Abstract
Since its discovery in the late eighteenth century and mass production in the early twentieth century, titanium dioxide has been used in a wide range of applications such as paints, cosmetics, energy storage, photocatalysis and food. Health concerns regarding TiO2 use as a food additive, named E171 in Europe, are mainly due to the presence of nanoparticles, whereas it should contain only microparticles. Here we present the history of the increasing use of TiO2 since the end of the Second World War, followed by rising concerns at the beginning of the twenty-first century, until the European decision to ban the use of TiO2 in food in 2022. We discuss the evolution of TiO2 regulation, within the regulation of chemicals products, particularly in Europe. We highlight the specific role played by the stakeholders: regulatory agencies, companies, scientists and associations. Two periods were identified. In the first period (1945–2000), marked by the growing use of chemical products, and of food additives in industry, the regulation of chemical products progressed with the double aim to master and adapt to risks. In the second period, beginning in the 2000s, the regulation of TiO2 as a food additive in Europe has evolved in the context of the regulation of nanotechnology. The liberal approach associating nanotechnologies with progress and the competitiveness of companies and of the economies has gradually been challenged by the accumulation of scientific work pointing out the risks to human health during the last period. In the context of a food safety governance based on the separation of risk assessment and risk management, the TiO2 case reveals the signaling role played by academic work, while civil society groups promote mediatization and can impose the precautionary principle as a basis for this regulation.
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Notes
ECHA and WHO (IARC) have not defined the same criteria to classify chemical products according their effects on human health. WHO (IARC) defines a classification which distinguishes four groups of products: 1(carcinogen), 2A (probably carcinogen), 2B (possibly carcinogen) and 3 (unclassifiable as to carcinogen product). The UE classification (ECHA) distinguishes only three groups of products: 1(carcinogen), 2 (highly suspected carcinogen) and 3 (carcinogen of concern). In 2017, the Risk Assessment Committee (RAC) of ECHA proposed the classification of TiO2 as a category 2 carcinogen after inhalation. On February 18th 2020, the European Union took over ECHA’s opinion and published the classification of TiO2 as a suspected carcinogen (category 2) by inhalation in powder form with at least 1% particles.
Abbreviations
- ADI:
-
Acceptable daily intake
- AIHC:
-
American Industrial Health Council
- ANSES:
-
Agence Nationale de Sécurité Sanitaire de l'alimentation, de l'environnement et du travail
- BSE:
-
Bovine spongiform encephalopathy
- ECHA:
-
European Chemical Agency
- EFSA:
-
European Food Safety Authority
- EC:
-
European Commission
- EU:
-
European Union
- FAO:
-
Food and Agriculture Organization
- FDA:
-
Food and Drug Administration
- GSFA:
-
General Standard for Food Additives
- IARC:
-
International Agency for Research on Cancer
- INCO:
-
Regulation (EU) No 1169/2011 of the European Parliament and of the Council of 25 October 2011 on the provision of food INformation to COnsumers
- INRAE:
-
Institut national de Recherche pour l’agriculture, l’alimentation et l’environnement
- JEFCA:
-
Joint FAO/WHO expert committee on food additives
- NGOs:
-
Non-governmental organizations
- NPs:
-
Nanoparticles
- OECD:
-
Organization for Economic Co-operation and Development
- REACH:
-
Registration, Evaluation, Authorization and Restriction of Chemicals
- SDGs:
-
Sustainable development goals
- TiO2 :
-
Titanium dioxide
- TDMA:
-
Titanium Dioxide Manufacturers Association
- UICC:
-
Union for International Cancer Control
- WHO:
-
World Health Organization
- WTO:
-
World Trade Organization
References
Ahmad Ruslan NAA, Kan S-Y, Hamzah AS, Chia PW (2021) Natural food additives as green catalysts in organic synthesis: a review. Environ Chem Lett. https://doi.org/10.1007/s10311-021-01209-8
ANSES (2017) Avis de l’Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail relatif à une demande d’avis relatif à l’exposition alimentaire aux nanoparticules de dioxyde de titane
ANSES (2019) Opinion of the french agency for food, environmental and occupational health & safety on the risks associated with ingestion of the food additive E171. Public Health 33:1–40
Arpaia MM (2017) The right to safe food. Eur Food Feed Law Rev 12:335–342
Banu AN, Kudesia N, Raut AM et al (2021) Toxicity, bioaccumulation, and transformation of silver nanoparticles in aqua biota: a review. Environ Chem Lett 19:4275–4296. https://doi.org/10.1007/s10311-021-01304-w
Baranowska-Wójcik E, Szwajgier D, Oleszczuk P, Winiarska-Mieczan A (2020) Effects of titanium dioxide nanoparticles exposure on human health—a review. Biol Trace Elem Res 193:118–129. https://doi.org/10.1007/s12011-019-01706-6
Bettini S, Boutet-Robinet E, Cartier C et al (2017) Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon. Sci Rep 7:1–13. https://doi.org/10.1038/srep40373
Biggi G, Giuliani E, Martinelli A, Benfenati E (2022) Patent toxicity. Res Policy 51:104329. https://doi.org/10.1016/j.respol.2021.104329
Bischoff NS, de Kok TM, Sijm DTHM et al (2021) Possible adverse effects of food additive E171 (Titanium Dioxide) Related to particle specific human toxicity, including the immune system. Int J Mol Sci 22:207. https://doi.org/10.3390/ijms22010207
Boudia S, Jas N (2013) Toxicants, health and regulation since 1945. Pickering & Chatto
Boudia S, Jas N (2007) Introduction: risk and ‘risk society’ in historical perspective. Hist Technol 23:317–331. https://doi.org/10.1080/07341510701527393
Boudia S, Jas N (2019) Gouverner un monde toxique. Quae, Versailles
Boutillier S, Fourmentin S, Laperche B (2020) Food additives and the future of health: an analysis of the ongoing controversy on titanium dioxide. Futures 122:102598. https://doi.org/10.1016/j.futures.2020.102598
Branen A, Davidson P, Salminen S, Thorngate III J (eds) (2001) Food additives. CRC Press
Brigand G, Chaumontet C, Guion P, et al (1998) Dossier scientifique De L’IFN N ° 10
Burrows JDA (2009) Palette of our palates: a brief history of food coloring and its regulation. Compr Rev Food Sci Food Saf 8:394–408. https://doi.org/10.1111/j.1541-4337.2009.00089.x
Carriere M, Arnal M-E, Douki T (2020) TiO2 genotoxicity: an update of the results published over the last six years. Mutat Res Toxicol Environ Mutagen 854–855:503198. https://doi.org/10.1016/j.mrgentox.2020.503198
Carson R (1962) Silent spring. Houghton Mifflin Company & Riverside Press (Cambridge, Mass.)
Chaker H, Cherif-Aouali L, Khaoulani S et al (2016) Photocatalytic degradation of methyl orange and real wastewater by silver doped mesoporous TiO2 catalysts. J Photochem Photobiol A Chem 318:142–149. https://doi.org/10.1016/j.jphotochem.2015.11.025
Chamundeeswari M, Jeslin J, Verma ML (2019) Nanocarriers for drug delivery applications. Environ Chem Lett 17:849–865. https://doi.org/10.1007/s10311-018-00841-1
Clémens S (1995) Les additifs alimentaires : législation et problèmes liés à leur utilisation. Joseph Fourier
Demortain D (2017) Expertise, regulatory science and the evaluation of technology and risk: introduction to the special issue. Minerva 55:139–159
EFSA (2016) Re-evaluation of titanium dioxide (E171) as a food additive. EFSA J 14:e04545. https://doi.org/10.2903/j.efsa.2016.4545
EFSA (2019) EFSA statement on the review of the risks related to the exposure to the food additive titanium dioxide (E171) performed by the french agency for food, environmental and occupational health and safety (ANSES). EFSA J. https://doi.org/10.2903/j.efsa.2019.5714
EFSA (2004) Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on Titanium dioxide related to the safety in use of rutile titanium dioxide as an alternative to the presently permitted anatase form. EFSA J 163:1–8. https://doi.org/10.2903/j.efsa.2005.163
Egalim Law (2018) LOI n° 2018–938 du 30 octobre 2018 pour l’équilibre des relations commerciales dans le secteur agricole et alimentaire et une alimentation saine, durable et accessible à tous | Legifrance. https://www.legifrance.gouv.fr/affichTexte.do;jsessionid=49FE08856A286D73F11C78E24DC846AC.tplgfr34s_2?cidTexte=JORFTEXT000037547946&categorieLien=id#JORFARTI000037548012. Accessed 27 Jun 2020
European Commission (2011) Commission recommendations on the definition of nanomaterial (2011/696/EU)
European Commission (1995) Commission directive 95/45/EC of 26 July 1995 laying down specific purity criteria concerning colours for use in foodstuffs. Off J Eur Union L 226:1–45
European Commission (2012) Commission regulation (EU) No 231/2012 of 9 March 2012 laying down specifications for food additives listed in annexes II and III to regulation (EC) No 1333/2008 of the European Parliament and of the Council. Off J Eur Union 1–295
European Parliament and the Concil of the European Union (2008a) Regulation (EC) No 1333/2008 of the european parliament ans of the council of 16 December 2008 on food additives. Off J Eur Union 16–33
European Parliament and the Concil of the European Union (1962) Council Directive 2645/62 on the approximation of the rules of the Member States concerning the colouring matters authorized for use in foodstuffs intended for human consumption
European Parliament and the Concil of the European Union (2008) Regulation (EC) No 1331/2008 of the European Parliament and of the Council of 16 December 2008 establishing a common authorisation procedure for food additives, food enzymes and food flavourings (Text with EEA relevance) THE. Off J Eur Union L 354:1–6
European Parliament and the Concil of the European Union (2011) REGULATION (EU) No 1169/2011. Off J Eur Communities L304:18–63
European Parliament and the Concil of the European Union (1994) DIRECTIVE 94/36/EC on colours for use in foodstuffs. Off J Eur Communities L237:13–29. https://doi.org/10.1039/ap9842100196
FAO/WHO (1969) Specifications for the identity and purity of food additives and their toxicological evaluation: some food colours, emulsifiers, stabilizers, anticaking agents, and certain other substances
FDA (1966) Electronic code of federal regulations (eCFR). https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&SID=17723345ba7c363ef25a68e9776aa2cd&r=PART&n=21y1.0.1.1.27#se21.1.73_1575. Accessed 27 Jun 2020
Feldberg C (1983) The food and drug administration’s redbook: toxicological principles for the safety assessment of direct food additives and color additives used in food—international implications. Food Drug Cosmet Law J 38:368–372
Floros JD, Newsome R, Fisher W et al (2010) Feeding the world today and tomorrow: the importance of food science and technology. Compr Rev Food Sci Food Saf 9:572–599. https://doi.org/10.1111/j.1541-4337.2010.00127.x
Gázquez MJ, Bolívar JP, Garcia-Tenorio R, Vaca F (2014) A review of the production cycle of titanium dioxide pigment. Mater Sci Appl 05:441–458. https://doi.org/10.4236/msa.2014.57048
Geiss O, Ponti J, Senaldi C et al (2020) Characterisation of food grade titania with respect to nanoparticle content in pristine additives and in their related food products. Food Addit Contam Part A 37:239–253. https://doi.org/10.1080/19440049.2019.1695067
Godin B (2019) The invention of technological innovation: languages, discourses and ideology in historical perspective. Edward Elgar Publishing
Guillard A, Gaultier E, Cartier C et al (2020) Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO2 nanoparticles in an ex vivo placental perfusion model. Part Fibre Toxicol 17:51. https://doi.org/10.1186/s12989-020-00381-z
Guo Z, Martucci NJ, Moreno-Olivas F et al (2017) Titanium dioxide nanoparticle ingestion alters nutrient absorption in an in vitro model of the small intestine. NanoImpact 5:70–82. https://doi.org/10.1016/j.impact.2017.01.002
Heringa MB, Geraets L, van Eijkeren JCH et al (2016) Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations. Nanotoxicology 10:1515–1525. https://doi.org/10.1080/17435390.2016.1238113
Houdeau E, Lamas B, Lison D, Pierre F (2018) Nanoparticules et alimentation : un risque émergent en santé humaine ? Cah Nutr Diététique 53:312–321. https://doi.org/10.1016/j.cnd.2018.09.001
IARC (2006) Carbon black, titanium dioxide, and talc
Jain A, Vaya D (2017) Photocatalytic activity of TiO2 nanomaterial. J Chil Chem Soc 62:3683–3690. https://doi.org/10.4067/s0717-97072017000403683
Jasanoff S (1990) The fifth branch: science advisers as policymakers. Harvard University Press, Cambridge, Mass
Joly P-B (2017) Beyond the competitiveness framework? Models of innovation revisited. J Innov Econ 22:79. https://doi.org/10.3917/jie.pr1.0005
Joly P-B (2012) La fabrique de l’expertise scientifique : contribution des STS. Hermes (Wiesb) n° 64:22. https://doi.org/10.4267/2042/48377
Jovanović B (2015) Critical review of public health regulations of titanium dioxide, a human food additive. Integr Environ Assess Manag 11:10–20. https://doi.org/10.1002/ieam.1571
Justo-Hanani R, Dayan T (2015) European risk governance of nanotechnology: explaining the emerging regulatory policy. Res Policy 44:1527–1536. https://doi.org/10.1016/j.respol.2015.05.001
Kastrinos N, Weber KM (2020) Sustainable development goals in the research and innovation policy of the European Union. Technol Forecast Soc Change 157:120056. https://doi.org/10.1016/j.techfore.2020.120056
Khaoulani S, Chaker H, Cadet C et al (2015) Wastewater treatment by cyclodextrin polymers and noble metal/mesoporous TiO2 photocatalysts. Comptes Rendus Chim 18:23–31. https://doi.org/10.1016/j.crci.2014.07.004
Le Maire B, De Rugy F (2020) Arrêté du 17 avril 2019 portant suspension de la mise sur le marché des denrées contenant l’additif E171 (dioxyde de titane - TiO2)
Le Maire B, Pompili B, Griset A (2021) French government decree - Order of 21 December 2020 suspending the placing on the market of foodstuffs containing the additive E171
Lecourt R (2004) Le Codex Alimentarius : bases et actualité. Bull Acad Vet Fr 157:67–71. https://doi.org/10.4267/2042/47725
Lee KP, Trochimowicz HJ, Reinhardt CF (1985) Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years. Toxicol Appl Pharmacol 79:179–192. https://doi.org/10.1016/0041-008X(85)90339-4
Lehto S, Buchweitz M, Klimm A et al (2017) Comparison of food colour regulations in the EU and the US: a review of current provisions. Food Addit Contam Part A 34:335–355. https://doi.org/10.1080/19440049.2016.1274431
Lim J-H, Bae D, Fong A (2018) Titanium dioxide in food products: quantitative analysis using ICP-MS and Raman spectroscopy. J Agric Food Chem 66:13533–13540. https://doi.org/10.1021/acs.jafc.8b06571
Lupien JR (2016) An overview on the risk assessment by the Joint FAO/WHO expert committee on food additives. Toxicol Lett 259:S64. https://doi.org/10.1016/j.toxlet.2016.07.164
Manickam V, Velusamy RK, Lochana R et al (2017) Applications and genotoxicity of nanomaterials in the food industry. Environ Chem Lett 15:399–412. https://doi.org/10.1007/s10311-017-0633-3
Meisterernst A, Daniel H, Thron M (2006) Nanoparticules in food and cosmetics - scientific and legal aspects. Eur Food Feed Law Rev 1:69–77
Millstone E (2009) Science, risk and governance: radical rhetorics and the realities of reform in food safety governance. Res Policy 38:624–636. https://doi.org/10.1016/j.respol.2009.01.012
Ministère de la Transition Ecologique et Solidaire and Ministère de l’Economie et des Finances (2019) Dioxyde de titane : l’additif E171 sera interdit dans les denrées alimentaires à partir du 1er janvier 2020
Mobhe Bokoko D (2020) Responsible innovation and social innovation. J Innov Econ Manag n° 32:229. https://doi.org/10.3917/jie.032.0229
Musial J, Krakowiak R, Mlynarczyk DT et al (2020) Titanium dioxide nanoparticles in food and personal care products—What do we know about their safety? Nanomaterials 10:1110. https://doi.org/10.3390/nano10061110
National Research Council (US) Committee on the Institutional Means for Assessment of Risks to Public Health (1983) Risk assessment in the federal government. National Academies Press, Washington, D.C.
Oil and Colour Chemists’ Association (1983) Titanium dioxide pigments. Surface coatings. Springer, Netherlands, Dordrecht, pp 305–312
Oreskes N, Conway EM (2010) Defeating the merchants of doubt. Nature 465:686–687. https://doi.org/10.1038/465686a
Patel G, Patra C, Srinivas SP et al (2021) Methods to evaluate the toxicity of engineered nanomaterials for biomedical applications: a review. Environ Chem Lett 19:4253–4274. https://doi.org/10.1007/s10311-021-01280-1
Peters RJB, van Bemmel G, Herrera-Rivera Z et al (2014) Characterization of titanium dioxide nanoparticles in food products: analytical methods to define nanoparticles. J Agric Food Chem 62:6285–6293. https://doi.org/10.1021/jf5011885
Proquin H, Rodríguez-Ibarra C, Moonen CGJ et al (2017) Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nano-sized fractions. Mutagenesis 33:267–268. https://doi.org/10.1093/mutage/gew051
Ranjan S, Dasgupta N, Singh S, Gandhi M (2019) Toxicity and regulations of food nanomaterials. Environ Chem Lett 17:929–944. https://doi.org/10.1007/s10311-018-00851-z
Ranjan S, Ramalingam C (2016) Titanium dioxide nanoparticles induce bacterial membrane rupture by reactive oxygen species generation. Environ Chem Lett 14:487–494. https://doi.org/10.1007/s10311-016-0586-y
Romi R (2001) Codex alimentarius : de l’ambivalence à l’ambiguïté. Rev Jurid L’environnement 26:201–213. https://doi.org/10.3406/rjenv.2001.3897
Romig AD (2004) Nanotechnology: Scientific challenges and societal benefits and risks. Metall Mater Trans A 35:3641–3648. https://doi.org/10.1007/s11661-004-0270-x
Ropers M-H, Terrisse H, Mercier-Bonin M, Humbert B (2017) Titanium dioxide as food additive. In: Application of titanium dioxide. InTech, pp 3–22
Schot J, Steinmueller WE (2018) Three frames for innovation policy: R&D, systems of innovation and transformative change. Res Policy 47:1554–1567. https://doi.org/10.1016/j.respol.2018.08.011
Sengul AB, Asmatulu E (2020) Toxicity of metal and metal oxide nanoparticles: a review. Environ Chem Lett 18:1659–1683. https://doi.org/10.1007/s10311-020-01033-6
Skocaj M, Filipic M, Petkovic J, Novak S (2011) Titanium dioxide in our everyday life; is it safe? Radiol Oncol 45:227–247. https://doi.org/10.2478/v10019-011-0037-0
Sodano V (2018) Food nanotechnologies and policy challenges. Environ Chem Lett 16:5–10. https://doi.org/10.1007/s10311-017-0655-x
Sodano V, Gorgitano MT, Quaglietta M, Verneau F (2016) Regulating food nanotechnologies in the European Union: open issues and political challenges. Trends Food Sci Technol 54:216–226. https://doi.org/10.1016/j.tifs.2016.05.022
Sridhar A, Ponnuchamy M, Kumar PS, Kapoor A (2021) Food preservation techniques and nanotechnology for increased shelf life of fruits, vegetables, beverages and spices: a review. Environ Chem Lett 19:1715–1735. https://doi.org/10.1007/s10311-020-01126-2
St. Clair K (2017) The secret lives of color. Penguin Books
Sungur Ş, Kaya P, Koroglu M (2020) Determination of titanium dioxide nanoparticles used in various foods. Food Addit Contam Part B 13:260–267. https://doi.org/10.1080/19393210.2020.1769193
Touraine M, Le Foll S, Pinville M (2017) Dioxyde de titane (E171) : le Gouvernement saisit l’Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (Anses) sur les conclusions d’une étude de l’INRA
United Nations (1993) Report of the united nations conference on environment and development
USGS (2021) Titanium statistics and information. https://www.usgs.gov/centers/nmic/titanium-statistics-and-information. Accessed 31 Oct 2021
Uzunidis D, Kasmi F, Adatto L (eds) (2021a) Innovation economics, engineering and management Handbook 2. Wiley
Uzunidis D, Kasmi F, Adatto L (eds) (2021b) Innovation economics, engineering and management handbook 1. Wiley
Verleysen E, Waegeneers N, Brassinne F et al (2020) Physicochemical characterization of the pristine E171 food additive by standardized and validated methods. Nanomaterials 10:592. https://doi.org/10.3390/nano10030592
von Schomberg R, Hankins J (2019) International handbook on responsible innovation: a global resource. Edward Elgar Publishing, Cheltenham, UK
Weir A, Westerhoff P, Fabricius L et al (2012) Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol 46:2242–2250. https://doi.org/10.1021/es204168d
Yang Y, Doudrick K, Bi X et al (2014) Characterization of food-grade titanium dioxide: the presence of nanosized particles. Environ Sci Technol 48:6391–6400. https://doi.org/10.1021/es500436x
Yata VK (2019) Engineered nanostructured materials: benefits and risks. Environ Chem Lett 17:1523–1527. https://doi.org/10.1007/s10311-019-00893-x
Younes M, Aggett P, Aguilar F et al (2018) Evaluation of four new studies on the potential toxicity of titanium dioxide used as a food additive (E171). EFSA J. https://doi.org/10.2903/j.efsa.2018.5366
Younes M, Aquilina G, Castle L et al (2021) Safety assessment of titanium dioxide (E171) as a food additive. EFSA J. https://doi.org/10.2903/j.efsa.2021.6585
Younes M, Aquilina G, Castle L et al (2019) Scientific opinion on the proposed amendment of the EU specifications for titanium dioxide (E171) with respect to the inclusion of additional parameters related to its particle size distribution. EFSA J. https://doi.org/10.2903/j.efsa.2019.5760
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Boutillier, S., Fourmentin, S. & Laperche, B. History of titanium dioxide regulation as a food additive: a review. Environ Chem Lett 20, 1017–1033 (2022). https://doi.org/10.1007/s10311-021-01360-2
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DOI: https://doi.org/10.1007/s10311-021-01360-2