Lacto--tetraose (LNT) is a human milk oligosaccharide with average concentrations ranging from 0.74 to 1.07 g/L in breastmilk, depending on the lactation stage. In this study, the preclinical safety of LNT produced by the K-12 E2083 production strain was assessed. LNT was negative in both the bacterial reverse mutation assay and the micronucleus assay, demonstrating the absence of genotoxic potential for this substance. In the OECD 408 guideline compliant 90-day oral toxicity study rat, LNT did not induce any adverse effects in any treatment group up to and including the highest dose tested, and no LOAEL could be determined. Therefore, the no-observed-adverse effect level (NOAEL) is set at the highest dose level tested, i.e. a dietary level of 5 % (w/w), corresponding to ≥2856 mg/kg bw/day and ≥3253 mg/kg bw/day for males and females, respectively. This might be an underestimation of the NOAEL, caused by the range of dose levels tested. The results obtained in the current study are in good agreement with available data generated using other biotechnologically produced LNT batches and therefore support its safe use as a food ingredient.

中文翻译：

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生物技术生产的乳-N-四糖 (LNT) 的临床前安全性评估


乳四糖 (LNT) 是一种人乳低聚糖，母乳中的平均浓度范围为 0.74 至 1.07 g/L，具体取决于哺乳阶段。在本研究中，评估了 K-12 E2083 生产菌株产生的 LNT 的临床前安全性。 LNT 在细菌回复突变试验和微核试验中均为阴性，表明该物质不存在潜在的遗传毒性。在符合 OECD 408 指南的 90 天口服毒性研究大鼠中，LNT 在任何治疗组中均未引起任何不良反应，直至并包括最高测试剂量，并且无法确定 LOAEL。因此，未观察到不良反应水平（NOAEL）设定为测试的最高剂量水平，即饮食水平为5%（w/w），相当于≥2856 mg/kg bw/天和≥3253 mg/天。男性和女性分别为公斤体重/天。这可能低估了 NOAEL，这是由测试的剂量水平范围引起的。当前研究中获得的结果与使用其他生物技术生产的 LNT 批次生成的可用数据非常一致，因此支持其作为食品成分的安全使用。