Subacute Inhalation Toxicity of Ivermectin to Rats

  Objective To study the subacute inhalation toxicity of ivermectin to rats and find the maximum non-effect dose.

  Method SPF-grade Sprague-Dawley (SD) rats, a total of 72 rats, were randomly divided into 6 groups, each with 12 rats, half male and female. Set up three dose groups of 190, 380, 750 mg/m3 and a solvent control group (0.03% Tween-80 solution), and set up a blank control and an additional group (750 mg/m3). The animals in the additional group were exposed to the poison by inhalation, once a day, for 4 hours, 5 days a week, until 28 days, and the additional group animals continued to observe for 14 days after stopping the poisoning. After the experiment, the animals were tested for blood routine, biochemistry, body weight and organ coefficients, and histopathological examination was performed.

  Results Female and male rats in the 750 mg/m3 dose group showed toxic reactions such as fluffy coat, sluggishness, salivation, and tremor in the late stage of exposure. In the 750 mg/m3 dose group, the food utilization rate of female rats decreased, the serum alanine aminotransferase (ALT) level increased (P<0.01), the liver organ coefficient (visceral body ratio) increased (P <0.05), and pathology Histological examination revealed that some rats hepatocytes were turbid and swollen; the weight of male rats in the 750 mg/m3 dose group decreased in the 4th week, serum urea nitrogen (BUN) and ALT levels increased (P <0.01), total cholesterol ( CHOL) level decreased (P <0.05).

  Conclusion The maximum non-effect dose of ivermectin in the subacute inhalation toxicity test for rats is 380 mg/m3 (4 h/d) for both female and male.