动物造模 z-bio 2022-02-09 276

　　Objective To study the subacute inhalation toxicity of ivermectin original drug to rats and find out the maximum ineffective dose.

　　Methods A total of 72 SPF grade Sprague-Dawley (SD) rats were used and randomly divided into 6 groups with 12 rats in each group, half male and half male. Three dose groups of 190, 380, and 750 mg/m3 and one solvent control group (0.03% Tween-80 solution) were set, and one blank control and one additional group (750 mg/m3) were set. Active (oral-nose) inhalation was used for exposure once a day for 4 hours, 5 days a week until 28 days, and the animals in the additional group were kept under observation for 14 days after the exposure was stopped. After the experiment, the blood routine, biochemistry, body weight and organ coefficient of the animals were measured, and the histopathological examination was stopped.

　　Results The male and female rats in the 750 mg/m3 dose group exhibited toxic reactions such as loose coat, stagnation, salivation and tremor in the late stage of exposure. In the 750 mg/m3 dose group, the food application rate decreased, the serum alanine aminotransferase (ALT) level increased (P < 0.01), the liver organ coefficient (visceral body ratio) increased (P < 0.05), and the pathological Histological examination found that the local rat hepatocytes were cloudy and swollen; the body weight of male rats in the 750 mg/m3 dose group decreased, the serum urea nitrogen (BUN) and ALT levels increased (P < 0.01), and the total cholesterol ( CHOL) level decreased (P < 0.05).

　　Conclusion The maximum no-effect dose of ivermectin original drug to rats in subacute inhalation toxicity test was 380 mg/m3 (4 h/d) for both males and females.