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 | Hao Wu, Wenlong Xiao, Keyu Zhang, Feiqun Xue, Chong Zhang, Ming Yan, Xiaoyang Wang, Shanxiang Jiang |
Journal | Regulatory toxicology and pharmacology : RTP
(Regul Toxicol Pharmacol)
Vol. 69
Issue 3
Pg. 487-95
(Aug 2014)
ISSN: 1096-0295 [Electronic] Netherlands |
PMID | 24878239
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
|
Topics |
- Adenine
(adverse effects, analogs & derivatives)
- Administration, Oral
- Animals
- Body Weight
(drug effects)
- Diet
(methods)
- Fatty Liver
(chemically induced)
- Female
- Kidney Tubules
(drug effects)
- Male
- No-Observed-Adverse-Effect Level
- Organ Size
(drug effects)
- Rats
- Rats, Sprague-Dawley
|