scholarly journals Study of Acute Toxicity and Irritant Effect of Nasal Spray Naltrexone Hydrochloride

2021 ◽  
Vol 10 (2) ◽  
pp. 101-105
Author(s):  
Yu. M. Domnina ◽  
V. V. Suslov ◽  
S. A. Kedik ◽  
D. A. Akhmedova ◽  
A. P. Malkova
Keyword(s):  
Acute Toxicity ◽  
Toxic Effect ◽  
Nasal Spray ◽  
The Body ◽  
Laboratory Animals ◽  
Intragastric Administration ◽  
Naltrexone Hydrochloride ◽  
Adult Mice ◽  
High Doses ◽  
Low Dose Naltrexone

Introduction. Acute toxicity of naltrexone hydrochloride nasal spray during intragastric administration to mice and local irritant effect on rabbits was studied. At all stages of the experiment, observations were made on the General condition of the animals. The state of homeostasis was evaluated using functional, hematological and morphometric methods. According to the results of research, there was no local irritant effect on the eyes of rabbits, as well as no toxic effect of high doses of the drug on animals. Introduction. Naltrexone hydrochloride in doses of 1.5– 5 mg/day has shown its effectiveness in the treatment of a number of diseases. Due to the lack of such a "low-dose" naltrexone registered on the pharmaceutical market, we have developed the composition of the nasal spray naltrexone hydrochloride. One of the stages of our research is to study the safety of the drug being developed. The first step in this direction was to study its acute toxicity and local irritant effect.Aim. Study of acute toxicity and local irritant effect of naltrexone hydrochloride nasal spray.Materials and methods. The object of the study was a nasal spray of naltrexone hydrochloride. Acute toxicity studies were performed on outbred adult mice (females). Study of local irritant effect on Soviet chinchilla rabbits (males).Results and discussion. The study of acute toxicity showed that the drug, at a dose significantly higher than the estimated maximum daily therapeutic dose for humans, did not have a significant toxic effect on the body of laboratory animals. The presence of a local irritant effect in the studied drug was not established in the framework of the experiment.Conclusion. As part of the experiment, the drug under study did not have a local irritant or toxic effect on the animal body. The results obtained allow us to continue the development and study of the nasal spray naltrexone hydrochloride.

scholarly journals Determination of acute toxicity of the ‘Bondarmin’ disinfectant

2019 ◽  
Vol 5 (2) ◽  
pp. 26-30
Author(s):  
A. O. Bondarchuk ◽  
A. P. Paliy ◽  
M. Ye. Blazheyevskiy
Keyword(s):  
Acute Toxicity ◽  
Toxic Effect ◽  
Toxicity Assessment ◽  
Laboratory Animals ◽  
Intragastric Administration ◽  
Toxic Substances ◽  
Internal Organs ◽  
National University ◽  
Scientific Laboratory ◽  
High Doses

In the article the results of the study of toxic effect of the designed disinfectant (active ingredient potassium peroxomonosulfate) on laboratory animals (mice) are presented. For the recent years a variety of scientific works both by domestic and by foreign scientists has been devoted to the study of different disinfectants’ toxicity. However today there is a number of issues that require more detailed studying and scientific justification. Among them the problem of toxic effects of disinfectants on the animal organism occupies a special place. The aim of our work was to study the toxic effect on the laboratory animals and to assess the acute toxicity (LD50) of the designed ‘Bondarmin’ disinfectant. Tests were carried out at the Laboratory of pharmacology and toxicology of the National University of Pharmacy (Kharkiv) and on the base of Educational and scientific laboratory of genetic and molecular research methods named after P. I. Verbitskiy in the Kharkiv State Zooveterinary Academy. Acute toxicity assessment (LD50) was carried out with intragastrointestinal administration of the designed drug to laboratory animals (mice). Changes in the internal organs of animals that were removed from the experiment for humane reasons and those who died after the experiment were detected by macroscopic examination. The lethality of laboratory animals after the intragastric administration of disinfectant was determined by the Prozorovskiy method The dynamic of changes in body weight of mice after the administration of disinfectant in high doses (from 1,500 to 3,500 mg/kg) was found out. The influence of the disinfectant on the mass coefficients of the internal organs of male mice after intragastric administration was evaluated. Toxic effect of the designed disinfectant ‘Bondarmin’, when using intragastric method of administration to laboratory animals (mice), according to the age and sexual index (LD50 = 2,702.40 ± 156.32 mg/kg), was established. Disinfectant ‘Bondarmin’ refers to IV toxicity class (low toxic substances).

scholarly journals Acute Toxicity of Hydrogel Polyhexamethylene Guanidine Hydrochloride

2020 ◽  
Vol 5 (4) ◽  
pp. 103-107
Author(s):  
S. N. Lebedeva ◽  
O. S. Ochirov ◽  
M. N. Grigoryeva ◽  
S. D. Zhamsaranova ◽  
S. A. Stelmakh ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Guanidine Hydrochloride ◽  
Lethal Dose ◽  
The Body ◽  
Laboratory Animals ◽  
Intragastric Administration ◽  
Test Substance ◽  
Hazard Class ◽  
Polyhexamethylene Guanidine ◽  
Medicinal Substances

Background. Previously, we have shown that the polyhexamethylene guanidine hydrochloride hydrogel exhibits a pronounced wound healing. At the same time, no studies of the toxic effect of the hydrogel on animals have been conducted. Aim of the research. In the framework of this work, the acute toxicity of the hydrogel polyhexamethylene guanidine hydrochloride was studied in laboratory animals with intragastric administration. Materials and methods. The polyhexamethylene guanidine hydrochloride hydrogel was obtained by crosslinking the amino end groups with formaldehyde. An acute toxicity study was carried out (P 1.2.3156-13, GOST 32644-2014 and the Guidelines for conducting preclinical studies of drugs) in an experiment on outbred mice with a single addition of the test substance in different doses (1000, 3000, 5000, 8000 mg/kg) with fixing indicators (appearance, behavior, condition of the body hair coat, water and food consumption, excretion, body weight and its growth) during 14 days. After the animals were withdrawn from the experiment, autopsy, macroscopic evaluation and weighing of the internal organs were performed. The results showed that with the introduction of the test substance into the animal organism, death during the observation period (14 days) did not occur. It was not possible to determine the semi-lethal dose for the test compound. Conclusion. The conducted studies allow us to conclude that this substance is practically non-toxic and can be classified as hazard class V. Further research will be directed to the formation of hydrogel compositions with medicinal substances.

scholarly journals Preclinical evaluation of the veterinary drug “Amoxidev 15” for its use in surgical and obstetric practice

2021 ◽  
Vol 23 (103) ◽  
pp. 109-115
Author(s):  
L.-M. Kostyshyn ◽  
R. Sachuk ◽  
Ye. Kostyshyn ◽  
O. Katsaraba
Keyword(s):  
Body Weight ◽  
Soft Tissues ◽  
Control Level ◽  
Subcutaneous Administration ◽  
The Body ◽  
Laboratory Animals ◽  
Veterinary Drug ◽  
Intragastric Administration ◽  
Toxicological Evaluation ◽  
White Rats

Suspension for injection “Amoxidev 15” is prescribed to fur-bearing animals (mink, fox), dogs and cats for the treatment of respiratory diseases (tonsillitis, tracheitis, pneumonia, bronchitis, rhinitis, sinusitis, bronchopneumonia), digestive (gastritis, enteritis, enteritis). genitourinary systems (nephritis, urethritis, urocystitis, mastitis, metritis, agalactia), musculoskeletal system (arthritis, osteoarthritis, joint injuries, tendonitis, hoof lesions), skin and soft tissues (eczema, dermatitis) caused by sensitive drug by microorganisms, including colibacillosis, streptococcus, bronchopneumonia, etc. Toxicological evaluation of the veterinary drug “Amoxidev 15” under the conditions of acute and subacute toxicological experiments on a model of white rats. According to the results of an acute toxicological experiment with intragastric administration of the drug “Amoxidev 15” white rats DL50 could not be calculated because the death of laboratory animals was not detected within 14 days after administration. The maximum administered dose (in absolute weight of the drug) was 20000.0 mg/kg body weight, which allows to refer the drug to class VI toxicity of relatively harmless substances (DL50 > 15000 mg/kg body weight), and the degree of safety to class IV – low-hazard substances (DL50 > 5000 mg/kg). According to the results of an acute toxicological experiment with subcutaneous administration of the drug “Amoxidev 15” white rats DL50 could not be calculated because the death of laboratory animals was not detected within 14 days after administration, the maximum dose was 5000.0 mg/kg body weight, therefore, the drug “Amoxidev 15” when administered subcutaneously by toxicity can be classified as class VI substances relatively harmless (DL50 Subcut > 4500.0 mg/kg). When administered subcutaneously to white rats, the drug “Amoxidev 15” under conditions of subacute toxicological experiment in doses of 0.1–1.0 ml/kg does not cause hemo-, hepato- and nephrotoxic effects on the body of laboratory animals, although 3-day administration of the drug in a dose 1.0 ml/kg body weight caused an increase in the activity of hepatospecific enzymes ALT and AST by 12.5 and 11.1 % (P < 0.05), respectively, relative to the control, which was restored to the control level 7 days after cessation.

scholarly journals Research of acute toxicity, allergizing and local-irritative action of the veterinary drug “Yodozol”

2019 ◽  
pp. 54-58
Author(s):  
R. M. Sachuk ◽  
S. V. Zhyhalyuk ◽  
I. M. Lukyanik ◽  
M. S. Mandyhra ◽  
Ya. S. Stravsky ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Behavioral Responses ◽  
Physiological Parameters ◽  
Laboratory Animals ◽  
Veterinary Drug ◽  
Intragastric Administration ◽  
Toxic Substances ◽  
Treatment And Prevention ◽  
Mucous Membranes

The purpose of the work was to determine, in experiments on rodents, the parameters of acute toxicity, allergenic and locally irritative effects of iodine-containing uterine drug for the treatment and prevention of intrauterine infections of animals. Materials and methods. Preclinical studies of acute toxicity of “Yodosol” containing iodine and potassium iodide were performed on 90 white mice, 30 white outbred rats and 6 rabbits. Clinical, pharmacotoxicological and statistical methods were used. Results of work. It has been found that at intragastric administration in experimental rats and mice, DL50 values exceed 8,000 mg/kg body weight and have no effect on the behavioral responses and physiological parameters of laboratory animals. It has been investigated that “Yodosol” aerosol has no local toxic and irritant effects on the skin and mucous membranes of laboratory animals (rabbits). Conclusions. The use of the drug «Yodosol», in doses above 8,000 mg/kg body weight, does not affect the behavioral responses and physiological parameters of laboratory animals. The drug has no local toxic and irritant effects on the skin and mucous membranes. According to the requirements of SOU 85.2-37-736:2011 and GOST 12.1.007-76, the newly developed drug “Yodosol” belongs to low-toxic substances — 4 toxicity classes

scholarly journals Acute Oral Toxicity of the Supramolecular Complex Based on Albendazole and Triclabendazole (Altric-Extra) in Laboratory Outbred Mice and Rats

2020 ◽  
Vol 14 (1) ◽  
pp. 64-69
Author(s):  
Ekaterina V. Lagereva ◽  
Vladislav E. Abramov
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
The Body ◽  
Male Rats ◽  
Laboratory Animals ◽  
Oral Toxicity ◽  
Hazard Class ◽  
Russian Research Institute ◽  
Starch Gel ◽  
Outbred Mice

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).

Results of Preclinical Safety Tests of Radiopharmaceutical with 90Y for Intra-arterial Radioembolization of Liver Cancer

2021 ◽  
Vol 65 (5) ◽  
pp. 51-59
Author(s):  
O. Klement'eva ◽  
O Vlasova ◽  
D Stepchenkov ◽  
K Luneva ◽  
K Ternovskaya ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Acute Toxicity ◽  
The Body ◽  
Laboratory Animals ◽  
Preclinical Studies ◽  
Subchronic Toxicity ◽  
Safety Study ◽  
Preclinical Safety ◽  
Safe Dose ◽  
Observation Period

Purpose: Performing a safety study of a radiopharmaceutical drug with yttrium-90 for intra-arterial radioembolization of inoperable patients with primary and metastatic liver cancer. Material and methods: The developed radiopharmaceutical is a microspheres of human blood albumin with a diameter of 25-40 microns, modified with diethylenetriaminpentaacetic acid and labeled with 90Y radionuclide. The safety of the radiopharmaceutical was studied by the following indicators: acute toxicity of lyophilized reagents, subchronic toxicity of the radiopharmaceutical on two types of animals, local irritant effect of the radiopharmaceutical therapeutic activity in equivalent terms on laboratory animals, specific toxicity (allergizing effect) of lyophilized reagents for the preparation of a radiopharmaceutical drug. Female and male BALB/C mice, Wistar rats, chinchilla rabbits, and albino Guinea pigs were taken as experimental animals. All animals were obtained from certified laboratory animal nurseries. Results: During acute toxicity studies, the maximum safe dose of an inactive drug was determined. In terms of per person, it exceeds the intended dose for clinical use by almost 20 times. The study of the subchronic toxicity of the radiopharmaceutical did not reveal any symptoms of intoxication. The survival rate of the animals during the entire observation period was absolute. Standard behavior and appearance were observed in animals. The dynamics of body weight was positive, and the body temperature of rats and rabbits did not exceed the limits allowed. Samples of the finished dosage form of the drug did not have a local irritant effect. The solution of inactive components of lyophilized reagents for the preparation of a radiopharmaceutical drug did not have an allergenic effect in quantities ten times higher than the doses administered to a person. Conclusion: According to the results of preclinical studies, the radiopharmaceutical should be considered safe for use. The results of preclinical studies allow us to recommend the drug for clinical research.

ACUTE TOXICITY OF A NEW BENZIMIDAZOLE DERIVATIVE WITH ANTITHROMBOGENIC PROPERTIES

2021 ◽  
Vol 1 (1) ◽  
pp. 52-57
Author(s):  
A. A. Spasov ◽  
A. F. Kucheryavenko ◽  
D. V. Maltsev ◽  
М. V. Miroshnikov ◽  
V. S. Sirotenko ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Toxic Effect ◽  
Benzimidazole Derivative ◽  
Test Sample ◽  
The Body ◽  
Peroral Administration ◽  
Toxic Dose ◽  
Pharmaceutical Substance ◽  
Experimental Animals ◽  
Toxicological Profile

The paper presents the results of studying the toxicological profile of a new pharmaceutical substance RU891 with antithrombogenic properties. The minimum toxic dose (TDmin) for RU-891 by peroral administration is 230 mg/kg < TDmin ≤ 460 mg/kg. In experiments on the acute toxicity of the compound RU-891, the nature and severity of its damaging effect on the body of experimental animals were established and the safety of its action was evaluated. When studying the toxic effect of the test sample, the tolerated and toxic doses of RU-891 were determined, and the most sensitive organs and systems of the body were identified.

scholarly journals Effects of microbicide based on lactic acid and metal nanoparticles on laboratory animals

2017 ◽  
Vol 7 (4) ◽  
pp. 482-485 ◽  
Author(s):  
G. V. Ponomarenko ◽  
V. L. Kovalenko ◽  
O. V. Ponomarenko ◽  
Yu. O. Balackiy
Keyword(s):  
Lactic Acid ◽  
Acute Toxicity ◽  
Metal Nanoparticles ◽  
Guinea Pigs ◽  
The Body ◽  
Farm Animals ◽  
Laboratory Animals ◽  
Harmful Effects ◽  
Nanoparticles Of Silver

<p>Modern complex disinfectants should not only be highly effective against most pathogens, but also safe for the body of laboratory and farm animals. To determine the effect of microbicides on animal organism, there are several commonly accepted parameters that are regulated by relevant methodological documents. Taking into account the urgency of the development and implementation of modern disinfectants, the purpose of the researche was to study the effects of the drug "Orgsept" on the indicators of acute toxicity and its harmful effects on laboratory animals. The determination of acute toxicity, the study of the cumulative and skin-resorptive action of the drug "Orgasept" was performed on clinically healthy white mice, and the irritating effect and sensitizing properties were studied on Guinea pigs. The studies were conducted using generally accepted techniques (Yakubchak et al., 2005). According to the results of the research, acute toxicity, cumulative, sensitizing, irritating, skin-resorptive action of the disinfectant based on lactic acid and nanoparticles of silver "Orgasept" on laboratory animals were determined. It has been determined that the investigated preparation according to sanitary-and-hygienic norms GOST 12.1.007-76 belongs to the 3 groups of toxicity in concentrations which are significantly higher than bactericidal, it does not have a pronounced cumulative, sensitizing and skin-resorptive action.</p>

scholarly journals Toxicological characteristics of the preparation FORTICEPTTM Hoof Oinment

2018 ◽  
Vol 20 (92) ◽  
pp. 117-120
Author(s):  
V. D. Ishchenko ◽  
A. M. Shevchenko ◽  
N. M. Slobodyuk ◽  
R. O. Vasiv ◽  
H. V. Yarova ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
The Body ◽  
Average Weight ◽  
Intragastric Administration ◽  
Laboratory Mice ◽  
White Rats ◽  
Medicinal Preparations ◽  
Medicinal Substances

Antibiotic resistance of the main infectious disease pathogens is one of the biggest problems of present time, which causes the need for searching for new antimicrobial medicinal substances and developing effective medicinal agents. One of the innovative medicinal preparations with the antimicrobial action, which is recommended for application for animals with hoof diseases, is ForticeptTM Hoof Oinment. Integration in the practice new medicinal preparations needs their strict toxicological control, which involves the exploring of acute and chronic toxicity and remote effects of possible side effect. The purpose of work was the determination of the acute toxicity parameters of the ForticeptTM Hoof Oinmentduring the oral administration to white laboratory mice and evaluation of the skin resorptive action of the preparation after it was administrated on rats’ skin. For determination of the acute toxicity there were used male laboratory mice with the average weight of the body 20 g – two groups with 10 animals in each. For the first group (the control one) with the help of the probe there was injected the distilled water (0.1 ml) into stomach. For the second group there was injected ForticeptTM Hoof Oinment (0.1 g), where the dose of the preparation is equal 500 mg/kg. For evaluation of the skin resorptive action of the preparation there were used 6 white rats with the average weight of the body 175 g. On the pre-prepared patch of skin there was administrated the preparation in the number that is equal 2857 mg/kg of body weight. For control there was leaved a free from preparation patch of bare skin. Exposition lasted for 4 hours. The indicators were explored in dynamics after 6, 24, 48 hours from the exposition started. After the research results there was established that ForticeptTM Hoof Oinment doesn’t cause death after its intragastric administration to the white laboratory mice in the number that is equal 5000 mg/kg of the body weight, that’s why depending on the degree of toxicity it belongs to the V toxicity class (Practically nontoxic). After one-time application of the preparation to the white rats in the number which is equal 2857 mg/kg of the body weight there wasn’t observes no death or pronounced changes in the behavior reactions, motor activity, state of the nervous system, amount of the consumed food and water. Therefore ForticeptTM Hoof Oinmentaccording to the results of the determination of the acute toxicity after its administration on the skin to the white rats depending on the degree of toxicity it belongs to the V toxicity class (Practically nontoxic). ForticeptTM Hoof Oinment doesn’t detect skin resorptive action, that points on the absence of toxic effects of the preparation due to its application on the skin.

scholarly journals PECULIARITIES OF THE TOXIC EFFECT OF DIISONONYL PHTHALATE PLASTICIZER PHTHALATE ON EXPERIMENTAL MODELS

2018 ◽  
Vol 97 (5) ◽  
pp. 474-477
Author(s):  
Vitaly A. Grynchak ◽  
S. I. Sychik
Keyword(s):  
Toxic Effect ◽  
Experimental Models ◽  
Laboratory Animals ◽  
In Vitro Tests ◽  
Intragastric Administration ◽  
Blood Calcium ◽  
Phthalate Plasticizer ◽  
Diisononyl Phthalate

Introduction. The purpose of the study was to determine the characteristics of the biological effect of diisononyl phthalate, a new plasticizer for polymer products. Material and methods. Toxic properties of the compound have been studied in various ways of its entering in the organism of laboratory animals, local irritating, cumulative and skin-resorptive actions have been established, the potential ability of the compound to induce remote effects in experimental models in vivo/in vitro has been revealed. Results and discussion. The obtained data show diisononyl phthalate do not pose a risk of the acute poisoning under intragastric, intraperitoneal, epicutaneous and inhalation modes of exposure, being incapable of inducing signs of the irritation of the skin and mucous membranes, is not allergic. With subchronic intragastric administration of diisononyl phthalate in doses from 10,000 to 100 mg/kg, the dose dependence of toxic effect and its ability to cause chronic polytropic poisoning of the action in the form of disturbance of the pattern of peripheral blood, calcium and phosphorus metabolism and changes in the functional state of internal organs are revealed. In the study of the reproductive toxicity against the background of the administration of the drug at a dose of 10,000 mg/kg, an increase in total postimplantation, embryonic and the postnatal mortality rate was established. Intragastric administration of diisononyl phthalate at the mentioned dose to female animals during pregnancy triggered the formation of multiple (combined), external and internal malformations of embryos that were single in response to a reduced dose of up to 100 mg/kg. Changes in the state of the reproductive function of males have not been established. In the study of mutagenic toxicity in the Ames test, the effect of the compound has not been established to lead to an increase in the number of revertant colonies, which indicates the lack of ability of diisononyl phthalate to induce point mutations. Conclusion. The results of the studies showed that further study of the toxic effect of diisononylphthalate in chronic exposure and in vitro tests is necessary.

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