Summary of animal safety studies with amino acids

Amino Acid	study period/animal species	Peer-reviewed articles
Monosodium Glutamate	Rat	Principles for the safety assessment of food additives and contaminants in food. World Health Organization, International Program on　Chemical Safety in　Cooperation with the Joint FAO/WHO Expert Committee on Food Additives, Geneva, Environmental Health Criteria 70 (1987).
L-Glutamine	13wks / Rat	Tsubuku, S., Hatayama, K., Mawatari, K., Smriga, M. & Kimura, T. (2004) Thirteen-week oral toxicity study of L-glutamine in rats. Int J Toxicol 23: 107-112.
L-Arginine	13wks / Rat 13wks / Pig	Anonymous (2004) Thirteen-week oral toxicity study of L-arginine in rats. Int J Toxicol 23: 101-105. Amino Acids. 2015 Feb 6. [Epub ahead of print] Safety of long-term dietary supplementation with L-arginine in pigs. Hu S1, Li X, Rezaei R, Meininger CJ, McNeal CJ, Wu G. 1Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA.
L-Valine	13wks / Rat	Tsubuku, S., Hatayama, K., Katsumata, T., Nishimura, N., Mawatari, K., Smriga, M. & Kimura, T. (2004) Thirteen-week oral toxicity study of branched-chain amino acids in rats. Int J Toxicol 23: 119-126
L-Leucine	13wks / Rat	Tsubuku, S., Hatayama, K., Katsumata, T., Nishimura, N., Mawatari, K., Smriga, M. & Kimura, T. (2004) Thirteen-week oral toxicity study of branched-chain amino acids in rats. Int J Toxicol 23: 119-126
L-Isoleucine	13wks / Rat	Tsubuku, S., Hatayama, K., Katsumata, T., Nishimura, N., Mawatari, K., Smriga, M. & Kimura, T. (2004) Thirteen-week oral toxicity study of branched-chain amino acids in rats. Int J Toxicol 23: 119-126
L-Lysine （L-Lysine HCl）	13wks / Rat	Tsubuku, S., Mochizuki, M., Mawatari, K., Smriga, M. & Kimura, T. (2004) Thirteen-week oral toxicity study of L-lysine hydrochloride in rats. Int J Toxicol 23: 113-118.
L-Alanine	4wks / Rat	A 4-week oral toxicity study of L-alanine in rats with a recovery period of 2 weeks Vol.1, No.2, p.63-72 Mami Aoki , Masahiro Mochizuki , Toshiya Okamura , Kazuhisa Hatayama , Atsushi Nakamura , Koji Morishita Released: October 23, 2023 Fundamental Toxicological Sciences
DL-Alanine	26wks / Rat	Fu-ho C. Chow, M.Irene Dysart, Dwayne W. Hamar, Lon D. Lewis, and Robert H. Udall (1976) Alanine : A Toxicity Study Tosicology and Applied Pharmacology 37,491-497
L-Asparagine	13wks / Rat	Yokohira, M., Hosokawa, K., Yamakawa, K., Hashimoto, N., Suzuki, S., Matsuda, Y., Saoo, K., Kuno, T. & Imaida, K. (2008) A 90-day toxicity study of L-asparagine, a food additive, in F344 rats. Food Chem Toxicol 46: 2568-2572.
L-Asparatic Acid	13wks / Rat	Tada, Y., Yano, N., Takahashi, H., Yuzawa, K., Ando, H., Kubo, Y., Nagasawa, A., Uehara, S., Ogata, A. & Nakae, D. (2008) Toxic effects of l-aspartic acid at high dose levels on kidneys and salivary glands in Fischer 344 rats detected in a 90-day feeding study. Food Chem Toxicol 46: 2789-2795.
L-Cystein（Monohydrochloride）	4wks / Rat 4wks / Rat	Sawamoto.O., Kyo, S., Kaneda,S., Harada, M., Kishimoto, S., Koshitani, O., Kurisu, K., Nakashima, Y. (2003) Four-week intravenous repeated dose toxicity study of L-systeine in male rats. The Journal of toxicological science 28: 95-107
Glycine （amino acetic acid）	4wks / Rat	A 4-week Repeated Dose Toxicity Study of Glycine in Rats by Gavage Administration Yusuke Shibui,1,* Tadashi Miwa,1,* Mayumi Yamashita,1 Keigi Chin,1 and Terutaka Kodama1 Journal of Toxicologic Pathology（Dec 2013; 26(4): 405–412）
L-Histidine	13wks / Rat	Ikezaki, S., Nishikawa, A., Furukawa, F., Imazawa, T., Enami, T., Mitsui, M. & Takahashi, M. (1994) [13-week subchronic toxicity study of L-histidine monohydrochloride in F344 rats]. Eisei Shikenjo Hokoku: 57-63.
DL-Methionine	100days / Pig	Fau D, Delhomme B, Bourdon D, Rerat A.(1980) Enzymatic activities in the liver, and muscle nucleic acids, in swine receiving an unbalanced diet with an exvedd of methionine for 100 days. Comptes rendus des seances de l'Academie des sciences. Serie D, Sciences naturelles 291 565-568
L-Methionine	2years / Rat 4wks / Rat	Peret J.(1984) Effects of hight protein or excess methionine diet ingested for 2 years. Federation Proceedings 43: Abstract2267. Meeting Info.: 68th Annual meeting of the American societies for experimental Biology.
L-Methionine	4wks / Rat	“A 4-Week Toxicity Study of Methionine in Male Rats” Authors: Keigi Chin, Sakino Toue, Yasuko Kawamata, Akiko Watanabe, Tadashi Miwa, Miro Smriga, Ryosei Sakai （International journal of toxicology. May 2015;34(3):233-241.）
L-Phenylalanine	4wks / Rat	28-Day dietary toxicity study of L-phenylalanine in rats Vol.1, No.2, p.29-38 Yusuke Shibui , Tadashi Miwa , Terutaka Kodama , Akinori Gonsho Released: September 27, 2023 Fundamental Toxicological Sciences（Vol.1, No.2, 29-38,2014）
L-Proline	13wks / Rat	Tada, Y., Yano, N., Takahashi, H., Yuzawa, K., Ando, H., Kubo, Y., Nagasawa, A., Ohashi, N., Ogata, A. & Nakae, D. (2010) Toxicological evaluation of L-proline in a 90-day feeding study with Fischer 344 rats. Regul Toxicol Pharmacol 58: 114-120.
L-Serine	13wks / Rat 13wks / Rat	Kaneko, I., Han, L., Liu, T., Li, J., Zhao, Y., Li, C., Yi, Y., Liang, A. & Hayamizu, K. (2009) A 13-week subchronic oral toxicity study of L-serine in rats. Food Chem Toxicol 47: 2356-2360. Tada, Y., Yano, N., Takahashi, H., Yuzawa, K., Ando, H., Kubo, Y., Nagasawa, A., Chin, K., Kawamata, Y. et al. (2010) A 90-day Feeding Toxicity Study of l-Serine in Male and Female Fischer 344 Rats. J Toxicol Pathol 23: 39-47.
L-Threonine	13wks / Rat	A 13-week feeding toxicity study of L-threonine in rats with a recovery period of 5 weeks Vol.1, No.2, p.49-62 Mami Aoki , Shigeru Ishida , Hideki Fukuzumi , Koji Morishita Released: October 23, 2023 Fundamental Toxicological Sciences
L-Tryptophan	13wks / Rat	Pharmacology. 1991;42(6):349-60. Effect of chronic dietary treatment with L-tryptophan on the development of cold-induced hypertension in rats. Riesselmann A, Baron A, Fregly MJ, Cade JR.
L-Ornithine Monohydrochloride	13wks / Rat	Genotoxicity and subchronic oral toxicity of L-ornithine monohydrochloride. Regul Toxicol Pharmacol. 2013 Dec;67(3):360-71.