Toxicological evaluation of combination products containing imidacloprid, moxidectin and pyriproxyfen

The purpose of the research is to investigate subacute cutaneous toxicity in rats, allergenic properties in guinea pigs and tolerance of increased doses of drugs based on imidacloprid, moxidectin and pyriproxyfen by dogs and cats of different age groups. Materials and methods . Toxicological studies (subacute cutaneous toxicity, study of allergenic properties) were conducted in the vivarium of the All-Russian Research Institute of Plant Protection, a branch of the Federal Scientific Center for Experimental Veterinary Medicine of the Russian Academy of Sciences, on male rats and guinea pigs. Experiments on the tolerance of drugs by target animal species (dogs, cats) were conducted in the Podolsk department of the All-Russian Research Institute of Plant Protection. The choice of doses, frequency and methods of administration of the studied drugs were determined in accordance with the Guidelines for Experimental (Preclinical) Study of New Pharmacological Substances. All doses were calculated for the drug taking into account the density (1.08 g/cm3). Results and discussion . When studying the acute cutaneous toxicity of the drug on rats, LD50 exceeded the maximum possible dose of 10 000 mg/kg (hazard class 4 according to GOST 12.1.007-76). In a subacute experiment on rats, it was established that doses of 1000 and 500 mg/kg are ineffective (safe), the threshold and toxic doses could not be established. These drugs, when treating animals 8 times with an interval of 3 days in a three- and five-fold increase in the maximum therapeutic dose during the experimental period, did not have a negative effect on the general condition of the animals, their physiological status and behavior; no statistically significant changes in the morphological and biochemical parameters of the blood, physicochemical parameters of urine were noted in animals from the experimental groups compared to the control. However, in one adult dog from the second experimental group, which was used a five-fold increase in the maximum therapeutic dose of the drug, depression was noted on the 20th day of the experiment. The physiological state of the animal returned to normal within 24 hours voluntarily without the use of symptomatic therapy.