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1

Verleysen, Eveline, Nadia Waegeneers, Frédéric Brassinne, et al. "Physicochemical Characterization of the Pristine E171 Food Additive by Standardized and Validated Methods." Nanomaterials 10, no. 3 (2020): 592. http://dx.doi.org/10.3390/nano10030592.

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E171 (titanium dioxide) is a food additive that has been authorized for use as a food colorant in the European Union. The application of E171 in food has become an issue of debate, since there are indications that it may alter the intestinal barrier. This work applied standardized and validated methodologies to characterize representative samples of 15 pristine E171 materials based on transmission electron microscopy (TEM) and single-particle inductively coupled plasma mass spectrometry (spICP-MS). The evaluation of selected sample preparation protocols allowed identifying and optimizing the critical factors that determine the measurement of the particle size distribution by TEM. By combining optimized sample preparation with method validation, a significant variation in the particle size and shape distributions, the crystallographic structure (rutile versus anatase), and the physicochemical form (pearlescent pigments versus anatase and rutile E171) was demonstrated among the representative samples. These results are important for risk assessment of the E171 food additive and can contribute to the implementation of the European Food Safety Authority (EFSA) guidance on risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain.
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Hwang, Ji-Soo, Jin Yu, Hyoung-Mi Kim, Jae-Min Oh, and Soo-Jin Choi. "Food Additive Titanium Dioxide and Its Fate in Commercial Foods." Nanomaterials 9, no. 8 (2019): 1175. http://dx.doi.org/10.3390/nano9081175.

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Titanium dioxide (TiO2) is one of the most extensively utilized food additives (E171) in the food industry. Along with nanotechnology development, the concern about the presence of nanostructured particles in E171 TiO2 and commercial food products is growing. In the present study, the physicochemical properties of commercially available E171 TiO2 particles, including particle size distribution, were investigated, followed by their cytotoxicity and intestinal transport evaluation. The fate determination and quantification of E171 TiO2 in commercial foods were carried out based on the analytical procedure developed using simulated foods. The results demonstrated that TiO2 is a material mainly composed of particles larger than 100 nm, but present as an agglomerated or aggregated particle in commercial foods with amounts of less than 1% (wt/wt). Titanium dioxide particles generated reactive oxygen species and inhibited long-term colony formation, but the cytotoxicity was not related to particle size distribution or particle type (food- or general-grade). All TiO2 particles were mainly transported by microfold (M) cells, but also by intestinal tight junction. These findings will be useful for TiO2 application in the food industry and predicting its potential toxicity.
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Ferrante, Margherita, Alfina Grasso, Rossella Salemi, et al. "DNA Damage and Apoptosis as In-Vitro Effect Biomarkers of Titanium Dioxide Nanoparticles (TiO2-NPs) and the Food Additive E171 Toxicity in Colon Cancer Cells: HCT-116 and Caco-2." International Journal of Environmental Research and Public Health 20, no. 3 (2023): 2002. http://dx.doi.org/10.3390/ijerph20032002.

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This study investigated the DNA damage and apoptosis in colon cancer cells HCT-116 and Caco-2 induced by engineered titanium dioxide nanoparticles (TiO2-NPs) (60 nm) and titanium dioxide food additive E171. MTT assays showed that both chemical forms significantly reduced cancer cell viability in a dose-dependent manner. In particular the food additive E171 induced a pronounced inhibitory effect on the growth of HCT-116 and Caco-2 cell lines (E171 IC50: 3.45 mg/L for HTC-116 and 1.88 mg/L Caco-2; TiO2-NPs 60 nm IC50: 41.1 mg/L for HTC-116 and 14.3 mg/L for Caco-2). A low level of genotoxicity was observed in Caco-2 cells, especially when treated with TiO2 60 nm. Western blot analysis showed that HCT116 and Caco-2 treated cells did not overexpress apoptotic markers such as cleaved Caspase 3 and cleaved Parp. Moreover, further analysis by quantitative real-time PCR (qRT-PCR) showed that TiO2-NPs and E171 did not promote the expression of Bax or downregulation of Bcl-2, nor did they increase the Bax/Bcl-2 ratio. The assay data provide clear evidence that TiO2 can cause DNA damage but does not induce apoptosis or decrease long-term cell proliferation. In addition, the results show that E171 has a slightly higher level of cytotoxicity and genotoxicity. This suggests that exposure to E171 may be hazardous to health and that further research on biological effects is needed to promote safer practices in the use of this compound.
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4

Tsareva, Anastasiya A., Olga V. Egorova, Yuliya V. Demidova, and Nataliya A. Ilyushina. "Studying the ability of the food additive E171 (titanium dioxide) to induce gene mutations in bacteria." Hygiene and sanitation 102, no. 12 (2023): 1361–66. http://dx.doi.org/10.47470/0016-9900-2023-102-12-1361-1366.

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Introduction. Titanium dioxide in the Russian Federation is approved for use in the food industry, in the production of medicines and hygiene products. The food additive E171 is a mixture of micro- and nanoparticles of TiO2. In 2010, IARC classified TiO2 in nanoform as a probably carcinogenic to humans (Group 2B). In vitro and in vivo studies of the genotoxicity of titanium dioxide revealed contradictory results, indicating both the presence and absence of TiO2 mutagenicity. 
 The aim of the work is to evaluate the mutagenicity of the food additive E171 in the Ames test using standard and modified protocols.
 Materials and methods. The ability of food additive E171 (China) to induce reverse gene mutations in 5 strains of Salmonella typhimurium was studied under standard and modified conditions (cultivation of bacteria in the presence of methylated b-cyclodextrin (MCD) and/or pre-incubation for 1 hour in potassium phosphate buffer, pH 5.5 containing 10 mM NaCl and/or 3M MCD).
 Results. A sample of food additive E171 based on rutile titanium dioxide does not induce gene mutations in S. typhimurium in standard experiments. Modification of the Ames test protocol (decrease of the incubation mixture pH, addition of 10 mM NaCl) revealed statistically significant dose-dependent effects in TA100, TA98, and TA97 strains under metabolic incubation conditions. However, the fold increase of the number of revertants in the experimental plates compared to the negative control was < 2.
 Limitations. The research is limited to the mutagenicity assessment of food additive E171 (titanium dioxide) in the Ames test.
 Conclusion. The evaluation of the mutagenicity of titanium dioxide in other in vitro and in vivo tests taking into account the size and shape of the particles, is necessary to resolve the issue of its genetic safety as a food dye. A full range of studies will be performed on other samples of titanium dioxide presented in the market of the Russian Federation.
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5

Bischoff, Nicolaj S., Héloïse Proquin, Marlon J. Jetten, et al. "The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer." Nanomaterials 12, no. 8 (2022): 1256. http://dx.doi.org/10.3390/nano12081256.

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Titanium dioxide (TiO2) is present in many different food products as the food additive E171, which is currently scrutinized due to its potential adverse effects, including the stimulation of tumor formation in the gastrointestinal tract. We developed a transgenic mouse model to examine the effects of E171 on colorectal cancer (CRC), using the Cre-LoxP system to create an Apc-gene-knockout model which spontaneously develops colorectal tumors. A pilot study showed that E171 exposed mice developed colorectal adenocarcinomas, which were accompanied by enhanced hyperplasia in epithelial cells, lymphatic nodules at the base of the polyps, and increased tumor size. In the main study, tumor formation was studied following the exposure to 5 mg/kgbw/day of E171 for 9 weeks (Phase I). E171 exposure showed a statistically nonsignificant increase in the number of colorectal tumors in these transgenic mice, as well as a statistically nonsignificant increase in the average number of mice with tumors. Gene expression changes in the colon were analyzed after exposure to 1, 2, and 5 mg/kgbw/day of E171 for 2, 7, 14, and 21 days (Phase II). Whole-genome mRNA analysis revealed the modulation of genes in pathways involved in the regulation of gene expression, cell cycle, post-translational modification, nuclear receptor signaling, and circadian rhythm. The processes associated with these genes might be involved in the enhanced tumor formation and suggest that E171 may contribute to tumor formation and progression by modulation of events related to inflammation, activation of immune responses, cell cycle, and cancer signaling.
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6

Brassinne, F., S. De Vos, E. Verleysen, P. J. De Temmerman, M. Ledecq, and J. Mast. "Characterization of the TiO2 E171 food additive." Toxicology Letters 295 (October 2018): S208. http://dx.doi.org/10.1016/j.toxlet.2018.06.909.

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7

Rudometkina, T. F. "PHOTOMETRIC DETERMINATION OF E171 ADDITIVE IN FOOD PRODUCTS." EurasianUnionScientists 5, no. 63 (2019): 56–59. http://dx.doi.org/10.31618/esu.2413-9335.2019.5.63.177.

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8

Dorier, Marie, David Béal, Céline Tisseyre, et al. "The food additive E171 and titanium dioxide nanoparticles indirectly alter the homeostasis of human intestinal epithelial cells in vitro." Environmental Science: Nano 6, no. 5 (2019): 1549–61. http://dx.doi.org/10.1039/c8en01188e.

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9

Song, In-Gyu, Kanghee Kim, Hakwon Yoon, and June Woo Park. "Toxicity assessment of food additive (E171) in aquatic environments." Environmental Biology Research 41, no. 1 (2023): 41–53. http://dx.doi.org/10.11626/kjeb.2023.41.1.041.

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10

Baranowska-Wójcik, Ewa, Klaudia Gustaw, Dominik Szwajgier, et al. "Four Types of TiO2 Reduced the Growth of Selected Lactic Acid Bacteria Strains." Foods 10, no. 5 (2021): 939. http://dx.doi.org/10.3390/foods10050939.

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Food-grade titanium dioxide (TiO2) containing a nanoparticle fraction (TiO2 NPs -nanoparticles) is widely used as a food additive (E171 in the EU). In recent years, it has increasingly been raising controversies as to the presence or absence of its harmful effects on the gastrointestinal microbiota. The complexity and variability of microbiota species present in the human gastrointestinal tract impede the assessment of the impact of food additives on this ecosystem. As unicellular organisms, bacteria are a very convenient research model for investigation of the toxicity of nanoparticles. We examined the effect of TiO2 (three types of food-grade E171 and one TiO2 NPs, 21 nm) on the growth of 17 strains of lactic acid bacteria colonizing the human digestive tract. Each bacterial strain was treated with TiO2 at four concentrations (60, 150, 300, and 600 mg/L TiO2). The differences in the growth of the individual strains were caused by the type and concentration of TiO2. It was shown that the growth of a majority of the analyzed strains was decreased by the application of E171 and TiO2 NPs already at the concentration of 150 and 300 mg/L. At the highest dose (600 mg/L) of the nanoparticles, the reactions of the bacteria to the different TiO2 types used in the experiment varied.
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11

Baranowska-Wójcik, Ewa, Anna Rymuszka, Anna Sierosławska, and Dominik Szwajgier. "Effect of Food Additive E171 and Titanium Dioxide Nanoparticles (TiO2-NPs) on Caco-2 Colon Cancer Cells." Applied Sciences 14, no. 20 (2024): 9387. http://dx.doi.org/10.3390/app14209387.

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The food coloring agent E171 raises many questions concerning its negative impact on human health because of the fact that it contains nanoparticle fractions (NPs, diameter < 100 nm). Numerous studies showed its influence on organisms, including the ability to disrupt the intestinal barrier. In the present study, we verified the potential toxicity and pro-inflammatory activity of three different E171 samples (containing NPs fractions) and one TiO2 NPs sample (60–600 µg mL−1) towards Caco-2 colon cancer cells. The experiments revealed no significant changes in terms of the vitality of Caco-2 cells after 24 h of exposure (XTT test). However, after 72 h, a decrease in the proliferation of Caco-2 cells caused by three TiO2 substances was observed. Moreover, deterioration of the metabolic activity of Caco-2 cells (ATP test) by all analyzed substances at 300 and 600 µg mL−1 was seen. While a 24-h exposure to each tested substance resulted in a negligible release of LDH, a prolonged exposure (72 h) indicated an elevated release of LDH, suggesting potential toxicity. All TiO2 samples induced the elevated release of two primary proinflammatory cytokines, i.e., IL-1β and TNF-α, in a dose-independent manner. The discrepancies in the results come from the differences in the share of individual sizes in four TiO2 products.
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12

PONTI, Jessica. "Extraction of E171 or E172 food additives from sugar-based or lipid-based complex matrices for primary particles identification by electron microscopy." Open Research Europe 4 (December 18, 2024): 265. https://doi.org/10.12688/openreseurope.18678.1.

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Measurement of primary particle size distributions is fundamental to determining if a material should be classified as a nanomaterial according to the European Commission recommended definition. This is of particular relevance to alimentary products, where current regulation requires that any additives containing nanoforms be explicitly declared as such in the ingredients’ list. Currently, Electron Microscopy is the only instrumental technique able to reliably classify materials as nanomaterials. To verify the nanostatus of a material using this technique, it is essential to firstly extract the additives from the matrix in which they are dispersed, and then measure a wide size distribution while avoiding artefacts from the food matrix. In this operating procedure, extraction protocols, developed and applied for sugar-based or lipid-based food, are described. In particular, case studies for titanium dioxide E171 and iron oxide/iron hydroxide based materials such as E172 are considered. The protocols are based on gentle extraction of the additive materials and could, in principle, be used for other nanomaterials provided they are not soluble in water or ethanol and are resistant to enzymatic reactions. The size distribution of the extracted material can then be determined from images acquired using scanning and/or transmission electron microscopy.
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13

Grasso, Alfina, Margherita Ferrante, Pietro Zuccarello, et al. "Chemical Characterization and Quantification of Titanium Dioxide Nanoparticles (TiO2-NPs) in Seafood by Single-Particle ICP-MS: Assessment of Dietary Exposure." International Journal of Environmental Research and Public Health 17, no. 24 (2020): 9547. http://dx.doi.org/10.3390/ijerph17249547.

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The significant increase in the production and variety of nanoparticles (NPs) has led to their release into the environment, especially into the marine environment. Titanium dioxide nanoparticles (TiO2-NPs) are used in different industrial sectors, from the food industry to several consumer and household products. Since the aquatic environment is highly sensitive to contamination by TiO2-NPs, this work aimed to give a preliminary assessment of the contamination of packaged seafood, where the food additive TiO2 (E171) is not to be intentionally added. This allowed providing a chemical characterization and quantification of TiO2-NPs in processed canned fish products belonging to different trophic positions of the pelagic compartment and in canned clam. The new emerging technique called single-particle inductively coupled plasma mass spectrometry (spICP-MS) was applied, which allows the determination of nanoparticle number-based concentration, as well as the dissolved titanium. This study highlights how processed food, where the pigment E171 was not intentionally added, contains TiO2 in its nanoparticle form, as well as dissolved titanium. Processed clam represented the seafood with the highest content of TiO2-NPs. In pelagic fish species, we found progressively higher levels and smaller sizes of TiO2-NPs from smaller to larger fish. Our results highlight the importance of planning the characterization and quantification of TiO2-NPs in food both processed and not, as well as where the pigment E171 is intentionally added and not, as it is not the only source of TiO2-NPs. This result represents a solid step toward being able to estimate the real level of dietary exposure to TiO2-NPs for the general population and the related health risks.
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14

Krivobok, V. S., A. V. Kolobov, S. E. Dimitrieva, et al. "Raman Markers of Toxic Nanofraction in Anatase TiO2 Micropowder Used as E171 Food Additive." Journal of Russian Laser Research 42, no. 4 (2021): 388–98. http://dx.doi.org/10.1007/s10946-021-09974-1.

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15

Proquin, Héloïse, Marlon J. Jetten, Marloes C. M. Jonkhout, et al. "Gene expression profiling in colon of mice exposed to food additive titanium dioxide (E171)." Food and Chemical Toxicology 111 (January 2018): 153–65. http://dx.doi.org/10.1016/j.fct.2017.11.011.

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16

Blaznik, Urška, Sanja Krušič, Maša Hribar, Anita Kušar, Katja Žmitek, and Igor Pravst. "Use of Food Additive Titanium Dioxide (E171) before the Introduction of Regulatory Restrictions Due to Concern for Genotoxicity." Foods 10, no. 8 (2021): 1910. http://dx.doi.org/10.3390/foods10081910.

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Food-grade titanium dioxide (TiO2; E171) is a coloring food additive. In May 2021, a scientific opinion was published by the European Food Safety Authority concluding that TiO2 can no longer be considered as a safe food additive. Our aim was to investigate the trends in the use of TiO2 in the food supply. A case study was conducted in Slovenia using two nationally representative cross-sectional datasets of branded foods. Analysis was performed on N = 12,644 foods (6012 and 6632 in 2017 and 2020, respectively) from 15 food subcategories where TiO2 was found as a food additive. A significant decrease was observed in the use of TiO2 (3.6% vs. 1.8%; p < 0.01). TiO2 was most often used in the chewing gum category (36.3%) in 2017, and chocolate and sweets category (45.9%) in 2020. Meanwhile, in 2017, the largest share of TiO2-containing foods was observed in the chewing gum category, namely, 70.3%, and these products presented over 85% of the market share. In 2020, only 24.6% of chewing gums contained TiO2, which accounted for only 3% of the market share. In conclusion, we showed an overall decrease in TiO2 use, even though it has not yet been officially removed from the list of authorized food additives.
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17

Proquin, Héloïse, Carolina Rodríguez-Ibarra, Carolyn G. J. Moonen, et al. "Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nano-sized fractions." Mutagenesis 32, no. 1 (2016): 139–49. http://dx.doi.org/10.1093/mutage/gew051.

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18

Proquin, Héloïse, Carolina Rodríguez-Ibarra, Carolyn Moonen, et al. "Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nano-sized fractions." Mutagenesis 33, no. 3 (2018): 267–68. http://dx.doi.org/10.1093/mutage/gey011.

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19

Bischoff, N. S., S. G. Breda, J. J. Briedé, et al. "P13-25 Evaluating the effects of food additive E171 on colorectal cancer risk: a human dietary intervention study." Toxicology Letters 399 (September 2024): S220. http://dx.doi.org/10.1016/j.toxlet.2024.07.541.

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20

Bellani, Lorenza, Simonetta Muccifora, Francesco Barbieri, Eliana Tassi, Monica Ruffini Castiglione, and Lucia Giorgetti. "Genotoxicity of the food additive E171, titanium dioxide, in the plants Lens culinaris L. and Allium cepa L." Mutation Research/Genetic Toxicology and Environmental Mutagenesis 849 (January 2020): 503142. http://dx.doi.org/10.1016/j.mrgentox.2020.503142.

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21

Bischoff, Nicolaj S., Theo M. de Kok, Dick T. H. M. Sijm, et al. "Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System." International Journal of Molecular Sciences 22, no. 1 (2020): 207. http://dx.doi.org/10.3390/ijms22010207.

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Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2.
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22

Brugiroux, Sandrine, Thomas Sauvaitre, Gwenaelle Roche, et al. "Su1976 – Impacts of Additive Food E171 (Titanium Dioxide) on the Gut Microbiota and Colorectal Carcinogenesis in ApcMIN/+ Murine Model." Gastroenterology 156, no. 6 (2019): S—679. http://dx.doi.org/10.1016/s0016-5085(19)38610-x.

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23

A.R.Ergashov. "THE IMPORTANCE OF E171 DYE IN THE FOOD INDUSTRY AND ITS EFFECT ON THE BODY." INTERNATIONAL BULLETIN OF MEDICAL SCIENCES AND CLINICAL RESEARCH 3, no. 5 (2023): 284–88. https://doi.org/10.5281/zenodo.8000688.

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TiO2 (E 171) is a pigment used to alter the visual properties of food and beverages. It is also used in cosmetics, pharmaceuticals, and toothpastes, which means that we may also come in contact with the substance while taking medicines or using personal hygiene products such as toothpastes or mouthwashes. Titanium dioxide (TiO2) nanoparticles (NPs) have been widely applied in various industrial fields, such as electronics, packaging, food, and cosmetics. Titanium dioxide (TiO2) is commonly applied to enhance the white colour and brightness of food products. TiO2 is also used as white pigment in other products such as toothpaste. A small fraction of the pigment is known to be present as nanoparticles (NPs). Submicron-sized TiO2 particles, in Europe listed as E 171, are widely used as a food additive although the relevant risk assessment has never been satisfactorily completed. For example, it is not possible to derive a safe daily intake of TiO2 from the available long-term feeding studies in rodents.
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24

Gmoshinski, I. V., O. V. Bagryantseva, and S. A. Khotimchenko. "Toxicological and hygienic assessment of titanium dioxide nanoparticles as a component of E171 food additive (review of the literature and metahanalysis)." Health Risk Analysis, no. 2 (June 2019): 145–63. http://dx.doi.org/10.21668/health.risk/2019.2.17.

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25

Gmoshinski, I. V., O. V. Bagryantseva, and S. A. Khotimchenko. "Toxicological and hygienic assessment of titanium dioxide nanoparticles as a component of E171 food additive (review of the literature and metahanalysis)." Health Risk Analysis, no. 2 (June 2019): 145–63. http://dx.doi.org/10.21668/health.risk/2019.2.17.eng.

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Talamini, Laura, Sara Gimondi, Martina B. Violatto, et al. "Repeated administration of the food additive E171 to mice results in accumulation in intestine and liver and promotes an inflammatory status." Nanotoxicology 13, no. 8 (2019): 1087–101. http://dx.doi.org/10.1080/17435390.2019.1640910.

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27

Warheit, D. "P24-38: EFSA Made a Manifest Error on the Safety of Titanium Dioxide (E171) Particles as a Food Additive for Humans." Toxicology Letters 384 (September 2023): S279. http://dx.doi.org/10.1016/s0378-4274(23)00920-7.

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Bencherit, Djihad, Kheira Laoues, Imane Karboua, and Mohamed Lounis. "Survey of harmful dyes in food color additives in Algeria." Electronic Journal of Medical and Dental Studies 13, no. 3 (2023): em0106. http://dx.doi.org/10.29333/ejmds/13105.

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Food colors are pervasive in our diet. However, some of them are involved in health concerns reaching carcinogenicity and reproductive toxicity. This is a survey of prepackaged color additives marketed to the simple consumer in Algeria. This exploration aimed to assess the compliance of the labeling of color additives, as well as the investigation of the presence of harmful dyes, namely E102, E110, E 121, E122, E123, E124, E127, E129, E132, E133, E143, and E171, in their composition. Our findings reveal the labeling compliance of 50.5% of analyzed coloring products and the absence of ingredient labeling for 1.6% of analyzed coloring products. While 47.8% of the products displayed different labeling flaws. Except for the dyes E121, E129, and E143, the other requested dyes have been determined. In fact, dyes E102 (39%), E110 (23%), and E171 (20%) were the most frequent. Moreover, 32.6% of all analyzed coloring products included two harmful dyes. Surprisingly, almost 3% of all assessed coloring products provided three harmful dyes simultaneously. Taken together, these results encourage further investigations of the presence of harmful dyes in our food and to establish more stringent rules governing the marketing and the use of coloring additives.
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Dorier, Marie, Céline Tisseyre, Fanny Dussert, et al. "Toxicological impact of acute exposure to E171 food additive and TiO2 nanoparticles on a co-culture of Caco-2 and HT29-MTX intestinal cells." Mutation Research/Genetic Toxicology and Environmental Mutagenesis 845 (September 2019): 402980. http://dx.doi.org/10.1016/j.mrgentox.2018.11.004.

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Tassinari, Roberta, Alessia Tammaro, Andrea Martinelli, Mauro Valeri, and Francesca Maranghi. "Sex-Specific Effects of Short-Term Oral Administration of Food-Grade Titanium Dioxide Nanoparticles in the Liver and Kidneys of Adult Rats." Toxics 11, no. 9 (2023): 776. http://dx.doi.org/10.3390/toxics11090776.

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Titanium dioxide (TiO2) nanomaterial is used in several items (implant materials, pills composition, cosmetics, etc.). Although TiO2 is no longer considered safe as a food additive, the general population is exposed daily through different routes, and information is lacking on some aspects of animal and human health. This study evaluated liver and kidney toxicity of food-grade TiO2 nanoparticles (NPs) (primary size < 25 nm) in male and female rats that were orally exposed for 5 days to 0, 1, and 2 mg/kg body weight per day (comparable with daily E171 consumption). Selected liver and kidney toxicity endpoints included serum biomarkers, histopathological analysis and expression of osteopontin (SPP1), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and neuropeptide Y (NPY). Although TiO2 NPs are known to affect the gastric mucosa, short-term exposure induced sex-specific effects: general toxicity parameters were predominantly altered in female rats, whereas the liver appeared to be more affected than the kidneys in male rats, which also showed overexpression of NPY and SPP1. In the kidneys, the TiO2 NP effects were quantitatively similar but qualitatively different in the two sexes. In conclusion, careful consideration should be paid to the presence of TiO2 NPs in other items that can lead to human exposure.
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Bucher, Guillaume, Hind El Hadri, Océane Asensio, François Auger, Josefa Barrero, and Jean-Philippe Rosec. "Large-scale screening of E171 food additive (TiO2) on the French market from 2018 to 2022: Occurrence and particle size distribution in various food categories." Food Control 155 (January 2024): 110102. http://dx.doi.org/10.1016/j.foodcont.2023.110102.

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Laisney, Jérôme, Mireille Chevallet, Caroline Fauquant, et al. "Ligand-Promoted Surface Solubilization of TiO2 Nanoparticles by the Enterobactin Siderophore in Biological Medium." Biomolecules 12, no. 10 (2022): 1516. http://dx.doi.org/10.3390/biom12101516.

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Titanium dioxide nanoparticles (TiO2-NPs) are increasingly used in consumer products for their particular properties. Even though TiO2 is considered chemically stable and insoluble, studying their behavior in biological environments is of great importance to figure their potential dissolution and transformation. The interaction between TiO2-NPs with different sizes and crystallographic forms (anatase and rutile) and the strong chelating enterobactin (ent) siderophore was investigated to look at a possible dissolution. For the first time, direct evidence of anatase TiO2-NP surface dissolution or solubilization (i.e., the removal of Ti atoms located at the surface) in a biological medium by this siderophore was shown and the progressive formation of a hexacoordinated titanium–enterobactin (Ti–ent) complex observed. This complex was characterized by UV–visible and Fourier transform infrared (FTIR) spectroscopy (both supported by Density Functional Theory calculations) as well as electrospray ionization mass spectrometry (ESI-MS) and X-ray photoelectron spectroscopy (XPS). A maximum of ca. 6.3% of Ti surface atoms were found to be solubilized after 24 h of incubation, releasing Ti–ent complexes in the micromolar range that could then be taken up by bacteria in an iron-depleted medium. From a health and environmental point of view, the effects associated to the solubilization of the E171 TiO2 food additive in the presence of enterobactin and the entrance of the Ti–enterobactin complex in bacteria were questioned.
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Wang, Yidan, Allan Sauvat, Celine Lacrouts, et al. "TiO2 Nanomaterials Non-Controlled Contamination Could Be Hazardous for Normal Cells Located in the Field of Radiotherapy." International Journal of Molecular Sciences 21, no. 3 (2020): 940. http://dx.doi.org/10.3390/ijms21030940.

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Among nanomaterials (NMs), titanium dioxide (TiO2) is one of the most manufactured NMs and can be found in many consumers’ products such as skin care products, textiles and food (as E171 additive). Moreover, due to its most attractive property, a photoactivation upon non-ionizing UVA radiation, TiO2 NMs is widely used as a decontaminating agent. Uncontrolled contaminations by TiO2 NMs during their production (professional exposure) or by using products (consumer exposure) are rather frequent. So far, TiO2 NMs cytotoxicity is still a matter of controversy depending on biological models, types of TiO2 NMs, suspension preparation and biological endpoints. TiO2 NMs photoactivation has been widely described for UV light radiation exposure, it could lead to reactive oxygen species production, known to be both cyto- and genotoxic on human cells. After higher photon energy exposition, such as X-rays used for radiotherapy and for medical imaging, TiO2 NMs photoactivation still occurs. Importantly, the question of its hazard in the case of body contamination of persons receiving radiotherapy was never addressed, knowing that healthy tissues surrounding the tumor are indeed exposed. The present work focuses on the analysis of human normal bronchiolar cell response after co-exposition TiO2 NMs (with different coatings) and ionizing radiation. Our results show a clear synergistic effect, in terms of cell viability, cell death and oxidative stress, between TiO2 NMS and radiation.
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Espada-Bernabé, Elena, Gustavo Moreno-Martín, Beatriz Gómez-Gómez, and Yolanda Madrid. "Assesing the behaviour of particulate/nanoparticulate form of E171 (TiO2) food additive in colored chocolate candies before and after in vitro oral ingestion by spICP-MS, TEM and cellular in vitro models." Food Chemistry 432 (January 2024): 137201. http://dx.doi.org/10.1016/j.foodchem.2023.137201.

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Bischoff, Nicolaj, Héloïse Proquin, Marlon Jetten, et al. "Correction: Bischoff et al. The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer. Nanomaterials 2022, 12, 1256." Nanomaterials 13, no. 21 (2023): 2888. http://dx.doi.org/10.3390/nano13212888.

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Kaminski, Norbert E., and Samuel M. Cohen. "Comment on Bischoff et al. The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer. Nanomaterials 2022, 12, 1256." Nanomaterials 13, no. 9 (2023): 1551. http://dx.doi.org/10.3390/nano13091551.

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Bautista-Pérez, Rocío, Agustina Cano-Martínez, Manuel Alejandro Herrera-Rodríguez, et al. "Oral Exposure to Titanium Dioxide E171 and Zinc Oxide Nanoparticles Induces Multi-Organ Damage in Rats: Role of Ceramide." International Journal of Molecular Sciences 25, no. 11 (2024): 5881. http://dx.doi.org/10.3390/ijms25115881.

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Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed. Histological examination was performed with hematoxylin–eosin (HE) staining and transmission electron microscopy (TEM). Ceramide (Cer), 3-nitrotyrosine (NT), and lysosome-associated membrane protein 2 (LAMP-2) were detected by immunofluorescence. Relevant histological changes were observed: disorganization, inflammatory cell infiltration, and mitochondrial damage. Increased levels of Cer, NT, and LAMP-2 were observed in the liver, kidney, and brain of E171- and ZnO NPs-exposed rats, and in rat hearts exposed to ZnO NPs. E171 up-regulated Cer and NT levels in the aorta and heart, while ZnO NPs up-regulated them in the aorta. Both NPs increased LAMP-2 expression in the intestine. In conclusion, chronic oral exposure to metallic NPs causes multi-organ injury, reflecting how these food additives pose a threat to human health. Our results suggest how complex interplay between ROS, Cer, LAMP-2, and NT may modulate organ function during NP damage.
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Waegeneers, Nadia, Sandra De Vos, Eveline Verleysen, Ann Ruttens, and Jan Mast. "Estimation of the Uncertainties Related to the Measurement of the Size and Quantities of Individual Silver Nanoparticles in Confectionery." Materials 12, no. 17 (2019): 2677. http://dx.doi.org/10.3390/ma12172677.

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E174 (silver) is a food additive that may contain silver nanoparticles (AgNP). Validated methods are needed to size and quantify these particles in a regulatory context. However, no validations have yet been performed with food additives or real samples containing food additives requiring a sample preparation step prior to analysis. A single-particle inductively coupled plasma mass spectrometry (spICP-MS) method was developed and validated for sizing and quantifying the fraction of AgNP in E174 and in products containing E174, and associated uncertainties related to sample preparation, analysis and data interpretation were unraveled. The expanded measurement uncertainty for AgNP sizing was calculated to be 16% in E174-containing food products and increased up to 23% in E174 itself. The E174 food additives showed a large silver background concentration combined with a relatively low number of nanoparticles, making data interpretation more challenging than in the products. The standard uncertainties related to sample preparation, analysis, and challenging data interpretation were respectively 4.7%, 6.5%, and 6.0% for triplicate performances. For a single replicate sample, the uncertainty related to sample preparation increased to 6.8%. The expanded measurement uncertainty related to the concentration determination was 25–45% in these complex samples, without a clear distinction between additives and products. Overall, the validation parameters obtained for spICP-MS seem to be fit for the purpose of characterizing AgNP in E174 or E174-containing products.
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Vitulo, Manuela, Elisa Gnodi, Raffaella Meneveri, and Donatella Barisani. "Interactions between Nanoparticles and Intestine." International Journal of Molecular Sciences 23, no. 8 (2022): 4339. http://dx.doi.org/10.3390/ijms23084339.

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The use of nanoparticles (NPs) has surely grown in recent years due to their versatility, with a spectrum of applications that range from nanomedicine to the food industry. Recent research focuses on the development of NPs for the oral administration route rather than the intravenous one, placing the interactions between NPs and the intestine at the centre of the attention. This allows the NPs functionalization to exploit the different characteristics of the digestive tract, such as the different pH, the intestinal mucus layer, or the intestinal absorption capacity. On the other hand, these same characteristics can represent a problem for their complexity, also considering the potential interactions with the food matrix or the microbiota. This review intends to give a comprehensive look into three main branches of NPs delivery through the oral route: the functionalization of NPs drug carriers for systemic targets, with the case of insulin carriers as an example; NPs for the delivery of drugs locally active in the intestine, for the treatment of inflammatory bowel diseases and colon cancer; finally, the potential concerns and side effects of the accidental and uncontrolled exposure to NPs employed as food additives, with focus on E171 (titanium dioxide) and E174 (silver NPs).
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Pannek, Carolin, Karina R. Tarantik, Laura Engel, Thomas Vetter, and Jürgen Wöllenstein. "Gasochromic Detection of NO2 on the Example of the Food Additive E141 (ii)." Proceedings 2, no. 13 (2018): 721. http://dx.doi.org/10.3390/proceedings2130721.

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We present our investigation on the gasochromic reaction of E141 (ii) towards the toxic gas nitrogen dioxide (NO2). E141 (ii) is a chlorophyllin-based food additive, typically used as green coloring for nearly all kinds of sweets. In this presentation we show an alternative approach for using E141 (ii) as optical gas indicator. All solid samples are prepared by multi-layer screen printing on different substrates like paper and PE-foil. Gas measurements are performed using an UV/Vis spectrometer. The influence of the substrate and according layer thickness is shown.
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Bischoff, Nicolaj S., Héloïse Proquin, Marlon J. Jetten, et al. "Reply to Kaminski, N.E.; Cohen, S.M. Comment on “Bischoff et al. The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer. Nanomaterials 2022, 12, 1256”." Nanomaterials 13, no. 9 (2023): 1552. http://dx.doi.org/10.3390/nano13091552.

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42

Abuzaid, Hanan O., Abdelmnim M. Altwaiq, Leen N. Ali, Manal Alkhabbas, and Sa’ib Khouri. "Quantitative Analysis of Titanium Dioxide (TiO2) Levels as Food Additives in Various Food Samples from the Jordanian Market." Methods and Objects of Chemical Analysis 20, no. 2 (2025): 135–42. https://doi.org/10.17721/moca.2025.135-142.

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This study presents a quantitative determination of titanium dioxide (TiO2, E171) in food products frequently consumed by children. An optimized acid digestion method using concentrated sulfuric acid, nitric acid, and hydrogen peroxide at 200 °C for 45 minutes was developed to efficiently extract TiO2 from food matrices. The recovered TiO2 was quantified using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) and UV–Visible spectrophotometry. Both methods were successfully applied to twentyfive food products from the Jordanian market, including chewing gums, candies, and powdered juices. Structural and morphological characterization of the extracted TiO2 was carried out using Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), and Dynamic Light Scattering (DLS). XRD confirmed the presence of both anatase and rutile crystalline phases, while SEM revealed irregular particle morphology. FTIR spectra showed characteristic Ti–O vibrations, and DLS analysis indicated that the particle sizes were in the micrometer range, with no evidence of engineered nanoparticles. The proposed approach enables accurate monitoring of TiO2 content in foods and supports regulatory efforts to evaluate consumer exposure to E171, particularly in products marketed to children.
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De Vos, Sandra, Nadia Waegeneers, Eveline Verleysen, Karen Smeets, and Jan Mast. "Physico-chemical characterisation of the fraction of silver (nano)particles in pristine food additive E174 and in E174-containing confectionery." Food Additives & Contaminants: Part A 37, no. 11 (2020): 1831–46. http://dx.doi.org/10.1080/19440049.2020.1809719.

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Aldabayan, Yousef Saad. "Effect of Artificial Food Additives on Lung Health—An Overview." Medicina 61, no. 4 (2025): 684. https://doi.org/10.3390/medicina61040684.

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This review focuses on the potential health risks of artificial food additives, especially their effects on lung health. Preservatives, synthetic colorants, and flavor enhancers, which are commonly used in processed foods, play roles in worsening respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). These additives cause oxidative stress, systemic inflammation, and immune dysregulation, often through the gut-lung axis. The preservatives sodium nitrite and sulfites have the risk of causing bronchial hyper-responsiveness and allergic reactions. The synthetic colorant, Ponceau 4R, is also related to immune-mediated lung inflammation. Flavoring agents such as diacetyl contribute to occupational respiratory diseases like bronchiolitis obliterans. In animal models, prenatal exposure to additives, such as titanium dioxide (E171), might disrupt the development of respiratory neural networks, with long-term consequences. Ultra-processed foods (UPFs), which also contain a high concentration of additives, lead to systemic inflammation and impair lung function. Despite their wide usage, the use of these additives has become a warning sign due to their safety issue, particularly in sensitive people like children, pregnant women, and patients with pre-existing respiratory and chronic conditions. The review highlights the serious need for strict regulation and further research on the long-term effects of food additives on respiratory health. Policymakers should ban these food additives that are more harmful to human health. As an alternative to artificial additives, natural flavors and colors from fruits and vegetables, safe preservatives, and minimally processed ingredients can be used.
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ABDULLAHI, Xhabir, Gafur XHABIRI, Erhan SULEJMANI, and Faton SELIMI. "The effect of some additives on the rheology of dough and quality of bread." Acta agriculturae Slovenica 118, no. 2 (2022): 1. http://dx.doi.org/10.14720/aas.2022.118.2.2601.

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<p class="042abstractstekst"><span lang="EN-US">The technology of production of baking products today can not be imagined without the use of food additives. In this research it was aimed to investigate the use of some additives in wheat flour type 500 for bread production. The formulations and additives used in this study are: without additives for M0, emulsifiers (E 472e) for M1, calcium phosphate (E341 ii) for M2, L-ascorbic acid (E300) for M3 and Damil additive complex (antifouling E170 - 0.06 %; emulsifier E472e -0.08 %; antioxidant E300 -0.01 %; fungal a-amylase - 0.01 %) for M4 formulation. The results showed that the use of additives positively affects some rheological qualities such as water absorption capacity, stability and energy of the dough. M4 bread had a higher specific volume than all breads with 5.14 cm <sup>3 </sup>g<sup>-1</sup>, while M1 and M3 breads were similar. From the total points accumulated for the sensory qualities the M4 bread with a total of 88.8 points accumulated had the best qualities with volume, external appearance and very good crust and crumb taste. It is therefore recommended to use the Damil additive complex in bread production.</span></p>
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46

Zucchetti, Andrés E., Ismael R. Barosso, Andrea Boaglio та ін. "Prevention of estradiol 17β-d-glucuronide–induced canalicular transporter internalization by hormonal modulation of cAMP in rat hepatocytes". Molecular Biology of the Cell 22, № 20 (2011): 3902–15. http://dx.doi.org/10.1091/mbc.e11-01-0047.

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In estradiol 17β-d-glucuronide (E17G)–induced cholestasis, the canalicular hepatocellular transporters bile salt export pump (Abcb11) and multidrug-resistance associated protein 2 (Abcc2) undergo endocytic internalization. cAMP stimulates the trafficking of transporter-containing vesicles to the apical membrane and is able to prevent internalization of these transporters in estrogen-induced cholestasis. Hepatocyte levels of cAMP are regulated by hormones such as glucagon and adrenaline (via the β2 receptor). We analyzed the effects of glucagon and salbutamol (a β2 adrenergic agonist) on function and localization of Abcb11 and Abcc2 in isolated rat hepatocyte couplets exposed to E17G and compared the mechanistic bases of their effects. Glucagon and salbutamol partially prevented the impairment in Abcb11 and Abcc2 transport capacity. E17G also induced endocytic internalization of Abcb11 and Abcc2, which partially colocalized with the endosomal marker Rab11a. This effect was completely prevented by salbutamol, whereas some transporter-containing vesicles remained internalized and mainly colocalizing with Rab11a in the perinuclear region after incubation with glucagon. Glucagon prevention was dependent on cAMP-dependent protein kinase (PKA) and independent of exchange proteins activated directly by cAMP (Epac) and microtubules. In contrast, salbutamol prevention was PKA independent and Epac/MEK and microtubule dependent. Anticholestatic effects of glucagon and salbutamol were additive in nature. Our results show that increases in cAMP could activate different anticholestatic signaling pathways, depending on the hormonal mediator involved.
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Oktaviani, Amelia, Muhammad Agus Suprayudi, Mia Setiawati, and Ichsan Achmad Fauzi. "Evaluation of food digestibility in Nile tilapia fish Oreochromis niloticus given NSP enzymes and organic chromiium." Jurnal Akuakultur Indonesia 24, no. 1 (2025): 136–47. https://doi.org/10.19027/jai.24.1.136-147.

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Feed is a crucial factor in tilapia farming because it contributes 92% of the total production cost. This study aims to evaluate the digestibility and utilization of carbohydrates in low-protein feed supplemented with NSP enzymes and organic chromium. The research method employed a factorial completely randomized design with treatments of organic chromium (0, 1, 2) and NSP enzymes (0, 1). The study used 18 aquariums, each measuring 50×40×35 cm. The fish used were tilapia with an average weight of 33.09 ± 0.06 g per fish. The feed used was commercial feed supplemented with organic chromium and NSP enzymes. The study focused on digestibility performance, digestive enzyme activity, growth performance, and antioxidant status. The results showed that the treatments E1C1 and E0C2 resulted in better total digestibility, energy digestibility, and protein digestibility compared to the control and other treatments. Lipase, protease, and amylase enzymes in tilapia fed with the E1C1 treatment showed significantly higher results (P<0.05) compared to the control. Growth performance in tilapia fed with NSP enzymes and organic chromium did not show significant differences from the control (P>0.05). However, antioxidant status, specifically SOD and GPx, was significantly higher in the E0C1 treatment compared to the control (P<0.05). The conclusion of this study is that the addition of NSP enzymes and organic chromium to low-protein feed can improve digestibility and optimize carbohydrate utilization, with the best results achieved with the E1C1 treatment. Keywords: antioxidant, digestive enzymes, Nile tilapia, nutrient digestibility ABSTRAK Pakan menjadi factor krusial dalam usaha budidaya ikan nila karena memiliki kontribusi sebesar 92% dari total biaya produksi. Penelitian ini bertujuan untuk mengevaluasi kecernaan dan kemampuanpemanfaatan karbohidrat pada pakan protein rendah yang diberienzim NSP dan kromium organik. Metode penelitian ini menggunakan rancangan acak lengkap faktorial dengan perlakuan kromium organic (0,1,2) dan enzim NSP (0,1). Wadah yang digunakan merupakan aquarium yang berukuran 50×40×35 cm sebanyak 18 unit. Ikan yang digunakan dalam penelitian ini adalah ikan nila dengan bobot rata-rata 33,09 ± 0,06 g/ekor. Pakan yang digunakan merupakan pakan komersial yang diberi penambahan kromium organik dan enzim NSP. Penelitian ini difokuskan pada kinerja kecernaan, aktivitas enzim pencernaan, kinerja Pertumbuhan serta status Antioksidan. Hasil penelitian menunjukkan bahwa perlakuan E1C1 dan E0C2 menghasilkan nilai kecernaan total, kecernaan energi dan kecernaan protein yang lebih baik dibanding perlakuan kontrol dan perlakuan lainnya. Enzim lipase, protease dan amilase pada ikan nila yang diberipakan perlakuan E1C1 menunjukkan hasil yang lebih tinggi secarasignifikan (P<0,05) terhadap kontrol. Kinerja pertumbuhan pada ikan nila yang diberienzim NSP dan kromium organik menghasilkan nilai yang tidak signifikan dengan kontrol (P>0,05). Walaupun demikian, status antioksidan yang dihasilkan yaitu SOD dan GPx pada perlakuan E0C1 menghasilkan nilai yang lebih tinggi secara signifikan terhadap kontrol (P<0,05). Kesimpulan dari penelitian ini adalah penambahan enzim NSP dan kromium organik pada pakan rendah protein mampu meningkatkan kinerja kecernaan dan memanfaatkan karbohidrat dengan optimal. Hasil terbaik pada perlakuan E1C1. Kata kunci: antioksidan, enzim pencernaan, kecernaan nutrient, ikan nila
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48

Williams, Sally R., Tareq A. Juratli, Brandyn A. Castro, et al. "Genomic Analysis of Posterior Fossa Meningioma Demonstrates Frequent AKT1 E17K Mutations in Foramen Magnum Meningiomas." Journal of Neurological Surgery Part B: Skull Base 80, no. 06 (2019): 562–67. http://dx.doi.org/10.1055/s-0038-1676821.

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Objective Posterior fossa meningiomas are surgically challenging tumors that are associated with high morbidity and mortality. We sought to investigate the anatomical distribution of clinically actionable mutations in posterior fossa meningioma to facilitate identifying patients amenable for systemic targeted therapy trials. Methods Targeted sequencing of clinically targetable AKT1, SMO, and PIK3CA mutations was performed in 61 posterior fossa meningioma using Illumina NextSeq 500 to a target depth of >500 × . Samples were further interrogated for 53 cancer-relevant RNA fusions by the Archer FusionPlex panel to detect gene rearrangements. Results AKT1 (E17K) mutations were detected in five cases (8.2%), four in the foramen magnum and one in the cerebellopontine angle. In contrast, none of the posterior fossa tumors harbored an SMO (L412F) or a PIK3CA (E545K) mutation. Notably, the majority of foramen magnum meningiomas (4/7, 57%) harbored an AKT1 mutation. In addition, common clinically targetable gene fusions were not detected in any of the cases. Conclusion A large subset of foramen magnum meningiomas harbor AKT1 E17K mutations and are therefore potentially amenable to targeted medical therapy. Genotyping of foramen magnum meningiomas may enable more therapeutic alternatives and guide their treatment decision process.
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Fang, Luo. "The Effectiveness and Safety of 42°C Pulsed Radiofrequency Combined with 60°C Continuous Radiofrequency for Refractory Infraorbital Neuralgia: A Prospective Study." Pain Physician 3, no. 22;3 (2019): E171—E179. http://dx.doi.org/10.36076/ppj/2019.22.e171.

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Background: Infraorbital neuralgia, one of the rare causes of facial pain, lacks systematic treatment guidelines because few studies on the topic have been published. We previously found that 42°C percutaneous nondestructive pulsed radiofrequency (PRF) treatment could achieve satisfactory pain relief for infraorbital neuralgia patients. However, patients who responded poorly to PRF had no other ideal treatment options until now. Recently, standard PRF combined with 60°C continuous radiofrequency (CRF) was successfully performed on trigeminal neuralgia patients and achieved a promising effective rate with mild complications. However, the efficacy of the combined therapy in the treatment of infraorbital neuralgia has not yet been reported. Objectives: To evaluate the effectiveness and safety of 42°C PRF combined with 60°C CRF in infraorbital neuralgia patients who responded poorly to 42°C PRF and were reluctant to receive destructive therapies or nerve decompression surgery. Study Design: Prospective, single-center, observational clinical trial. Setting: The interventional pain management center in Beijing Tiantan Hospital. Methods: We prospectively investigated the effects of 10 minutes of 3-dimensional computer tomography-guided 42°C PRF combined with 270 seconds of 60°C CRF in the treatment of 28 patients with refractory infraorbital neuralgia. The response criterion was a postoperative verbal pain numeric rating scale score reduction of > 50%. The response rates at different time points during a 2-year follow-up were calculated. Results: The effective rates of combined PRF and CRF treatment were 95.5%, 86.4%, 81.8%, 72.7%, 72.7%, and 72.7% postoperative at 1 month, 3 months, 6 months, 1 year, 18 months, and 2 years, respectively. Except for 16 patients (72.7%) experiencing mild numbness that gradually disappeared within 1 week to 2 months after the operation, no obvious complications were observed. Limitations: This study examined the therapeutic effectiveness over a period of only 2 years; no further follow-up was conducted. In addition, this study is a single-center observational clinical study with small sample sizes. Conclusions: For patients with intractable infraorbital neuralgia, 42°C PRF combined with 60°C CRF is an effective and safe treatment. Prospective, double-blind randomized controlled trials with longer follow-up periods are needed to evaluate whether the combined treatment could become an alternative option for those who do not respond to conservative treatment, sparing those patients from destructive therapies or more invasive nerve decompression surgery. Key words: Infraorbital neuralgia, effectiveness, safety, pulsed radiofrequency, continuous radiofrequency, combined therapy
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Dydykin, A. S., E. R. Vasilevskaya, M. A. Aslanova, et al. "Development of a dietary supplement with iron oxide nanoparticles and study of its chronic toxicity and biological effects." Food systems 8, no. 1 (2025): 114–23. https://doi.org/10.21323/2618-9771-2025-8-1-114-123.

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Anemia is a global public health problem, the main cause of which is iron deficiency in the body. The difficulty of enriching the diet with iron is explained by the oxidative nature of iron, which leads to undesirable sensory changes and a decrease in the quality and shelf life of food. The work is devoted to the selection of bioavailable forms of iron, which, when added to food in an appropriate amount, are not rejected by the body. The aim of the work was to study in experiments on laboratory rats the chronic toxicity and effectiveness of the developed dietary supplement “PoliFerVit” in comparison with commercial preparations of iron oxides E172 (Fe2O3 + FeO) and iron sulfate (FeSO4 × 7H2O). The objects of the study were iron (II) sulfate heptahydrate (FeSO4 × 7H2O), a mixture of iron oxides E172 (Fe2O3 + FeO), dietary supplement “PoliFerVit” for use as a source of iron (FeO, Fe2O3, Fe3O4), vitamin C, and dihydroquercetin. In the process of work, a biologically active food additive (dietary supplement) “PoliFerVit” was developed, the iron content in the additive is 136% of the daily requirement. A comparison of the biological activity and chronic toxicity of the dietary supplement “PoliFerVit” and commercial iron preparations showed that all studied objects, when administered daily to laboratory animals for 32 days, did not affect the body weight of animals and their physiological state, and also did not cause changes in the main indicators of the general blood test, in particular, in the leukocyte formula. The revealed dynamics towards an increase in serum iron content when using a mixture of iron oxides (up to 17%) and dietary supplement “PoliFerVit” (up to 22%) indicates similar bioavailability, and the bioavailability of dietary supplement “PoliFerVit” is higher, which is probably due to the nanoscale size of iron particles and the combined composition of the additive. An important advantage of the dietary supplement “PoliFerVit” is a less pronounced negative effect on the antioxidant system, which was expressed in an increase in the superoxide dismutase index to 44%.
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