Risks associated with silver nanoparticles

The risks associated with silver nanoparticles

By the AVICENN team – Last updated August 2022

Hundreds of tons of silver nanoparticles are produced every year in the world for their antibacterial or antifungal properties, despite worrying environmental risks, especially for microorganisms, aquatic flora and fauna¹See for example:
– Proteomics reveals multiple effects of titanium dioxide and silver nanoparticles in the metabolism of turbot, Scophthalmus maximus, Araújo MJ et al, Chemosphere, 2022
– The Biological Cost of Antimicrobial Nanosilver Exposure, AzoNano, 30 May 2022 > Whole-lake nanosilver additions reduce northern pike (Esox lucius) growth, Slongo BD et al, Science of The Total Environment, 838(2), 56219, 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
– Nanoparticles disrupt algae, University of Geneva, November 25, 2020(Metabolomics for early detection of stress in freshwater alga Poterioochromonas malhamensis exposed to silver nanoparticles, Liu W et al., Scientific Reports, 10, November 2020)
– How Nanosilver Gets Into Our Freshwater, and What We Need To Do About It, Lauren Hayhusrt, Fisheries Research Biologist, IISD Experimental Lakes Area, April 16, 2020
– Silver Uncontrolled: How nanosilver gets into our fresh water, and what we need to do about it, Lauren Hayhusrt, Fisheries Research Biologist, Experimental Lakes Area, November 29, 2019
– Comparative multi-generation study on long-term effects of pristine and wastewater-borne silver and titanium dioxide nanoparticles on key lifecycle parameters in Daphnia magna, Hartmann S et al, NanoImpact, 14, February 2019
– Phytotoxicity of Silver Nanoparticles to Aquatic Plants, Algae, and Microorganisms, Domingo G et al, Nanomaterials in Plants, Algae and Microorganisms – Concepts and Controversies, volume 2: 143-168, 2019
– France Diplomatie, Silver nanoparticles are toxic to aquatic organisms, October 26, 2018 ; Waterborne exposure of adult zebrafish to silver nanoparticles and to ionic silver results in differential silver accumulation and effects at cellular and molecular levels, Lacave JM et al, Science of The Total Environment, 642: 1209-1220, November 2018
– Accumulation of Silver in Yellow Perch (Perca flavescens) and Northern Pike (Esox lucius) From a Lake Dosed with Nanosilver, Jonathan D. Martin, Paul C. Frost, Holger Hintelmann, Karla Newman, Michael J. Paterson, Lauren Hayhurst, Michael D. Rennie, Margerite A. Xenopoulos, Viviane Yargeau, Chris D. Metcalfe, Environmental Science & Technology, 2018, soil microorganisms²See in particular:
– 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
– Effect of silver nanoparticle contaminated biosolids on the soil microbial community, Dias Samarajeewa A et al, NanoImpact, 14, February 2019 Colloidal silver in question, RFJ, November 11, 2021 and health risks (argyrism at high doses³L’argent colloïdal en question, RFJ, 11 novembre 2021 and above all, bacterial resistance).

Risk Assessments

Towards a classification of silver

In 2015, ANSES called for a classification of silver nanoparticles under the European CLP regulation⁴ANSES recommends limiting the marketing of products containing silver nanoparticles, veillenanos.fr, March 2015 and Assessment of health and environmental risks related to exposure to silver nanoparticles, ANSES, last updated March 2018.

On October 19, 2020, after a long process⁵ A risk assessment of silver (including its nanoforms) was to be conducted by the Netherlands in 2014 under the ECHA Action Plan (CORAP) due to concerns about the ecotoxicity and environmental fate of silver, particularly in nano form. A 2016 document suggested that the information collected from manufacturers still needed to be completed (see DECISION ON SUBSTANCE EVALUATION PURSUANT TO ARTICLE 46(1) OF REGULATION (EC) NO 1907/2006 For Silver, CAS No 7440-22-4 (EC No 23 1-131-3), ECHA, July 2016).
In 2018, the evaluation of the biocidal use of different forms of silver (including nanocomposite forms) and silver salts was underway, by Sweden, with a view to proposals for harmonized classification and labeling (CLH) of these forms of silver (Cf. SUBSTANCE EVALUATION CONCLUSION and EVALUATION REPORT for Silver EC No. 231-131-3 CAS No. 7440-22-4, November 2018). In 2019, the dedicated page on the ECHA website indicated that a CLH proposal had indeed been formalized in May 2019 by Sweden., the European Chemicals Agency (ECHA) submitted for consultation a proposal for the classification of silver and nano-silver ⁶Cf. proposal for the classification of silver and nano silver, ECHA, October 2020 with, for the latter, the following values :

• skin sensitization category 1, H317 (may cause skin allergy)
• germ cell mutagenicity category 2, H341 (likely to induce genetic defects)
• reproductive toxicity category 1B, H360FD (may impair fertility, may cause harm to the fetus)
• hazardous to the aquatic environment H400 and H410 (acute and chronic toxicity category 1).

The classification was announced for March 2022 at the latest but was postponed to July 30, 2022 during the review by the Risk Assessment Committee (RAC) of ECHA in early June 2022. It should result in the implementation of protective measures and probably the withdrawal of certain consumer applications (to be specified according to the chosen classification).

Non-approval as a biocide of silver “as a nanomaterial”

In August 2021, the decision not to approve silver “as a nanomaterial” in biocidal products was published in the Official Journal of the European Union (OJEU) for product types 2, 4 and 9.

This decision was taken because of a legal technicality: an industrialist had not applied for an authorization to use nano-silver for biocidal purposes⁷Indeed, manufacturers sometimes do not file (or withdraw or do not renew) an application for a biocide that does not meet the stricter requirements of the new Biocidal Regulation (or for which they feel the cost will be too high to meet them). – and not because of the (proven) risks of nano silver for health and/or the environment.

Studies on the toxicity of nanosilver

In 2020, a scientific literature review⁸Cf. Pulmonary toxicity of silver vapours, nanoparticles and fine dusts: A review, Hadrup N et al, Regulatory Toxicology and Pharmacology, 115, August 2020 conducted by Danish researchers showed that some of the inhaled silver nanoparticles end up in the lungs, lymph nodes, liver, kidneys, spleen, ovaries and testicles and lead to lung function failures and lung inflammation. While ions have a greater effect, the toxicity pattern is similar for nanoparticles. Silver has been evaluated as genotoxic based on in vitro and in vivo studies.

In 2021, the U.S. National Institute of Occupational Health (NIOSH) analyzed more than 100 studies on silver nanomaterials⁹Cf. Health Effects of Occupational Exposure to Silver Nanomaterials, Current Intelligence Bulletin 70, NIOSH, May 2021:

• In human cell studies, silver nanomaterials were associated with toxicity (cell death and DNA damage) that varied with particle size.
• In animals exposed to silver nanomaterials (by inhalation or other routes of exposure), tissue concentrations of silver were elevated in all organs tested and exposure to silver nanomaterials was associated with a decreased lung function, to an inflammation of the lung tissue and to histopathological (microscopic tissue) changes in the liver and kidneys.

In the (relatively few) studies that have compared the effects of exposure to silver at the nanoscale or microscale, nanoscale silver particles are more absorbed and more toxic than microscale particles.
NIOSH also evaluated data from two subchronic (intermediate duration) inhalation studies in rats that showed adverse effects on the lungs and liver (including early pulmonary inflammation and liver bile duct hyperplasia).

In a paper published in June 2021 by Nature nanotechnology, researchers from the University of Pittsburgh (USA) warned against the widespread use of silver nanoparticles in consumer products (washing machines, textiles, paints, …) and insist that the use of silver nanoparticles should be reserved only for health equipment in order to limit bacterial resistance.

In July 2021, silver nanoparticles were identified as one of the four most risky categories of nanoparticles by a team from University College Dublin¹⁰Cf. A semiquantitative risk ranking of potential human exposure to engineered nanoparticles (ENPs) in Europe, Li, Y and Cummins, E, Science of the Total Environment, 778, July 2021.

Risk assessment by application area

In the food sector

In 2011, the Institute for a Culture of Industrial Safety (ICSI) conducted a study that analyzed the cost-benefit ratio of using nanoparticles in refrigerators and its findings suggested that“the net benefit of silver nanoparticles in household refrigerators is negative, i.e. the costs exceed the benefits.”

In April 2015, the presence of silver nanoparticles in the additive E174 (used as a silver and decorative coloring for pastries and chocolates) was confirmed. Nevertheless, in December 2015, EFSA considered that “the available information is insufficient to assess the safety of silver as a food additive”¹¹Cf. Scientific opinion on the re-evaluation of silver (E 174) as food additive, EFSA, December 2015, which was confirmed by the SCCS in 2018 in the cosmetic field (see below).
ANSES also reiterated that silver, whether in nanoparticulate form or not, is not included in the list of minerals that can be used for the manufacture of food supplements. Given the presence of nanosilver in food supplements distributed through online trade, the Agency recommended to strengthen consumer information and control of the distribution of these products that could contain nanosilver particles.

An Italian study published in 2021 showed the accumulation and slow elimination of silver nanoparticles in the brain of mice after a low-dose oral administration, associated with effects on glial cells and ultrastructural alterations of the blood-brain barrier¹²Repeated oral administration of low doses of silver in mice: tissue distribution and effects on central nervous system, Recordati et al, Particle and Fibre Toxicology, 18:23, 2021.

A review of the scientific literature published in March 2022 alerted on the pro-inflammatory potential, in the intestine, of silver nanoparticles, after human oral exposure (generation of oxidative stress, accompanied by mitochondrial dysfunction, interference with transcription factors and cytokine production)¹³Pro-inflammatory effects of silver nanoparticles in the intestine, Sousa A et al, Archives of Toxicology, 96: 1551-1571, 2022.

In cosmetics

In the cosmetic field, colloidal silver (nano) has been, since 2015, the subject of an evaluation procedure by the European Scientific Committee European Scientific Committee on Consumer Safety (SCCS) . 63 notifications of products containing colloidal silver were made to the Commission and the SCCS issued an opinion in October 2018 reiterating that the data collected did not provide assurance of the safety of nano-silver in cosmetic applications¹⁴See in particular:
– OPINION ON Colloidal Silver (nano) – final version, SCCS, October 2018
– OPINION ON Colloidal Silver (nano) – preliminary version, SCCS, February 2018
– Call for data on ingredients of Colloidial silver nano in the framework of Regulation 1223/2009 on Cosmetic products, SCCS, March 2015
– Request for a scientific opinion: Colloidal Silver (nano) CAS No 7440-22-4, EC No 231-131-3, SCCS, date ?
– Minutes of the 5th Plenary Meeting of the Scientific Committee on Consumer Safety (SCCS), October 24-25, 2017: “A request for information and clarification was sent back to Applicants with a deadline by 30 September 2017. Four replies from 3 Applicants have been received and are under assessment.”.

In textiles

Many articles of sportswear appear to be treated with nano silver.

In December 2018, Svenskt Vattens, the Swedish water and wastewater union alerted on antibacterial and anti-odor silver from sports textiles¹⁵Cf. Adidas continues to sell clothing treated with toxic silver despite the risk to aquatic environments, Svenskt Vattens, December 17, 2018. It is the largest known source of silver in water treatment plants, a threat to our lakes and seas, and a risk for the spread of antimicrobial resistance. Brands and retailers are asked to stop selling clothing treated with silver to protect water (Adidas was singled out as the worst performer).

In April 2019, the NGO Women’s Voices for the Earth expressed concern about the use of nanosilver in menstrual pads and underwear¹⁶Cf. Concerns About Nanosilver in Period Products, Womens voice, April 24, 2019, due to health and environmental risks.

In March 2020 in the United States, several associations challenged the request for authorization from the U.S. Environmental Protection Agency (EPA) of a nanosilver-based product intended to be applied to textiles, in view of the health and environmental risks that it could entail¹⁷See Current EPA Proceeding – Docket ID: EPA-HQ-OPP-2020-0043; see in particular:
– Comments on EPA’s Proposed Registration Decision for a New Active Ingredient, NSPW Nanosilver, the International Center for Technology Assessment, the Center for Biological Diversity, and the Institute for Agriculture and Trade Policy, March 30, 2020;
– EPA Ruling Could Allow Controversial Nanoparticles in Pesticides, Bloomberg Environment, March 23, 2020
– Toxic Textiles Infused with Antimicrobial Nanosilver Poised for EPA Pesticide Registration, Beyond Pesticides, March 23, 2020.

In the medical field

Even in the medical field, the use of nanosilver must be better evaluated, as the association Health Care without Harm (HCWM) underlines¹⁸Cf. Dorota Napierska, Health Care Without Harm Europe (HCWH), Nanosilver in healthcare – does the silver bullet exist?.

Protection of workers exposed to nano silver

In the same report as above¹⁹Cf. Health Effects of Occupational Exposure to Silver Nanomaterials, Current Intelligence Bulletin 70, NIOSH, May 2021, the U.S. National Institute of Occupational Health (NIOSH) established an occupational exposure limit value (OELV) recommendation for silver nanoparticles of 0.9 ^μg/m3 as an 8-hour weighted average concentration. In addition, NIOSH continues to recommend an OEL of 10 ^μg/m3 as an 8-hour weighted average concentration for total silver (metal dust, smoke, and soluble compounds, such as Ag). NIOSH also recommends the use of workplace exposure assessments, engineering controls, safe work procedures, training and education, and established medical surveillance procedures to protect workers.

Towards “safer by design” silver nanoparticles?

In August 2020, French researchers announced that they had developed a “safer by design” biocidal nanomaterial that contained an assembly of silver nanoparticles linked together by a bio-inspired molecule. It releases Ag(I) ions in a slow and controlled manner, unlike the silver nanoparticles currently used which undergo uncontrolled processes of transformation and product release²⁰Cf. New “Safer-by-Design” biocides based on silver nanoparticle assemblies, CEA, August 26, 2020.