编号 5 (2022)

封面

Articles

Dear colleagues!

Хамидулина Х.

摘要

В этот знаменательный год — год 100-летия Санитарно-эпидемиологической службы России, своё 130-летие отмечает Всероссийское  общество гигиенистов, токсикологов и санитарных врачей, которое берёт своё начало в 1892 г., когда по инициативе Ф.Ф. Эрисмана было создано Московское гигиеническое общество, активно занимавшееся вопросами обеспечения населения питанием, школьной гигиеной, устройством и содержанием московских ночлежных домов, специальное внимание было обращено на улучшение санитарного надзора за знаменитым Хитровым рынком – центром ночлежных домов. На различных этапах развития государства поднимались и успешно решались различные вопросы гигиены и эпидемиологии.

В разные годы Обществом руководили выдающиеся деятели науки: Ф.Ф. Эрисман, А.В. Мольков, Н.А. Семашко, А.Н. Сысин, Ф.Г. Кротков, Г.Н. Сердюковская, А.П. Шицкова, Н.Н. Литвинов, Г.В. Селюжитский, Е.Н. Беляев, А.В. Истомин, Н.В. Шестопалов. С февраля 2021 г. председатель общества – академик РАН В.Н. Ракитский.

26–28 октября 2022 г. в г. Москве состоялся XIII Всероссийский съезд гигиенистов, токсикологов и санитарных врачей, где на секции «Профилактическая и клиническая токсикология» были заслушаны доклады ведущих специалистов страны в области токсикологии. Отдельные доклады в виде статей представлены в данном выпуске журнала.

С уважением и добрыми пожеланиями,
Главный редактор  Х.Х. Хамидулина

Toxicological Review. 2022;30(5):269-269
pages 269-269 views

Original articles

Genetic toxicology in hygiene

Ilyushina N.

摘要

The article discusses the directions of research in the field of genetic toxicology, which allow solving problems important for hygiene, aimed at ensuring the genetic health of the population. The main areas of research are: assessment of the genetic hazard of environmental factors and the level of pollution by genotoxicants; analysis of the total mutagenic activity of mixtures of chemical pollutants; control over mutational events in the somatic cells of people working in hazardous production conditions, which is necessary to improve the prevention, diagnosis and treatment of occupational diseases and multifactorial pathology; study of individual genetically determined human sensitivity to the impacts of adverse environmental factors in order to improve professional selection and development of personalized preventive medicine; assessment of mutagenicity in short-term tests to predict the carcinogenicity of the studied substances; search for antimutagens. The methods used in genetic toxicology are described. The main directions and results of the work of the Department of Genetic Toxicology of the FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Rospotrebnadzor are given.

Conclusion. The results of genotoxicological studies allow us to evaluate and establish hazard classes of the tested substances, predict possible long-term effects. Monitoring of mutational events in the somatic cells of people exposed to various environmental factors, assessment of individual human sensitivity to specific factors or their combinations make it possible to identify and evaluate potentially dangerous factors for genetic health, develop preventive measures and carry out reasonable professional selection of persons to work in harmful production conditions.

Conflict of Interests. Author declare no conflict interests.

Funding. The study had no funding.

Received: September 08, 2022 / Accepted: September 22, 2022 / Published: October 30, 2022

Toxicological Review. 2022;30(5):271-276
pages 271-276 views

Comparative evaluation of the genotoxicity of carbendazim technical grade active ingredients in the Ames test and micronucleus in vivo test

Egorova O., Averyanova N., Kara L., Ilyushina N.

摘要

Introduction. Carbendazim is a systemic benzimidazole fungicide used against a wide range of crop diseases. The ability of carbendazim to induce the incidence of chromosomal aberrations and micronuclei in mammalian cells by influencing the processes of mitotic spindle formation in the cell cycle have been shown in various in vitro and in vivo tests. Contradictory data were obtained in the bacterial test system Salmonella/microsomes, indicating both the absence and the presence of mutagenic activity of carbendazim. The discrepancy in the results may stem from the presence of impurities.

The aim of the study was a comparative evaluation of the genotoxicity of various technical products of carbendazim.

Materials and methods. The genotoxicity of carbendazim was studied using the plate incorporation version of the Ames test on 5 strains of Salmonella typhimurium in the presence and the absence of metabolic activation system (+S9/-S9) and in a micronucleus test in CD-1 mice. Two technical grade active ingredients (TGAI) and an analytical standard for carbendazim were tested.

Results. In the Ames test, the analytical standard of carbendazim possessed no mutagenic activity (±S9) on any of the strains. The most pronounced mutagenic effect was observed for the TGAI I in TA98 strain, the number of revertants at the maximum concentration was 5–7 times higher than that in the negative control. The positive effects of carbendazim TGAIs in the Ames test are likely mediated by the presence of impurities. Under in vivo conditions, all tested TGAIs of carbendazim induced a statistically significant and dose-dependent formation of micronuclei in polychromatic erythrocytes (PCE) of mouse bone marrow. The mean frequency of PCE with micronuclei at the maximum dose exceeded this rate in the negative control by 21–24 times.

Research limitations. The study is limited to testing the mutagenic activity of two samples of carbendazim technical products and one sample of its analytical standard in both in vivo and in vitro tests.

Conclusion. Taking into account the high content of the active substance in the tested TGAIs, the bacterial reverse mutation test is a highly sensitive method for assessment of the equivalence of carbendazim generic products. The use of a micronucleus test for evaluating of the equivalence of carbendazim TGAIs to the original substance is inappropriate due to the pronounced aneugenic effect.

Compliance with ethical standards. The study involving animals was approved by the FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing.

Author contribution:
Egorova O.V. — the concept and design of the study, collection and processing of material, writing a text;
Averyanova N.S. — collection and processing of material;
Kara L.A. — collection of material, statistical analysis;
Ilyushina N.A. — the concept and design of the study, processing of material, writing a text.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. Authors declare no conflict of interest.

Funding. The study was not sponsored.

Received: September 08, 2022 / Accepted: September 22, 2022 / Published: October 30, 2022

Toxicological Review. 2022;30(5):277-285
pages 277-285 views

Toxicometabolomics — integration of preventive and analytical toxicology

Radilov A., Ukolov A.

摘要

Introduction. This paper considers aspects of the development of a toxicokinetically based model for scaling the limit concentrations of toxic compounds in the air, estimating the coefficients of their material cumulation, as well as estimating the concentrations of toxicants in biological media expected in the course of biological control. The results of testing the model on the example of organophosphorus pesticides (OP) and volatile industrial pollutants (VIP) are presented.

Material and methods. For experimental modeling of intoxication, male chinchilla rabbits obtained from the Rappolovo nursery were used. Blood sampling was carried out from the marginal vein of the ear. For the highly sensitive determination of OP and VIP in biological samples, previously developed highly sensitive gas chromatographic techniques were used. Calculation of toxicokinetic parameters was made using a two-compartment model.

Results. A toxicokinetically based model for scaling the limit concentrations of toxic compounds in the air, estimating the coefficients of their material cumulation, and estimating the concentrations of toxicants in biological media expected in the course of biological control is proposed.

Research limitations. The proposed algorithm for scaling toxicokinetic parameters can be applied under the condition that the bioavailability of chemical compounds for the animal and human body is close, as well as the area under the toxicokinetic curve that is close to a linear dependence on the dose.

Conclusion. Using the proposed toxicokinetically substantiated model for scaling the threshold concentrations, recommendations were made on chemical-analytical methods of biological control in the working area and atmospheric air for OP and VIP.

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

Author contributions:
Radilov A.S. — the concept and design of the study, analysis of results;
Ukolov A.I. — study planning, sample preparation, study execution and data processing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgements. The authors are grateful to S.A. Dulov for many valuable comments that contributed to the quality of the publication. 

Conflict of interests. the authors declare no conflict of interests.

Funding. The study was not sponsored.

Received: September 08, 2022 / Accepted: September 22, 2022 / Published: October 30, 2022

Toxicological Review. 2022;30(5):286-296
pages 286-296 views

The effect of the combined effects of carbon monoxide and harmful physical factors on the behavioral activity of animals

Kriyt V., Reinyuk V., Sladkova Y., Pyatibrat A.

摘要

Introduction. In the course of their work, firefighters are exposed to many harmful and dangerous factors, among which the chemical factor takes the leading place. Carbon monoxide is an integral part of any combustion, and its leading role in the toxic effect of combustion products is confirmed by numerous experimental data. The results obtained in the experiment on animals are of great importance in the study of combined effects.

The purpose of the study was to study the behavioral activity of animals under combined exposure to carbon monoxide and harmful physical factors.

Material and methods. The study was performed on outbred white male rats 3 months of age, in two directions: the study of the combined effects of carbon monoxide and elevated air temperature and the study of the combined effects of carbon monoxide and vibroacoustic factor. In each of the experimental models, rats were randomly divided into 6 groups: the first group was exposed to a single physical factor under study, the second group was exposed to multiple physical factors (for 14 days), the third group was exposed to a single exposure to carbon monoxide, the fourth group was exposed to multiple exposures to monoxide carbon, the fifth group was subjected to a single combined effect of a physical factor and carbon monoxide; the sixth group was subjected to multiple combined effects of the physical factor and carbon monoxide. The study of the behavioral activity of animals was carried out using the “Open field” and “Elevated plus maze” methods.

Results. The data obtained indicate that the combined effect of carbon monoxide and harmful physical factors causes a change in the indicators of behavioral reactions of animals, while if with a single exposure most of the indicators return to the background values in a day, then with repeated exposure they remain significantly changed.

Conclusion. The data obtained can be applied in studying the long-term effects of the combined effects of carbon monoxide and harmful physical factors on the body of firefighters.

Compliance with ethical standards. The Local ethics committee of the North-West Public Health Research Center of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing approved this study carried out under the European Convention for the Protection of Vertebrate Animals Used for Experiments or Other Scientific Purposes (ETS N 123), Directive of the European Parliament and Council of the European Union 2010/63/EU of 22.09.2010 on the protection of animals used for scientific purposes.

Author contributions:
Kriyt V.E. — the concept and design of the study, writing a text;
Reinyuk V.L. — editing;
Sladkova Yu.N. — the collection and processing of material, editing;
Pyatibrat A.O. — statistical 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 study had no sponsorship.

Received: September 08, 2022 / Accepted: September 22, 2022 / Published: October 30, 2022

Toxicological Review. 2022;30(5):297-306
pages 297-306 views

The use of neurotoxins in fundamental, medical and biological sciences on the example of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Safandeev V., Sinitskaya T.

摘要

Introduction. Neurotoxins are a class of chemicals that damage neurons. Some pesticides have a similar effect. The increase in areas with developed heavy industry and agriculture, uncontrolled use of pesticides contribute to the emergence and progression of Alzheimer’s and Parkinson’s disease (PD). The insidiousness of PD is that it is still incurable, since there is no early diagnosis: for decades it has been asymptomatic, and by the time of manifestation there are no target neurons for therapy. Considering that the diagnosis is made at the late stages of PD development, the treatment of the disease is ineffective. It follows that in order to increase the effectiveness of treatment, it should be started as early as possible – before the appearance of motor symptoms, at the preclinical stage. To do this, it is first necessary to develop an early (preclinical) diagnosis of PD based on an in-depth study of the cellular and molecular mechanisms of pathogenesis. 

In order to develop early diagnosis and preventive therapy of PD, proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used in this study. 

Material and methods. To simulate the preclinical and clinical stages of PD, inbred lines of animals were injected with MPTP according to certain schemes. The behavior of experimental animals was assessed, and after their decapitation, the content of monoamines in the structures of the brain, peripheral organs, and blood plasma was determined by HPLC, and a morphofunctional analysis of the studied tissues and organs was performed.

Results. The clinical stage of PD was modeled in animals, which corresponds to the key characteristics of PD in humans. A hypothetical preclinical stage of PD was modeled in animals, on which the method of early diagnosis was successfully tested. This model shows a number of important biochemical changes in peripheral organs, indicating the systemic nature of the disease and preceding the onset of the clinical stage of PD.

Research limitations. The results of this study can only be applied to humans only after similar results have been obtained in monkeys. 

Limitations. Only after obtaining similar results in monkeys the results of this study can be translated to humans.

Conclusion. Knowledge about the mechanisms of action of some neurotoxins is expanding, which are successfully used for the needs of fundamental, medical and biological sciences.

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

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: September 08, 2022 / Accepted: September 22, 2022 / Published: October 30, 2022

Toxicological Review. 2022;30(5):307-314
pages 307-314 views

Ecological Toxicology

Methods of biodiagnostics in aquatic ecotoxicology

Chuiko G., Tomilina I., Kholmogorova N.

摘要

Introduction. Modern ecotoxicology for the detection, quantitative and qualitative assessment of the content of toxicants in the environment and living organisms uses the entire spectrum of chemical-analytical methods. However, methods of biodiagnostics are specific to this science.

Materials and methods. The paper summarizes information on the use of modern methods of biodiagnostics in aquatic ecotoxicology: biomarking, biotesting and bioindication.

Results. The main advantage of biodiagnostics over physicochemical methods of analysis is the ability to identify the biological consequences of the action of a single stress factor or their combination. At the same time, biodiagnostic methods allow fixing the additivity, antagonism and synergy of their joint action. Biomarking differs from other biodiagnostic methods in response time from several minutes to several days, high sensitivity and sufficient specificity, since it gives the ability to register the changes occurring in the biological system at the early stages of the action of factors at their low intensity and at the same time identify the nature of the stress factor. Biotesting has a slower response time than biomarking (from several hours to several weeks), but the ecological significance at the level of an individual is more obvious: the death of an organism, a decrease in reproductive ability up to the cessation of reproduction, disruption of growth, development, various types of behavior, etc. Bioindication is characterized by a sufficiently long-time delay of responses of supraorganismal biosystems to the action of a stress factor from several weeks to several years. At the same time, it makes possible assess more adequately and reliably the changes that have occurred over a long period of timeоf stress factor action in order to predict options for the further development of ecosystems.

Limitations. Methods of biodiagnostics in aquatic ecotoxicology have no restrictions on their use. However, unlike the methods of physicochemical analysis, they do not allow a quantitative, and sometimes a qualitative assessment of the stress factor. Therefore, they should be used in conjunction with the methods of qualitative and quantitative physicochemical analysis.

Conclusion. Thus, the biodiagnostic approach, including biomarking, biotesting, and bioindication, together with physics and chemicals analysis plays an important role in the modern integrated system for assessing the ecological state of water bodies and anthropogenic impact on them.

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

Author contributions:
Chuiko G.M. — the concept of the study, the collection and processing of material, writing the text;
Tomilina I.I., Kholmogorova N.V. — collection and processing of material, 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 interests. The authors declare no conflict of interest.

Acknowledgements: The work was carried out within the framework of the planned theme No. 121050500046-8, with partial support from RFBR grants (No AAAA-A18-118052590015-9.) 

Received: September 08, 2022 / Accepted: September 22, 2022 / Published: October 30, 2022

Toxicological Review. 2022;30(5):315-322
pages 315-322 views

Research methods

Development of guidelines for the control of lead content in paint and varnishes

Fedorova N., Egorova M., Rodionov A., Bogdanova Y., Khamidulina K., Tarasova E., Nazarenko A.

摘要

Introduction. Determination of low concentrations of lead in paint and varnishes is one of the actual problems in ensuring the safety of these products. The requirements set out in the draft Technical Regulation of the Eurasian Economic Union «on the Safety of Paint and Coating Materials» for a standard of 0.009% lead on a dry weight basis stipulate the availability of precision methods for determining lead in paint and varnishes with low detection limits.

Materials and methods. Nine different types of paint samples were selected as test objects. The study was carried out by atomic absorption spectrometry with electrothermal atomisation with pre-microwave sample preparation. Paint samples were preliminarily applied on a sheet of sanded FC plywood, dried and taken from the surface with a spatula in the form of fine shavings. The absolutely dry chips were microwaved, centrifuged to separate the undecomposed sludge and analysed.

The efficiency of the developed approach was proven by validating the method on 20 model samples of one of the paint types investigated.

Results. Validation of the proposed method of lead determination in paints gave satisfactory results in terms of recovery rate and repeatability, so it can be concluded that the method is suitable for the solution of the posed analytical problem.

Having analysed the results obtained by measuring lead content in 9 samples of paint products according to the proposed scheme in the described methodology, one can make a confident conclusion about the absence of exceeding the maximum permissible lead content, considering the expected reduction of the standard to 0.009%.

Conclusion. The usage of the proposed method will make it possible to successfully control the lead content in paintwork materials at levels that comply with international standards and, in the long term, ensure that the requirements of the Technical Regulation of the Eurasian Economic Union «on the Safety of Paint and Coating Materials» are met in terms of reducing the regulatory indicator to 0.009%.

Author contribution:
Fedorova N.E. — research concept and design, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Egorova M.V. — research concept and design, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Rodionov A.S. — collection and processing of material, statistical analysis, writing the manuscript, collection of the literature data;
Bogdanova Yu.Yu. — collection and processing of material;
Khamidulina Kh.Kh. — research concept and design, approval of the final version of the article;
Tarasova E.V., Nazarenko A.K. — editing.

Conflict of interests. Authors declare no conflict of interests.

Acknowledgement. The state program «Ensuring the chemical and biological safety of the Russian Federation» funded the study.

Received: September 08, 2022 / Accepted: September 22, 2022 / Published: October 30, 2022

Toxicological Review. 2022;30(5):323-331
pages 323-331 views

Chemical safety

Development of principles for coding production and consumption waste by hazardous properties (carcinogenicity, mutagenicity and reprotoxicity)

Rabikova D., Khamidulina K., Tarasova E.

摘要

Introduction. The world practice of classifying wastes according to the degree of danger involves the simultaneous consideration of the physicochemical, toxic and ecotoxic properties of the waste components. According to Directive 2008/98/EC, waste is divided into hazardous, non-hazardous and mirror, i.e. waste that can be classified as hazardous or non-hazardous depending on the percentage of components. 

In order to implement part 2 of subparagraph "d" of paragraph 1 of the list of instructions of the President of the Russian Federation dated January 24, 2017 No. Pr-140GS on the harmonization of legislation in the field of environmental protection and legislation in the field of ensuring the sanitary and epidemiological welfare of the population and the development of unified approaches to the classification of waste with taking into account the world experience Russian Register of Potentially Hazardous Chemical and Biological Substances together with the Federal state budgetary institution "Ural state research institute of regional environmental problems", carried out research work to identify wastes with carcinogenic, mutagenic and reprotoxic properties.

The aim of the study was to prepare lists of substances contained in production and consumption waste that have a carcinogenic, mutagenic and reprotoxic effects, indicating the forms and preferred route of entry into the body, and develop a methodology for coding waste by hazardous factors.

Materials and methods. The analysis of domestic and foreign normative-legal acts on the regulation of waste hazards has been carried out.

Results. A method for coding production and consumption wastes has been developed, taking into account carcinogenic, mutagenic and reprotoxic effects. The 905 of the 6130 wastes included in the FWC were coded according to these types of hazard, which requires a revision of their classification.

Conclusion. The introduction of the developed coding methodology into the practice of waste management will make it possible to harmonize the classifications of wastes according to their impact on human health and the environment. Coding is an effective tool for waste management regulation, including disposal, recycling and reuse.

Author contribution:
Khamidulina Kh.Kh. — the 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;
Rabikova D.N. — the concept and design of the study, the collection and processing of material, writing the text;
Tarasova E.V. — collection and processing of material, the concept and design of the study.

Conflict of interests. Authors declare no conflict of interest.

Funding. The study was not sponsored.

Received: September 08, 2022 / Accepted: September 22, 2022 / Published: October 30, 2022

Toxicological Review. 2022;30(5):332-342
pages 332-342 views

Obituaries

In memory of Boris Alexandrovich Katsnelson

Article E.

摘要

20 августа 2022 года на 96-м году жизни скоропостижно скончался Заслуженный деятель науки Российской Федерации, действительный член Нью-Йоркской Академии наук, доктор медицинских наук, профессор Борис Aлександрович Кацнельсон.

Toxicological Review. 2022;30(5):343-344
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In memory of Tatiana Anatolyevna Guskova

Article E.

摘要

14 сентября 2022 г. на 82-м году ушла из жизни член-корреспондент РАН, доктор медицинских наук, профессор Гуськова Татьяна Анатольевна — ведущий учёный России в области лекарственной токсикологии, а также доклинической и клинической оценки безопасности лекарственных средств.

Toxicological Review. 2022;30(5):345-346
pages 345-346 views