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

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.

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.


2020 ◽  
Vol 64 (2) ◽  
pp. 83-87 ◽  
Author(s):  
Valery N. Rakitskii ◽  
E.G. Chkhvirkiya ◽  
T.M. Epishina

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).


2020 ◽  
Vol 99 (9) ◽  
pp. 986-989
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya

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.


2021 ◽  
Vol 65 (1) ◽  
pp. 45-49
Author(s):  
Valery N. Rakitskii ◽  
Elena G. Chkhvirkiya ◽  
Tatiana M. Epishina

Introduction. Entering the body in various ways, pesticides, being biologically highly active compounds, can pose a real danger to public health, causing changes in non-specific biochemical reactions of metabolism occurring in all living cells. The antioxidant system, represented as a balance of lipid peroxidation and antioxidant protection (POL - AOZ), is one of the metabolic regulatory mechanisms of these responses. The aim of the study was to study the effect of a technical product (TP), a derivative of triazoles, on the acti-vity of antioxidant enzymes in the rat body, under its repeated oral intake in a chronic 12-month experiment. Material and methods. A chronic (12 months) experiment was performed on male rats with a bodyweight of 200-210 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 groups, 20 individuals each). In the dynamics of the experiment, after 1, 3, 6 and 12 months, the state and behavior of animals, water and food consumption were observed. Changes in the enzymatic indices of the body’s antioxidant defense system (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) were registered. Results. It was found that TP at a dose of 5.0 mg/kg of body weight does not cause significant changes in the activity of antioxidant enzymes, doses of 16.0 and 55.0 mg/kg of body weight cause an increase in the activity of superoxide dismutase (SOD) and a decrease in the activity of catalase in the body of experimental animals compared to control animals. Discussion. In the conducted chronic experiment, it was found that the studied TP at a dose of 5.0 mg/kg of body weight does not cause significant changes in the activity of the studied antioxidant enzymes in the body of rats. The introduction of TP at doses of 16.0 and 55.0 mg/kg of body weight causes a significant change in the activity of such antioxidant enzymes as SOD and catalase. Our results are consistent with the literature data, according to which the cell quickly reacts to oxidative stress by increasing the activity of SOD, and SOD is considered even as a stress protein synthesized in response to oxidative stress. Conclusions. The conducted research shows the feasibility of studying antioxidant enzymes’ activity in the mammalian body in sanitary and toxicological studies to increase the reliability of the developed hygienic standards of xenobiotics in environmental objects and food products.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Florence Nalimu ◽  
Joseph Oloro ◽  
Emanuel L. Peter ◽  
Patrick Engeu Ogwang

Abstract Background Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. Methods Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals’ relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. Results There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats’ relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium’s inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. Conclusion The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.


Author(s):  
Adetutu Adewale ◽  
Olaniyi Deborah Temitope ◽  
Awodugba Tamilore ◽  
Owoade Abiodun Olusoji ◽  
Olaniyan, Lamidi Waheed B. ◽  
...  

Typhoidal salmonella infections remain a challenge in the health care system in sub-Saharan Africa. Carrier status and advent of multi-drug resistant S. Typhi strains have necessitated the search for new drug leads. Hence, this study aims at investigating P. guajava and A. indica leaves for anti-salmonella activities. Guava and neem leaves were extracted by maceration in methanol and fractionated by solvent partitioning. In vitro activities were assessed by agar well diffusion and broth micro-dilution methods. Sixty male rats were randomized to 10 groups of 6 animals each for the in vivo experiments. Groups of rats except, normal control, were induced with 0.5McFarland of S. Typhi suspension orally. Treatment groups received 200 mg/kg body weight of extracts and fractions, and the control groups were treated with 14.29mg/kg body weight of ciprofloxacin and 1%v/v DMSO for 7 days post-infection. Biochemical parameters were determined spectrophotometrically. Hematological parameters were analyzed with automated hematology diagnostic machine. All fractions of P. guajava and three of A. indica inhibited S. Typhi growth with Zone of Inhibition (ZI) ranging from 11-15 mm. Active fractions inhibited 48.60-62.45% of S. Typhi biofilm formation at 25 mg/mL with Minimum Bactericidal Inhibitory Concentration (MBIC) of 0.39-12.5 mg/mL. All fractions improved body weight of treated rats and inhibited bacteremia at 44.75 and 95.94%. Hematological parameters improved in all fractions-treated rats. MDA was not significantly (p<0.05) altered in all groups. One fraction of P. guajava (ePg) lowered the elevated level in concentration of Nitric oxide (NO) while all fractions enhanced the lowered activity of SOD. Elevated (lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin (BIL) were lowered by all fractions to various extents in treated rats. Fractions of P. guajava, and A. indica could be further considered for identification of active anti-salmonella principle(s).


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Komlan M. Dossou-Yovo ◽  
Aboudoulatif Diallo ◽  
Povi Lawson-Evi ◽  
Yendubé T. Kantati ◽  
Tchin Darré ◽  
...  

Background. Herbal medication is a worldwide and ancient practice, mostly in developing countries, where a large part of the population is involved in this practice. Hence, studies must be conducted to evaluate their safety and efficiency to avoid or prevent toxicological risks due to their usage. In Togo, Carissa spinarum is a medicinal plant belonging to Apocynaceae family, used as an aphrodisiac or to heal some ailments including malaria, sickle cell anemia, hypertension, pain, and asthma. Notwithstanding its several ethnomedicinal benefits, just a few toxicological data associated with its chronic use are available. Objective. Therefore, this study aims to assess the toxicity of an ethanolic root extract of Carissa spinarum in Wistar rats. Methods. The 90-day oral toxicity process following OECD TG 408 guidelines is used. Male Wistar rats received Carissa spinarum root hydroethanolic extract at 500 and 1000 mg/kg for 90 days by oral gavage. Body weight changes, hematological and blood biochemical parameters, organ weight changes, malondialdehyde as a lipoperoxidation marker expressed according to tissue proteins, and histopathology of vital organs were assessed. Results. No signs of toxicity or mortality were observed during the 90 days experiment. Hematological parameters have not shown any treatment-related abnormalities. According to biochemical parameters, an increase in the chloride ion level was observed at 1000 mg/kg p < 0.01 . There was no significant difference between the treated groups and the control group concerning the malondialdehyde concentration, body weight, and organ relative weight. No changes in necropsy and histopathology of vital organs associated with extract treatment were observed. Conclusion. The results indicated that an ethanolic root extract of Carissa spinarum does not cause adverse effects, which can lead to Wistar rats’ death after 90-day oral administration at 500 and 1000 mg.


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.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 684-684
Author(s):  
Maria Amelita Estacio ◽  
Liezl Atienza ◽  
Roxanne Gapasin ◽  
Jonna Rose Maniwang ◽  
James Ryan Aranzado ◽  
...  

Abstract Objectives “Bignay” (Antidesma bunius), “lipote” (Syzygium polycephaloides) and “duhat” (Syzgium cumini) are indigenous berries in the Philippines that are known to contain high antioxidant properties and other health-promoting and disease-preventing compounds. However, oral toxicity studies on these berries are not yet explored. Hence, this study evaluated the acute oral toxicity of these berries in freeze-dried forms using 6-week old ICR mice following the OECD guidelines 425 (up and down method). Methods Treatment groups were administered with freeze-dried powders of “bignay”, “lipote” and “duhat” reconstituted in distilled water at various doses: 55 mg/kg body weight (BW), 175 mg/kg BW, 550 mg/kg BW, 2000 mg/kg BW and 5000 mg/kg BW while control group was administered with distilled water. Body weight, feed and water intake were obtained daily. Biochemical profiles were measured prior to administration of reconstituted berries at day 1 and prior to euthanasia. Toxicity, morbidity and mortality cases were observed daily. Euthanasia and necropsy were performed to check for gross organ abnormalities. Results Mice that received the different concentrations of “bignay”, “lipote” and “duhat” had normal feed and water consumption and gained weight during the test period. No clinical and behavioral signs of toxicity were observed and there was zero morbidity and mortality. Post-mortem evaluation showed no lesions on various organs examined. Blood ALT, BUN and creatinine levels were within normal published values. Conclusions These results show that different concentrations of freeze-dried “bignay”, “lipote” and “duhat” are non-toxic using ICR mice and therefore have high potential to be developed into food supplements and nutraceuticals. Funding Sources Philippine Council for Health Research and Development - Department of Food Science and Technology Enhanced Creative Work and Research Grant - Office of Vice Chancellor for Academic Affairs, University of the Philippines.


Author(s):  
Savin Chanthala Ganapathi ◽  
Rajendra Holla ◽  
Shivaraja Shankara Ym ◽  
Ravi Mundugaru

Objective: To study the acute oral toxicity of ethanolic extract of Actinoscirpus grossus (L.f.) Goetgh. and D.A. Simpson in Wistar albino rats.Methods: Ethanolic extract of the plant was assessed for single dose acute toxicity by employing Organisation for Economic Co-Operation and Development(OECD) guidelines 425 using Acute Oral Toxicity(AOT) software. The dosed (up or down as per the requirement) rats were observed for 14 days for general appearance, behavior, mortality, and necropsy. A total of 5 healthy female rats of body weight 225±25 g were used.Results: The test substance did not produce any mortality up to the dose of 2000 mg/kg per oral.Conclusion: Test substance is without any toxic potential even at the dose of 2000 mg/kg in animals and the Lethal Dose (LD50) value of A. grossus (L.f.) Goetgh. and D.A. Simpson was found to be more than 2000 mg/kg body weight.


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