To determine toxicodynamics we have to pay attention to clinical signs of animal poisoning with esfenvalerate and also morphological, biochemical, immunological blood parameters, pathological anatomical changes in the internal organs and tissues of rabbits that died as a result of experimental poisoning.When determining toxicokinetics, the main attention is paid to the accumulation of pyrethroids after they enter the body, their distribution in internal organs and tissues, its decomposition and how it leaves the body. To determine these parameters, we have used the internal organs and tissues of experimental rabbits that died as a result of poisoning with esfenvalerate. Determination of pyrethroid residues in organs and tissues was carried out using special chemotoxicological analyzes, that is, by the method of liquid gas chromatography [1].

To determine the toxicodynamics of esfenvalerate in rabbits at the Sukhrobjon Agro Gold farm, Ishtikhon district, Samarkand region, 20 heads of 6-7-month-old rabbits weighing 2.8-3.0 kg were used. The rabbits in this experiment were divided into three groups. Five rabbit heads in the first experimental group were orally administered at a dose of 196 mg / kg (LD₁₆) of a single oral effervescent drug. The second group of 10 rabbits was injected with the same amount of pyrethroid. The third group of rabbits constituted the control group.In rabbits received esfenvalerate pyrethroid, clinical signs of intoxication were mainly manifested first by agitation and then weakness, salivation, diarrhea, tremors in the muscles of the body and shortness of breath. Then there was a decrease in body temperature, impaired coordination of movements and paralysis. 1 rabbit in experiment died within the first 48 hours.Clinical recovery of the poisoned rabbits began after 8-14 days. Conclusion by the symptoms of such poisoning observed in rabbits, it can be concluded that esfenvalerate is a neurotropic poison with a sudden effect.

The hematological parameters of rabbits treated with esfenvalerate in the amount of LD₁₆ are shown in (Table 1).  The results of this table show that the number of erythrocytes in the blood of rabbits poisoned with experimental esfenvalerate with LD₁₆ increased by 20-28% (P?0,05), leukocytes by 11-14% (P?0,05) and hemoglobin by 16% (P?0,05) Decreased. He also showed that the activity of acetylcholinesterase in the blood decreased by 13-37% (P ? 0.05) compared with the initial values due to the action of pyrethroid. The activity of the enzymes AST and ALT increased by 1,7–2,7 (P?0,05) and 1,6–2,3 (P?0,05), respectively.

Table 1: Blood test of rabbits taking esfenvalerate eat a dose of 196 mg / kg (LD₁₆) (X ± Sx.).

It can be seen from this table that in rabbits receiving esfenvalerate at a dose of 196 mg / kg (LD₁₆), the number of erythrocytes in the blood 3 days after administration of the drug increased by 18% compared with the initial level, by 26% on days 7 and 21. Showed a decrease of 16%. From 7 to 14 days of the experiment, the number of leukocytes decreased from 15 to 12% compared with the initial values. If we take the amount of hemoglobin in the blood relative to the initial values, then on the 7th day of the experiment there was a decrease by 16%, and on the 21st day of the experiment it was close to the initial values. The activity of the enzyme acetylcholinesterase decreased by 37% on the 3rd day of the experiment, by 27% on the 7th day, by 13% on the 14th day and by 5% on the 21st day of the experiment. The activity of  AST and ALT from day 3 of the experiment to the last 21 days increased by 0.41-0.56 and 0.54-0.92 times, respectively, compared with the initial values. We think that this figure in them is probably due to the fact that these drugs are reabsorbed into the bloodstream without being degraded in the liver in the body. Analysis of the experimental results showed that rabbits poisoned with esfenvalerate showed symptoms characteristic of neurotropic effects in the body (agitation, weakness, tremor, slight paralysis of the legs). When determining the toxicodynamics of pyrethroid esfenvalerate poisoning, we needed to study its effect on the activity of the immune system, which is the main protector of the body. According to many authors, the study of the activity of the immune system of animals serves as the basis for determining the causes of various diseases occurring in the body [2]. Research data are presented in (Table 2).In the immunological parameters of the blood of rabbits (the number of LD ₅₀) in experiments with esfenvalerate poisoning, the relative values ??of mainly T-lymphocytes decreased by 11% on the 7th day, 20% on the 14th day, and 7% on the 21st day. The absolute T-lymphocyte count also decreased by 27% on day 7, 24% on day 14, and 15% on day 21 from baseline. We observed that the relative values ??of similar B-lymphocytes increased by 40% on day 7, 46% on day 14 and 25% on day 21 compared to the state before the experiment. We also observed that the absolute values ??of  B-lymphocytes increased by 31% on the 7th day and by 35% on the 14th day of a similar experiment and were close to the initial norm by the 21st day of the experiment.

Table 2: Immunological blood of rabbits poisoned by esfenvalerate indicators (LD₁₆ -196 ??/??) (?±S_?).

Phagocytic activity of neutrophils on the 7th day of the experiment decreased by 43%, on the 14th day - by 49%, on the 21st day - by 30%. Accordingly, these signs indicate that the amount of esfenvalerate in the amount of LD¹⁶ when administered once orally to rabbits has an adverse effect on the body's immune system. In general, the data from the study of the effect of esfenvalerate on the immune system of experimental rabbits show that the relative values ??of T-lymphocytes in the peripheral blood of rabbits decreased by 20% compared with the initial state, and the absolute values ??by 27%. Also, the relative values ??of B-lymphocytes increased by 140% compared to the baseline, and the absolute values ??increased by 135%. Phagocytic activity of neutrophils decreased by almost 2 times (P ?0.05) due to the effect of pyrethroid.

These data from research experiments indicate that esfenvalerate pyrethroid can cause weakness in rabbits due to its significant adverse effects on the immune system[3,4]. When determining the toxicodynamic properties of pyrethroid esfenvalerate in the body, it is also necessary to pay attention to pathological changes in the internal organs and tissues of animals that died as a result of poisoning with this drug. Therefore, as a result of our experiments, the bodies of rabbits that died as a result of poisoning were opened, and changes in their internal organs were revealed. The main changes: congestive hyperemia, bleeding and catarrhal hemorrhagic inflammation were observed in the brain, lungs and spleen, as well as on the mucous membranes of the small intestine. In the parenchymal organs, protein dystrophy and albiloid dystrophy were observed. Inflammation was particularly observed when mucus and intestinal nutrients were mixed with mucous and bloody exudates. Histological specimens were taken from the indicated organs. We stained the incisions with hemotoxylin-eosin dyes and revealed the following changes. In the kidney, congestive hyperemia of the capillary vessels between the tubules was found. The liver was filled with blood and increased in size, and the kidneys and heart were in a flabby condition. Accordingly, when evaluating the toxic effect of esfenvalerate, it was shown that this drug has the property of significantly negatively affecting the body of rabbits. It has been shown that the basis for the occurrence of cases of pyrethroid poisoning in animals arises from non-compliance with the rules established by law for the practical use of these drugs.The main side effects of pyrethroids on the animal body: neurotoxic, hepatotoxic, membranotoxic, anticholesterol and anti-immune effects, and, finally, that it has a mechanism of sudden toxicity to the body.

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