RESUMO
Objective To evaluate the repeated dose toxicity of MNT-016 in SD rats and to provide reference for toxicity evaluation.Methods MNT-016 was administered to rats at 5, 20 and 80 mg/kg for 90 days.The toxic effects on the animals were evaluated by observing the clinical signs and measuring the body weight, hematology and blood biochemistry as well as histopathological examination.NOAEL and benchmark dose lower confidence limit(BMDL) were observed by the end point of toxicity.Results Compared with the control group, the AST, TBIL, DBIL and Crea of male rats were increased in a dose-dependent manner, while TG and CHOL decreased.The body mass(before anatomy), heart, liver, thymus, epididymis of male rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of the heart and lung was increased.The body mass (before anatomy) and thymus of female rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of lungs was increased.Vacuolation of hepatocytes was observed in groups each dose, tubule atrophy was found in the kidneys of 20 and 5 mg/kg groups, and tubule basophilia was observed in 80 mg/kg group.The incidence of the above lesions was higher in male animals than in female ones.Conclusion The NOAEL of MNT-016 is lower than 5 mg/kg in male rats and 5 mg/kg in female rats.BMDL value is 2.65 mg/kg in male animals and more accurate than NOAEL, and is 9.04 mg/kg in female animals,which is slightly larger than the corresponding NOAEL.
RESUMO
Objective To observe toxic symptoms and signs , toxic damage extents and reversibility in rats after oral administration of Tangwang Mingmu granules .Methods Four dose groups with 40 rats in each group were designed in this study, including control group fed with distilled water and three groups at different dosages of the test drug .Tangwang Mingmu granules were orally administered to SD rats at the dosage of 8.4, 4.2 and 2.1 g/kg for 3 weeks and 14.0, 8.4 and 4.2 g/kg for 23 weeks, for 26 consecutive weeks .The general state of the rats was observed every day , while body mass and food consumption were calculated once a week .Halfway through and at the end of the administration (13 and 26 weeks) and after four weeks of recovery, parameters of body mass, hematology, hematological biochemistry, organ/body mass ratio and histopathology were measured .Results Compared with the control group at the same time-point, body mass of male rats in the other three groups was slightly reduced .Food consumption in high and medium dose groups was reduced (P<0.05), MCHC, ALT, TBIL and Na +in high dose group were decreased (P<0.05), TP, ALB and D-BIL were increased (P<0.05), the mean body mass and relative organ weight of thymus in medium dose male rats were decreased (P<0.05), relative organ weight of the liver and kidney in high dose male rats was increased (P<0.05), and focal chronic inflammation to different extent was observed in the liver , kidney and prostate gland .No dose-effect relationship was found in these perturbations that were all within the normal range of animals .No significant drug-related pathological changes were found.Conclusion The NOAEL of Tangwang Mingmu granules is considered to be 14.0 g/kg body mass/day (equal to 50 times the proposed clinical adult dosage ) for the 26-week repeated dose oral toxicity study in male andfemale rats.