Risks associated with silica nanoparticles

Risks associated with silica nanoparticles

By the AVICENN team – Last updated February 2024

General information: increasingly documented adverse effects

Risks, classification and evaluation

Silica nanoparticles (SiO2) are used in a wide range of applications: in the food industry, cosmetics, pharmaceuticals, diapers and sanitary napkins, but also elastomers, resins, paints, inks, etc.
As confirmed by the annual assessments of the French declaration of substances in the nanoparticulate state published since the end of 2013, various nanoforms of silica are imported or produced in France.

The potentially harmful effects of silica nanoparticles on health¹See the references listed at the bottom of the page, section “elsewhere on the web” are increasingly documented.

In 2021, silica nanoparticles were identified as one of the four categories of most hazardous nanoparticles by a team from University College Dublin²Cf. 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.

At the end of 2023, ECHA published the Dutch proposal to classify silica nanoparticles as STOT RE 1, H372: risk of serious effects to organs (or a specific organ) through repeated or prolonged exposure³Cf. https://echa.europa.eu/fr/registry-of-clh-intentions-until-outcome/-/dislist/details/0b0236e1809d3513.

As early as 2014, the French Health Safety Agency (ANSES) had advocated a classification of silica dioxide nanoparticles in the CLP Regulation so that measures to restrict or even ban the use of certain consumer applications could be put in place.

The assessment of silica dioxide and its nanoforms by the Netherlands was initially planned for 2012 under REACH, as part of the “Community Continuous Action Plan” (CoRAP) of the European Chemicals Agency (ECHA). It was launched in 2014⁴Cf. Community rolling action plan (CoRAP) update covering years 2014, 2015 and 2016, ECHA, March 2014 but was not successful due to insufficient data from silica manufacturers.
In March 2015, ECHA requested more information from industrialists on the silica nanoforms they manufacture, in order to complete the evaluation of these substances⁵DECISION ON SUBSTANCE EVALUATION PURSUANT TO ARTICLE 46(1) OF REGULATION (EC) NO 1907/2006 For Silicon dioxide, CAS No 7631-86-9 (EC No 23 1-545-4), March 2015. However, in June 2015, ECHA’s “Board of Appeal” was notified of 2 appeals by nanosilica manufacturers refusing to give the requested information: one from Grace (Germany)⁶Announcement of appeal – Grace GmbH & Co. KG, ECHA, August 2015: “The Agency has based its decision very largely on its own classification of SAS as a nanomaterial, a classification that the Agency is not empowered to make and that in any event is irrelevant to the toxicity of SAS; (d) The Contested Decision is disproportionate in that it is not appropriate or necessary to achieve the objective of protecting human health, and places an unduly heavy burden on the Appellants”, and the other from a group of 35 companies⁷Announcement of appeal – Evonik Degussa GmbH and others, ECHA, August 2015: “On 29 February 2012, silicon dioxide was included on the CoRAP due to initial grounds for concern relating to ‘the substance characterisation, nanoparticles and toxicity of different forms of the substance’. The Appellants claim, however, that none of those alleged grounds for concern are criteria for inclusion of a substance on the CoRAP. The Appellants argue that as a result the Agencys decision to include the substance on the CoRAP was adopted in breach of Article 44 of the REACH Regulation and must be set aside. (…) The Appellants claim that the mere fact that the substance meets the non-legally binding definition of ‘nanomaterials’ in Commission Recommendation 2011/696/EU on the definition of nanomaterial is not sufficient to justify the requests for information in the Contested Decision. By requesting information on the substance on the grounds that the substance meets the non-legally binding definition of ‘nanomaterials’ in the Commission Recommendation, the Agency failed to identify a valid concern that needs to be addressed through the substance evaluation procedure.”
In addition to the French companies mentioned above, the signatories were companies :
– German: Evonik Degussa GmbH, Evonik Industries AG, Akzo Nobel Chemicals GmbH, BASF SE, Cabot Aerogel GmbH, Cabot GmbH, Clariant Produkte (Deutschland) GmbH, Grace Silica GmbH, Johnson Matthey Chemicals GmbH, Merck KGaA, Wacker Chemie AG
– Spanish: Evonik Silquilmica SA, IQESIL S.A, Instituto Suizo Para el Fomento de la Seguridad Swissi-España, S.L.U
– Belgium: Evonik Degussa Antwerpen NV, SCAS Europe S.A./N.V, Specialty Chemicals Coordination Center SA/NV
– Swedish: Akzo Nobel Pulp and Performance Chemicals AB
– Finland: Akzo Nobel Finland OY, Albemarle Europe Sprl, J.M. Huber Finland OY
– Dutch: Albermarle Catalysts Company B.V., PPG Industries Chemicals BV
– UK: Cabot Carbon Limited, LSR Associates Ltd, PQ Silicas UK Ltd, PPG CENTRAL (UK) Ltd.
– Italian: Deltagran Europe srl, Silysiamont SpA, Solvay Solutions Italia SpA
– Greek : Hellenic Petroleum SA
See also: 35 firms fight Echa decision on nano silicon dioxide, Chemical Watch, August 2015. Four companies based in France were among the signatories (Evonik Aerosil France Sarl, Clariant Production S.A.S, Merck Performance Materials SAS, Rhodia Operations SAS).
A March 2015 ECHA document states that a possible underestimation of hazards cannot be ruled out based on the data provided by silica manufacturers, who are called upon to clarify their information. The current status of this case is not very clear.

The results of a Silimmun research project conducted by French researchers and presented in 2021, show that amorphous silica nanoparticles, while not displaying the sustained pro-inflammatory character of crystalline silica, do exhibit marked effects on the cells of the immune system which could lead to a deregulation of immune responses. However, the subject is far from being fully explored. In particular, genotoxicity should be analyzed in detail with respect to the internalization capacity of silica vs. the intrinsic defense of cells against genotoxic stress⁸See The effects of amorphous silica nanoparticles on the immune system, Thierry Rabilloud, The Research Papers. Health, Environment, WorkANSES, 2021, Microplastics and nanomaterials, pp.17-19, 2021.

Silica nanoparticles are likely to carry genotoxic agents on their surface which aggravate their harmful effects on DNA⁹See Dussert F et al, Toxicity to RAW264.7 Macrophages of Silica Nanoparticles and the E551 Food Additive, in Combination with Genotoxic Agents, Nanomaterials, MDPI, 10 (7): 1418, 2020.

Aggregates should not necessarily be considered less toxic than primary particles

In early 2020, the results of research conducted in Belgium showed that aggregates larger than 100 nm should not necessarily be considered less toxic than their nanoscale counterparts¹⁰Cf. Assessing the Toxicological Relevance of Nanomaterial Agglomerates and Aggregates Using Realistic Exposure In Vitro, Murugadoss S et al, Nanomaterials, 11, 1793, 2021 and Is aggregated synthetic amorphous silica toxicologically relevant, Murugadoss S et al, Particle and Fibre Toxicology, 17(1), 2020.

Specific risks of silica for different applications

Specific risks of silica in cosmetics

Regarding cosmetics, the Scientific Committee on Consumer Safety (SCCS) reported in September 2015 that data was too disparate, inadequate and insufficient to be able to draw any conclusion concerning the safety of silica nanoforms¹¹Opinion on Silica, Hydrated Silica, and Silica Surface Modified with Alkyl Silylates (nano form), Scientific Committee on Consumer Safety (SCCS), September 2015.
In 2019, the SCCS issued an opinion stating that none of the SAS materials (hydrophilic or hydrophobic) included in the dossier can be considered soluble¹²Cf. Opinion on solubility of Synthetic Amorphous Silica (SAS), Scientific Committee on Consumer Safety (SCCS), June 20-21, 2019 (corrigendum December 6, 2019).
In 2021, the same committee concluded again that “there is a basis for concern that the use of SAS materials can pose a health risk to the consumer”¹³Cf. Scientific advice on the safety of nanomaterials in cosmetics, SCCS, 2021 (annex IV).

Specific risks of silica in food

Since at least 2011, it has been known that dietary silica (E551) contains nanoparticles, and researchers have estimated that we consume 124 mg of nano-silica per day.

Concerning the risks associated with their oral exposure (via food), the re-evaluation of silica in the form of E551 (nano and non-nano) was decided by EFSA at the end of 2017, much later than the initial schedule and without definitive conclusions being drawn regarding the safety or toxicity of this additive¹⁴See in particular:
– Re-evaluation of silicon dioxide (E 551) as a food additive, adopted November 2017, Younes M et al, EFSA Journal, 6(1):5088, 2018
– Commission Regulation (EU) No 257/2010 of 25 March 2010 establishing a programme for the re-evaluation of approved food additives in accordance with Regulation (EC) No 1333/2008 of the European Parliament and of the Council on food additives
– Food additives re-evaluation work programme, Paolo Colombo, Senior Scientific Officer – Food Additives Team, Food Ingredients and Packaging (FIP) Unit, EFSA, 28 April 2014. A call for data was opened by EFSA between October 2018 and May 2020. There will be no new call for additional data and if no conclusive data can be obtained, the current authorization of this food additive would be revised on the basis of EFSA’s current scientific opinion and the additive could be withdrawn from the European Union’s list of authorized additives.
While waiting for the results, scientists are reporting significant side effects. In particular, silica nanoparticles could promote gluten¹⁵Cf. Evaluating the Effects of Chronic Oral Exposure to the Food Additive Silicon Dioxide on Oral Tolerance Induction and Food Sensitivities in Mice, Lamas B. et al., Environmental Health Perspectives, 132, 2, 2024, DOI : 10.1289/EHP12758.

The first nano substance authorized as a biocide

In April 2014, the synthetic amorphous silica nano dioxide became the first (and until the end of 2016 at least, the only) nano substance to have been approved for marketing as a biocidal substance as of November 1, 2015¹⁶ COMMISSION EXECUTIVE REGULATION (EU) No 408/2014 approving synthetic amorphous silicon dioxide as an existing active substance for use in biocidal products of product-type 18, 23 April 2014.
See also our info sheet What regulation of nanomaterials in biocides in Europe?.
The antibacterial properties of silica, sought after for certain targeted applications, can have undesirable effects on certain bacterial communities necessary for the health or balance of ecosystems. Vigilance is therefore required.

And in the medical field?

In the medical field, a paper published on January 28, 2019, in Nature Nanotechnology shows that silica dioxide nanoparticles can induce changes in the endothelium and thus leakage of tumor cells, which causes metastasis. According to Frédéric Lagarce, professor of biopharmacy and hospital practitioner in Angers: “What is interesting / original is to show a potential risk of nanotechnologies in the treatment of tumors while these technologies are often presented as the answer to improve the performance of anticancer drugs. It is now necessary to verify if these endothelial modifications are also found with polymeric or lipidic nanoparticles, which are much more used to encapsulate active ingredients and target tumors. If this were unfortunately the case, the whole strategy of nanomedicine (very cancer-oriented) would be compromised.

Workers are the first to be exposed

In April 2019, as part of an occupational health research project, INRS issued a call to companies using nanostructured amorphous silica. There were apparently only few candidates because INRS relaunched a new identical call in September 2021…

In May 2019, the French National Health Security Agency (Anses) warned of the high health risks associated with crystalline silica, including quartz, particularly for the 365,000 workers exposed to it. The risks of amorphous silicas are particularly important, because of their nanometric size. Anses recommends a series of measures in terms of prevention and control of exposure in the workplace, medical surveillance and recognition of occupational diseases.

In February 2022, INRS published a specific safety sheet on synthetic amorphous silicas which outlines the prevention and protection measures to be implemented to protect workers.