<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sivakumar Murugadoss</style></author><author><style face="normal" font="default" size="100%">van den Brûle, Sybille</style></author><author><style face="normal" font="default" size="100%">Frederic Brassinne</style></author><author><style face="normal" font="default" size="100%">Sebaihi, Noham</style></author><author><style face="normal" font="default" size="100%">Jorge Mejia</style></author><author><style face="normal" font="default" size="100%">Stéphane Lucas</style></author><author><style face="normal" font="default" size="100%">Jasmine Petry</style></author><author><style face="normal" font="default" size="100%">Godderis, Lode</style></author><author><style face="normal" font="default" size="100%">Jan Mast</style></author><author><style face="normal" font="default" size="100%">Lison, Dominique</style></author><author><style face="normal" font="default" size="100%">Hoet, Peter H.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Is aggregated synthetic amorphous silica toxicologically relevant?</style></title><secondary-title><style face="normal" font="default" size="100%">Particle and Fibre Toxicology</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Aggregates</style></keyword><keyword><style  face="normal" font="default" size="100%">Biological activity</style></keyword><keyword><style  face="normal" font="default" size="100%">In vitro toxicity</style></keyword><keyword><style  face="normal" font="default" size="100%">nanomaterials</style></keyword><keyword><style  face="normal" font="default" size="100%">synthetic amorphous silica</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Jan-12-2020</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">17</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Background:&lt;/p&gt;

&lt;p&gt;The regulatory definition(s) of nanomaterials (NMs) frequently uses the term ‘agglomerates and aggregates’ (AA) despite the paucity of evidence that AA are significantly relevant from a nanotoxicological perspective.This knowledge gap greatly afects the safety assessment and regulation of NMs, such as synthetic amorphous silica (SAS). SAS is used in a large panel of industrial applications. They are primarily produced as nanosized particles (1–100 nm in diameter) and considered safe as they form large aggregates (&amp;gt; 100 nm) during the production process. So far, it is indeed believed that large aggregates represent a weaker hazard compared to their nano counterpart. Thus, we assessed the impact of SAS aggregation on in vitro cytotoxicity/biological activity to address the toxicological relevance of aggregates of different sizes.&lt;/p&gt;

&lt;p&gt;&lt;br&gt;
Results:&lt;/p&gt;

&lt;p&gt;We used a precipitated SAS dispersed by different methods, generating 4 ad-hoc suspensions with different aggregate size distributions. Their effect on cell metabolic activity, cell viability, epithelial barrier integrity, total glutathione content and, IL-8 and IL-6 secretion were investigated after 24 h exposure in human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic cells (THP-1). We observed that the de-aggregated suspension (DE-AGGR), predominantly composed of nano-sized aggregates, induced stronger effects in all the cell lines than the aggregated suspension (AGGR). We then compared DE-AGGR with 2 suspensions fractionated from AGGR: the precipitated fraction (PREC) and the supernatant fraction (SuperN). Very large aggregates in PREC were found to be the least cytotoxic/biologically active compared to other suspensions. SuperN, which contains aggregates larger in size (&amp;gt; 100 nm) than in DE-AGGR but smaller than PREC, exhibited similar activity as DE-AGGR.&lt;/p&gt;

&lt;p&gt;Conclusion:&lt;/p&gt;

&lt;p&gt;Overall, aggregation resulted in reduced toxicological activity of SAS. However, when comparing aggregates of different sizes, it appeared that aggregates &amp;gt; 100 nm were not necessarily less cytotoxic than their nano-sized counterparts. This study suggests that aggregates of SAS are toxicologically relevant for the definition of NMs.&lt;/p&gt;
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