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Toxicological Review

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Vol 33, No 4 (2025)
https://doi.org/10.47470/0869-7922-2025-33-4

PREVENTIVE TOXICOLOGY

221-228 35
Abstract

Introduction. Cylindrospermopsin (CSP) is a toxin produced by a variety of cyanobacteria species in aquatic areas, increased multiplication associated with climatic changes on the planet.

A series of foreign studies indicate the possibility of CSP ingestion into the human organism both with drinking water and recreational use of lake and river water. Along with the general toxic properties of CSP revealed in experiments, the effects of its low doses on morphofunctional state of internal organs of warm-blooded animals under conditions of long-term oral intake remain poorly studied.

The aim of the study is to investigate the peculiarities of morphofunctional changes of internal organs of animals under the influence of CSP on the body of white rats at intragastric intake under conditions of chronic experiment.

Material and methods. The analytical test sample of cylindrospermopsin, manufactured in Spain, CAS 143545-90-8, was used as an experimental target, the internal organs of outbred white male rats. The toxin was injected intragastrically into male white rats at doses of 0.1 µg/kg, 1.0 µg/kg, 10.0 µg/kg daily for 90 days. Morphofunctional changes were explored using morphological, morphometric and stereometric research methods.

Results. It was found that CSP only at a dose of 10 mcg/kg under conditions of chronic oral exposure causes the following structural and functional disorders in experimental animals, the severity of which remained in comparison with the control: liver fatty degeneration by 2.1 times, micronecrosis by 80%; kidney necrotic changes in the renal glomeruli by 2 times; stomach and in the large intestine – hypersecretion of its own glands by 3.5–4 times; in the thyroid gland – desquamation of thyrocytes by 5 times; in the testes, there is a pronounced rarefaction of spermatids and spermatozoa in the absence of the control group.

Limitations. The study is limited by the conditions of intragastric intake into the body of experimental animals and the use of one species and sex of warm-blooded animals in the experiment.

Conclusion. Chronic oral exposure to CSP at a dose of 10 micrograms/kg causes significant morphofunctional changes in the internal organs of experimental animals compared with the control, with the most stimulating effects in the stomach and large intestine and structural and functional abnormalities in the testes and thyroid gland, as well as necrotic disorders in the liver and kidneys.

Compliance with ethical standards. A positive conclusion was received from the Commission on Biomedical Ethics of the Federal Scientific Center of Hygiene named after F.F. Erisman (Protocol No. 03/22 dated 11/21/2022).

Authors’ contribution:
Kuz N.V. – conception and design of the study, collection and processing of material;
Turbinskii V.V. – research concept and design, text writing, editing;
Pushkareva M.V. – research concept and design, summary of results, text writing, editing;
Sinitsyna O.O. – research concept and design, summary of results, editing;
Masaltsev G.V. – text writing and material processing;
Shiryaeva M.A., Ryashentseva T.M., Vostrikova M.V., Malinovskaya N.N., Belyaeva N.N. – collection and processing of the material.
All co-authors – responsibility for the integrity of all parts of the article, approval of the final version of the article.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgments. The study was carried out as part of the implementation of the state program “Ensuring Chemical and Biological Safety of the Russian Federation” for 2021–2027.

Received: February 27, 2025 / Revised: May 27, 2025 / Accepted: July 14, 2025 / Published: August 29, 2025

229-236 32
Abstract

Introduction. To protect the population in conditions of polymetallic pollution of the environment, the enterosorption method is used, the purpose of which is to remove excess amounts of incoming metals from the body. Specialized literature mainly describes the clinical effectiveness of enterosorbents, while information on their sorption capacity is extremely insufficient. One of the approaches to increasing the sorption capacity of monoenterosorbents is the use of combinations of enterosorbents with different sorption mechanisms.

The purpose of the study is to conduct a comparative assessment of the sorption capacity of various types of enterosorbents, and to search for optimal combinations of biopolymer and mineral enterosorbents with higher effective sorption capacity compared to monoeutosorbents.

Material and methods. The sorption capacity of enterosorbents was estimated experimentally. To create combinations, the sorption capacity of the main types of biopolymer and mineral enterosorbents was determined. Of the biopolymer enterosorbents, based on the results of testing monoenterosorbents, chitin-containing preparations “Chitosan” and “Mikoton” were selected to create combinations. The most common mineral enterosorbents were selected to create combinations: dioctahedral smectite (“Smecta”), finely dispersed silicon dioxide (“Polysorb MP”), activated carbon, granulated zeolite based on a mineral of sedimentary-volcanic origin with a clinoptilolite content of up to 95% “ZeoDetox”. To model the complex composition of the internal environment of the body, it is proposed to use whey, which is a multicomponent matrix consisting of water with minerals and an organic fraction (proteins, carbohydrates, fats and vitamins) dissolved in it.

Results. A method for obtaining combinations of enterosorbents has been developed experimentally, allowing one to obtain their optimal homogeneous mixture with qualitatively new properties. The effectiveness of combinations of enterosorbents was determined based on the results of testing monoenterosorbents, with an assessment of the sorption capacity. The possibility of using whey, which simulates the liquid phase in which sorption processes occur in the body, to assess the sorption capacity of combinations of enterosorbents has been demonstrated. The created combinations of enterosorbents showed a higher sorption capacity with respect to the metals under study, compared to individual monoenterosorbents.

Limitations. The experiment was conducted in vitro, which, on the one hand, removes ethical restrictions, but forms certain qualitative limitations in the interpretation of the results of the efficiency of the obtained sorption materials as enterosorbents.

Conclusion. When high concentrations of metals are received, the optimal composition is a mixture combining biopolymers with established high sorption capacity and one of the mineral enterosorbents. Thus, a combined enterosorbent based on zeolite and activated carbon showed a relatively high absolute efficiency compared to other combinations of mineral enterosorbents. At the same time, it has high selectivity, which, in combination with low hydrophilicity, is optimal for regular use.

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

Authors’ contributions:
Tunakova Y.A. – concept and design of the study;
Galimova A.R. – conducting experimental studies;
Valiev V.S. – planning the study;
Faizullin R.I. – analysis and interpretation of the obtained data;
Shrom I.A. – literature analysis.
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 research was carried out with the financial support of the Ministry of Education and Science of the Russian Federation as part of the fulfillment of obligations under Agreement No. 075-03-2024-067 dated 17.01.2024 (topic number FZSU-2023-0005).

Received: December 24, 2024 / Revised: March 31, 2025 / Accepted: July 14, 2025 / Published: August 29, 2025

237-248 31
Abstract

Introduction. Testing of new methodological approaches to the system of hygienic regulation of chemicals in water using the example of substantiating the group maximum permissible concentration (MPC) of benzoic acid and its derivatives (sodium benzoate, potassium benzoate and benzyl alcohol).

The purpose of the study is to substantiate the group MPC of benzoic acid and its derivatives (sodium benzoate, potassium benzoate and benzyl alcohol) in water, taking into account current data on their toxicity and new methodological approaches to the existing system of hygienic regulation of chemicals in water.

Material and methods. The research material was Russian and foreign regulatory and methodological documents, domestic and foreign scientific publications containing information on the physicochemical properties, biotransformation and bioaccumulation abilities, and the effects of benzoic acid and its derivatives on laboratory animals and humans. The research was searched using the databases of scientific literature MedLine/PubMed/PubChem, Scopus, eLIBRARY.ru, WATERTOX databases (RAMS. STC: 02296014904). Research methods included searching and sorting information, identifying common and distinct signs of substance toxicity, comparative analysis, and expert evaluation.

Results. The threshold concentration of benzoic acid and its derivatives (sodium benzoate, potassium benzoate, benzyl alcohol) for the effect on the organoleptic properties of water (TCorg.) is 6.0 mg/l (for benzoic acid). The threshold concentration by influence on the processes of self-purification of water bodies (TCsan.) to justify the group MPC of benzoic acid and its derivatives is 0.1 mg/l (for benzoic acid). The value (calculated) of the maximum no-effect concentration of benzoic acid and its derivatives according to the sanitary-toxicological indicator of harmfulness is 20 mg/l (for benzoic acid).

Limitations. There is limited data in the literature on the parameters of toxicometry of benzoic acid and its derivatives (sodium benzoate, potassium benzoate, benzyl alcohol).

Conclusion. To introduce a group standard for benzoic acid and its derivatives (sodium benzoate, potassium benzoate, benzyl alcohol): 1) for water bodies of domestic and drinking water, cultural and household water use 0.1 mg/l (for benzoic acid), hazard class 3, limiting harm index – general sanitary; 2) for centralized water supply systems, including hot water supply, and non-centralized water supply 6 mg/l (for benzoic acid), hazard class 3, limiting harm index – organoleptic. Based on the principle of “unity of the standard and the method of its control”, to ensure the group PAC of benzoic acid and its derivatives, use the method of determining benzoic acid in water.

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

Authors’contribution:
Sinitsyna O.O. – conception and design of the study, generalization of data, writing and text editing;
Turbinskii V.V. – concept and design of the study, text editing;
Tulskaya E.A., Belyaeva N.I. – collection and processing of material;
Pivneva O.S. – conducting experiments.
All authors – responsibility for the integrity of all parts of the article, approval of the final version of the article.

Funding. The research was not financially supported.

Conflict of interest. The authors declare no conflict of interest.

Received: February 13, 2025 / Revised: May 13, 2025 / Accepted: July 14, 2025 / Published: August 29, 2025

249-257 32
Abstract

Toxicokinetic studies are a key aspect of preclinical drug safety studies. Regulatory documents describe methodological approaches to the toxicokinetic study, but do not answer many questions that arise during their planning.

The purpose of this work was the analysis of literature data, domestic and foreign methodological documents related to the preclinical study of drugs toxicokinetic, own experience in conducting such studies to propose possible designs for experiments on the study of toxicokinetic in concomitant studies and in studies with the formation of satellite groups.

The study materials were regulatory documents, literature sources, and guidelines for the preclinical study of toxicokinetics of drugs in the public domain (including, according to the PubMed, Web of Science, RISC (eLibrary.ru), Google scholar electronic databases), which were subjected to further general scientific analysis and generalization.

The toxicokinetic data as part of the drug registration dossier are necessary to establish the relationship between the detected toxicity and the administered dose of the drug, are important for planning clinical studies, contributing to the determination of threshold values of the substance in blood plasma to assess early exposure to humans. The features of planning and experimental toxicokinetic study in various formats are considered, designs of such studies are proposed.

A review of the literature data, regulatory documents, and experimental experience related to the study of toxicokinetics, which is an important element of drug development, was carried out.

Authors’contribution:
Karlina M.V. – concept of research, analysis of domestic and foreign methodological documents, preparation of the text;
Kosman V.M. – discussion of data, integration of materials from their own experience, additions to the text;
Makarova М.N. – critical revision of the manuscript;
Makarov V.G. – approval of the final version of the article.
All co-authors – responsibility for the integrity of all parts of the article.

Conflict of interests. The authors declare no conflict of interest.

Funding. The study had no sponsorship.

Received: February 02, 2025 / Revised: March 12, 2025 / Accepted: July 14, 2025 / Published: August 29, 2025

CLINICAL TOXICOLOGY

258-271 24
Abstract

Introduction. The lack of analytical determination of toxic chemicals in biological environments and environmental objects complicates the assessment of the prognosis of the poisoned person’s condition and the choice of medical tactics at the advanced stages of medical evacuation. This problem is extremely relevant in cases of poisoning with fast-acting substances in conditions where therapeutic measures are severely limited in time. Taking this into account, an attempt was made to develop a diagnostic algorithm based on the mathematical method of binary discrimination of objective signs of poisoning.

Material and methods. Tables of 56 bivariantly manifesting (yes/no) signs of 89 etiological types of poisoning were compiled taking into account national guidelines and the authors’ experience in the presence of analytical confirmation of the diagnosis. Using the discriminant binarization method, sets of 11 signs were selected that unambiguously determine all types of poisoning and a decision rule was compiled for their express diagnostics at the advanced stages of medical evacuation.

Results. Assessments of the presence or absence of objective manifestations of intoxication in the format of a reduced matrix made it possible to formulate a version of a decision rule for diagnosing poisoning with the most common types of military, industrial and medicinal toxicants, modern narcotic and psychotropic drugs, and substances of natural origin. The compiled algorithm is currently being tested to determine the objective characteristics of prognostic significance in the context of providing medical care of unknown structure toxic agent intoxication.

Limitations. Binary discrimination acceptability for data objectification on a probable toxic chemical class does not apply to home foodborne intoxications and iatrogenies, and their methodic interpretabilities are limited by preventive prescription of symptomatic therapeutics.

Conclusion. The method of multiple binary discrimination of alternatively expressed features is applicable in the formation of express assessments of the state and prognosis of the course of the disease allows reducing redundant information and compiling primary diagnostic algorithms applicable until analytical confirmation of the etiology of poisoning is available.

Compliance with ethical standards. The study does not require the provision of an opinion from the biomedical the ethics committee.

Author contribution:
Chepur S.V. – article idea, writing and editing the text;
Vinnik P.M. – mathematical solution of the applied problem;
Yudin M.A., Mosin A.V. – compilation of the matrix based on the clinical material;
Kobelev M.V, Kraenkov M.S. – numerical solutions.
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.

Received: October 17, 2024 / Accepted: July 14, 2025 / Published: August 29, 2025

ECOLOGICAL TOXICOLOGY

272-279 27
Abstract

Introduction. Ammonium polyphosphate (APP) is widely used as a fire retardant, fertilizer, food additive and emulsifier, so it is relevant to study its ecotoxicity in relation to aquatic and soil organisms.

Material and methods. The paper presents the results of assessing the toxic effect of aqueous solutions of APP in concentrations of 3.5, 17.5 and 35 mg/l, corresponding to 1, 5 and 10 the maximum permissible concentration (MPC) in water for domestic and drinking water use, using a complex of test organisms.

Results. Species differences in the effects of aqueous solutions of APP on test organisms and dose-dependent effects were established. An aqueous solution with a concentration of 3.5 mg/l APP had no effect on the development of the green algae Chlorella vulgaris Beijer and on the viability of the branchial crustaceans Daphnia magna Straus. At the same time, dose-dependent inhibition (by 57.6 and 69.3%) of C. vulgaris Beijer colony growth was observed with an increase in the concentration of APP in aqueous solutions to 17.5 and 35 mg/l and a death of D. magna Straus (53.3% after 72 h) at the maximum tested concentration. The toxic effect of aqueous solutions containing APP in all tested concentrations on the Lemna minor L. appeared after 7 days of exposure in the form of a decrease in the number of plants and the chlorophyll content in the leaves, and an increase in the number of roots and leaves.

Limitations. The use of these methods is possible only in a specially equipped laboratory with qualified personnel.

Conclusion. The data on the toxicity of APP have been expanded. The toxic effect of its solutions on the water test organisms C. vulgaris Beijer, D. magna Straus and L. minor L. and the absence of toxic effects on the soil test microorganism Dietzia maris AM3 have been shown.

Compliance with ethical standards: Animal (Daphnia magna Straus) protocols were approved by the Ethics Committee of the Scientific Medical Center of Saratov State University (protocol No. 12 dated December 23, 2024).

Authors’ contribution:
Demysheva A.D. – conducting experimental studies, writing the text;
Savenkova M.S., Kosheleva I.S. – conducting experimental studies;
Gusev Yu.S. – design of the study, processing and discussion of the results;
Pleshakova E.V. – discussion of the results, writing and editing 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 interests: The authors declare no conflict of interest.

Funding. The study had no sponsorship.

Received: January 14, 2025 / Revised: March 26, 2025 / Accepted: July 14, 2025 / Published: August 29, 2025

RESEARCH METHODS

280-287 22
Abstract

Introduction. As part of the development of a new method for in vitro hemocompatibility testing, it is necessary to study the blood compatibility of various medical devices on an artificial blood flow test model.

Material and methods. To study the blood compatibility of 13 polymeric and metallic medical devices, a method based on an in vitro artificial blood flow test model simulating the conditions of human arterial blood flow was used. Morphofunctional blood parameters were studied: levels of platelets, leukocytes, prothrombin fragment F1+2, thrombin-antithrombin complex III, beta-thromboglobulin, thromboxane B2 and complement cleavage proteins C3 after incubation with medical devices, positive and negative control samples.

Results. It has been established that the degree of changes in the parameters reflecting the enhancement of platelet activation processes and blood forming elements, complement system and coagulation processes has a dependence on the time of incubation of medical devices with heparinized human blood in the test model of artificial blood flow in vitro. After 20 minutes of incubation of 13 medical devices, blood parameters did not statistically significantly differ from the positive control, but when the incubation time was increased to 60 and 120 minutes, 6 out of 13 devices, both polymeric and metallic, affected cellular and humoral components of blood, indicating their less pronounced hemocompatibility properties.

Limitation. The study is limited to evaluating the hemocompatibility of polymeric and metallic medical devices only using a dynamic in vitro artificial blood flow test model.

Conclusion. All studied polymeric and metallic medical devices were blood compatible after 20 minutes of incubation on an in vitro artificial blood flow test model using whole heparinized blood.

Compliance with ethical standards. A positive opinion was received from the Bioethics Commission of the Research Institute of GT Computer Science of the Russian Center for Ethics and Health Care (Protocol No. 2 dated 03/29/2022). All participants gave informed voluntary written consent to participate in the study.

Authors’ contributions:
Lappo L.G. – data collection and processing, text writing, statistical analysis, editing;
Grynchak V.A. – research concept and design, editing;
Sychik S.I. – material processing, editing.
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 was carried out within the framework of the task 04.08. “To develop a method for evaluating the in vitro hemocompatibility of medical devices based on the test model of artificial blood flow” of the State Scientific and Technological Program “Scientific and Technical Support of Quality and Availability of Medical Services” for 2021–2025 of the subprogram “Safety of Human Environment” (State registration number 20220371 dated 03/28/2022).

Received: February 12, 2025 / Revised: February 25, 2025 / Accepted: July 14, 2025 / Published: August 29, 2025



ISSN 0869-7922 (Print)
ISSN 3034-4611 (Online)