| Monensin isolated from the fermentation product of Streptomyces cinnamomi is a representative drug of polyether ionophore antibiotics.It is an ideal anticoccidial drug widely used around the world.The objectives of this study was to investigate 6-month chronic toxicity study of monesin premix in rats.Our results might contribute to the assessment of the quality and safety of fermentation method of monensin.Acute toxicity was examined in Sprague Dawley rats.In a GLP-compliant study,male rats（5 rats per dose）were exposed to a single dose of 167,290,501,867 or 1500 mg/kg bw by gavage and female rats（5 rats per dose）were exposed to a single dose of 33,57,99,173,or 300 mg/kg bw by gavage.All rats were monitored for 7 days.The medial lethal dose(LD50)for male and female rats were 578 mg/kg and 252 mg/kg,respectively.In a GLP-compliant study,5-to 6-week-old male（20 animals per dose groups）were maintained on a diet containing 29,145,or 723 mg monensin/kg and female（20 animals per dose groups）were maintained on a diet containing 13,63,or 315 mg monensin/kg,whereas control rats received a normal diet for 6 months.All the rats were monitored for change in body and organ weight,food consumption,hematology,clinical chemistry and pathology.The results showed that the weight gain,hematology,clinical chemistry and histopathology of the middle-dose group rats were not significantly affected by monensin intake.In summary,we conformed that a NOAEL in diet was 63 mg/kg（equal to 1.86mg/kg·bw per day）for females,while 145 mg/kg in diet（equal to 4.05 mg/kg·bw per day）for males. |
