{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:56:25Z","timestamp":1788980185535,"version":"build-2803163510"},"reference-count":20,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Ind Health"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>\n                    Synthetic amorphous silica (SAS) nanomaterial\u00a0\u2013 consisting of aggregates and agglomerates of primary silicon dioxide (SiO\n                    <jats:sub>2<\/jats:sub>\n                    ) particles in the nanorange (&lt;100 nm)\u00a0\u2013 is commonly used as excipient\u00a0in pharmaceuticals, in cosmetics and as food additive (E551). The available data suggest that SAS nanoparticles (NP) after intravenous (IV) exposure persist in liver and spleen; however, insufficient data exist to verify whether SAS may also induce adverse effects. The aim of the present study was to verify the potential long-term effects of SAS NP (NM-203) on spleen and liver as target organs following short-term exposure. Adult male and female Sprague-Dawley rats were treated by IV injection in the tail vein with a single (1-day) dose (SD) and repeated (5-day) doses (RD) of 20 mg\/kg bw per day of SAS dispersed in sterile saline solution as vehicle. Histopathological examinations of target organs were performed after 90 days. Tissue biodistribution and full characterization of NM-203, primary particle size 13\u201345 nm, was performed within the framework of the Nanogenotox project. No mortality or general toxicity occurred; histopathological analysis showed splenomegaly in the RD group accompanied by inflammatory granulomas in both sexes. Granulomas were also present in liver parenchyma in the RD (both sexes) and SD groups (male only). The histopathological results indicated that SAS NP have the potential to persist and induce sex-specific chronic inflammatory lesions in spleen and liver upon short-term treatment. Overall, the data showed that the widespread use of silica in drugs might elicit chronic reactions in spleen and liver prompting to the need of further investigations on the safety of SAS NP.[Formula: see text]\n                  <\/jats:p>","DOI":"10.1177\/07482337211010579","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T03:44:39Z","timestamp":1619667879000},"page":"328-335","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Amorphous silica nanoparticles induced spleen and liver toxicity after acute intravenous exposure in male and female rats"],"prefix":"10.1177","volume":"37","author":[{"given":"Roberta","family":"Tassinari","sequence":"first","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Experimental Animal Welfare Sector, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Valeri","sequence":"additional","affiliation":[{"name":"Experimental Animal Welfare Sector, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1736-2262","authenticated-orcid":false,"given":"Francesca","family":"Maranghi","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"bibr1-07482337211010579","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S118196"},{"key":"bibr2-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1080\/17435390.2020.1834634"},{"key":"bibr3-07482337211010579","unstructured":"De Jong WH, Jacobsen NR, Wallin H. et al. (2013) NANOGENOTOX, Deliverable 7: Identification of target organs and biodistribution including ADME parameters, Final Report. Netherlands: National Institute for Public Health and Environment (RIVM), Bilthoven. Available at: http:\/\/www.Nanogenotox.Eu\/Files\/PDF\/DELIVRABLES2\/Deliverable7__biodistribution.Pdf (accessed 1 July 2016)."},{"key":"bibr4-07482337211010579","doi-asserted-by":"publisher","DOI":"10.3390\/nano10091761"},{"issue":"1","key":"bibr5-07482337211010579","first-page":"5088","volume":"16","author":"European food safety authority (EFSA)","year":"2018","journal-title":"EFSA Journal"},{"key":"bibr6-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1039\/C7EN00716G"},{"key":"bibr7-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-016-1850-4"},{"key":"bibr8-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2959414"},{"key":"bibr9-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1002\/em.21928"},{"key":"bibr10-07482337211010579","unstructured":"Jensen KA, Clausen PA, Birkedal R. et al. (2011) NANOGENOTOX, WP 4: Physicochemical characterisation of manufactured nanomaterials (MNs) and exposure media (EMs). Available at: https:\/\/www.anses.fr\/en\/system\/files\/Work_package_5.pdf"},{"key":"bibr11-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2013.02.056"},{"key":"bibr12-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-017-1993-y"},{"key":"bibr13-07482337211010579","unstructured":"Nanogenotox: The project (2013) Available at: http:\/\/www.Nanogenotox.Eu\/Files\/PDF\/Nanogenotox_web.Pdf. (accessed September 2020)"},{"key":"bibr14-07482337211010579","unstructured":"Rasmussen K, Mech A, Mast J, et al. (2013) Synthetic Amorphous Silicon Dioxide (NM-200, NM-201, NM-202, NM-203, NM-204): Characterisation and Physico-Chemical Properties. EUR 26046. Luxembourg (Luxembourg): Publications Office of the European Union, 2013. JRC83506. Available at: http:\/\/publications.jrc.ec.europa.eu\/repository\/handle\/JRC83506 (accessed September 2020)."},{"key":"bibr151-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600867750"},{"key":"bibr15-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111168"},{"key":"bibr16-07482337211010579","doi-asserted-by":"publisher","DOI":"10.3109\/17435390.2014.940408"},{"key":"bibr152-07482337211010579","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2018.05.004"},{"key":"bibr17-07482337211010579","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S132304"},{"key":"bibr18-07482337211010579","doi-asserted-by":"publisher","DOI":"10.3109\/15376516.2016.1169341"}],"container-title":["Toxicology and Industrial Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/07482337211010579","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/07482337211010579","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/07482337211010579","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:42:59Z","timestamp":1777668179000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/07482337211010579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,29]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1177\/07482337211010579"],"URL":"https:\/\/doi.org\/10.1177\/07482337211010579","relation":{},"ISSN":["0748-2337","1477-0393"],"issn-type":[{"value":"0748-2337","type":"print"},{"value":"1477-0393","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,29]]}}}