


No 6 (2023)
- Year: 2023
- Published: 15.01.2024
- Articles: 10
- URL: https://rjsocmed.com/0869-7922/issue/view/9772
- DOI: https://doi.org/10.47470/0869-7922-2023-31-6
Articles
Колонка Главного редактора
Abstract
В связи с 30-летием журнала «Токсикологический вестник» в целях привлечения к токсикологической науке и поощрения активности молодых учёных и специалистов, на основании Решения Правления Общероссийской общественной организации «Общество гигиенистов, токсикологов и санитарных врачей» (протокол от 14.02.2023 г.) проведён конкурс работ молодых учёных и специалистов.



Original articles
New 3D in vitro models for assessing the toxicity of carbon nanotubes
Abstract
Introduction. In recent years, there has been interest in 3D cellular models that more accurately reflect in vivo conditions and can become an alternative to animal experiments in assessing the toxicity of nanomaterials. There is a need to develop 3D models of the human respiratory tract that can bridge the gap between traditional in vitro cell cultures and laboratory animals.
Material and methods. Mono- and co-culture 3D-models based on bronchial epithelial cells BEAS-2B and lung fibroblasts MRC5-SV40 have been developed. Pristine and purified from metal impurities TUBALL™ SWCNTs and Taunit-M MWCNTs were used as materials for the study. The range of concentrations studied included concentrations corresponding to actual occupational exposures (0.0006–100 µg/ml). To assess the cytotoxicity of CNTs in cell models, the level of lactate dehydrogenase (LDH) activity was determined after 72 hours of exposure.
Results. The cytotoxic effects of CNTs in 2D and 3D cell models manifested themselves in different concentration ranges: a three-dimensional model of bronchial epithelial cells turned out to be more sensitive to the effects of CNTs compared to a monolayer one, while in a spheroid model of fibroblasts a higher cytotoxicity threshold was noted for multi-walled carbon nanotubes compared to traditional cell culture. In three-dimensional cell co-cultures, a significant increase in LDH was observed starting at higher concentrations compared to monocultures.
Limitations. The present study was limited to the use of one type of cytotoxicity test when examining the effects of CNTs on cells of the respiratory system.
Conclusion. A method has been developed for three-dimensional cultivation of cells of the human respiratory system to simulate the interaction of epithelial and stromal cells of the lower respiratory tract. Traditional 2D cell models may underestimate or overestimate the toxicity of materials. Improved 3D in vitro models, closer in their properties and morphology to native tissue, are more reliable in determining toxic doses and targets.
Compliance with ethical standards. The study does not require the submission of a biomedical ethics committee opinion or other documents.
Author contribution:
Gabidinova G.F. — literature review, development of approaches for cultivating 3D-models, conducting tests on cells, statistical data processing, summarizing the results obtained, writing text;
Timerbulatova G.A. — cell culturing, conducting tests on cells, summarizing the results obtained, editing;
Ubeikina E.V. — literature review, cell culturing, data processing;
Sayagfarova A.A. — literature review, conducting tests on cells, data processing;
Fatkhutdinova L.M. — research design, analysis of the results, editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.
Conflict of interests. The authors declare no conflict of interest.
Acknowledgment. The study was supported by the Russian Science Foundation grant No. 22-25-00512. https://rscf.ru/project/22-25-00512/
Date of receipt: September 9, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 2023



Comparative analysis of cytology of rat bronchoalveolar lavage fluid after single exposure to metal oxide nanoparticles
Abstract
Introduction. Human production activities (metallurgical, mining, electronics production and processing, batteries) are related to air pollution of the working area and the environments of complex composition aerosols. Among the aerosol components, ultrathin particles of the nanometer range (including metal nano-oxides) are considered to be the most dangerous. Due to their prevalence, study to assess the cytotoxicity of metal oxide nanoparticles are relevant.
Material and methods. CuO, PbO, CdO, Fe2O3, NiO nanoparticle (NP) suspension were obtained by laser ablation. The study was done on white outbred female rats. A single intratracheal instillation of different chemical NPs was performed (in dose 0.5 mg/animal); control animals received a similar amount of deionized water. A day after the NP instillation bronchoalveolar lavage (BAL) was carried out with the subsequent assessment of its cytological indices.
Results. The cytotoxic action of the studied NPs, based on the cytological indices of the BAL fluid, is changed as follows (from greater to lesser): CuO NP > CdO NP > PbO NP > NiO NP > Fe2O3 NP.
Limitations. Such physical characteristics of nanoparticles as solubility in water and biological fluids, charge, adsorption capacity, resistance to aggregation, hydrophobicity, adhesion to surfaces, and the ability to generate free radicals have not been studied. Extrapolation of data from rodents to humans shall be done with caution, since cytotoxicity has been characterized only based on the main cellular parameters.
Conclusion. Bronchoalveolar lavage cytology can be used as an effective screening method for the cytotoxic effect of NPs.
Compliance with ethical standards. The animal study protocols were approved by the Institutional Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (Protocol No. 2 of April 20, 2020).
Contribution of the authors:
Sutunkova M.P., Minigalieva I.A., Privalova L.I. — the concept and design of the study, editing;
Klinova S.V., Ryabova Yu.V. — conducting a study, the collection and processing of the material, writing text, editing;
Tazhigulova A.V. — conducting a study, the collection and processing of the material, editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.
Acknowledgment. Authors express their gratitude to the team of the Ural Center for Collective Use “Modern Nanotechnologies” of the Ural Federal University named after the first President of Russia B.N. Yeltsin and personally to the director of the Ural Center for Collective Use “Modern Nanotechnologies”, professor, doctor of physical and mathematical sciences Vladimir Yakovlevich Shur, for the synthesis of suspensions, studied nanoparticles of a given characteristic on the basis of the “Modern Nanotechnologies” center.
Conflict of interests. The authors declare no conflict of interests.
Funding. The study had no sponsorship.
Date of receipt: May 18, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 2023



Effect of a phthalimide pesticide on human peripheral blood lymphocytes in vitro: induction of DNA damage
Abstract
Introduction. Captan is a contact fungicide from the phthalimide class, used in agriculture to combat plant diseases. However, the question of its genotoxicity for humans remains open. Various studies examining the mutagenic activity of captan using different tests have yielded conflicting results. This study aims to investigate the potential of captan to induce DNA damage in human peripheral blood lymphocytes in vitro using single-cell alkaline gel electrophoresis.
Material and methods. The DNA-damaging effect of captan (0; 2.5; 5.0; 10.0; 12.5 and 25 µg/ml) on lymphocytes of 26 donors was assessed with metabolic activation (+S9) and without it (–S9) using DNA comet analysis.
Results. In the absence of metabolic activation, captan exhibited a pronounced genotoxic effect on cells. Statistically significant effects of captan was found on lymphocytes of all donors. The level of DNA-damaging effect on lymphocytes from 20 out of 26 donors depended on the concentration. The fold increase in the “%DNA in the tail of comets” indicator compared to the negative control at a concentration of 25 µg/ml varied in the range of 4,3–226 times. In the presence of the S9 mixture, weak but significant effects meeting the criteria for a positive response were detected only in three donors.
Limitations. The genotoxicity of captan was studied only in vitro.
Conclusion. Captan induces DNA damage in human peripheral blood lymphocytes in vitro in the absence of metabolic activation. Under conditions of metabolic activation, genotoxic effects were low. The levels of DNA damage in peripheral blood lymphocytes of different donors after exposure to captan varied markedly, indicating the necessity to consider individual sensitivity to genotoxicants when utilizing the DNA comet method to assess the potential mutagenic activity of chemicals.
Compliance with ethical standards. The study was approved by the Ethics Committee of the Federal Scientific Center for Hygiene. F.F. Erisman” of Rospotrebnadzor (Protocol No. 1, September 29, 2020).
Author contribution:
Tsareva A.A. — the collection of material;
Ignatyev S.D. — processing of material;
Egorova O.V. — concept and design of the study, collecting and processing of material, analysis of the results; writing the text;
Kotnova A.P. — the collection of material;
Averianova N.S. — the collection of material;
Ilyushina N.A. — concept and design of the study, processing of material, analysis of the results; writing the text.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.
Conflict of interests. The authors declare no conflict of interest.
Funding. The study had no sponsorship.
Date of receipt: November 10, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 2023



Toxicity of products of thermal oxidative degradation of nitrogen-containing building polymer materials
Abstract
Introduction. In the event of fires in residential premises in which nitrogen-containing thermal insulation materials (foam rubber, polyisocyanurate foam) are used, the victims will be exposed to toxic thermal degradation products. Data on long-term disorders caused by intoxication by thermal degradation products of these materials could not be found in the available literature.
The aim of the study was to assess the toxicity of the products of thermal oxidative degradation of nitrogen-containing thermal insulation materials, both in the early and long-term post-intoxication period.
Material and methods. Static inhalation intoxication of rats with products of thermooxidative destruction of polyfoam and polyisocyanurate foam (at a concentration of 0,8HLC50) was simulated. The concentration of carboxyhemoglobin in the blood of rats, indicators of vital functions were determined immediately before and on days 1, 7 and 28 after exposure. To assess learning disabilities in rats, a conditioned reflex of active avoidance by swimming was developed. To assess spatial memory in rats, the method of developing and reproducing the conditioned reflex of searching for food was used.
Results and discussion. The intoxication of rats with products of thermooxidative destruction of the studied materials of moderate severity was simulated. Violations of the functions of the respiratory and cardiovascular system of rats in the early (7 days) and long-term (28 days) post-intoxication period were not detected. In the long-term (28 days) post-intoxication period, an increase in the duration of the latent period of active avoidance by swimming of rats was determined (compared with the control), an increase in the number of spatial memory errors in rats and the time of testing (compared with the control) was revealed.
Limitation of the study. Limitations are due to the methodology of the research being conducted. A quantitative analysis of only some gaseous products of thermal oxidative destruction was perfomed.
Conclusion. It was found that intoxication of rats with products of thermooxidative destruction of foam rubber and foam polyiysocyanurate (at a concentration of 0,8HLC50) led to impaired learning and spatial memory of rats in the long-term post-intoxication period.
Compliance with ethical standards. the study was approved by the local ethics committee of the The S.M. Kirov Military Medical. The work was guided by the requirements of legal acts on the procedure for experimental work using animals, including humane treatment of them.
Conflict of interest. The author declare no conflict of interest.
Acknowledgment. The study had no sponsorship.
Date of receipt: May 3, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 2023



Changes in the mitochondrial function of fibroblast-like cells exposed to copper oxide nanoparticles
Abstract
Introduction. Mitochondria are targets for almost all types of damaging agents, including toxins and oxidative stress. There is no doubt that possible effects on mitochondria should be taken into account in a comprehensive assessment of metal toxicity. Our objective was to establish changes in the mitochondrial function under the effect of copper oxide nanoparticles in vitro.
Material and methods. A monolayer culture of human lung fibroblast-like cells of the FLECH-104 line were exposed to copper oxide nanoparticles (CuO NPs) 21±4 nm in size, final concentrations of which in the media were 25, 50, and 100 µg/mL. We measured the rate of oxygen consumption by the cells and its changes under the influence of modulators, such as oligomycin, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and rotenone combined with antimycin A. We estimated parameters of mitochondrial function and the bioenergetics index.
Results. At the concentration of 100 µg/mL in the incubation medium, CuO NPs induced changes in the culture of fibroblast-like cells that impeded further assessment of the mitochondrial function. At the lower concentrations of 25 and 50 µg/mL, we observed a dose-dependent trend toward a decrease in ATP-related respiration and bioenergetics index. It is noteworthy that the concentration of 25 µg/mL increased the maximum and reserve respiratory capacity of the cells, which was probably related to the dual effect of copper as a toxicant and an essential element.
Limitations of the study. The study was conducted using only one cell line and three concentrations of CuO nanoparticles suspended in the culture medium.
Conclusion. We established that copper oxide nanoparticles, when added to the incubation medium, have a multidirectional effect on the mitochondrial function of fibroblast-like cells potentially attributed to biotic properties of this metal.
Compliance with ethical standards. The study does not require the opinion of an ethics committee.
Contribution of the authors:
Ryabova Yu.V. — data collection and analysis, draft manuscript preparation;
Bushueva T.V. — data collection and analysis, draft manuscript preparation;
Minigalieva I.A. — study conception and design, draft manuscript preparation;
Karpova E.P. — data collection and analysis;
Sutunkova M.P. — study conception and design, editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.
Conflict of interests. Authors declare no conflict of interest.
Funding. The study had no sponsorship.
Date of receipt: October 31, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 2023



Biomarkers of arsenic exposure in biogeochemical provinces
Abstract
Introduction. One of the direct methods of assessing the impact of contaminants on public health is the use of biological markers that allow determining the presence of a substance or its metabolite in human biological tissues and the dose received from all sources of this substance.
The purpose of this study was to determine the dependence of arsenic content in biological samples (hair)
of exposed residents on the level of its content in drinking water and to substantiate the effectiveness of the use of this biomarker in the conditions of a hydrogeochemical province in the Republic of Dagestan.
Material and methods. During this research the arsenic content in the hair of the exposed residents was measured with further comparison of the data obtained with its content in drinking groundwater. To determine the arsenic content in the hair of the exposed residents, an atomic absorption method was used with preliminary preparation of biosubstrate samples. Socio-demographic data were obtained from a questionnaire. Statistical data processing was carried out using Microsoft Excel.
Results. In the course of this study, a correlation was revealed between the arsenic content in the hair of the exposed residents and its content in the drinking water consumed, and a direct proportional relationship between these values was also revealed. Thus, with an increase in the concentration of arsenic in water by
0.1 mg/l, the arsenic content in the hair increases by 0.14 mkg/g. So, using of the hair of exposed residents as a biomarker of long-term exposure is recommended to small doses of arsenic in a biogeochemical province.
limitation of the study is the small sample size. However, this does not prevent the assessment of the effectiveness of using hair as a biomarker of arsenic exposure and preliminary conclusions for subsequent in-depth analysis of biomonitoring in the conditions of biogeochemical provinces.
Conclusion. As a rule, the content of natural toxic elements is characterized by trace amounts in the conditions of biogeochemical provinces. Biomonitoring will reveal the level of stress on the body and timely apply preventive methods before the clinical signs of intoxication are revealed.
Compliance with ethical standards. The study does not require the submission of a biomedical ethics committee opinion or other documents.
Authors contribution:
Abdulmutalimova T.O. — setting the purpose of the study, concept and design of the study, statistical data processing, text writing, editing;
Ramazanov O.M. — conducting field work, collecting and processing material, conducting chemical analysis, writing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.
Conflict of interest. The authors declare no conflict of interest.
Funding. The study had no sponsorship.
Date of receipt: October 23, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 2023



Problems of providing the Leningrad region`s population with full-fledged drinking water from underground sources
Abstract
Introduction. There are about 2,900 settlements in the Leningrad Region, the centralized water supply of most of which is based on the underground aquifers’ exploitation, which water is a significant source of essential elements.
Material and methods. The paper analyzes the results of 143,578 drinking water samples from 10 aquifers used as sources of drinking water supply. Within the framework of this study, the content of the following elements was evaluated: calcium, magnesium, potassium, copper, zinc, phosphorus, iron, manganese, selenium, molybdenum, chromium, sodium, chlorides, fluorides in comparison with the methodological recommendations of MP 2.3.1.0253–21 “Norms of physiological energy and nutritional needs for various population groups of the Russian Federation”.
Results. None of the aquifers of the Leningrad region provide the concentrations of phosphates, copper, potassium, zinc and selenium did not satisfy 20% of the minimum required intake from drinking water. Insufficient intake of essential macro- and microelements with drinking water can become one of the causes of metabolic disorders and lead to health disorders.
Limitations. Within the framework of this article, water quality is characterized by sanitary and chemical indicators, the chemical harmlessness of water is evaluated. The issues of microbiological and radiological safety of underground water in the Leningrad region, despite their relevance, aren`t considered in this article. In addition, the quality of drinking water in Sosnovy Bor wasn`t studied, since the centralized water supply of this locality is carried out from surface water sources.
Conclusion. Despite the undoubted advantages of groundwater, they are not able to satisfy the physiological need of the body for macro- and microelements. In this regard, it is necessary to develop targeted preventive programs aimed at replenishing the deficiency of micro- and macroelements in the body for each territory of the Leningrad region. These include the consumption of foods rich in microelements, the intake of biologically active additives containing scarce micro- and macroelements, as well as the use of mineral waters.
Compliance with ethical standards. The study doesn`t require the submission of the Biomedical ethics committee conclusion or other documents.
Authors contribution:
Stepanyan A.A. — content formation, statistical processing of results;
Isaev D.S. — content formation;
Markova O.L. — content formation;
Yeremin G.B. — content formation;
Shilov V.V. — content formation, text editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.
Funding. The study had no sponsorship.
Conflict of interest. The authors declare no conflict of interest.
Date of receipt: September 19, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 2023



The problem of selecting relevant descriptors in predicting the toxicity of chemicals
Abstract
Introduction. Mathematical models are widely applicable in conducting toxicological studies and can be used to fill gaps that arise in the assessment of chemical safety. Most of the attention is paid to the study of algorithms for constructing models, rather than approaches to choosing the most informative features.
The purpose of this study is to highlight aspects of the problem of choosing useful variables during mathematical modeling.
Material and methods. SMILES and molecular descriptors for organothiophosphates were generated in the interactive Google Colaboratory environment based on the program code using the RDKit, Mordred software. Using the tools of the scikit-learn Ver. 1.2.2 library, features were selected by filtering and by recursive feature exclusion. The values of acute oral toxicity parameters were taken from official information sources about chemicals. The obtained models are subjected to an internal validation procedure to evaluate the performance of the models.
Results. It should be noted that models where recursive exclusion of features was used have better characteristics than models based on descriptors selected by the filtering method. In particular, the acute toxicity prediction model for organothiophosphates based on the decision tree method with recursive exclusion of features has a high coefficient of determination (R2=0,91713), a relatively small root-mean-square error (RMSE= 0,35099), as well as high values of the cross-validation coefficient of determination (Q2LOO= 0,79756).
Limitations. The results obtained can be used only in predicting the toxicity of the specified group of chemicals with a similar mechanism of action.
Conclusion. The use of mathematical modeling is a promising tool for assessing the toxicity of chemicals, which has a number of features: on the one hand, it is a quick and convenient resource for screening the toxicity of substances, on the other hand, the model needs to be trained based not only on reliable research data, but also to carry out a qualitative selection procedure for signs that make a significant contribution to the functioning of the prognostic model.
Compliance with ethical standards. The study does not require the submission of the conclusion of the Biomedical ethics committee or other documents.
Conflict of interest. Author declare no conflict of interest.
Funding. The study had no sponsorship.
Date of receipt: September 21, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 202



Research methods
Ethylene oxide: methodological approaches to the determination of residues in food products (literature review)
Abstract
Introduction. Ethylene oxide is a prohibited fumigant in the Russian Federation and the states of the European Union (EU), however, the substance is used in a number of other countries to disinfect food before they are sold, so there is a risk of such products entering the Russian market, which can lead to negative consequences for public health. The residues of the fumigant in consumed products can cause neurological disorders and the development of cancer in humans. In addition, the presence of 2-chloroethanol in foodstuffs, the main transformation product of ethylene oxide, which is formed during the interaction of the fumigant with the matrix, is of concern.
Material and methods. The analysis of domestic and foreign databases and regulatory legal acts on the regulation of the dangers of ethylene oxide and 2-chloroethanol was carried out.
Results. The toxicological characterization of ethylene oxide and 2-chloroethanol shows the need to establish acceptable levels of contaminants in food, and, as a result, to create a simple and effective analytical control method.
Limitations.The study is limited to a review of open literature sources in describing the toxicological characterization and methods of analysis of ethylene oxide in food products.
Conclusion. The analysis of open literature sources has shown the need for scientific substantiation of hygienic standards and the development of a method for controlling the content of ethylene oxide and 2-chloroethanol in food products.
Compliance with ethical standards. The study does not require the submission of a biomedical ethics committee opinion or other documents.
Contribution of the authors. All co-authors made an equal contribution to the research and preparation of the article for publication.
Conflict of interests. The authors declare no conflict of interest.
Funding. The study had no sponsorship.
Date of receipt: October 19, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 2023


