Cumulative effect and subchronic toxicity of the supramolecular complex of fenbendazole

Abstract

The purpose of the research is to study the cumulative effect and subchronic toxicity of supramolecular complex of fenbendazole (SMCF).Materials and methods. The cumulative effect of SMCF was studied on 20 outbred white rats weighing 180 g that were divided into experimental and control groups of 10 animals each. SMCF was administered intragastrically to rats of the experimental groups for 24 days at the dose of 2000 mg/kg (1/10 of the previously established single LD50 (20000 mg/kg)) on the first day, then the dose was increased by 1.5 times every four day. The main criterion for evaluation of the results was the death of animals; we also observed the overall condition and behavior of rats. Subchronic toxicity was studied on 40 male white rats weighing 220–240 g. The animals were divided into 4 equal groups. The drug was administered daily to rats of the 1st, 2nd and 3rd experimental groups intragastrically using the doses of 1/5 (4000 mg/kg), 1/10 (2000 mg/ kg) and 1/20 (1000 mg/kg) of LD50 (20000 mg/kg) respectively for 7 days. The control group received 1% starch paste in an appropriate volume throughout the experiment. During the experiment, we observed physical signs and behavior of animals, food and water consumption; weight gains of animals on the 1st, 3rd, 5th and 7th days of the experiment. After the drug administration, animals were sacrificed by cervical dislocation. The laboratory examinations for hematological parameters and biochemical parameters were performed after treatment. Samples of organs (liver, heart, lungs, kidneys, spleen) were taken during necropsy to calculate mass coefficients and to make macroscopic examinations.Results and discussion. We found that the SMCF did not have any cumulative properties. The overall condition and behavior of rats was within the physiological range; animals consumed food and water and showed no signs of intoxication after oral administration of SMCF at doses of 1/5, 1/10 and 1/20 of LD50 for 7 days. The drug did not have influence on weight gains of animals. Hematological and biochemical parameters did not undergo significant changes and were comparable with the parameters of the control group. The mass coefficients of the internal organs did not differ statistically in experimental and control groups of rats.