title: Toxicological evaluation of ferrous N-carbamylglycinate chelate: Acute, Sub-acute toxicity and mutagenicity.
abstract: Iron is an essential trace element that is vital important in various biological process. A deficiency in iron could induce public health problem e.g. anaemia, while an overload could induce ROS production, lipid peroxidation and DNA bases modifications. In the present study, a new iron fortifier was synthesized, and its acute/sub-acute toxicity was investigated. According to the improved Karber's method, the median lethal dose (LD50) of the ferrous N-carbamylglycinate in SD rat was 3.02 g/kg and the 95% confidence intervals were between 2.78 and 3.31 g/kg. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, organ weights, histopathology, ophthalmology, hematology, and clinical chemistry parameters in any of the treatment groups of ferrous N-carbamylglycinate at target concentrations corresponding to 150, 300, and 600 mg/kg/day for 28 days. The no observed adverse effect level (NOAEL) for ferrous N-carbamylglycinate was at least 600 mg/kg b.w. day in rats. In addition, no evidence of mutagenicity 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 ferrous N-carbamylglycinate is a low-toxic substance with no genotoxicity.
authors.affiliation: 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: Dan
authors.initials: D
authors.lastname: Wan
authors.affiliation: 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: Xihong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 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: College of Chemistry and Chemical Engineering, Zhongkai University of Agriculture and Engineering, Guangzhou, 510225, China.
authors.forename: Xugang
authors.initials: X
authors.lastname: Shu
authors.affiliation: 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: wu-xin@foxmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: 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: yinyulong@isa.ac.cn.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005296:Ferrous Compounds / Q000633:toxicity*; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D023382:Toxicity Tests, Acute / Q000379:methods*; D059551:Toxicity Tests, Subacute / Q000379:methods*
chemical_list: D005296:Ferrous Compounds
keywords: Acute toxicity; Ferrous N-carbamylglycinate; Iron amino acid chelates; Mutagenicity; Sub-acute toxicity