| Abstrakt: |
The toxicology of monensin has been studied in several laboratory animal species. There was considerable species variation in acute oral LD50values. The consistent signs of acute toxicity were: anorexia, hypoactivity, skeletal muscle weakness, ataxia, diarrhea, decreased weight gain and delayed deaths. The 3-mo study in rats fed diets containing 0, 50, 150 or 500 ppm monensin resulted in no effects at the lowest dose level, slight reduction of body weight gain in the middle-dose group and severe depression in body weight gain, skeletal and cardiac lesions, and deaths in the highest dose group. The 3-mo study in dogs given daily oral doses of 0, 5, 15 or 50 mg/kg monensin resulted in no effects at the lowest dose level. Dogs in the 15 and 50 mg/kg groups developed, during test wk 1 to 4, anorexia, weakness, ataxia, labored respiration, body weight loss, increased serum muscle enzyme values, severe skeletal muscle degeneration and necrosis with less severe heart lesions and deaths. Mice fed diets containing 0, 37.5, 75, 150 or 300 ppm monensin for 3 mo had reduced body weight gain in all test groups but no other physical signs. Serum creatine phosphokinase (CPK) values were increased in mice in the two highest dose groups and minimal heart lesions were found in the highest dose group. Dogs given daily oral doses of 0, 1.25, 2.5, 5 or 7.5 mg/kg monensin for 1 yr survived with no evidence of toxicity in the two lowest dose groups. Dogs in the two highest dose groups had transient signs of anorexia, hypoactivity, and increased alanine transaminase (SGPT) and CPK values. There was a decrease in body weight in the highest dose group but no pathologic lesions. Four generations of rats were continuously maintained on diets containing 0, 33, 50 or 80 ppm monensin. Except for a decrease in body weight gain, there were no compound-related effects on reproduction and no teratogenic effects. Groups of rats were fed diets containing 0, 33, 50 or 80 ppm monensin for 2 yr with no increase in chronic lesions or neoplasms. The primary target organs affected by toxic doses of monensin were skeletal and cardiac muscles. |
