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VeilleNanos - Risks associated with zinc oxide (ZnO) nanoparticles

Risks associated with zinc oxide (ZnO) nanoparticles

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Info sheet
zinc zinc oxide risks

By the AVICENN team – Last updated May 2023

Risks associated with zinc oxide (ZnO) nanoparticles

General considerations on the risks associated with zinc oxide nanoparticles

In May 2014, the French Health Security Agency (ANSES) recommended a classification of zinc oxide nanoparticles (and others) as hazardous substances so that measures to restrict or even ban the use of some consumer applications could be put in place1Cf. Évaluation des risques liés aux nanomatériaux, ANSES, avril 2014 (page 9).

The risk assessment of zinc oxide (including its nanoforms) conducted as part of the REACH program, conducted by Baua (Federal Office for Occupational Safety and Health in Germany), was originally scheduled to be conducted in 20172See in particular Evaluation of substances – Community rolling action plan: Zinc oxide, ECHA but in July 2019, due to insufficient data, ECHA requested additional data from zinc oxide manufacturers to be provided by February 20223Cf. Decision on substance evaluation – Zinc oxide, ECHA, 9 July 2019. ECHA points out the potential for zinc oxide nanoforms to cause target organ toxicity by repeated exposure, germ cell mutagenicity, adverse reproductive effects and aquatic toxicity. Hence its warning that “based on this information on exposure and hazards, there is a potential risk to consumers and the environment.

Health risks of zinc oxide nanoparticles

Prior to the publication of the 2019 ECHA report mentioned above4See footnote 3, health risks had already been identified by the scientific community5See:
– Zinc Oxide Nanoparticles: Therapeutic Benefits and Toxicological Hazards, Elshama SS et al., The Open Nanomedicine Journal, 5 : 16-22, 2018
Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells, P. Ickrath et al.Nano-Bio Interactions: Nanomedicine and Nanotoxicology, 18 décembre 2017
Zinc oxide nanoparticles induce toxic responses in human neuroblastoma SHSY5Y cells in a size-dependent manner, J. Liu et al.International Journal of Nanomedicine, 1er novembre 2017
Zinc oxide nanoparticles harness autophagy to induce cell death in lung epithelial cells, J. Zhang et al.Cell Death & Disease, 27 juillet 2017
L’effet des nanoparticules d’oxyde de zinc sur l’activité respiratoire centrale, D. Morin, Institut de Neurosciences cognitives et intégratives d’Aquitaine, 2016
Zinc-Oxide Nanoparticles Exhibit Genotoxic, Clastogenic, Cytotoxic and Actin Depolymerization Effects by Inducing Oxidative Stress Responses in Macrophages and Adult Mice, R. Pati et al.Toxicological Sciences, avril 2016
In vitro toxicity of zinc oxide nanoparticles: a review, M. Pandurangan, D. H. Kim, Journal of Nanoparticle Research, 2015
Neurotoxicity induced by zinc oxide nanoparticles: age-related differences and interaction, L. Tian et al.Scientific Reports, 3 novembre 2015
Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles, V. Sharma et al.Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 14 juin 2012
, including toxic effects in different organs (liver, spleen, kidneys, stomach, pancreas, heart and lungs) and body systems (neurological system, lymphatic system, hematological indices, sex hormone levels and fetal development).

According to neuroscience researchers at the University of Bordeaux, brain function impairment has been reported in animals: zinc nanoparticles disrupt the neuronal mechanisms involved in memory and induce a disruption in the functioning of the blood-brain barrier; they can trigger the production of free radicals (called oxidative stress) in nerve cells that can induce neuronal death and brain damage; acute exposure to zinc nanoparticles triggers an abnormal acceleration followed by a definitive stop of the respiratory rhythm6Exposure to nanoparticles: a risk for the brain to be taken very seriously, Didier Morin and Laurent Juvin, The Conversation, August 2018 (Acute exposure to zinc oxide nanoparticles critically disrupts operation of the respiratory neural network in neonatal rat, Nicolosi A et al, NeuroToxicology, 67, 150-160, July 2018).

In 2018, researchers showed that zinc oxide nanoparticles on the lining of food cans get into food and may lead to poorer nutrient absorption and increased permeability of the gut, transferring unwanted compounds into the bloodstream.

Potential adverse effects of zinc oxide nanoparticles continue to be the subject of disturbing publications7See for example:
Exposure to Zinc Oxide Nanoparticles Increases Estradiol Levels and Induces an Antioxidant Response in Antral Ovarian Follicles In Vitro, Santacruz-Márquez R et al., Toxics, 11(7):602, 2023
Review of Zinc Oxide Nanoparticles: Toxicokinetics, Tissue Distribution for Various Exposure Routes, Toxicological Effects, Toxicity Mechanism in Mammals, and an Approach for Toxicity Reduction, Fujihara J & Nishimoto N, Biological Trace Element Research, 2023
Preparation of Nano Zinc Particles and Evaluation of Its Application in Mouse Myocardial Infarction Model, Song, Y et al, J. Nanosci. Nanotechnol., 21:1196-1201, 2021
Hormonal and molecular alterations induced by sub-lethal toxicity of zinc oxide nanoparticles on Oreochromis niloticus, Saudi Journal of Biological Sciences, 27(5): 1296-1301, May 2020
Neurotoxicity and biomarkers of zinc oxide nanoparticles in main functional brain regions and dopaminergic neurons, Science of The Total Environment, 705, February 2020
ZnO and CuO nanoparticles: a threat to soil organisms, plants, and human health, Rajput V et al, Environmental Geochemistry and Health, 42: 147-158, 2020
Zinc oxide nanoparticles effect on thyroid and testosterone hormones in male rats, N M Luabi, N A Zayed, LQ Ali, Journal of Physics: Conference Series, 1 September 2019
Zinc oxide nanoparticles impacts: cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity, Sanjiv Singh, Toxicology Mechanisms and Methods, Volume 29, 2019
Inhaled Engineered Zinc Oxide Nanoparticles Induce Acute Toxicity in the Lungs of Rats, P. Upadhyay, R. Abarca, X. Luo, L.S. Van Winkle, K.E. Pinkerton, American Journal of Respiratory and Critical Care Medicine, 2019
especially in cosmetics8See: – Penetration of Zinc into Human Skin after Topical Application of Nano Zinc Oxide Used in Commercial Sunscreen Formulations, Holmes AM et al, ACS Appl. Bio Mater., 2020
Sunscreen: FDA regulation, and environmental and health impact, Shanthi Narla, Henry W. Lim, Photochemical & Photobiological Sciences, 2020
Titanium Dioxide and Zinc Oxide Nanoparticles in Sunscreens: A Review of Toxicological Data, Vujovic M, Kostic E, Journal of Cosmetic Science, 1 September 2019
Health hazards of nanoparticles: understanding the toxicity mechanism of nanosized ZnO in cosmetic products, Subramaniam VD et al, Drug and Chemical Toxicology, Volume 42, 2019
where its use in nano form has been strictly restricted by the European Union9The SCCS original zinc oxide advisory published in 2012 was supplemented in April 2014 and again in September 2014 (with a June 2015 publication). In April 2016, zinc oxide nanoparticles were thus added to Annex VI of the Cosmetics Regulation, authorizing from May 2016 their use in cosmetics at a maximum concentration of 25% (except for applications that may result in exposure of users’ lungs; use in a spray is therefore prohibited to avoid inhalation) (cf. Regulation (EU) 2016/621 amending Annex VI of Regulation (EC) No 1223/2009 of the European Parliament and of the Council on cosmetic products, European Commission, April 21, 2016)..

Environmental risks of zinc oxide nanoparticles

Already before the publication of its 2019 report mentioned above10See footnote 3, ECHA considered nano zinc oxide to be “highly toxic to aquatic life, with persistent effects over time”.

In 2018, the European project SOS-Nano highlighted that zinc oxide nanoparticles lead to a high level of toxicity in oyster larvae, as seawater does not prevent dissolution11Cf. The real effects of nanoparticles in their environment, Cordis, March 2018.

In 2020, research conducted by French and Spanish researchers showed that zinc oxide nanoparticles are absorbed by reeds, with various toxic effects (reduction of their growth, chlorophyll content, photosynthetic efficiency and transpiration)12
Sunscreens containing zinc oxide nanoparticles can trigger oxidative stress and toxicity to the marine copepod Tigriopus japonicus, Stella W.Y. Wong, Guang-Jie Zhou, Priscilla T.Y. Leung, Jeonghoon Han, Jae-Seong Lee, Kevin W.H. Kwok, Kenneth M.Y. Leung, Marine Pollution Bulletin, Volume 154, May 2020
Stable Zn isotopes reveal the uptake and toxicity of zinc oxide engineered nanomaterials in Phragmites australis, BioRxiv, Caldelas C et al., 2020

Other studies published since then have added to the list of worrying environmental effects13See for example:
Zinc oxide nanoparticles induce oxidative stress, genotoxicity, and apoptosis in the hemocytes of Bombyx mori larvae, Belal, R., Gad, A., Scientific Reports, 13, 3520, 2023
Zinc oxide, titanium dioxide and C60 fullerene nanoparticles, alone and in mixture, differently affect biomarker responses and proteome in the clam Ruditapes philippinarum, Marisa I et al, Science of the Total Environment, 838 (2), September 2022
Comparative evaluation on the toxic effect of silver (Ag) and zinc oxide (ZnO) nanoparticles on different trophic levels in aquatic ecosystems: A review, Sibiya A et al, Journal of applied toxicology, 2022
Destruction of Cell Topography, Morphology, Membrane, Inhibition of Respiration, Biofilm Formation, and Bioactive Molecule Production by Nanoparticles of Ag, ZnO, CuO, TiO2, and Al2O3 toward Beneficial Soil Bacteria, Ahmed B et al, ACS Omega, 5, 14, 7861-7876, 2020
Impact of inorganic UV filters contained in sunscreen products on tropical stony corals (Acropora spp.), Corinaldesi C, Marcellini F, Nepote E, Damiani E, Danovaro R , Sci Total Environ, October 2018
Effects of zinc-oxide nanoparticles on soil, plants, animals and soil organisms: A review, V. D. Rajput et al, Environmental Nanotechnology, Monitoring & Management, May 2018
Effects of ZnO nanoparticles in the Caspian roach (Rutilus rutilus caspicus), Khosravi-Katuli K et al, Science of The Total Environment, 626: 30-41, June 2018
Toxic effects of different types of zinc oxide nanoparticles on algae, plants, invertebrates, vertebrates and microorganisms, J. Hou et al, Chemosphere, 193: 852-860, February 2018
Chronic dietary toxicity of zinc oxide nanoparticles in common carp (Cyprinus carpio L.): Tissue accumulation and physiological responses, Latifeh C et al, Ecotoxicology and Environmental Safety, 147: 110-116, January 2018
Synthesis Approaches of Zinc Oxide Nanoparticles: The Dilemma of Ecotoxicity, A. N. U.Haq et al, Journal of Nanomaterials, 2017
Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria-mediated apoptosis in zebrafish embryos, X. Zhao et al, Aquatic Toxicology, November 2016
Zinc Oxide Nanoparticles Affect Biomass Accumulation and Photosynthesis in Arabidopsis, X. Wang et al, Frontiers in Plant Science, January 12, 2016
Effects of Natural Organic Matter Properties on the Dissolution Kinetics of Zinc Oxide Nanoparticles, C. Jiang, G. R. Aiken, H. Hsu-Kim, Environmental Science & Technology, 2015
Effects of zinc oxide nanoparticles on bioaccumulation and oxidative stress in different organs of tilapia (Oreochromis niloticus), H. Kaya et al, Environmental Toxicology and Pharmacology, November 2015

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Sheet originally created in May 2018

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