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No 3 (2023)

Original articles

The role of the toxicological service in the drug situation monitoring system: problems and ways of improvement

Shikalova I.A., Lodyagin A.N., Barsukova I.M., Panov A.M., Sinenchenko A.G.

Abstract

Introduction. The relevance of the research topic is determined by the high significance of measures aimed at combating and preventing the illegal distribution and non-medical use of narcotic substances.

The aim of the study. Show the importance of toxicological monitoring in the drug situation assessment system, identify existing problems and ways to improve it.

Material and methods. Analiysis of the regulatory legal framework regulating the provision of toxicological care to the population and the drug situation monitoring system, analysis of the toxicological monitoring system in St. Petersburg. Statistical and analytical methods along with content analysis were used.

Results. The article presents the contribution of the toxicological service to the drug situation monitoring system in the Russian Federation and identifies a number of organizational problems related to the diagnosis and accounting of acute poisoning with narcotic substances. Proposed the ways of improving toxicological monitoring, which will improve the quality and efficiency of information capturing — organization and equipping with modern diagnostic equipment of toxicological centers (departments) in all subjects of Russian Federation; ensuring the availability of toxicological counseling through the development of a system of regional information and advisory toxicological centers; coordination of poisoning by new narcotic substances and their precursors with the unified coding system ICD-10; development of a control system for filling out registration form No. 58-1/у “Emergency notification of acute poisoning of chemical etiology”; supplement the group “drug poisoning” of Federal Forms of Statistical Observation No. 57 and No. 14 with nosological units - cannabis poisoning (T40.7), LSD poisoning (T40.8), poisoning with other and unspecified psychodisleptics (T40.9); organization of a stationary post of the Ministry of Internal Affairs on the basis of toxicological centers, which will allow more effective measures to prevent spread and use of drugs.

Limitations. Regulatory and legal framework in the field of official statistical accounting of acute poisoning with drugs and psychosleptics.

Conclusion. The data obtained in the course of the study will allow improving the system of monitoring the drug situation in the country, conducting a comparative interregional analysis, promptly and objectively evaluating the quality of work on the prevention of illegal distribution and non-medical use of narcotic substances and drug trafficking control.

Compliance with ethical standards. The study does not require the submission of the conclusion of the Biomedical ethics committee and other documents.

Author contribution:
Shikalova I.A. — the concept and design of the study, the collection and processing of material, statistical analysis, writing the text;
Lodyagin A.N. — study concept and design, editing;
Barsukova I.M. — text writing, editing;
Panov A.M. — collection and processing of material, writing the text, editing;
Sinenchenko A.G. — writing 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 was not sponsored.

Received: December 27, 2022 / Accepted: May 26, 2023 / Published: June 30, 2023

Toxicological Review. 2023;31(3):142-149
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A case of a favorable outcome of acute oral poisoning with a mixture of narcotic and psychoactive substances of severe degree, complicated by the development of acute respiratory failure and exotoxic shock (clinical observation)

Narzikulov R.A., Lodyagin A.N., Sinenchenko A.G., Батоцыренов Ч.Б., Rustamov B.R., Lisitsa I.A., Zapasnikov N.D.

Abstract

Introduction. The article considers a case of a favorable outcome of acute oral poisoning with a mixture of narcotic and psychoactive substances of severe degree, complicated by the development of acute respiratory failure and exotoxic shock.

Clinical observation. An episode of acute oral poisoning with a mixture of narcotic and psychoactive substances of severe degree (baclofen, (4-amino-3-(4-chlorophenyl) is presented-butyric acid — ethylglucuronide >2000 mg/ml), methadone 83 mg/ml, methylenedioxypyrovaleron 57 ng/ml, complicated by the development of exotoxic shock in a 32-year-old patient. The clinical picture of acute poisoning was manifested by depression of consciousness to the level of coma II, acute respiratory failure, mixed respiratory and metabolic acidosis (pH 7.18; partial pressure of carbon dioxide 64.0 mmHg, lactic acidosis up to 5 mmol/l), swelling of the brain, exotoxic shock (BP — 60/20 mmHg, heart rate — 110 beats per minute).

Intensive therapy included: respiratory, infusion, detoxification, anticoagulation, antibacterial therapy, correction of acid-base state disorders, water-electrolyte balance, nutritional support, normalization of metabolic disorders through the use of a substrate antihypoxant. The calculation of the required amount of sodium bicarbonate was carried out according to the Mellengaard-Astrup formula: the amount of mmol of sodium bicarbonate is equal to the product of VE • body weight in kg • 0.3. According to the calculation, the amount of required bicarbonate was 195 mmol, that is, in terms of 5% bicarbonate solution — 195 ml.

Conclusion. As a result of basic resuscitation care in the form of artificial lung ventilation, correction of mixed respiratory and metabolic acidosis by using sodium bicarbonate, infusion therapy to correct hypovolemia, ensuring optimal perfusion of organs and tissues, elimination of key links of hypoxia by using cytoflavin, improvement of rheological properties of blood and symptomatic therapy allowed for a favorable outcome of severe poisoning with a mixture of narcotic and psychoactive substances complicated by the development of exotoxic shock.

Compliance with ethical standards. The study was approved by the Local Ethics Committee of the I.I. Janelidze St. Petersburg Research Institute of SP Protocol No. 1 of 12.02.2022.

Author contribution:
Narzikulov R.A. — concept and design of the study, collection and processing of material, writing of the text;
Lodyagin A.N. — concept and design of the study, editing;
Sinenchenko A.G., Batotsyrenov Ch.B. — collection and processing of material;
Lisitsyna I.A., Zapadnikov N.D., Rustamov B.R. — writing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. The authors declare that there are no conflicts of interest.

Financing. The study had no sponsorship.

Received: January 23, 2023 / Accepted: May 26, 2023 / Published: June 30, 2023

Toxicological Review. 2023;31(3):150-156
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Changes in indicators of the autonomic nervous system in acute poisoning with 1,4-butanediol complicated by withdrawal syndrome

Lodyagin A.N., Sinenchenko A.G., Kuczalo A.L., Batocyrenov B.V., Sinenchenko G.I., Kuzneczov S.V.

Abstract

Introduction. The article presents an assessment of the functional state of the autonomic nervous system in patients with acute 1,4-butanediol poisoning complicated by withdrawal syndrome using pupillometry. Purpose of the study: to analyze changes in the indicators of the autonomic nervous system in patients with acute 1,4-butanediol poisoning complicated by withdrawal syndrome.

Material and methods. In the course of the work, a prospective examination of 30 patients with acute 1,4-butanediol poisoning, complicated by withdrawal syndrome, aged 19 to 39 years (median age was 25.3 [20.1; 24.9] years) was carried out. All patients were treated at the Center for the Treatment of St. Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine. Pupullometry was performed using the hardware-software complex KSRZRts-01. Statistical processing of the obtained results was carried out in the program Statistica for Windows (version 10).

Results. In the course of the study, patients with acute poisoning with 1,4-butanediol develop a neurovegetative variant of AS, manifested by signs of parasympathicotonia, expressed in changes in the bioelectrical activity of the brain in the form of irritation of cortical-subcortical structures with rapid exhaustion and instability of the functional tone of cortical neurons, cognitive impairment, ideation and motor retardation, deviations of pupillometry parameters (decrease in the initial pupil diameter and constriction amplitude, increase in the time of onset of the pupillary reaction).

limitations. In the study of the effect of 1,4-butanediol on the indicators of the autonomic nervous system in the course of a prospective examination of 30 male patients of the Center for the Treatment of St. Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine with acute poisoning by a toxicant, it was found that there were significant changes in the parameters of this system in the withdrawal period.

Conclusion. The indicators revealed during the study prove the predominance of the neurovegetative variant of the withdrawal syndrome with a characteristic change in the bioelectrical activity of the brain, cognitive functions and pupillometry parameters.

Compliance with ethical standards. The study was approved by the Local Ethics Committee of the I.I. Dzhanelidze St. Petersburg Research Institute of SP Protocol No. 1 of 12.02.2021.

Author contribution:
Lodyagin A.N. — concept and design of the study, collection and processing of material, statistical processing, writing the text, editing;
Sinenchenko A.G. — collection and processing of material, statistical processing, writing the text;
Kutsalo A.L. — collection and processing of material, statistical processing;
Batotsyrenov B.V. — concept and design of the study, editing;
Sinenchenko G.I. — concept and design of the study, writing the text;
Kuznetsov S.V. — writing the text.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version. 

Conflict of interest. The authors acknowledge that there are no known conflicts of interest related to this publication.

Funding. The study was not sponsored.

Received: January 23, 2023 / Accepted: May 26, 2023 / Published: June 30, 2023

Toxicological Review. 2023;31(3):157-162
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Experimental study of the effectiveness of ademethionine and inosine glycyl-cysteinyl-glutamate disodium in the treatment of dichloroethane-induced toxic hepatitis

Orlov Y.V., Gaiduk S.V., Kuzmich V.G.

Abstract

Introduction. Currently, in the search for drugs for the toxic liver damage treatment, considerable attention is paid to glutathione preparations and its metabolic precursors. There are separate reports in the literature on the hepatoprotective and antifibrotic effects of glutathione disulfide in viral liver lesions, which gives grounds for their additional study when exposed to hepatotropic substances.

Material and methods. Performing a comparative assessment of the hepatoprotective effect of inosine glycyl-cysteinyl-glutamate disodium and ademetionine on the model of dichloroethane-induced toxic hepatitis in rats was carried out with the formation of the following experimental groups of animals: no treatment; with the introduction of physiological saline; with the introduction of inosine glycyl-cysteinyl-glutamate disodium; with the introduction of ademetionine, as well as a group of intact animals. The study drugs were administered intraperitoneally for 10 days. In the course of the study, biochemical indicators of cytolytic and cholestatic syndromes of liver damage were determined, the activity of its detoxification system and plastic function were assessed.

Results. In groups that did not receive treatment, but received physiological saline, the lethality of experimental animals by the 20th day of observation was 40%, in the group treated with ademetionine — 10%. In the group treated with inosine glycyl-cysteinyl-glutamate disodium, no death of animals was observed. The use of inosine glycyl-cysteinyl-glutamate disodium led to a more significant decrease in the indicators of cytolytic and cholestatic syndromes, as well as normalization of the functional activity of the liver (restoration of the content of glutathione in the liver tissue) and its plastic function (restoration of the level of total blood serum protein and glycogen content in the liver parenchyma) to a greater extent than with ademetionine.

limitation. The experimental study was carried out on outbred male rats weighing 180–220 g, kept under standard vivarium conditions in one cage, no more than 6 individuals, divided into groups by randomization with the exclusion of weakened and sick animals from the study.

Conclusion. The study provided an experimental justification for further study of the hepatoprotective effect of inosine glycylcysteinylglutamate disodium in toxic liver damage.

Compliance with ethical standards. This experimental study was approved by the decision of the ethical committee (extract from protocol No. 247 dated November 22, 2022) of the Military medical academy of S.M. Kirov, Ministry of Defense of the Russian Federation. Animal handling was organized in accordance with the rules of good laboratory practice (GOST 33044–2014).

Author contribution:
Orlov Yu.V. — design of the study, setting up the experiment, collecting and processing the material, statistical analysis, writing the text;
Gaiduk S.V., Kuzmich V.G. — concept, 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 that there is no conflict of interest.

Financing. The study had no sponsorship.

Received: May 10, 2023 / Accepted: May 26, 2023 / Published: June 30, 2023

Toxicological Review. 2023;31(3):163-168
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Evaluation of bioaccumulation and toxic effect of aluminum and molybdenum oxide nanoparticles used as an active component of bactericidal agents

Stepankov M.S.

Abstract

Introduction. Nanoparticles (NPs) of aluminum oxide (Al2O3) and molybdenum oxide (MoO3) have the potential to be used as an active component of bactericidal agents. At the same time, there is information in the scientific literature about the negative effects of these NPs on organism. Given that, it seems relevant to perform the study and comparative analysis of the toxicity of Al2O3 and MoO3 NPs.

Materials and methods. We examined physical properties of Al2O3 NPs and MoO3 NPs. In an experiment on Wistar rats, peculiarities of bioaccumulation and toxic action at multiply inhalation exposure was researched. 

Results. The examined samples were a nanomaterial judging by such parameters as particle size, shape, surface area and total pore volume. Under exposure to Al2O3 NPs, aluminum concentrations were statistically significant increase in the lungs, brain, liver and blood relative to the control; under exposure to MoO3 NPs — molybdenum concentration in heart, lungs, brain, kidney and blood. Under exposure to MoO3 NPs, a wider range of negative effects changed relative to the control of biochemical parameters (increased activity of ALP, LDH, concentrations of total and direct bilirubin, urea, creatinine) was established than during exposure to Al2O3 NPs (increased activity of ALT, AST, ALP, LDH, concentrations direct bilirubin). Pathomorphological changes were identified in the lungs, brain, heart and liver under exposure to Al2O3 NPs; in lungs, brain and liver under exposure to MoO3 NPs in the lungs. However, tissue changes upon exposure to MoO3 NPs are more pronounced than those upon exposure to Al2O3 NPs. 

Limitations. The study involved only multiple inhalation exposure to Al2O3 NPs and MoO3 NPs in an experiment on Wistar rats.

Conclusion. Differences in the toxicokinetics of Al2O3 and MoO3 NPs do not make it possible to single out among them those that are more dangerous for human health, and therefore additional studies are needed.

Compliance with ethical standards. The study was accomplished in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS No. 123) and requirements of the Local Committee on Ethics of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies (the Meeting Report No. 5 and 6 issued on January 20, 2021).

Conflict of interests. The author declares no conflict of interest.

Funding. The research was granted financial support from the federal budget.

Received: December 27, 2022 / Accepted: May 26, 2023 / Published: June 30, 2023

Toxicological Review. 2023;31(3):169-177
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Toxicological and hygienic assessment of phthalate content in bottled drinking water

Shilov V.V., Khurtsilava O.G., Markova O.L., Isaev D.S., Mikheeva A.Y.

Abstract

Introduction. One of the most common materials containing phthalate impurities is packaging made of polymer materials (bottles). Bottles made of the following material are used for packaged (bottled) drinking water — polyethylene terephthalate (PET). The toxicological properties of phthalates, the increase in consumption of bottled water and uncertainty about the effect of storage conditions on the migration of phthalates into water initiates research on the toxicological and hygienic assessment of the content of phthalates in polymer packaging for bottled drinking water.The purpose of study was the toxicological and hygienic assessment of the content of di(2-ethylhexyl)-phthalate (DEHP); di-n-butyl phthalate (DnBP); diisobutyl phthalate (DiBP) in drinking water packed in polymer material.

Materials and methods. The objects of the study were bottles samples made in the Russian Federation. The obtained extracts (containers and model medium) were analyzed by gas chromatography with mass spectrometric detection. The values of daily consumption of phthalates with bottled water for adults and children were calculated, safety coefficients were determined taking into account the maximum concentrations obtained in the experiment.

Results. As a result of polymer materials studies, it was found that bottle samples contain residual amounts of phthalates – DEHP 1.7–4.2 mg/kg; DnBP < 2.4–31.3 mg/kg; DiBP 2.2–10.2 2 mg/kg. Migration of phthalates into aqueous model media was noted from all the samples studied.In the samples of model solutions in contact with PET material, on the 30th day at a temperature of 20 °C, the presence of 2 phthalates: DEHP 8.6–71.0 µ/l and DiBF <2.6 to 19.2 µ/l. Comparison of phthalate concentrations in model media with the values of permissible daily consumption showed that bottled water provides a limited contribution to the total daily exposure of phthalates.

Conclusion. The study results showed that the packaging made of PET is a source of chemical contamination of bottled water, which is based on the processes of migration of organic components from polymer materials. At the same time, special attention should be paid to the ability to migrate di(2-ethylhexyl)-phthalate, which can lead to excess of hygienic standards for drinking water.

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

Contribution of the authors:
Shilov V.V. — the concept and design of the study, editing;
Khurtsilava O.G. — writing a text, editing;
Markova O.L. — the concept and design of the study, collection and processing of material, writing a text;
Isaev D.S. — statistical analysis, editing;
Mikheyeva A.Yu. — collection and processing of material.
All co-authors — are approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. Authors declare no conflict of interest. 

Funding. The study had no sponsorship. 

Received: March 24, 2023 / Accepted: May 26, 2023 / Published: June 30, 2023

Toxicological Review. 2023;31(3):178-184
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Ecological and toxicological assessment of hazard of contamination of water bodies by the γ-polyoxymethylene

Maslennikov A.A., Demidova S.A., Ilchenko O.I., Antonov V.A.

Abstract

Introduction. In the process of production, storage and application of the representative of new components of solid rocket fuels — γ-polyoxymethylene, its ingress into the water of reservoirs is not excluded, which determines the mandatory assessment of the danger of its single contamination of this ecosystem.

Material and methods. As an object of research, γ-polyoxymethylene (γ-POM, polyformaldehyde, acetal copolymer) was used — a mixture of dimethyl esters of polyoxymethylene glycols — a fine amorphous white powder, CAS registration number 66455-31-0. The empirical formula is CH3O(CH2O)nCH3 at n = 100–300. It is practically insoluble in water.

Results. It was found that the ecotoxicant content in water at a concentration of 50.0 mg/l led to a change in its transparency. The indicated concentration of γ-POM was determined as a threshold for organoleptic harmfulness.

In the course of studying the effect of the toxicant on the general sanitary regime of reservoirs, in the absence of changes in the indicators of biochemical oxygen consumption, its negative impact on nitrification processes and saprophytic microflora was revealed. The threshold concentration of the substance according to the general sanitary indicator of harmfulness is 3.5 mg/l.

In experiments on laboratory animals, it was noted that a single intragastric administration of the tested xenobiotic in the form of a suspension in a 2.5% solution of aqueous starch caused a significant decrease in heart rate and a change in a number of hematological parameters. The threshold of a single general toxic effect of γ-POM is 90.0 mg/kg.

Limitations of the study. The revealed features of the behavior of γ-polyoxymethylene must be taken into account when it once pollutes the water of reservoirs (in case of an emergency). However, the data obtained are insufficient to substantiate the hygienic standard of the connection in the water of water bodies.

Conclusion. The results of the performed experiments indicate that a single ingress of γ-polyoxymethylene into the water represents an ecological and toxicological hazard registered for all three basic signs of harmfulness, which is taken into account when justifying its maximum permissible concentration in the water of reservoirs.

Compliance with ethical standards. The studies were carried out in accordance with the requirements of good laboratory practice.

Contribution:
Maslennikov A.A. — research concept and design, analysis of results, writing text;
Demidova S.A. — planning and execution of research;
Ilchenko O.I. — statistical data processing;
Antonov V.A. — 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 interests.

Acknowledgements. The study was conducted within the framework of a State contract on the topic “Development of hygienic standards, regulatory and methodological documents regulating the implementation of state sanitary and epidemiological supervision in the production of solid rocket fuels”.

Received: January 23, 2023 / Accepted: May 26, 2023 / Published: June 30, 2023

Toxicological Review. 2023;31(3):185-191
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Ecological Toxicology

The effect of zaleplon on metabolic changes in neurotransmitters and toxic effects in Danio fish

Volkova A.A., Kalekin R.A., Orlova A.M., Pavlova A.Z., Astashkina O.G., Pavlov A.L.

Abstract

Introduction. Z-drugs are a group of “non-benzodiazepine” drugs with the main mode of action regulating sleep behavior in humans through exposure to GABA receptors. There are reports indicating the toxic effects of overdose and abuse of zaleplon. However, information on the effect of Z-drugs on neurotransmitter levels is scarce.

The aim of this study was to study the effect of zaleplon exposure on neurotransmitter levels in the larvae of Danio fish using targeted metabolomics.

Material and methods. 4-hour exposure to zaleplon in concentrations of 0.1, 1.0, 10, 100 and 1000 μg/l was carried out on the larvae of Danio fish. Intervention groups were compared with control groups. Each group consisted of 20 larvae of Danio fish. Neurotransmitters and their metabolites were measured using high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS).

Results. Twenty-two metabolites associated with neurotransmission were quantified. Significantly increased metabolites were tryptophan, serotonin, 5-hydroxyindolacetic acid, acetylserotonin, epinephrine and choline. Significantly reduced metabolites were 5-hydroxytryptophan, 5-methoxytryptamine, dopamine, normetanephrine, metanephrine, kynurenine, 3-hydroxykinurenine, anthranilic acid and gamma-aminobutyric acid.

Limitation. When studying metabolic changes in neurotransmitters and toxic effects in Danio fish, the results of a group of 20 larvae were analyzed, which is a sufficient sample to state the results obtained.

Conclusion. Exposure to zaleplon caused metabolic changes in the concentrations of neurotransmitters associated with most major neurotransmitter systems.

Compliance with ethical standards. The study does not require the submission of a biomedical ethics committee opinion or other documents, as the study was conducted on fish embryos in accordance with SIS 33774-2016 “Testing chemicals that pose a danger to the environment. Acute toxicity of fish embryos (FET)”.

Author contribution. All co-authors made an equal contribution to the research and preparation of the article for publication.

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

Funding. The study was not sponsored.

Received: December 27, 2022 / Accepted: May 26, 2023 / Published: June 30, 2023

Toxicological Review. 2023;31(3):192-203
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Chemical safety

Assessment and classification of the danger of endocrine disruptors

Editorial Р.

Abstract

Научно-практический журнал «Токсикологический вестник» продолжает публикацию научно обоснованного списка  эндокринных разрушителей, который лёг в основу методических рекомендаций МР 1.2.0313–22 «Оценка и классификация опасности эндокринных разрушителей», утверждённых Руководителем Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека А.Ю. Поповой 30 декабря 2022 г. 

Toxicological Review. 2023;31(3):204-207
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Congresses, conferences, meetings, seminars

Outcomes of the xi meeting of the Conference of the Parties to the Rotterdam convention on the prior informed consent procedure for certain hazardous chemicals and pesticides in international trade

Editorial Р.

Abstract

С 1 по 12 мая 2023 г. в г. Женева (Швейцария) состоялась очередная тройная Конференция Сторон химических конвенций: шестнадцатое совещание Конференции Сторон Базельской конвенции о контроле за трансграничной перевозкой опасных отходов и их удалением, одиннадцатое совещание Конференции Сторон Роттердамской конвенции о процедуре предварительного обоснованного согласия в отношении отдельных опасных химических веществ и пестицидов в международной торговле и одиннадцатое совещание Конференции Сторон Стокгольмской конвенции о стойких органических загрязнителях.

Toxicological Review. 2023;31(3):208-208
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Anniversary

To the 75th anniversary of Larisa Ivanovna Privalova

Editorial Р.

Abstract

7 июля 2023 г. исполнилось 75 лет со дня рождения доктора медицинских наук, профессора, главного научного сотрудника ФБУН «Екатеринбургский медицинский-научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора Ларисы Ивановны Приваловой.

Toxicological Review. 2023;31(3):209-209
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Obituaries

In memory of Isaac Mikhailovich Trachtenberg

Editorial Р.

Abstract

27 января 2023 года на 99 году жизни скончался известный ученый-гигиенист, токсиколог, академик АМН Украины, член-корреспондент Национальной академии наук Украины, заслуженный деятель науки и техники, лауреат Государственной премии, руководитель лаборатории промышленной токсикологии и гигиены труда при использовании химических веществ Института медицины труда АМН Украины, доктор медицинских наук, профессор Исаак Михайлович Трахтенберг.

Toxicological Review. 2023;31(3):210-210
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