Risks associated with zinc oxide (ZnO) nanoparticles

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.