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大鼠十三周喂养试验研究 L-色氨酸的毒性,恢复期为五周。

Thirteen week toxicity study of dietary l-tryptophan in rats with a recovery period of 5 weeks.

机构信息

Institute for Innovation, Ajinomoto Co., Inc., 1-1, Suzuki-cho, Kawasaki-shi, Kanagawa, 210-8681, Japan.

Gotemba Laboratory, Bozo Research Center Inc., 1284, Kamado, Gotemba-shi, Shizuoka, 412-0039, Japan.

出版信息

J Appl Toxicol. 2018 Apr;38(4):552-563. doi: 10.1002/jat.3562. Epub 2017 Nov 16.

DOI:10.1002/jat.3562
PMID:29143967
Abstract

Although l-tryptophan is nutritionally important and widely used in medical applications, toxicity data for its oral administration are limited. The purpose of this study was to evaluate the potential toxicity of an experimental diet containing added l-tryptophan at doses of 0 (basal diet), 1.25%, 2.5% and 5.0% when administered to Sprague-Dawley rats for 13 weeks. There were no toxicological changes in clinical signs, ophthalmology, urinalysis, hematology, necropsy, organ weight and histopathology between control rats and those fed additional l-tryptophan. Body weight gain and food consumption significantly decreased throughout the administration period in males in the 2.5% group and in both sexes in the 5.0% group. At the end of the dosing period, decreases in water intake in males in the 5.0% group and in serum glucose in females in the 5.0% group were observed. The changes described above were considered toxicologically significant; however, they were not observed after a 5 week recovery period, suggesting reversibility. Consequently, the no-observed-adverse-effect level of l-tryptophan in the present study was 1.25% for males and 2.5% for females (mean intake of l-tryptophan: 779 mg kg body weight day [males] and 1765 mg kg body weight day [females]). As the basal diet used in this study contained 0.27% of proteinaceous l-tryptophan, the no-observed-adverse-effect level of overall l-tryptophan was 1.52% for males and 2.77% for females (mean intake of overall l-tryptophan: 948 mg kg body weight day (males) and 1956 mg kg body weight day (females)). We conclude that l-tryptophan has a low toxicity profile in terms of human use.

摘要

尽管 l-色氨酸在营养上很重要,并且在医学应用中被广泛使用,但关于其口服给药的毒性数据有限。本研究的目的是评估在给 Sprague-Dawley 大鼠喂食添加 l-色氨酸的实验饮食时,0(基础饮食)、1.25%、2.5%和 5.0%剂量下的潜在毒性,为期 13 周。在对照组大鼠和喂食额外 l-色氨酸的大鼠之间,临床症状、眼科、尿液分析、血液学、尸检、器官重量和组织病理学均无毒性变化。在 2.5%组的雄性和 5.0%组的雌雄大鼠中,整个给药期间体重增加和食物消耗均显著减少。在给药期末,5.0%组雄性大鼠的饮水量减少,5.0%组雌性大鼠的血清葡萄糖减少。上述变化被认为具有毒理学意义;然而,在 5 周恢复期后未观察到这些变化,表明这些变化具有可逆性。因此,在本研究中,l-色氨酸的未观察到不良效应水平为 1.25%(雄性)和 2.5%(雌性)(雄性 l-色氨酸的平均摄入量:779mg kg 体重日,雌性 l-色氨酸的平均摄入量:1765mg kg 体重日)。由于本研究中使用的基础饮食含有 0.27%的蛋白质 l-色氨酸,因此,总体 l-色氨酸的未观察到不良效应水平为 1.52%(雄性)和 2.77%(雌性)(雄性总体 l-色氨酸的平均摄入量:948mg kg 体重日,雌性总体 l-色氨酸的平均摄入量:1956mg kg 体重日)。我们得出结论,l-色氨酸在人类使用方面具有低毒性特征。

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