toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0869-7922-2025-33-3-149-157toxreview-979Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯPREVENTIVE TOXICOLOGYОценка подострой токсичности наночастиц оксида свинца при ингаляционной экспозиции (экспериментальное исследование)Assessment of subacute toxicity of lead oxide nanoparticles during inhalation exposure (experimental study)https://orcid.org/0000-0002-0097-7845МинигалиеваИльзира АмировнаMinigalievaIlzira A.ilzira-minigalieva@yandex.ruhttps://orcid.org/0000-0002-4694-0175БатеневаВлада АндреевнаBatenevaVlada A.bateneva@ymrc.ruhttps://orcid.org/0000-0002-8284-0008ШабардинаЛада ВладимировнаShabardinaLada V.shabardinalv@ymrc.ruhttps://orcid.org/0000-0003-0902-7157СутунковаЮлия МаксимовнаSutunkovaJulia M.sutunkovaym@yandex.ruhttps://orcid.org/0009-0003-0780-5733НикогосянКарен МерсоповичNikogosyanKaren M.nikoghosyankm@ymrc.ruhttps://orcid.org/0000-0002-8795-8777ШеломенцевИван ГлебовичShelomentsevIvan G.shelomencev@ymrc.ruФБУН «Екатеринбургский медицинский–научный центр профилактики и охраны здоровья рабочих промпредприятий» РоспотребнадзораРоссияYekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial WorkersRussian Federation202530062025333149157Copyright © Минигалиева И.А., Батенева В.А., Шабардина Л.В., Сутункова Ю.М., Никогосян К.М., Шеломенцев И.Г., 20252025Минигалиева И.А., Батенева В.А., Шабардина Л.В., Сутункова Ю.М., Никогосян К.М., Шеломенцев И.Г.Minigalieva I.A., Bateneva V.A., Shabardina L.V., Sutunkova J.M., Nikogosyan K.M., Shelomentsev I.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.toxreview.ru/jour/article/view/979

Введение. В ходе высокотемпературных технологических процессов на многих добывающих и обрабатывающих предприятиях образуются наночастицы различных элементов, в том числе свинца. Попадая в атмосферу, такие наночастицы, как правило, окисляются до наночастиц оксида свинца. Широкая распространённость такого загрязнения рабочих помещений и прилегающих к промпредприятиям территорий, а также их общепризнанная токсичность обусловливают важность экспериментального исследования токсичности наночастиц свинца. Цель исследования – экспериментальное изучение токсичности наночастиц оксида свинца на крысах в условиях подострой ингаляционной экспозиции. Материал и методы. Генерацию наночастиц свинца осуществляли путем электрического искрения из чистого свинцового стержня. Поток наночастиц смешивался с воздухом для окисления до оксида свинца и подавался в экспозиционную башню «только нос». Крысы-самки опытной группы («НЧ PbO») подвергались воздействию нанооксида свинца в концентрации 0,215 мг/м3 по 4 ч, 5 раз в неделю, в течение 3 нед. Вторая группа была контрольной и дышала чистым нефильтрованным воздухом в аналогичной установке. После завершения эксперимента у крыс определяли показатели состояния организма: гематологических и биохимических параметров крови и мочи, а также поведенческие тесты: «Приподнятый крестообразный лабиринт», «Открытое поле» и «Лабиринт Барнса», оценивали суммационно-пороговый показатель. Оценку различий между выборками осуществляли с использованием t-критерия Стьюдента. Различия считали значимыми при p < 0,05. Результаты. Подострое ингаляционное воздействие аэрозоля наночастиц оксида свинца приводило к развитию воспалительной реакции у крыс, которая проявилась в виде лейкоцитоза. При этом не было зафиксировано у них изменений со стороны порфиринового обмена и поведенческих реакций. Ограничения исследования. Исследование было ограничено изучением показателей общетоксического действия в экспериментальном исследовании при подостром воздействии наночастиц оксида свинца на крыс-самок с использованием только одной дозы. Заключение. Полученные результаты подчеркивают необходимость комплексной оценки наночастиц, особенно тех, которые имеют промышленное значение.

Introduction. Nanoparticles of various elements, including lead, are produced during high-temperature technological processes in many mining and processing facilities. Once in the atmosphere, such nanoparticles are usually oxidized to lead oxide nanoparticles. The widespread occurrence of such contamination of work premises and territories adjacent to industrial enterprises, as well as their generally recognized toxicity, determine the importance of experimental study of the toxicity of lead nanoparticles. The aim of the study was to experimentally investigate the toxicity of lead oxide nanoparticles on rats under subacute inhalation exposure conditions. Material and methods. Lead nanoparticles were generated by electric sparking from a pure lead rod. Their flow was mixed with air for oxidation to lead oxide and fed to the “nose only” inhalation exposure chamber. Female rats of the experimental group were exposed to lead nanoxide at a concentration of 0.215 mg/m3 for 4 hours, 5 times a week, for 3 weeks. The second group was a control group and breathed clean unfiltered air. After the experiment was completed, the rats’ body condition parameters were determined: hematological and biochemical parameters of blood and urine, as well as behavioral tests: the elevated plus maze test, open field test, and Barnes maze, and the summation threshold index was estimated. Differences between samples were assessed using the Student’s t-test. The differences were considered significant at p<0.05. Results. Subacute inhalation exposure to lead oxide nanoparticles aerosol led to the development of inflammatory reaction in rats, which manifested itself in the form of leukocytosis. At the same time, no changes in porphyrin metabolism and behavioral reactions were recorded in them. Limitations. The study was limited to investigate the indices of general toxic effects in an experimental study on subacute exposure of female rats to lead oxide nanoparticles using only one dose. Conclusion. Our findings emphasize the necessity of a comprehensive assessment of nanoparticles, especially those of industrial importance.

наночастицысвинецоксид свинцатоксичностьингаляционная экспозицияэкспериментnanoparticlesleadlead oxidetoxicityinhalation exposureexperimentReferencesHossain N., Mobarak M.H., Mimona M.A., Islam M.A., Hossain A., Zohura F.T., et al. Advances and significances of nanoparticles in semiconductor applications – A review. Results in Engineering, 2023; 18: 101347. https://doi.org/10.1016/j.rineng.2023.101347Hossain N., Mobarak M.H., Mimona M.A., Islam M.A., Hossain A., Zohura F.T., et al. Advances and significances of nanoparticles in semiconductor applications – A review. Results in Engineering, 2023; 18: 101347. https://doi.org/10.1016/j.rineng.2023.101347Saidi A.K.A.A., Baek A., Liu S., Mengesha T.T., Ahmad M.Y., Zhao D., et al. Lead oxide nanoparticles as X-ray contrast agents for in vitro and in vivo imaging. ACS Applied Nano Materials. 2023; 6(21): 20129–38. https://doi.org/10.1021/acsanm.3c03928Saidi A.K.A.A., Baek A., Liu S., Mengesha T.T., Ahmad M.Y., Zhao D., et al. Lead oxide nanoparticles as X-ray contrast agents for in vitro and in vivo imaging. ACS Applied Nano Materials. 2023; 6(21): 20129–38. https://doi.org/10.1021/acsanm.3c03928Khan I., Saeed K., Khan I. Nanoparticles: Properties, applications and toxicities. Arabian Journal of Chemistry. 2019; 12: 908–31. https://doi.org/10.1016/j.arabjc.2017.05.011Khan I., Saeed K., Khan I. Nanoparticles: Properties, applications and toxicities. Arabian Journal of Chemistry. 2019; 12: 908–31. https://doi.org/10.1016/j.arabjc.2017.05.011Уланова Т.С., Антипьева М.В., Забирова М.И., Волкова М.В. Определение частиц нанодиапазона в воздухе рабочей зоны металлургического производства. Анализ риска здоровью. 2015; (1): 77–81. https://doi.org/10.21668/health.risk/2015.1.10Уланова Т.С., Антипьева М.В., Забирова М.И., Волкова М.В. Определение частиц нанодиапазона в воздухе рабочей зоны металлургического производства. Анализ риска здоровью. 2015; (1): 77–81. https://doi.org/10.21668/health.risk/2015.1.10Ghugal S.G., Umare S.S., Sasikala R. A stable, efficient and reusable CdS–SnO2 heterostructured photocatalyst for the mineralization of Acid Violet 7 dye. Applied Catalysis A: General. 2015; 496: 25–31. https://doi.org/10.1016/j.apcata.2015.02.035Ghugal S.G., Umare S.S., Sasikala R. A stable, efficient and reusable CdS–SnO2 heterostructured photocatalyst for the mineralization of Acid Violet 7 dye. Applied Catalysis A: General. 2015; 496: 25–31. https://doi.org/10.1016/j.apcata.2015.02.035Shimizu K., Horie M., Tabei Y., Kashiwada S. Proinflammatory response caused by lead nanoparticles triggered by engulfed nanoparticles. Environmental Toxicology. 2021; 36(10): 2040–50. https://doi.org/10.1002/tox.23321Shimizu K., Horie M., Tabei Y., Kashiwada S. Proinflammatory response caused by lead nanoparticles triggered by engulfed nanoparticles. Environmental Toxicology. 2021; 36(10): 2040–50. https://doi.org/10.1002/tox.23321Srinivas A., Rao P.J., Selvam G., Murthy P.B., Reddy P.N. Acute inhalation toxicity of cerium oxide nanoparticles in rats. Toxicology Letters. 2011; 205(2): 105–15. https://doi.org/10.1016/j.toxlet.2011.05.1027Srinivas A., Rao P.J., Selvam G., Murthy P.B., Reddy P.N. Acute inhalation toxicity of cerium oxide nanoparticles in rats. Toxicology Letters. 2011; 205(2): 105–15. https://doi.org/10.1016/j.toxlet.2011.05.1027Elgharabawy R.M., Alhowail A.H., Emara A.M., Aldubayan M.A., Ahmed A.S. The impact of chicory (Cichoriumintybus L.) on hemodynamic functions and oxidative stress in cardiac toxicity induced by lead oxide nanoparticles in male rats. Biomedicine & Pharmacotherapy. 2021; 137: 111324. https://doi.org/10.1016/j.biopha.2021.111324Elgharabawy R.M., Alhowail A.H., Emara A.M., Aldubayan M.A., Ahmed A.S. The impact of chicory (Cichoriumintybus L.) on hemodynamic functions and oxidative stress in cardiac toxicity induced by lead oxide nanoparticles in male rats. Biomedicine & Pharmacotherapy. 2021; 137: 111324. https://doi.org/10.1016/j.biopha.2021.111324Rocha A., Trujillo K.A. Neurotoxicity of low-level lead exposure: History, mechanisms of action, and behavioral effects in humans and preclinical models. Neurotoxicology. 2019; 73: 58–80. https://doi.org/10.1016/j.neuro.2019.02.021Rocha A., Trujillo K.A. Neurotoxicity of low-level lead exposure: History, mechanisms of action, and behavioral effects in humans and preclinical models. Neurotoxicology. 2019; 73: 58–80. https://doi.org/10.1016/j.neuro.2019.02.021Dobrakowski M., Pawlas N., Kasperczyk A., Kozłowska A., Olewińska E., Machoń-Grecka A., et al. Oxidative DNA damage and oxidative stress in lead-exposed workers. Human & Experimental Toxicology. 2017; 36(7): 744–54. https://doi.org/10.1177/0960327116665674Dobrakowski M., Pawlas N., Kasperczyk A., Kozłowska A., Olewińska E., Machoń-Grecka A., et al. Oxidative DNA damage and oxidative stress in lead-exposed workers. Human & Experimental Toxicology. 2017; 36(7): 744–54. https://doi.org/10.1177/0960327116665674Bláhová L., Nováková Z., Večeřa Z., Vrlíková L., Dočekal B., Dumková J., et al. The effects of nano-sized PbO on biomarkers of mem-brane disruption and DNA damage in a sub-chronic inhalation study on mice. Nanotoxicology. 2020; 14(2): 214–31. https://doi.org/10.1080/17435390.2019.1685696Bláhová L., Nováková Z., Večeřa Z., Vrlíková L., Dočekal B., Dumková J., et al. The effects of nano-sized PbO on biomarkers of mem-brane disruption and DNA damage in a sub-chronic inhalation study on mice. Nanotoxicology. 2020; 14(2): 214–31. https://doi.org/10.1080/17435390.2019.1685696Sutunkova M.P., Solovyeva S.N., Chernyshov I.N., Klinova S.V., Gurvich V.B., Shur V.Ya., et al. Manifestation of systemic toxicity in rats after a short-time inhalation of lead oxide nanoparticles. International Journal of Molecular Sciences. 2020; 21(3): 690. https://doi.org/10.3390/ijms21030690Sutunkova M.P., Solovyeva S.N., Chernyshov I.N., Klinova S.V., Gurvich V.B., Shur V.Ya., et al. Manifestation of systemic toxicity in rats after a short-time inhalation of lead oxide nanoparticles. International Journal of Molecular Sciences. 2020; 21(3): 690. https://doi.org/10.3390/ijms21030690Khusainov D.R., Korenyuk I.I., Shakhmatova V.I., Tumanyants K.N., Tribrat K.N., Khorolskaya E.D., et al. Features of cognitive processes in rats in a moderate hypomagnetic environment. Biofizika. 2020; 65(5): 102533. https://doi.org/10.31857/S000630292005021X (in Russian)Khusainov D.R., Korenyuk I.I., Shakhmatova V.I., Tumanyants K.N., Tribrat K.N., Khorolskaya E.D., et al. Features of cognitive processes in rats in a moderate hypomagnetic environment. Biofizika. 2020; 65(5): 102533. https://doi.org/10.31857/S000630292005021X (in Russian)Willard M.D., Tvedten H. Small Animal Clinical Diagnosis by Laboratory Methods. 5th ed. Saunders; 2012. https://doi.org/10.1016/C2009-0-59996-5Willard M.D., Tvedten H. Small Animal Clinical Diagnosis by Laboratory Methods. 5th ed. Saunders; 2012. https://doi.org/10.1016/C2009-0-59996-5Christopher M.M., Harvey J.W. Specialized hematology tests. Seminars in Veterinary Medicine and Surgery. 1992; 7(4): 301–10.Christopher M.M., Harvey J.W. Specialized hematology tests. Seminars in Veterinary Medicine and Surgery. 1992; 7(4): 301–10.Lumley T., Diehr P., Emerson S., Chen L. The importance of the normality assumption in large public health data sets. Annual Review of Public Health. 2002; 23: 151–69. https://doi.org/10.1146/annurev.publhealth.23.100901.140546Lumley T., Diehr P., Emerson S., Chen L. The importance of the normality assumption in large public health data sets. Annual Review of Public Health. 2002; 23: 151–69. https://doi.org/10.1146/annurev.publhealth.23.100901.140546Smutná T., Dumková J., Kristeková D., Laštovičková M., Jedličková A., Vrlíková L., et al. Macrophage-mediated tissue response evoked by subchronic inhalation of lead oxide nanoparticles is associated with the alteration of phospholipases C and cholesterol transporters. Particle and Fibre Toxicology. 2022; 19(1): 52. https://doi.org/10.1186/s12989-022-00494-7Smutná T., Dumková J., Kristeková D., Laštovičková M., Jedličková A., Vrlíková L., et al. Macrophage-mediated tissue response evoked by subchronic inhalation of lead oxide nanoparticles is associated with the alteration of phospholipases C and cholesterol transporters. Particle and Fibre Toxicology. 2022; 19(1): 52. https://doi.org/10.1186/s12989-022-00494-7Farkhondeh T., Boskabady M.H., Kohi M.K., Sadeghi-Hashjin G., Moin M. Lead exposure affects inflammatory mediators, total and differential white blood cells in sensitized guinea pigs during and after sensitization. Drug and Chemical Toxicology. 2014; 37(3): 329–35. https://doi.org/10.3109/01480545.2013.866133Farkhondeh T., Boskabady M.H., Kohi M.K., Sadeghi-Hashjin G., Moin M. Lead exposure affects inflammatory mediators, total and differential white blood cells in sensitized guinea pigs during and after sensitization. Drug and Chemical Toxicology. 2014; 37(3): 329–35. https://doi.org/10.3109/01480545.2013.866133Lopes A.C., Peixe T.S., Mesas A.E., Paoliello M.M.. Lead exposure and oxidative stress: A systematic review. Reviews of Environmental Contamination and Toxicology. 2016; 236: 193–238. https://doi.org/10.1007/978-3-319-20013-2_3Lopes A.C., Peixe T.S., Mesas A.E., Paoliello M.M.. Lead exposure and oxidative stress: A systematic review. Reviews of Environmental Contamination and Toxicology. 2016; 236: 193–238. https://doi.org/10.1007/978-3-319-20013-2_3Mauzerall D., Granick S. The occurrence and determination of delta-amino-levulinic acid and porphobilinogen in urine. Journal of Biological Chemistry. 1956; 219(1): 435–46.Mauzerall D., Granick S. The occurrence and determination of delta-amino-levulinic acid and porphobilinogen in urine. Journal of Biological Chemistry. 1956; 219(1): 435–46.Li X., Li X., Xiang C., Ye F. Lead exposure represses mitochondrial metabolism by activation of heme-binding protein BACH1 in differentiated SH-SY5Y cell. Science of the Total Environment. 2022; 853: 158665. https://doi.org/10.1016/j.scitotenv.2022.158665Li X., Li X., Xiang C., Ye F. Lead exposure represses mitochondrial metabolism by activation of heme-binding protein BACH1 in differentiated SH-SY5Y cell. Science of the Total Environment. 2022; 853: 158665. https://doi.org/10.1016/j.scitotenv.2022.158665Tomokuni K., Ichiba M., Hirai Y. Species difference of urinary excretion of delta-aminolevulinic acid and coproporphyrin in mice and rats exposed to lead. Toxicology Letters. 1988; 41(3): 255–9. https://doi.org/10.1016/0378-4274(88)90062-8Tomokuni K., Ichiba M., Hirai Y. Species difference of urinary excretion of delta-aminolevulinic acid and coproporphyrin in mice and rats exposed to lead. Toxicology Letters. 1988; 41(3): 255–9. https://doi.org/10.1016/0378-4274(88)90062-8Oszlánczi G., Papp A., Szabó A., Nagymajtényi L., Sápi A., Kónya Z., et al. Nervous system effects in rats on subacute exposure by lead-containing nanoparticles via the airways. Inhalation Toxicology. 2011; 23(4): 173–81. https://doi.org/10.3109/08958378.2011.553248Oszlánczi G., Papp A., Szabó A., Nagymajtényi L., Sápi A., Kónya Z., et al. Nervous system effects in rats on subacute exposure by lead-containing nanoparticles via the airways. Inhalation Toxicology. 2011; 23(4): 173–81. https://doi.org/10.3109/08958378.2011.553248Minigaliyeva I.A., Sutunkova M.P., Gurvich V.B., Bushueva T.V., Klinova S.V., Solovyeva S.N., et al. An overview of experiments with lead-containing nanoparticles performed by the Ekaterinburg nanotoxicological research team. Nanotoxicology. 2020; 14(6): 788–806. https://doi.org/10.1080/17435390.2020.1762132Minigaliyeva I.A., Sutunkova M.P., Gurvich V.B., Bushueva T.V., Klinova S.V., Solovyeva S.N., et al. An overview of experiments with lead-containing nanoparticles performed by the Ekaterinburg nanotoxicological research team. Nanotoxicology. 2020; 14(6): 788–806. https://doi.org/10.1080/17435390.2020.1762132Lebedová J., Nováková Z., Večeřa Z., Buchtová M., Dumková J., Dočekal B., et al. Impact of acute and subchronic inhalation exposure to PbO nanoparticles on mice. Nanotoxicology. 2018; 12(4): 290–304. https://doi.org/10.1080/17435390.2018.1438679Lebedová J., Nováková Z., Večeřa Z., Buchtová M., Dumková J., Dočekal B., et al. Impact of acute and subchronic inhalation exposure to PbO nanoparticles on mice. Nanotoxicology. 2018; 12(4): 290–304. https://doi.org/10.1080/17435390.2018.1438679

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