Wu Hao, Xiao Wenlong, Zhang Keyu, Xue Feiqun, Zhang Chong, Yan Ming, Wang Xiaoyang, Jiang Shanxiang
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.
Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China.
Regul Toxicol Pharmacol. 2014 Aug;69(3):487-95. doi: 10.1016/j.yrtph.2014.05.017. Epub 2014 May 27.
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).
作为安全性评估的一部分，我们按照毒理学指南，对作为抗球虫药使用的核苷类似物阿普立西进行了急性和为期13周的亚慢性经口毒性试验，受试动物为Sprague-Dawley大鼠。在急性研究中，通过灌胃法一次性给予大鼠阿普立西，剂量范围为292.4至506.0mg/kg体重。计算得出雄性大鼠的半数致死量（LD50）为442.9mg/kg体重，雌性大鼠为378.7mg/kg体重。在亚慢性研究中，雄性和雌性大鼠连续13周喂食添加了0、25、187.5或500ppm阿普立西的饲料。在500ppm组的雌性大鼠中观察到体重显著降低。500ppm组雌性大鼠的平均体重比对照组低12.9%。在500ppm组和187.5ppm组之间检测到血液学和生化参数以及器官重量存在显著差异。组织病理学观察显示，500ppm和187.5ppm的阿普立西可诱导肝脂肪变性和局灶性肝细胞坏死。在两个性别的高剂量组中均观察到一些肾小管中有轻微的蛋白管型和肾小管再生。大鼠经口摄入阿普立西13周的无观察到有害作用水平（NOAEL）为25ppm（约1.7mg/kg体重/天）。
