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CEEC","doi-asserted-by":"publisher","award":["CEECIND\/03143\/2017"],"award-info":[{"award-number":["CEECIND\/03143\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT Individual CEEC","doi-asserted-by":"publisher","award":["CEECIND\/01570\/2018"],"award-info":[{"award-number":["CEECIND\/01570\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Titanium dioxide nanoparticles (TiO2-NPs) are widely used, and humans are exposed through food (E171), cosmetics (e.g., toothpaste), and pharmaceuticals. The oral and gastrointestinal (GIT) tract are the first contact sites, but it may be systemically distributed. However, a robust adverse outcome pathway (AOP) has not been developed upon GIT exposure to TiO2-NPs. The aim of this review was to provide an integrative analysis of the published data on cellular and molecular mechanisms triggered after the ingestion of TiO2-NPs, proposing plausible AOPs that may drive policy decisions. A systematic review according to Prisma Methodology was performed in three databases of peer-reviewed literature: Pubmed, Scopus, and Web of Science. A total of 787 records were identified, screened in title\/abstract, being 185 used for data extraction. The main endpoints identified were oxidative stress, cytotoxicity\/apoptosis\/cell death, inflammation, cellular and systemic uptake, genotoxicity, and carcinogenicity. From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA).<\/jats:p>","DOI":"10.3390\/nano12193275","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T05:33:14Z","timestamp":1663824794000},"page":"3275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles\u2014A Systematic Review"],"prefix":"10.3390","volume":"12","author":[{"given":"Dora","family":"Rolo","sequence":"first","affiliation":[{"name":"National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"ToxOmics\u2014Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-0456","authenticated-orcid":false,"given":"Ricardo","family":"Assun\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"CESAM, Centre for Environmental and Marine Studies, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"IUEM, Instituto Universit\u00e1rio Egas Moniz, Egas Moniz-Cooperativa de Ensino Superior, CRL, 2829-511 Monte de Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0637-2222","authenticated-orcid":false,"given":"C\u00e9lia","family":"Ventura","sequence":"additional","affiliation":[{"name":"National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"ToxOmics\u2014Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-1357","authenticated-orcid":false,"given":"Paula","family":"Alvito","sequence":"additional","affiliation":[{"name":"National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"CESAM, Centre for Environmental and Marine Studies, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-2740","authenticated-orcid":false,"given":"L\u00eddia","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7930-2914","authenticated-orcid":false,"given":"Carla","family":"Martins","sequence":"additional","affiliation":[{"name":"National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"NOVA National School of Public Health, Public Health Research Centre, Universidade NOVA de Lisboa, 1600-560 Lisbon, Portugal"},{"name":"Comprehensive Health Research Center (CHRC), 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-5892","authenticated-orcid":false,"given":"Ana","family":"Bettencourt","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-9211","authenticated-orcid":false,"given":"Peter","family":"Jordan","sequence":"additional","affiliation":[{"name":"National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"BioISI\u2014Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]},{"given":"N\u00e1dia","family":"Vital","sequence":"additional","affiliation":[{"name":"National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"ToxOmics\u2014Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]},{"given":"Joana","family":"Pereira","sequence":"additional","affiliation":[{"name":"National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"BioISI\u2014Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9377-4085","authenticated-orcid":false,"given":"F\u00e1tima","family":"Pinto","sequence":"additional","affiliation":[{"name":"National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"ToxOmics\u2014Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, 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1649-016 Lisbon, Portugal"},{"name":"ToxOmics\u2014Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vieira, A., Gramacho, A., Rolo, D., Vital, N., Silva, M.J., and Louro, H. 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