title: Safety evaluation of a triazine compound nitromezuril by assessing bacterial reverse mutation, sperm abnormalities, micronucleus and chromosomal aberration.
abstract: Nitromezuril (NZL) is a novel triazine compound that exhibits remarkable anticoccidial activity. However, mutagenicity and genotoxicity of NZL have not been evaluated to date. This study evaluated the potential risks of NZL by testing for bacterial reverse mutation (Ames), mouse sperm abnormality (SA), bone marrow micronucleus (MN) and chromosomal aberration (CA). Mice were orally administered with NZL at 385, 192 and 96 mg/kg, corresponding to 0.5 ×, 0.25 × and 0.125 × the LD50 of NZL, respectively. No significant increases in SA and CA were found in mice treated with NZL for 5d and 3d, respectively (P>0.05). NZL at 96-385 mg/kg did not have significant influence on micronucleated polychromatic erythrocyte counts (P>0.05). These results suggest that NZL is not genotoxic. However, Ames test results were positive both with and without the S9 system for Salmonella typhimurium TA98 and TA100, suggesting that NZL may be mutagenic. The mutagenic effects of NZL were different in in vitro and in vivo assays. Further studies should be conducted to confirm the safety of using and developing NZL as a novel anticoccidial drug.
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
authors: Chenzhong
authors: C
authors: Fei
authors: Chinese Medicine Hospital of Pudong New Area, Shanghai 201200, PR China.
authors: Jie
authors: J
authors: Zhang
authors: Institute of Veterinary Feed Control of Zhengzhou, Henan 450003, PR China.
authors: Yang
authors: Y
authors: Lin
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
authors: Xiaoyang
authors: X
authors: Wang
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
authors: Keyu
authors: K
authors: Zhang
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
authors: Lifang
authors: L
authors: Zhang
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
authors: Wenli
authors: W
authors: Zheng
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
authors: Mi
authors: M
authors: Wang
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
authors: Tao
authors: T
authors: Li
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
authors: Sui
authors: S
authors: Xiao
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China. Electronic address: fqxue@shvri.ac.cn.
authors: Feiqun
authors: F
authors: Xue
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
authors: Chunmei
authors: C
authors: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002869:Chromosome Aberrations / Q000139:chemically induced*; D003049:Coccidiostats / Q000008:administration & dosage / Q000633:toxicity*; D004269:DNA, Bacterial / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D009154:Mutation; D018570:Risk Assessment; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D014227:Triazines / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: C000588635:2-(3-methyl-4-(4-nitrophenoxy)phenyl)-1,2,4-triazine-3,5(2H,4H)-dione; D003049:Coccidiostats; D004269:DNA, Bacterial; D014227:Triazines
keywords: Anticoccidials; Bacterial reverse mutation (Ames); Bone marrow micronucleus; Chromosome aberration; Coccidiosis; Nitromezuril; Sperm abnormalities