Is aggregated synthetic amorphous silica toxicologically relevant?

Sivakumar Murugadoss, Sybille van den Brule, Frederic Brassinne, Noham Sebaihi, Jorge Mejia, Stéphane Lucas, Jasmine Petry, Lode Godderis, Jan Mast, Dominique Lison, Peter H. Hoet

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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 nano-sized 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.

Original languageEnglish
Number of pages1
JournalParticle and Fibre Toxicology
Volume17
Issue number1
DOIs
Publication statusPublished - 3 Jan 2020

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Silicon Dioxide
Suspensions
Nanostructures
Nanostructured materials
Toxicology
Agglomeration
Interleukin-8
Glutathione
Cytotoxicity
Bioactivity
Interleukin-6
Cell Survival
Colon
Industrial applications
Hazards
Safety
Cell Line
Cells

Keywords

  • Aggregates
  • Biological activity
  • In vitro toxicity
  • Nanomaterials
  • Synthetic amorphous silica

Cite this

Murugadoss, Sivakumar ; van den Brule, Sybille ; Brassinne, Frederic ; Sebaihi, Noham ; Mejia, Jorge ; Lucas, Stéphane ; Petry, Jasmine ; Godderis, Lode ; Mast, Jan ; Lison, Dominique ; Hoet, Peter H. / Is aggregated synthetic amorphous silica toxicologically relevant?. In: Particle and Fibre Toxicology. 2020 ; Vol. 17, No. 1.
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title = "Is aggregated synthetic amorphous silica toxicologically relevant?",
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 nano-sized 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.",
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Murugadoss, S, van den Brule, S, Brassinne, F, Sebaihi, N, Mejia, J, Lucas, S, Petry, J, Godderis, L, Mast, J, Lison, D & Hoet, PH 2020, 'Is aggregated synthetic amorphous silica toxicologically relevant?', Particle and Fibre Toxicology, vol. 17, no. 1. https://doi.org/10.1186/s12989-019-0331-3

Is aggregated synthetic amorphous silica toxicologically relevant? / Murugadoss, Sivakumar; van den Brule, Sybille; Brassinne, Frederic; Sebaihi, Noham; Mejia, Jorge; Lucas, Stéphane; Petry, Jasmine; Godderis, Lode; Mast, Jan; Lison, Dominique; Hoet, Peter H.

In: Particle and Fibre Toxicology, Vol. 17, No. 1, 03.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Is aggregated synthetic amorphous silica toxicologically relevant?

AU - Murugadoss, Sivakumar

AU - van den Brule, Sybille

AU - Brassinne, Frederic

AU - Sebaihi, Noham

AU - Mejia, Jorge

AU - Lucas, Stéphane

AU - Petry, Jasmine

AU - Godderis, Lode

AU - Mast, Jan

AU - Lison, Dominique

AU - Hoet, Peter H.

PY - 2020/1/3

Y1 - 2020/1/3

N2 - 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 nano-sized 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.

AB - 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 nano-sized 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.

KW - Aggregates

KW - Biological activity

KW - In vitro toxicity

KW - Nanomaterials

KW - Synthetic amorphous silica

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U2 - 10.1186/s12989-019-0331-3

DO - 10.1186/s12989-019-0331-3

M3 - Article

C2 - 31900181

AN - SCOPUS:85077479834

VL - 17

JO - Particle and Fibre Toxicology

JF - Particle and Fibre Toxicology

SN - 1743-8977

IS - 1

ER -