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

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).

2021 ◽  
Vol 15 (3) ◽  
pp. 76-82
Author(s):  
E. N. Indyuhova ◽  
G. B. Arisova ◽  
I. P. Belykh ◽  
D. S. Poselov ◽  
A. A. Stepanov

The purpose of the research is to study the acute oral toxicity of the medicinal product for veterinary use Iverbutan, intended for the treatment and prevention of arachnoentomoses and nematodoses of poultry.Materials and methods. The studies were carried out on 30 outbred male rats weighing 210-240 g and 60 mice weighing 18–21 g. The animals were divided into experimental and control groups. The drug was administered once without dilution in the form of the provided solution using an intragastric tube. Doses of 2000, 4000, 6000, 8000 and 10 000 mg/kg were tested on mice, and on rats – 10 000, 8000, 5000, 4000 mg/kg. The animals of the control groups were injected with drinking water. Within 14 days after a single dose of the drug, the physiological state and behavior of animals, possible death, as well as the manifestation of symptoms of intoxication were monitored. The control of the body weight of the animals of the experimental and control groups was carried out on the day of the experiment (before drug administration), as well as on the 1st, 3rd, 7th, 9th and 14th days.Results and discussion. It was found that after oral administration of iverbutan to experimental animals, the average lethal dose, calculated by the Kerber method, was 5600 mg/kg of body weight in mice and 7000 mg/kg of body weight in rats (hazard class 4 according to GOST 12.1.007-76). The average lethal dose, calculated by the Miller and Tainter method, was 5292.0±1058.6 (4233.4÷6350.6) mg/kg of body weight in mice and 6463.2±1496.9 (4966.3÷7960.1) mg/kg of body weight of rats (hazard class 3 according to GOST 12.1.007-76), which indicates species sensitivity.


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.


2019 ◽  
pp. 72-77
Author(s):  
D. A. Yevseyenko ◽  
Z. A. Dundarov ◽  
E. A. Nadyrov

Objective: to develop and justify the application of a new experimental method of the simulation of liver cirrhosis in laboratory animals. Material and methods. The simulation of liver cirrhosis was performed on 11 eugamic white Wistar male rats with the body weight of 203.5 ± 22.2 g (experimental group). The control group consisted of 12 healthy laboratory animals. Acute toxic liver injury resulting in cirrhosis was caused by means of the intraperitoneal administration of 50 % solution of carbon tetrachloride (CCl4) in olive oil on the first day of the experiment at a dosage of 0.1 ml of CCl4 + 0.4 ml of olive oil per 100 g of the body weight of the animals, on the second day of the experiment - 0.3 ml of CCl4 + 0.2 ml of olive oil per 100 g of the body weight of the animals. For synergism and potentiation of the hepatotoxic effect of CCl4, the animals daily had free access to 10% ethanol solution. The duration of the experiment was 65 days. The clinical and laboratory parameters were evaluated, the histological assessment of the preparations was carried out. The obtained data were compared with the same parameters of the control group of the animals. Results. The reproducibility of the model was 81.8% (9 animals). The values of the biochemical blood analysis indicated statistically significant increases in the levels of total bilirubin, serum transaminases (AST, ALT), creatinine, a decrease in the glucose level in the animals of the experimental group. The complex morphological confirmation of liver cirrhosis in progress was obtained. Conclusion. The proposed method of the liver cirrhosis modeling correlate with the values of the biochemical blood analysis, pathological changes in the tissue of the liver and internal organs of liver cirrhosis in humans. With the help of the original model, it is possible to investigate the pathogenesis and effects of various groups of pharmacological drugs on liver cirrhosis and its complications (acute blood loss associated with the syndrome of portal hypertension).


2020 ◽  
Vol 5 (4) ◽  
pp. 103-107
Author(s):  
S. N. Lebedeva ◽  
O. S. Ochirov ◽  
M. N. Grigoryeva ◽  
S. D. Zhamsaranova ◽  
S. A. Stelmakh ◽  
...  

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.


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.


2019 ◽  
Vol 2 (2) ◽  
pp. 41-44
Author(s):  
O. L. Nechyporenko ◽  
A. V. Berezovskyy ◽  
H. A. Fotina ◽  
R. V. Petrov ◽  
T. I. Fotina

An important element in ensuring the epizootic well-being of the poultry industry is disinfection. Modern poultry farming requires a large number of effective disinfectants. It is known that the resistance of microorganisms to the effects of disinfectants is based on a genotypic mechanism. The nature of the formation of resistance to disinfectants and antiseptics is different than antibiotics. With regard to disinfectants, resistance is formed more slowly and the proportion of resistant strains in the population of microorganisms may not be high for a long time. This is due to different mechanisms of formation of resistance to antibiotics and disinfectants, in the first case – plasmid mechanism, in the second – chromosomal. However, increasing the resistance to the active substance in disinfectants can be widespread, so it is necessary to periodically rotate disinfectants. The goal of the work – to investigate the parameters of acute toxicity of the disinfectant biocide “Zodizin”. The studies were conducted in the laboratory of Veterinary Pharmacy and the Vivarium of Sumy National Agrarian University. The drug “Zodizine” contains: polyhexamethyleneguanidine hydrochloride – 21.0 %, alkylldimethylbenzylammonium chloride – 3.0 %. For toxicological examination of the disinfectant, healthy white male rats and white female rats weighing 200 ± 10 g 1.5 years of age were used. In the study of acute toxicity of animals observed daily, noted the general condition of the animals, features of their behavior. Studies have found that the toxic effect of the disinfectant “Zodizin” clinically manifested almost equally in both males and females. The average lethal dose for the rat female was 1000.0 ± 35.0 mg/kg body weight, males 1033.0 ± 34.3 mg/kg. Therefore, according to the classification of substances by toxicity, the drug by intragastric administration can be attributed to low-toxic substances. Observations on animals revealed that 1–3 hours after oral administration of the drug in a subtoxic dose in laboratory animals, shortness of breath and inhibition of the central nervous system were noted. Most of them died during the first day. Subsequent observations of the surviving animals indicated that their motor response was suppressed over the next 24–72 hours. Conclusions and prospects for further research: 1. It was found that the average lethal dose of the drug “Zodizin” with oral administration to rats-females was 1000.0 ± 35.0 mg/kg body weight, males – 1033.0 ± 34.3 mg/kg. 2. Experimental studies have proved that the disinfectant “Zodizin” according to GOST 12.1.007-76, belongs to the IV class of danger, that is, to the low-dangerous compounds, and according to GOST 12.1.07 – to the III class of hazard of substances and can be used for disinfection premises where animals and poultry are kept. Further, the sporoсide and corrosion properties of the “Zoodizin” biocide will be studied.


2020 ◽  
Vol 8 (1) ◽  
pp. 1 ◽  
Author(s):  
Nikolay Yakovlevich Golovenko ◽  
Valentina Nikolayevna Kovalenko ◽  
Vitalii Borisovich Larionov ◽  
Аnatoliy Semenovich Reder

Propoxazepam, 7-bromo-5 - (o-chlorophenyl)-3-propoxy - 1,2-dihydro - 3H-1,4-benzodiazepin-2-one, in the models of nociceptive and neuropathic pain showed significant analgesic activity. In order to explore clinical potential of propoxazepam for long term human consumption, toxicology testing in laboratory animals using well-accepted international guidelines is required. Acute toxicity tests were conducted by the oral administration of 2500; 3500; 4000; 4500 and 5000 mg/kg body weight to male and female mice and rats for a period of 3, 7 and 14 day. In subacute study, male rats were administered with various doses of propoxazepam (0.9, 4.5, and 9.0 mg/kg) to evaluate its toxicity for a period of 90 days. The effect of propoxazepam on body weight gain and organ weights, food and water consumptions were analyzed. From the present study, it can be concluded that the acute (3, 7 and 14 days) and subchronic (90 days) oral administrations of propoxazepam did not produce any clinical signs of toxicity or mortality of the male and female mice and rats. These results revealed that the LD50 of propoxazepam is greater than 5000 mg/kg and it therefore, belongs to the category V of relatively non-toxic substances according to the GHS. In the acute toxicity study, neither mortality no significant change in the body weight and the relative organ weights were recorded in all treated mice and rats. Present data set revealed that there wasn`t a strong correlation between body weight with food and water consumptions. The result indicates that the oral administration of propoxazepam did not produce any significant toxic effect in mice and rats and the substance can be safely used for therapeutic use in pharmaceutical formulations.  


Author(s):  
Redzuan Nul Hakim Abdul Razak ◽  
Suzanah Abdul Rahman ◽  
Asmah Hanim Hamdan ◽  
Roszaman Ramli ◽  
Muhammad Lokman Md Isa ◽  
...  

Aquilaria malaccensis or commonly known as ‘gaharu’ is a species of Aquilaria genus and belongs to the Thymelaeaceae family. It is widely distributed in Malaysia, Indonesia, and the Borneo Islands. Traditionally, its leaves were used to relieve bruises and studies have shown that they function as an antioxidant, aphrodisiac, and tranquilizer. Despite its proven beneficial medicinal properties, information regarding its toxicity is limited. Therefore, we performed a safety evaluation on the aqueous A. malaccensis leaves extract (AMAE) in Sprague Dawley rats. The assessment of acute toxicity based on the Organization for Economic Cooperation and Development (OECD) Guideline 420 revealed that AMAE did not influence mortality, clinical appearance, body weight gain, or necropsy findings at a dose of 2000 mg/kg body weight. In the sub-acute toxicity, all doses did not significantly modify the body weight and food and water intake. In male rats treated with 2000 mg/kg, there was a significant reduction in the relative weight of liver. Not only that, an increase in alkaline phosphatase and alanine transaminase was also observed in different groups among the female rats. A significant decrease in the creatinine level was also seen among male rats administered with different doses of AMAE. In both sexes, histopathological analysis had shown abnormalities in the liver and kidney of rats treated at the dose of 2000 mg/kg. In conclusion, the 50% lethal dose (LD50) of AMAE was estimated to be greater than 2000 mg/kg. In sub-acute duration, the findings suggested that AMAE administered orally is slightly toxic at higher doses (2000 mg/kg) and could provoke functional and structural changes in the kidney and liver of rats. Thus, the extract should be used with caution.


2020 ◽  
pp. 31-32
Author(s):  
Mikhail A. Levchenko ◽  
◽  
Natalia A. Sennikova ◽  

Toxicological assessment is a mandatory research step in the development of new insecticidal drugs. At the All-Russian Research Institute of Veterinary Entomology and Arachnology, a prototype of the insecticidal bait Mukhnet IF was obtained with an active ingredient content of 0.06% ivermectin and 0.015% fipronil, which showed a highly effective effect against houseflies. This work presents the results of the study of acute oral toxicity of the above agent. For this, male white mice with a live weight of 16-26 g were selected. They were kept on a starvation diet for one day in individual houses with water. The drug was given in mg/kg body weight the next day. A total of 33 doses have been tested, ranging from 100 mg/kg to 40,000 mg/kg. The animals were observed for 14 days. According to the research results, it was revealed that at doses up to 20,000 mg/kg there were no signs of intoxication, but when tested at 25,000 mg/kg in some mice, these signs were noted, and at 30,000, 35,000 and 40,000 mg/kg deaths were recorded 20±10, 45±30 and 60±20%, respectively. It was not possible to test the drug over the last above dose due to incomplete eaten by mice. According to the degree of danger for warm-blooded animals, the drug belongs to the 4th class of low-hazard drugs (average lethal dose of 5000 mg/kg or more) in accordance with the classification of GOST 12.1.007-76. When analyzing the literature data on the toxicological characteristics of preparations containing ivermectin and chlorfenapyr, it was revealed that the insecticidal agent in its acute toxicity for warm-blooded animals is comparable to known analogues.


Author(s):  
Meenakshi Sundaram Malayappan ◽  
Gayathri Natarajan ◽  
Logamanian Mockaiyathevar ◽  
Meenakumari Ramasamy

Abstract Objectives Madhulai Manappagu – a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate (Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats. Methods The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses. Conclusions The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured.


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