{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:48:27Z","timestamp":1787240907937,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T00:00:00Z","timestamp":1735084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Maastricht University","award":["ARVODI-2018 Overeenkomst Onderzoeksopdracht E171"],"award-info":[{"award-number":["ARVODI-2018 Overeenkomst Onderzoeksopdracht E171"]}]},{"name":"NVWA (The Netherlands Food and Consumer Product Safety Authority) ARVODI-2018 Overeenkomst Onderzoeksopdracht","award":["ARVODI-2018 Overeenkomst Onderzoeksopdracht E171"],"award-info":[{"award-number":["ARVODI-2018 Overeenkomst Onderzoeksopdracht E171"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>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\u2013mass 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\u201375% of particles in the nano-size range (&lt;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.<\/jats:p>","DOI":"10.3390\/nano15010008","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T19:29:52Z","timestamp":1735154992000},"page":"8","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Investigating the ROS Formation and Particle Behavior of Food-Grade Titanium Dioxide (E171) in the TIM-1 Dynamic Gastrointestinal Digestion Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5032-6314","authenticated-orcid":false,"given":"Nicolaj S.","family":"Bischoff","sequence":"first","affiliation":[{"name":"Department of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Undas","sequence":"additional","affiliation":[{"name":"Wageningen Food Safety Research (WFSR), Wageningen University & Research, 6708 WB Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9986-5976","authenticated-orcid":false,"given":"Greet","family":"van Bemmel","sequence":"additional","affiliation":[{"name":"Wageningen Food Safety Research (WFSR), Wageningen University & Research, 6708 WB Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1405-5232","authenticated-orcid":false,"given":"Jacco J.","family":"Bried\u00e9","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1421-8214","authenticated-orcid":false,"given":"Simone G.","family":"van Breda","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3762-7508","authenticated-orcid":false,"given":"Jessica","family":"Verhoeven","sequence":"additional","affiliation":[{"name":"Centre for Healthy Eating & Food Innovation, Maastricht University\u2014Campus Venlo, Villafloraweg 1, 5928 SZ Venlo, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"Verbruggen","sequence":"additional","affiliation":[{"name":"Centre for Healthy Eating & Food Innovation, Maastricht University\u2014Campus Venlo, Villafloraweg 1, 5928 SZ Venlo, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-5127","authenticated-orcid":false,"given":"Koen","family":"Venema","sequence":"additional","affiliation":[{"name":"Centre for Healthy Eating & Food Innovation, Maastricht University\u2014Campus Venlo, Villafloraweg 1, 5928 SZ Venlo, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick T. H. M.","family":"Sijm","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Office of Risk Assessment and Research, Netherlands Food and Consumer Product Safety Authority, P.O. Box 43006, 3540 AA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo M.","family":"de Kok","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3390\/ijms22010207","article-title":"Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System","volume":"22","author":"Bischoff","year":"2021","journal-title":"Int. J. Mol. 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