Research Article
Volume 16 Issue 4 - 2021
Safety and Toxicological Evaluation of 2’-Fucosyllactose Produced by Fermentation via Genetically Engineered Corynebacterium glutamicum
Iris L Case1, Young-Ha Song2, Chang-Ku Jeong2, Jung-Min Kim2, Chun-Ja Nam3, Yunji Seol1 and Jong-Won Yoon2*
1Ace One RS, Inc., Clarksville, Maryland, USA
2Advance Protein Technologies Corp., Gyeonggi-do, Republic of Korea
3BiotoxTech Co., Ltd., Chungcheongbuk-do, Republic of Korea, Present Address, Chemon Inc., Republic of Korea
*Corresponding Author: Jong-Won Yoon, Advance Protein Technologies Corp., Gyeonggi-do, Republic of Korea.
Received: February 18, 2021; Published: March 29, 2021




Abstract

The safety of 2’-fucosyllactose (2’-FL) produced by fermentation via genetically engineered Corynebacterium glutamicum was evaluated in acute and subchronic toxicity studies as well as a battery of mutagenicity and genotoxicity studies. An in vitro mutagenicity study using reverse bacterial mutation tests and an in vitro genotoxicity study with Chinese hamster lung cells demonstrated that 2’-FL was not mutagenic or clastogenic in the presence or absence of metabolic activation. An in vivo mouse micronucleus assay, 2’-FL did not induce micronuclei formation in the bone marrow cells of mice, indicating that it is non-clastogenic. An acute toxicity study found that the approximate lethal dose of 2’-FL was much greater than 7,500 mg/kg, the highest dose tested, in male and female juvenile rats (7 days old). In the 90-day oral toxicity study, the no observed adverse effect level (NOAEL) of 2’-FL was determined to be 7,500 mg/kg bw/day, the highest dose tested, for male and female rats. The results of these studies support the safety of 2’-FL as a food ingredient.

Keywords: 2’-Fucosyllactose; Safety; Acute Toxicity; Subchronic Toxicity; Mutagenicity; Clastogenicity; Genotoxicity

References

  1. Castanys-Muñoz E., et al. “2'-fucosyllactose: an abundant, genetically determined soluble glycan present in human milk”. Nutrition Reviews 12 (2013): 773-789.
  2. Gabrielli O., et al. “Preterm milk oligosaccharides during the first month of lactation”. Pediatrics6 (2011): e1520-1531.
  3. Leo F., et al. “Improved determination of milk oligosaccharides using a single derivatization with anthranilic acid and separation by reversed-phase high-performance liquid chromatography”. Journal of Chromatography A 9 (2009): 1520-1523.
  4. Musumeci M., et al. “Oligosaccharides in colostrum of Italian and Burkinabe women”. Journal of Pediatric Gastroenterology and Nutrition 3 (2006): 372-378.
  5. Brand-Miller JC., et al. “Digestion of human milk oligosaccharides by healthy infants evaluated by the lactulose hydrogen breath test”. The Journal of Pediatrics 1 (1998): 95-98.
  6. Gnoth MJ., et al. “Human milk oligosaccharides are minimally digested in vitro”. Journal of Nutrition 12 (2000): 3014-3020.
  7. Newburg DS. “Oligosaccharides in human milk and bacterial colonization”. Journal of Pediatric Gastroenterology and Nutrition 30 (2000): S8-S17.
  8. United States Department of Agriculture (USDA). “United States Department of Health and Human Services. Dietary Guidelines for Americans (8th ed.)” U.S. Government Printing Office; Washington, DC, USA (2015).
  9. Elison E., et al. “Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota”. British Journal of Nutrition 8 (2016): 1356-1368.
  10. Rudloff S., et al. “Metabolism of milk oligosaccharides in preterm pigs sensitive to necrotizing enterocolitis”. Frontiers in Nutrition 6 (2019): 23.
  11. Thongaram T., et al. “Human milk oligosaccharide consumption by probiotic and human-associated bifidobacteria and lactobacilli”. Journal of Dairy Science 10 (2017): 7825-7833.
  12. Institute of Medicine (IOM). “Dietary Reference Intakes for energy, carbohydrates, fiber, fat, fatty acids, cholesterol, protein, and amino acids”. National Academy Press, Washington, DC (2002).
  13. Van Berlo D., et al. “Safety assessment of biotechnologically produced 2'-Fucosyllactose, a novel food additive”. Food and Chemical Toxicology 118 (2018): 84-93.
  14. Coulet M., et al. “Pre-clinical safety evaluation of the synthetic human milk, nature-identical, oligosaccharide 2'-O-fucosyllactose (2'FL)”. Regulatory Toxicology and Pharmacology 1 (2014): 59-69.
  15. Sengupta P. “The laboratory rat: Relating its rge with human's”. International Journal of Preventive Medicine 6 (2013): 624-630.
Citation: Jong-Won Yoon., et al. “Safety and Toxicological Evaluation of 2’-Fucosyllactose Produced by Fermentation via Genetically Engineered Corynebacterium glutamicum”. EC Nutrition 16.4 (2021): 04-19.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


August Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the August issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before August 18, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.