Introduction. Carbon nanotubes (CNTs) are high-tech materials, but their genotoxic and carcinogenic potential has not been sufficiently studied. To assess the genotoxicity of CNTs, alternative in vitro methods are needed, the development of which is impossible without a preliminary study of DNA damage mechanisms.

Material and methods. The study was conducted on 2D and 3D human respiratory cell cultures. The effects of Russian single-wall (SWCNT TUBALL™, purified and unpurified) and multi-wall (MWCNT Taunit-M) CNTs were investigated. The cytotoxicity of CNTs was assessed using the MTS assay and lactate dehydrogenase (LDH) assay. The genotoxic potential was investigated using the DNA comet method. The localization of CNTs in cells was determined by transmission electron microscopy. To detect oxidative stress, reactive oxygen species (ROS) levels were measured using a DCFDA kit. The pro-fibrogenic and pro-apoptotic activities of CNTs were determined by assessing gene expression (TGF-β1, P53, Bax, Bcl2) using real-time PCR.

Results. Fibroblasts demonstrated the highest sensitivity to CNT cytotoxicity, while A549 cells demonstrated the lowest. CNT genotoxicity was detected in all cells at a concentration of 20 µg/ml. All CNTs penetrated the cells, and MWCNTs were detected in the cell nucleus. Oxidative stress was induced dose-dependently by all types of CNTs, with unpurified SWCNTs producing the most pronounced effect. In BEAS-2B cells, MWCNTs induced an increase in TGF-β1 expression at low concentrations, while SWCNTs induced a similar effect only at high concentrations. In A549 cells, all types of CNTs exhibited a pro-fibrogenic effect at all concentrations. In fibroblasts, no significant increase in TGF-β1 gene expression was observed. In BEAS-2B and A549 cells, CNTs demonstrated the ability to initiate apoptotic signaling pathways, while in MRC5-SV40 cells, no signs of apoptosis in response to CNTs were detected. Studies in 3D cell culture models demonstrated signs of oxidative stress in response to CNTs; no pro-apoptotic or pro-fibrogenic effects of CNTs were detected.

Limitations. The possible role of DNA repair was not assessed in this study. The study covers a limited number of specific types of domestically produced CNTs.

Conclusion. The genotoxicity of CNTs is determined by their type and type of target cells, manifesting itself in a subtoxic concentration range. Key mechanisms include oxidative stress, direct DNA damage, and induction of apoptosis. The results obtained on 3D models demonstrate lower sensitivity, which may indicate a protective role of the tissue organization.

Compliance with ethical standards. The study does not require a biomedical ethics committee opinion or other documents.

Authors’ contribution:
Fatkhutdinova L.M. – study design, analysis of material, editing;
Timerbulatova G.A. – cell culturing, cell testing, summarizing the results, editing;
Gabidinova G.F. – development of approaches for culturing 3D models, cell testing, literature review, statistical data processing, summarizing the results.
All co-authors approved the final version of the article and are responsible for the integrity of all parts of the article.

Conflict of interest. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.

Funding. The study was supported by the Russian Science Foundation grant No. 22-25-00512. https://rscf.ru/project/22-25-00512/

Received: January 22, 2026 / Accepted: February 2, 2026 / Published: March 18, 2026

Introduction. The etiology of acute toxic hepatitis induces a multifaceted and time-dependent profile of transcriptomic remodeling, simultaneously engaging several pathogenic axes. For accurate etiological classification, classical differential expression analysis should be complemented by methods focused on recognizing multidimensional feature combinations and quantifying their contributions. The aim of this study was to evaluate the expression profile of a gene panel reflecting the antioxidant response, glutathione-dependent detoxification, cell cycle control, and programmed cell death for differentiating the etiology of acute toxic hepatitis and identifying the contribution of these markers to class discrimination.

Material and methods. The experiment was performed on 210 male rats. Models of carbon tetrachloride-induced, paracetamol-induced, and ethanol-induced toxic hepatitis were established. The expression of Nfe2l2, Nqo1, Hmox1, Sod1, Gclc, Gstm1, Gstp1, Gstt1, Ripk1, Chek1, Casp7 genes in liver tissue was assessed 24 and 72 hours after exposure. The level of statistical significance was evaluated using the Mann-Whitney U test followed by the Benjamini-Hochberg correction for multiple comparisons. For integrative analysis, a multiclass classification task was performed on tabular features using XGBoost, LightGBM, and CatBoost algorithms. Performance was assessed by ROC/AUC in a one-vs-rest scheme with a 75/25 hold-out split and hyperparameter tuning via stratified cross-validation. Interpretation was performed using SHAP and catboost-evaluation methods.

Results. Transcriptomic responses depended on the toxicant and time point, involving bidirectional shifts within functional pathways. All three algorithms demonstrated very high class discrimination (AUC 0.987–0.9998). For carbon tetrachloride, XGBoost achieved the highest AUC (0.9998), while for paracetamol and ethanol, CatBoost showed the most balanced performance (0.9967 and 0.9960, respectively). SHAP analysis revealed that discrimination was primarily driven by markers of oxidative stress and detoxification, foremost Hmox1, followed by Gstm1, Sod1, and Gstt1. CatBoostEvaluation confirmed a robust performance gain upon inclusion of Hmox1 (Score 23.145%; p=0.000089), Gclc (13.627%; p=0.000089), and Gstm1 (12.898%; p=0.000089), whereas Gstp1 and Chek1 did not demonstrate significant incremental contribution in this setting.

Limitations. The study was conducted on a single in vivo model, within an acute experimental design, and using specific toxicant doses. This may limit the extrapolation of the results to chronic exposure scenarios or other dose regimens, animals of a different species and sex.

Conclusion. The expression profile of a compact gene panel provides reliable etiological classification of acute toxic hepatitis. An approach combining classical statistics and interpretable machine learning establishes a foundation for subsequent validation on independent series and expansion to multimodal features in tasks of early diagnosis and assessment of corrective interventions.

Compliance with ethical standards. The study was approved by the Bioethics Committee of the Ufa Research Institute of Occupational Medicine and Human Ecology (protocol No. 06-09 dated 05.09.2024). The study was conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS N 123) and with the Directive 2010/63/EC of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes.

Authors’ contribution.
Karimov D.O. – study concept and design, material processing, statistical analysis, application of machine learning methods, manuscript writing, editing, approval of the final version of the article, responsibility for the integrity of all its parts.

Conflict of interests. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.

Funding. The work was carried out as part of the state assignment for the industry research program of Rospotrebnadzor “Scientific substantiation of the national system for ensuring sanitary and epidemiological welfare, managing health risks and improving the quality of life of the population of Russia” for 2021–2025. clause 6.1.8, state registration number 121062100058-8.

Received: January 26, 2026 / Accepted: February 2, 2026 / Published: March 18, 2026

Introduction. One of the reasons for the observed increase in the incidence of malignant neoplasms is the lack of control over the spread of non-genotoxic carcinogens. The purpose of this review is to analyze the problems in testing non-genotoxic carcinogens and ways to develop adequate approaches to their detection by analyzing the epigenetic activity of compounds.

Material and methods. The analysis of more than 200 scientific publications on the topic of detection of carcinogenic hazards has been carried out. The databases PubMed (149), Scopus (62), Web of Science (33), ResearchGate (15), RSCI (12) were used. Based on the analysis, 50 most informative publications reflecting the main aspects of the problem of testing non-genotoxic carcinogens have been selected.

Results. The article presents the problem of preventing carcinogenesis caused by non-genotoxic compounds, the relevance and scientific justification for testing these compounds, and discusses existing approaches to developing regulated control measures for non-genotoxic carcinogens. An author’s method for detecting epigenetically active compounds using genetically modified cellular systems with a reporter epigenetically suppressed fluorophore protein gene is proposed as an integral screening test for the potential effect of a compound on the system of epigenetic regulation of gene expression.

Limitations. The study is based on an analysis of open data on testing of genotoxic and non-genotoxic compounds in the aforementioned databases.

Conclusion. The data confirming the relevance and necessity of testing non-genotoxic carcinogens, existing challenges and ways to solve problems in the field of preventing the incidence of malignant neoplasms are systematically reviewed.

Compliance with ethical standards. The opinion of the Bioethics Commission is not required.

Authors’ contribution:
Yakubovskaya M.G. – concept and design of the study, writing, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Maksimova V.P. – collection and processing of the material, writing the text for testing epigenetically active compounds, editing;
Belitsky G.A. – writing the text, editing, approval of the final version;
Kirsanov K.I. – research concept and design, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The research was supported by the Russian Science Foundation, grant No. 25-15-00432.

Received: December 24, 2025 / Revised: January 12, 2026 / Accepted: February 2, 2026 / Published: March 18, 2026

Introduction. The toxic effect of gasoline is associated with CNS dysfunction and respiratory damage, such as chemical pneumonitis, which contributes to the severity of the condition of patients with acute oral poisoning. Currently, there are no pathogenetically based approaches to the treatment of chemical pneumonitis caused by oral intake of gasoline. Adequate experimental models in animals are necessary for the development of pathogenetic therapy.

The aim of this study was to develop an experimental model of chemical pneumonitis in rats caused by intragastric gasoline administration.

Material and methods. The experimental study was performed on 128 rats. AI-92 gasoline (hereinafter referred to as gasoline) was used as a toxicant, which was administered intragastrically once using a probe at a dose of 10.3 ± 0.44 ml / kg, (n = 6 in the group). At stage 1, the acute toxicity of gasoline was assessed using the Finney probit analysis method, and the mean lethal dose (LD₅₀) was determined. At stage 2, the adequacy of the mathematically selected dose was checked. At stage 3, morphological, histological, and radiological changes in the lungs were studied on days 1, 2, 5, and 14 after intragastric administration of gasoline (LD₅₀).

Results. It was found that the mean lethal dose of gasoline after a single intragastric administration was 10.3±0.44 ml/kg. Lethal outcomes due to direct neurotoxic effects occurred within the first two hours after exposure to gasoline (30 ± 14%), while lethal outcomes due to respiratory failure occurred within the first five days after exposure (60 ± 15%). An increase in the pulmonary coefficient was observed at all observation periods, with the most pronounced increase occurring 24 hours after exposure. The increase in the pulmonary coefficient was accompanied by the appearance of macroscopic changes: the surface of the lungs is cherry-blue in color with multiple subpleural hemorrhages, foamy exudate in the trachea, foci of hemorrhagic impregnation of the lung parenchyma; histological changes: subtotal interstitial edema with a pronounced cellular reaction, swelling and fragmentation of collagen fibers, areas of disatelectasis, destruction of alveolocytes with the formation of detritus and ruptures of the interalveolar septa; radiological changes: increased pulmonary pattern, focal infiltration in the upper segments of the lungs. By day 14 after exposure, histological changes in the lung tissues characteristic of chronic inflammation with moderate lymphoid infiltration, hyalinization of the alveolar membranes and local fibrous changes persisted. These identified changes in the lung tissues were caused by the direct damaging effect of gasoline on the components of the aerogematic barrier, which was associated with its excretion through exhaled air.

Limitations. The study is limited by its methodology. Gasoline blood concentrations were not measured.

Conclusion. A reproducible experimental model of chemical pneumonitis in rats was developed using intragastric gasoline administration (LD₅₀), with disease severity determined by acute respiratory failure.

Compliance with ethical standards. The study was approved by the Independent Ethics Committee of the S.M. Kirov Military Medical Academy (Protocol No. 287 dated January 23, 2024), The study was conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS N 123) and with the Directive 2010/63/EC of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes.

Authors’ contribution:
Smirnov A.N. – concept and design of research, collection of material, writing;
Bugorskiy I.B. – collection of material and data processing, writing;
Blinov A.K. – collection and processing of material;
Smirnova A.E. – collection and processing of material;
Kuzmich V.G. – collection and processing of material;
Tolkach P.G. – responsibility for the integrity of all parts of the article, writing;
Yazenok A.V. – editing, approval of the final version of the article.
All co-authors are responsible for approving the final version of the article and ensuring the integrity of all its parts.

Conflict of interest. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.

Funding. The study had no sponsorship.

Received: May 10, 2025 / Revised: June 10, 2025 / Accepted: February 2, 2026 / Published: March 18, 2026

Introduction. During the development of methodological approaches to accelerated shelf life determination for new medical devices, it is important to determine the toxic properties of devices after their stay in specially created conditions of aggravated aging at elevated temperatures using laboratory animals and alternative test models.

Material and methods. To assess the toxicity of medical devices after accelerated aging, we selected disposable sterile devices subjected to single short-term, long-term, or continuous contact with the internal environment of patients, and both domestically and internationally manufactured non-sterile devices subjected to short-term contact with the patient’s body surface. Aggravated aging conditions were simulated by thermostating the devices. The experimental samples were aged at temperature of plus 80–95 °C for 3.7, 11.2, and 18.7 days. After thermostating, clinical conditions were simulated, for which extracts were prepared from each medical device. The toxic properties of the extracts were subsequently assessed in in vitro and in vivo test models, including sensitizing and pyrogenic effects, hemocompatibility, and cytotoxicity.

Results. All studied medical devices, with varying durations and method of contact with patients, did not exhibit sensitizing effects in the mouse paw swelling test model and complied with hygiene standards after aging under aggravated conditions. Cell death of primary embryonic fibroblast cultures in the in vitro test model was observed after the addition of extracts from the devices, as well as changes in the pyrogenic properties of the devices and a decrease in their compatibility with blood.

Limitations. Are related to in vitro and in vivo test models used to assess the toxic properties of devices after accelerated aging, as well as the medical devices used in the experiments.

Conclusion. The toxic effects of medical devices with varying durations and method of contact with patients depended on the aging time under aggravated conditions. The highest toxic effects were demonstrated by medical devices with short-term contact with the patient’s body surface, while the lowest were demonstrated by devices with prolonged or continuous contact with the patient’s internal environment. The most sensitive test model for studying the biological effects of medical devices under accelerated aging conditions was the primary culture of embryonic fibroblasts from white rats. To establish the shelf life of new medical devices, it is necessary to study their toxic properties after modeling accelerated aging.

Compliance with ethical standards. A positive conclusion was received from the Bioethics Committee of the Research Institute of Hygiene, Toxicology, Epidemiology, Virology, and Microbiology of the Republican Center for Hygiene, Epidemiology, and Public Health (Protocol No. 4 of August 22, 2023). The study was conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS N 123) and with the Directive 2010/63/EC of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes.

Authors’ contributions:
Hrynchak V.A. – study concept and design, material processing, editing;
Protasevich U.S. – data collection and processing, writing, statistical analysis, editing.
All co-authors are responsible for approving the final version of the article and ensuring the integrity of all its parts.

Conflict of interest. The authors declare no obvious or potential conflicts of interest in connection with the publication of this article.

Funding. The evaluation was conducted as part of the “Human Environment Safety” subprogram of the State Scientific and Technical Program “Scientific and Technical Support for the Quality and Availability of Medical Services” – Task 02.15. “Develop and implement a method for determining the expiration dates of single-use medical devices” (state registration number 2023166).

Received: December 19, 2025 / Revised: January 26, 2026 / Accepted: February 2, 2026 / Published: March 18, 2026

Introduction. One of the significant issues of our time is the widespread distribution of chemicals in various fields of human activity, their pollution of the environment and the associated increase in chemical effects on humans. Any person can be exposed to a wide variety of chemicals, which can lead to the development of various pathologies, from acute poisoning to malignant neoplasms. In this regard, high-quality training of medical and pharmaceutical specialists in toxicology is necessary.

The aim of the study is to evaluate the experience of the St. Petersburg State Chemical and Pharmaceutical University in training students, master’s students, postgraduate students and practicing pharmaceutical specialists in toxicology.

Material and methods. The materials of the work were documents of educational and methodological complexes on toxicology for students of the pharmaceutical faculty, master’s students, postgraduate students and students of advanced training courses of the St. Petersburg Chemical and Pharmaceutical University.

Results. Toxicology as an independent academic discipline has been taught to students of the Faculty of Pharmacy of St. Petersburg State Chemical and Pharmaceutical University for 15 years. During this period, a lot of methodological work has been done, two textbooks, three manuals and schoolbooks, a large amount of test questions and situational tasks, and electronic educational and methodological complex have been prepared. Over the past five years, toxicology has also been taught to master’s students and students in advanced training courses in "Industrial pharmacy". Since 2023, the St. Petersburg State Chemical and Pharmaceutical University has opened a postgraduate program in scientific specialty 3.3.4 "Toxicology", which can be considered a significant success in the training of highly qualified personnel in the field of higher pharmaceutical education on current issues of toxicology.

Limitations. The study is limited to an analysis of the experience of teaching toxicology at the Department of Pharmaceutical Chemistry of the St. Petersburg State Chemical and Pharmaceutical University.

Conclusion. Studying toxicology during initial training and additional education at St. Petersburg State Chemical and Pharmaceutical University allows pharmaceutical specialists to acquire the necessary competencies for high-quality performance of professional duties when working in their specialty.

Compliance with ethical standards. The study does not require the submission of a conclusion from the biomedical ethics committee or other documents.

Authors’ contributions:
Strelova O.Yu. – concept and design of research, collection, processing and analysis of the material, writing, editing;
Grebenyuk A.N. – concept and design of research, collection, processing and analysis of the material, writing, editing;
Tikhonova V.V. – collection of the material, writing;
Balabanova O.L. – collection of the material, writing.
All co-authors are responsible for approving the final version of the article and ensuring the integrity of all its parts.

Conflict of interest. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.

Funding. The study had no financial support.

Accepted: January 12, 2026 / Revised: January 30, 2026 / Accepted: February 2, 2026 / Published: March 18, 2026

Introduction. In the international practice of chemical safety, the priority areas are the identification and prohibition (restriction) of highly hazardous chemicals (carcinogens, mutagens, reprotoxicants, endocrine disruptors, toxic, persistent and bioaccumulative compounds, substances toxic to the aquatic biota) in products in order to prevent their impact on human health and the environment. Phthalate plasticizers are among the substances of serious concern. They are widely used in various industries and can cause chronic negative effects when they migrate from materials and products.

The purpose of this study was to conduct a comparative analysis of the toxicity and hazard of six phthalate plasticizers for human health and the environment, and identify priority areas for their subsequent regulation.

Material and methods. The phthalate plasticizers most commonly used in the production of construction and finishing materials were selected as the objects of this study: 1-O-butyl-2-O-(phenylmethyl)benzene-1,2-dicarbonate (BBP), dibutylbenzene-1,2-dicarbonate (DBP), diisobutylbenzene-1,2-dicarbonate (DIBP), 1,4-dibutylbenzene-1,4-dicarbonate (DBTP), di(2-ethylhexyl)benzene-1,4-dicarbonate (DOTP), and di(2-ethylhexyl)benzene-1,2-dicarbonate (DEHP). The assessment of toxicity and hazard was based on data from official open national and international sources of information (databases, scientific articles, reports, monographs, and reference books).

Results. Terephthalic acid-based plasticizers (DBTP and DOTP) are the safest in terms of toxicity and health hazards compared to ortho-phthalic acid-based plasticizers (BBP, DIBP, DBP, and DEHP). The last ones have a significant hazardous effect on humans and the environment, including: hepatotoxic effects in animal experiments with prolonged exposure; negative effects on reproductive function and developing offspring, and are classified as hazard class 1B according to the GHS criteria; disruption of the morphology and functions of endocrine system organs (thyroid, adrenal glands, pituitary gland, male reproductive organs, etc.), and lipid metabolism; acute and chronic toxicity for aquatic biota (Class 1 according to toxicometry indicators); hazard class 2 (highly hazardous substances) according to GOST 12.1.007–76 based on the maximum permissible concentration in the air of the working area.

Limitations. The study is limited to the analysis of open literature sources, including databases such as Scopus, Web of Science, PubMed, ResearchGate, Cyberleninka, RSCI, and eLIBRARY.

Conclusion. The decision to replace a chemical substance with alternatives (analogues) is based not only on data on toxicity and hazard, but also on an assessment of the actual risk of exposure, which depends on the substance’s ability to migrate into boundary environments (air, water, and model environments).

To use DBTP as an alternative to hazardous plasticizers, it is necessary to study effects on the liver, reproductive function, and developing offspring, as well as on the endocrine system. Additionally, it is required to scientifically substantiate and approve the hygienic standards for DBTP in the air of the work area, in the atmospheric air of urban and rural settlements, and in water, since the legislation of the Russian Federation permits the activities of economic entities with chemicals only if there are hygienic standards.

It is advisable to study the migration of DBTP and DOTP from various materials in order to establish correlation between the content in products and the level of migration into the boundary environment.

Compliance with ethical standards. The study does not require a report from the Bioethics Commission.

Authors’ contribution:
Khamidulina Kh.Kh., Tarasova E.V. – concept and design of the study, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Nazarenko A.K., Tverskaya A.S., Zamkova I.V., Proskurina A.S., Rabikova D.N., Araslanov I.N., Zherenova A.A., Gorbunova D.I., Gonyukova E.S., Leontyeva A.N. – collecting and processing material, writing text, editing.

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The study was conducted as part of the implementation of the research project “Development and Scientific Justification of Chemical Alternatives for Replacing Highly Hazardous Components in Various Types of Products” under the state program of the Russian Federation “Scientific and Technological Development of the Russian Federation in 2026–2028”.

Received: December 26, 2025 / Accepted: February 2, 2026 / Published: March 18, 2026