Characterization of partially soluble copper oxide nanoparticles for evaluating the role of deposited dose rate in respiratory tract target cell responses
EMSL Project ID
47663
Abstract
The increasing use of nanoparticles (NPs < 100 nm in at least one dimension) in industrial settings has led to a greater concern about the potential for human exposures. Although there are several likely routes of exposure to NPs, our laboratory focuses on the respiratory tract (RT) and subsequent effects in the lungs. Since there is a lack of real world exposure and hazard assessment data for NPs, there are no regulations regarding RT exposures. Due to the overwhelming number of NPs being produced, it is not possible to interrogate all of them for hazard assessment purposes. Therefore, there is a need for experimental models that reflect real world exposures, are adequately predictive of NP hazard, and that successfully link the in vitro responses of target cells to the observed effects in vivo. Although studies have been done to assess toxicological responses to NPs, they often involve high dose rate, or bolus, delivery of NPs that may not reflect real world exposure conditions. In addition, little has been published regarding the role of high dose rate NP delivery in response outcomes. Research Plan: In order to address these research gaps, we will determine how dose rate affects toxicological responses in the RT. We hypothesize that the NP delivered dose rate affects the acute inflammatory responses of RT target cells. We will expose rat type I alveolar epithelial cells and F-344 male rats to partially soluble copper oxide NPs to assess the role of NP delivered dose rate. In order to test this, the deposited mass dose will be held constant for high dose rate and low dose rate NP delivery. High dose rate exposures will consist of conventional bolus delivery of NPs in cell culture medium to R-3/1 cells and intratracheal instillations of NPs suspended in saline to the RT of rats. In contrast, low dose rate exposures will be achieved via aerosol delivery using a novel air-liquid interface (ALI) exposure system with R 3/1 cells and whole body inhalation with rats. Our objectives will be met through collaboration with EMSL by: 1) characterizing the NPs used for exposure, and; 2) optimizing the delivered dose for in vitro and in vivo exposure systems with ISDD and MPPD software, respectively. Following the completion of the aforementioned aims, we will assess the impact of delivered dose rate on NP-induced inflammatory responses in RT target cells. Expected Results: These studies are designed to evaluate the predictive nature of current in vitro and in vivo high dose rate (bolus) NP delivery techniques. This proposal incorporates the EMSL mission of integrating both experimental and computational resources for nanotoxicology studies, which are ultimately aimed at understanding the effects of NP exposures under realistic exposure conditions. The information gained is critical to a more fundamental understanding of the mechanisms of response to NPs and is also important for establishing safety regulations regarding the production and disposal of NPs in occupational settings.
Project Details
Project type
Exploratory Research
Start Date
2012-12-05
End Date
2013-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Baer DR, MH Engelhard, GE Johnson, J Laskin, J Lai, KT Mueller, P Munusamy, S Thevuthasan, H Wang, NM Washton, AC Elder, BL Baisch, AS Karakoti, SVNT Kuchibhatla, and DW Moon. 2013. "Surface Characterization of Nanomaterials and Nanoparticles: important needs and challenging opportunities." Journal of Vacuum Science and Technology A--Vacuum, Surfaces and Films 31(5):Article No. 050820. doi:10.1116/1.4818423