title: Acute and subchronic toxicity of arprinocid in Sprague-Dawley rats.
abstract: We subjected Sprague-Dawley rats to an acute and 13-week subchronic oral toxicity of arprinocid, a nucleoside analogue used as a coccidiostat, according to toxicological guidelines as part of its safety assessment. In the acute study, arprinocid was administered once by oral gavage to rats at doses ranging from 292.4 to 506.0mg/kgb.w. The calculated LD50 was 442.9mg/kgb.w. in males and 378.7mg/kgb.w. in females. In the subchronic study, male and female rats were fed with diets supplemented with 0, 25, 187.5 or 500ppm arprinocid for 13weeks. Significantly lower body weights were noted in the 500ppm group females. The mean body weights of the 500ppm group females were 12.9% lower than that of the controls. Significant differences in haematological and biochemical parameters as well as organ weights were detected between the 500 and 187.5ppm groups. Histopathological observations revealed that 500 and 187.5ppm arprinocid could induce hepatic steatosis and focal hepatocellular necrosis. Slight protein cast in some renal tubules and tubular regeneration were observed in the high dose group of both genders. The dietary no-observed-adverse-effect level (NOAEL) of arprinocid in rats for 13weeks is 25ppm (approximately 1.7mg/kgb.w./day).
authors.affiliation: Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, PR China; Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China. Electronic address: z_cole@sina.com.
authors.forename: Keyu
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China.
authors.forename: Feiqun
authors.initials: F
authors.lastname: Xue
authors.affiliation: Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, PR China.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.affiliation: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, PR China. Electronic address: nauvy@sina.com.
authors.forename: Shanxiang
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet / Q000379:methods; D005234:Fatty Liver / Q000139:chemically induced; D005260:Female; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C016245:arprinocid; D000225:Adenine
keywords: Acute; Arprinocid; Rats; Subchronic; Toxicity