Genotoxicity and neonatal subchronic toxicity assessment of a novel mixture of the human-identical milk oligosaccharides lacto-N-fucopentaose I and 2'-fucosyllactose
| Autor: | Marta H. Mikš, Barry Lynch, Ben Gilby, Annette Lau, Kirt R. Phipps, Christoph H. Röhrig, Nigel Baldwin, Diane R. Stannard |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Salmonella typhimurium Oligosaccharides 010501 environmental sciences Pharmacology Breast milk Toxicology medicine.disease_cause 01 natural sciences Rats Sprague-Dawley 03 medical and health sciences Ingredient chemistry.chemical_compound 2'-Fucosyllactose Medicine Animals Humans Adverse effect 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences Milk Human business.industry Mutagenicity Tests Infant Newborn In vitro Infant Formula United Kingdom Rats Disease Models Animal chemistry Infant formula Animals Newborn Micronucleus test Female business Trisaccharides Genotoxicity DNA Damage |
| Zdroj: | Journal of applied toxicology : JATREFERENCES. 41(4) |
| ISSN: | 1099-1263 |
| Popis: | Human milk oligosaccharides (HMOs) are a complex group of bioactive molecules largely observed in human breast milk but also occurring in limited amounts in other mammalian milks. Advances in biotechnology have enabled production of human-identical milk oligosaccharides (HiMOs), structurally identical molecules to HMOs found naturally in human milk, intended for addition to infant formula to more closely replicate breast milk. Biosynthesis of a novel mixture of two major HMOs, lacto-N-fucopentaose I and 2'-fucosyllactose (LNFP-I/2'-FL), recently became possible. To support the safety of LNFP-I/2'-FL for use in infant formula and other foods, it was subject to a safety assessment comprising a bacterial reverse mutation test, an in vitro mammalian cell micronucleus test, and a 90-day oral gavage study in neonatal rats. In the 90-day study (the first HiMO study to include the new endocrine-sensitive endpoints described in the 2018 version of OECD Test Guideline 408), LNFP-I/2'-FL was administered by oral gavage to neonatal rats once daily (from Day 7 of age) for 90 consecutive days, at doses up to 5000 mg/kg bw/day, followed by a 4-week recovery period. Concurrent reference controls received 5000 mg/kg bw/day of the approved infant formula ingredient oligofructose. LNFP-I/2'-FL was nongenotoxic in vitro. The highest dose tested (5000 mg/kg bw/day) was established as the no-observed-adverse-effect level in the 90-day study, as there were no test article-related adverse effects on clinical observations, body weight, food consumption, clinical pathology, and organ weights nor any noteworthy macroscopic or microscopic findings. This supports the safety of LNFP-I/2'-FL for its intended uses in food. |
| Databáze: | OpenAIRE |
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