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The biodistribution of silver, hematological parameters and GSH\/GSSG levels in the lung and liver were studied in mice that were intratracheally instilled with AgNP (5 and 50 nm) and AgNO3 once a week for 5 weeks, followed by a recovery period of up to 28 days (dpi). Data was gathered to build a PBPK model after the entry of AgNPs into the lungs. AgNPs could be absorbed into the blood and might cross the physiological barriers and be distributed extensively in mice. Similar to AgNO3, AgNP5 induced longer-lasting toxicity toward blood cells and increased GSH levels in the lung. The exposure to AgNP50 increased the GSH from 1 dpi onward in the liver and silver was distributed to the organs after exposure, but its concentration decreased over time. In AgNP5 treated mice, silver levels were highest in the spleen, kidney, liver and blood, persisting for at least 28 days, suggesting accumulation. The major route for excretion seemed to be through the urine, despite a high concentration of AgNP5 also being found in feces. The modeled silver concentration was in line with the in vivo data for the heart and liver.<\/jats:p>","DOI":"10.3390\/toxics10050260","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T23:14:26Z","timestamp":1652915666000},"page":"260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Impact of Particle Size on Toxicity, Tissue Distribution and Excretion Kinetics of Subchronic Intratracheal Instilled Silver Nanoparticles in Mice"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1269-8915","authenticated-orcid":false,"given":"Fernanda","family":"Ros\u00e1rio","sequence":"first","affiliation":[{"name":"Department of Biology & CESAM, University of Aveiro, Campus Universit\u00e1rio de Santiago, 3810-193 Aveiro, Portugal"}]},{"given":"Jan","family":"Creylman","sequence":"additional","affiliation":[{"name":"RADIUS Group, Thomas More University College, Campus Kempen, Kleinhoefstraat 4, 2440 Geel, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9268-9228","authenticated-orcid":false,"given":"Geert","family":"Verheyen","sequence":"additional","affiliation":[{"name":"RADIUS Group, Thomas More University College, Campus Kempen, Kleinhoefstraat 4, 2440 Geel, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2328-3130","authenticated-orcid":false,"given":"Sabine","family":"Van Miert","sequence":"additional","affiliation":[{"name":"RADIUS Group, Thomas More University College, Campus Kempen, Kleinhoefstraat 4, 2440 Geel, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4129-6381","authenticated-orcid":false,"given":"Concei\u00e7\u00e3o","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0292-6603","authenticated-orcid":false,"given":"Peter","family":"Hoet","sequence":"additional","affiliation":[{"name":"Occupational and Environmental Toxicology, KU Leuven, ON1 Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4673-0696","authenticated-orcid":false,"given":"Helena","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biology & CESAM, University of Aveiro, Campus Universit\u00e1rio de Santiago, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S0196-6553(99)70055-6","article-title":"Efficacy of Topical Silver against Fungal Burn Wound Pathogens","volume":"27","author":"Wright","year":"1999","journal-title":"Am. 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