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.

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 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).

scholarly journals Experimental evaluation of allergenic properties of Bisphenol-5

2020 ◽  
Vol 27 ◽  
pp. 00063
Author(s):  
R. M. Ahmadullin ◽  
R. S. Muhammadiev ◽  
L. R. Valiullin
Keyword(s):  
Experimental Study ◽  
Anaphylactic Shock ◽  
The Body ◽  
Laboratory Animals ◽  
Preclinical Studies ◽  
Test Drug ◽  
Experimental Conditions ◽  
Negative Effect ◽  
And Control ◽  
Respiratory Movements

The paper presents the results of preclinical studies of the allergenic properties of a new drug bisphenol-5, which has pronounced anti-radical activity. An experimental study of the antioxidant was carried out in doses of 2, 5, 20 mg/kg in guinea pigs and rabbits. It was shown that bisphenol-5 is not able to cause a general anaphylaxis reaction (anaphylactic shock). By the method of skin applications, the absence of allergenic effects of the drug in animals was found. During the formulation of conjunctival tests in experimental and control animals, signs of hypersensitivity, both immediate and delayed, were not observed with respect to the test drug. Changes in body temperature, pulse rate, and the number of respiratory movements as a result of clinical studies of the state of the animal organism after applying bisphenol-5 were also not recorded. Thus, the drug Besphenol-5 in the studied doses and under the selected experimental conditions does not have a negative effect on the body of laboratory animals and does not have allergenic properties.

scholarly journals Acute and Subchronic (28-day) Oral Toxicity Studies on the Film Formulation of k-Carrageenan and Konjac Glucomannan for Soft Capsule Application

2019 ◽  
Vol 87 (2) ◽  
pp. 9 ◽  
Author(s):  
Ni Sutrisni ◽  
Sundani Soewandhi ◽  
I Adnyana ◽  
Lucy Sasongko
Keyword(s):  
Acute Toxicity ◽  
Experimental Period ◽  
Konjac Glucomannan ◽  
Toxicity Study ◽  
Oral Toxicity ◽  
Subchronic Toxicity ◽  
Acute Toxicity Study ◽  
Relative Organ Weight ◽  
Film Formulation ◽  
Safe Dose

The aim of this study was to investigate the acute and subchronic toxicity of a film formulation that combines κ-Carrageenan and konjac glucomannan for soft capsule application. For the acute toxicity study, a dose of 2000 mg/kg body weight (bw) of the film suspension was administered orally to rats. The animals were observed for toxic symptoms and mortality daily for 14 days. In a subchronic toxicity study, the film suspension, at doses of 10, 30 and 75 mg/kg bw for 28 days, were orally administered to rats. After 28 days, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity study, neither signs of toxicity nor death among the rats were observed for up to 14 days of the experimental period. The results of the subchronic toxicity study show that there were no significant changes observed in the hematology and organ histology. Some alterations to the relative organ weight and blood biochemistry were observed, but they were considered to be temporary effects and not an indication of toxic effects. The overall findings of this study indicate that the film formulation of κ-Carrageenan and konjac glucomannan is non-toxic up to a dose of 75 mg/kg bw, which could be considered a safe dose for soft capsule application.

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 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.

Acute Oral Safety Study of Rosemary Extracts in Rats

2008 ◽  
Vol 71 (4) ◽  
pp. 790-795 ◽  
Author(s):  
ARTURO ANADÓN ◽  
MARIA R. MARTÍNEZ-LARRAÑAGA ◽  
MARIA A. MARTÍNEZ ◽  
IRMA ARES ◽  
MONICA R. GARCÍA-RISCO ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Behavioral Changes ◽  
Female Rats ◽  
Rosemary Extract ◽  
Weight Changes ◽  
Safety Study ◽  
Male And Female Rats ◽  
Histological Characteristics ◽  
Observation Period

Increasing interest in rosemary plants is due to their antioxidant and health-enhancing properties. The aim of this study was to evaluate the potential acute toxicity of two supercritical fluid extracts of rosemary. An acute safety study of rosemary extracts was conducted in Wistar rats at a single oral gavage dosage of 2,000 mg/kg of body weight. Rosemary extracts were well tolerated; no adverse effects or mortality were observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or change in food and water consumption occurred. Two weeks after a single oral rosemary extract dose of 2,000 mg/kg of body weight, there were no changes in hematological and serum chemistry values, organ weights, or gross or histological characteristics. Rosemary extracts appear to have low acute toxicity, and the oral lethal doses (LD50) for male and female rats are greater than 2,000 mg/kg of body weight.

scholarly journals Toxicity of Cypermethrin-chlorpyrifos and Butachlor to Tadpole of Quasipaa boulengeri

2021 ◽  
Vol 293 ◽  
pp. 01012
Author(s):  
Zhang Xiaoqin ◽  
Zhao Changju ◽  
Wu Haoyang
Keyword(s):  
Regression Analysis ◽  
Acute Toxicity ◽  
Scientific Basis ◽  
The Body ◽  
Analysis Method ◽  
Subchronic Toxicity ◽  
Accumulation Effect ◽  
Frog Tadpoles ◽  
Different Types ◽  
Long Time

The tadpole of Quasipaa boulangeri was taken as the research object in this paper. The toxic effects of cypermethrin-chlorpyrifos and butachlor on tadpole of Q.boulangeri were studied by acute toxicity experiment and subchronic toxicity experiment in order to master the toxicity of different types of pesticides on tadpole of Q.boulangeri and provide scientific basis for amphibian protection. The results of acute toxicity experiment were analyzed by the method of probability unit regression analysis. The results of the acute toxicity experiment were analyzed by means of the probability-unit regression analysis method, and the LC50 of cypermethrin-chlorpyrifos and butachlor to the 2-month-old frog tadpoles at 24h, 48h, 72h and 96h were 0.419, 0.357, 0.346L, 0.332 and 1.183, 1.108, 0.925 and 0.876(mg/L), respectively. In the subchronic toxicity experiment, we observed the accumulation effect of different concentrations of pesticides on tadpoles through the statistics of the growth and development of tadpoles exposed to the drugs for a long time. The results suggested that the body length and body weight of tadpoles increased slowly with the increase of time and concentration of pesticide in the solution during the experiment.

Determination of acute toxicity of Tiacyclin solution for injection in laboratory animals

2019 ◽  
Vol 331 (8) ◽  
pp. 25-27
Author(s):  
N.Y. Morozov ◽  
◽  
S.I. Tchukina ◽  
E.I. Koveshnikova ◽  
◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Laboratory Animals

PHARMACOGNOSTIC, ANTIOXIDANT AND ACUTE TOXICITY STUDY OF Ficus sycomorus (Linn) (Moraceae) ROOT AND STEM BARK

2020 ◽  
Vol 4 (2) ◽  
pp. 605-614
Author(s):  
Murtala M. Namadina ◽  
H. Haruna ◽  
U. Sanusi
Keyword(s):  
Acute Toxicity ◽  
Radical Scavenging ◽  
Stem Bark ◽  
The Body ◽  
Toxicity Study ◽  
Bark Extract ◽  
Root Extract ◽  
Acute Toxicity Study ◽  
Radical Scavenging Ability ◽  
Phytochemical Components

Most of biochemical reactions in the body generates Reactive Oxygen Species (ROS), which are involved in the pathogenesis of oxidative stress-related disorders like diabetes, nephrotoxicity, cancer, cardiovascular disorders, inflammation and neurological disorders when they attack biochemical molecules like proteins, lipids and nucleic acid. Antioxidants are used to protect the cells or tissues against potential attack by ROS. Most medicinal plants possess a rich source of antioxidants such as flavonoids, phenols, tannins, alkaloids among others. These phytochemicals are currently pursued as an alternative and complimentary drug. In this study, phytochemical components, antioxidant and acute toxicity study of the methanol extract of stem bark and root of F. sycomorus were carried out using standard methods. Findings from this study revealed the presence of some diagnostic microscopical features such as calcium oxalate, starch, gum/mucilage, lignin, Aleurone grain, suberized/Cuticular cell wall and inulin but calcium carbonate was absent in stem bark but present in the powdered root. Quantitative physical constants include moisture contents (6.40% and 7.82%), ash value (7.20% and 9.30 %) in stem bark and root respectively. Carbohydrates, alkaloid, flavonoids, saponins, tannins, glycoside, steroid, triterpenes and phenols were present in all the extracts. They were found to exhibit potent 1,1,-diphenyl 2-picryl hydrazyl (DPPH) free scavenging activity. The DPPH radical scavenging ability of the extracts showed the following trend Ascorbic acid < stem bark extract˃ root extract. The LD50 of the methanolic stem bark and root extracts were found to be greater than 5000 mg /kg and is considered safe for use. Nonetheless, further

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