Introduction. It is known that the antitumor drug doxorubicin (Dox) is a reprotoxicant that has a negative effect on reproductive function in mammals. In the male body, doxorubicin leads to significant damage to testicular cells, inducing DNA damage, the formation of double-stranded breaks, crosslinking, and free radicals.The purpose of this work was to examine the effect of doxorubicin on the development of spermatogenic epithelial cells in vitro.Material and methods. The study was performed on the primary culture of mouse spermatogenic epithelium. The cytotoxic effect of doxorubicin was studied at concentrations of 0.25, 0.05, and 0.005 µg/ml. The degree of cytotoxicity and viability of cells was assessed by their morphological state, DNA damage, and the dynamics of the number of living cells in culture for 40 days. Results. 24 hours after exposure to Dox, a dose-dependent statistically significant decrease in cell viability was observed in all the studied samples, with the maximum effect – a decrease in the number of live cells to 50% – observed at a concentration of 0.25 µg/ml, and a decrease to 13% at a concentration of 0.05 µg/ml. The decrease in cell viability persisted in subsequent stages of cultivation, which determined the nature of the monolayer, as well as changes in the morphology of the Sertoli cells. Limitations. The obtained results refer to a heterogeneous cell culture as the object of research.Conclusion. During the experimental work, all the studied concentrations of doxorubicin showed a cytotoxic effect on somatic and spermatogenic cells. The most harmful concentrations of doxorubicin for spermatogenic epithelial cells in vitro were 0.25 and 0.05, which led to the cell death within 24 hours and caused DNA damage after four hours of exposure. The study revealed characteristic features of pathomorphological changes in Sertoli cells. Even at low concentrations, doxorubicin can disrupt the formation of the feeder layer.Compliance with ethical standards. The study was approved by the Bioethics Commission of the Research Institute of General Prophylaxis and Epidemiology of the Federal Medical and Biological Agency of Russia (Minutes No. 2 dated March 28, 2023).The animals were removed from the experiment in accordance with GOST 33215-2014 and in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS N 123), 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: Golubentseva Yu.V. – study concept and design, data collection and processing, statistical analysis, text writing; Popov V.B. – text writing, editing; Radilov A.S. – writing and editing. All co-authors are responsible for approving the final version of the article and ensuring the integrity of all parts of the article.Conflict of interest. The authors declare that they have no apparent or potential conflicts of interest related to the publication of this article.Funding. The study had no sponsorship.Received: 28 апреля 2026 /Revised: 12 мая 2026 / Accepted: / Published: 2026

The Vostochny Space Center is a new facility of the Russian space industry, which began launching space technology in 2016. In the normal operation of the cosmodrome, the impact of rocket fuel components on personnel, taking into account the data of sanitary and hygienic monitoring, is not expected, however, the influence of a chemical factor is possible in cases of emergency situations. The purpose of the study is a hygienic assessment of the impact of harmful and dangerous factors of the production environment on the health of the personnel of the Vostochny cosmodrome using an information and analytical system of sanitary and hygienic monitoring. The study was based on the classical methodological basis of a comprehensive sanitary and epidemiological assessment of the production environment. The analysis showed the absence of differences in the levels and dynamics of morbidity by the main classes of the disease, the absence of professionally determined pathology, which indicates the sufficiency of the complex of organizational, technical and sanitary measures implemented during the creation of the Vostochny Space Center. Thus, the introduction of information and analytical approaches to the organization and implementation of monitoring studies makes it possible to obtain the necessary comprehensive information, timely and fully record the impact of negative factors of the production environment on employees, and perform a comprehensive assessment of the health status of the personnel of the Vostochny cosmodrome.

Introduction. General industrial pollutants, which includes volatile industrial pollutants (VIP) allyl chloride, butyl chloride, chloroacetonitrile, pentachloroethane, hexachloroethane, trans-1,4-dichloro-2-butene, acrylonitrile, methacrylonitrile, methyl methacrylate, ethyl methacrylate, methyl acrylate, 2-nitropropane, nitrobenzene , diethyl ether, tetrahydrofuran and carbon disulfide are widely used in the domestic chemical industry, but effective methods for the quantitative determination of their biomarkers in the biological media of chemical production workers have not yet been developed. The purpose of the study is to develop a highly sensitive gas chromatographic technique for the determination of compounds of the VIP group in whole blood and urine for their biological control, and its testing using modeling of intoxication in laboratory animals. Material and methods. Experimental modeling of intoxication was carried out with subcutaneous (s/c) injection of toxicants to male chinchilla rabbits. Determination of biomarkers of toxicants was performed using a gas chromatograph with a single quadrupole mass analyzer (GC-MS) with preliminary extraction of components from the vapor phase above the sample by solid-phase microextraction. Results. A method for the determination of allyl chloride, butyl chloride, chloroacetonitrile, pentachloroethane, hexachloroethane, trans-1,4-dichloro-2-butene, acrylonitrile, methacrylonitrile, methyl methacrylate, ethyl methacrylate, methyl acrylate, 2-nitropropane, nitrobenzene, diethyl ether, tetrahydrofuran, and carbon disulfide in blood and urine was developed and metrologically certified. The achieved limits of quantification are no more than 1 ng/ml with a detection limit of 0.2 ng/ml in blood and urine. Limitations. Toxicokinetic parameters were experimentally determined on one animal species; allometric scaling was used for extrapolation to humans. Conclusion. Analysis of the results of the assessment of the expected concentrations of VIP in blood and urine shows that biological control in the working area at the level of 0.5 MPC can be carried out for carbon disulfide, diethyl ether, butyl chloride, 1,4-dichlorobutene-2 and tetrahydrofuran in the study of blood and urine; methacrylonitrile and hexachloroethane (the lower value of the determination limit) – in the study of urine only. The developed approaches to substantiate methods of biological control of harmful substances are a scientific and methodological platform for the introduction of biological MPC and ensuring the chemical safety of the Russian Federation.

Rocket and space activities occupy an important place among modern sources of impact on the environment. Its results can manifest themselves in an area where a cosmodrome is located, adjacent territories, in areas where separated parts of a launch vehicle fall. This impact has certain specific features that create population health risks. Health risks for population of Tsiolkovsky settlement were assessed upon exposure to chemicals that pollute the environment in accordance with the methodical approaches stipulated in the valid Guide (R 2.1.10.3968-23). Initial data were represented by results of environmental surveillance accomplished within social-hygienic monitoring and in field conditions as well as by data collected for a project aimed at substantiating a sanitary protection zone for the Vostochny Cosmodrome launch sites. Average annual concentrations and their 95 % confidence intervals, which were established based on average daily concentrations, were used to calculate chronic chemical exposures. The 95 % percentile of maximum single concentrations was employed to calculate acute exposures. Ambient air was established to make the greatest contribution (88.99 %) into non-carcinogenic health risks for people residing in Tsiolkovsky settlement. Particulate matter made the greatest contribution (42.4 %) to the risk of chronic non-carcinogenic effects. Alerting chronic non-carcinogenic risks of respiratory diseases (up to 5.9 HI) and the blood system (up to 4.1 HI) were established under combined inhalation chemical exposures. Major contributions to non-carcinogenic risks are made by particulate matter (up to 42.4 %), lead (up to 25.9 %), nitrogen oxide (up to 20.2 %), nitrogen dioxide and carbon oxide (23.1 % each).

Introduction. Currently in the Russian Federation, the practice of industrial medicine does not use methods of biological monitoring of organic compounds – an addition to industrial control, which consists in regularly measuring the content of biomarkers of harmful chemicals in the body of workers. The purpose of the study is to analyze available scientific publications and methodological documents on biomarkers of harmful organic substances, to draw conclusions about the directions for the development of methodological support for biological monitoring of organic compounds in the Russian Federation. Material and methods. available scientific publications, methodological guidelines of Rospotrebnadzor, materials of the Russian Register of Potentially Hazardous Chemical and Biological Substances, and foreign methodological documents, in particular from the Agency for Toxic Substances and Disease Registry, USA, were used. Results. A list of the most common harmful organic substances circulating at hazardous chemical facilities, their biomarkers and methods for measuring them in biological media was compiled. An analysis of domestic and foreign hygienic standards for the content of toxicants or their markers in biological media was performed. Limitations. The analytical review of biological monitoring methods was carried out only for organic compounds and does not include inorganic substances. Conclusion. The analytical review made it possible to identify the following necessary methodological elements for the implementation of biological monitoring in the Russian Federation: the development of at least 9 chemical-analytical methods for determining biomarkers in the biological environments of workers, the introduction of immunochromatographic methods when conducting biological monitoring of workers to clarify the reliability of anamnesis data on attitudes towards alcohol, smoking and medications, experimental studies on the detection and identification of biomarkers of exposure to a number of organic compounds, experimental substantiation of hygienic standards for the content of 15 substances in the air of the working area.

Introduction. Osimertinib, a 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor, is currently the only drug registered for the treatment of metastatic non-small cell lung cancer in patients with a positive T790M mutation status. The production of osimertinib mesylate is planned on the territory of the Russian Federation, which necessitates research to substantiate the hygienic standard for the aerosol content of the substance in the air of the working area. Conducting research to substantiate the maximum permissible concentration of a substance requires significant material and time resources, while using the results of preclinical and clinical studies, mathematical modeling of processes, and risk assessment methodology allows for a comprehensive assessment of the substance, while significantly reducing the time and cost of work. The study aims to scientifically substantiate the maximum permissible concentration of the pharmaceutical substance osimertinib mesylate in the air of the working area using data from toxicological studies and mathematical modeling of the effects of the substance on humans in industrial conditions. Materials and methods. The materials used were domestic and international databases, reports, research protocols, scientific articles and monographs containing information on the physico-chemical and toxic properties, pharmacotherapeutic activity of osimertinib. Results. The specialists have conducted hygienic regulation of osimertinib, taking into account data on its toxicity, danger, pharmacotherapeutic activity, side effects, long-term consequences, pharmacokinetic studies and modeling. To substantiate the value of the maximum permissible concentration, the authors used the reference points: an inactive NOEL level of 1 mg/­kg/­day for general toxic effect, established in a 92-day experiment on rats with intragastric administration; the lowest observed level of adverse effects of LOAEL is 0.5 mg/kg/day for general toxic effect, established in a 180-day experiment on dogs with intragastric administration; the level that does not cause adverse effects of NOAEL is 10 mg/kg/day for general toxic effect, established in a 180-day experiment on mice with intragastric administration. Safe concentrations of osimertinib in the air of the work area were evaluated using reference points, including the pharmacological effect and the minimum daily therapeutic dose; toxicokinetic modeling of concentrations of a substance in the human body under production conditions and the level of minimal risk. Limitation. The study is limited to the review of open literature sources describing the toxicological/toxicokinetic characteristics of osimertinib mesylate. Conclusion. The most stringent indicators of safe exposure levels, established on the basis of pharmacological effect and toxicokinetic modeling in dogs, allowed us to recommend 0.005 mg/m3, aerosol, hazard class 1 as the maximum permissible concentration in the air of the working area for osimertinib mesylate. Ethics. This study did not require the conclusion of the Ethics Committee.

Introduction. The development of improved formulations of antidotes and remedies, which can be used not only by qualified medical personnel, but also in self- and mutual assistance, is an urgent task for extreme medicine.Objective. Evaluation of the possibility of using nanoscale polymer delivery systems for medicines and antidotes intended for intranasal administration (into the nasal cavity) in extreme medicine.Discussion. The main submicron-sized polymer carriers which are promising as the basis for the creation of an intranasal form of antidotes are identified. The bioavailability of the substance delivered is dependent on the physico-chemical properties of the carrier, the conditions for its production, as well as physiological and anatomical factors. Data is presented regarding possible ways of correcting these factors in order to increase bioavailability. Examples of the use of polymer nanocarriers in the treatment of poisoning with heavy metals and rocket fuel components, as well as lesions caused by radioactive substances, are presented. It is shown that carriers (dendrimers, cyclodextrins) can act as antidotes in certain cases. The study presents a list of antidotes approved for use within the territory of the Russian Federation, for which the development of intranasal forms is possible, taking their physico-chemical and pharmacokinetic properties into account.Conclusions. Following a review of literature sources, the most promising submicron-sized polymer carriers for the intensification of intranasal delivery of drugs and antidotes are herein proposed: dendrimers, liposomes, nanocapsules, nanoparticles, and cyclodextrins. Using the list of antidotes approved for use in the Russian Federation as an example, promising drugs that can be potentially developed on the basis of these carriers are proposed.

Synthetic short-acting opioids are commonly used in anesthesiology as painkillers because their effect is more pronounced compared to that of natural substances. However, they have a number of side effects that, when fentanyl is used in doses larger than therapeutic, can lead to a lethal outcome. This study aimed to assess the cardiotropic effects of high doses of fentanyl using a rat heart isolated in a Langendorff perfusion system. Parameters of the heart's contractile activity were recorded with the help of PowerLab Data acquisition system 8/30 (ADInstruments, USA) and processed in the LabChartProUpgrade 7.0 program. At the concentration of 3.7 × 10–6 M, which corresponds to the opioid content in blood after administration of a 5 ED50 dose, fentanyl caused the QT interval duration to grow by 22%, as registered on an ECG, and a 256% spike of T wave (compared to control; p < 0.05). At the concentration of 7.4 × 10–6 M (10 ED50), the drug decreased heart rate by 20.4% (p < 0.05) and triggered a coronary constrictor effect that raised the perfusion pressure by 18.6% (p < 0.05). Further increase of fentanyl concentration to 1.5 × 10–5 M (20 ED50) was accompanied by an 83.5% growth of the end diastolic pressure (p < 0.05). Administration of nalmefene, nonselective opioid receptor blocker, did not cancel the cardiovasotropic action of fentanyl. Thus, fentanyl has a dose-dependent cardiotoxic effect. Despite the drop in the registered values of isolated heart's parameters, the results of this experiment confirm that cardiac activity persists under the influence of high doses of the opioid.

As markers of intoxication, adducts of blood proteins with organophosphorus compounds (OPs) allow establishing the fact of poisoning and, furthermore, enable identification of the OPs by the attached residue. This study aimed to develop a method of specific and selective extraction of blood protein adducts carrying OPs on the surface of a matrix-assisted laser desorption/ionization (MALDI) target functionalized with multimolecular structures based on lanthanum stearate using metal affinity chromatography. We have shown the ability of adsorbent to retain both full-size and dealkylated adducts of blood proteins with OPs. The developed method allowed extraction and identification of peptides of human serum albumin and human butyrylcholinesterase modified with various OPs (after incubation of human blood plasma with OPs in concentrations from 1 to 100 ng/mL), which makes this approach applicable for the purposes of OPs identification in the context of investigation of real cases of intoxication.

Development of drug delivery systems based on branched biocompatible polymers is one of the most promising areas of modern nanopharmaceutics. Researchers have been exploring this area several decades now, and the results of their efforts quickly find their way into production. Dendrimers, a new class of universal synthetic polymers with a highly functional surface, have a number of unique properties: constant size, high degree of branching, multivalence, solubility in water, definite molecular weight, internal cavities. With the release of VivaSol gel, the first dendrimer-based commercialized product, the "model range" of dendrimer carriers has grown significantly. Poly(amide-amine) (PAMAM) dendrimers, which consist of an alkyldiamine core and tertiary amine branches, are believed to be among the most promising compounds that can be used in the development of the new generation drugs. However, they were kept out of the list of clinically acceptable compounds for a long time because of their toxicity, unclear behavior in living systems and pharmacokinetic profile, as well the difficulties associated with establishing a therapeutic dose. This review presents basic information about PAMAM dendrimers and attempts to assess the prospects of their application in treatment of various diseases, including COVID-19.

Федеральное государственное унитарное предприятие «Научно-исследовательский институт гигиены, профпатологии и экологии человека» Федерального медико-биологического агентства (ФГУП «НИИ ГПЭЧ» ФМБА России) — многопрофильное предприятие, одна из ведущих организаций в области медико-гигиенического сопровождения химических производств, диагностики, профилактики и лечения профессионально обусловленных заболеваний, гигиены окружающей среды, гигиены труда, организации здравоохранения.

Introduction. Currently, there are no standard methodological approaches that allow assessing the danger to human and animal reproduction of poorly soluble chemicals (industrial waste, products of destruction of organic substances, polymer materials), including substances that form complex poorly soluble systems with environmental objects. It may be impossible or ineffective to use standard routes of administration of such substances and complexes to assess their reproductive hazard. An attempt to find an experimental model for conducting toxicological and embryotoxicological studies that allow assessing the danger of prolonged interaction of poorly soluble compounds directly with tissue fluids was the main aim of the work. The study aims to investigate the possibility of using diffusion chambers to assess the reproductive hazard of poorly soluble chemicals. Material and methods. In experiments with chemicals, the researchers placed samples of dry preparations in the inner cavity of one of the rings. Experts sealed the ring on both sides with millipore membranes. The diffusion chambers obtained in this way were implanted into the abdominal cavity or under the skin in the cervical region of female rats during the most sensitive days of pregnancy to pathogenic effects. Results. When implanting diffusion chambers to animals, the possibility of assessing the embryotoxic properties of poorly soluble chemicals, such as bitumen-salt masses, polymer materials and coatings, etc., as well as soil contamination with substances potentially dangerous to the reproductive function of humans and animals is shown. With the help of diffusion chambers, experts assessed the embryotoxic activity of known dysmorphogens, cyclophosphamide, cadmium sulfate, as well as a number of polymer materials (di-paraxilylene film, acrylic acid copolymer, silloxane rubber), Scientists assessed soil contamination with a known insecticide and acaricide - endosulfan. Limitations. In the work, the experts used diffusion chambers with a volume of 400, 900 or 3000 m3. Conclusion. As a result of the experiments conducted, scientists determined that the presented method can be used to assess the reproductive hazard of poorly soluble chemicals (products of destruction of organic matter, polymer and endoprosthesis materials), when assessing the risk of prolonged presence of foreign bodies in tissues, when assessing soil contamination in places of chemical accidents, rocket crashes, storage and destruction of chemical weapons. Ethics. The study was carried out in compliance with the rules of bioethics approved by the European Convention for the Protection of Vertebrates Used for Experimental and Other Purposes (Protocol No. 4 of 8.11. 2022).

The relevance of considering the problems and prospects of biological control is associated with the need to form scientific, methodological and organizational foundations for the inclusion of biological control of industrial exposure to harmful chemicals in the system of social and hygienic monitoring to ensure the chemical safety of the Russian Federation. The purpose of the work is to substantiate the need to develop and implement methodological recommendations for the development and validation of chromatographic methods for biological control of industrial exposure to harmful substances with the system of sanitary and epidemiological regulation of the Russian Federation. The published results of works in the department of toxicology of the "Research Institute of Hygiene, Occupational Pathology and Human Ecology", carried out under the guidance of the authors, were used, and a number of new additions to the toxicokinetic equations were made, in particular, a method for calculating the material cumulation coefficient (Km.cum) was proposed for the first time.

The development of coronavirus infection outbreak into a pandemic, coupled with the lack of effective COVID-19 therapies, is a challenge for the entire pharmaceutical industry. This study aimed to assess the treatment and preventive efficacy of the amino acid-peptide complex (APC) in male Syrian hamsters infected with SARSCoV-2 (intranasal administration of 26 μl of the virus culture, titer of 4 × 104 TCD50/ml). In a modeled COVID-19 case, APC administered for treatment and preventive purposes reduced lung damage. Compared to the positive control group, test group had the lung weight factor 15.2% smaller (trend), which indicates a less pronounced edema. Microscopic examination revealed no alveolar edema, atypical hypertrophied forms of type II alveolocytes, pulmonary parenchyma fibrinization. The macrophage reaction intensified, which is probably a result of the APC-induced activation of regenerative processes in the lung tissues. Spleens of the animals that received APC for therapeutic and preventive purposes were less engorged and had fewer hemorrhages. The decrease of body weight of the test animals that received APC for treatment and prevention was insignificant (p < 0.05), which indicates a less severe course of COVID-19. Administered following a purely therapeutic protocol, APC proved ineffective against SARS-CoV-2 post-infection. Thus, APC-based drug used as a therapeutic and preventive agent reduces pulmonary edema and makes morphological signs of lung tissue damage less pronounced in male Syrian hamsters infected with SARS-CoV-2.

Показатель липофильности (logP) можно определять ВЭЖХ-методом в соответствии с принципами, отраженными в руководстве ОЭСР: «Partition Coefficient (n-Octanol/Water), High Performance Liquid Chromatography (HPLC) Method» (1989г.).Целью исследования являлось изучение влияния состава подвижной фазы и влияния типа модифицированного сорбента хроматографической колонки (С8/С18) на качество оценки липофильности ряда известных фармакологических средств ВЭЖХ-методом.Для построения калибровочной зависимости нами были предложены веществаионизирующиеся лекарственные средства, с хорошо изученной лиофильностью.В зависимости от комбинации подвижной фазы и хроматографической колонки получили 4 калибровочных зависимостей зависимости logP от логарифма коэффициента удерживания стандартных образцов (logk).По полученным калибровочным зависимостям рассчитали коэффициенты распределения для модельных веществ.

An approach for the preparation of a polymer delivery system consisting of sodium alginate (SA) and carbopol was developed. The efficiency of the inclusion of medicinal compounds in these systems was investigated using the polyphenols curcumin and resveratrol as examples. Curcumin and resveratrol possess anti-inflammatory, antitumor, and antibacterial effects, which makes them promising compounds for use in clinical practice. The main disadvantage of these polyphenols is their low bioavailability. The formation of microcapsules occurs due to the precipitation of a mixture of SA and carbopol (carbopol 940 or ETD 2020), containing a model object, in a calcium chloride solution. The dependence of the inclusion of drugs in microcapsules and their release into gastrointestinal environment imitators on the viscosity characteristics of carbopol, which is part of the microcapsule shell, was investigated.

The results of our own and foreign studies have shown the absence of sensitizing properties of terephthalic acid, and therefore there was a need to review the current hygienic standard – MAC – in the air of the working area and change the hazard class of the substance. The materials of the German Research Community (DFG) were used for substantiation of MAC. Recommended MAC in the air of working area is set at 5 mg/m3 (maximum single), a mixture of vapors and aerosol, hazard class 3.

Toxicity and hazard assessment of dioctyl terephthalate (DOTP) was performed in acute, subacute, and chronic experiments, and its principal toxicometry parameters were determined.It was found that on single exposure DOTP exhibits low toxicity and hazard. No resorptive and irritant effects on skin and mucous membrane of eyes were detected in animal experiments. The single inhalation exposure threshold limit value was set at 300 mg/m3, based on the results of monitoring of the functional state of the central nervous system and myocardium and hematological parameters.Thirty-day subacute experiments (oral administration, inhalation exposure, and skin applications) revealed no accumulation of the compound.Four-month chronic exposure to DOTP aerosols (concentration 96,8 mg/m3) caused disorder of the functional state of the central nervous system and myocardium, changes in the hematological and biochemical parameters, gas and acid-base status of the blood, and morphological changes in the lungs and heart. Embryotoxic, genotoxic and gonadotoxic effects were not detected.The chronic inhalation exposure threshold limit value for DOTP (Limch) was set at 18,6 mg/m3, and the concentration of 3,4 mg/m3 was found to be ineffective.The maximum allowable concentration of DOTP in the air of the working area was set at 3,0 mg/m3, hazard class 3.