ACUTE AND SUBACUTE TOXICITY OF SPRAY BASED ON CHLORTETRACYCLINE HYDROCHLORIDE

Aerosolized products based on tetracycline antibiotics are used in veterinary medicine to treat wounds, skin irritations, eczema, as well as hoof rot, skin diseases caused by microorganisms susceptible to tetracycline antibiotics. The study to determine the acute dermal toxicity of the spray was conducted in accordance with the requirements of OECD No. 402 (Acute Dermal Toxicity: Fixed Dose Procedure (October 9, 2017). For the experiment, healthy, young animals with intact skin, body weight 200-220 g were used. After application of the drug, the laboratory animals were monitored for 14 days. The following indicators were taken into account: appearance, behavior, coat condition, application site, visible mucous membranes, attitude to feed, rhythm, respiratory rate, time of onset and nature of intoxication, its severity and course. The study of dermal toxicity of the drug during prolonged use was performed in accordance with OECD No. 410 (Repeated Dose Dermal Toxicity: 21/28-day Study). For the experiment, healthy, young animals with intact skin, body weight 200-220 g were used. The day before the application of the test product, hair was removed from the dorsal surface (at least 10% of the total body surface area). Repeated hair removal was performed weekly. The study product was applied as evenly as possible to the prepared dorsal skin surface (i.e., at least 10% of the total body surface area). The study product was kept in contact with the skin with a porous gauze bandage and non-irritating tape, daily for 6 hours. The drug was applied to the skin daily for 28 days. At the end of the exposure period, the test product was removed, where possible, using water or a suitable solvent. For this purpose, 4 groups of animals were formed on the principle of analogs, 6 rats in each group. Water was applied to the previously prepared skin area of the control group. Animals of the first experimental group were treated with Cyclo Spray at a therapeutic dose of 0.4 ml per animal, animals of the second experimental group - 5 times the therapeutic dose - 2.0 ml per animal, and animals of the third experimental group - 10 times the therapeutic dose - 4.0 ml per animal. The next day after the end of the drug application, laboratory animals under light ether anesthesia were decapitated and blood samples were taken for further research in the laboratory of clinical and biological research of the State Research Institute of Veterinary Drugs and Feed Additives, while determining the coefficients of organ mass of white rats compared to the control group. The studies established that a single dermal application of the aerosol did not cause animal death, toxicity, or redness at the site of application, so according to the GHS, the test product belongs to category 5 (class 5, not classified). Prolonged topical application of the drug in high doses caused a decrease in protein synthesizing function of the liver, impaired renal function (decreased levels of urea and creatinine in the blood of animals) and liver (increased levels of ALT and ALP in the blood of animals).