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Is aggregated synthetic amorphous silica toxicologically relevant?
Sivakumar Murugadoss1, Sybille van den Brule2, Frederic Brassinne3
1Laboratory of Toxicology, Unit of Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3000, Leuven, Belgium.
Particle and Fibre Toxicology
|January 5, 2020
Summary
Aggregates of synthetic amorphous silica (SAS) show toxicological relevance, challenging the assumption that larger aggregates are less hazardous. This study highlights the importance of considering aggregate size in nanomaterial safety assessments.
Area of Science:
- Materials Science
- Toxicology
- Nanotechnology
Background:
- Regulatory definitions of nanomaterials (NMs) include 'agglomerates and aggregates' (AA), but their toxicological relevance is poorly understood.
- Synthetic amorphous silica (SAS), widely used industrially, is produced as nanoparticles but forms larger aggregates, presumed to be less hazardous.
- A knowledge gap exists regarding the nanotoxicological impact of AA, affecting NM safety assessment and regulation.
Purpose of the Study:
- To investigate the impact of synthetic amorphous silica (SAS) aggregation on in vitro cytotoxicity and biological activity.
- To address the toxicological relevance of aggregates of different sizes in relation to nanomaterial definitions.
- To evaluate how varying aggregate sizes of SAS influence cellular responses.
Main Methods:
- Prepared four SAS suspensions with distinct aggregate size distributions by employing different dispersion methods.
- Assessed the effects of SAS suspensions on cell metabolic activity, viability, epithelial barrier integrity, glutathione content, and cytokine secretion (IL-8, IL-6) in human bronchial epithelial, Caco2, and THP-1 cells.
- Compared the biological activity of de-aggregated (DE-AGGR), aggregated (AGGR), precipitated (PREC), and supernatant (SuperN) SAS fractions.
Main Results:
- The de-aggregated SAS suspension (DE-AGGR), with predominantly nano-sized aggregates, exhibited stronger effects across all cell lines compared to the aggregated suspension (AGGR).
- Very large aggregates in the precipitated fraction (PREC) showed the least cytotoxicity and biological activity.
- The supernatant fraction (SuperN), containing aggregates larger than DE-AGGR but smaller than PREC, displayed activity comparable to DE-AGGR.
Conclusions:
- Overall, SAS aggregation reduced toxicological activity, but aggregates larger than 100 nm were not consistently less cytotoxic than their nano-sized counterparts.
- This study indicates that aggregates of SAS are toxicologically relevant and should be considered in the definition of nanomaterials.
- The findings suggest a need to re-evaluate the assumption that larger aggregates pose a weaker hazard in nanomaterial safety assessments.
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