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-1β 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.

A novel TEM grid sampler for airborne particles to measure the cell culture surface dose

“…Using TEM, the primary size of the spherical shaped TiO 2 particle is determined as 117 nm (Feret minimum). Pristine (bare) TiO 2 nanoparticles are used and well dispersed in stock solution according Murugadoss et al 23 . It was confirmed that the TiO 2 nanoparticles predominantly exist as single particles or very small agglomerates.…”

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System

“…Aggregation describes the assembly of primary particles through covalent or metallic bindings, while agglomeration results from van-der-Waals interactions, hydrogen bonds, adhesion by surface tension, or electrostatic attraction [ 2 , 38 ]. The determination of agglomeration and aggregation status is crucial because it can significantly alter hydrodynamic diameter, size, and the stability of particle-complexes, thus affecting uptake, reactivity, and toxicity [ 39 ].…”

Cytotoxicity Effects of Curcumin Loaded on Chitosan Alginate Nanospheres on the KMBC-10 Spheroids Cell Line

“… 28 Also, the stability of the nanoparticle, crystalline structure, size and agglomeration affect the toxicity and biological distribution of the nanoparticles in the in vivo environment. 29 Chitosan has been mainly utilized in the mixture of nanocomposites that chitosan was a cationic and emulsifier. 30 Besides, chitosan is applied for delivering hydrophobic drugs such as curcumin to cancer cells.…”