4-Methyloxazole-5-carbonitrile,90-day oral toxicity study in rats after gavage administration
作者单位：National Beijing Center for Drug Safety Evaluation & ResearchBeijing Institute of Pharmacology and Toxicology
会议名称：《2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛》
会议日期：2013年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
关 键 词：4-methyloxazole-5-carbonitrile toxicity
摘 要：OBJECTIVE To evaluate the toxicity of 4-methyloxazole-5-carbonitrile(cyanomethyloxazol,CMO) in rats. METHODS Four groups of Sprague-Dawley(SD) rats,each consisting of 10 males and 10 females were dosed daily via oral gavage for 90 consecutive *** of ten animals per group per sex remained untreated for 14 d prior to euthanasia to evaluate recovery from *** article was dissolved in propylene glycol for *** dose levels were 0 (propylene glycol for gavage),2,10 and 50 mg·*** were conducted on the rats with respect to general demeanor,clinical signs,mortality,body weights/total body weight gains,food consumption,ophthalmologic changes, urinalysis,hematology,serum chemistry,gross necropsy,absolute and relative organ weights,and histopathology. RESULTS One male of the mid dose group and one male and one female of the high dose group died during the study. Gross pathology findings showed that the death of the mid dose male was the result of a gavaging *** on the necropsy findings(haemorrhage in the lungs),the deaths in the high dose group were considered to be accidental and caused by respiratory *** lethargy was the major clinical sign seen in the high dose group caused by CMO and found in both *** was reversible after cessation of *** clinical signs were seen in the mid and low dose *** ocular finding was attributed to the administration of test article during the *** were no treatment -related differences between the vehicle control group and rats receiving CMO for mean body weight,mean body weight gains and food consumption during the *** relevant findings were seen in haematology,clinical chemistry and *** were no test article-related changes in absolute organ weights,organ weight to body weight ratios, or macroscopic and microscopic *** Based upon the results from this study,the no observed adverse effect level of CMO in rats was established at 10 m