Article Cite This: J. Agric. Food Chem. 2018, 66, 6860−6868
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Realistic Evaluation of Titanium Dioxide Nanoparticle Exposure in Chewing Gum Fabio Fiordaliso,*,† Claudia Foray,† Monica Salio,† Mario Salmona,‡ and Luisa Diomede‡ †
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Unit of Bio-imaging, Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri”, 20156 Milan, Italy ‡ Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri”, 20156 Milan, Italy S Supporting Information *
ABSTRACT: There is growing concern about the presence of nanoparticles (NPs) in titanium dioxide (TiO2) as food additive (E171). To realistically estimate the number and the amount of TiO2 NPs ingested with food, we applied a transmission electron microscopy method combined with inductively coupled plasma optical emission spectrometry. Different percentages of TiO2 NPs (6−18%) were detected in E171 from various suppliers. In the eight chewing gums analyzed as food prototypes, TiO2 NPs were absent in one sample and ranged 0.01−0.66 mg/gum, corresponding to 7−568 billion NPs/gum, in the other seven. We estimated that the mass-based TiO2 NPs ingested with chewing gums by the European population ranged from 0.28 to 112.40 μg/kg b.w./day, and children ingested more nanosized titanium than adolescents and adults. Although this level may appear negligible it corresponds to 0.1−84 billion TiO2 NPs/kg b.w/day, raising important questions regarding their potential accumulation in the body, possibly causing long-term effects on consumers’ health. KEYWORDS: nanoparticles, titanium dioxide, E171, food, chewing gum
1. INTRODUCTION Titanium dioxide, with its whitening and brightening properties, is the most widespread pigment used in food products, cosmetics, paints and pigments as well as pharmaceuticals.1 It is authorized as a food color additive in the United States up to a concentration of 1% (w/w)2 and in Europe as E1713 to a quantum satis level.4 The presence of nanoparticles (NPs) in E171, defined as nano-objects with all external dimensions in the nanoscale range (500 nm), presumably of CaCO3, together with TiO2 particles similar to those in the other gums (Figure 5E). These cuboid crystals completely disappeared after acid treatment (Figure 5F), while TiO2 was still present with 15% of particles with diameter below 100 nm and 76% between 100 and 200 nm (SI Figure S2). We also examined an additional chewing gum (gum #8) which did not list E171 among its ingredients, but had a white coating similar in appearance to the other TiO2-containing coated gums. TEM analysis did not detect any TiO2 particles in the coating, even with the double number of gums (from 5 to 10) dissolved in 50 mL water (SI Figure S3). 3.3. Quantification of TiO2 and TiO2 NPs in Chewing Gums. ICP-OES analysis was carried out on each gum to quantify titanium and calculate the concentration of TiO2, expressed as mg/g of chewing gum and mg/piece of gum (Table 1). A great variability in the amount of TiO2 per chewing gum was found, ranging from the largest content of 15.25 mg/gum of gums #2 to 0.35 mg/gum of gum #7, in which CaCO3 was used as coating agent (Table 1). ICP-OES analysis did not reveal the presence of TiO2 in gum #8. These differences in TiO2 content among the chewing gums arise from the different amounts of E171 employed by the 6863
DOI: 10.1021/acs.jafc.8b00747 J. Agric. Food Chem. 2018, 66, 6860−6868
Article
Journal of Agricultural and Food Chemistry
Figure 4. TiO2 particle distribution in chewing gums. (A−F) Size distribution and representative images of TiO2 particles from gums #1 to #6. The percentages of TiO2 particles with diameter under 100 nm and 100−200 nm are reported. Scale bar = 200 nm.
3.4. Oral Intake Estimation of TiO2 and TiO2 NPs with Chewing Gums. These findings were employed to estimate the intake of TiO2 and TiO2 NPs resulting from chewing gum consumption. The daily intake of chewing gum at the 50th and 95th percentiles by European children (aged 6−12 years), adolescents (aged 13−17), and adults (aged 18−74 years) was considered.29 To estimate the TiO2 intake we took the range of 0.25−7.53 mg TiO2/g of gum resulting from ICP-OES analysis on our samples containing E171 (Table 1). In children, the mean TiO2 daily intake from chewing gum ranged from 0.47 to 14.08 mg/day, reaching 1.65−49.62 mg/day at the 95th percentile. Data were similar for adults (0.43−12.80 mg of TiO2/day and 1.79−53.84 mg of TiO2/day at the 50th and 95th percentiles) whereas a larger intake was estimated for adolescents, particularly those at the 95th percentile, for which we calculated a daily ingestion of 2.66−80.12 mg of TiO2 (Table 2A). When these values were normalized to the body weight (b.w.), children resulted to ingest 1.5 and 3 times more TiO2 than adolescents and adults (0.08−2.29 mg/kg b.w./day for children and 0.05−1.57 and 0.03−0.77 mg/kg b.w./day for
manufacturers, which ranged from a minimum of 0.03% (w/w) to a maximum of 0.75% (w/w) of the weight of the gum (Table 1). To quantify the TiO2 NPs in chewing gums, from the average diameter provided by TEM, we calculated at first the volume (as a sphere) for each TiO2 particle, and then from the volume, we computed the mass (considering anatase density 3.895 g/cm3). The sum of the weights of particles with diameter
