{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:46:06Z","timestamp":1793328366087,"version":"4.5.0"},"reference-count":104,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,11,10]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Silica particles with a population of nearly free silanols damage cellular membranes and initiate inflammatory reactions. Nearly free silanols are found on the surface of both fractured quartz and amorphous silica particles, and their occurrence initiates the toxicity of silica, thus revisiting the ancient paradigm whereby crystallinity is critical for silica toxicity. This finding resolves the lingering questions about the origin and the variability of the toxicity of silica particles. The discovery of the biological activity of nearly free silanols opens perspectives for the prevention of silicosis through a safer-by-design approach, and will have an impact on other fields that involve interfacial phenomena, including biomaterial design, nanofabrication, and catalysis.<\/jats:p>","DOI":"10.1073\/pnas.2008006117","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T20:30:55Z","timestamp":1603485055000},"page":"27836-27846","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":131,"title":["Nearly free surface silanols are the critical molecular moieties that initiate the toxicity of silica particles"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3786-426X","authenticated-orcid":false,"given":"Cristina","family":"Pavan","sequence":"first","affiliation":[{"name":"Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium;"},{"name":"Department of Chemistry, University of Turin, 10124 Turin, Italy;"},{"name":"\u201cG. Scansetti\u201d Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8775-5697","authenticated-orcid":false,"given":"Rosangela","family":"Santalucia","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Turin, 10124 Turin, Italy;"},{"name":"Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-3568","authenticated-orcid":false,"given":"Riccardo","family":"Leinardi","sequence":"additional","affiliation":[{"name":"Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium;"},{"name":"Department of Chemistry, University of Turin, 10124 Turin, Italy;"},{"name":"\u201cG. Scansetti\u201d Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9094-0279","authenticated-orcid":false,"given":"Marco","family":"Fabbiani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Turin, 10124 Turin, Italy;"},{"name":"Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousof","family":"Yakoub","sequence":"additional","affiliation":[{"name":"Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francine","family":"Uwambayinema","sequence":"additional","affiliation":[{"name":"Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8886-9832","authenticated-orcid":false,"given":"Piero","family":"Ugliengo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Turin, 10124 Turin, Italy;"},{"name":"Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9930-8181","authenticated-orcid":false,"given":"Maura","family":"Tomatis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Turin, 10124 Turin, Italy;"},{"name":"\u201cG. Scansetti\u201d Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy;"},{"name":"Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-5342","authenticated-orcid":false,"given":"Gianmario","family":"Martra","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Turin, 10124 Turin, Italy;"},{"name":"\u201cG. Scansetti\u201d Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy;"},{"name":"Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5806-829X","authenticated-orcid":false,"given":"Francesco","family":"Turci","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Turin, 10124 Turin, Italy;"},{"name":"\u201cG. Scansetti\u201d Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy;"},{"name":"Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-2518","authenticated-orcid":false,"given":"Dominique","family":"Lison","sequence":"additional","affiliation":[{"name":"Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5473-8102","authenticated-orcid":false,"given":"Bice","family":"Fubini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Turin, 10124 Turin, Italy;"},{"name":"\u201cG. Scansetti\u201d Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar700153u"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8128221"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009219107"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802608783790901"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2868"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805135105"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmat2442"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.97105s51013"},{"key":"e_1_3_4_9_2","first-page":"3","volume-title":"The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties, and Biochemistry","author":"Iler R. K.","year":"1979","unstructured":"R. K. Iler, The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties, and Biochemistry (Wiley, 1979), pp. 3\u201310, 624\u2013648."},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr3003054"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1917237117"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.108"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.7b03961"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)30424-6"},{"key":"e_1_3_4_15_2","first-page":"1","article-title":"Silica-related diseases in the modern world","volume":"00","author":"Hoy R. F.","year":"2020","unstructured":"R. F. Hoy, D. C. Chambers, Silica-related diseases in the modern world. Allergy 00, 1\u201313 (2020).","journal-title":"Allergy"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60235-9"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00097"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32203-7"},{"key":"e_1_3_4_19_2","first-page":"39","article-title":"\u201cSilica\u201d, in Silica, some silicates, coal dust and para-aramid fibrils","volume":"68","author":"International Agency for Research on Cancer (IARC)","year":"1997","unstructured":"International Agency for Research on Cancer (IARC), \u201cSilica\u201d, in Silica, some silicates, coal dust and para-aramid fibrils. IARC Monogr. Eval. Carcinog. Risks Hum. 68, 39\u2013242 (1997).","journal-title":"IARC Monogr. Eval. Carcinog. Risks Hum."},{"key":"e_1_3_4_20_2","first-page":"355","volume-title":"Arsenic, Metals, Fibres, and Dusts, IARC Monogr. Eval. Carcinog. Risks Hum. 100C","author":"International Agency for Research on Cancer (IARC)","year":"2012","unstructured":"International Agency for Research on Cancer (IARC), \u201cSilica dust, crystalline, in the form of quartz or cristobalite\u201d in Arsenic, Metals, Fibres, and Dusts, IARC Monogr. Eval. Carcinog. Risks Hum. 100C, (International Agency for Research on Cancer, 2012), pp. 355\u2013406."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1631"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1156995"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803933105"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-020-00345-3"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-017-1993-y"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-7-39"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.5.9707141"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002040100266"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.6b00409"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja304907c"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-019-0325-1"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2014.196"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1039\/jm9950501935"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-016-0136-6"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.6b04143"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2015.11.006"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S116492"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-019-0315-3"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/169538b0"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1722263115"},{"key":"e_1_3_4_41_2","first-page":"145","volume-title":"The Surface Properties of Silicas","author":"Burneau A.","year":"1998","unstructured":"A. Burneau, J.-P. Gallas, \u201cHydroxyl groups on silica surfaces\u201d in The Surface Properties of Silicas, A. P. Legrand, Ed. (Wiley, 1998), pp. 145\u2013312."},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/210259a0"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0013-9351(81)90226-7"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-014-0076-y"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx400105f"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.cgd.6b00183"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.11811"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11224-016-0906-7"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp9008724"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcc.5b07764"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9086327"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx980261a"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b03443"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp203988j"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-018-0259-z"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1021\/nn300223w"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja211307u"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja906190t"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1021\/jz300255x"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp905325m"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2cp40756f"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/138.2.445"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfv258"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(03)00149-7"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1615\/JEnvironPatholToxicolOncol.v20.iSuppl.1.80"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.12.027"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom5031399"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-020-00353-3"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2016.07.001"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/63.1.90"},{"key":"e_1_3_4_71_2","first-page":"111","article-title":"Generation of oxygen radicals by minerals and its correlation to cytotoxicity","volume":"102","author":"Vallyathan V.","year":"1994","unstructured":"V. Vallyathan, Generation of oxygen radicals by minerals and its correlation to cytotoxicity. Environ. Health Perspect. 102 (suppl. 10), 111\u2013115 (1994).","journal-title":"Environ. Health Perspect."},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287399009531393"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04388-z"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7NH00187H"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(00)01847-X"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2330"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2005.02.065"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1006\/jcis.1995.1285"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-020-02819-x"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-016-0150-8"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.05.036"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-9-32"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.3109\/17435390.2010.506957"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/56.2.405"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp048767r"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2007.04.001"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx900369x"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgg146"},{"key":"e_1_3_4_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(92)90277-Y"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.464913"},{"key":"e_1_3_4_92_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21759"},{"key":"e_1_3_4_93_2","doi-asserted-by":"publisher","DOI":"10.1080\/00268970500180808"},{"key":"e_1_3_4_94_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp400106s"},{"key":"e_1_3_4_95_2","first-page":"2","article-title":"Robust atomistic modeling of materials, organometallic, and biochemical systems","volume":"132","author":"Spicher S.","year":"2020","unstructured":"S. Spicher, S. Grimme, Robust atomistic modeling of materials, organometallic, and biochemical systems. Angew. Chem. Int. Ed. Engl. 132, 2\u201311 (2020).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"e_1_3_4_96_2","doi-asserted-by":"publisher","DOI":"10.26434\/chemrxiv.8326202.v1"},{"key":"e_1_3_4_97_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00275a013"},{"key":"e_1_3_4_98_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevB.92.045131"},{"key":"e_1_3_4_99_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.6b05652"},{"key":"e_1_3_4_100_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-015-0086-4"},{"key":"e_1_3_4_101_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2011.03.009"},{"key":"e_1_3_4_102_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-018-0277-x"},{"key":"e_1_3_4_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(85)90092-2"},{"key":"e_1_3_4_104_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm243"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2008006117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T07:20:49Z","timestamp":1649834449000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2008006117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,23]]},"references-count":104,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2020,11,10]]}},"alternative-id":["10.1073\/pnas.2008006117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2008006117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,23]]},"assertion":[{"value":"2020-10-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}