关键词: BUN, blood urea nitrogen DRF, dose range-finding Dried L-tryptophan fermentation product EMS, eosinophilia-myalgia syndrome Eosinophilia-myalgia syndrome FFPE, formalin-fixed paraffin-embedded GHS, globally harmonized system GLP, good laboratory practice HED, human equivalent dose IHC, immunohistochemistry Metabolically engineered Corynebacterium glutamicum NOAEL, no observed adverse effect level OECD, Organization for Economic Cooperation and Development Oral administration SD, Sprague-Dawley Subchronic toxicity WBC, white blood cell pAb, polyclonal antibody

来  源:   DOI:10.1016/j.toxrep.2022.05.005   PDF(Pubmed)

Abstract:
The subchronic toxicity of oral L-tryptophan produced by fermentation with metabolically engineered Corynebacterium glutamicum was evaluated in Sprague-Dawley rats. Doses of 0, 500, 1000, and 2000 mg/kg/day were administered to groups of 10 male and 10 female rats for 90 days. For the groups administered 0 and 2000 mg/kg/day, an additional 5 male and 5 female rats were tested as a recovery group. No adverse effects associated with the test substance were observed in all rats during the 90-day administration of the product, irrespective of dose, and at 4 weeks of recovery at dosages of 0 and 2000 mg/kg/day. Furthermore, histochemical and immunohistochemical analyses for L-tryptophan-associated eosinophilia-myalgia syndrome (EMS) did not reveal significant changes in both sexes of groups administered 0 or 2000 mg/kg/day. Based on these results, it could be concluded that there were no significant adverse effects related to the test substance in all animals; therefore, dried L-tryptophan fermentation product can be used as feed additive material.
摘要:
在Sprague-Dawley大鼠中评估了通过代谢工程化谷氨酸棒杆菌发酵产生的口服L-色氨酸的亚慢性毒性。将0、500、1000和2000mg/kg/天的剂量给予10只雄性和10只雌性大鼠的组90天。对于0和2000mg/kg/天的组,另外5只雄性和5只雌性大鼠作为恢复组进行测试。在90天的产品给药期间,在所有大鼠中均未观察到与测试物质相关的不良反应,无论剂量如何,并在0和2000mg/kg/天的剂量下恢复4周。此外,L-色氨酸相关的嗜酸性粒细胞增多-肌痛综合征(EMS)的组织化学和免疫组织化学分析未显示0或2000mg/kg/天给药组的两种性别均有显著变化.基于这些结果,可以得出结论,在所有动物中都没有与测试物质有关的明显不良反应;因此,干燥的L-色氨酸发酵产物可用作饲料添加剂材料。
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