Neonatal subchronic toxicity and in vitro genotoxicity studies of the human‐identical milk oligosaccharide 3‐fucosyllactose

Abstract

Human milk oligosaccharides, such as 3‐fucosyllactose (3‐FL), are bioactive components of breast milk associated with benefits for infant growth and development. Structurally identical compounds (human‐identical milk oligosaccharides—HiMOs) can be produced using microbial fermentation, allowing their use in infant formula to increase its similarity with human milk. Toxicological studies are required to demonstrate safety of HiMOs and that of any impurities potentially carried over from the manufacturing process. Biotechnologically produced 3‐FL was tested for potential genotoxicity (bacterial reverse mutation test and in vitro mammalian micronucleus test) and subchronic toxicity (90‐day study with neonatal rats). In the 90‐day study, 3‐FL was administered by gavage to rats once daily from Day 7 of age, at doses up to 4000 mg/kg body weight (bw)/day (the maximum feasible dose), followed by a 4‐week recovery period. Reference controls received 4000 mg/kg bw/day of oligofructose, an ingredient permitted for use in infant formula. Results for the genotoxicity studies were negative. In the 90‐day study, there were no adverse effects of 3‐FL on any of the parameters measured; thus, the no‐observed‐adverse‐effect level (NOAEL) was 4000 mg/kg bw/day (the highest dose tested). These results support the safety of biotechnologically produced 3‐FL for use in infant formula and other foods.

Safety of 3‐fucosyllactose (3‐FL) produced by a derivative strain of Escherichia coli K‐12 DH1 as a novel food pursuant to Regulation (EU) 2015/2283

“…These studies, which were claimed proprietary by the applicant, are listed in Table 9 . A publication on the assessment of the NF which describes these studies is also available (Phipps et al., 2022 ).…”

“…In the 90‐day study groups of 10 Crl:CD(SD) neonatal (from day 7 of age) rats/sex were given by oral gavage the vehicle (sterile water), 1,000, 2,000 or 4,000 mg 3‐FL/kg bw per day (unpublished study report, 2021d ; Phipps et al., 2022 ). An additional group was given oligofructose as the reference control group.…”