Pre-clinical safety assessment of the synthetic human milk, nature-identical, oligosaccharide Lacto-N-neotetraose (LNnT).
Lacto-N-neotetraose (LNnT) is a tetrasaccharide naturally occurring in human breast milk, but not in cow's milk. The safety data generated on a potential new LNnT ingredient produced by chemical synthesis is presented. Standard in vitro genotoxicity tests were performed. LNnT was also administered via gavage in 14-, 28- and 90-day studies at levels corresponding to 0 (control), 1000, 2500 and 5000 mg/kg bw/day in juvenile rats. Fructooligosaccharide (FOS) currently approved for use in infant formulae was used as a reference control at one dose level of 5000 mg/kg bw/day. LNnT was non-mutagenic in in vitro assays. Oral administration up to 5000 mg/kg bw/day to rats over 90 days was not associated with any adverse effects, based on clinical observations, body weight gain, feed consumption, clinical pathology, organ weights and histopathology findings. Regarding gastrointestinal effects, LNnT was better tolerated than FOS during the first 2 weeks of treatment. A No Observed Adverse Effect Level (NOAEL) of 5000 mg/kg bw/day for both male and female rats was identified for LNnT when administered by gavage for 90 days. These findings in the juvenile rat support the safety of LNnT for possible use in infant foods and allow further investigation in clinical studies.
Nestlé Research Center, Vers-chez-les-Blanc, PO Box 44, 1000 Lausanne 26, Switzerland. Electronic address: myriam.coulet@rdls.nestle.com.
Myriam
M
Coulet
Phoukham
P
Phothirath
Anne
A
Constable
Edward
E
Marsden
Benoit
B
Schilter
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008895:Milk, Human / Q000737:chemistry; D009152:Mutagenicity Tests; D009844:Oligosaccharides / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018675:Toxicity Tests / Q000379:methods*
D009844:Oligosaccharides; C116580:fructooligosaccharide; C013084:lacto-N-neotetraose
AG ratio; ALAT; ALP; ASAT; Alb; Bili; CP; Ca; Chol; Cl; Creat; FOS; GOS; Gavage; Glob; HMO; Hb; Human milk oligosaccharides; IF; Juvenile rats; K; LNnT; Lacto-N-neotetraose; MCH; MCHC; MCV; MF; MMS; MoE; Mutagenicity; NOAEL; Na; No Observed Adverse Effect Level; PCV; PND; Prot; RBC; RS; RTG; Reti; Sub-chronic toxicity; TFT; TK; WBC; alanine transferase; albumin; albumin/globulin ratio; alkaline phosphatase; aspartate aminotransferase; calcium; chloride; creatinine; cyclophosphamide; fructooligosaccharide; galactooligosaccharide; globulin; heamoglobin; human milk oligosaccharides; infant formula; margin of exposure; mean corpuscular heamoglobin; mean corpuscular heamoglobin concentration; mean corpuscular volume; methyl methanesulphonate; mutant frequency for 106 cells; nd; no data; pack cell volume; postnatal day; potassium; red blood cells; relative survival; relative total growth; reticulocytes; sodium; thymidine kinase; total bilirubin; total cholesterol; total protein; trifluorothymidine; white blood cells