Human milk oligosaccharides (HMOs) are indigestible carbohydrates representing the third largest fraction of solutes in human breastmilk. They provide valuable prebiotic and anti-pathogenic functions in breastfed infants, but are not yet included in most infant formula products. Recent biotechnological advances now facilitate large-scale production of HMOs, providing infant formula manufacturers with the ability to supplement their products with HMOs to mimic human breastmilk. Although the safety of individual HMOs has been confirmed in preclinical toxicological studies, the safety of HMO mixtures has not been tested. We therefore performed bacterial reverse mutation and in vitro micronucleus tests and conducted a repeated-dose oral toxicity study in rats with a mixture of five HMOs (HMO MIX I), containing 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL). HMO MIX I was not genotoxic and did not induce adverse effects in the repeated dose study. The no-observed-adverse-effect-level (NOAEL) for HMO MIX I in this study is 10% in the diet (equivalent to 5.67 g HMO MIX I/kg bw/day for males and 6.97 g HMO MIX I/kg bw/day for females). Our results provide strong evidence for the safety of HMO MIX I in infant products and general foods.

中文翻译：

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混合人乳低聚糖在大鼠中的安全性评估。

人乳寡糖（HMO）是不易消化的碳水化合物，是人乳中溶质的第三大部分。它们在母乳喂养的婴儿中提供了有价值的益生元和抗病原功能，但尚未在大多数婴儿配方食品中包含。现在，生物技术的最新发展促进了HMO的大规模生产，使婴儿配方奶粉制造商能够在其产品中添加HMO来模仿人类母乳。尽管在临床前毒理学研究中已确认了单个HMO的安全性，但尚未测试HMO混合物的安全性。因此，我们进行了细菌反向突变和体外微核试验，并在含有5种HMO（HMO MIX I）的混合物中对大鼠进行了重复剂量的口服毒性研究，其中HMOs含有2'-岩藻糖半乳糖（2'-FL），3-岩藻糖半乳糖（3-FL），乳酸-N-四糖（LNT），3'-唾液乳糖（3'-SL）和6'-唾液乳糖（6'-SL）。HMO MIX I没有遗传毒性，并且在重复剂量研究中没有引起不良反应。饮食中HMO MIX I的未观察到的不良影响水平（NOAEL）为饮食中的10％（相当于男性的5.67 g HMO MIX I / kg bw /天和6.97 g HMO MIX I / kg bw /天（女性）。我们的结果为HMO MIX I在婴儿产品和一般食品中的安全性提供了有力的证据。雌性，每天97克HMO MIX I /千克体重。我们的结果为HMO MIX I在婴儿产品和一般食品中的安全性提供了有力的证据。雌性，每天97克HMO MIX I /千克体重。我们的结果为HMO MIX I在婴儿产品和一般食品中的安全性提供了有力的证据。