title: Acute and sub-chronic toxicity study of diaveridine in Wistar rats.
abstract: Diaveridine, a developed dihydrofolate reductase inhibitor, has been widely used as anticoccidial drug and antibacterial synergist. However, few studies have been performed to investigate its toxicity. To provide detailed toxicity with a wide spectrum of doses for diaveridine, acute and sub-chronic toxicity studies were conducted. Calculated LD50 was 2330 mg/kg b.w. in females and 3100 mg/kg b.w. in males, and chromodacryorrhea was noted in some females before their death. In the sub-chronic study, diaveridine was fed to Wistar rats during 90 days at dietary levels of 0, 23, 230, 1150 and 2000 mg/kg, which were about 0, 2.0-2.3, 21.0-23.5, 115.2-126.9 and 212.4-217.9 mg/kg b.w., respectively. Significant decrease in body weights in both genders at 1150 and 2000 mg/kg groups and significant increases in relative weights of brain in both genders, liver in females, kidneys and testis in males, alkaline phosphatase and potassium in both genders at 2000 mg/kg diet were noted. Significant decrease in absolute weights of several organs, hemoglobin and red blood cell count in both genders, albumin and total protein in females were observed at 2000 mg/kg diet. Fibroblasts in the kidneys, cell swelling of the glomerular zone in the adrenals and inflammation in the liver were found at 2000 mg/kg group. The no-observed-adverse-effect level of diaveridine was 230 mg/kg diet (21.0-23.5 mg/kg b.w./day).
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Shijia
authors.initials: S
authors.lastname: Su
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Sahiwal, Pakistan.
authors.forename: Awais
authors.initials: A
authors.lastname: Ihsan
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Guyue
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China.
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China. Electronic address: wangyulian@mail.hzau.edu.cn.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China. Electronic address: yuan5802@mail.hzau.edu.cn.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests / Q000379:methods; D004032:Diet; D005260:Female; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced; D008099:Liver / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests / Q000379:methods; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011743:Pyrimidines / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011743:Pyrimidines; C033222:diaveridine
keywords: Acute study; Diaminopyrimidines; Diaveridine; Sub-chronic study; Toxicity