EN   EN 
 
 
 EUROPEAN  
COMMISSION   
Brussels, XXX   
SANTE/10896/2021 
(POOL/E2/2021/10896/10896 -EN)  
D075764/01  
[…](2021) XXX  draft  
 
COMMISSION REGULATION (EU) …/…  
of XXX  
amending Annexes II and III to Regulation (EC) No 1333/2008 of the European 
Parliament and of the Council as regards the food additive titanium dioxide (E 171)  
(Text with EEA relevance)   EN 1  EN COMMISSION REGULATION (EU) …/…  
of XXX  
amending Annexes II and III to Regulation (EC) No 1333/2008 of the European 
Parliament and of the Council as regards the food additive titanium dioxide (E 171)  
(Text with EEA relevance)  
THE EUROPEAN COMMISSION,  
Having regard to the Treaty on the Functioning of the European Union,  
Having regard to Regulation (EC) No 1333/2008 of the European Parliament and of the 
Council of 16 December 2008 on food additives1, and in particular Article 10(3) thereof,  
Having regard to 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 flavourings2, and in particular Article 7(5) thereof,  
Whereas:  
(1) Annex II to Regulation (EC) No 1333/2008 lays down a Union list of food additives 
approved for use in foods and their conditions of use.  
(2) Annex III to Regulation (EC) No 1333/2008 lays down a Union list of food additives 
approved for use in food additives, food enzymes, food flavourings, nutrients and their 
conditions of use.  
(3) Titanium dioxide (E 171) is a substance authorised as a colour in certain foods , in 
accordance with Annex II to Regulation (EC) No 1333/2008.  
(4) Pursuant to Article 3(1) of Regulation (EC) No 1331/2008, the Union list of food 
additives may be updated either on the initiative of the Commission or following an 
application.  
(5) Article 32(1) o f Regulation (EC) No 1333/2008  provides that all food additives that 
were already permitted in the Union before 20 January 2009 are  subject to a new risk 
assessment by the European Food Safety Authority (ʻthe Authority’).  
(6) On 14 September  2016, the Authority published a scientific opinion on the re -
evaluation of the safety of titanium dioxide (E 171) as a food additive3 concluding that 
the margins of safety calculated in the opinion would not be of concern. Nevertheless, 
the Authority recommended  additional toxicological testing, an extended 90 -day study 
or a multigeneration or extended -one generation reproduction toxicity study according 
to the current OECD guidelines, in order to be able to establish a health -based 
guidance value (acceptable dai ly intake - ADI) for titanium dioxide (E 171). The 
Authority also recommended amendments to the Union speciﬁcations for titanium 
dioxide (E 171) by introducing a characterisation of the particle size distribution and 
                                                 
1 OJ L 354, 31.12.2008, p. 16.  
2 OJ L 354, 31.12.2008, p. 1.  
3 EFSA Journal 2016;14(9):4545.  EN 2  EN the percentage of particles in the nano scale present in titanium dioxide (E 171) used as 
a food additive, and revising the maximum limits for impurities of toxic elements.  
(7) On 30 January 2017, the Commission launched a public call for scientific and 
technological data on titanium dioxide (E 171 ), targeting the data needs identified in 
the scientific opinion on the re -evaluation of this substance as a food additive.   
(8) On 2 October 2017 and 29 June 2018, in view of the recommendations made by the 
Authority, business operators made a proposal for th e amendment of the specifications 
for titanium dioxide (E 171) and submitted the necessary data. On 7 August 2018, the 
Commission requested the Authority to provide a scientific opinion on whether the 
data provided adequately support the proposed amendment  of the specifications for 
titanium dioxide (E 171).  
(9) On 12 July 2019, the Authority published a scientific opinion on the proposed 
amendments of the speciﬁcations for titanium dioxide (E 171) used as a food additive. 
The Authority concluded on additional parameters related to particle size distribution 
to be included in the specifications and recommended a revision of the definition of 
the food additive titanium dioxide (E 171) in the Union specifications. The Authority 
also concluded that, based on the pr oposed change in the specifications, revisiting the 
toxicological database on titanium dioxide (E 171) as a food additive should 
consequently be conducted in line with the data requirements specified in the 2018 
‘Guidance on risk assessment of the applicat ion of nanoscience and nanotechnologies 
in the food and feed chain’4. 
(10) On 6 March 2020, the Commission requested the Authority to assess the safety of the 
food additive titanium dioxide (E 171), taking into account the proposed amendments 
of the specificati ons, the data from an extended one generation reproductive study 
submitted by a consortium of interested business operators in reply to the public call 
for data launched in 2017 as well as all new relevant data available since the 
completion of the re -evaluation of titanium dioxide (E 171) in 2016, including the data 
considered to be in line with the data requirements specified in the 2018 Guidance on 
nanotechnology.  
(11) On 6 May 2021, the Authority published a scientific opinion on the safety assessment 
of tit anium dioxide (E 171) as a food additive5. In light of the opinion on the proposed 
amendments of the specifications and following the 2018 Guidance on 
nanotechnology, the opinion also takes into account, in addition to all new relevant 
data, the data on th e potential genotoxicity of titanium dioxide nanoparticles published 
before 2016, that had not previously been identified as relevant for the 2016 re -
evaluation. In its opinion the Authority indicated that,  based on all the evidence 
available, a concern fo r genotoxicity could not be ruled out, and given the many 
uncertainties, it concluded that titanium dioxide (E 171) can no longer be considered 
safe when used as a food additive. The Authority neither identified nor recommended 
any new studies that could a lleviate the genotoxicity concern and other remaining 
uncertainties.  
(12) In light of the conclusion of the 2021 Authority’s opinion about the safety of titanium 
dioxide (E 171) when used as a food additive, it is appropriate to remove the 
authorisation to use titanium dioxide (E 171) in foods.  Accordingly, titanium dioxide 
                                                 
4 EFSA Journal 2018;16(7):5327.  
5 EFSA Journal 2021;19(5):6585.  EN 3  EN (E 171) may no longer be used in foods . As titanium dioxide (E 171) would no longer 
be authorised for use in foods, it is also appropriate to remove the reference to it from 
the entry on the use of potassium aluminium silicate (E 555) as a carrier laid down in 
Part 1 of Annex III to Regulation (EC) No 1333/2008.   
(13) However, given that the Authority did not identify an immediate health concern linked 
to titanium dioxide (E 171) used as a food additive  and in order to allow for a smooth 
transition , it is appropriate that foods that contain titanium dioxide (E 171) used in 
accordance with the rules applicable before the date of entry into force of this 
Regulation may be placed on the market until six months after that date. Those foods  
may then continue to be marketed until their date of minimum durability or ‘use by’ 
date.  
(14) Directive 2009/35/EC of the European Parliament and of the Council6 restricts the use 
of colours in human and veterinary med icinal products to those authorised in 
accordance with Regulation (EC) No 1333/2008 on food additives, for which 
specifications are laid down in  Commission Regulation (EU) No 231/20127. Uses of 
excipients other than colours in medicinal products are subjec t to the Union rules on 
medicinal products and are evaluated as part of the overall benefit risk profile of a 
medicinal product.  
(15) In response to a request from the Commission, the European Medicines Agency 
(EMA) provided on 8 September 2021 a scientific an alysis on the technical purpose of 
the use of titanium dioxide (E 171) in medicinal products, the feasibility of 
replacement and possible timeframes for alternatives. In its conclusions, EMA 
indicated that t itanium dioxide is mainly used in medicinal produ cts as a colour and 
opacifier, even if it has  multiple  functions . It also stressed that titanium dioxide is used 
frequently in a number of essential medicinal products in oral -solid and oral semi -solid 
dosage forms. EMA also stressed that, from a technical  point of view, it should be 
possible to find alternatives to replace titanium dioxide (E 171) -containing coatings, 
both as colour and for other uses. However, it also underlined that its feasibility is not 
confirmed at this stage, as replacing titanium di oxide (E 171)  would impact in a 
negative manner the quality, safety and efficacy of medicinal products. EMA 
highlighted the need to carefully assess alternatives, notably to ensure their 
compatibility with the various components of individual pharmaceutica l products. The 
replacement of titanium dioxide (E 171)  in authorised medicinal products would 
require an individual review and assessment, possibly requiring bioequivalence 
studies. Furthermore, EMA concluded that it is difficult at this stage to recommen d a 
precise transition period timeframe for the replacement of titanium dioxide (E 171) 
used in medicinal products , as the time needed to reformulate each individual product 
could take several years, depending on the complexity of reformulation and studies  
required. Finally, considering the scale of the use of this excipient and the volume of 
products impacted, and taking into account  global supply chains, EMA stressed that a 
requirement to replace titanium dioxide (E 171) would almost certainly cause 
signi ficant medicines shortages on the Union market.   
                                                 
6 Direct ive 2009/35/EC of the European Parliament and of the Council of 23 April 2009 on the  colouring  
matters  which  may be added  to medicinal  products (OJ L 109, 30.4.2009, p. 10).  
7  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 (OJ L  83, 22.3.2012, p. 1).  EN 4  EN (16) On the basis of the EMA scientific analysis, and in order to avoid shortages of 
medicinal products that could have impacts on public health, titanium dioxide (E 171) 
should remain provisionally on the list of authorised additives to allow its use in 
medici nal products as a colour, pending the development of adequate alternatives to 
replace it while ensuring the quality, safety and efficacy of the medicinal products 
concerned.  During this time, titanium dioxide (E 171) should however be included in 
the list of colours that may not be sold directly to consumers.  
(17) It is of critical importance that the pharmaceutical industry makes any possible efforts 
to accelerate the research and development of alternatives that would be used as a 
replacement for titanium diox ide (E 171) in medicinal products , and to submit the 
necessary variation to the terms of the marketing authorisations concerned. In the 
absence of such efforts, competent authorities may request the concerned stakeholders 
to submit objective and verifiable  reason explaining the non -feasibility of the 
replacement .  
(18) The Commission is committed to review the necessity to maintain titanium dioxide (E 
171) or otherwise delete it from the Union list of food additives for exclusive use as a 
colour in medicinal pro ducts within three years after the date of entering into force of 
this Regulation.  This review should be based on an updated assessment of the EMA to 
be performed before 1 April 2024. It should take into account the progress made 
during this period to deve lop alternatives to titanium dioxide (E 171) in medicinal 
products both for new products and for replacing it in authorised products, and 
possible impacts on quality, safety and efficacy, as well as on the availability of 
medicinal products. Where replacem ent of titanium dioxide (E  171) in medicinal 
products has not taken place or been initiated within this period, only objective 
verifiable reasons related to the lack of  feasibility of its replacement should be taken 
into account.  
(19) Annexes II and III to Reg ulation (EC) No 1333/2008 should therefore be amended 
accordingly.  
(20) The measures provided for in this Regulation are in accordance with the opinion of the 
Standing Committee on Plants, Animals, Food and Feed,  
HAS ADOPTED THIS REGULATION:  
Article 1  
Annexes I I and III to Regulation (EC) No 1333/2008 are amended in accordance with the 
Annex to this Regulation.  
Article 2  
Until [publication office please introduce the date 6 months after the entry into force], foods 
produced in accordance with the rules applicab le before [publication office please introduce 
the date of entry into force] may continue to be placed on the market. After that date, they 
may remain on the market until their date of minimum durability or ‘use by’ date . 
Article 3  
The Commission shall, fo llowing consultation on the European Medicines Agency, review the 
necessity to maintain titanium dioxide (E 171) or to delete it from the Union list of food 
additives for the exclusive use as colour in medicinal products in Part B of Annex II to EN 5  EN Regulation  (EC) No 1333/2008 within three years after the date of entering into force of this 
Regulation.  
Article 4  
This Regulation shall enter into force on the twentieth day following that of its publication in 
the Official Journal of the European Union . 
This Regulation shall be binding in its entirety and directly applicable in all Member States.  
Done at Brussels,  
 For the Commission  
 The President  
 Ursula VON DER LEYEN