scholarly journals TOXICOLOGICAL EVALUATION OF INDOMETHACIN AS A RISK FACTOR FOR WORKERS’ HEALTH

2019 ◽  
Vol 98 (5) ◽  
pp. 503-508
Author(s):  
N. A. Martynova ◽  
Larisa G. Gorokhova ◽  
V. A. Shtaiger

Introduction. The toxicity of indomethacin was studied for its hygienic regulation. Material and methods. The toxic properties of indomethacin in the experiments on out-bred and linear mice, rats, Guinea pigs and rabbits contained in standard vivarium conditions and quarantined have been studied. In the experiments, various modes (single, repeated, chronic) and ways of exposure (intragastric, inhalation, epicutaneous) were modeled. The average lethal dose (LD50) of Indomethacin and the threshold of a single acute action (Limac) were determined; irritant effect on the skin and mucous membranes, cumulative and allergenic activity were revealed. In subacute and chronic intake to the body, the main target organs were determined on the based of the results of biochemical and hematological studies. Results. DL50 for male rats, females and male mice, when introduced into the stomach, were have been established to be 20, 15 and 25.6 mg/kg respectively. It refers to the substances of hazard class 2. DL50 in the intraperitoneal introduction for the rats accounted for 13.8 mg/kg, for Guinea pigs - 500 mg/kg. The clinical picture of acute poisoning in mice and rats was characterized by low mobility, decreasing breathing, ataxia, muscle relaxation, anorexia, diarrhea, ulceration with the perforation of the intestines, and the death on the 2-4th days after the poisoning. In the experiments on Guinea pigs, the ulcerogenic effect was not detected. Local irritant effect on the skin and mucous membranes of the eyes was not revealed. It has a marked skin-resorptive action causing ulcerogenic effect and the death of the animals after 6 applications. The introduction of verospiron to the rats in a dose of 25 mg/kg simultaneously with the application of indomethacin ointment on the skin prevented the ulcer development in the gastrointestinal tract and the death of the animals. No sensitizing effect was detected. It has an average cumulative ability: the cumulation coefficient amounted to 2.6. In a subacute experiment, there was a decrease in the body temperature and summation-threshold index, an increase in the vertical motor activity and a threshold of pain sensitivity. During the study of blood serum an increase in AcAt activity, a rise of chlorides in the blood serum and their decrease in the urine, and an increase in the number of erythrocytes and hemoglobin in peripheral blood were revealed. In the pathomorphological study, there was an increase in the coefficients of liver mass and ulceration of the stomach and intestines. The threshold of acute inhalation action accounted for 0.52 mg/m3 (by the reduction of the summation-threshold index and the content of sodium and chlorides in the urine). Conclusion. The maximum permissible concentration of indomethacin in the air of the working area was of 0.05 mg/m3 with the mark “special protection of the skin and eyes”, hazard class 1, aerosol.

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.


2021 ◽  
Vol 10 (2) ◽  
pp. 89-97
Author(s):  
EL Lappa ◽  
◽  
C Bogning Zangueu ◽  
EL Nguemfo ◽  
JJ Kojom Wanche ◽  
...  

Ficus vogelii is a medicinal plant mainly found in tropical Africa and reported to treat inflammatory complaints. This study aims to evaluate the acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii stem bark in wistar rats. For acute study, aqueous extract at a single dose of 5000 mg/kg body weight was administered to female rats and observed for 14 days. In the sub-chronic study, the extract was administered daily to both sex rats at the doses of 100, 200, 400, and 600 mg/kg body weight for 28 consecutive days. Body weight was measured weekly, while hematological, biochemical, and histopathological parameters were analyzed after euthanize. Aqueous extract of Ficus vogelii at all tested doses didn’t produced any mortality or significant change on the body weight and relative weight of rats on acute and sub-chronic studies. The lethal dose 50 was estimated greater than 5000 mg/kg (DL50˃5000 mg/kg). Hematological parameters were recorded non-significant in all treated rats. Aqueous extract at 600 mg/kg significantly changed transaminases and alkaline phosphatase activities, these changes were reversible in satellites. The concentrations of bilirubin was increased at 200 and 600 mg/kg in male rats, at 100, 400 mg/kg in female rats. The levels of lipids markers didn’t changed, except the significant decrease of LDL-cholesterol. Histological examination didn’t showed any change in the architecture of the liver and kidney of rats treated compared to control. Thus aqueous extract of Ficus vogelii stem bark didn’t produced adverse effects in rats after oral acute and sub-chronic treatment.


Author(s):  
D. Morozenko ◽  
F. Leontieva ◽  
K. Gliebova

Topicality. Hypokinesia is a condition of insufficient motor activity of the body with limited pace and volume of movement, and is currently the fourth leading cause of endemic death in the world. It is known that hypokinesia can affect the metabolism of components of bone and cartilage, which is the basis for the development of pathological processes, but there are no biochemical markers of this process in the literature. Thus, currently, there is insufficient number of experimental scientific works devoted to the study of biochemical parameters characterizing the state of the connective tissue in the experiment to assess the impact of hypokinesia on the body, and this fact determines the relevance of the study. Aim. To study the dynamics of the main metabolites characterizing the state of the connective tissue in the blood serum in hypokinesia in rats of different ages. Materials and methods. The studies were performed on 42 white male rats aged 3 and 12 months, kept in the vivarium of the Sytenko Institute of Spine and Joint Pathology National Academy of Medical Sciences of Ukraine, Kharkiv. The conditions of hypokinesia were reproduced using a specially designed device that limited the mobility of the animal without disturbing the ventilation of the body. Animals were removed from the experiment by decapitation in Day 7 and 30 of immobilization under thiopental anesthesia. The content of sialic acids in the serum was determined by the Hess method, chondroitin sulfate – by Nemeth-Csoka method modified by L. I. Slutsky, the fractional composition of glycosaminoglycans (GAG) – by the reaction with resoquine. Results and discussion. In the study of the rat serum, it was found that in intact animals of 3 and 12 months of age the content of sialic acids was different; it was 2.94 ± 0.16 and 1.98 ± 0.09 mmol/L, respectively. After 7 days of hypokinesia, their concentration in young animals did not change, but in older animals, this figure increased. By Day 30, the serum sialic acid levels suddenly increased compared to intact animals. In animals of 12 months of age, the concentration of sialic acids in the blood serum increased by both Day 7 and Day 30 of hypokinesia, especially at the end of the experiment. Hypokinesia also showed a significant increase in serum concentrations of chondroitin sulfates on Day 7 of the experiment in animals of both age groups. At the same time, the level of these metabolites on Day 30 was at the same level. In young rats on Day 7 the fraction of GAG remained unchanged, but on Day 30 there was a significant decrease. During this period, the second fraction of GAG increased. In animals aged 12 months on Day 7 and 30, the content of most GAG fractions was lower than the values characterizing the fractional composition of GAG in intact rats. Conclusions. Thus, the determination of sialic acids, GAG fractions and chondroitin sulfates in the serum can be presented as a set of biochemical tests to assess disorders of the connective tissue metabolism while limiting the motor activity of the body. It has been found that the 30-day hypokinesia causes significant disorders of the connective tissue, and it is reflected in changes in the biochemical parameters of the serum of experimental 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 29 (5) ◽  
pp. 58-63
Author(s):  
Susanna Babken Poghosyan ◽  
Natalya Stepan Tadevosyan ◽  
Susanna Arshavir Muradyan ◽  
Siranush Hovhannes Ter-Zakaryan ◽  
Ashot Norayr Jzhandzhapanyan ◽  
...  

Introduction. Herbal medicines are unique therapeutic agents that represent multicomponent complexes of biologically active substances. They have low toxicity, a wide spectrum of therapeutic action with a minimum of side effects and a relatively low cost. Capparis spinosa L. has been widely used in traditional medicine for the treatment of various diseases and health conditions. Material and methods. An assessment of the toxicometric parameters of Capparis spinosa L. seed’s oil was done by a single oral and dermal exposure, the average lethal doses have been calculated for both routes, sensitivity by sex has been studied. The local irritant, skin resorptive, effect on the mucous membranes of the eyes of experimental animals was investigated. Sensitizing activity was studied according to the complex sensitization scheme. Processing of the results was carried out by the method of variation statistics. Standard errors and other indicators were calculated using the Litchfield-Wilcoxon probabilistic analysis method modified by Prozorovsky. The difference in mean values was estimated using Student’s t-test. Results. The acute toxicity of the oil was not expressed, death of animals was not observed. Average lethal dose for a single oral exposure was above 7000 mg/kg and dermal more than 3000 mg/kg. Sensitivity by sex in an acute experiment has not been established. The oil had a mild irritating effect on the mucous membranes of the eyes. It did not show skin-irritating, resorptive-toxic and sensitizing effects. Conclusion. Capparis spinosa L seed’s oil belongs to the 4th hazard class (low hazard) according to the hygienic classification and safety requirements of substances.


2019 ◽  
Vol 15 (2) ◽  
pp. 27-35 ◽  
Author(s):  
O. L. Romanova ◽  
D. V. Sudukov ◽  
M. A. Golubev ◽  
M. L. Blagonravov ◽  
V. V. Goshkoev ◽  
...  

Purpose: identification of pathological changes in the liver at early stages of the effect of clozapine and clozapine combined with ethanol to improve the diagnosis of this acute exposure.Materials and methods. The experiments were carried out on outbred male rats (n=15). The animals were split into 3 groups, 5 animals in each: 1) control (intact rats); 2) clozapine, 3) clozapine and ethanol. Clozapine at a dose of 150 mg/kg of the animal’s body weight was administered orally under anesthesia (chloralose), clozapine (150 mg/kg) with ethanol at a dose of 5 ml/kg — orally. Rats were removed from the experiment after 3 hours by decapitation. Samples of liver tissue were studied using light microscopy. During histological examination, the following morphological signs were evaluated: blood circulation disorder (presence of venous, capillary, and arterial congestion, appearance of venous hemorrhage), absence of nuclei staining, cytoplasm lumpiness, cytoplasm vacuolation, presence of necrosis foci, appearance of cellular response (a large quantity of leukocytes per power field). The assessment was done using the F-test. Forensic chemical analysis was carried out using a high-performance liquid chromatograph equipped with a mass detector. The content of clozapine, norclozapine, and clozapine-N-oxide in blood serum and liver homogenate of rats was evaluated.Results. In the control group, no pathological changes in liver tissue were observed. 3 hours after clozapine administration, venous congestion was detected. 3 hours after administration of clozapine and ethanol combination, venous congestion and absence hepatocyte nuclei staining were observed. It was found that after combined administration of clozapine and ethanol, the blood serum clozapine was 1.94-fold and clozapine-N-oxide was 2.3-fold lower than when clozapine was administered as a single drug while the content of norclozapine showed no difference.Conclusion. Changes detected in the liver, together with changes in other organs and findings of the forensic chemical analysis, allow establishing the fact of clozapine poisoning. Understanding of the processes going on in the body during such intoxications helps rendering medical assistance to victims more effectively.


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.


2021 ◽  
Vol 6 (1) ◽  
pp. 25
Author(s):  
Helmi M. El-bendary ◽  
Abdel Moniem S. Hassan ◽  
Amr R. Zaki ◽  
Fatma I. Abo El-Ela

Acute pesticide poisoning is an important public health problem worldwide and accounts for a significant number of deaths occurring each year. The present article aimed to investigate toxic effects of imidacloprid (IMD) nanoemulsion formulated using ultrasound dispersion technique, and characterized using FTIR, TEM anddynamic light scattering in adult rats. The synthesized Nano-emulsion droplets are mainly spherical in shape and their sizes ranged between (19nm –128 nm) with zeta potential of −38.8± 0.mV. Also, The median lethal dose (LD50) of nano imidacloprid in rats was 39 mg/kg body weight. Administration of different doses of 3, 1.4 and 0.8 mg.kg mg/kg b.wt. of IMD Nano emulsion to rats for 21 days, adversely affects the body weight and weight gain, and resulted in a significant increase in serum serum ALT, AST activities , glucose, Creatinine, urea and cholesterol concentrations, as well as reduced serum total proteins, Albumin and globulin as compared to control rats. The results clearly suggest that treatment with IMD nanoemulsion adversely affects the liver & kidney functions which confirmed by the histopathological findings. Nanoemulsion form and also increases the DNA damage as confirmed by the comet test


Author(s):  
Galina I. Pavlenko ◽  
◽  
Vasiliy I. Dorozhkin ◽  
Galina V. Filipenkova ◽  
◽  
...  

The article presents the results of toxicological studies, investigated the cumulative properties of disinfectant Astradez Bioxy, as well as its effect on the body of experimental animals: white male rats and white mice. It has been established that disinfectant Astradez Bioxy is a moderately toxic compound (3rd hazard class), does not have a negative effect on the body of animals and can be used for disinfection in veterinary practice. According to the degree on human impact Astradez Bioxy belongs to the 4th class of low-hazard 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.


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