Effects of physicochemical properties of TiO2 nanomaterials for pulmonary inflammation, acute phase response and alveolar proteinosis in intratracheally exposed mice

Danielsen, Pernille Høgh; Knudsen, Kristina Bram; Štrancar, Janez; Umek, Polona; Koklic, Tilen; Garvas, Maja; Vanhala, Esa; Savukoski, Sauli; Ding, Yaobo; Madsen, Anne Mette; Jacobsen, Nicklas Raun; Weydahl, Ingrid Konow; Berthing, Trine; Poulsen, Sarah Søs; Schmid, Otmar; Wolff, Henrik; Vogel, Ulla

doi:10.1016/j.taap.2019.114830

Cited by 68 publications

(79 citation statements)

References 52 publications

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“…We note that the exposed epithelium also produces cauliflowers in our co-culture (SI section S0h), reproducing the bio-nano agglomerates observed in vivo in the alveolar region of the lungs of particle exposed mice ( Fig. 1b) 13 .…”

Section: The Role Of Actinsupporting

confidence: 83%

“…Note, that similar structures were observed both in vivo and in vitro after exposure to crystalline quartz (DQ12), a well-known occupational hazard causing pulmonary alveolar proteinosis (PAP) 13 , but not for all carbon nanotubes (CNTs) 27,28 .…”

Section: Passivation Of Nanomaterialsmentioning

confidence: 73%

“…TiO2 nanotubes were selected as the model material because they induce very high and long-lasting chronic inflammatory responses in vivo accompanied by markedly disturbed alveolar integrity of the lungs, defined as alveolar proteinosis 13 , with bio-nano agglomerates in the alveoli (Fig. 1b, violet structures).…”

Section: Passivation Of Nanomaterialsmentioning

confidence: 99%

“…The average hydrodynamic particle size of the TiO2 nanotube in suspension (3.24 mg/ ml) was determined by Dynamic Light Scattering (DLS). The TiO2 nanotube suspension had a bimodal size distribution with a major peak at 60 nm and a narrow peak at 21 nm 13 .The intensity-based zaverage size was 168.7 nm and the polydispersity index (PI) was 0.586, indicating some polydispersity in the suspensions. Endotoxin levels were measured using the Limulus Amebocyte Lysate Assay.…”

Section: Transcriptomics In Vitromentioning

confidence: 99%

“…Exceptionally long-lasting inflammatory responses, reflected in prolonged accumulation of infiltrated leukocytes in the lungs, have been shown to follow both single [13][14][15][16][17][18] and repetitive exposure [19][20][21] to some nanomaterials. The insolubility and bio-persistency of the particles have been associated with continuous release of pro-inflammatory mediators from irritated resident cells or dying immune cells, frequently co-observed with chronic dysregulated lipid metabolism [22][23][24][25][26][27] .…”

Section: Introduction -Mechanism Of Persistent Inflammation Unknownmentioning

confidence: 99%

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From the Roundabout of Molecular Events to Nanomaterial-Induced Chronic Inflammation Prediction

Majaron

Kokot

Sebastijanović

et al. 2020

Preprint

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Many chronic diseases manifest in prolonged inflammation and often ignored dysregulated lipid metabolism. When associated with inhalation of nanomaterials, limited information is available on the relevant molecular events and their causal connections. This prevents reliable prediction of outcomes by efficient testing strategies. To unravel how acute nanomaterial exposure leads to chronic conditions, we employed advanced microscopy and omics in vitro and in vivo together with in silico modelling.For selected metal-oxide nanomaterials, we show that lung epithelial cells survive the exposure by excreting internalized nanomaterials and passivating them on the surface, employing elevated lipid synthesis. Macrophages, on the contrary, lose their integrity whilst degrading the passivized bio-nano agglomerates, releasing the nanomaterials, which are taken up again by the epithelial cells. Constant proinflammatory signalling recruits new phagocytes that feed the vicious cycle of events, resulting in a long-lasting response to a single exposure. The proposed mechanism explains the nanomaterialassociated in vivo chronic outcomes and allows its prediction based on in vitro measurements. Similar mechanisms may trigger other chronic diseases affecting millions of lives worldwide.

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Section: The Role Of Actinsupporting

confidence: 83%

Section: Passivation Of Nanomaterialsmentioning

confidence: 73%

Section: Passivation Of Nanomaterialsmentioning

confidence: 99%

Section: Transcriptomics In Vitromentioning

confidence: 99%

Section: Introduction -Mechanism Of Persistent Inflammation Unknownmentioning

confidence: 99%

See 3 more Smart Citations

From the Roundabout of Molecular Events to Nanomaterial-Induced Chronic Inflammation Prediction

Majaron

Kokot

Sebastijanović

et al. 2020

Preprint

Self Cite

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Titanium Dioxide

Battersby,

Warheit

2023

Patty's Toxicology

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Titanium is a naturally occurring element. The commercially most important titanium compound is pigmentary TiO 2 , whereas nano‐scaled TiO 2 represents only a small amount on the market. Since humans are exposed to TiO 2 at workplace or through consumer products, a thorough evaluation of its potential toxicity has been summarized herein. Dermal absorption of TiO 2 is deemed to be negligible, whereas oral and inhalation absorption has been reported but is assumed to be very low. TiO 2 has been shown to be of low acute oral, dermal, and inhalation toxicity and is considered to be void of skin and eye‐irritating properties. It also does not show any potential for skin and respiratory sensitization. Oral long‐term toxicity studies in rats report no adverse effects, and due to lack of dermal absorption of TiO 2 , it is assumed that dermal exposure is also not a hazard. TiO 2 does not show any primary mutagenicity and is also void of reproductive or developmental toxicity. However, in long‐term inhalation toxicity studies in rats, inflammation, fibroproliferative effects, and lung tumor formation has been observed but only under conditions of excessive particle lung overload. Carcinogenicity under such extreme conditions with complete cessation of lung clearance is considered to not imply a cancer hazard for humans, which is in line with epidemiological studies showing no causative link between TiO 2 particle exposure and cancer risk in humans. However, based on the available animal database, IARC in the past classified TiO 2 as possibly carcinogenic to humans, and the Risk Assessment Committee of ECHA also concluded that TiO 2 warrants a Category 2 classification for carcinogenicity.

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