Kim JC, Kang SS, Han HJ, Park SH. Preventive effect of natural pigments against ultraviolet B-induced cell death in HaCat cells. Biomed. Sci. Lett. 17: 55-60 (2011)
32 Lv LZ, Tong CQ, Yu J, Han M, Gao JQ. Mechanism of enhanced oral absorption of hydrophilic drug incorporated in hydrophobic nanoparticles. Int. J. Nanomed. 8: 2709-2717 (2013)
33 Mabbott NA, Donaldson DS, Ohno H, Williams IR, Mahajan A. Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium. Mucosal Immunol. 6: 666-677 (2013)   DOI
34 Ministry of Food and Drug Safety (MFDS), Food Sanitation Act. No. 17091 (2020a)
35 Rommele C, Brueckner J, Messmann H, Golder SK. Clinical experience with the PillCam patency capsule prior to video capsule endoscopy: a real-world experience. Gastroent. Res. Pract. 2016: 1-6 (2016)
36 Papich MG, Martinez MN. Applying biopharmaceutical classification system (BCS) criteria to predict oral absorption of drugs in dogs: challenges and pitfalls. AAPS J. 17: 948-964 (2015)   DOI
37 Phan TNQ, Iram S, Bernkop-Schnurch A. Hydrophobic ion-pairs and lipid-based nanocarrier systems: The perfect match for delivery of BCS class 3 drugs. J. Control. Release 304: 146-155 (2019)   DOI
38 Rein MJ, Renouf M, Cruz-Hernandez C, Actis-Goretta L, Thakkar SK, da Silva Pinto M. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy. Br. J. Clin. Pharmacol. 75: 588-602 (2012)   DOI
39 Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai, A. Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: an overview. Medicines 5: 1-16 (2018)   DOI
40 Salehi B, Fokou, PVT, Sharifi-Rad M, Zucca P, Pezzani R, Martins N, Sharifi-Rad J. The therapeutic potential of naringenin: a review of clinical trials. Pharmaceuticals 12: 1-18 (2019)   DOI
41 United States Environmental Protection Agency (US EPA). Guidance for evaluating the oral bioavailability of metals in soils for use in human health risk assessment. Available from: https://semspub.epa.gov/work/HQ/175333.pdf. Accessed Sep. 18, 2020
42 Wang MJ, Chao PDL, Hou YC, Hsiu SL, Wen KC, Tsai SY. Pharmacokinetics and conjugation metabolism of naringin and naringenin in rats after single dose and multiple dose administrations. J. Food Drug Anal. 14: 247-253 (2006)
43 Wang Y, Ning ZH, Tai HW, Long S, Qin WC, Su LM, Zhao YH. Relationship between lethal toxicity in oral administration and injection to mice: effect of exposure routes. Regul. Toxicol. Pharm. 71: 205-212 (2015)   DOI
44 Nigam PS, Luke JS. Food additives: production of microbial pigments and their antioxidant properties. Curr. Opin. Food Sci. 7: 93-100 (2016)   DOI
45 Ministry of Food and Drug Safety (MFDS). Article in 2018. Available from: https://www.mfds.go.kr/brd/m_99/view.do?seq=40094&srchFr=&srchTo=&srchWord=%EC%B2%A8%EA%B0%80%EB%AC%BC&srchTp=8&itm_seq_1=0&itm_seq_2=0&multi_itm_seq=0&company_cd=&company_nm=&Data_stts_gubun=C9999&page=4. Accessed Aug. 4, 2020b
46 Ministry of Food and Drug Safety (MFDS). Food Additives Code. Ministry of Food and Drug Safety, Osong, South Korea (2020c)
47 Min JY, Park HY, Kim Y, Hong JS, Choi HD. Antioxidant activity and stability of natural pigment extracted from red beetroot (Beta vulgaris L.). J. Korean Soc. Food Sci. Nutr. 47: 725-732 (2018)   DOI
48 Mohamad MF, Dailin DJ, Gomaa SE, Nurjayadi M, Enshasy HE. Natural colorant for food: a healthy alternative. Int. J. Sci. Technol. Res. 8: 3161-3166 (2019)
49 Mudie DM, Murray K, Hoad CL, Pritchard SE, Garnett MC, Amidon GL, Gowland PA, Spiller RC, Amidon GE, Marciani L. Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state. Mol. Pharm. 11: 3039-3047 (2014)   DOI
50 Okafor SN, Obonga W, Ezeokonkwo MA, Nurudeen J, Orovwigho U, Ahiabuike J. Assessment of the health implications of synthetic and natural food colourants-a critical review. UK J. Pharm. Biosci. 4: 1-11 (2016)
51 Olivas-Aguirre FJ, Rodrigo-Garcia J, Martinez-Ruiz NDR, Cardenas-Robles AI, Mendoza-Diaz SO, Alvarez-Parrilla E, Gonzalez-Aguilar GA, de la Rosa LA, Ramos-Jimenez A, Wall-Medrano A. Cyanidin-3-O-glucoside: physical-chemistry, foodomics and health effects. Molecules 21: 1-30 (2016)   DOI
52 Oplatowska-Stachowiak M, Elliott CT. Food colors: existing and emerging food safety concerns. Crit. Rev. Food Sci. Nutr. 57: 524-548 (2017)   DOI