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Introduction. The study of the effects of the long-term effect of the active substances of pesticides on the body of warm-blooded animals is an obligatory stage of their comprehensive toxicological and hygienic assessment. The aim of the study was to establish the levels of inactive doses of the effects of the long-term (NOEL) action of a compound of the oxatiine class. Materials and methods. In accordance with the planned purpose of the study in the biological testing laboratory of the Federal Scientific Center of Hygiene named after F.F. Erisman of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing еxperiments were conducted to establish the parameters of acute oral toxicity, the presence of possible teratogenic and embryotoxic effects, and the effect on the reproductive function of a technical product of the oxatiin class (TPO) on the body of warm-blooded (rats). Previously, studies in this volume have not been conducted. Results. LD50 of the studied compound with a single oral administration to male rats is more than 4500 mg/kg of body weight. When studying the embryotoxic effect, the inactive dose for the maternal organism and offspring is set at the level of – 1/52 LD50; the inactive dose for the teratogenic effect for the maternal organism is 1/52 LD50, offspring – 1/27 LD50. As a result of studying the effect of the oxatiine derivative on the indicators of reproductive function, the inactive dose for maternal, paternal organisms, and offspring, is 1/313 LD50. Limitations. In our study to establish the levels of inactive doses of the long-term effects of toxicity of a technical product derived from oxatiines, there are no data on the results of the mutagenic effect of the studied compound on the body of warm-blooded (rats, mice). Conclusion. It has been established that according to the “Hygienic classification of pesticides and agrochemicals according to the degree of danger” (Methodological Recommendations of MP No. 1.2.0235-21* dated 02/15/2022), the studied chemical product belongs to the 4th hazard class for acute oral toxicity (LD50) and teratogenic effect (low-hazard compound; for embryotoxic effect and reproductive toxicity to the 3rd hazard class (moderately dangerous compound).

Introduction. The study of the remote effects (embryotoxicity, teratogenicity and reproductive toxicity) of new technical products on the mammalian body is the scientific basis for the safe use of pesticides. The purpose of the study is to study the effect of a new technical product of the benzoyl urea class on the development of remote effects in warm-blooded animals (rats). Material and methods. The evaluation of embryotoxic and teratogenic effects was carried out on laboratory animals (rats, males and females). Doses were studied: 0, 1/5000, 1/2500 and 1/1250 LD50. Each group of females consisted of 15 animals with a body weight of 230-240 g at the beginning of the study. The technical product was administered orally to female rats daily during 6-20 days of pregnancy. Fertilization of females with intact males was carried out in a ratio of 2 : 1. Reproductive toxicity was studied on two generations of rats (males; 10 individuals per group and females; 20 individuals per group) at doses of 0, 1/5000, 1/2500 and 1/624 LD50. Results. Embryotoxic and teratogenic effects were not detected, significant changes in reproductive toxicity were established at the maximum dose (for parents and offspring). Limitations. In study, there are no data on the study of organ tissues, nor have the processes of cell damage as a result of exposure to a new technical product derived from the benzoyl urea class been studied. Conclusion. The conducted studies have confirmed that the studied product of the benzoyl urea class belongs to low-risk compounds in terms of embryotoxicity and teratogenicity; moderately dangerous in terms of its effect on the reproductive function of warm-blooded (rats).

Introduction. Entering the body in various ways, pesticides, being biologically highly active compounds, can pose a real danger to public health, causing changes in non-specific biochemical reactions of metabolism occurring in all living cells. The antioxidant system, represented as a balance of lipid peroxidation and antioxidant protection (POL - AOZ), is one of the metabolic regulatory mechanisms of these responses. The aim of the study was to study the effect of a technical product (TP), a derivative of triazoles, on the acti-vity of antioxidant enzymes in the rat body, under its repeated oral intake in a chronic 12-month experiment. Material and methods. A chronic (12 months) experiment was performed on male rats with a bodyweight of 200-210 g at the beginning of the study. Tested doses: 5.0, 16.0 and 55.0 mg/kg of body weight (1 control and 3 experimental groups, 20 individuals each). In the dynamics of the experiment, after 1, 3, 6 and 12 months, the state and behavior of animals, water and food consumption were observed. Changes in the enzymatic indices of the body’s antioxidant defense system (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) were registered. Results. It was found that TP at a dose of 5.0 mg/kg of body weight does not cause significant changes in the activity of antioxidant enzymes, doses of 16.0 and 55.0 mg/kg of body weight cause an increase in the activity of superoxide dismutase (SOD) and a decrease in the activity of catalase in the body of experimental animals compared to control animals. Discussion. In the conducted chronic experiment, it was found that the studied TP at a dose of 5.0 mg/kg of body weight does not cause significant changes in the activity of the studied antioxidant enzymes in the body of rats. The introduction of TP at doses of 16.0 and 55.0 mg/kg of body weight causes a significant change in the activity of such antioxidant enzymes as SOD and catalase. Our results are consistent with the literature data, according to which the cell quickly reacts to oxidative stress by increasing the activity of SOD, and SOD is considered even as a stress protein synthesized in response to oxidative stress. Conclusions. The conducted research shows the feasibility of studying antioxidant enzymes’ activity in the mammalian body in sanitary and toxicological studies to increase the reliability of the developed hygienic standards of xenobiotics in environmental objects and food products.

Introduction. Historically, pesticides are evaluated more strictly from a medical point of view than other chemicals. Since their features, such as deliberate introduction into the environment, the possibility of contact with them by large masses of the population, and the high biological activity determine their potential danger to humans. Purpose of research - study of the biological effect of a technical product derived from triazoles when it is repeatedly ingested orally in mammals (rats), establishment of inactive and active doses, justification of the permissible daily dose (DSD) for humans. Material and methods. In acute experiments, white rats were used, including 6 animals in the group. Tested dose: 500-4000 mg/kg of body weight. A chronic (12 months) experiment was performed on 80 male rats with a bodyweight of 180-190 g at the beginning of the study. Tested doses: 5.0; 16.0 and 55.0 mg/kg of body weight (1 control and 3 experimental animals, 20 individuals each). In the dynamics of the experiment, we observed the condition and behavior of animals, water, and food consumption, recorded the timing of death, changes in body weight, physiological, biochemical, and hematological indices. Results. Indices of the acute oral toxicity on the studied product LD50 male rats were 2250 ± 483 mg/kg body weight. The dose of 5.0 mg / kg of body weight was not found to cause significant changes in all studied indices. The doses of 16.0 and 55.0 mg/kg of body weight had a polytropic effect on the body in experimental animals. Discussion. The studied product for the acute oral toxicity refers to low-hazard compounds, the doses of 16.0 and 55.0 mg/kg of body weight has a polytropic effect on the mammalian body, causing changes in carbohydrate, lipid, and lipoprotein metabolism in the body of rats - was accepted as acting. The dose of 5.0 mg / kg of body weight, when administered in rats, there are no changes in all the studied parameters throughout the experiment, is accepted as invalid. Based on the inactive dose-5.0 mg/kg of body weight and taking into account the reserve factor of 100, we have scientifically justified DSD for a person at the level of 0.05 mg/kg. Summary. The conducted sanitary and Toxicological studies indicate the need to assess the toxicity of new technical products to the mammalian body, to increase the reliability of the developed hygiene standards in environmental objects and food products.

Introduction. Currently, many xenobiotics are widely used in industry and agriculture, which can cause serious disorders of pregnancy and fetal development. In this regard, the study of the effect of pesticides on embryogenesis in experiments on laboratory animals is a mandatory stage of sanitary and Toxicological research. The aim of the study was to investigate the long-term effects of a compound of the class of benzothiadiazinones for the assessment of embryotoxic and teratogenic effects, as well as reproductive toxicity by the method of two generations, with repeated oral intake of it into the body of warm-blooded animals (rats), establishing the levels of inactive doses for parents and offspring, and determining the hazard class. Material and methods. The embryotoxic and teratogenic effects were evaluated in female and male rats with a bodyweight of 230-240 g at the beginning of the study. Tested doses: 40.0; 100.0 and 250.0 mg / kg body weight (1 control and 3 experimental groups, 15 individuals each). Mating of females was performed with intact males in a ratio of 2:1. the Compound was introduced during 20 days of pregnancy. In the dynamics of the experiment, the state and behavior of rats, water and feed consumption, and changes in body weight were observed. The analysis of embryonic material took into account: the absolute and relative mass of internal organs (thymus, heart, lungs, liver, kidneys), to determine the teratogenic effect, a group of fruits (1/3) was fixed in Buena fluid and used to study internal organs using the Wilson method modified by Dyban the remaining 1/3 of the fetuses was fixed in ethanol to study the state of the skeleton using the Dawson method. When studying the reproductive toxicity of benzothiadiazinones in mammals (rats) using the method of two generations at doses of 15.0; 50.0 and 200.0 mg/kg of body weight (1 control and 3 experimental groups, 20 individuals each). Female F0 of the parent generation was primed during the mating period, pregnancy, and continued until the end of the feeding of the F2 generation. Mating 2:1. Results. Based on the results of studying the embryotoxic and teratogenic effects, invalid doses were established at the following levels: Noel for the mother - 100.0 mg/kg of body weight; Noel for embryotoxicity - 100.0 mg/kg of body weight; NOEL for teratogenicity-100.0 mg/kg of body weight. Results on the study of reproductive activity: NOEL for parents and offspring-50.0 mg/kg of body weight. Discussion. Studies on the effects of a long-term action of a technical product - “generic”, belonging to the class of benzothiadiazinones, found the studied compound for teratogenic, embryotoxic effects, as well as for its effect on reproductive toxicity, in accordance with the hygienic classification of pesticides by hazard (SanPiN 1.2.2584-10)to be a moderately dangerous compound (hazard class 3). Studied product class benzothiadiazinones on toxicological parameters are identical with the technical product is “originator”. Conclusion. Thus, the research shows that it is necessary to study the effects of long-term action of xenobiotics on the mammalian body when conducting sanitary and toxicological studies, to increase the reliability of the developed hygiene standards in environmental objects and food products.

Introduction. Technical products that are part of pesticides recommended for use in agriculture must undergo a comprehensive sanitary and Toxicological examination, which is the basis for preventing the adverse effects of pesticides on the health of workers and the population, as well as on the sanitary state of the environment. Purpose of research - the study of the biological effect of the technical product derived triazolinthionov, with its repeated oral intake in mammals (rats), justification of the permissible daily dose (DSD) for humans. Material and methods. Chronic (12 months) experiment was conducted on male rats with a body weight of 200-210 g tested doses: 5.0; 50.0 and 500.0 mg/kg body weight (1 control and 3 experimental groups and 20 individuals each). In the dynamics of the experiment, we observed the condition and behavior of animals, water and food consumption, fixed the timing of death, recorded changes in body weight, physiological, biochemical and hematological parameters. Results. It was found that the dose of 5.0 mg/kg body weight does not cause significant changes in all studied parameters, doses of 50.0 and 500.0 mg/kg body weight had a polytropic effect on the body of experimental animals. Discussion. The studied technical product at repeated intake in doses of 50,0 and 500,0 mg/kg of body weight causes changes in the state of the Central nervous system of animals (statistically significant changes in SPP, total activity, path length, rest time), as well as changes in carbohydrate, lipid, and lipoprotein metabolism in the body, as evidenced by statistically significant changes in biochemical and hematological indicators. Consequently, doses of 50,0 and 500,0 mg/kg of body weight have a polytropic effect on the body of male rats and are effective. The dose of 5.0 mg/kg of body weight, when administered in animals of the experimental group in comparison with animals of the control group, there are no changes in all the studied parameters throughout the experiment, is accepted as invalid. On the basis of an inactive dose of 5.0 mg/kg of body weight and a reserve factor of 100, we have scientifically justified DSD for humans at the level of 0.05 mg/kg. Conclusion. Studies have shown that long-term repeated oral administration of the studied product into the body of animals (male rats) at a dose of 5.0 mg per 1 kg of body weight does not cause statistically significant changes in all the studied parameters, so the indicated dose is invalid. Doses of 50,0 and 500,0 mg/kg MT have a polytropic effect on the body of male rats and are effective. DSD for humans at the level of 0.05 mg/kg is justified based on the inactive dose at the level of 5.0 mg per 1 kg of body weight, established in a 12-month chronic experiment conducted on male rats, and the reserve coefficient of 100 (taking into account the unexpressed specific and long-term effects).

Introduction. The antidote of chloroquinoline derivative contains in the stuff of selective, post-emergence herbicide of systemic action against a broad spectrum of annual cereals weeds for one-time ground handings of spring and winter weed crops. Cultural cereals are protected by the presence of the antidote chlorhinoline derivative in the preparation. The aim of the study. To investigate the exploring chronic influence of the antidote chloroquinoline derivative in its multiple entering warm-blooded organisms (male rats) for finding out the kind of the biological influence, active and non-active doses, were conducted. Material and methods. White rats were used in the acute experiments (6 animals per group). Doses of 1000-7000 mg/kg were tested. The chronic experiment was executed on 80 rats. Doses of 0.4; 4.0 and 40 mg/kg were tested. The estimation of the animals behavior, food, and water consumption, terms of animals death was fixed, alterations in body weight, physiological, biochemical and hematological indices were registered in the experiment were conducted. Results. The evaluation of general behavior of animals received antidote in dose of 40.0 mg/kg gave such a result as the deviation in such indices as behavior responses and SPP, analysis of hematological and biochemical tests showed the alteration in lipid and lipoprotein metabolism; aminoalkyl metabolism; anaerobic glycolic to take place in animals’organisms. Conclusion. Indices of the acute peroral toxicity of antidote LD50 in male rats, peroral: 4349 ± 840 mg/kg b.w. hazard class - 4 according to hygienic pesticide classification on hazard class (SanPin 1.2.2584-10) were established. 2. Active 40,0 mg/kg and non-active (NOELch) 4,0 mg/kg the dose was established. 3. The admissible day dose (ADD) for a human of 0.04 mg/kg b.w. was justified.

Introduction. The study of the character of reactions of lipid peroxidation, as well as the state of the antioxidant system regulating their course under the conditions of the action of chemical products on the body, is an important stage of investigations. There is not enough data on the development of oxidative stress in cells exposed to pesticides, and this concerns, first of all, studies of the activity of antioxidant enzymes. The aim of the study is to execute the experimental assessment of the influence of a surface active substances (SAS) on the basis of the rape oil on antioxidant status of white male rats during its multiple peroral intakes for 6 months in doses of 0.5, 5.0 and 50.0 mg/kg body weight (on a.s.). Material and methods. Studies on the determination of enzymatic indices of the body's antioxidant defense system (superoxide dismutase, glutathione peroxidase and glutathione reductase) were performed on a ChemWell biochemical analyzer (Awareness Technology, USA) with the use of diagnostic reagent kits by Randox Laboratories Ltd (England). The catalase activity was determined by the colorimetric method. Results. Under the prolonged action of surfactants on warm-blooded organisms, changes in the activity of antioxidant enzymes were established to occur in doses of 5,0 and 50,0 mg/kg b.m. Discussion. The test substance used in a dose of 0.5 mg/kg bm does not have an inhibitory effect on the antioxidant status of the organism. The use of a surfactant based on rapeseed oil at doses of 5.0 and 50.0 mg/kg mt has a negative effect on the antioxidant status of an organism of male rats. Conclusion. Surfactants based on rapeseed oil in doses of 5.0 and 500 mg/kg b.m. have a negative effect on the antioxidant status of an organism of male rats, which is probably due to the high content of erucic acid and glucosinolates in rapeseed oil.