{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:32:28Z","timestamp":1793381548869,"version":"4.5.0"},"update-to":[{"DOI":"10.12688\/openreseurope.13264.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000}}],"reference-count":50,"publisher":"CERN","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission","award":["814654"],"award-info":[{"award-number":["814654"]}],"id":[{"id":"https:\/\/ror.org\/00k4n6c32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Open Res Europe"],"abstract":"<jats:p>Background: When particles deposit for instance in the lung after inhalation or in the hip joint after local release from a hip implant material they can initiate a defense response. Even though these particles originate from inert materials such as polyethylene (PE) or titanium, they may cause harm when reaching high local doses and overwhelming local defense mechanisms.\n                \n                    Main body: This paper describes the parallels between adverse outcome pathways (AOP) and particle properties in lung overload and periprosthetic osteolysis (PPOL). It is noted that in both outcomes in different organs, the macrophage and cytokine orchestrated persistent inflammation is the common driver of events, in the joint leading to loss of bone density and structure, and in the lung leading to fibrosis and cancer. Most evidence on lung overload and its AOP is derived from chronic inhalation studies in rats, and the relevance to man is questioned. In PPOL, the paradigms and metrics are based on human clinical data, with additional insights generated from \n                    in vitro and animal studies. In both organ pathologies the total volume of particle deposition has been used to set threshold values for the onset of pathological alterations. The estimated clinical threshold for PPOL of 130 mg\/ml is much higher than the amount to cause lung overload in the rat (10 mg\/ml).  although the threshold in PPOL is not necessarily synonymous to particle overload.\n                \n                    Conclusions: The paradigms developed in two very different areas of particle response in the human body have major similarities in their AOP. Connecting the clinical evidence in PPOL to lung overload challenges current paradigms and relevance of rat inhalation studies to the human lung cancer hazard.<\/jats:p>","DOI":"10.12688\/openreseurope.13264.2","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T03:50:09Z","timestamp":1646797809000},"update-policy":"https:\/\/doi.org\/10.68336\/openreseurope.updatepolicy","source":"Crossref","is-referenced-by-count":5,"title":["The parallels between particle induced lung overload and particle induced periprosthetic osteolysis (PPOL)"],"prefix":"10.68336","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5219-8782","authenticated-orcid":false,"given":"Paul J.A.","family":"Borm","sequence":"first","affiliation":[{"name":"Nanoconsult, Meerssen, The Netherlands"},{"name":"University of Dusseldorf, Dusseldorf, 50224, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"13904","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"980","doi-asserted-by":"publisher","DOI":"10.1111\/cid.12742"},{"key":"981","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.O.00736"},{"key":"982","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/70.1.86"},{"key":"983","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583042"},{"key":"984","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-015-0086-4"},{"key":"985","doi-asserted-by":"publisher","DOI":"10.1080\/08958378.2020.1735581"},{"key":"986","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/18.2.423"},{"key":"987","doi-asserted-by":"publisher","DOI":"10.1054\/arth.2002.33664"},{"key":"988","unstructured":"ECETOC: Poorly soluble particles\/Lung overload- technical report 122. CEFIC- Brussels.2013. Reference Source (https:\/\/www.ecetoc.org\/wp-content\/uploads\/2014\/08\/ECETOC-TR-122-Poorly-Soluble-Particles-Lung-Overload.pdf)"},{"key":"989","unstructured":"ECHA: RAC Committee for risk assessment. Opinion proposing harmonised classification and labelling at EU level of Titanium dioxide. EC Number: 236-675-5 CAS Number: 13463-67-7, CLH-O-0000001412.2017. Reference Source (https:\/\/echa.europa.eu\/documents\/10162\/682fac9f-5b01-86d3-2f70-3d40277a53c2)"},{"key":"990","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfi327"},{"key":"991","doi-asserted-by":"publisher","DOI":"10.1177\/0954411918784982"},{"key":"992","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0675-0"},{"key":"993","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2014.02.003"},{"key":"994","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.33676"},{"key":"995","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8122091"},{"key":"996","doi-asserted-by":"publisher","DOI":"10.1080\/17434440.2020.1702024"},{"key":"997","doi-asserted-by":"publisher","DOI":"10.3109\/08958379509015211"},{"key":"998","doi-asserted-by":"publisher","DOI":"10.1002\/jat.2550060602"},{"key":"999","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02364"},{"key":"1000","unstructured":"IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Carbon Black, Titanium Dioxide, and Talc. Lyon, France: World Health Organization.2010; 93."},{"key":"1001","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.14"},{"key":"1002","doi-asserted-by":"publisher","DOI":"10.1080\/01926230601064787"},{"key":"1003","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2020.09.010"},{"key":"1004","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-019-1119-8https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/6421644"},{"key":"1005","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01060"},{"key":"1006","doi-asserted-by":"publisher","DOI":"10.1002\/3527600418.mb0230stwe5314"},{"key":"1007","doi-asserted-by":"publisher","DOI":"10.3109\/17453674.2013.878830"},{"key":"1008","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93356"},{"key":"1009","doi-asserted-by":"publisher","DOI":"10.3390\/ma12030495"},{"key":"1010","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24750"},{"key":"1011","doi-asserted-by":"publisher","DOI":"10.1080\/08958370500444320"},{"key":"1012","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(88)90284-9"},{"key":"1013","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.208.1.9646791"},{"key":"1014","doi-asserted-by":"publisher","DOI":"10.1615\/jlongtermeffmedimplants.2014010562"},{"key":"1015","doi-asserted-by":"publisher","DOI":"10.1615\/JLongTermEffMedImplants.2017011287"},{"key":"1016","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.01109311"},{"key":"1017","doi-asserted-by":"publisher","DOI":"10.3390\/ma7020980"},{"key":"1018","unstructured":"Oberdorster G: Significance of particle parameters in the evaluation of exposure-dose-response relationships of inhaled particles. 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