title: Acute and sub-acute oral toxicological evaluations and mutagenicity of N-carbamylglutamate (NCG).
abstract: N-carbamylglutamate (NCG) is a metabolically stable analog of N-acetylglutamate that activates carbamyl phosphate synthase-1, a key arginine synthesis enzyme in enterocytes. It is a promising feed additive in swine in China. In this study, we assessed the acute and sub-acute toxicity of NCG in Sprague-Dawley (SD) rats. All rats survived until they were killed at a scheduled time point. No adverse effects or mortality was observed following acute oral administration of 5000 mg/kg NCG to SD rats. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, a functional observational battery, organ weights, histopathology, ophthalmology, hematology, coagulation, and clinical chemistry parameters in any of the treatment groups in sub-acute doses of NCG at target concentrations corresponding to 500, 2000, and 3000 mg/kg/day for 28 days neither. In addition, no evidence of mutagenicity or genotoxicity was found, either in vitro in bacterial reverse mutation assay or in vivo in mice bone marrow micronucleus assay and sperm shape abnormality assay. On the basis of our findings, we conclude that NCG is a non-toxic substance with no genotoxicity.
authors.affiliation: Observation and Experiment Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China; State Key Laboratory of Food Science and Technology and College of Life Science and Food Engineering, Nanchang University, Nanchang 330031, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Observation and Experiment Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China. Electronic address: w.dan@isa.ac.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Wan
authors.affiliation: Observation and Experiment Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Xie
authors.affiliation: Observation and Experiment Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Li
authors.affiliation: Observation and Experiment Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China.
authors.forename: Ruilin
authors.initials: R
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Food Science and Technology and College of Life Science and Food Engineering, Nanchang University, Nanchang 330031, China; Guangzhou Tanke BIO-TECH Co. Ltd., Guangzhou 510800, China.
authors.forename: Xugang
authors.initials: X
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Food Science and Technology and College of Life Science and Food Engineering, Nanchang University, Nanchang 330031, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: State Key Laboratory of Food Science and Technology and College of Life Science and Food Engineering, Nanchang University, Nanchang 330031, China.
authors.forename: Zeyuan
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Observation and Experiment Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China; State Key Laboratory of Food Science and Technology and College of Life Science and Food Engineering, Nanchang University, Nanchang 330031, China. Electronic address: yinyulong@isa.ac.cn.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002681:China; D004435:Eating; D005260:Female; D005971:Glutamates / Q000009:adverse effects*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000009:adverse effects*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
chemical_list: D005971:Glutamates; D009153:Mutagens; C006895:N-carbamylglutamate
keywords: Acute/subacute toxicity; Mutagenicity; N-carbamylglutamate; Toxicology