ASSESSMENT OF TOXICITY AND HAZARD OF TECHNICAL PRODUCT OF TRIAZINONE’S DERIVATIVE

Author(s):  
V. N. Rakitskii ◽  
T. M. Еpishina ◽  
E. G. Chkhvirkiya ◽  
T A. Sinitskaya ◽  
Е. A. Mukhina

Experimental assessment of toxicity and hazard of technical product of triazinone’s derivative at its peroral administration into warm-blooded animals’ bodies (male rats) has been conducted to determine the character of the substance biological action. Its acute peroral toxicity was at the level of LD50 -1693 ± 470 mg/kg of body weight, hazard class – 4 according to Hygienic Classification of Pesticides (Sanitary Rules & Standards 1.2.2584-10). Effective dose was 62.5 mg/kg b.w., non-effective dose (NOEL) was 12.5 mg/kg b.w. ADI was 0.1 mg/kg b.w.

2020 ◽  
Vol 99 (9) ◽  
pp. 986-989
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya

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.


2020 ◽  
Vol 99 (11) ◽  
pp. 1276-1279
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya

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.


2020 ◽  
Vol 14 (1) ◽  
pp. 64-69
Author(s):  
Ekaterina V. Lagereva ◽  
Vladislav E. Abramov

The purpose of the research is to evaluate the acute toxicity of Altric-Extra when introduced into the stomach to mice and rats. Materials and methods. The studies were conducted in the vivarium of the All-Russian Research Institute of Fundamental and Applied Parasitology of Animals and Plants. The acute toxicity of Altric-Extra was determined on 20 white outbred male mice weighing 19.3–23.3 g, 10 animals in a group and on 30 white outbred male rats weighing 150–196 g, 6 animals in a group. Altric-Extra was administered to mice of the experimental group once into the stomach in the form of a suspension in a dose of 5,986 mg/kg at the rate of 0.2 ml/10 g of body weight. Altric-Extra rats were also administered once into the stomach in the form of a suspension at the rate of 2.0 ml/100 g body weight. As a carrier in the preparation of the suspension, 1% starch gel was used. The experimental rats of groups 1, 2, 3 and 4 were given Altric-Extra at doses of 4,580.2 mg/kg, 3,846.2; 3,088.8 and 1,577.9 mg/ kg respectively. Mice and rats of the control groups were administered once with 1% starch gel. For 14 days, the behavior and condition of the animals was monitored. The body weight of the experimental animals was measured on the 1st, 3rd, 7th, 9th and 14th days of the experiment. Results and discussion. Medium lethal doses of LD50 have been established for oral administration to laboratory animals. For mice, the LD50 was more than 5 986 mg/kg, i.e., according to the generally accepted hygienic classification, Altrick-Extra belongs to hazard class 4 (low-hazard substances). On rats, the LD50 was 3 103.1±48.5 mg/kg (2,354.6÷3,851.5 mg/kg). Therefore, Altrik-Extra belongs to hazard class 3 (substances are moderately hazardous).


2020 ◽  
Vol 64 (2) ◽  
pp. 83-87 ◽  
Author(s):  
Valery N. Rakitskii ◽  
E.G. Chkhvirkiya ◽  
T.M. Epishina

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).


2021 ◽  
Vol 65 (1) ◽  
pp. 45-49
Author(s):  
Valery N. Rakitskii ◽  
Elena G. Chkhvirkiya ◽  
Tatiana M. Epishina

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.


Author(s):  
Marina P. Marinicheva ◽  
◽  
Vladimir V. Strogov ◽  
Vasiliy I. Dorozhkin ◽  
◽  
...  

The article presents data on the toxicological properties of the disinfectant, which includes alkyldimethylammonium propyl ketone chloride, glutaraldehyde, glyoxal. Based on the results of a series of experiments, the main parameters of the toxicity of the disinfectant were determined. For male mice, the acute toxicity LD50 was 325±14.5 mg / kg, for male rats – 350±50 mg/kg, according to the classification of GOST 12.1.007-76, the agent belongs to the 3rd hazard class. The LD50 with repeated administration of the drug was 217±13.5 mg/kg of animal weight, the cumulation coefficient was 0.67, which indicates the ability of the drug with repeated intragastric administration to accumulate in the body of animals.


Author(s):  
M. Khrabko ◽  
R. Fedoruk

The aim of research was to study the effect of different doses of Ge citrate on the growth and development of F1 male, the activity of their immune system and the state of hemostasis under these conditions. Research performed by methods of groups and periods with using F1 male rats, which were watering during the milk-feeding period up to 120 days with Ge citrate obtained by nanotechnology method in doses 10 (I), 20 (II), 200 (III) mcg Ge/kg body weight and chemically synthesized Ge citrate in dose 2,000 (IV) mcg Ge/kg body weight. According to the research findings the most pronounced effect watering of Ge citrate on the growth and development of male rats organism was noted in dose 20 mcg Ge/kg body weight. Biological action of Ge citrate stimulated the immunophysiological activity of the organism with increasing of total Ig, molecules of average mass, sialic acid, number of white blood cells by the increasing number of lymphocytes and granulocytes, against the background of reduction of circulating immune complexes and hexoses bound to proteins. The positive dose-dependent effect of Ge citrate on the growth and development of the rats' organism and its immunophysiological and hematological parameters was noted.


2018 ◽  
Vol 97 (6) ◽  
pp. 505-508 ◽  
Author(s):  
Tatiana M. Epishina

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.


2020 ◽  
Vol 17 (1) ◽  
pp. 77-85
Author(s):  
Lusi Agus Setiani ◽  
Moerfiah Moerfiah ◽  
Yulianita Yulianita

Inflammation is one of the immune system's main responses to infection and irritation. One of the medicinal plants that can be used as anti-inflammatory is African leaves because there have flavonoid compounds. Flavonoid compounds have anti-inflammatory effects that can regulate arachidonic acid metabolism by inhibiting cyclooxygenase (COX) and lipooxygenase activity.This study aims to determine the effectiveness and determine the effective dose of African leaf infusion as anti-inflammatory in sparague dawley strain  induced carrageenan male white rats. The method used is measurement of udema with subplantar 1% carrageenan induction.Test animals used were 20 male rats divided into 5 groups. Each group consisted of 4 rats. Group I as a negative control was given CMC-Na solution, the second group as a positive control was given diclofenac sodium with 1.26 mg/200 gBB body weight, group III, IV and V were given African leaf infusion with three dose ratings namely 100, 150, 200 mg/kgBB bodyweight. The results showed that the infusion of African leaves had Antiinflammatory Activity with dose 200 mg/kg body weight as the most effective dose against inhibition of inflammation.           


2019 ◽  
Vol 63 (3) ◽  
pp. 147-151
Author(s):  
Valery N. Rakitskiy ◽  
E. G. Chkhvirkiya ◽  
T. M. Epishina

Introduction. The scientific basis for the safe use of pesticides are comprehensive sanitary and toxicological studies to study the parameters of their toxicity and biological action, hygienic regulation for the purpose of scientific justification of regulations and safety measures when working with them. Purpose of research. The study of parameters of acute and chronic toxicity, biological actions technical product derived chloracetamide, at oral intake of mammals (rats), the rationale of the acceptable daily intake (ADI) for humans. Material and methods of research. In acute experiments used white male rats weighing 210-220 g Tested doses 1000 and 4000 mg/kg of body weight. Statistical group for each dose consisted of 6 animals. Chronic experiment was carried out on male rats with body weight 180-190 g. Doses were tested: 3,5; 17,6 and 70,0 mg/kg body weight. Statistical groups of each dose and control group included 20 animals. In the dynamics of the experiment, the state and behavior of animals, water and food consumption were observed, the terms of death were fixed, changes in body weight, physiological, biochemical and hematological parameters were recorded. The value of the permissible daily dose was determined by the ratio of the maximum inactive dose to the reserve ratio. Results. As a result of the research it was found that LD50 of the studied compound is 2172 ± 370 mg/kg. In the chronic experiment, the dose of 3.5 mg/kg b.w. does not cause significant changes in all the studied parameters, at a dose of 17.6 mg/kg b.w. single changes, the dose of 70.0 mg/kg. had a polytropic effect on the body of experimental animals. Discussion. The studied technical product for acute oral toxicity refers to low-hazard compounds. It was found that multiple oral intake of the studied product at a dose of 70.0 mg/kg weight body revealed changes in the state of the Central nervous system, and the analysis of biochemical and hematological parameters of blood showed that changes in carbohydrate, lipid and lipoprotein metabolism, aminobelic metabolism occur in animals. Conclusions. The studied compound for acute oral toxicity according to the hygienic classification of pesticides (SanPiN 1.2.2584-10) belongs to the 4th hazard class. Dose: 70,0 mg/kg weight body - acting; 17,6 mg/kg weight body - threshold; 3.5 mg/kg weight body - inactive. The permissible daily dose (DSD) for a person is 0.035 mg/kg.


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