Risks associated with titanium dioxide nanoparticles

Risks associated with titanium dioxide nanoparticles

By AVICENN Team – Last Modified February 2023

Very strong presumptions of risks

Even non-nano, inhaled TiO₂ is possibly carcinogenic

In 2006 the International Agency for Research on Cancer (IARC) classified titanium dioxide (TiO₂) as possibly carcinogenic to humans (class 2 B)¹Carcinogenic Hazards from Inhaled Carbon Black, Titanium Dioxide, and Talc not Containing Asbestos or Asbestiform Fibers: Recent Evaluations by an IARC Monographs Working Group, Baan RA, Inhalation Toxicology, 2007, 19(1): 213-228. Note the fact that this classification has been challenged on the grounds that the cited studies were on rats, whose respiratory system is different from that of humans. – and this, all sizes combined: the nanometric scale is therefore concerned, but no more nor less than non-nanometric TiO₂. The studies that were considered for this classification were on TiO₂ in powder form. The presumption of inhalation risks primarily concerns potentially exposed workers.

Thirteen years later, at the end of a long standoff between manufacturers and French and European health authorities² As early as September 2014, the "Board of Appeals" of the European Chemicals Agency (ECHA) had been seized by nine manufacturers of titanium dioxide (Tioxide Europe / Huntsman, Cinkarna, Cristal Pigment, Du Pont, Evonik, Kronos, Precheza , Sachtleben Chemie GmbH and Tronox Pigments) who refused to provide the data requested by ECHA as part of the risk assessment of titanium dioxide (including its nanoforms) under REACH. In March 2017, they won their case, on the grounds that the term "nanoform" was not defined in Reach. see Decision of the board of appeal of the European Chemicals AgencyMarch 2017., the classification of TiO₂ as a category 2 carcinogen by inhalation was adopted by the European Commission on October 4, 2019 and published in February 2020³See COMMISSION DELEGATED REGULATION (EU) 2020/217 of 4 October 2019 amending, for the purposes of its adaptation to technical and scientific progress, Regulation (EC) No 1272/2008 of the European Parliament and of the Council on the classification, labeling and packaging of substances and mixtures and correcting this regulation published in the Official Journal of the European Union on February 18, 2020 and Corrigendum to Commission Delegated Regulation (EU) 2020/217 of 4 October 2019 amending, for the purposes of its adaptation to technical and scientific progress, Regulation (EC) No 1272/2008 of the European Parliament and of the Council on classification, on the labeling and packaging of substances and mixtures and correcting this regulation, OJ, 25 February 2020. . The cause: retention (biopersistence) in the lungs and the low solubility of titanium dioxide.

The classification of TiO₂ came into effect on October 1, 2021. When used in the form of a powder containing 1% or more of particles with an aerodynamic diameter less than or equal to 10 μm, it is necessary to inform users of the precautionary measures that must be taken to reduce the risk to human health as far as possible, for example with the following statement on liquid mixtures: " Attention ! Hazardous respirable droplets may form when sprayed. Do not breathe aerosols or mists » or, for solid mixtures: " Attention ! Hazardous respirable dust may form during use. Do not breathe this dust”.

The Professional Association of Titanium Dioxide Manufacturers (TDMA) had nevertheless announced that on May 13, 2020, some of its members had brought an action before the General Court of the European Union against the harmonized classification of TiO₂, for which they requested cancellation⁴See in particular:
- Legal action against the classification of titanium dioxide, TDMA, June 4, 2020
- Action brought on 13 May 2020 – Brillux and Daw v Commission (Case T-288/20), General Court of the EU. The TDMA had indicated that it and its members “will endeavor to find a way to implement the regulations from this date, despite the uncertainties of the classification”.
On November 23, 2022, the Court of Justice of the European Union delivered its judgment in their favor, annulling the classification⁵See Titanium Dioxide Professionals Obtain TiO₂'s Classification as a Carcinogen by Inhalation (Temporarily), EveNanos, November 23, 2022 ; but in February 2023, the french government, Then European Commission, appealed against this cancellation: the classification will therefore remain in force until the end of the procedure at least, expected to last one to two years.

At the nano scale, the risks could be even greater

A recent publication established the presence of titanium dioxide nanoparticles (TiO₂) in the liver and spleen of 15 humans (and no longer only in laboratory rats). In half of the cases, the levels were higher than that deemed safe for the liver⁶See Detection of titanium particles in human liver and spleen and possible health implications, Heringa MB et al, Particle and Fiber Toxicology, 15: 15, 2018..

For several years, scientific publications on the risks associated with titanium dioxide nanoparticles have been accumulating.

In 2014, the French Health Security Agency (ANSES) recommended a classification of titanium dioxide nanoparticles (among others) as hazardous substances to put in place measures to restriction of use or evenprohibition the use of certain consumer applications. This recommendation was taken up in action no. 72 of the 3rd national Health and Environment plan (PNSE 3) (2015-2019) and in action 1.13 of the Occupational Health Plan (PST 3) (2016-2019).

The impact of the crystalline form on the toxicity of titanium dioxide remains to be clarified, but it would seem that at equal surface the anatase forms induce less inflammation than the rutile forms and that the inflammatory and acute phase response is greater. and more persistent for TiO₂ tubes⁷See Effects of physicochemical properties of TiO₂ nanomaterials for pulmonary inflammation, acute phase response and alveolar proteinosis in intratracheally exposed mice, Danielsen PH et al., Toxicology and Applied Pharmacology, 386(1), January 2020; these results qualify those of a 2018 study, the results of which leaned to the opposite for a greater harmfulness of anatases for the immune system when they are inhaled: cf. The crystal structure of titanium dioxide nanoparticles influences immune activity in vitro and in vivo, Vandebriel RJ et al., Particle and Fiber Toxicology, 15: 9, 2018.

Finally, it is now scientifically proven that (nano)particles of titanium dioxide, combined with other contaminants (PCBs, pesticides, etc.) can lead to "cocktail effects" more harmful than the effects of these substances taken in isolation !

In 2021, titanium dioxide nanoparticles were identified as one of the four categories of nanoparticles most at risk by a team from University College Dublin⁸See 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.

In addition to the toxicity and ecotoxicity associated with TiO₂ nanoparticles themselves, there is the question of the production and toxicity of compounds resulting from the photocatalytic reaction: researchers have found that the breakdown of volatile organic compounds (VOCs) by TiO₂ nanoparticles incorporated into coatings or paints is not always complete and may generate other harmful molecules (acetone, acetaldehyde, formaldehyde in particular)⁹See for example:
–ADEME, Purification of indoor air by photocatalysis, Technical notice, September 2020
– Gandolfo A et al., Unexpectedly High Levels of Organic Compounds Released by Indoor Photocatalytic Paints, About. Science. Technology., 52, 19, 11328-11337, 2018
– Indoor air quality observatory, Purification by photocatalysis – Opportunity or threat for indoor air quality?, OQAI Bulletin n°4, June 2012
– Vivagora, CoExNano, Nano-silver and titanium dioxides in coatings: State of knowledge, uncertainties and controversies November 2010.

Workers are the first exposed

The particularly exposed workers¹⁰Exposure to nanometric titanium dioxide in the construction industry, Bertrand Honnert, Archives of Occupational and Environmental Diseases, INRS, May 2018(particularly in the chemicals, building, cosmetics, textiles or diet) should be subject to targeted education and monitoring.

Efforts are being made in this direction:

• From 2014, the data relating to titanium dioxide nanoparticles collected within the framework of the French mandatory declaration (r-nano) were communicated to the National Institute for Health Surveillance (InVS) / Public Health France within the framework of the Epinano project for monitoring cohorts of workers exposed to nanomaterials. But the device has implementation difficulties.
• In 2018, the High Council for Public Health (HCSP) called for the protection of workers and populations near industrial sites producing or handling nano-TiO₂, and published various practical recommendations for public authorities and industrialists¹¹See Protect workers and people near titanium dioxide nanoparticle production or handling sites, High Council for Public Health, June 25, 2018.
• In early April 2019, ANSES published a recommendation chronic toxicological reference value (TRV) by inhalation for the P25 form of titanium dioxide in nanoparticulate form of 0,12 µg/m3 (close to that recommended by INERIS in 2016). This is the first TRV developed for a nanomaterial in France. ANSES will study the feasibility of extending this TRV to other forms of TiO₂-NP. Based on this reference value, health risk assessments will be carried out as part of management actions for industrial facilities and sites in France.
• In a December 2020 report made public in March 2021, ANSES revealed its recommendations for occupational exposure limit values ​​(OELV) to reinforce risk prevention for workers exposed to TiO₂ nanoparticles by inhalation: OEL-8h of 0,80 µg/m³ and pragmatic VLCT-15 min of 4 µg/m³.
• In early 2022, INRS published an updated version of the toxicological data sheet on titanium dioxide presenting information and recommendations on the micro- and nanometric forms of TiO₂ : uses, physical properties, chemical properties, occupational exposure limit values ​​(OELV), methods for assessing occupational exposure, toxicokinetics – metabolism, toxicity and genotoxicity, carcinogenic effects, effects on reproduction, regulations and recommendations.
  

Environmental risks are also of concern

Finally the dissemination in the environment of manufactured nanoparticles, especially those of titanium dioxide, can be a source of toxicity for terrestrial and aquatic ecosystems¹²See for example:
In French :
- Doc' en clip – the risk associated with nanoparticles contained in sunscreens (video), Riccardo Catalano, Aix-Marseille University, October 14, 2019
- Dynamics, reactivity and ecotoxicity of metal oxide nanoparticles in soils: impact on the functions and diversity of microbial communities, thesis by Marie Simonin (Microbial Ecology / UMR CNRS 5557 University Claude Bernard – Lyon 1), defended in October 2015
- Nano or not: TiO₂ is toxic to the environment, The Observatory of cosmetics, October (summary in French of the report " Environmental hazard of selected TiO₂ nanomaterials under consideration of relevant exposure scenarios“, Umwelt bundesamt, October 2014).
In English :
- Proteomics reveals multiple effects of titanium dioxide and silver nanoparticles in the metabolism of turbot, Scophthalmus maximus, Araújo MJ et al., Chemosphere 2022
- 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
- Toxicity of titanium nano-oxide nanoparticles (TiO₂) on the pacific oyster, crassostrea gigas: immunity and antioxidant defense, Arash Javanshir Khoei and Kiadokht Rezaei, Toxin Reviews, 41, 2022
- Lethal and sub-lethal effects of nanosized titanium dioxide particles on Hydropsyche exocellata Dufour, 1841, Torres-Garcia D et al., Aquatic Insects – International Journal of Freshwater Entomology, 41 (1), 2020
- Silver and titanium nanomaterials present in wastewater have toxic effects on crustaceans and fish cells, Norwegian Institute for Water Research (NIVA), November 2019
- Evaluation of the effects of titanium dioxide and aluminum oxide nanoparticles through tarsal contact exposure in the model insect Oncopeltus fasciatus, López-Muñoz D. et al., Science of the Total Environment, 666: 759-765, May 2019
- Titanium dioxide nanoparticles impaired both photochemical and non-photochemical phases of photosynthesis in wheat, Dias MC, Protoplasm, 256(1): 69–78, January 2019
- Transfer and Ecotoxicity of Titanium Dioxide Nanoparticles in the Terrestrial and Aquatic Ecosystems: A Microcosm Study, Vijayaraj V et al., Environmental Science and Technology, 52(21): 12757-12764, Oct 2018
- Toxicological impact of TiO₂ nanoparticles on Eudrilus euginiae, Priyanka KP et al., IET Nanobiotechnology, 12 (5):579, Aug 2018
- Ecotoxicological Effects of Transformed Silver and Titanium Dioxide Nanoparticles in the Effluent from a Lab-Scale Wastewater Treatment System, Georgantzopoulou A et al., About. Science. Technology., 52, 16, 9431-9441, 2018
- Environmental exposure to TiO₂ nanomaterials incorporated in building material, Bossa N et al., environmental pollutionJanuary 2017
- Titanium dioxide nanoparticles strongly impact soil microbial function by affecting archaeal nitrifiers, Simonin M et al., Scientific Reports, 6, 2016
- Ecotoxicity of engineered TiO₂ nanoparticles to saltwater organisms: An overview, D. Minetto, G. Libralato, A. Volpi Ghirardini, Environment InternationalMay 2014 – hence the need for environmental monitoring.

Confusion over assessments

Under REACH

The assessment of the risks associated with titanium dioxide (including its nanoforms), foreseen within the framework of REACH, was to be carried out by ANSES since 2012-2013, but it was hampered by the refusal of manufacturers to communicate the data necessary for this assessment.

in food

The food additive E171 consists of particles of TiO₂ (part of which in nano form). He was banned since 2020 in France and since 2022 in Europe.

Many publications report deleterious health effects related to the ingestion of TiO₂ nanoparticles: risks for the liver, ovaries and testicles in humans, immune problems and precancerous lesions in the colon in rats, disturbances intestinal microbiota, inflammation and alterations of the intestinal barrier in animals as in humans, harmful effects for offspring in rodents, etc.

At the end of 2022, ANSES published its opinion on the risk assessment of the nanometric fraction of the food additive E171 which points to the lack of toxicological data available to carry out a complete assessment of the additive E171 and recommends limiting the uses and exposure of workers and consumers to nanomaterials, “by promoting the use of safe products, devoid of manufactured nanomaterials, and by limiting these uses to those ultimately considered to be duly justified and subject to a documented demonstration of the acceptability of the risk”.

In cosmetics

The safety of titanium dioxide nanoparticles in cosmetics is not as established as has long been believed¹³See in particular Titanium dioxide nanoparticles, their place in the cosmetics industry and their dangers, Laura Daragnes, Thesis for obtaining the state diploma of doctor of pharmacy, under the supervision of Isabelle Bestel, University of Bordeaux, September 2018 et several associations ask the prohibition of TiO2 in cosmetic products likely to be ingested (toothpaste, balms and lipsticks in particular).

In sunscreens and beauty products, TiO₂ nanoparticles (Cl 77891) have been evaluated by the Scientific Committee for Consumer Safety (CSSC), which approved their use as UV stabilizers, with an authorization for a maximum concentration of 25% (applications in the form spray are not allowed)¹⁴The SCCS issued a first opinion on July 23, 2013, revised in 2014: Scientific Committee on Consumer Safety SCCS OPINION ON Titanium Dioxide (nano form) COLIPA n° S75, SCCS, April 2014 and completed in September 2014: Scientific Opinion for clarification of the meaning of the term “sprayable applications/products” for the nano forms of Carbon Black CI 77266, Titanium Oxide and Zinc Oxide, SCCS, September 2014 (published June 2015)). ; the nano form of titanium dioxide particles has been listed since August 2016 in appendix VI of the Cosmetics Regulation¹⁵See our file Regulation of nanomaterials in cosmetics,veillenanos.fr . They are mainly used in rutile form (or anatase / rutile mixture) and often coated with a layer of silica or alumina to prevent the formation of free radicals (which cause skin aging).
But several problems were noted:

• chlorine from swimming pools can degrade this coating, but in contact with water and under the effect of light, TiO₂ can then release free radicals, responsible for skin aging and the appearance of cancers¹⁶In 2012, researchers from Cincinnati in the United States showed that chlorine from swimming pools can degrade the aluminum hydroxide coating that surrounds the nanoparticles of titanium dioxide (TiO₂) integrated into certain sunscreens (here Neutrogena SPF 30 ). In contact with water and under the effect of light, the core of the nanomaterial, the nano  TiO₂ can then release free radicals, responsible for skin aging and the appearance of cancers
  – Cf. Depletion of the protective aluminum hydroxide coating in TiO2-based sunscreens by swimming pool water ingredients, Chemical Engineering Journal, 191: 95-103, May 2012
  – See also this more recent article: UV filters interaction in the chlorinated swimming pool, a new challenge for urbanization, a need for community scale investigations, Sharifan H et al., About Res., 148:273-276, July 2016
• research in Spain and France thus estimated that the quantities of titanium dioxide nanoparticles released in summer on Mediterranean beaches and showed a significant increase in the concentration of hydrogen peroxide, a molecule toxic to phytoplankton which constitutes food basic marine animals¹⁷In 2014, Spanish researchers thus estimated that tourist activity on a Mediterranean beach during a summer day can release around 4 kg of titanium dioxide nanoparticles into the water, and lead to an increase of 270 nM/day of the concentration of hydrogen peroxide (a molecule with toxic potential, in particular for phytoplankton which constitutes the basic food of marine animals). see Nano UV screens: a danger to marine life, The Cosmetics Observatory, September 5 2014
  – In 2017, researchers from CEREGE in France measured the concentration of titanium in the water of three beaches in Marseille and estimated at 54 kilos per day the weight of TiO₂ released in the two summer months for a small beach. See :
  - Scientists find titanium dioxide from sunscreen is polluting beaches Scientists find titanium dioxide from sunscreen is polluting beaches, presentation by Labille J., Goldschmidt Conference, August 2018
  - Estimation and minimization of the risk associated with TiO2 nanoparticles used in sunscreens, presentation by Labille J, “Nano and cosmetics” technical day organized by the LNE, March 29, 2018
  - Pollution of coastal waters by UV absorbers from sunscreens, generated by summer activities, Labille J, OHM Littoral Project, 2017.
• dermatologists from Bichat and Rothschild Hospitals have, for the first time, observed the presence of titanium dioxide nanoparticles (TiO₂) along the hair follicles of a patient with frontal fibrosing alopecia (hair loss at the top forehead) who has been using sunscreen containing TiO₂ daily for 15 years¹⁸See in particular:
  - Identification of titanium dioxide on the hair shaft of patients with and without frontal fibrosing alopecia: a pilot study of 20 patients, CT Thompson, ZQ Chen , A Kolivras, A Tosti, British Journal of Dermatology 2019
  - Titanium dioxide nanoparticles and frontal fibrosing alopecia: cause or consequence?, O. Aerts, A. Bracke, A. Goossens, V. Meuleman, J. Lambert, Journal of The European Academy of Dermatology and VenereologyJune 2018
  - Sunscreen, nanoparticles and frontal alopecia, Sun Synchrotron, February 2018
  - Detection of titanium nanoparticles in the hair shafts of a patient with frontal fibrosing alopecia, Brunet-Possenti F, Deschamps L, Colboc H, et al., Eur Acad Dermatol Venereol., 2018..
• researchers in the Czech Republic have tested a sunscreen containing titanium dioxide nanoparticles and found that it does NOT prevent skin cancer (although it prevents the skin from reddening, it does not protect it from stress oxidative caused by UV!)¹⁹See NanoTiO2 Sunscreen Does Not Prevent Systemic Oxidative Stress Caused by UV Radiation and a Minor Amount of NanoTiO2 is Absorbed in Humans, Pelclova D et al., Nanomaterials, 9(6), 888, 2019.

In March 2019, due to these risks and uncertainties surrounding the safety of titanium dioxide nanoparticles, Cosmébio recommended²⁰Titanium dioxide in organic cosmetics, Cosmebio, March 2019 its members to eliminate titanium dioxide from their products or to replace it with an alternative when one exists.

The potentially adverse effects of titanium dioxide nanoparticles in sunscreens continue to be studied²¹See in particular:
- 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, September 2019
- Fueling a Hot Debate on the Application of TiO2 Nanoparticles in Sunscreen, Sharma S et al., MaterialsJuly 2019and controversies²²See for example:
- Sunscreen products for children – Too many substances of concern, Acting for the Environment and WECF France, July 2020
- Titanium dioxide nanoparticles, their place in the cosmetics industry and their dangers, Laura Daragnes, Thesis for obtaining the state diploma of doctor of pharmacy, under the supervision of Isabelle Bestel, University of Bordeaux, September 2018
- Nanoparticles – Beware, they are hiding everywhere!, Que Choisir, Monthly n° 566, February 2018.

To note : titanium dioxide nanoparticles are not expressly authorized for uses other than UV filtering. Yet we find them in toothpaste, shower gels, etc. for which UV filtering is not necessary…

In nanomedicine

Un article published on January 28, 2019 in Nature Nanotechnology shows that nanoparticles of titanium dioxide, silica and gold can induce changes in the endothelium and therefore leakage of tumor cells, causing metastases. According to Frederic 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 tumours, whereas these technologies are often presented as the answer to improving the performance of anti-cancer drugs. It should now be checked whether these endothelial modifications are also found with polymer or lipid nanoparticles, which are much more widely used to encapsulate active ingredients and target tumours. If this were unfortunately the case, the whole strategy of nanomedicine (very cancer-oriented) would be called into question.« 

Discover more here.

In paintings and building

Recent research has shown that the effectiveness of paints containing TiO₂ nanoparticles is not optimal and that the benefit / risk balance is not conclusive.²³See in particular:
- Paints to purify the ambient air, CEA Liten, November 2020.

The “Release_NanoTox” project (funding ANSES 2015-2018) attempted to provide new knowledge about the potential impact of nano-objects made from nanocomposite materials under stress of use, on brain functions. The scientific teams have developed an experimental bench making it possible to carry out a realistic exposure from TiO₂ nanoparticles resulting from the sanding of nanoadditive materials. The Scientific and Technical Center for Building (CSTB) and the LNE (MONA Platform) participated in the aeraulic characterization phase of this bench and in the physico-chemical characterization of the nano-objects emitted in the exposure chamber. Then ANSES and the CarMeN laboratory were involved in the phases of exposure by inhalation and in vivo analysis of cerebral morphofunctional alterations in mice during exposure. The results are being processed²⁴See in particular:
- In vivo evaluation of the potential neurotoxicity of aerosols released from mechanical stress of nano-TiO2 additived paints in mice chronically exposed by inhalation, Maxinay S et al., J. Phys.: Conf. Ser., 838, 012025
- Research activity report 2016, LNE, 2016.

A European research project entitled NanoHouse conducted between 2010 and 2013 observed the cycle de life titanium dioxide nanoparticles contained in paints and coatings used inside and outside homes. The work evaluated the rate of release of nanoparticles from only 1 to 2% – and in the form of agglomerates²⁵Research into the safety of nanoparticles – No nano-dust danger from façade paint, EMPA, 13 January 2014; subsidized to the tune of 2,4 million euros by the European Commission, out of an overall budget of 3,1 million euros, the NanoHouse project ran from January 2010 to June 2013, with French partners CEA et ISearth.. But other studies are much less reassuring: a study by INERIS and the University of Compiègne published in early 2015 showed that an existing commercial titanium dioxide nanocoating, once applied to a building facade, may deteriorate from sun and rain; in doing so, it leads to the release of titanium particles into the air in a few months – and what is more, in the form of free particles (more dangerous than when they are agglomerated together or with residues of other materials)²⁶See Emission of titanium dioxide nanoparticles from building materials to the environment by wear and weather, Shandilya, N et al., Environmental Science & Technology, 49(4): 2163-2170, 2015; a lay summary is available free of charge here: Nanocoating on buildings releases potentially toxic particles to the air, “Science for Environment Policy”, European Commission, 28 May 2015, it is therefore appropriate under these conditions to minimize the use of nanocoatings.

What environmental monitoring?

In June 2020, the High Council for Public Health (HCSP) published a report concerning the metrological monitoring in the environment of titanium dioxide nanoparticles (TiO₂) finalized in October 2019²⁷See Interim report – elements relating to the metrological monitoring in the environment of titanium dioxide nanoparticles (TiO₂) and the examination of the feasibility, HCSP, October 2019 (publication June 2020). For the HCSP, it is possible to carry out measurements of the concentration rates of TiO₂ nanoparticles in the air around industrial sites. In the absence of a single operational method to simultaneously measure the number / mass of particles and to perform the chemical analysis of nanoparticle TiO₂, the HCSP considers that different approaches and measurement methods must be considered, depending on the specificities of each situation.

Since 2019, the Tronox plant (ex-Cristal) in the Haut-Rhin has been required to carry out environmental monitoring of the impact of its emissions of titanium dioxide particles including nanometric forms, at the rate of two measurement campaigns each year.²⁸See Order laying down additional requirements for CRISTAL France SAS in Thann , Haut-Rhin Prefecture, August 3, 2018; See as well Estimation of the average annual concentrations in the air around an industrial site producing substances in the nanoparticle state – Cristal – Thann site, titanium dioxide production unit, INERIS, October 2017. In October 2020, the Haut-Rhin DREAL told Avicenn²⁹See Letter from the Haut-Rhin DREAL in response to Avicenn's request , Oct. 2 2020 that no isolated nanometric particle of TiO₂ had been detected during the last campaign with known results at the time (June 2019); two types of elements were observed: a small minority of agglomerates larger than 250 nm composed of nanoparticles and a large majority of spheroids larger than 100 nm for some larger than 400 nm. The 2019 concentrations were down compared to the exploratory campaigns carried out in 2013, 2016 and 2018; those of February 2020 in levels close to the limit of quantification. The results of subsequent campaigns in the summer of 2020 were not yet available.

Caution: large agglomerates should not be considered as necessarily less toxic than small agglomerates. At the beginning of 2020, the results of research carried out in Belgium were published showing that large agglomerates of TiO₂ nanoparticles do not seem to be less active than small agglomerates.³⁰See Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo, Murugadoss S et al., Particle and Fiber Toxicology, 17 (10), 2020.

Restrictions in Switzerland

In 2008, the Grand Council of the Republic and Canton of Geneva advised against the use of nanoparticle TiO₂ on State construction sites as well as in the constructions of private companies.³¹Health: straight into the wall… self-cleaning, Alternative Santé, 6 January 2016 and Report M 1741-A from the Council of State to the Grand Council of Geneva, 2008. It was based in particular on the study carried out by the Cantonal Service for Industrial Toxicology and Protection against Indoor Pollution, which considered “Irresponsible to use such a product before even researching known hazards and assessing their risks”, lamented "premature use of these products in Italy, France and Belgium" and wished "that these imprudences are not repeated on the territory of our Canton"³²Annex 2 of the previous document.

Large agglomerates should not be considered necessarily less toxic than small agglomerates

Caution: large agglomerates should not be considered as necessarily less toxic than small agglomerates. At the beginning of 2020, the results of research carried out in Belgium were published showing that large agglomerates of TiO₂ nanoparticles do not seem to be less active than small agglomerates.³³See Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo, Murugadoss S et al., Particle and Fiber Toxicology, 17 (10), 2020..

Explore the bibliography below to learn more!