**2.1. Food categories with permitted use of TiO<sup>2</sup>**

The food colours of Group II, including titanium dioxide, are authorized in most food categories,1,2 such as (i) dairy products and analogues (flavoured fermented milk products and some creams), (ii) cheese and cheese products such as unripened cheese (Mozzarella, Codex Stan 262-2006 or fresh cheese, Codex Stan 221-2001), edible cheese rind, whey cheese, processed cheese, cheese products and dairy analogues including beverage whiteners, (iii) edible ices, (iv) confectionary (chewing gum, decorations, coatings and non-fruit-based fillings), (v) surimi and similar products and salmon substitutes, (vi) seasonings and condiments, mustard, soups and broths and sauces, and (vii) food supplements (Official Journal of the European Union, No 1129/2011). This list, despite its length, is in fact not exhaustive and the whole list with some restrictions of use is available on specialized websites.

Titanium dioxide was actually identified in chewing gums [1–3], confectionary [4, 5], sauces and dressings [5], non-dairy creamers [2, 5] and in dietary supplements [6]. According to a database collecting the details of new products (278,705) introduced on the market in 62 of the world's major economies, the use of TiO<sup>2</sup> increased constantly until 2014, representing a labelling on more than 3500 foods or drinks (Mintel GNPD database cited by the European Food Safety Agency EFSA [7]). If TiO<sup>2</sup> is found in only 1.3% of new products, it is nevertheless found in 51% of gums, 25% of stick, liquid and sprays, 21% of mixed assortments, 10% of

<sup>1</sup> https://webgate.ec.europa.eu/foods\_system/.

<sup>2</sup> http://www.fao.org/gsfaonline/additives/index.html.

pastilles, gums, jellies and chews and 10% of lollipops [7]. Chewing gums and confectionary, including pastilles, gums, jellies and chews, are the most widely concerned food categories, both in number of products labelled with TiO2 per category and in number of new products available on the market. Cakes and pastries represent a second category of importance. This scenario has to be regularly refined as the composition of food products may evolve [8, 9].

#### **2.2. Levels of consumption**

in food products (with a recent re-approval for a permitted use in food by the European Food Safety Agency), the use of titanium dioxide in food has risen some concerns in Western populations due to the presence of nanoparticles, that is, particles having one or more external dimensions in the size range of 1–100 nm. This review chapter targets an audience of practicing researchers, academics and PhD students, who are interested in the food applications of

 **in foods: function, properties and safety**

Titanium dioxide is a food additive without any nutritive value and added in processed foods to provide a whitening effect. It was first approved for use in food by the United States Food and Drug Administration (FDA) in 1966, then by the European Union in 1969, on the basis of the Codex Alimentarius of the Food and Agriculture Organization/World Health Organization (FAO/WHO). When used as a food colouring, it is labelled as E171 in Europe or INS171 in USA. In other fields, it is also called titanium white, Pigment White 6 or CI 77891. Time to time, it was re-evaluated for minor revisions of specifications in 2006, 2009, 2010 and 2012. In particular, the European Union decided in 2006 to allow the crystalline structure rutile in food in addition to the former authorized form anatase (COMMISSION DIRECTIVE 2006/33/ EC of 20 March 2006). Then, it was subjected to an in-depth evaluation in 2016 (EFSA 2016).

The food colours of Group II, including titanium dioxide, are authorized in most food

and some creams), (ii) cheese and cheese products such as unripened cheese (Mozzarella, Codex Stan 262-2006 or fresh cheese, Codex Stan 221-2001), edible cheese rind, whey cheese, processed cheese, cheese products and dairy analogues including beverage whiteners, (iii) edible ices, (iv) confectionary (chewing gum, decorations, coatings and non-fruit-based fillings), (v) surimi and similar products and salmon substitutes, (vi) seasonings and condiments, mustard, soups and broths and sauces, and (vii) food supplements (Official Journal of the European Union, No 1129/2011). This list, despite its length, is in fact not exhaustive and

Titanium dioxide was actually identified in chewing gums [1–3], confectionary [4, 5], sauces and dressings [5], non-dairy creamers [2, 5] and in dietary supplements [6]. According to a database collecting the details of new products (278,705) introduced on the market in 62 of

labelling on more than 3500 foods or drinks (Mintel GNPD database cited by the European

less found in 51% of gums, 25% of stick, liquid and sprays, 21% of mixed assortments, 10% of

the whole list with some restrictions of use is available on specialized websites.

such as (i) dairy products and analogues (flavoured fermented milk products

increased constantly until 2014, representing a

is found in only 1.3% of new products, it is neverthe-

this compound and the reasons of controversy.

**2.1. Food categories with permitted use of TiO<sup>2</sup>**

the world's major economies, the use of TiO<sup>2</sup>

Food Safety Agency EFSA [7]). If TiO<sup>2</sup>

https://webgate.ec.europa.eu/foods\_system/.

http://www.fao.org/gsfaonline/additives/index.html.

**2. Use of TiO2**

4 Application of Titanium Dioxide

categories,1,2

1

2

The amount of TiO2 consumed in the USA on a daily basis was estimated around 0.2–0.7 mg of TiO2 per kg of body weight per day (mg/kg bw/d), while the UK and German populations consume around 1 mg TiO2 /kg bw/day [4, 10]. These data were refined for all food categories, subpopulations and exposure scenarios in Netherlands [11, 12], in Germany [10] and in Europe [7]. For example, the estimate of the median long-term exposure to titanium dioxide (E 171) ranges from 0.5 (upper limit 1.1 mg/kg bw/d) for elderly adults to 1.4 mg/kg bw/d (upper limit 3.2 mg/kg bw/d) for children in Netherlands [12], close to the estimate in Germany [10].

Whatever the scenario of exposure and methodological choices, the biggest consumers of TiO2 are children (3–9 years) and teenagers (10–17 years) [4, 7, 10–12]. In the scenario exposure of EFSA, the contribution of chewing gums is weak in comparison to other confectionary including breath-refreshing microsweets, or sauces, salads and savoury-based sandwich spreads [7]. In the study based on the Dutch National Food Consumption Survey, the products most contributing to TiO2 intake for young children (2–6-year-olds) are confectionary (sweets, chocolate products and chewing gums) and fine bakery wares (biscuits). For 7–69-year-olds and elderly (70+), the same food items are identified but in a different decreasing order: chewing gums, coffee creamers, sauces, then fine bakery wares. As 10 food items most contributing to TiO2 intake represent 55%, we must keep in mind that TiO<sup>2</sup> intake is spread over many products, chewing gums contributing by only a few percentage points more than other food categories [11]. In a similar study performed in Germany, the food products that contribute the most to the total titanium intake by adults are savoury sauces, dressings, soft drinks and cheese (more than 75%) [10]. In addition to food products, tablets such as medicine and food supplements contain TiO2 up to 3.6 mg/g [13], resulting in a higher total daily intake of TiO2 .

#### **2.3. Specifications of TiO<sup>2</sup> for food applications**

In addition to the respect of the permitted use in the above-mentioned food categories, the powder introduced in these food products must respect five criteria, namely synthesis pathways, structure, purity, amounts and, certainly, absence of toxicity (Commission Regulation (EU) No 231/2012 and Joint FAO/WHO Expert Committee on Food Additives (JECFA) [14]). Firstly, these criteria are described according to the recommended specifications, then they are commented and discussed with literature data.

#### *2.3.1. Synthesis: sulphate and chloride processes*

Depending on the desired crystalline phase, titanium dioxide is produced by either the sulphate or the chloride process. The anatase phase of titanium dioxide can only be made by the sulphate process, while the rutile phase of titanium dioxide can be obtained from both processes but the chloride process is more sustainable and provides crystals with a narrower particle size distribution than the sulphate process [15].

Briefly, in the sulphate process, sulphuric acid is used to digest the ilmenite ore (FeTiO3 or FeO/TiO2 ) into iron(II) sulphate and titanium salt (Ti(SO<sup>4</sup> ) 2 ). Iron(II) sulphate is removed from the liquor after dilution and crystallization/filtration to yield only the titanium salt (Ti(SO<sup>4</sup> )2 ) in the digestion solution. Then, some microcrystals of anatase are introduced into the liquor which is then hydrolysed under carefully controlled conditions to produce crystals of anatase. These are subsequently filtered, washed, calcined and micronized [13, 15, 16]. The chloride process, which generates rutile crystals, consists of a chlorination of the ore into titanium and iron chlorides which are then separated by distillation. Titanium chloride is then treated to remove impurities and oxidized in a controlled flame reactor to yield TiO<sup>2</sup> rutile crystals with the desired size [15, 16]. In addition, titanium dioxide may be coated with small amounts of alumina and/or silica to improve the technological properties of the product, which are described as blocker for photocatalytic activity [14].

Certain rutile grades of titanium dioxide as platelet form are produced using mica as a template. The specific properties of this pigment (interference colour) are controlled by the thickness of the coated titanium dioxide layer and by the coating process [13].

#### *2.3.2. Crystallographic structure*

Currently, E171 forms consist essentially of pure anatase and/or rutile. Until 2006, only the anatase form was authorized for food applications. Rutile has been authorized to replace anatase in food products especially in film coatings for food supplement tablets and foodstuffs [13]. In both anatase and rutile structures, the basic building block consists of a titanium atom surrounded by six oxygen atoms (**Figure 1**). The structures differ by the distortion and assembly of the octahedra [17]. In rutile, these octahedra are connected via their corners and edges (**Figure 1**) and the unit cell dimensions are *a* = *b* = 4.587 and c = 2.953 Å. For anatase, the octahedra are linked via edges and planes forming a unit cell with *a* = *b* = 3.782 and c = 9.502 Å (**Figure 1**). In each structure, the two bonds between the titanium and the apical oxygen atoms are slightly longer than the others (1.983 and 1.946 Å in the rutile structure, 1.966 and 1.937 Å in the anatase structure). Moreover, a sizeable deviation from a 90° bond angle was observed in anatase (92.6 and 102.3 Å, **Figure 1**).

Although both forms are authorized in foods, the characterization of samples in American and European laboratories shows that anatase is the predominant crystalline structure found in food applications [1, 3, 4, 18–20]. For example, five out of six chewing gums contained TiO2 as anatase and only one contained a mixture of anatase and rutile [1]. Thus, the sulphate process seems to be predominant for obtaining pigmentary TiO2 for food applications.

In the bulk structure, the titanium cations have a coordination number of 6 meaning the oxygen anions have a coordination number of 3 resulting from the trigonal planar coordination (**Figure 1**). But at the surface, anions and cations are said to be 'coordinatively unsaturated'. The lowly coordinated cations (Ti5c) thus act as Lewis acids (electron pair acceptor) and are able to interact with electron donors like H<sup>2</sup> O. Similarly, twofold-coordinated O atoms

**Figure 1.** Bulk structures of (A) anatase, (B) rutile with (C) bond lengths and angles of the octahedrally coordinated Ti atoms in anatase, arranged from Diebold [17] and (D) arrangement of atoms on the (101) surface of anatase after adsorption and dissociation of water with Ti (grey filled balls), O from TiO2 structure (empty balls), O from water (big hatched balls) and H from water (small hatched balls).

(O2c) and named bridging oxygen atoms are Lewis base sites and are able to interact with electron acceptors like H<sup>+</sup> . Thus, once the oxide surface is exposed to moisture present in the atmosphere, it becomes fully covered with adsorbed water and hydroxyl groups. Molecularly adsorbed water in vacancies partly dissociates to form two kinds of hydroxyl groups: (1) terminal hydroxyls which are adsorbed onto Ti5c sites (TiOH) and (2) bridging hydroxyls which result from protonation of O2c atoms (Ti2 OH) [21]. Surface hydroxyl groups are able to behave as Brønsted acid or base sites when TiO2 particles are dispersed in water.

#### *2.3.3. Purity*

the sulphate process, while the rutile phase of titanium dioxide can be obtained from both processes but the chloride process is more sustainable and provides crystals with a narrower

Briefly, in the sulphate process, sulphuric acid is used to digest the ilmenite ore (FeTiO3

the liquor after dilution and crystallization/filtration to yield only the titanium salt (Ti(SO<sup>4</sup>

in the digestion solution. Then, some microcrystals of anatase are introduced into the liquor which is then hydrolysed under carefully controlled conditions to produce crystals of anatase. These are subsequently filtered, washed, calcined and micronized [13, 15, 16]. The chloride process, which generates rutile crystals, consists of a chlorination of the ore into titanium and iron chlorides which are then separated by distillation. Titanium chloride is then treated to

the desired size [15, 16]. In addition, titanium dioxide may be coated with small amounts of alumina and/or silica to improve the technological properties of the product, which are

Certain rutile grades of titanium dioxide as platelet form are produced using mica as a template. The specific properties of this pigment (interference colour) are controlled by the thick-

Currently, E171 forms consist essentially of pure anatase and/or rutile. Until 2006, only the anatase form was authorized for food applications. Rutile has been authorized to replace anatase in food products especially in film coatings for food supplement tablets and foodstuffs [13]. In both anatase and rutile structures, the basic building block consists of a titanium atom surrounded by six oxygen atoms (**Figure 1**). The structures differ by the distortion and assembly of the octahedra [17]. In rutile, these octahedra are connected via their corners and edges (**Figure 1**) and the unit cell dimensions are *a* = *b* = 4.587 and c = 2.953 Å. For anatase, the octahedra are linked via edges and planes forming a unit cell with *a* = *b* = 3.782 and c = 9.502 Å (**Figure 1**). In each structure, the two bonds between the titanium and the apical oxygen atoms are slightly longer than the others (1.983 and 1.946 Å in the rutile structure, 1.966 and 1.937 Å in the anatase structure). Moreover, a sizeable deviation from a 90° bond angle was observed in anatase (92.6 and 102.3 Å, **Figure 1**). Although both forms are authorized in foods, the characterization of samples in American and European laboratories shows that anatase is the predominant crystalline structure found in food applications [1, 3, 4, 18–20]. For example, five out of six chewing gums contained

as anatase and only one contained a mixture of anatase and rutile [1]. Thus, the sulphate

In the bulk structure, the titanium cations have a coordination number of 6 meaning the oxygen anions have a coordination number of 3 resulting from the trigonal planar coordination (**Figure 1**). But at the surface, anions and cations are said to be 'coordinatively unsaturated'. The lowly coordinated cations (Ti5c) thus act as Lewis acids (electron pair acceptor) and

) 2 or

)2 )

rutile crystals with

). Iron(II) sulphate is removed from

for food applications.

O. Similarly, twofold-coordinated O atoms

particle size distribution than the sulphate process [15].

described as blocker for photocatalytic activity [14].

*2.3.2. Crystallographic structure*

) into iron(II) sulphate and titanium salt (Ti(SO<sup>4</sup>

remove impurities and oxidized in a controlled flame reactor to yield TiO<sup>2</sup>

ness of the coated titanium dioxide layer and by the coating process [13].

process seems to be predominant for obtaining pigmentary TiO2

are able to interact with electron donors like H<sup>2</sup>

FeO/TiO2

6 Application of Titanium Dioxide

TiO2

In Europe as well as in the USA, the content in titanium dioxide must be no less than 99.0% on an aluminium oxide and silicon dioxide-free basis (Commission Regulation (EU) No 231/2012) and the amount of alumina and/or silica must not exceed 2%. The investigated samples complied with these specifications [18–20, 22]. Additionally, the Commission specifies that the loss on drying must be lower than 0.5% (105°C, 3 h) and the loss on ignition must represent less than 1.0% (800°C) on the dried basis. The acid-soluble substances must represent less than 0.5% (less than 1.5% for products containing alumina or silica) and the water-soluble matter must represent less than 0.5%. For impurities soluble in 0.5 N hydrochloric acid, their amount must be lower than 1 mg/kg for arsenic, cadmium and mercury, lower than 2 mg/kg for antimony and lower than 10 mg/kg for lead. These specifications are very similar to those given by JECFA [14].

#### *2.3.4. Amounts*

In Europe, titanium dioxide is authorized *at quantum satis*, whereas it is used in the USA in the limit of 1% by weight of food. Although no maximum use level is specified for this additive in Europe, it shall be used in accordance with the good manufacturing practices (GMPs), that is, at a level not higher than is necessary to achieve the intended technical effect. This decision was motivated by the fact that TiO2 was considered as an inactive ingredient in human food, and that neither significant absorption nor tissue storage following the ingestion of TiO<sup>2</sup> was possible. In its last report, the Panel of EFSA concluded that definitive and reliable data on the reproductive toxicity of E 171 are not yet available to enable the Panel to establish an acceptable daily intake (ADI) [7].

The quantification of TiO<sup>2</sup> in commercial products indicates that chewing gums are the food products richest in titanium dioxide [2, 4]. They contain between 0.7 and 5.4 mg Ti/g of food. The next category is sweets with 0–2.5 mg Ti/g food, followed by pastry with 0–0.5 mg Ti/g food [2]. In the report of EFSA, including more numerous food categories and data provided by industry, the highest maximum level in TiO2 is in decorations, coatings and fillings [7] with 20 mg TiO2 /g food which corresponds to 12 mg Ti/g food, a little bit above the maximum level reported for chewing gums (16 mg TiO<sup>2</sup> /g, i.e., 9.6 mg Ti/g food). Considering the mean use level, it is a little bit higher in processed nuts (3.8 mg Ti/g food) than in chewing gums (3.4 and 2.8 mg Ti/g food, depending on manufacturers), food supplements (2.8 mg Ti/g food) and salads and savoury-based sandwich spreads (2.5 mg Ti/g food).
