Safety assessment of aditoprim acute, subchronic toxicity and mutagenicity studies

• DOI: 10.1002/jat.3107
• Publication Date: 2015-02-07T05:41:30Z
• Authors: Xu Wang; Ziqiang Tan; Yuanhu Pan; Awais Ihsan; Qianying Liu; Lingli Huang; Guyue Cheng; Dongmei Chen; Yanfei Tao; Zhenli Liu; Zonghui Yuan
• Keywords: Male; No-Observed-Adverse-Effect Level; 0303 health sciences; Micronucleus Tests; Dose-Response Relationship, Drug; Mutagenicity Tests; Body Weight; Toxicity Tests, Subchronic; CHO Cells; Organ Size; Kidney; Risk Assessment; 3. Good health; Diet; Rats; Mice; 03 medical and health sciences; Cricetulus; Liver; Toxicity Tests, Acute; Animals; Female; Rats, Wistar

Aditoprim (ADP), a new developed dihydrofolate reductase (DHFR) inhibitor, has great potential in clinical veterinary medicine because of its greater pharmacokinetic properties than structural analogs. Preclinical toxicology studies were performed to assess the safety ADP including an acute oral toxicity test, subchronic test and five mutagenicity tests. In was administered singly by gavage Wistar rats Kunming mice. The LD50 calculated 1400 mg kg(-1) body weight (BW) day(-1) 1130 BW study, at dose levels 0, 20, 100 1000 diet for 90 days. Significant decreases observed on food efficiency high-dose group. Treatment-related changes serum biochemistry found medium- groups. increases relative weights livers kidneys females testis males diet, significant decrease noted. Histopathological observations revealed that could induce lymphocytic infiltration hepatocytic necrosis near hepatic portal area. genotoxicity negative tests, such as bacterial reverse mutation assay, mice bone marrow erythrocyte micronucleus vitro chromosomal aberration cho/hgprt mammalian cell mutagenesis assay testicle cells chromosome aberration. Based no-observed-adverse-effect level 20 which is about 1.44-1.53 rats.