medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2023-102-2-181-190medlit-2932Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯ И ГИГИЕНИЧЕСКОЕ НОРМИРОВАНИЕPREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATIONНаноцеллюлозы: характеристика опасности и возможные риски (обзор литературы)Nanocelluloses: hazard characteristics and possible risks (literature review)https://orcid.org/0000-0002-3671-6508ГмошинскийИван ВсеволодовичGmoshinskiIvan V.

Доктор биол. наук, гл. науч. сотр. лаб. пищевой токсикологии и оценки безопасности нанотехнологий ФГБУН «Федеральный исследовательский центр питания, биотехнологии и безопасности пищи», 109240, Москва.

e-mail: gmosh@ion.ru

MD, PhD, DSci., Leading Researcher at the Laboratory of Food Toxicology and Safety Assessment of Nanotechnology, Federal Research Centre of Nutrition, Biotechnology and food Safety. Department of food toxicology and nanotechnology safety evaluation, Moscow, 109240, Russian Federation.

e-mail: gmosh@ion.ru

gmosh@ion.ruhttps://orcid.org/0000-0002-0015-8735ШипелинВладимир А.SchipelinVladimir A.noemail@neicon.ruhttps://orcid.org/0000-0002-5340-9649ХотимченкоСергей А.KhotimchenkoSergey A.noemail@neicon.ruФГБУН «Федеральный исследовательский центр питания, биотехнологии и безопасности пищи», лаборатория пищевой токсикологии и оценки безопасности нанотехнологийРоссияFederal Research Centre of Nutrition, Biotechnology and food Safety, Department of food toxicology and nanotechnology safety evaluationRussian FederationФГБУН «Федеральный исследовательский центр питания, биотехнологии и безопасности пищи», лаборатория пищевой токсикологии и оценки безопасности нанотехнологий; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)»РоссияFederal Research Centre of Nutrition, Biotechnology and food Safety, Department of food toxicology and nanotechnology safety evaluation; First Moscow State Medical University named after I.M. Sechenov of the Ministry of Health of the Russian Federation (Sechenov University), Department of Food Hygiene and ToxicologyRussian Federation2023250320231022181190Copyright © Гмошинский И.В., Шипелин В.А., Хотимченко С.А., 20232023Гмошинский И.В., Шипелин В.А., Хотимченко С.А.Gmoshinski I.V., Schipelin V.A., Khotimchenko S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rjhas.ru/jour/article/view/2932

Наноцеллюлозы (НЦ) имеют широкие перспективы применения в производстве изделий медицинского назначения, композиционных материалов и покрытий, электроники, пищевой и фармацевтической продукции. К основным видам НЦ относятся нановолокнистая (НВЦ), нанокристаллическая (НКЦ), выделяемые из природного (преимущественно растительного) сырья, и получаемая путём микробного синтеза бактериальная наноцеллюлоза (БНЦ). Производственный процесс НЦ может включать множество факторов, способных влиять на её токсикологические характеристики, такие как остаточные количества химикатов и ферментных препаратов, используемых при выделении и модификации НЦ, контаминация НЦ из природных источников микотоксинами, тяжёлыми металлами, пестицидами, диоксинами. В случае НЦ микробного происхождения остаётся открытым вопрос о безопасности соответствующих штаммов-продуцентов, большинство из которых являются генетически модифицированными. Отдельного внимания заслуживает способность НЦ проявлять токсичность для живых организмов в отличие от её химического аналога в традиционной форме. Расширение ассортимента продукции, содержащей НЦ и тесно контактирующей с человеком, в первую очередь пищевой продукции, упаковочных материалов, фармакологических препаратов и изделий медицинского назначения, требует тщательной оценки возможных рисков, связанных с воздействием НЦ на организм человека.

Целью настоящей статьи является обзор литературы о потенциальных рисках, обусловленных токсическим действием НЦ на живые организмы при различных путях экспозиции, за период с 2010 по 2021 г.

Приводятся сведения о токсичности в системах in vitro, в частности о способности к индукции окислительного стресса и воспаления. Представлены результаты исследований ингаляционной и пероральной токсичности in vivo, данные о канцерогенности, реакции иммунных клеток на НЦ и её способности к индукции иммунологической толерантности. По результатам сравнительного анализа проведённых исследований установлено, что различные виды НЦ слабо влияют на жизнеспособность клеток in vitro и не обладают выраженной острой токсичностью in vivo. Однако противоречивые результаты исследований провоспалительных и иммунологических эффектов различных форм НЦ указывают на необходимость проведения дальнейшего их изучения с целью установления максимальных недействующих доз, в первую очередь при ингаляционном и пероральном путях поступления.

Участие авторов

Участие авторов. Все соавторы внесли равнозначный вклад в исследование и подготовку статьи к публикации.

Конфликт интересов

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Финансирование

Финансирование. Поисково-аналитическая работа проведена за счёт средств субсидии на выполнение государственного задания в рамках Программы фундаментальных научных исследований (тема Минобрнауки России № 0410-2022-0003).

Поступила

Поступила: 05.08.2022 / Принята к печати: 08.12.2022 / Опубликована: 25.03.2023

Nanocelluloses (NCs) have broad application prospects in medicine as implants, cell scaffolds and dressings, in the production of composite materials and coatings, electronics, food and pharmaceutical products. The main types of NCs include nanofibrous (NFC), nanocrystalline (NCC) cellulose isolated from natural, predominantly plant materials, and bacterial nanocellulose (BNC) obtained by microbial synthesis. The production process of NC can include many factors potent of affecting their toxicological characteristics, such as residual amounts of chemicals and enzyme preparations used in the isolation and modification of NC, contamination of NC from natural sources with mycotoxins, heavy metals, pesticides, and dioxins. In the case of NCs of microbial origin, the question of the safety of the respective producer strains remains open, most of which are genetically modified. Special attention deserves the ability of NC to exhibit toxicity to living organisms, different from their chemical counterpart in its traditional form. Expanding the range of products containing NC in close contact with human, primarily food products, packaging materials, pharmacological preparations and medical materials, requires a thorough assessment of the possible risks associated with the impact of NC on the human body.

The purpose of the research is to review the literature over 2010 to 2021 on the potential risks associated with the toxic effects of NC on living organisms through various exposure routes.

Information is provided on toxicity in in vitro systems, in particular, the ability to induce oxidative stress and inflammation. There are presented results of studies on inhalation and oral toxicity in vivo, data on carcinogenicity, immune cell response to NC and its ability to induce immunological tolerance. Based on the results of a comparative analysis of the studies, various NC types were found to have little effect on cell viability d and acute toxicity in vivo, however, the conflicting results of studies of the pro-inflammatory and immunological effects of different NCs indicate the need for further long-term studies to establish the maximum inactive doses of NC, primarily, with their inhalation and oral intake.

Contribution

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

Conflict of interest

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

Acknowledgments

Acknowledgments. The search and analytical work were carried out using the funds of the state assignment grant as part of the Basic Research Program (subject of the Ministry of Education and Science of the Russian Federation No. 0410-2022-0003).

Received

Received: August 5, 2022 / Accepted: December 8, 2022 / Published: March 25, 2023

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