АКТУАЛЬНОСТЬ

safetyrisk

Безопасность и риск фармакотерапии

Safety and Risk of Pharmacotherapy

2312-78212619-1164

Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)

10.30895/2312-7821-2023-379

safetyrisk-379

Research Article

ДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ

PRECLINICAL STUDIES

Возможности и перспективы доклинической оценки лекарственной безопасности с использованием альтернативных методов: опыт реализации программы «Токсикология в XXI веке» в США

Opportunities and Prospects for Preclinical Drug Safety Assessment Using Alternative Methods: Experience from the Toxicology in the 21st Century (Tox21) Programme in the USA

https://orcid.org/0000-0002-2457-8486

Перфилова

В. Н.

Perfilova

V. N.

Перфилова Валентина Николаевна, д-р биол. наук, профессор

Площадь Павших Борцов, д. 1, Волгоград, 400131

Valentina N. Perfilova, Dr. Sci. (Biol.), Professor

1 Pavshikh Bortsov Sq., Volgograd 400131

vnperfilova@mail.ru

Федеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации; Государственное бюджетное учреждение «Волгоградский медицинский научный центр»РоссияVolgograd State Medical University; Volgograd Medical Scientific CentreRussian Federation

2024

26092023

1216882

2024

Перфилова В.Н.

Perfilova V.N.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.risksafety.ru/jour/article/view/379

АКТУАЛЬНОСТЬ

АКТУАЛЬНОСТЬ. Консорциумом Tox21 (США) разработана и успешно реализуется «Программа по токсикологии в XXI веке», направленная на переход к новой стратегии, согласно которой изучение токсичности химических веществ на животных будет заменено широким спектром подходов, базирующихся на тестах in vitro и вычислительных методах.

ЦЕЛЬ

ЦЕЛЬ. Обзор информации об альтернативных моделях in vitro, разработанных для изучения токсичности химических соединений в рамках программы «Токсикология в XXI веке».

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Анализ информации, представленной Национальной токсикологической программой США (National Toxicology Program), Агентством по охране окружающей среды США (Environmental Protection Agency), Национальным центром развития трансляционных наук (National Center for Advancing Translational Sciences) и другими участниками консорциума Tox21 на официальных сайтах и в научной литературе, показал, что к настоящему времени разработана технология высокопроизводительного скрининга для тестирования безопасности химических веществ. С использованием этой технологии сформирована библиотека химических соединений Tox21 10К. Находящаяся в ней информация успешно используется для создания моделей, позволяющих прогнозировать токсичность химических веществ до начала доклинических исследований. Предложены новые подходы к изучению безопасности соединений на клеточных линиях человека для замены in vivo исследований. Создание моделей с использованием органов-на-чипах, мультиорганов-на-чипах и органоидов позволит преодолеть недостатки и ограничения применения моделей на основе клеточных линий и обеспечить более точное воспроизведение сложных взаимодействий клеток и матрикса, а также органов между собой. Новые технологии транскриптомики (токсикогеномики), разработанные в ходе реализации программы Tox21 для выявления новых биомаркеров и генных сигнатур токсичности химических веществ, могут быть применены для классификации токсикантов в соответствии со степенью риска для здоровья и выявления потенциальных побочных эффектов задолго до того, как будут обнаружены какие-либо патологические изменения в организме. Межведомственный координационный комитет по валидации альтернативных методов (Interagency Coordinating Committee on the Validation of Alternative Methods) проводит техническую оценку альтернативных методов испытаний и способствует их внедрению в регуляторную практику.

ВЫВОДЫ

ВЫВОДЫ. Разработанные в рамках программы Тох21 новые подходы к изучению токсичности позволят осуществить переход от тестирования потенциальных лекарственных средств in vivo к компьютерным и in vitro методам, обеспеченным новыми инструментами и технологиями.

SCIENTIFIC RELEVANCE

SCIENTIFIC RELEVANCE. The Tox21 (Toxicology in the 21st Century) programme was developed by the US Tox21 Consortium with the aim to replace animal-based toxicity assessments of chemicals with a wide range of in vitro and in silico testing approaches and has since been successfully applied in practice.

AIM

AIM. The study aimed to review information on alternative in vitro models developed as part of the Tox21 programme for testing the toxicity of chemical compounds.

DISCUSSION

DISCUSSION. According to the information provided by the National Toxicology Program, Environmental Protection Agency, National Center for Advancing Translational Sciences, and other Tox21 Consortium members on their official websites and in the literature, the Tox21 Consortium has developed a quantitative high-throughput screening technology for testing the safety of chemicals and created the Tox21 10K library of chemical compounds using this screening technology. The library has been successfully used to create models that predict the toxicity of chemicals prior to preclinical studies. Researchers have proposed new approaches to studying the safety of chemical compounds in human cell lines to replace in vivo studies. Innovative organ-on-chip, multi-organ-on-chip, and organoid models are free from the drawbacks and limitations of cell-line models and offer more accurate representations of complex cell–matrix and organ–organ interactions. Developed under the Tox21 programme to search for new chemical toxicity biomarkers and gene signatures, novel transcriptomics (toxicogenomics) technologies can be used to classify toxicants according to their health risks and to identify potential side effects long before discovering any pathological changes in the body. The Interagency Coordinating Committee on the Validation of Alternative Methods conducts technical evaluation of alternative testing methods and promotes their implementation into regulatory practice.

CONCLUSIONS

CONCLUSIONS. Thus, new tools and technologies provide an opportunity for switching from in vivo toxicity testing of candidate medicinal products to in silico and in vitro methods.

консорциум Tox21библиотека химических соединенийальтернативные моделибиоинформатикавысокопроизводительный скринингin vitro токсикологияклеточные культурыорганы-на-чипахтоксикогеномика

Tox21 Consortiumlibrary of chemical compoundsTox21 10Kalternative modelsbioinformaticshigh-throughput screeningin vitro toxicologycell culturesorgans-on-chipstoxicogenomics

Работа выполнена без спонсорской поддержки

The study was performed without external funding

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