Semester
Summer
Date of Graduation
2020
Document Type
Thesis
Degree Type
MS
College
Statler College of Engineering and Mineral Resources
Department
Chemical and Biomedical Engineering
Committee Chair
Cerasela Zoica Dinu
Committee Member
Rakesh Gupta
Committee Member
Charter Stinespring
Committee Member
Todd Stueckle
Abstract
Organomodified nanoclays (ONCs: i.e., smectite clays with different organic coatings), act as nanofillers in applications ranging from automotive, to aerospace, and biomedical implementations. Because of their large utilization, ONC industry is projected to be a U.S. $3.3 billion industry by 2023. However, emerging studies showed that ONCs and ONC-nanocomposites could harbor health risks upon pulmonary exposure and along their life cycle, namely during synthesis, handling, use, manipulation, and disposal. Specifically, the potential for exposure and adverse effects on human health primarily includes release of dry particulate during handling, manipulation, release during use, and release during the end-of-life disposal or recycling scenarios. Compared to other ENMs, however, little information exists describing which physicochemical properties contribute to their health risk.
My M.S. work at West Virginia University in Prof. Dinu's group aimed to evaluate acute toxicity of a library of ONCs prior to and after simulated disposal by incineration. The analysis conducted high content screening and real-time electric cell impedance sensing on bronchial epithelial cell monolayers for coupled high-throughput in vitro assessment strategies aimed to evaluate acute toxicity of a library of ONCs prior to and after simulated disposal by incinceration. Coating-, incineration status-, and time-dependent effects were considered to determine changes in the pulmonary airway epithelial monolayer integrity, cell transepithelial resistance, apoptosis, and cell metabolism respectively.
Results showed that after exposure to each particle at its IC50, pristine nanoclay displayed acute loss of monolayer coverage, resistance, and metabolism, coupled with increased number of apoptotic cells. Conversely, three different ONCs of prevalent use displayed little loss of monolayer integrity but exhibited differential coating-depended increased apoptosis and up to 40-45% initial reduction in cell metabolism. Moreover, incinerated byproducts of ONCs exhibited significant loss of monolayer coverage and integrity, increased necrosis, and little evidence of monolayer re-establishment.
These findings indicate that characteristics of organic coating type largely determine mechanism of cytotoxicity and the ability of the monolayer to recover. Use of high content screening, coupled with traditional in vitro assays prove to serve as a rapid pulmonary toxicity assessment tool to thus help define prevention by targeted physicochemical material properties design strategies.
The above contributions to understanding deleterious effect of nanomaterials on human model systems is meritorious and transformative and allows for creating new tools for toxicological pathways assessment to be considered for improved prevention by design strategies and enhanced safety practices.
The above contributions has been included in a co-first author publication, namely: Stueckle, T.*, White, A.*, Wager, A., Gupta, R., Rojanasakul, Y., Dinu, C.Z., "Impacts of Organomodified Nanoclays and their Incincerated Byproducts on Bronchial Cell Monolayer Integrity", Chemical Research in Toxicology (2019) 32, 12, 2445-2458 (*Authors contributed equally).
Recommended Citation
White, Andrew Philip, "In vitro assessment of deleterious impacts of organomodified nanoclays and their incinerated byproducts on human cells" (2020). Graduate Theses, Dissertations, and Problem Reports. 7730.
https://researchrepository.wvu.edu/etd/7730