ACUTE TOXICITY OF OCTENIDINE HEXAFLUOROSILICATE

Author(s):  
I. O. Shyshkin ◽  
V. Yu. Anisimov ◽  
A. V. Nikitin ◽  
V. O. Gelmboldt

The aim of the work. Determination of toxicometric characteristics of octenidine hexafluorosilicate (OHFS), characterized by significant pharmaceutical potential, in an acute experiment on rats by oral administration. Materials and Methods. A study of the acute toxicity of octenidine hexafluorosilicate was carry out on 42 male Wistar rats weighing 180–200 grams. The main criterion for quantifying the toxicity of octenidine hexafluorosilicate was LD50, which was determined using the least squares method. In addition, the following hazard indicators were calculated: 1/LD50 – median lethal dose (absolute toxicity), LD84/LD16 – the range of lethal doses (zone of acute toxic effect), 1/(LD50-S) – the total toxicity index and the S-function angle of inclination (variability of lethal doses). Statistical processing of the results was carry out using the «StatPlus 2009» software (AnalystSoft, USA, 2009). Results and Discussion. The results of the acute toxicity determination of octenidine hexafluorosilicate show that this compound, in the oral route of administration, belongs to the III class of toxicity for the human (slightly hazardous) and to the IV class of toxicity for the animals (white rats). Based on the variability of lethal doses, the studied hexafluorosilicate can be attribute to compounds that do not pose a high potential risk of the onset and development of poisoning. The calculated toxicity and hazard values of octenidine hexafluorosilicate show that it does not pose a particular danger to humans. Extrapolation to humans of acute toxicity parameters obtained in animals was determined using the coefficient of resistance to the species and is 132.15 mg/kg body weight. Conclusions. The results of determining the toxicometric characteristics of octenidine hexafluorosilicate in rats by oral administration allow to classify this compound as moderately toxic substances (LD50 = 555.05 mg / kg, toxicity class IV). The determined parameter of acute toxicity of OHFS is close to the LD50 values of other hexafluorosilicates known from the literature; relative safety and high caries-prophylactic and periodontal-protective efficacies of OHFS indicate the prospects for further studies of this compound.

2017 ◽  
Vol 19 (74) ◽  
pp. 20-23
Author(s):  
Yu. V. Loboiko ◽  
M. M. Danko ◽  
O. V. Krushelnytska ◽  
S. I. Kravets

The paper presents the results of research to determine the parameters of acute toxicity of «Brovermectin-granulate». The material for the study of acute toxicity were of carp earlings. In experiment used drug «Brovermectin-granulate» (1 g of the drug contains: active actiion substance ivermectin – 3.5 mg, tocopherol acetate – 20 mg). The introduction of the drug  was carried out orally using a probe in anterior intestine of fish. The drug was administered to fish in the form of a homogeneous suspension produced 1 % starch solution individually, in doses of 1000, 4000, 8000, 12000, 16000 and 20000 mg/kg of body weight. For settings acute toxicity determined the general condition and death of fish; for a dose of the drug (DL50) calculated by methods G. Kerber, H. Pershyn, least squares analysis of probit mortality curves for V.B. Prozorovskyj, means three points for B.M. Shtabskyj. At this stage of research it was found lethal (DL100) and maximum tolerated (DL0) dose of «Brovermectin-granulate» for earlings carp. As a result of studies found that 100% death of fish following the dose of 20000 mg/kg (DL100), and for the drug at a dose of 4000 mg/kg (DL0) set to survival of 100% fish. Established that the value of average lethal dose of «Brovermectin-granulate» for fish regardless of the method of calculation mainly coincided and were 10932,8–11200 mg/kg for earlings carp. Thus, the drug «Brovermectin-granulate» for oral administration to fish belongs to grade 4 toxicity – low toxic substances.


Author(s):  
Roman Dotsenko ◽  
Yevheniia Vashchyk ◽  
Andriy Zakhariev ◽  
Andrii Zemlianskyi ◽  
Ekaterina Dotsenko ◽  
...  

The aim: to determine the parameters of acute toxicity of the preparative form of an antiemeric agent based on maduramycin and nicarbazine for white mice, white rats and guinea pigs with a single oral administration. Materials and methods. Determination of acute toxicity of the formulation by oral administration was performed on 48 adult male mice, 48 adult nonlinear male rats, 48 adult male guinea pigs. To conduct an experiment on the principle analogues were formed seven experimental and one control group, 6 animal each. The dose of the formulation was calculated individually based on body weight values. It should be noted that the total volume of the emulsion of the formulation administered orally is not exceeded 1.0 cm3per 100 gram b. w. Results. Toxicometric parameters of the formulation were calculated by the method of least squares for probit analysis of mortality curves. It was found that the LD50 of the preparative form of antiemeric agent for white mice for a single oral administration is 238.05±28.08 mg/kg, LD16 – 128.71 mg/kg, LD84 – 347.39 mg/kg, LD100 - 402, 06 mg/kg body weight, respectively. LD50 of the preparative form of antiemeric agent for white rats with a single oral administration is 260.51±28.83 mg/kg, LD16 – 148.39 mg/kg, LD84 – 372.65 mg/kg, LD100 – 428.71 mg/kg body weight, respectively. LD50 of the preparative form of antiemeric agent for guinea pigs for a single oral administration is 275±21.12 mg/kg, LD16 – 201.74 mg/kg, LD84 – 348.25 mg/kg, LD100 – 384.88 mg/kg body weight body respectively. Conclusions. According to SOU 85.2-37-736: 2011 "Veterinary drugs. Determination of acute toxicity” preparative form of a complex antiemeric agent based on maduramycin and nicarbazine on the degree of toxicity can be attributed to moderately dangerous substances (3rd hazard class)


Author(s):  
O. L. Orobchenko ◽  
M. Ye. Romanko ◽  
M. O. Yaroshenko ◽  
I. O. Gerilovych ◽  
N. A. Zhukova ◽  
...  

The experiments were performed on 58 males of nonlinear white rats 3–4 months old and weighing 180–200 g and 64 females of nonlinear white mice 2.5–3 months old and weighing 18–22 g. In the main experiment on rats, six experimental groups were formed, the animals of which were injected intragastrically with the drug ‘MEGASTOP for dogs’ (by absolute weight) in doses of 1,000.0, 2,000.0, 3,000.0, 4,000.0, 5,000.0, and 6,000.0 mg/kg body weight; in the main experiment on mice, seven experimental groups were formed, the animals of which were administered the drug in doses of 100.0, 500.0, 1,000.0, 1,500.0, 2,000.0, 2,500.0, and 3,000.0 mg/kg body weight. Control rats and mice were injected with 2.0 cm3 and 0.2 cm3 of polyethylene glycol-400, respectively. Clinical symptoms of poisoning with the drug ‘MEGASTOP for dogs’ of white rats (at doses of 2,000.0–6,000.0 mg/kg body weight) and mice (at doses of 1,000.0–3,000.0 mg/kg body weight) were refusals of food and water, loss of coordination, sitting in one place, a dose-dependent increase in depression with subsequent complete depression, lack of response to external stimuli and death on the first or fourth day after administration. During autopsy in rats and mice that died as a result of poisoning with the drug ‘MEGASTOP for dogs’, we recorded pallor of the mucous membranes of the mouth, trachea, pharynx, and esophagus; increase in heart volume, atrial blood supply; pulmonary hyperemia; uncoagulated blood; increase in liver volume, dark cherry color, flabby consistency; catarrhal inflammation of the mucous membrane of the small intestine. According to the results of determining the parameters of acute toxicity of the drug ‘MEGASTOP for dogs’ in the case of a single intragastric injection, LD50 for male rats is 3,384.98 ± 444.94 mg/kg, and for female mice — 2,025.88 ± 279.46 mg/kg body weight, which allows to classify it to class IV by the toxicity — low-toxic substances (LD50 — 501–5,000 mg/kg) and by the degree of danger to class III— moderately dangerous substances (LD50 — 151–5,000 mg/kg)


2015 ◽  
Vol 96 (2) ◽  
pp. 208-213
Author(s):  
N Yu Alimzhanov ◽  
I Sh Chakeev ◽  
Sh Zh Zhorobekova ◽  
I O Kudaybergenova ◽  
B N Lepshin

Aim. To determine the acute toxicity and hazard class of nanosized low-esterified beet pectin.Methods. To study the acute toxicity of substances, Kerber’s method was used. Probit analysis for different values of lethal dose calculated by least squares method, as well as morphologic studies, statistical analysis (non-parametric methods - Wilcoxon-Mann-Whitney test) were used. Pectin toxicity was studies on 40 mature Wistar rats of both gender and body weight of 160-230 g.Results. Enteral administration of 12 000 mg/kg of pectin did not affect the general condition and did not lead to lethal outcome. The following values of lethal doses were calculated using probit analysis: LD16=34 990.6542056074≈35 g/kg, LD50=74 242.9906542057≈74 g/kg, LD84=113 495.327102804≈113 g/kg, LD100=133 121.495327103≈133 g/kg. Histological study of rat organ tissues that received 12 000 mg/kg of pectin showed no structural changes in tissues of examined organs. Study drug - nanosized low molecular weight pectin, might be referred to hazard class IV (low hazard substances) according to GOST 12.1.007-76. and classification K.K. Sidorov Pectin substance may be considered as practically nontoxic drug (LD50 >10,000 mg/kg), which corresponds to Class V compounds according to Hodge and Sterner classification and classification by K.K. Sidorov.Conclusion. The results indicate complete safety of nanosized forms of pectin, which opens up prospects for further studies of the biological properties of this substance.


Author(s):  
Roman Sachuk ◽  
Yaroslav Stravskyy ◽  
Bogdan Gutyj ◽  
Tetiana Velesyk ◽  
Orest Katsaraba ◽  
...  

«Kolidev 8M» (powder for oral use) is a veterinary drug used to treat ornamental birds (pheasants, peacocks) in diseases of the digestive tract caused by microorganisms sensitive to colistin. In the study of the drug «Kolidev 8M» for oral administration, along with the confirmation of therapeutic properties, it is necessary to determine the LD50 obtained in the process of studying acute toxicity. The aim of research. The aim of research was to determine the acute toxicity of the veterinary drug «Kolidev 8M» (powder for oral administration) under the conditions of intragastric administration to white mice. Materials and methods of research. To achieve this aim, an experiment was conducted on 114 males of nonlinear white mice kept under optimal conditions in the vivarium of DEVIE LLC (Rivne, Ukraine). In the first series of experiments on the principle of analogues was formed control and three experimental groups of 6 animals each (n=6). The drug in the form of a solution was administered once orally using a esophageal gastric tube in doses of 500,0; 2000,0 and 4000,0 mg/kg body weight by absolute weight of the drug. The animals of the control group were injected with distilled water. After taking into account the results of the first experiment in the next experiment, 6 experimental groups were formed – mice, which were administered the drug «Kolidev 8M» in the form of a solution in doses (by absolute weight of the drug) – 500,0; 1000,0; 1500,0; 2000.0; 2500,0; 3000,0; 3500 and 4000,0 mg/kg body weight, as well as the control group – animals that were injected with distilled water with a volume of 0.5 cm3 according to similar regulations (Zapadniuk, 1983; Kotsiumbas, 2005; Karkyshchenko & Hrachev, 2010). There were 6 animals in each group (n=6). After their death, a pathological autopsy was performed (Zharov A. et al., 2003). The average lethal dose of LD50 was calculated by the method of probit analysis by Prozorovsky V.B. Research results. According to the results of research, it was found that the LD50 of the drug «Kolidev 8M» (powder for oral administration) under the conditions of its single intragastric administration to male mice is 2024,72±232,45 mg/kg, LD10 – 392,87 mg/kg, LD16 – 751,56 mg/kg, LD84 – 3297,88 mg/kg, LD90 – 3656,57 mg/kg, LD100 – 3934,47 mg/kg body weight, respectively. According to the results of an acute toxicological experiment with intragastric administration of the drug «Kolidev 8M» to white male mice, LD50 was 2024,72±232,45 mg/kg body weight. This allows, according to toxicity, to refer this drug to class IV – low-toxic substances (LD50 501,0-5000,0 mg/kg body weight), and the degree of danger to class III – moderately safe substances (LD50 151,0-5000,0 mg/kg body weight). Conclusions and prospects for further research. The drug «Kolidev 8M» in terms of toxicity belongs to class IV – low-toxic substances, and the degree of danger to class III – moderately safe substances. Further studies will be the next stage of pre-registration trials aimed at studying the subacute toxicity of the drug «Kolidev 8M»


Author(s):  
Л. І. Лєві

Розглянута у роботі технологія дає змогу шляхомпоєднання переваг м’яких обчислень і реґресійного ана-лізу будувати багатофакторні залежності з неперерв-ним виходом, враховуючи як можливість визначенняступеня важливості вхідних змінних, так і їх взаємодійнеобхідного порядку. Проте під час моделюванняоб’єктів із неперервним виходом, коли необхідна до-статня точність визначення чіткого значення вихідноївеличини, знаходження параметрів нечіткого рівнянняреґресії за методом найменших квадратів та парамет-рів функцій належностей шляхом статистичної оброб-ки експертної інформації не може в повній мірі забез-печити потрібну точність. Для цього потрібно налаш-тувати за навчальною вибіркою нечітку реґресійну мо-дель у відповідності до тестуючої вибірки. In work considered technology allows to build multivariate dependence with continuous output by combining the advantages of soft computing and regression analysis, given the opportunity, the definition of importance of input variables and their necessary interactions. However, when modeling objects with continuous output when a sufficient accuracy of the determination of a precise value of the output value is necessary, the identification of the parameters of fuzzy regression equations using the least squares method and parameters of membership functions by statistical processing of expert information is not sufficient to provide the desired accuracy. It requires configuration on the training set of a fuzzy regression model in accordance with the testing sample.


In the course of investigations on the production, distribution, and rate of disappearance in the body of immune substances, we were occupied in 1908 and previous years with a series of experiments on agglutinins, and we arrived at conclusions pointing to their close relationship to the blood and blood-forming organs (1, 2). In association with these inquiries, one of us (G. D.), together with W. Ray, published a communication on the relation­ship between the blood volume and the distribution of agglutinins within the circulation (3). It was there shown that the concentration of this substance (agglutinin) in the blood after inoculation into an animal was proportional to the body surface of the animal concerned, and was thus approximately proportional to the two-thirds power of the weight. Hence was deduced the conclusion that the blood volume of the animals examined was proportional to their body surface.


Toxicon ◽  
2020 ◽  
Vol 177 ◽  
pp. 16-24 ◽  
Author(s):  
Andrea Boente-Juncal ◽  
Carmen Vale ◽  
Mercedes Camiña ◽  
J. Manuel Cifuentes ◽  
Mercedes R. Vieytes ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
C. Christian Chibuogwu ◽  
U. Obioma Njoku ◽  
F. C. Okwesili Nwodo ◽  
E. O. Vincent Ozougwu ◽  
N. Victor Nweze

Abstract Background The leaves of Jatropha tanjorensis have been found to have important application both in traditional medicine and as an edible vegetable in Nigerian soups. It is popularly employed in Nigeria for the treatment of anemia, diabetes, and malaria. The dearth of information on its toxicity prompted this study. Mice were administered single oral doses of 10, 100, 1000, 1600, 2900, and 5000 mg/kg b.wt (n = 3/group) of the extract and were observed for 24 h for any sign of toxicity and mortality in the acute toxicity study. For the sub-acute toxicity study, doses of 100, 200, and 400 mg/kg b.wt of the extract were administered to experimental rats (n = 6/group) for 28 days after which the assessment of hematological and biochemical parameters, as well as liver and kidney histology was conducted post-treatment. Body weight of the animals was also taken weekly. Results The result showed that percentage weight gain decreased as the dose of extract increased. The haematological and biochemical parameters showed that the extract had no toxic effect on experimental animals, though there was a non-significant dose-dependent decrease in WBC. The extract also showed potential to cause hepatotoxicity at the highest dose. Conclusion Though the median lethal dose of the plant extract suggests relative safety of the plant material, consuming large amounts over a prolonged time may need to be discouraged to avoid potential damage to vital organs such as the liver.


2020 ◽  
Author(s):  
Nela Pavlíková ◽  
Jan Šrámek ◽  
Michael Jelínek ◽  
Petr Halada ◽  
Jan Kovář

ABSTRACTMany compounds have the potential to harm pancreatic beta-cells; organochlorine pollutants belong to those compounds. In this work, we aimed to find markers of acute toxicity of p,p‘-DDT among proteins expressed in human pancreatic beta-cells NES2Y and visible at 2-D electrophoresis. We exposed NES2Y cells to a lethal dose of p,p‘-DDT (150 μM) for 24 hours and 30 hours and determined changes in protein expression using 2-D electrophoresis. We also stained the cells exposed to p,p‘-DDT to visualize the altered phenotype of the exposed cells. Among proteins with changed expression, we identified proteins involved in ER stress (GRP78, and endoplasmin), mitochondrial proteins (GRP75, ECHM, IDH3A, NDUS1, and NDUS3), proteins with potential to change the cell morphology (EFHD2, TCPA, NDRG1, and ezrin), and some other proteins (HNRPF, HNRH1, K2C8, vimentin, PBDC1, EF2, PCNA, biliverdin reductase, G3BP1, FRIL, and HSP27). These proteins can be used as markers of acute DDT toxicity.


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