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

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

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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.
Department of Nutrition, School of Human Cultures, The University of Shiga Prefecture, 2500, Hassaka-cho, Hikone-shi, Shiga, 522-8533, Japan.


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-1 body weight day-1 [males] and 1765 mg kg-1 body weight day-1 [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-1 body weight day-1 (males) and 1956 mg kg-1 body weight day-1 (females)). We conclude that l-tryptophan has a low toxicity profile in terms of human use.


L-tryptophan; NOAEL; acceptable daily intake; amino acid; body weight; food intake; rat; subchronic toxicity; uncertainty factor

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