Acute and sub-chronic oral toxicological evaluations of quinocetone in Wistar rats

To provide a detailed toxicity with wide spectrum of doses for quinocetone, a new antimicrobial growth promoting agent, acute and sub-chronic toxicological studies were conducted. For acute study, quinocetone was administered singly by oral gavage to Wistar rats and Kunming mice. Calculated LD50 was 8687.31 mg/kg b.w./day in rats and 15848.93 mg/kg b.w./day in mice. In sub-chronic study, quinocetone was fed to Wistar rats at dietary levels of 0, 50, 300 and 1800 mg/kg or olaquindox (300 mg/kg), approximately equivalent to quinocetone 5, 30, 180 or olaquindox 30 mg/kg b.w./day. There was significant decrease in body weight in both genders, total protein and creatinine in females and alkaline phosphatase in males fed with 1800 mg/kg diet, while alkaline aminotransferase values decreased in all treated groups. Significant increase in relative weights of liver and kidneys in both genders and testis in male rats were noted at 1800 mg/kg diet. Histopathological observations revealed that 1800 mg/kg quinocetone diet and 300 mg/kg olaquindox diet could induce proliferation of bile canaliculi in the portal area. In conclusion, quinocetone can induce hepatic histological changes as well as leaking of different serum enzymes. The no-observed-adverse-effect level of quinocetone was considered to be 300 mg/kg diet. (C) 2010 Elsevier Inc. All rights reserved.