Toxicological safety assessment of the human‐identical milk oligosaccharide 3′‐sialyllactose sodium salt. Issue 10 (16th August 2019)

• Record Type: Journal Article
• Authors: Phipps, Kirt R.; Baldwin, Nigel J.; Lynch, Barry; Stannard, Diane R.; Šoltésová, Alica; Gilby, Ben; Mikš, Marta H.; Röhrig, Christoph H.
• Is Part Of: Journal of applied toxicology. Volume 39:Issue 10(2019)
• Page Start: 1378
• Page End: 1393
• Publication Date: 2019-08-16
• Subjects: 3′‐sialyllactose -- 3′‐sialyllactose sodium salt -- genotoxicity -- human‐identical milk oligosaccharide -- infant formula -- safety -- subchronic toxicity; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3824
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: Human breastmilk is a mixture of nutrients, hormones and bioactive molecules that are vital for infant growth and development. Infant formula (IF) lacks many of these compounds, most notably human milk oligosaccharides (HMOs), which are abundant in breastmilk but scarce in IF. Sialyllactoses, such as 3′‐sialyllactose, constitute a large portion of the HMO fraction. To produce IF that matches breastmilk more closely, biosynthesized human‐identical milk oligosaccharides (structurally identical to HMOs) such as 3′‐sialyllactose sodium salt (3′‐SL) are proposed for use in IF and foods for the general population. The safety assessment of 3′‐SL comprised in vitro genotoxicity tests and a 90‐day oral (gavage) toxicity study. This is the first 90‐day study conducted with 3′‐SL using neonatal rats (7 days old at the start of dosing—equivalent age to newborn human infants in terms of central nervous system and reproductive development), demonstrating the safety of 3′‐SL for consumption by infants, the most sensitive age group. The neonatal rats received 3′‐SL at doses up to 5, 000 mg/kg body weight (BW)/day and reference controls received 5, 000 mg/kg BW/day of fructooligosaccharide (an ingredient approved for use in IF) for comparison with the high‐dose 3′‐SL group, followed by a 4‐week recovery period. There was no evidence of genotoxicity in vitro . In the absence of any test item‐related adverse effects in the 90‐day study, the high dose (5, 000 mg/kg BW/day) was established as the no‐observed‐adverse‐effect level. This confirms the safety of 3′‐SL for use in IF for infants, as well as in functional foods for the general population. Abstract : Infant formula lacks many of the important compounds found in human breastmilk, most notably human milk oligosaccharides, such as 3′‐sialyllactose. To support the safe use of biosynthesized 3′‐sialyllactose sodium salt in infant formula and other functional foods for the general population, in vitro genotoxicity tests and a 90‐day oral (gavage) toxicity study (using neonatal rats) were conducted. There was no evidence of genotoxicity and the high dose in the 90‐day study (5, 000 mg/kg body weight/day) was established as the no‐observed‐adverse‐effect level.