Validation of an in vitro exposure system for toxicity assessment of air-delivered nanomaterials

Jong Sung Kim; Thomas M Peters; Patrick T O’Shaughnessy; Andrea Adamcakova-Dodd; Peter S Thorne

doi:10.1016/j.tiv.2012.08.030

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Validation of an in vitro exposure system for toxicity assessment of air-delivered nanomaterials

Journal article

Open access

Peer reviewed

Validation of an in vitro exposure system for toxicity assessment of air-delivered nanomaterials

Jong Sung Kim, Thomas M Peters, Patrick T O’Shaughnessy, Andrea Adamcakova-Dodd and Peter S Thorne

Toxicology in vitro, Vol.27(1), pp.164-173

02/2013

DOI: 10.1016/j.tiv.2012.08.030

PMCID: PMC3950355

PMID: 22981796

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Abstract

[Display omitted] ► A nanoparticle generation and in vitro exposure system was validated. ► Lung epithelial cells withstood repeated 4h exposures without losing viability. ► Airborne nanoparticles were delivered to cells with deposition efficiency of 70.3%. ► Dissolution delivered 62% of the Cu mass to the basolateral medium after 8h. ► Cu nanoparticles induced similar toxicity to that seen in mouse inhalation studies. To overcome the limitations of in vitro exposure of submerged lung cells to nanoparticles (NPs), we validated an integrated low flow system capable of generating and depositing airborne NPs directly onto cells at an air–liquid interface (ALI). The in vitro exposure system was shown to provide uniform and controlled dosing of particles with 70.3% efficiency to epithelial cells grown on transwells. This system delivered a continuous airborne exposure of NPs to lung cells without loss of cell viability in repeated 4h exposure periods. We sequentially exposed cells to air-delivered copper (Cu) NPs in vitro to compare toxicity results to our prior in vivo inhalation studies. The evaluation of cellular dosimetry indicated that a large amount of Cu was taken up, dissolved and released into the basolateral medium (62% of total mass). Exposure to Cu NPs decreased cell viability to 73% (p<0.01) and significantly (p<0.05) elevated levels of lactate dehydrogenase, intracellular reactive oxygen species and interleukin-8 that mirrored our findings from subacute in vivo inhalation studies in mice. Our results show that this exposure system is useful for screening of NP toxicity in a manner that represents cellular responses of the pulmonary epithelium in vivo.

Nanoparticles

Spatial uniformity

Air–liquid interface

Deposition efficiency

Lung cells

Cellular dose

Details

Title: Subtitle: Validation of an in vitro exposure system for toxicity assessment of air-delivered nanomaterials
Creators: Jong Sung Kim - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242, USA
Thomas M Peters - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242, USA
Patrick T O’Shaughnessy - Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA
Andrea Adamcakova-Dodd - Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA
Peter S Thorne - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Toxicology in vitro, Vol.27(1), pp.164-173
DOI: 10.1016/j.tiv.2012.08.030
PMID: 22981796
PMCID: PMC3950355
NLM abbreviation: Toxicol In Vitro
ISSN: 0887-2333
eISSN: 1879-3177
Publisher: Elsevier Ltd
Grant note: name: NIEHS/NIH, award: P30 ES005605
Language: English
Date published: 02/2013
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Civil and Environmental Engineering; Occupational and Environmental Health; Stead Family Department of Pediatrics
Record Identifier: 9983997367402771

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