scholarly journals Study of the parameters of acute toxicity of the drug “Devimectin 1 %” with a single subcutaneous injection in white rats

2020 ◽  
Vol 22 (100) ◽  
pp. 28-31
Author(s):  
Yu. R. Hunchak ◽  
B. V. Gutyj ◽  
R. M. Sachuk ◽  
Ya. S. Stravsky

In the study of the drug for injectable use – “Devimectin 1 %”, together with the confirmation of therapeutic properties, it is necessary to determine the LD50 obtained in the study of acute toxicity. The aim of the work was to study the acute toxicity of “Devimectin 1 %” in white rats by injection. To fulfill this goal on the principle of analogues was formed control and three experimental groups of 4 animals each (n = 4). The drug was administered in doses of 5000.0; 10000.0; 20000.0 mg/kg body weight in absolute weight of the drug once subcutaneously in the withers. The control animals were injected subcutaneously with sterile saline 1.0 cm3. After taking into account the results of the previous experiment in the main experiment, 7 experimental groups were formed, whose rats were injected subcutaneously with “Devimectin 1 %” in doses of 5000.0; 7500.0; 10000.0; 12500.0; 15000.0; 17500.0 and 20000.0 mg/kg body weight, as well as a control group to which animals were injected with sterile saline with a volume of 1.0 cm3. There were 6 animals in each group (n = 6). It was found that for the administration of the drug at a dose of 5000 mg / kg body weight, no animal died, for 10000.0 and 20000.0 mg/kg body weight, respectively, one and 4 animals died. Death occurred for 2–6 days depending on the administered dose. In the main experiment with subcutaneous administration of “Devimectin 1 %” at a dose of 5000.0 mg/kg body weight during the 14-day period of the study, no animal died; for the introduction of the drug at a dose of 7500.0 mg/kg killed one animal; for 10000.0 – 2; for 12500.0 and 15000.0 – 3 rats; for 17500.0 – 5 rats and for the introduction of the drug at a dose of 20000.0 mg/kg body weight, all experimental animals died. The death of laboratory animals occurred for 2–6 days depending on the administered dose. According to the results of studies, it was found that the LD50 of the drug “Devimectin 1 %” under the conditions of its single subcutaneous administration to female rats is 12881.20 ± 1390.54 mg/kg, LD10 – 5978.43 mg/kg, LD16 – 7495.68 mg/kg, LD84 – 18266.73 mg/kg, LD90 – 19783.98 mg/kg, LD100 – 20959.49 mg/kg body weight, respectively. Therefore, the drug “Devimectin 1%” when administered subcutaneously can be classified as toxicity class VI – substances relatively harmless (LD50subcut> 4500,0 mg/kg). Further studies will be the next step in pre-registration trials to examine the subacute toxicity of “Devimectin 1 %”.

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)


2021 ◽  
Vol 23 (103) ◽  
pp. 109-115
Author(s):  
L.-M. Kostyshyn ◽  
R. Sachuk ◽  
Ye. Kostyshyn ◽  
O. Katsaraba

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.


2016 ◽  
Vol 5 (2) ◽  
pp. 50-52
Author(s):  
B R Bhagyalakshmi ◽  
◽  
R Galib ◽  
Mukesh Nariya ◽  
PK Prajapati ◽  
...  

Introduction: Kajjali is considered as the base in maximum Rasa Yogas (Herbo-mineral formulations). Shwasakuthara Rasa (SKR) is a well-known herbo-mineral formulation indicated in different kinds of Shwasa (respiratory diseases) and Kasa (cough) having Kajjali as a base ingredient. The present study is to evaluate the acute toxicity and anti-tussive activity of SKR one prepared with Kajjali (SKR1) and another without Kajjali (SKR2) in sulphur dioxide induced cough model in albino mice. Materials and Methods: Acute toxicity study was carried as per the OECD 425 guideline in wistar female rats. Anti-tussive activity was carried out against sulphur dioxide-induced cough reflex in mice. Results: Animals did not manifest any signs of toxicity and mortality at the dose of 2000mg/kg body weight, orally. Both test drugs (32.5 mg/kg, po) showed significant reduction in cough reflexes compared with control. SKR1 showed pronounced anti-tussive activity followed by SKR2 when compared to control group. Conclusion: The presence of Kajjali in the formulation is safe on acute administration and further enhances anti-tussive activity of the formulation may be due to increasing bioavailability of Ayurvedic formulation.


Author(s):  
Hamzah Alfarisi ◽  
Mawar Subangkit ◽  
Siti Sa’diah ◽  
Tutik Wresdiyati

This research aims to evaluate the safety of ethanolic extract of Acalypha hispida (A. hispida) leaves with acute toxicity test using 15 female rats strain Sprague-Dawley. A single dose of different doses of extract (2, 4, 8, and 16 g/kg body weight) was administrated orally, and theobservation was conducted for 14 days. The results revealed that the ethanolic extract of A. hispida leaves was relatively harmless (LD50 16 g/kg BW), did not affect body weight, and did not show clinical signs of toxicity during the observation periods. The parameters of blood serumbiochemistry of all extract-treated groups (alanine aminotransferase, aspartate aminotransferase, creatinine, and urea) did not change significantly  compared to the control group. The histological observation of the liver showed a significant increase in eosinophilic cytoplasm and basophilic nuclei at all doses. However, the ethanolic extract of A. hispida leaves did not significantly affect glomerulus/Bowman’s capsule ratio, glomerular cell density, and the proportion of normal cell tubule. In conclusion, the ethanolic extract of A. hispida leaves was relatively harmless with LD5016 g/kg BW and seems to be safe in low doses (2 g/kg BW).


Author(s):  
I. Ja. Kotsyumbas ◽  
O. M. Brezvyn ◽  
Y. A. Ivashkiv ◽  
H. V. Rudyk ◽  
Ju. V. Muzika

The article presents the results of the study of «Indez» disinfectant. An effective disinfectant for use in animal husbandry should be easy to use, be non-toxic, have broad bactericidal spectrum, be non-carcinogenic, have non-addictive micro-flora and provide a permanent bactericidal effect in the presence of animals, while sanitizing the air environment. «Indez» disinfectant is a small, amorphous grey powder with a specific odour, well sprayed. It is composed of triiodomethane (iodoform), zinc oxide, iron sulphate (II) (iron sulphate), copper sulphate, silicon dioxide, zeolite, active essential oils, a complex of surfactants and pH regulators, auxiliaries. This preparation can be used in the presence of animals; the disinfectant effect is based on the spectrum of antimicrobial action of its constituents. In the experiment of the study of the cumulative properties of «Indez» 80 white rats weighing 180-200 ± 10 g, tested doses of 1/5, 1/10, 1/20, from DL50 were used. To the animals of the experimental group, the suspension of the preparation was administered orally: in the first 4 days - 1/5 of DL50, then 1/10 and 1/20. Animals of the control group were administered saline at a dose of 0.5 ml. Observations on rats were carried out for 22 days. Depending on the dose of the drug, the cumulation coefficient. As a result of the study of the cumulative properties of the drug it is established that the introduction of a total dose of «Indez» 56,8 cm3 per 1 kg body weight does not cause death of white rats. When conducting a total dose of 63,4 cm3 / kg body weight one animal died, representing 5 %. Further administration of the drug lethality was on the 18-th day (total dose 83,13 cm3 / kg) – 15 %, on the 19-th day (total dose 93,0 cm3 / kg) – 20 % and the 20-th day (total dose 102,87 cm3 / kg) – 45 %. With an increase of 9,873 1,5 times (1,8095 cm3 / kg) on the 21-st day, the mortality rate was 80 %, and on the 22-nd day of the studies 90 % of laboratory animals were killed, the total dose was 1032,49 cm3 / kg. Under the study of the cumulative properties of «Indez» disinfectant, it was found that the cumulation coefficient in rats is 2,2 units. This, in turn, indicates that the test agent has moderately pronounced properties for cumulation. In this case, white rats inhibit the hematopoietic function of the bone marrow and reduce the body’s defences, as evidenced by a probable decrease in leukocyte count and a slight decrease in haemoglobin, lymphocyte count, spleen mass factor, and increased segmentation.


2021 ◽  
Vol 52 (1) ◽  
pp. 218-231
Author(s):  
I. Donowarti ◽  
S. B. Widjanarko ◽  
Y. Yunianta ◽  
P. Pudjiastuti

A field experiment Porang (Amorphophallus mueleri Blume) has the potential to be developed as a functional food ingredient because it contains high levels of glucomannan. Research on the acute toxicity test of macerated porang flour has been carried out. The results of research showed a toxic effect which was characterized by high SGOT and sodium levels. The purpose of this study was to find out the safety level of consuming porang flour with lowered calcium oxalate content. This research was an experimental study designed in one directional-pattern Completely Randomized Design using 5 treatments of porang flour administration with doses of 0; 5; 50; 500; 5000 and 15000 mg/kgbw and 6 repetitions for 60 days using Wistar-strain white rats (Rattus norvegicus) as laboratory animals. The results showed that during the treatment, the administration up to a dose of 500 mg/kgbw did not give a significant difference to all observed variables. The administration of 5000 and 15000 mg/kgbw gave a significant difference on the changes in body weight, the addition of the amount of water drunk, the levels of Calcium, Potassium and Sodium in the blood, SGOT and SGPT values, and observation on necrotic cells in the kidneys. The administration of the highest porang flour dosage, namely 15000 mg/kgbw did not cause any rat mortality and did not cause any real cell damage to the liver, but caused hyperactive behavior in female rats.


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.


Author(s):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov

The article presents the results of a study of the "Bisolbi" drug toxicity (powder of light ash color, poorly soluble in water). When it is mixed with water it forms a suspension of particles that settle rapidly. Values of acute drug toxicity were determined on rats. We studied groups of six animals of the same sex, as well as similar control ones. The "Bisolbi" drug was injected to white rats intragastrically, males weighing 310 ... 320 g in doses of 2500 and 2740 mg / kg. Each dose was used in six animals; distilled water (3 ml) was used for the controls. The LD50 was calculated by the probit analysis method proposed by Litchfield and Wilcoxon modified by Z. Roth. When administered orally, an atraumatic metal probe was immersed in the stomach. Within 14 days monitored the overall health status and behavior of animals, the manifestation or absence of symptoms of intoxication; noted the features of feed and water ingestion, assessed the condition of the coat, physiological functions. Then groups of experimental rats were euthanized and pathomorphologically examined. We studied the effect of "Bisolbi" with repeated introduction and on not purebred dogs. Two groups of 3-4 years of age were completed with an average initial body weight of 13.63 ... 15.11 kg. Before use, the additive was thoroughly mixed with feed. The drug was injected during 31 days at a dose of 0.5 g / kg. Dogs of the control group (three) were fed wheat flour. After 15 and 31 days in laboratory animals in order to characterize the general condition in the blood, the amount of protein, urea, glucose, creatinine, cholesterol were determined. Based on studies it was found that the drug daily application by animals, is low toxic and safe, does not provoke the development of pathological reactions. According to the Hodge and Sterner classification "Bisolbi" can be attributed to the 6th class of toxicity - relatively harmless. Accordingto GOST 12.1.007-76 LD50 of the drug is more than 151 mg / kg, but less than 5000 mg / kg it is the 3rd hazard class (moderately hazardous).


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.


1996 ◽  
Vol 271 (1) ◽  
pp. R48-R54 ◽  
Author(s):  
K. Ackroff ◽  
A. Sclafani

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.


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