Dataset Information

Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo.

ABSTRACT:

Background

The terms agglomerates and aggregates are frequently used in the regulatory definition(s) of nanomaterials (NMs) and hence attract attention in view of their potential influence on health effects. However, the influence of nanoparticle (NP) agglomeration and aggregation on toxicity is poorly understood although it is strongly believed that smaller the size of the NPs greater the toxicity. A toxicologically relevant definition of NMs is therefore not yet available, which affects not only the risk assessment process but also hinders the regulation of nano-products. In this study, we assessed the influence of NP agglomeration on their toxicity/biological responses in vitro and in vivo.

Results

We tested two TiO₂ NPs with different primary sizes (17 and 117?nm) and prepared ad-hoc suspensions composed of small or large agglomerates with similar dispersion medium composition. For in vitro testing, human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic (THP-1) cell lines were exposed to these suspensions for 24?h and endpoints such as cytotoxicity, total glutathione, epithelial barrier integrity, inflammatory mediators and DNA damage were measured. Large agglomerates of 17?nm TiO₂ induced stronger responses than small agglomerates for glutathione depletion, IL-8 and IL-1? increase, and DNA damage in THP-1, while no effect of agglomeration was observed with 117?nm TiO₂. In vivo, C57BL/6JRj mice were exposed via oropharyngeal aspiration or oral gavage to TiO₂ suspensions and, after 3?days, biological parameters including cytotoxicity, inflammatory cell recruitment, DNA damage and biopersistence were measured. Mainly, we observed that large agglomerates of 117?nm TiO₂ induced higher pulmonary responses in aspirated mice and blood DNA damage in gavaged mice compared to small agglomerates.

Conclusion

Agglomeration of TiO₂ NPs influences their toxicity/biological responses and, large agglomerates do not appear less active than small agglomerates. This study provides a deeper insight on the toxicological relevance of NP agglomerates and contributes to the establishment of a toxicologically relevant definition for NMs.

SUBMITTER: Murugadoss S

PROVIDER: S-EPMC7045370 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo.

Murugadoss Sivakumar S Brassinne Frederic F Sebaihi Noham N Petry Jasmine J Cokic Stevan M SM Van Landuyt Kirsten L KL Godderis Lode L Mast Jan J Lison Dominique D Hoet Peter H PH van den Brule Sybille S

Particle and fibre toxicology 20200226 1

<h4>Background</h4>The terms agglomerates and aggregates are frequently used in the regulatory definition(s) of nanomaterials (NMs) and hence attract attention in view of their potential influence on health effects. However, the influence of nanoparticle (NP) agglomeration and aggregation on toxicity is poorly understood although it is strongly believed that smaller the size of the NPs greater the toxicity. A toxicologically relevant definition of NMs is therefore not yet available, which affect ...[more]

PMID: 32101144

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Project description:Changes in tissue transcriptomes and productivity of Arabidopsis thaliana were investigated during exposure of plants to 2 widely used engineered metal oxide nanoparticles, titanium dioxide (nano-titania) and cerium dioxide (nano-ceria). Microarray analyses confirmed that exposure to either nanoparticle altered the transcriptomes of rosette leaves and roots, with comparatively larger numbers of differentially expressed genes found under nano-titania exposure. Nano-titania induced more differentially expressed genes in rosette leaves, whereas roots had more differentially expressed genes under nano-ceria exposure. MapMan analyses indicated that although nano-titania up-regulated overall metabolism in both tissues, metabolic processes under nano-ceria remained mostly unchanged. Gene enrichment analysis indicated that both nanoparticles mainly enriched ontology groups such as responses to stress (abiotic and biotic), and defense responses (pathogens), and responses to endogenous stimuli (hormones). Nano-titania specifically induced genes associated with photosynthesis, whereas nano-ceria induced expression of genes related to activating transcription factors, most notably those belonging to the ethylene responsive element binding protein family. Interestingly, there were also increased numbers of rosette leaves and plant biomass under nano-ceria exposure, but not under nano-titania. Other transcriptomic responses did not clearly relate to responses observed at the organism level, possibly because of functional and genomic redundancy in Arabidopsis, which may mask expression of morphological changes, despite discernable responses at the transcriptome level. In addition, transcriptomic changes often relate to transgenerational phenotypic development, and hence it may be productive to direct further experimental work to integrate high-throughput genomic results with longer term changes in subsequent generations. Environ Toxicol Chem 2017;36:71-82. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Dataset Information

Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo.

Background

Results

Conclusion

Publications

Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo.

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