Is aggregated synthetic amorphous silica toxicologically relevant?
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(2020) 17:1
RESEARCH
Open Access
Is aggregated synthetic amorphous silica toxicologically relevant? Sivakumar Murugadoss1, Sybille van den Brule2, Frederic Brassinne3, Noham Sebaihi4, Jorge Mejia5, Stéphane Lucas6, Jasmine Petry4, Lode Godderis7,8, Jan Mast3, Dominique Lison2 and Peter H. Hoet1*
Abstract Background: 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 affects 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 (> 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. Results: 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 (> 100 nm) than in DE-AGGR but smaller than PREC, exhibited similar activity as DE-AGGR. Conclusion: Overall, aggregation resulted in reduced toxicological activity of SAS. However, when comparing aggregates of different sizes, it appeared that aggregates > 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. Keywords: Nanomaterials, Synthetic amorphous silica, Aggregates, In vitro toxicity, Biological activity
Background Synthetic amorphous silica (SAS) represents a group of nanomaterials (NMs) manufactured either by thermal (pyrogenic/fumed) or wet route (precipitated, gel and colloidal) [1]. SAS is primarily produced as nano-sized primary particles (1–100 nm in diameter) that form micron-sized aggregates and agglomerates of aggregates during their production process [2, 3]. Aggregates are composed of particles that are strongly linked by * Correspond
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