scholarly journals Studying of the remote effects of the action on the organism of rats of the compaund from the class benzothiadiazinones

2020 ◽  
Vol 99 (9) ◽  
pp. 986-989
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya
Keyword(s):  
Body Weight ◽  
Reproductive Toxicity ◽  
The State ◽  
Male Rats ◽  
Hazard Class ◽  
Internal Organs ◽  
Teratogenic Effects ◽  
Technical Product ◽  
Two Generations

Introduction. Currently, many xenobiotics are widely used in industry and agriculture, which can cause serious disorders of pregnancy and fetal development. In this regard, the study of the effect of pesticides on embryogenesis in experiments on laboratory animals is a mandatory stage of sanitary and Toxicological research. The aim of the study was to investigate the long-term effects of a compound of the class of benzothiadiazinones for the assessment of embryotoxic and teratogenic effects, as well as reproductive toxicity by the method of two generations, with repeated oral intake of it into the body of warm-blooded animals (rats), establishing the levels of inactive doses for parents and offspring, and determining the hazard class. Material and methods. The embryotoxic and teratogenic effects were evaluated in female and male rats with a bodyweight of 230-240 g at the beginning of the study. Tested doses: 40.0; 100.0 and 250.0 mg / kg body weight (1 control and 3 experimental groups, 15 individuals each). Mating of females was performed with intact males in a ratio of 2:1. the Compound was introduced during 20 days of pregnancy. In the dynamics of the experiment, the state and behavior of rats, water and feed consumption, and changes in body weight were observed. The analysis of embryonic material took into account: the absolute and relative mass of internal organs (thymus, heart, lungs, liver, kidneys), to determine the teratogenic effect, a group of fruits (1/3) was fixed in Buena fluid and used to study internal organs using the Wilson method modified by Dyban the remaining 1/3 of the fetuses was fixed in ethanol to study the state of the skeleton using the Dawson method. When studying the reproductive toxicity of benzothiadiazinones in mammals (rats) using the method of two generations at doses of 15.0; 50.0 and 200.0 mg/kg of body weight (1 control and 3 experimental groups, 20 individuals each). Female F0 of the parent generation was primed during the mating period, pregnancy, and continued until the end of the feeding of the F2 generation. Mating 2:1. Results. Based on the results of studying the embryotoxic and teratogenic effects, invalid doses were established at the following levels: Noel for the mother - 100.0 mg/kg of body weight; Noel for embryotoxicity - 100.0 mg/kg of body weight; NOEL for teratogenicity-100.0 mg/kg of body weight. Results on the study of reproductive activity: NOEL for parents and offspring-50.0 mg/kg of body weight. Discussion. Studies on the effects of a long-term action of a technical product - “generic”, belonging to the class of benzothiadiazinones, found the studied compound for teratogenic, embryotoxic effects, as well as for its effect on reproductive toxicity, in accordance with the hygienic classification of pesticides by hazard (SanPiN 1.2.2584-10)to be a moderately dangerous compound (hazard class 3). Studied product class benzothiadiazinones on toxicological parameters are identical with the technical product is “originator”. Conclusion. Thus, the research shows that it is necessary to study the effects of long-term action of xenobiotics on the mammalian body when conducting sanitary and toxicological studies, to increase the reliability of the developed hygiene standards in environmental objects and food products.

ASSESSMENT OF TOXICITY AND HAZARD OF TECHNICAL PRODUCT OF TRIAZINONE’S DERIVATIVE

2019 ◽  
pp. 39-42
Author(s):  
V. N. Rakitskii ◽  
T. M. Еpishina ◽  
E. G. Chkhvirkiya ◽  
T A. Sinitskaya ◽  
Е. A. Mukhina
Keyword(s):  
Body Weight ◽  
Effective Dose ◽  
Biological Action ◽  
Male Rats ◽  
Peroral Administration ◽  
Hazard Class ◽  
Experimental Assessment ◽  
Technical Product

Experimental assessment of toxicity and hazard of technical product of triazinone’s derivative at its peroral administration into warm-blooded animals’ bodies (male rats) has been conducted to determine the character of the substance biological action. Its acute peroral toxicity was at the level of LD50 -1693 ± 470 mg/kg of body weight, hazard class – 4 according to Hygienic Classification of Pesticides (Sanitary Rules & Standards 1.2.2584-10). Effective dose was 62.5 mg/kg b.w., non-effective dose (NOEL) was 12.5 mg/kg b.w. ADI was 0.1 mg/kg b.w.

scholarly journals The toxicity of the technical product, derived triazolinones

2020 ◽  
Vol 64 (2) ◽  
pp. 83-87 ◽  
Author(s):  
Valery N. Rakitskii ◽  
E.G. Chkhvirkiya ◽  
T.M. Epishina
Keyword(s):  
Body Weight ◽  
Hematological Parameters ◽  
Oral Intake ◽  
Total Activity ◽  
The Body ◽  
Male Rats ◽  
Control Group ◽  
Long Term Effects ◽  
Technical Product

Introduction. Technical products that are part of pesticides recommended for use in agriculture must undergo a comprehensive sanitary and Toxicological examination, which is the basis for preventing the adverse effects of pesticides on the health of workers and the population, as well as on the sanitary state of the environment. Purpose of research - the study of the biological effect of the technical product derived triazolinthionov, with its repeated oral intake in mammals (rats), justification of the permissible daily dose (DSD) for humans. Material and methods. Chronic (12 months) experiment was conducted on male rats with a body weight of 200-210 g tested doses: 5.0; 50.0 and 500.0 mg/kg body weight (1 control and 3 experimental groups and 20 individuals each). In the dynamics of the experiment, we observed the condition and behavior of animals, water and food consumption, fixed the timing of death, recorded changes in body weight, physiological, biochemical and hematological parameters. Results. It was found that the dose of 5.0 mg/kg body weight does not cause significant changes in all studied parameters, doses of 50.0 and 500.0 mg/kg body weight had a polytropic effect on the body of experimental animals. Discussion. The studied technical product at repeated intake in doses of 50,0 and 500,0 mg/kg of body weight causes changes in the state of the Central nervous system of animals (statistically significant changes in SPP, total activity, path length, rest time), as well as changes in carbohydrate, lipid, and lipoprotein metabolism in the body, as evidenced by statistically significant changes in biochemical and hematological indicators. Consequently, doses of 50,0 and 500,0 mg/kg of body weight have a polytropic effect on the body of male rats and are effective. The dose of 5.0 mg/kg of body weight, when administered in animals of the experimental group in comparison with animals of the control group, there are no changes in all the studied parameters throughout the experiment, is accepted as invalid. On the basis of an inactive dose of 5.0 mg/kg of body weight and a reserve factor of 100, we have scientifically justified DSD for humans at the level of 0.05 mg/kg. Conclusion. Studies have shown that long-term repeated oral administration of the studied product into the body of animals (male rats) at a dose of 5.0 mg per 1 kg of body weight does not cause statistically significant changes in all the studied parameters, so the indicated dose is invalid. Doses of 50,0 and 500,0 mg/kg MT have a polytropic effect on the body of male rats and are effective. DSD for humans at the level of 0.05 mg/kg is justified based on the inactive dose at the level of 5.0 mg per 1 kg of body weight, established in a 12-month chronic experiment conducted on male rats, and the reserve coefficient of 100 (taking into account the unexpressed specific and long-term effects).

scholarly journals SCIENTIFIC SUBSTANTIATION OF THE PERMISSIBLE DAILY DOSE OF A TECHNICAL PRODUCT DERIVED FROM CHLOROACETAMIDES

2019 ◽  
Vol 63 (3) ◽  
pp. 147-151
Author(s):  
Valery N. Rakitskiy ◽  
E. G. Chkhvirkiya ◽  
T. M. Epishina
Keyword(s):  
Body Weight ◽  
Hematological Parameters ◽  
Oral Intake ◽  
The State ◽  
Chronic Experiment ◽  
Male Rats ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Technical Product ◽  
Daily Dose

Introduction. The scientific basis for the safe use of pesticides are comprehensive sanitary and toxicological studies to study the parameters of their toxicity and biological action, hygienic regulation for the purpose of scientific justification of regulations and safety measures when working with them. Purpose of research. The study of parameters of acute and chronic toxicity, biological actions technical product derived chloracetamide, at oral intake of mammals (rats), the rationale of the acceptable daily intake (ADI) for humans. Material and methods of research. In acute experiments used white male rats weighing 210-220 g Tested doses 1000 and 4000 mg/kg of body weight. Statistical group for each dose consisted of 6 animals. Chronic experiment was carried out on male rats with body weight 180-190 g. Doses were tested: 3,5; 17,6 and 70,0 mg/kg body weight. Statistical groups of each dose and control group included 20 animals. In the dynamics of the experiment, the state and behavior of animals, water and food consumption were observed, the terms of death were fixed, changes in body weight, physiological, biochemical and hematological parameters were recorded. The value of the permissible daily dose was determined by the ratio of the maximum inactive dose to the reserve ratio. Results. As a result of the research it was found that LD50 of the studied compound is 2172 ± 370 mg/kg. In the chronic experiment, the dose of 3.5 mg/kg b.w. does not cause significant changes in all the studied parameters, at a dose of 17.6 mg/kg b.w. single changes, the dose of 70.0 mg/kg. had a polytropic effect on the body of experimental animals. Discussion. The studied technical product for acute oral toxicity refers to low-hazard compounds. It was found that multiple oral intake of the studied product at a dose of 70.0 mg/kg weight body revealed changes in the state of the Central nervous system, and the analysis of biochemical and hematological parameters of blood showed that changes in carbohydrate, lipid and lipoprotein metabolism, aminobelic metabolism occur in animals. Conclusions. The studied compound for acute oral toxicity according to the hygienic classification of pesticides (SanPiN 1.2.2584-10) belongs to the 4th hazard class. Dose: 70,0 mg/kg weight body - acting; 17,6 mg/kg weight body - threshold; 3.5 mg/kg weight body - inactive. The permissible daily dose (DSD) for a person is 0.035 mg/kg.

Effect of oral administration of carbofuran on male reproductive system of rat

1995 ◽  
Vol 14 (11) ◽  
pp. 889-894 ◽  
Author(s):  
N. Pant ◽  
AK Prasad ◽  
SC Srivastava ◽  
R. Shankar ◽  
SP Srivastava
Keyword(s):  
Body Weight ◽  
Sperm Count ◽  
Reproductive Toxicity ◽  
Giant Cells ◽  
Toxicity Assessment ◽  
Male Rats ◽  
Ventral Prostate ◽  
Seminiferous Tubules ◽  
Effect Level ◽  
Dose Dependent Decrease

1 Carbofuran was administered orally to adult male rats at dose levels of 0.1, 0.2, 0.4 or 0.8 mg kg -1 body weight, 5 d wk-1 for 60 days. A dose dependent decrease was observed in body weight of rats treated with 0.2-0.8 mg carbofuran kg -1 body weight 2 A significant decrease in the weight of epididymides, seminal vesicles, ventral prostate and coagulating glands was observed at various test doses of carbofuran except at the lowest dose. 3 Decreased sperm motility, reduced epididymal sperm count along with increased morphological abnormali ties in head, neck and tail regions of spermatozoa were observed in rats exposed to 0.2, 0.4, or 0.8 mg carbo furan kg-1 body weight. 4 In addition, significant alterations were observed in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH) (decreased), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT) (increased) depending on dose. 5 Histologically, the results indicated the toxicity of carbo furan on testes depending on dose. The changes pre dominantly consisted of moderate oedema, congestion, damage to Sertoli cells and germ cells, along with the accumulation of cellular debris and presence of giant cells in the lumen of a few seminiferous tubules which showed disturbed spermatogenesis with the higher doses of carbofuran. 6 These observations determined a no effect level dose of 0.1 mg kg-1 body weight of carbofuran on the biochemi cal and morphological indices studied for male repro ductive toxicity assessment in the rat model. The results of the present study provide first hand information on the reproductive toxicity of carbofuran in male rats.

scholarly journals Toxicity assessment of a technical product of the triazole class

2020 ◽  
Vol 99 (11) ◽  
pp. 1276-1279
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya
Keyword(s):  
Body Weight ◽  
The Body ◽  
Male Rats ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
High Biological Activity ◽  
Experimental Animals ◽  
Technical Product ◽  
White Rats ◽  
Toxicological Studies

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.

scholarly journals Reproductive toxicity of triazole fungicides cyproconazole and epoxiconazole when exposed to male and female wistar rats during gametogenesis

2021 ◽  
Vol 54 (1) ◽  
pp. 52-61
Author(s):  
NR Shepelskaya ◽  
YaV Kolyanchuk
Keyword(s):  
Body Weight ◽  
Reproductive Toxicity ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Corpora Lutea ◽  
Disruptive Effect ◽  
Male And Female ◽  
Two Samples ◽  
Adverse Effect Level

Aim. Studying the effect of generic pesticides cyproconazole (98 %) and two samples of epoxiconazole (epoxiconazole 1 — 95,75 % and epoxiconazole 2 — 98,7 %) on the reproductive system of male and female Wistar Han rats at the level of the organism when exposed during gametogenesis, identification and characterization of their hazard, as well as assessment of the risk of reproductive toxicity of these compounds. Materials and Methods. The test samples were administered daily (5 days a week) by oral gavage at doses of 0.2 and 2.0 mg/kg for cyproconazole and 0.5 and 2.0 mg/kg for epoxiconazoles during 11 weeks for males, and 10 weeks for females. Also, there were kept intact males and females, intended for crossover mating with experimental animals. After the end of the exposure, functional indicators of the state of the gonads and the ability of animals to reproduce offspring were studied. The duration and the frequency of each stage of the estrous cycle in female rats and the number of motile sperm, the total amount of sperm and the number of abnormal forms of germ cells of the male rats were studied. The reproductive function state in females was evaluated on day 20th of pregnancy. Thereby the number of corpora lutea in the ovaries, number of alive, dead and resorbed foetuses and embryos, the foetus weight, total weight of litters were registered. The studies were carried out in accordance with the recommendations of the Bioethics Commission and the Centre’s standard operating procedures, developed in accordance with the recommendations and requirements of Good Laboratory Practice (GLP). Conclusions. Test substances at a maximum dose of 2.0 mg/kg of body weight have reproductive toxicity and endocrine-disruptive effect, exerting a significant antiandrogenic effect on males and antiestrogenic effect on female rats. No-observed-adverse-effect-level (NOАEL) for gonadal and reproductive toxicity for male and female Wistar Han rats were established. They are 0.2 mg/kg body weight for cyproconazole and 0.5 mg/kg body weight for epoxiconazole. Key Words: azole fungicides, cyproconazole, epoxiconazole, reproductive toxicity, antiandrogenic and antiestrogenic effects, Wistar Han rats.

Reproductive Toxicity Study of Clarified Slurry Oil in the Rat

1995 ◽  
Vol 14 (2) ◽  
pp. 119-128 ◽  
Author(s):  
A. M. Hoberman ◽  
M. S. Christian ◽  
R. Roth ◽  
S. Lovre ◽  
F. Koschier
Keyword(s):  
Body Weight ◽  
Reproductive Toxicity ◽  
Reproductive Organ ◽  
Female Rats ◽  
Male Rats ◽  
Feed Consumption ◽  
Clinical Effects ◽  
Weight Losses ◽  
Male And Female Rats ◽  
Weight Gains

Clarified slurry oil (CSO, CAS #64741–62-4; also termed carbon black oil), a residual product from the fluidized catalytic cracker in petroleum refining, has the potential to be absorbed through the skin. The reproductive toxicity of CSO in male and female rats was evaluated by the topical route of exposure. CSO was administered dermally to male rats at dosages of 0 (vehicle), 0.1, 1, 10, 50, and 250 mg/kg/day for 70 days before a cohabitation period with untreated female rats. CSO was administered also to female rats at the same dosages for 14 days prior to a 7-day cohabitation period and continuing until Day 0 of gestation (day spermatozoa was present in a smear of the vaginal contents or a copulatory plug was observed in situ). The dosage volume in both experiments was 1 ml/kg, adjusted on each day of dosage based on individual body weights recorded immediately before application of CSO. Under the conditions of these experiments, the paternal no-observable-adverse-effect-level (NOAEL) for CSO administered dermally was 1 mg/kg/day. The 10, 50, and 250 mg/kg/day dosages of CSO caused body weight losses and/or decreased body weight gains and reduced feed consumption. The 50- and 250-mg/kg/day dosages also caused adverse clinical effects. No mating, fertility, or testicular end points in male rats were affected by the highest dosages tested; therefore, the reproductive NOAEL for male rats is <250 mg/kg/day. The maternal NOAEL for CSO administered dermally was 10 mg/kg/day. The 50-and 250-mg/kg/day dosages of CSO reduced body weight gains; 250 mg/kg/day also reduced feed consumption. There were no adverse effects on gonadal function, estrous cycles, mating behavior, conception rates, or reproductive organ weights; therefore, the reproductive NOAEL for female rats administered CSO dermally is at least 250 mg/kg/day.

The influence of long-term melatonin administration on basic physiological and metabolic variables of young Wistar:Han rats

Biologia ◽  
2006 ◽  
Vol 61 (3) ◽  
Author(s):  
Monika Kassayová ◽  
Martina Marková ◽  
Bianka Bojková ◽  
Eva Adámeková ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Body Weight ◽  
Water Intake ◽  
Glucose Concentration ◽  
Tap Water ◽  
Serum Glucose ◽  
The Body ◽  
Male Rats ◽  
Epididymal Fat ◽  
Food And Water Intake

AbstractThe question of effects of long-term melatonin (MEL) administration have not yet been explained sufficiently, especially its metabolic consequences in young persons and animals. The aim of the present study was to analyze the effects of MEL given during prolonged time (for 3 months) and chronically (for 6 months) at the dose of 4 µg/mL of tap water, on the selected metabolic and hormonal parameters in young female and male Wistar:Han (WH) rats. The weights of selected organs, tissues, body weight gains and food and water intake were registered. Six weeks aged rats were adapted to standard housing conditions and light regimen L:D=12:12 h, fed standard laboratory diet and drank tap water (controls) or MEL solution ad libitum; finally they were sacrificed after overnight fasting. Prolonged MEL administration decreased serum glucose concentration and increased triacylglycerol and malondialdehyde concentration/content in the liver in females. In males MEL increased concentrations of serum phospholipids, corticosterone and liver malondialdehyde. MEL treatment reduced the body weight in both sexes and weight of epididymal fat in males, without any alterations of food and water intake. Chronic MEL administration reduced serum glucose concentration and increased concentration/content of glycogen, triacylglycerol and cholesterol in the liver and glycogen concentration/content in heart muscle in males. In females, the significant rise of serum corticosterone concentration and liver malondialdehyde content was recorded. MEL significantly increased liver weight and decreased thymus weight in males. MEL administration increased temporarily water intake in males, body and epididymal fat weights were similar to that in controls. Body weight of MEL drinking females was reduced in the 1st half of experiment only; the food and water intake did not differ from control group. The response in WH rats on MEL was more prominent as in the Sprague-Dawley strain (our previous studies). Male rats were generally more affected, probably due to higher daily and total consumption of melatonin.

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).

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