{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T11:29:12Z","timestamp":1774870152533,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:00:00Z","timestamp":1665187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["0410-2022-0003"],"award-info":[{"award-number":["0410-2022-0003"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Nickel (Ni) nanoparticles (NPs) are used as technological aids\u2013catalysts in the oil and fat industry, in pharmaceuticals, and in the production of cosmetics and pesticides. The acute and subchronic oral toxicity of metallic Ni in the nanoform is not well understood. The study aimed to investigate the acute and subchronic oral toxicity of Ni NPs to rats. We used two NP preparations (Ni NP1 and Ni NP2) with spherical particles and an average diameter of 53.7 and 70.9 nm according to the electron microscopy data. In the study of acute toxicity, both kinds of Ni NPs were administered to male and female Wistar rats aged 8 weeks as a single dose of 2000 mg\/kg b.w. through a gastric gavage. In the subchronic experiment, male Wistar rats initially aged 7 weeks received for 92 days Ni NP1 and Ni NP2 as well as the \u201ctraditional\u201d soluble salt form of Ni (Ni basic carbonate) at doses of 0.1, 1, and 10 mg\/kg body weight (mg\/kg b.w.) in terms of Ni content as a part of the diet consumed. As a result, in an acute study, the oral LD50 for Ni NP2 in male and female rats was about 1600 mg\/kg b.w. (IV hazard class). The oral dose of Ni NP1 equal to 2000 mg\/kg b.w. exceeded LD100 for males and corresponded to LD90 for females. In the subchronic study, the bioaccumulation of both Ni NPs as well as Ni salt was observed in the kidney but not in the liver and spleen. Ni NP1 decreased body weight only at a dose of 1 mg\/kg b.w.; affected the relative weight of the spleen at 0.1 mg\/kg, the brain at 1.0 mg\/kg, and the thymus at 10 mg\/kg; and decreased locomotor activity at 0.1 and 10 mg\/kg. Thus, for Ni NP1, in such cases where a monotonic dose\u2013response relationship could be traced, LOEL could be stated at 10 mg\/kg b.w.\/day for 92 days of oral intake. However, for some endpoints where such a monotonic relationship could be absent, significant toxic effects were observed even at a dose 0.1 mg\/kg. In the case of Ni NP2, changes in the relative weight of the liver, thymus, and brain were recorded starting from 0.1 mg\/kg b.w.; locomotor activity decreased starting from 0.1 mg\/kg. Other effects, including basophiles count and platelet system indexes, were observed at a dose of 1 mg\/kg or higher. Thus, the LOEL value for Ni NP2 can be fixed at 0.1 mg\/kg. The critical organs affected by both Ni NPs were the brain and immune system. Most of the toxic effects exhibited by metallic Ni NPs were absent or had an opposite orientation upon administration of equivalent doses of Ni in the salt form which indicates the signs of \u201cnanotoxicity\u201d in metallic Ni NPs. In conclusion, the data obtained show that there may be some additional health risks caused by the intake of Ni in a nanoform compared to soluble ionized forms of this element at equivalent doses.<\/jats:p>","DOI":"10.3390\/nano12193523","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T23:31:43Z","timestamp":1665358303000},"page":"3523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Peroral Toxicological Assessment of Two-Dimensional Forms of Nickel Nanoparticles Sized between 20 and 120 nm"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0015-8735","authenticated-orcid":false,"given":"Vladimir A.","family":"Shipelin","sequence":"first","affiliation":[{"name":"Laboratory of Food Toxicology and Safety Assessment of Nanotechnology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia"},{"name":"Academic Department of Innovational Materials and Technologies Chemistry, Plekhanov Russian University of Economics, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1373-4436","authenticated-orcid":false,"given":"Antonina A.","family":"Shumakova","sequence":"additional","affiliation":[{"name":"Laboratory of Food Toxicology and Safety Assessment of Nanotechnology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora N.","family":"Trushina","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oksana K.","family":"Mustafina","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander G.","family":"Masyutin","sequence":"additional","affiliation":[{"name":"Department of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey I.","family":"Kolobanov","sequence":"additional","affiliation":[{"name":"Laboratory of Food Toxicology and Safety Assessment of Nanotechnology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya E.","family":"Sokolov","sequence":"additional","affiliation":[{"name":"Laboratory of Food Toxicology and Safety Assessment of Nanotechnology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3671-6508","authenticated-orcid":false,"given":"Ivan V.","family":"Gmoshinski","sequence":"additional","affiliation":[{"name":"Laboratory of Food Toxicology and Safety Assessment of Nanotechnology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey A.","family":"Khotimchenko","sequence":"additional","affiliation":[{"name":"Laboratory of Food Toxicology and Safety Assessment of Nanotechnology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia"},{"name":"Department of Food Hygiene and Toxicology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry B.","family":"Nikityuk","sequence":"additional","affiliation":[{"name":"Laboratory of Sports Anthropology and Nutriciology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia"},{"name":"Department of Operative Surgery and Topographic Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, R.D. (2008). Fats and Oils: Formulating and Processing for Applications, CRC Press.","DOI":"10.1201\/9781420061673"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1002\/tox.22329","article-title":"Role of NF-\u03ba B activation and Th1\/Th2 imbalance in pulmonary toxicity induced by nano NiO","volume":"32","author":"Chang","year":"2016","journal-title":"Environ. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15020","DOI":"10.1038\/ncomms15020","article-title":"Solid-state synthesis of ordered mesoporous carbon catalysts via a mechanochemical assembly through coordination cross-linking","volume":"8","author":"Zhang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5018","DOI":"10.1016\/j.bmc.2018.08.033","article-title":"A reusable magnetic nickel nanoparticle based catalyst for the aqueous synthesis of diverse heterocycles and their evaluation as potential anti-bacterial agent","volume":"26","author":"Bhattacharjee","year":"2018","journal-title":"Bioorganic Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1016\/j.jmmm.2011.04.004","article-title":"Synthesis of copper\u2013nickel nanoparticles prepared by mechanical milling for use in magnetic hyperthermia","volume":"323","author":"Ban","year":"2011","journal-title":"J. Magn. Magn. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/jat.3129","article-title":"Metals in cosmetics: Implications for human health","volume":"35","author":"Borowska","year":"2015","journal-title":"J. Appl. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jphotobiol.2016.06.045","article-title":"Spectroscopic investigation of biosynthesized nickel nanoparticles and its larvicidal, pesticidal activities","volume":"162","author":"Elango","year":"2016","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.envpol.2018.10.123","article-title":"High-throughput transcriptomics: Insights into the pathways involved in (nano) nickel toxicity in a key invertebrate test species","volume":"245","author":"Gomes","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.2147\/IJN.S80843","article-title":"Some inferences from in vivo experiments with metal and metal oxide nanoparticles: The pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview)","volume":"10","author":"Katsnelson","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.etap.2012.08.012","article-title":"Recent progress in studies of metallic nickel and nickel-based nanoparticles\u2019 genotoxicity and carcinogenicity","volume":"34","author":"Magaye","year":"2012","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1166\/jnn.2016.10885","article-title":"Nanomaterial Induced Immune Responses and Cytotoxicity","volume":"16","author":"Ali","year":"2016","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/15459624.2017.1326699","article-title":"Nano-metal oxides: Exposure and engineering control assessment","volume":"14","author":"Garcia","year":"2017","journal-title":"J. Occup. Environ. Hyg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/mutage\/gex007","article-title":"Genotoxicity study of nickel oxide nanoparticles in female Wistar rats after acute oral exposure","volume":"32","author":"Dumala","year":"2017","journal-title":"Mutagenesis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/jat.3790","article-title":"Repeated oral dose toxicity study of nickel oxide nanoparticles in Wistar rats: A histological and biochemical perspective","volume":"39","author":"Dumala","year":"2019","journal-title":"J. Appl. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s10735-016-9671-6","article-title":"In vitro and in vivo evaluation of the toxicities induced by metallic nickel nano and fine particles","volume":"47","author":"Magaye","year":"2016","journal-title":"Histochem. J."},{"key":"ref_16","first-page":"563","article-title":"Role of nitrative stress in nano nickel ox-ide-induced lung injury in rats","volume":"45","author":"Liu","year":"2016","journal-title":"Wei Sheng Yan Jiu"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12162","DOI":"10.1002\/1348-9585.12162","article-title":"Changes over time in pulmonary inflammatory response in rat lungs after intratracheal instillation of nickel oxide nanoparticles","volume":"62","author":"Nishi","year":"2020","journal-title":"J. Occup. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1093\/toxsci\/kfr206","article-title":"Bioavailability, Intracellular Mobilization of Nickel, and HIF-1\u03b1 Activation in Human Lung Epithelial Cells Exposed to Metallic Nickel and Nickel Oxide Nanoparticles","volume":"124","author":"Pietruska","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_19","unstructured":"(2011). Guide for the Care and Use of Laboratory Animals, The National Academies Press. [8th ed.]."},{"key":"ref_20","unstructured":"OECD (2002). Test No. 420: Acute Oral Toxicity-Fixed Dose Procedure. OECD Guidelines for the Testing of Chemicals, Organisation for Economic Co-Operation and Development. Section 4."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"838S","DOI":"10.1093\/jn\/127.5.838S","article-title":"Components of the AIN-93 Diets as Improvements in the AIN-76A Diet","volume":"127","author":"Reeves","year":"1997","journal-title":"J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112270","DOI":"10.1016\/j.bbr.2019.112270","article-title":"Effects of quercetin on the neuromotor function and behavioral responses of Wistar and Zucker rats fed a high-fat and high-carbohydrate diet","volume":"378","author":"Mzhelskaya","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-1-61779-108-6_8","article-title":"Annexin V\/7-AAD Staining in Keratinocytes","volume":"740","author":"Zimmermann","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_24","unstructured":"(2011). Globally Harmonized System of Classification and Labelling of Chemicals (GHS), United Nations."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.partic.2021.11.007","article-title":"Toxicity of manufactured nanomaterials","volume":"69","author":"Liu","year":"2022","journal-title":"Particuology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"EFSA Scientific Committee, More, S., Bampidis, V., Benford, D., Bragard, C., Halldorsson, T., Hern\u00e1ndez-Jerez, A., Bennekou, S.H., Koutsoumanis, K., and Lambr\u00e9, C. (2021). Guidance on risk assessment of nanomaterials to be applied in the food and feed chain: Human and animal health. EFSA J., 19, e06768.","DOI":"10.2903\/j.efsa.2021.6768"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1080\/0265203021000031573","article-title":"Determination of several elements in duplicate meals from catering establishments using closed vessel microwave digestion with inductively coupled plasma mass spectrometry detection: Estimation of daily dietary intake","volume":"20","author":"Leblanc","year":"2003","journal-title":"Food Addit. Contam."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ijbiomac.2017.07.032","article-title":"p53, MAPKAPK-2 and caspases regulate nickel oxide nanoparticles induce cell death and cytogenetic anomalies in rats","volume":"105","author":"Saquib","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1002\/tox.22288","article-title":"Mechanisms involved in reproductive toxicity caused by nickel nanoparticle in female rats","volume":"31","author":"Kong","year":"2016","journal-title":"Environ. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.chemosphere.2018.11.128","article-title":"Mechanisms underlying nickel nanoparticle induced reproductive toxicity and chemo-protective effects of vitamin C in male rats","volume":"218","author":"Kong","year":"2018","journal-title":"Chemosphere"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/444267a","article-title":"Safe handling of nanotechnology","volume":"444","author":"Maynard","year":"2006","journal-title":"Nature"},{"key":"ref_32","first-page":"211","article-title":"Genotoxic and mutagenic properties of Ni and NiO nanoparticles investigated by comet assay, \u03b3-H2AX staining, Hprt mutation assay and ToxTracker reporter cell lines","volume":"59","author":"Cappellini","year":"2017","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.ijbiomac.2018.12.062","article-title":"Biophysical, molecular dynamics and cellular studies on the interaction of nickel oxide nanoparticles with tau proteins and neuron-like cells","volume":"125","author":"Hosseinali","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.fct.2015.11.012","article-title":"Some patterns of metallic nanoparticles\u2019 combined subchronic toxicity as exemplified by a combination of nickel and manganese oxide nanoparticles","volume":"86","author":"Katsnelson","year":"2015","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12989-018-0268-y","article-title":"Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells","volume":"15","author":"Gliga","year":"2018","journal-title":"Part. Fibre Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2011.12.014","article-title":"Elucidating the mechanisms of nickel compound uptake: A review of particulate and nano-nickel endocytosis and toxicity","volume":"260","author":"Costa","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.fct.2017.09.032","article-title":"Are in vivo and in vitro assessments of comparative and combined toxicity of the same metallic nanoparticles compatible, or contradictory, or both? A juxtaposition of data obtained in respective experiments with NiO and Mn3O4 nanoparticles","volume":"109","author":"Minigalieva","year":"2017","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/12\/19\/3523\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:48:18Z","timestamp":1760143698000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/12\/19\/3523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,8]]},"references-count":37,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["nano12193523"],"URL":"https:\/\/doi.org\/10.3390\/nano12193523","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,8]]}}}