Investigating the ROS Formation and Particle Behavior of Food-Grade Titanium Dioxide (E171) in the TIM-1 Dynamic Gastrointestinal Digestion Model

Food-grade titanium dioxide (E171) is widely used in food, feed, and pharmaceuticals for its opacifying and coloring properties. This study investigates the formation of reactive oxygen species (ROS) and the aggregation behavior of E171 using the TNO Gastrointestinal (GI) model, which simulates the...

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Main Authors: Nicolaj S. Bischoff, Anna K. Undas, Greet van Bemmel, Jacco J. Briedé, Simone G. van Breda, Jessica Verhoeven, Sanne Verbruggen, Koen Venema, Dick T. H. M. Sijm, Theo M. de Kok
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Nanomaterials
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Online Access:https://www.mdpi.com/2079-4991/15/1/8
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author Nicolaj S. Bischoff
Anna K. Undas
Greet van Bemmel
Jacco J. Briedé
Simone G. van Breda
Jessica Verhoeven
Sanne Verbruggen
Koen Venema
Dick T. H. M. Sijm
Theo M. de Kok
author_facet Nicolaj S. Bischoff
Anna K. Undas
Greet van Bemmel
Jacco J. Briedé
Simone G. van Breda
Jessica Verhoeven
Sanne Verbruggen
Koen Venema
Dick T. H. M. Sijm
Theo M. de Kok
author_sort Nicolaj S. Bischoff
collection DOAJ
description Food-grade titanium dioxide (E171) is widely used in food, feed, and pharmaceuticals for its opacifying and coloring properties. This study investigates the formation of reactive oxygen species (ROS) and the aggregation behavior of E171 using the TNO Gastrointestinal (GI) model, which simulates the stomach and small intestine. E171 was characterized using multiple techniques, including electron spin resonance spectroscopy, single-particle inductively coupled plasma–mass spectrometry, transmission electron microscopy, and dynamic light scattering. In an aqueous dispersion (E171-aq), E171 displayed a median particle size of 79 nm, with 73–75% of particles in the nano-size range (<100 nm), and significantly increased ROS production at concentrations of 0.22 and 20 mg/mL. In contrast, when E171 was mixed with yogurt (E171-yog), the particle size increased to 330 nm, with only 20% of nanoparticles, and ROS production was inhibited entirely. After GI digestion, the size of dE171-aq increased to 330 nm, while dE171-yog decreased to 290 nm, with both conditions showing a strongly reduced nanoparticle fraction. ROS formation was inhibited post-digestion in this cell-free environment, likely due to increased particle aggregation and protein corona formation. These findings highlight the innate potential of E171 to induce ROS and the need to consider GI digestion and food matrices in the hazard identification/characterization and risk assessment of E171.
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spelling doaj-art-9645d4ab613145c2a2a70c036abfd2f62025-01-10T13:19:14ZengMDPI AGNanomaterials2079-49912024-12-01151810.3390/nano15010008Investigating the ROS Formation and Particle Behavior of Food-Grade Titanium Dioxide (E171) in the TIM-1 Dynamic Gastrointestinal Digestion ModelNicolaj S. Bischoff0Anna K. Undas1Greet van Bemmel2Jacco J. Briedé3Simone G. van Breda4Jessica Verhoeven5Sanne Verbruggen6Koen Venema7Dick T. H. M. Sijm8Theo M. de Kok9Department of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, The NetherlandsWageningen Food Safety Research (WFSR), Wageningen University & Research, 6708 WB Wageningen, The NetherlandsWageningen Food Safety Research (WFSR), Wageningen University & Research, 6708 WB Wageningen, The NetherlandsDepartment of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, The NetherlandsDepartment of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, The NetherlandsCentre for Healthy Eating & Food Innovation, Maastricht University—Campus Venlo, Villafloraweg 1, 5928 SZ Venlo, The NetherlandsCentre for Healthy Eating & Food Innovation, Maastricht University—Campus Venlo, Villafloraweg 1, 5928 SZ Venlo, The NetherlandsCentre for Healthy Eating & Food Innovation, Maastricht University—Campus Venlo, Villafloraweg 1, 5928 SZ Venlo, The NetherlandsDepartment of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, The NetherlandsFood-grade titanium dioxide (E171) is widely used in food, feed, and pharmaceuticals for its opacifying and coloring properties. This study investigates the formation of reactive oxygen species (ROS) and the aggregation behavior of E171 using the TNO Gastrointestinal (GI) model, which simulates the stomach and small intestine. E171 was characterized using multiple techniques, including electron spin resonance spectroscopy, single-particle inductively coupled plasma–mass spectrometry, transmission electron microscopy, and dynamic light scattering. In an aqueous dispersion (E171-aq), E171 displayed a median particle size of 79 nm, with 73–75% of particles in the nano-size range (<100 nm), and significantly increased ROS production at concentrations of 0.22 and 20 mg/mL. In contrast, when E171 was mixed with yogurt (E171-yog), the particle size increased to 330 nm, with only 20% of nanoparticles, and ROS production was inhibited entirely. After GI digestion, the size of dE171-aq increased to 330 nm, while dE171-yog decreased to 290 nm, with both conditions showing a strongly reduced nanoparticle fraction. ROS formation was inhibited post-digestion in this cell-free environment, likely due to increased particle aggregation and protein corona formation. These findings highlight the innate potential of E171 to induce ROS and the need to consider GI digestion and food matrices in the hazard identification/characterization and risk assessment of E171.https://www.mdpi.com/2079-4991/15/1/8E171titanium dioxidehuman gastrointestinal digestionagglomerationROSphysicochemical characterization
spellingShingle Nicolaj S. Bischoff
Anna K. Undas
Greet van Bemmel
Jacco J. Briedé
Simone G. van Breda
Jessica Verhoeven
Sanne Verbruggen
Koen Venema
Dick T. H. M. Sijm
Theo M. de Kok
Investigating the ROS Formation and Particle Behavior of Food-Grade Titanium Dioxide (E171) in the TIM-1 Dynamic Gastrointestinal Digestion Model
Nanomaterials
E171
titanium dioxide
human gastrointestinal digestion
agglomeration
ROS
physicochemical characterization
title Investigating the ROS Formation and Particle Behavior of Food-Grade Titanium Dioxide (E171) in the TIM-1 Dynamic Gastrointestinal Digestion Model
title_full Investigating the ROS Formation and Particle Behavior of Food-Grade Titanium Dioxide (E171) in the TIM-1 Dynamic Gastrointestinal Digestion Model
title_fullStr Investigating the ROS Formation and Particle Behavior of Food-Grade Titanium Dioxide (E171) in the TIM-1 Dynamic Gastrointestinal Digestion Model
title_full_unstemmed Investigating the ROS Formation and Particle Behavior of Food-Grade Titanium Dioxide (E171) in the TIM-1 Dynamic Gastrointestinal Digestion Model
title_short Investigating the ROS Formation and Particle Behavior of Food-Grade Titanium Dioxide (E171) in the TIM-1 Dynamic Gastrointestinal Digestion Model
title_sort investigating the ros formation and particle behavior of food grade titanium dioxide e171 in the tim 1 dynamic gastrointestinal digestion model
topic E171
titanium dioxide
human gastrointestinal digestion
agglomeration
ROS
physicochemical characterization
url https://www.mdpi.com/2079-4991/15/1/8
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