sredobЗдоровье населения и среда обитания – ЗНиСОPublic Health and Life Environment – PH&LE2219-52382619-0788ФБУЗ ФЦГиЭ Роспотребнадзора10.35627/2219-5238/2021-339-6-34-40sredob-568Research ArticleГИГИЕНА ТРУДАOCCUPATIONAL HEALTHОценка комбинированной и сравнительной токсичности наночастиц оксида цинка и оксида меди в эксперименте in vivoAssessment of Combined and Comparative Toxicity of Zinc Oxide and Copper Oxide Nanoparticles in the In Vivo Experimenthttps://orcid.org/0000-0002-1871-8593МинигалиеваИ. А.MinigaliyevaI. A.

Минигалиева Ильзира Амировна – доктор биологических наук, зав. отделом токсикологии и биопрофилактики

ул. Попова, д. 30, г. Екатеринбург, 620014

Ilzira A. Minigalieva, D.Biol.Sc., Head of the Department of Toxicology and Bioprophylaxis

30 Popov Street, Yekaterinburg, 620014

ilzira-minigalieva@yandex.ruhttps://orcid.org/0000-0002-1743-7642СутунковаМ. П.SutunkovaM. P.

Сутункова Марина Петровна – доктор медицинских наук, директор

ул. Попова, д. 30, г. Екатеринбург, 620014

Marina P. Sutunkova, MD, D.M.Sc., Director

30 Popov Street, Yekaterinburg, 620014

sutunkova@ymrc.ruhttps://orcid.org/0000-0001-8750-9624КацнельсонБ. А.KatsnelsonB. A.

Кацнельсон Борис Александрович – доктор медицинских наук, профессор, научный консультант

ул. Попова, д. 30, г. Екатеринбург, 620014

Boris A. Katsnelson, MD, D.M.Sc., Professor, Research Adviser

30 Popov Street, Yekaterinburg, 620014

bkaznelson@ymrc.ruhttps://orcid.org/0000-0002-1442-6737ПриваловаЛ. И.PrivalovaL. I.

Привалова Лариса Ивановна – доктор медицинских наук, профессор, зав. лабораторией научных основ биопрофилактики

ул. Попова, д. 30, г. Екатеринбург, 620014

Larisa I. Privalova, MD, D.M.Sc., Professor, Chief Research Scientist, Head of the Laboratory of Scientific Foundations of Biological Prophylaxis

30 Popov Street, Yekaterinburg, 620014

privalova@ymrc.ruhttps://orcid.org/0000-0001-6718-3217ПановВ. Г.PanovV. G.

Панов Владимир Григорьевич – кандидат физико-математических наук, старший научный сотрудник лаборатории промышленной токсикологии ФБУН ЕМНЦ ПОЗРПП Роспотребнадзора, старший научный сотрудник лаборатории математического моделирования в экологии и медицине ИПЭ УрО РАН

ул. Попова, д. 30, г. Екатеринбург, 620014,

ул. С. Ковалевской, д. 20, г. Екатеринбург, 620990

Vladimir G. Panov, Candidate of Physical and Mathematical Sciences, Senior Research Scientist, Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers of Rospotrebnadzor; Senior Research Scientist, Laboratory of Mathematical Modeling in Ecology and Medicine, Institute of Industrial Ecology of the Ural Branch of the Russian Academy of Sciences

30 Popov Street, Yekaterinburg, 620014,

20 Sofia Kovalevskaya Street, Yekaterinburg, 620990

panov.wlad1mir@yandex.ruhttps://orcid.org/0000-0002-6475-7753ГурвичВ. Б.GurvichV. B.

Гурвич Владимир Борисович – доктор медицинских наук, научный руководитель

ул. Попова, д. 30, г. Екатеринбург, 620014

Vladimir B. Gurvich, D.M.Sc., Scientific Director

30 Popov Street, Yekaterinburg, 620014

gurvich@ymrc.ruhttps://orcid.org/0000-0002-2018-5386ЧернышовИ. Н.ChernyshovI. N.

Чернышов Иван Николаевич – младший научный сотрудник отдела токсикологии и биопрофилактики

ул. Попова, д. 30, г. Екатеринбург, 620014

Ivan N. Chernyshov, Junior Research Scientist, Department of Toxicology and Bioprophylaxis

30 Popov Street, Yekaterinburg, 620014

chernishov@ymrc.ruhttps://orcid.org/0000-0001-8580-403XСоловьеваС. Н.SolovyevaS. N.

Соловьева Светлана Николаевна – заведующий клиникой экспериментальных животных

ул. Попова, д. 30, г. Екатеринбург, 620014

Svetlana N. Solovyеva, Head of the Experimental Animal Clinic

30 Popov Street, Yekaterinburg, 620014

solovyevasn@ymrc.ruhttps://orcid.org/0000-0001-6819-3185МакеевО. Г.MakeyevO. G.

Макеев Олег Германович – доктор медицинских наук, профессор, заведующий кафедрой медицинской биологии и генетики

ул. Репина, д. 3, г. Екатеринбург, 620028

Oleg G. Makeyev, D.M.Sc., Professor, Head of the Department of Medical Biology and Genetics

3 Repin Street, Yekaterinburg, 620028

larim@mail.ruhttps://orcid.org/0000-0002-5872-2001БушуеваТ. В.BushuyevaT. V.

Бушуева Татьяна Викторовна – кандидат медицинских наук, заведующий НПО лабораторно-диагностических технологий

ул. Попова, д. 30, г. Екатеринбург, 620014

Tatiana V. Bushueva, Candidate of Medical Sciences, Head of Scientific and Production Association of Laboratory and Diagnostic Technologies

30 Popov Street, Yekaterinburg, 620014

bushueva@ymrc.ruФБУН «Екатеринбургский медицинский – научный центр профилактики и охраны здоровья рабочих промпредприятий» РоспотребнадзораРоссияYekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial WorkersRussian FederationФБУН «Екатеринбургский медицинский – научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора; ФГБУН Институт промышленной экологии Уральского отделения Российской академии наукРоссияYekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Institute of Industrial Ecology of the Ural Branch of the Russian Academy of SciencesRussian FederationФГБОУ ВО «Уральский государственный медицинский университет»РоссияUral State Medical UniversityRussian Federation202110072021063440Copyright © Минигалиева И.А., Сутункова М.П., Кацнельсон Б.А., Привалова Л.И., Панов В.Г., Гурвич В.Б., Чернышов И.Н., Соловьева С.Н., Макеев О.Г., Бушуева Т.В., 20212021Минигалиева И.А., Сутункова М.П., Кацнельсон Б.А., Привалова Л.И., Панов В.Г., Гурвич В.Б., Чернышов И.Н., Соловьева С.Н., Макеев О.Г., Бушуева Т.В.Minigaliyeva I.A., Sutunkova M.P., Katsnelson B.A., Privalova L.I., Panov V.G., Gurvich V.B., Chernyshov I.N., Solovyeva S.N., Makeyev O.G., Bushuyeva T.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://zniso.fcgie.ru/jour/article/view/568Введение

Введение. Наряду с целенаправленным производством многих металлических и оксидных наноматериалов, обладающих заданными свойствами (так называемые «инженерные» наночастицы), и их широким и разнообразным использованием в технике, науке и медицине с некоторыми старыми технологиями могут быть связаны еще более важные потенциальные риски для здоровья человека. Неинженерные (самопроизвольно возникающие) наночастицы оксида металла (далее – МеО-НЧ), образующиеся при дуговой сварке, металлургии стали и цветных металлов, загрязняют рабочее место и окружающий воздух вместе с субмикронными частицами тех же оксидов металлов размером > 100 нм. В частности, наиболее важными источниками побочного производства наночастиц оксида цинка являются первичная плавка или переплавка латуни, представляющей собой сплав меди и цинка в различных пропорциях (иногда с гораздо меньшей примесью свинца, олова и других металлов). Обоснованием проведения исследования сравнительной и комбинированной токсичности наночастиц оксида цинка (далее – ZnO-НЧ) и наночастиц оксида меди (далее – CuO-НЧ) является их одновременное присутствие в аэрозольных выбросах, образующихся при металлургии латуни.

Цель настоящего исследования – провести оценку комбинированной и сравнительной токсичности ZnO-НЧ и CuO-НЧ.

Методы

Методы. Стабильные суспензии МеО-НЧ, полученные методом лазерной абляции из металлической пластинки (чистота 99,99 %) цинка и меди под слоем деионизированной воды, вводили внутрибрюшинно беспородным крысам-самцам 18 раз в течение 6 недель отдельно (в равных массовых дозах) или в комбинации для сравнительной оценки и анализа типа комбинированного действия изучаемых наночастиц по большому количеству признаков (включая фрагментацию ДНК).

Результаты

Результаты. Установлено, что, судя по некоторым прямым и косвенным свидетельствам, субхроническое воздействие ZnO-НЧ на организм является более опасным по сравнению с воздействием CuO-НЧ. Математическое описание результатов с помощью методологии поверхности отклика показало, что, как и в случае любых других ранее исследованных нами бинарных токсических комбинаций, реакция организма на одновременное воздействие исследуемых МеО-НЧ характеризовалась сложным взаимодействием различных видов комбинированной токсичности в зависимости от того, по какому эффекту она оценивалась, а также от уровней эффекта и доз. При анализе типа комбинированного действия ZnO-НЧ и CuO-НЧ по некоторым показателям состояния организма был выявлен антагонизм, а по другим показателям выявилась аддитивность, что заставляет оценивать их совместное воздействие как опасное.

Introduction

Introduction: Apart from the targeted production of many metal and oxide nanomaterials with desired properties (socalled engineered nanoparticles) and their wide and diverse use in engineering, science, and medicine, even more important potential health risks to human health may be associated with some old technologies. Non-engineered metal oxide nanoparticles (MeO-NPs) generated spontaneously during arc welding, production of steel and non-ferrous metals, pollute the workplace and ambient air along with submicron particles (> 100 nm) of the same metal oxides. The most important sources of by-production of zinc oxide nanoparticles include primary smelting or re-smelting of brass, an alloy of copper and zinc of various proportions (sometimes with a much lower amount of lead, tin, and other metals). The rationale of the study of the comparative and combined toxicity of zinc oxide nanoparticles (ZnO-NPs) and copper oxide nanoparticles (CuO-NPs) is their simultaneous presence in aerosol emissions from brass metallurgy.

The objective of our study was to estimate the comparative and combined toxicity of ZnO-NPs and CuO-NPs.

Methods

Methods: Stable suspensions of MeO-NPs obtained by laser ablation of 99.99 % pure zinc and copper under a layer of deionized water, were injected intraperitoneally 18 times during 6 weeks to outbred male rats separately (in equal mass doses) or in combination for a comparative assessment and analysis of the type of the combined exposure to the studied nanoparticles for a large number of signs (including DNA fragmentation).

Results

Results: We established that, judging by some direct and indirect evidence, the subchronic effect of ZnO-NPs on the body was more detrimental than that of CuO-NPs. The mathematical description of the results using the response surface method showed that, similar to other previously studied binary toxic combinations, the response of the body to the combined exposure to CuO and ZnO nanoparticles was characterized by a complex interaction of various types of combined toxicity, depending on the effect it was evaluated for, the levels of the effect and doses. When analyzing the type of the combined effect of ZnO-NPs and CuO-NPs, we observed both the antagonism and additivity according to some indicators of the state of the body, which makes us evaluate their combined exposure as dangerous.

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