Toxicity of Silver Nanoparticles at the Air-Liquid Interface

Silver nanoparticles are one of the most prevalent nanomaterials in consumer products. Some of these products are likely to be aerosolized, making silver nanoparticles a high priority for inhalation toxicity assessment. To study the inhalation toxicity of silver nanoparticles, we have exposed cultured lung cells to them at the air-liquid interface. Cells were exposed to suspensions of silver or nickel oxide (positive control) nanoparticles at concentrations of 2.6, 6.6, and 13.2 μg cm−2(volume concentrations of 10, 25, and 50 μg ml−1) and to 0.7 μg cm−2silver or 2.1 μg cm−2nickel oxide aerosol at the air-liquid interface. Unlike a number ofin vitrostudies employing suspensions of silver nanoparticles, which have shown strong toxic effects, both suspensions and aerosolized nanoparticles caused negligible cytotoxicity and only a mild inflammatory response, in agreement with animal exposures. Additionally, we have developed a novel method using a differential mobility analyzer to select aerosolized nanoparticles of a single diameter to assess the size-dependent toxicity of silver nanoparticles.

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Use of Cause-and-Effect Analysis to Optimize the Reliability of In Vitro Inhalation Toxicity Measurements Using an Air–Liquid Interface

Chemical Research in Toxicology ◽

10.1021/acs.chemrestox.1c00080 ◽

2021 ◽

Author(s):

Elijah J. Petersen ◽

Monita Sharma ◽

Amy J. Clippinger ◽

John Gordon ◽

Aaron Katz ◽

...

Keyword(s):

Liquid Interface ◽

Inhalation Toxicity ◽

Effect Analysis ◽

Cause And Effect ◽

Cause And Effect Analysis ◽

Air Liquid Interface

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Air-liquid interface exposure of in vitro lung models:improvement and application to study inhalation toxicity of aircraft-related air pollutants

10.33540/108 ◽

2021 ◽

Author(s):

◽

Ruiwen He

Keyword(s):

Air Pollutants ◽

Liquid Interface ◽

Inhalation Toxicity ◽

Air Liquid Interface

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Parametric Optimization of an Air–Liquid Interface System for Flow-Through Inhalation Exposure to Nanoparticles: Assessing Dosimetry and Intracellular Uptake of CeO2 Nanoparticles

Nanomaterials ◽

10.3390/nano10122369 ◽

2020 ◽

Vol 10 (12) ◽

pp. 2369 ◽

Cited By ~ 1

Author(s):

Lars Leibrock ◽

Harald Jungnickel ◽

Jutta Tentschert ◽

Aaron Katz ◽

Blaza Toman ◽

...

Keyword(s):

Co2 Concentration ◽

Liquid Interface ◽

In Vivo Studies ◽

Inhalation Toxicity ◽

Exposure System ◽

Inhalation Study ◽

Flow Through ◽

Air Liquid Interface

Air–liquid interface (ALI) systems have been widely used in recent years to investigate the inhalation toxicity of many gaseous compounds, chemicals, and nanomaterials and represent an emerging and promising in vitro method to supplement in vivo studies. ALI exposure reflects the physiological conditions of the deep lung more closely to subacute in vivo inhalation scenarios compared to submerged exposure. The comparability of the toxicological results obtained from in vivo and in vitro inhalation data is still challenging. The robustness of ALI exposure scenarios is not yet well understood, but critical for the potential standardization of these methods. We report a cause-and-effect (C&E) analysis of a flow through ALI exposure system. The influence of five different instrumental and physiological parameters affecting cell viability and exposure parameters of a human lung cell line in vitro (exposure duration, relative humidity, temperature, CO2 concentration and flow rate) was investigated. After exposing lung epithelia cells to a CeO2 nanoparticle (NP) aerosol, intracellular CeO2 concentrations reached values similar to those found in a recent subacute rat inhalation study in vivo. This is the first study showing that the NP concentration reached in vitro using a flow through ALI system were the same as those in an in vivo study.

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Mimicking exposures to acute and lifetime concentrations of inhaled silver nanoparticles by two different in vitro approaches

Beilstein Journal of Nanotechnology ◽

10.3762/bjnano.5.149 ◽

2014 ◽

Vol 5 ◽

pp. 1357-1370 ◽

Cited By ~ 30

Author(s):

Fabian Herzog ◽

Kateryna Loza ◽

Sandor Balog ◽

Martin J D Clift ◽

Matthias Epple ◽

...

Keyword(s):

Silver Nanoparticles ◽

Emerging Market ◽

Real Life ◽

Liquid Interface ◽

Human Interaction ◽

Primary Concern ◽

Ag Nps ◽

Air Liquid Interface ◽

Submerged Conditions

In the emerging market of nano-sized products, silver nanoparticles (Ag NPs) are widely used due to their antimicrobial properties. Human interaction with Ag NPs can occur through the lung, skin, gastrointestinal tract, and bloodstream. However, the inhalation of Ag NP aerosols is a primary concern. To study the possible effects of inhaled Ag NPs, an in vitro triple cell co-culture model of the human alveolar/airway barrier (A549 epithelial cells, human peripheral blood monocyte derived dendritic and macrophage cells) together with an air–liquid interface cell exposure (ALICE) system was used in order to reflect a real-life exposure scenario. Cells were exposed at the air–liquid interface (ALI) to 0.03, 0.3, and 3 µg Ag/cm2 of Ag NPs (diameter 100 nm; coated with polyvinylpyrrolidone: PVP). Ag NPs were found to be highly aggregated within ALI exposed cells with no impairment of cell morphology. Furthermore, a significant increase in release of cytotoxic (LDH), oxidative stress (SOD-1, HMOX-1) or pro-inflammatory markers (TNF-α, IL-8) was absent. As a comparison, cells were exposed to Ag NPs in submerged conditions to 10, 20, and 30 µg Ag/mL. The deposited dose per surface area was estimated by using a dosimetry model (ISDD) to directly compare submerged vs ALI exposure concentrations after 4 and 24 h. Unlike ALI exposures, the two highest concentrations under submerged conditions promoted a cytotoxic and pro-inflammatory response after 24 h. Interestingly, when cell cultures were co-incubated with lipopolysaccharide (LPS), no synergistic inflammatory effects were observed. By using two different exposure scenarios it has been shown that the ALI as well as the suspension conditions for the lower concentrations after 4 h, reflecting real-life concentrations of an acute 24 h exposure, did not induce any adverse effects in a complex 3D model mimicking the human alveolar/airway barrier. However, the highest concentrations used in the ALI setup, as well as all concentrations under submerged conditions after 24 h, reflecting more of a chronic lifetime exposure concentration, showed cytotoxic as well as pro-inflammatory effects. In conclusion, more studies need to address long-term and chronic Ag NP exposure effects.

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