Acute and chronic toxicity of an antifungal agent based on 1,2,4-triazole

In the course of experimental studies, it was determined that the investigated antifungal agent for local application, with thiophene derivative of 1,2,4-triazole as the active ingredient and pumpkin and lavender oils as the base, is low in toxicity. The DL50 of the drug upon single dermal application is higher than 2000 mg/kg (Category 5), and for intragastric administration, it is above 5000 mg/kg (Class IV toxicity, “low-toxicity substances”). It was found that during the acute toxicity studies, “Fungimazole” did not cause any mortality in animals or any clinical signs of intoxication. Observations of the test animals showed that they had a satisfactory appetite, were active and mobile, and their behavioral and reflex responses were preserved. A transient suppression of the central nervous system state was noted in the animals at the highest applied dose of the investigated agent, but it was short-lived and recoverable. With prolonged (28-day) dermal application of the “Fungimazole” liniment at a therapeutic dose, no reactions were noted in the laboratory animals, particularly in the skin. The local and post-resorptive effects of the investigated agent at multiple (5 and 10 times) therapeutic doses were characterized by specific shifts in the homeostasis system of the animals. In the absence of characteristic changes in the hematopoietic system, signs indicating a depressed liver functional state were observed. In laboratory rats, the weight coefficients of the liver, spleen, and heart increased under these conditions. The number of platelets and lymphocytes in the blood also rose. The creatinine level in the blood serum and AsAT, AlAT, AP, and LDH activity were higher than the control values. Further studies showed that just 5–7 days after the last liniment application on the skin, the functional state of the experimental animals fully recovered and was similar to that before the experiment.