One of the areas of scientific research that deeply interested I.V. Sanotsky was the study of the long-term effects of the influence of chemical compounds on the body, which is one of the most urgent problems of modern toxicology.
The study aims to analyze and evaluate the results of experimental studies of chemicals with long-term effects, on the basis of which a methodology for hygienic rationing of these substances in preventive toxicology.
The researchers have conducted a literature search for the period 1975–2020 according to the data of the scientific electronic library elibrary.ru and the archive of the Izmerov Research Institute of Occupational Health by keywords: preventive toxicology, long-term effects, hygienic standardization.
The results of experimental studies of chemicals with long-term effects allowed us to scientifically substantiate the basic principles of establishing MPC during hygienic rationing:
– selection of an experimental model, issues of data transfer from animals to humans;
– dependence of the studied effects on the dose or concentration of chemicals;
– threshold of effects;
– dependence of the effect on the time of exposure and observation;
– selectivity of the effect of poisons on reproductive function;
– sanitary standardization of the content of chemical compounds with a specific effect on reproductive function.
As a result of the long-term work of the Department of Industrial Toxicology, specialists have developed methodological approaches, and also have created tested, modernized, unified guidelines for the system of institutions whose task was to obtain data for the toxicological assessment of new substances with long-term effects to determine harm thresholds.
Contribution:
Fesenko M.A. — research concept and design, data analysis and interpretation.
Funding. The study had no funding.
Conflict of interests. The author declares no conflict of interests.
Received: 17.11.2022 / Accepted: 23.11.2022 / Published: 12.12.2022
Introduction. The creation of adequate models for studying the processes of human interaction with the environment is a key problem of modern experimental biology and medicine. This is due to the fact that both the results of the conducted studies and the recommendations developed on their basis depend on the choice of the biological object and the characteristics of the factor directly affecting it. It should be noted that errors related to both the discrepancy between the developed experimental pathology and the simulated conditions for humans, and the choice of a method for assessing the safety of xenobiotics are critical and can lead to serious consequences.
The study aims to determine the existing trends in biomodeling and extrapolation of the results currently being implemented in experimental toxicology and medicine based on the analysis of literature data.
Materials and methods. We have used forty five domestic and foreign scientific publications as materials. The research method was the analysis and generalization of the materials presented in scientific publications.
Results. The scientists considered such components of extrapolation modeling as the creation of an adequate model, compliance with the principles of proper laboratory, as well as extrapolation of the obtained data to humans. We have given the definition of an experimental model of the disease as a condition developing in a laboratory animal under the influence of an etiological factor, which most fully reflects the main manifestations of the disease that arose on the basis of a common human and used biomodel of pathogenesis. We introduced the term "zero-order biomodels" and defined it as an object used for biomodeling and also presented a classification of zero-order biomodels.
Conclusion. Currently, issues related to their standardization are of increasing importance in conducting biomedical research, which is reflected in the appearance of a large number of regulatory documents regulating not only the procedure for conducting them, but also the requirements for biological models used for these studies. However, despite the existing trends, the key point in conducting all studies was and still is the issues related to the extrapolation of the data obtained to humans.
The conducted analysis suggests that new biological models (of the zero-order) are being actively introduced into the practice of biomedical research according to their characteristics fully corresponding to the prototype — human biological material obtained from various sources. A distinctive feature of these models is the absence of the need to extrapolate the results obtained to humans.
The analysis shows that at present there are all prerequisites for conducting preclinical studies using almost the entire spectrum of biological models of the zero-order specified in this publication within the existing legal framework.
Contribution:
Bonitenko E.Yu. — the concept and design of the study, data collection and processing, writing the text;
Kashuro V.A. — the concept and design of the study, data collection and processing, writing the text;
Basharin V.A. — the concept and design of the study, data collection and processing, writing the text.
Funding. The study had no funding.
Conflict of interests. The authors declare no conflict of interests.
Received: 12.10.2022 / Accepted: 18.11.2022 / Published: 12.12.2022
Introduction. The concept of chemical substitution is now increasingly included in policy and regulatory efforts around the world to reduce the risks of chemicals to human health and the environment, as well as in industry initiatives for the sustainable management of chemicals. With the exception of conventional substances regulated by EEC documents, unfortunately, there is no legislatively established mechanism for identifying, banning and limiting the production and consumption of highly hazardous chemical compounds in the Russian Federation.
The purpose of the research is to develop and scientifically substantiate the concept of replacing highly hazardous chemicals with safer alternatives.
Materials and methods. The guidelines and recommendations of the OECD, WHO, ILO, FAO, UNEP, as well as regulatory and methodological documents of the EU, the USA, Canada and other states on the criteria for classifying substances as highly hazardous, organizing and monitoring them in environmental objects and selection of safe chemical alternatives were studied and analyzed.
Results. The concept of substitution includes the scientific substantiation of the criteria for classifying substances as highly hazardous, the organization and generalization of data from monitoring the human environment and the circulation of hazardous chemical products on the market, the development of a list of highly hazardous chemicals that are priority for regulation; selection of safe alternatives and their comparative analysis, taking into account the assessment of the advantages of the alternative over the existing technology/substance, implementation of management decisions.
The criteria for identifying substances of highly concern and selecting their alternatives are the following indicators: biological activity (carcinogens, mutagens, reprotoxicants class 1A and 1B in accordance with GHS, endocrine disruptors); stability in the environment; bioaccumulative potential; the possibility of cross-media transfer; aquatic toxicity (acute and chronic toxicity of hazard class 1 in accordance with GHS); production volumes (volumes of emissions and discharges); number of contacts.
Conclusion. The analysis of the international practice of regulating highly hazardous chemicals indicates the need to implement at the national level and within the framework of the Eurasian Economic Union a program for the systematic monitoring of high-risk chemicals circulating on the market in order to withdraw them from circulation and replace them with safe analogues.
Implementation of the concept of replacing highly hazardous substances with safe chemical alternatives allows to create a draft national list of banned and restricted highly hazardous chemicals relevant to various industries (food, materials, basic chemistry).
Contribution:
Khamidulina Kh.Kh. — 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;
Proskurina A.S. — collection and processing of material, writing the text;
Tarasova E.V. — research concept, editing.
Conflict of interests. The authors declare no conflict of interest
Funding. The study was funded by the state program "Ensuring the chemical and biological safety of the Russian Federation".
Received: 01.12.2022 / Accepted: 06.12.2022 / Published: 12.12.2022
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.
Funding. The study had no funding.
Conflict of interests. The authors declare no conflict of interest.
Received: 01.12.2022 / Accepted: 08.12.2022 / Published: 12.12.2022
Introduction. In the structure of occupational diseases associated with the effects of chemical factors, the pathology of the respiratory organs due to the action of dust, occupies the first place. Among the recommended methods of treating occupational dust pathology, there are no procedures for removing foreign particles from the respiratory tract aimed at eliminating the cause of the disease. Despite the effectiveness of total bronchoalveolar lavage in the treatment of professional dust bronchitis, the method has a number of disadvantages due to the need to use large volumes of saline solution, which can lead to undesirable side effects associated with water balance disorders in the body caused by the absorption of fluid by the lungs during the procedure. In this regard, attention is drawn to the possibility of using perfluorocarbon compounds with low bioavailability for the elimination of foreign microparticles from the lungs by bronchoalveolar lavage or total liquid ventilation (TLV).
The study aims to give an experimental assessment of a possible method for the treatment of occupational lung diseases of dust etiology, based on the removal of dust foreign particles from the respiratory tract using perfluorocarbon compounds.
Materials and methods. Scientists performed a study on male rabbits of the Soviet Chinchilla breed aged 3–4 months, weighing 2.8–3.6 kg. They used a device of their own design with an open circuit to carry out the procedure of TLV, in which the liquid "washed" the lungs and drained into a special container. Perfluorodecalin was used as a respiratory fluid. At the first stage, rabbits on TLV inhaled for 3 minutes microparticles of silica gel of the LL-254 brand (5/40 microns) marked with a luminescent indicator. At the second stage, after the end of inhalation, the rabbits of the control group continued to be on artificial ventilation with air, and the rabbits of the experimental group were transferred to the TVL for 5 minutes. At the third stage, artificial ventilation of the lungs with air was performed until the end of the action of the muscle relaxant and the restoration of independent breathing. Estimated indicators: the presence of luminous particles on the surface of the trachea, bronchi, on sections of lung tissue and in perfluorodecalin passed through the rabbit's lungs; histomorphological picture of the lungs; indicators of respiratory gases and acid-base state in arterial blood.
Results. Elimination of silica gel from airways by TLV procedure was detected by luminescent visualization and histomorphologically. Complete recovery respiratory gases and acid-base status or arterial blood in one hour after procedure proved safety of TLV procedure.
Conclusion. TLV procedure is able to remove foreign particles from the respiratory tract. The researchers proved the effectiveness of the procedure according to three criteria: presence of luminescent labeled particles in waste perfluorodecalin after TLV; decrease of luminescent labeled silica gel macroscopic visualization in trachea and bronchi; decrease of silica gel amount in lung tissue detected by microscopic histomorphological methothods; Perfluorodecalin application for foreign (including radioactive) particles removing from respiratory tract is more preferably than saline, because of saline lungs absorption that potentiate particles incorporation in tissue. Five-minutes TLV procedure does not induce markable disturbances of gas exchange monitored by respiratory gases and acid-base status or arterial blood. Complete recovery of these parameters was detected within one hour after procedure.
Ethics. The scientists conducted studies involving laboratory animals in compliance with the necessary regulations (the Helsinki Declaration of 2000 on Humane Treatment of Animals and the "Rules for carrying out work using experimental animals" (Order of the Ministry of Health of the USSR No. 755 of 12.08.1977)). The protocol of the study was approved by the Ethics Committee of the Izmerov Research Institute of Occupational Health.
Contribution:
Tonshin A.A. — writing the text;
Barinov V.A. — the concept and design of the study, editing, approval of the final version of the article;
Bonitenko E.Yu. — the concept and design of the study;
Belyakova N.A. — data collection and processing;
Gaikova O.N. — data collection and processing;
Barinov V.V. — data collection and processing;
Nosov A.V. — data collection and processing.
Funding. The work was carried out with the financial support of the Foundation for Advanced Research.
Conflict of interests. The authors declare no conflict of interests.
Received: 11.11.2022 / Accepted: 17.11.2022 / Published: 12.12.2022
Introduction. When new industrial enterprises appear, whose activities are related to the use and/or production of chemicals, pollutants that do not have approved hygiene standards may appear in the air of the working area. We note that the introduction of new chemicals into the production process does not always require the development of a hygienic standard in the air of the working area, since conditions can be met for these compounds, namely compliance with hygienic criteria, under which the development and approval of hygienic standards is not required.
The study aims to demonstrate a practical approach to the application of hygienic criteria for substances that do not need to establish hygienic standards in the air of the working area on the example of paraformaldehyde.
Materials and methods. The theoretical basis of the work was the methods of substantiating the need to develop hygienic standards: maximum permissible concentration (MPC) and approximate safe level of exposure (ASLE) to harmful substances in the air of the working area. The practical basis of the work was methodological guidelines for measuring mass concentrations of formaldehyde in the air of the working area by a photometric method based on the reaction of formaldehyde with acetylacetone in an ammonium acetic acid medium and subsequent photometric measurement of the optical density of the yellow-colored reaction product.
Results. The conducted experiment simulating the processes of formaldehyde emission from paraformaldehyde in various production conditions showed that paraformaldehyde under the influence of temperature releases formaldehyde, while the rate of formaldehyde release increases with increasing temperature.
Conclusion. Analysis of the technology of production (application) of paraformaldehyde, toxicological data, as well as an experiment modeling the processes of formaldehyde emission from paraformaldehyde in various production conditions allows us to conclude that the development of a hygienic standard for paraformaldehyde in the air of the working area is impractical, according to paragraph 2.1.1. GN 1.1.701-98 "For substances containing the ingress of which into the air of the working area in the form of vapors and aerosols or a mixture thereof is excluded due to the physico-chemical properties, as well as production and application conditions" and p.2.1.3. GN 1.1.701-98 "For substances that easily hydrolyze in the air with the formation of hydrolysis products, the toxicity of which has been studied and the hygienic standards of which have been established".
Contribution:
Fedotova L.A. — data collection and processing, text writing, editing;
Potapchenko T.D. — data collection and processing, text writing;
Mamonov R.A. — editing.
Funding. The study had no funding.
Conflict of interests. The authors declare no conflict of interests.
Received: 09.11.2022 / Accepted: 18.11.2022 / Published: 12.12.2022
Introduction. The impact of a complex chemical load on the population of the whole world, the use of pharmacological preparations, alcohol-containing products are the main factors that determine the high frequency and prevalence of toxic hepatitis. The search for new approaches for the treatment of toxic liver damage in order to restore structural and functional disorders is one of the urgent tasks of medicine. Of particular interest are the methods of regenerative medicine based on the use of various types of stem cells.
Purpose of the study — study of the effect of transplantation of multipotent mesenchymal stem cells on the processes of regeneration in the liver of rats with induced acute toxic hepatitis.
Materials and methods. An experimental study was conducted on 114 outbred male rats (3–5 months old) weighing 250–390 g. The animals were divided into 3 main groups. Group 1 — control animals (n=15). Group 2 (positive control) single intragastric injection of an oil solution of carbon tetrachloride (CCl4) at a dose of 1500 mg/kg (n=41); Group 3 (n=58) intragastrically injected with CCl4 at a dose of 1500 mg/kg, and intravenous transplantation of MMSC of 2×106, was carried out.
On the 1st, 3rd, 5th, 7th day of the experiment as well as the collection of organs and tissues for histological and morphometric studies was made.
Results. According to immunofluorescent analysis, intravenously transplanted MMSCs were found in the liver of rats at the 3rd and all subsequent periods of observation. In the present study, MMSC transplantation led to a statistically significant decrease in infiltrative processes in the liver tissue on the 3rd and 5th days of the study by 28.3% (p<0.0001) and 18.75% (p=0.0074) according to compared with the positive control group. On day 7, MMSC transplantation reduced the degree of fatty degeneration of the organ. The decrease in pathological manifestations of toxic hepatitis in rats is associated with an earlier activation of the mechanisms of reparative regeneration. Implementation of liver regeneration against the background of MMSC transplantation was carried out by enhancing protein-synthetic processes in liver cells, as well as increasing the mitotic activity of hepatocytes.
Conclusions. The conducted experimental study showed that MMSC transplantation is an effective method of stimulating regenerative processes in the liver after its acute toxic damage.
Limitations. In this experiment, lipid peroxidation processes in rat liver cells were not assessed, these criteria were not included in the study, and may be the subject of further study.
Ethics. Work with laboratory animals was carried out with the approval of the bioethical committee of the North-Western State Medical University. I.I. Mechnikov dated November 11, 2020, as well as in accordance with the international GLP rules adopted in the Russian Federation (Rules for Good Laboratory Practice), Order No. 267 of the Ministry of Health of the Russian Federation dated June 19, 2003.
Contribution:
Trapeznikova E.G. — the concept and design of the study, processing of the material, writing the text;
Shilov V.V. — the concept and design of the study, editing.
Funding. The study had no funding.
Conflict of interests. The authors declare no conflict of interest.
Received: 05.12.2022 / Accepted: 08.12.2022 / Published: 12.12.2022
Introduction. Imidourea is widely used as an antibacterial preservative in the pharmaceutical and cosmetic industries. There are literature data on the toxicity and specific effect of the substance, but there are no hygienic standards in the air of the working area necessary to protect the health of workers.
The study aims to substantiate the approximate safe level of exposure (ASLE) of imidourea in the air of the working area based on the study of the nature of biological action in various ways of entry into the body.
Materials and methods. The researchers chose the methods for studying the functions of organs and systems of experimental animals after a single inhalation of the substance at concentrations of 35.3±5.7 mg/m3 and 6.1±1.7 mg/m3 taking into account the literature data on the biological effect of the compound under study. We studied the antimicrobial effect of the substance on the intestinal microbiota of rats after 24 hours and 144 hours after inhalation exposure.
Results. During inhalation of the substance in both concentrations, the researchers observed disturbances in the balance of the intestinal microflora, which were characterized by changes in the number of individual representatives of the normal microbiota, which corresponds to the initial signs of dysbiosis of the 1st degree. 144 hours after exposure, the microflora balance was almost restored. Inhalation exposure to imidourea at a concentration of 35.3 mg /m3 also revealed changes in the functional parameters of the liver (decreased activity of alkaline phosphatase and glucose concentration in blood serum) and kidneys (decreased content and rate of protein excretion in urine).
Conclusion. Imidourea in the inhalation route of admission has a general toxic, sensitizing, weak antimicrobial effect. We recommend to use the ASLE of imidourea in the air of the working area of 1.5 mg/m3 (aerosol).
Ethics. The Ethics Commission of JSC "VNC BAS" adopted and approved the imidourea research program (Protocol No. 3 of 11.02.2020).
Contribution:
Golubeva M.I. — concept and design, collection and processing of material, writing the text, editing;
Bidevkina M.V. — concept and design, writing the text, editing;
Sheina N.I. — concept and design, writing the text, editing;
Budanova E.V. — collection and processing of material, statistical processing, writing the text, editing;
Vinogradova A.I. — collection and processing of material, statistical processing;
Bobrineva I.A. — collection and processing of material;
Fedorova E.A. — statistical processing.
Funding. The study had no funding.
Conflict of interests. The authors declare no conflict of interests.
Received: 27.10.2022 / Accepted: 24.11.2022 / Published: 12.12.2022
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 mm3.
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).
Contrubution:
Shabasheva L.V. — concept and design of research, collection and processing of material, statistical analysis, writing, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Protasova G.A. — concept and design of research, collection and processing of material, statistical analysis, writing, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Popov V.B. — concept and design of research, collection and processing of material, statistical analysis, writing, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Radilov A.S. — concept and design of research, collection and processing of material, statistical analysis, writing, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article.
Funding. The study had no funding.
Conflict of interests. The authors declare no conflict of interests.
Received: 01.12.2022 / Accepted: 05.12.2022 / Published: 12.12.2022
Technogenic effects on the production of oil, coal tar, other hydrocarbons and products of their processing can lead to diseases of the sebaceous glands. Gum-related factors trigger common links in the pathogenesis of vulgar and oily acne, which are inflammation, increased sebum production, excessive follicular hyperkeratosis.
There is a description of the clinical manifestations of severe oily acne in a railway worker on previously unchanged skin. We also have a description of the severe stage of the course of vulgar acne in the assistant engineer of the railway, who has a genetic predisposition, also has a history of juvenile acne of mild severity.
Chemical factors such as a mixture of hydrocarbons, phenol, creosote, asbestos-containing dust can provoke oily acne in a railway worker.
Oxides of nitrogen, carbon, sulfur, nitrogen dioxide, technical mixtures of hydrocarbons, violation of physiological rhythms of nutrition, sleep, rest, severity and intensity of the labor process, constant stress can lead to a relapse of vulgar acne with a more severe course in workers of locomotive crews.
The given clinical examples reveal the need for interdisciplinary interaction of dermatologists-venereologists and occupational pathologists in the treatment of skin pathology in workers of harmful industries.
Ethics. The patients signed a voluntary informed consent to post their photos in the journal.
Funding. The study had no funding.
Conflict of interests. The authors declare no conflict of interests.
Received: 01.11.2022 / Accepted: 16.11.2022 / Published: 12.12.2022
ISSN 2618-8945 (Online)
