编号 4 (2022)

封面

Articles

Изучение комбинированного действия наночастиц оксидов селена и меди в субхроническом эксперименте на крысах

Минигалиева И., Рябова Ю., Привалова Л., Гурвич В., Сутункова М., Панов В., Клинова С., Сахаутдинова Р., Кацнельсон Б.

摘要

Введение. Экспозиция организма к наночастицам оксида селена, связанная с условиями труда, может сочетаться с экспозициям к наночастицами оксида меди. Характер такого комбинированного действия на организм ране не изучался

Материалы и методы. Стабильные суспензии наночастиц оксида селена и меди (при разовой дозе 1 либо 2 мг/кг массы тела) или деионизированная вода (контроль) вводились крысам-самцам 3 раза в неделю в течении 6 недель. По завершении экспозиции состояние организма животных оценивалось по ряду общепризнанных критериев оценки токсического действия. Статистическая значимость межгрупповых различий средних значений оценивалась с помощью t-критерия Стьюдента. Для анализа закономерностей двухфакторной комбинированной токсичности, использовали метод построения поверхности отклика (RSM-анализ).

Результаты. При комбинированной интоксикации наночастицами оксидов селена и меди наблюдалось повреждение печени, исходя из снижения альбумино-глобулинового индекса и содержания щелочной фосфатазы в сыворотке крови, увеличения числа дегенеративно изменённых гепатоцитов. О нарушении функции почек свидетельствуют снижение уровня мочевины и мочевой кислоты в моче, креатинина в сыворотке крови, увеличение дегенеративно изменённых клеток дистальных и проксимальных канальцев почек. Анализ изоболограмм, полученных с помощью построения поверхности отклика, выявил неоднозначность типа комбинированного действия наночастиц оксидов селена в зависимости от того, по какому эффекту и на каком уровне доз он оценивается.

Выводы. Субхроническая токсичность наночастиц оксидов селена и меди характеризуется качественно сходными вредными эффектами. При этом комбинированное действие этих наночастиц на организм является типологически неоднозначным, варьируя от противонраправленности до синергизма.

Toxicological Review. 2022;30(4):
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Main unit

ВЛИЯНИЕ ГИПЕРАММОНИЕМИИ НА ТЕЧЕНИЕ ДЕЛИРИОЗНОГО СИНДРОМА ПРИ ОСТРЫХ ТЯЖЕЛЫХ ОТРАВЛЕНИЯХ 1,4-БУТАНДИОЛОМ И СПОСОБЫ ЕЕ КОРРЕКЦИИ

Лодягин А., Синенченко А., Батоцыренов Б., Синенченко Г.

摘要

Введение. В статье представлена оценка влияния гипераммониемии на течение делириозного синдрома при острых тяжелых отравлениях 1,4-бутандиолом и способы ее коррекции. Цель исследования: провести анализ влияния свободного аммиака на выраженность делирия при острых тяжелых отравлениях 1,4-бутандиолом и разработать методы коррекции гипераммониемии.

Материалы и методы. В ходе работы проведено проспективное обследование 59 пациентов мужского пола в возрасте от 20 до 45 лет (средний возраст составил – 29,2 ± 4,47 лет) отделения реанимации и интенсивной терапии центра лечения острых отравлений ГБУ СПб НИИ СП им. И.И. Джанелидзе с острыми тяжелыми отравлениями 1,4-бутандиолом, осложненные делириозным синдромом. Статистическую обработку полученных результатов осуществляли в программе Statistica for Windows (версия 10).

Результаты. В ходе проведения исследования у больных с делириозным синдромом диагностировали транзиторную гипераммониемию средней выраженности по классификации, предложенной Лазебник Л.Б. и соавт. (2019) с синдром печеночно-клеточной недостаточности. Фактором повышение свободного аммиака в крови стал катаболизм белков и гипоксия тканей. Использование гепатопротектора на основе соединения аргинина и глутаминовой кислоты «Глутаргина» позволило скорректировать нарушения обменных процессов и значительно уменьшить длительность экзогенного психоза и минимизировать постделириозные осложнения в виде психоорганического синдрома и тяжелой постпсихотической астении.

Заключение

Полученные в настоящем исследовании результаты демонстрируют высокую эффективность гепатопротектора аргинина глутамата в отношении замедления прогрессирования клинического течения постинтоксикационного делирия при острых тяжелых отравлениях 1,4-бутандиолом.

 

Toxicological Review. 2022;30(4):
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Original articles

Industrial toxicology as an important part of occupational medicine: retrospective, reality and development prospects (literature review)

Maksimov G.

摘要

Introduction. The stages of development of industrial toxicology and the contribution of the main scientific schools to the theory and practice of hygienic regulation of industrial substances in the air of the working area are considered, the main tasks for the near future are identified.

Material and methods. The analysis of domestic literature, materials of scientific conferences and 25 years of experience in the section “Industrial toxicology” of the Commission “Scientific foundations of occupational health and occupational diseases” of the USSR Academy of Medical Sciences was carried out.

Results. On the edge of the XX–XXI centuries, there was a significant reduction in industrial toxicology laboratories in specialized institutes, which led to a multiple decrease in the number of annual substantiation of maximum allowable concentration and indicative limit values for chemicals in the air of the working area, while maintaining a great need for this work. The lack of hygienic regulations for chemicals used in technological processes reduces the quality of a special assessment of the working conditions of workers. Against this background, due to the intensive development of the nanoindustry, in which known substances in the nanoscale acquire new properties, the chemical safety strategy becomes even more relevant. The absence of a medical specialty “preventive toxicology” complicates the quality training of relevant specialists.

Limitations. The study was based on the materials of domestic publications in the open press.

Conclusion. The experimental base of industrial toxicology needs to be significantly expanded, and the system of hygienic regulation of chemicals in the air of the working area needs to be optimized and transferred from initiative research to a planned distribution process.

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

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

Financing. The study was carried out as part of a personal initiative.

Received: April 25, 2021 / Accepted: July 21, 2022 / Published: August 30, 2022

Toxicological Review. 2022;30(4):206-216
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The effectiveness of psychological-pedagogical methods for preventing the risk of re-poisoning

Oksuzyan A., Galieva A., Mitryakov K.

摘要

Introduction. In the present article correlations of internal consistency of family and personal, social and environmental, anamnestic and physical data in persons with acute poisonings were determined for the first time. Also the pedagogical and psychological methods of prevention of the above nosology, directed to the prevention of acute poisonings, were reviewed. A corrective program of repeated poisonings prevention, carried out in the project “School of Health” in the form of conversations, lectures, autogenic training, reduced the number of repeated poisonings.

Material and methods. The study was carried out on the basis of the archive of the Budget Health Care Institution of the Udmurt Republic, “City Clinical Hospital No. 6” of the Ministry of Health of the Udmurt Republic, by copying data from the medical history. The analysis was carried out in three groups of patients: those with acute alcohol and drug poisoning, as well as those hospitalized due to non-compliance with safety regulations. After discharge from the hospital, they were offered to attend a “Health School,” during which topical talks on the prevention of re-poisoning were given. The analysis was carried out according to the developed diagnostic card, the data obtained were processed with the help of statistical programs.

Results. The analysis yielded theoretical validity, which indicated correlation of the results of psychodiagnostics, with the categories of the developed scale. It was determined by the correspondence of the results with possible similar related techniques. Based on the conducted statistical analysis, a rating scale of poisoning risk assessment was derived and preventive measures were developed, which proved to be effective in preventing recurrent acute poisonings.

Limitations. The analysis of medical records of the patients treated in the medical care institution of the Udmurt Republic, “City Clinical Hospital No. 6”, Ministry of Health Care of the Udmurt Republic, assessed 190 medical records, which represents a sufficient reference sample.

Conclusion. The developed technique can be introduced in practical public health care for the prevention of repeated acute poisonings.

Compliance with ethical standards. The study was carried out in accordance with Article 20 of the Federal Law No. 323 “On the basis of health protection of citizens in the Russian Federation” from 22.12.2020.

Authors contribution. All co-authors contributed equally 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 28, 2021 / Accepted: July 21, 2022 / Published: August 30, 2022

Toxicological Review. 2022;30(4):217-222
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Effect of hyperammoniemia on the course of delirious syndrome in acute severe poisoning with 1,4-butandiol and methods of its correction

Lodyagin A., Sinenchenko A., Batotsyrenov B., Sinenchenko G.

摘要

Introduction. The article presents an assessment of the effect of hyperammonemia on the course of delirious syndrome in acute severe poisoning with 1,4-butanediol and methods of its correction.

Purpose of the study. To analyze the effect of free ammonia on the severity of delirium in acute severe poisoning with 1,4-butanediol and to develop methods for correcting hyperammonemia.

Material and methods. In the course of the work, a prospective examination was carried out of 59 male patients aged 20 to 45 years (the average age was 29.2 ± 4.47 years) of the intensive care unit and intensive care center of the center for the treatment of acute poisoning of the St. I.I. Dzhanelidze with acute severe poisoning with 1,4-butanediol, complicated by delirious syndrome. The results were statistically processed using the Statistica for Windows software (version 10).

Results. During the study, patients with delirious syndrome were diagnosed with transient hyperammonemia of moderate severity according to the classification proposed by Lazebnik L.B. et al. (2019) with hepatocellular insufficiency syndrome. The factor of the increase in free ammonia in the blood was protein catabolism and tissue hypoxia. The use of a hepatoprotector based on a compound of arginine and glutamic acid “Glutargin” made it possible to correct metabolic disorders and significantly reduce the duration of exogenous psychosis and minimize post-delirious complications in the form of psychoorganic syndrome and severe postpsychotic asthenia.

Limitations. When studying the effect of hyperammonemia on the course of the delirious syndrome in acute severe poisoning with 1,4-butanediol, a prospective examination of 59 male patients of the intensive care unit was carried out, whose intensive care included arginine glutamate (Glutargin), which made it possible to establish the cause of the prolonged course of delirium and improve the tactics of its treatment.

Conclusion. Obtained in the present The study results demonstrate the high efficacy of the hepatoprotector “Glutargin” in relation to slowing the progression of the clinical course of post-intoxication delirium in acute severe poisoning with 1,4-butanediol.

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 12.02.2021.

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;  
Batotsyrenov B.V. — concept and design of the study, editing;  
Sinenchenko G.I. — concept and design of the study, 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: November 23, 2021 / Accepted: July 21, 2022 / Published: August 30, 2022

Toxicological Review. 2022;30(4):223-230
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Histological and ultrastructural changes in rat kidneys in the early period after paraoxone poisoning

Sokolova M., Sobolev V., Goncharov N.

摘要

Introduction. Toxic nephropathies are not limited to a single morphological type of kidney tissue damage. The widespread distribution of organophosphorus compounds (OPs) in the modern world makes it necessary to study the morphological manifestations and delayed effects of OPs on various organs and tissues of the human and animal body.

Material and methods. The article presents the results of a study of changes in the kidneys of rats at the ultrastructural level in the early stages after a single injection of paraoxon at doses of LD50 and LD84.

Results. It has been shown that after the introduction of paraoxon, the epithelial cells of the convoluted tubules are initially damaged, and a week after the poisoning, changes are recorded in the renal corpuscle, manifested in an increase in the thickness of the glomerular basement membrane.

Limitations. Morphological changes in the renal tissues were analyzed in a single poisoning at doses of LD50 and LD84.

Conclusion. The changes detected in the renal corpuscles indicate the feasibility of further studies on the effect of FOS on the nature, sequence and mechanism of nephrotoxic effects of FOS in models of acute and chronic intoxication.

Compliance with ethical standards. The experimental study was approved by the local ethical committee of the I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences.

Contribution of the authors:
Sokolova M.O. — collecting and processing of the material, statistical analysis, writing a text.
Sobolev V.E. — the concept and design of the study, collecting and processing of the material, editing.
Goncharov N.V. — the concept and design of the study, collecting and processing of the material, editing.
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 interests.

Acknowledgments. The work was carried out with the support of the state program АААА-А18-118012290142-9.

Received: September 13, 2021 / Accepted: July 21, 2022 / Published: August 30, 2022

Toxicological Review. 2022;30(4):231-237
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Study of the selenium oxide and copper oxide nanoparticles combined action in a subchronic experiment on rats

Minigalieva I., Ryabova Y., Sutunkova M., Gurvich V., Privalova L., Panov V., Tazhigulova A., Solovieva S., Sutunkova Y., Katsnelson B.

摘要

Introduction. Exposure to selenium oxide nanoparticles can be combined with exposure to copper oxide nanoparticles at working place. The type of this combined action has not been previously studied.

Material and methods. Stable suspensions of selenium oxide and copper oxide nanoparticles (at a single dose of 1 or 2 mg/kg of body weight) or deionized water (control) were administered to male rats 3 times a week for 6 weeks. At the end of the exposure, the toxic effect was evaluated by a large number of the animal organism indices. The statistical significance of intergroup differences was assessed using Student’s t-test. To analyze the patterns of two-factor combined toxicity, we used the Response Surface Methodology (RSM analysis).

Results. Under combined intoxication with selenium oxide and copper oxide nanoparticles, liver damage was observed, assessed by a decrease in the albumin-globulin index and the content of alkaline phosphatase in the blood serum, an increase in the number of degenerated hepatocytes. Kidney function altered as indicated by a decrease in the level of urea and uric acid in the urine, creatinine in the blood serum, an increase in degenerated cells of proximal and distal tubules. The analysis of isobolograms obtained by RSM revealed the ambiguity of the type of selenium oxide and copper oxide nanoparticles combined action, depending on which effect and at which dose level it is estimated by.

Conclusion. The subchronic toxicity of selenium oxide and copper oxide nanoparticles is characterized by qualitatively similar harmful effects. At the same time, the combined action of these nanoparticles is typologically ambiguous, varying from contradirectionality to synergism.

Compliance with ethical standards. The study was carried out in accordance with the "International guiding principles for biomedical research involving animals" (the Council for International Organizations of Medical Sciences, the International Council For Laboratory Animal Science, 2012). The work was approved by the Local Independent Ethics Committee of the Federal State Budgetary Institution EMNC POSRPP of Rospotrebnadzor.

Autors contribution:
Katsnelson B.A., Gurvich V.B., Minigalieva I.A., Privalova L.I., Ryabova Yu.V. — the concept and design of the study;
Klinova S.V., Ryabova Yu.V. — conducting experiments;
Panov V.G., Sakhautdinova R.R., Ryabova Yu.V. — data obtaining and processing.
All co-authors — discussing the draft paper, editing, and approving the final version of the article.

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

Acknowledgments. Funded by the budget of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers.

Received: May 05, 2022 / Accepted: July 21, 2022 / Published: August 30, 2022

Toxicological Review. 2022;30(4):238-247
pages 238-247 views

ГИСТОЛОГИЧЕСКИЕ И УЛЬТРАСТРУКТУРНЫЕ ИЗМЕНЕНИЯ В ПОЧКАХ КРЫС НА РАННИХ СРОКАХ ПОСЛЕ ОТРАВЛЕНИЯ ПАРАОКСОНОМ

Соколова М., Соболев В., Гончаров Н.

摘要

Токсические нефропатии не ограничиваются единственным морфологическим типом повреждения ткани почек. Широкое распространение фосфорорганических соединений (ФОС) в современном мире делает необходимым изучение отставленных последствий их влияния на разные органы и ткани организма человека и животных. В статье представлены результаты исследования по изучению изменений в почках крыс на ультраструктурном уровне в ранние сроки после однократного подкожного введения параоксона в дозах ЛД50 и ЛД84. Показано, что после введения параоксона первоначально повреждаются эпителиальные клетки извитых канальцев, а через неделю после отравления изменения регистрируются в почечном тельце. Характер выявленных изменений в почечном тельце, а именно увеличение толщины гломерулярной базальной мембраны, создает предпосылки для дальнейшего исследования влияния ФОС на характер, последовательность и механизм влияния ФОС на ультраструктурные характеристики почек в моделях острой и хронической интоксикации.

Toxicological Review. 2022;30(4):
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New information on toxicity and hazard of chemical and biological substances

Hygienic regulation of the antiretroviral drug tenofovir in the air of the working area

Golubeva M., Bidevkina M., Bobrineva I., Fedorova E., Krymova L.

摘要

Introduction. Tenofovir is an antiviral drug of the group of nucleoside reverse transcriptase inhibitors of retrovirus – human immunodeficiency virus.

Material and methods. A toxicological and hygienic study of the toxicity and danger of tenofovir in laboratory animals (mice, rats, rabbits) was carried out with various routes of intake: orally (mice, rats), intraperitoneally (mice), cutaneous (mice, rabbits), inhalation (rats) for development and justification of indicative limit values of tenofovir in the air of the working area.

Results. When injected into the stomach, tenofovir belongs to the 4th hazard class in terms of DL50 for mice and rats over 10,000 mg/kg (GOST 12.1.007-76). When injected into the abdominal cavity DL50 for male mice 1443 mg/kg (OECD toxicity class 5). Tenofovir has a moderate irritant effect on the mucous membranes of the eyes of rabbits, does not irritate the skin; does not have a skin-resorptive, cumulative and sensitizing effect. In a subacute experiment in rats with intragastric administration (1000 mg/kg, 28 days), tenofovir had a general toxic effect with a predominant impairment of kidney and liver function. Tenofovir Limac is set at 17.3 mg/m3 for effects on renal function.

Limitations. When developing and substantiating hygienic standards for the anti-retroviral drug tenofovir in the air of the working area.

Conclusion. The recommended indicative limit values for tenofovir disoproxil fumarate aerosol in the air of the working area is 0.1 mg/m3.

Compliance with ethical standards. The study complies with the rules for the humane treatment of animals.

Autors contribution:
Golubeva M.I., Bidevkina M.V. — research concept and design, text writing, editing;
Bobrineva I.A., Krymova L.I. — collection and processing of material, editing;
Fedorova E.A. — material processing, statistical analysis, editing. 
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: November 10, 2021 / Accepted: July 21, 2022 / Published: August 30, 2022

Toxicological Review. 2022;30(4):248-254
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ГИГИЕНИЧЕСКОЕ НОРМИРОВАНИЕ ПРОТИВОРЕТРОВИРУСНОГО ПРЕПАРАТА ТЕНОФОВИР В ВОЗДУХЕ РАБОЧЕЙ ЗОНЫ

Голубева М.

摘要

Тенофовир – противовирусный препарат группы нуклеозидных ингибиторов обратной транскриптазы ретровируса – вируса иммунодефицита человека. При введении в желудок тенофовир относится к 4 классу опасности по величине DL50 для мышей и крыс более 10 000 мг/кг (ГОСТ 12.1.007-76). При введении в брюшную полость DL50 для мышей самцов 1443 мг/кг (5 класс токсичности по классификации OECD). Тенофовир оказывает умеренное раздражающее действие на слизистые оболочки глаз кроликов, не раздражает кожу; не обладает кожно-резорбтивным, кумулятивным и сенсибилизирующим действием. В подостром эксперименте на крысах при внутрижелудочном введении (1000 мг/кг, 28 дней) тенофовир оказывал общетоксическое действие с преимущественным нарушением функции почек и печени. Limac тенофовира установлен на уровне 17,3 мг/м3 по влиянию на функцию почек. Рекомендован ОБУВ аэрозоля тенофовира дизопроксила фумарата в воздухе рабочей зоны 0,1 мг/м3.

Toxicological Review. 2022;30(4):
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Chemical safety

Approaches of European to the regulation of waste management (review)

Khamidulina K., Nazarenko A., Tarasova E., Rabikova D., Petrova E., Filin A.

摘要

Introduction. Waste management, including hazardous waste, is one of the issues that are regulated at the level of the European Union with the help of Directives that are binding on all EU member states. Various EU Waste Directives have been approved since 1975, and in 2008 the fundamental EU Waste Framework Directive (Directive 2008/98/EC of the European Parliament and of the Council of 19 November 2008 on waste and repealing certain Directives) was adopted, which describes the waste management policy, defines the classification of waste and methods for their processing and disposal.

Material and methods. When preparing the review, legal documents (in particular, Directives, EU Regulations in the field of waste management) and guidelines for practical waste management in the EU were used.

Results and discussions. The review presents a methodology for classifying waste, dividing it into non-hazardous and hazardous. Hazard codes and classes, threshold values, i.e. criteria for classifying waste as hazardous.

Conclusion. At the stage of analysis of European legislation concerning waste management, the EU pays special attention to the classification of waste as an important tool for differentiating their flow and planning the management of their individual types. The main principle of classification is the differentiation of waste according to the degree of danger to the environment and humans, which allows minimizing their negative impact.

Author contribution:
Khamidulina Kh.Kh. — editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Nazarenko A.K. — the concept and design of the study, collection and processing of materials, writing the text, editing;
Tarasova E.V. — collection of materials;
Rabikova D.N., Petrova E.S., Filin A.S. — editing.

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

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

Received: July 13, 2022 / Accepted: July 21, 2022 / Published: August 30, 2022

Toxicological Review. 2022;30(4):255-266
pages 255-266 views