Date of Graduation

2016

Document Type

Thesis

Degree Type

MS

College

School of Medicine

Department

Microbiology, Immunology, and Cell Biology

Committee Chair

Aaron Erdely

Committee Co-Chair

Jim Antonini

Committee Member

Vince Castranova

Committee Member

Tim Nurkiewicz

Abstract

Nanotechnology is the science of developing and manipulating molecular structures smaller than one hundred nanometers in at least one dimension. These structures are collectively called engineered nanomaterials. A subgroup of these engineered nanomaterials are multi-walled carbon nanotubes (MWCNT). They are of great interest to industry because of their small size, large surface area, strength, and conductivity in comparison to materials currently used. Practical applications of MWCNT include improvements for water filtration systems, composites, and drug delivery. The same properties that make them advantageous for industry may also confer adverse health effects. For workers in the U.S. handling CNTs, the process of synthesizing and handling the dry powder form has been shown to be the greatest risk for inhalation exposure.;Companies synthesize or purchase as-produced multi-walled carbon nanotubes (AP-MW), apply a polymer coating (PC-MW), then embed the PC-MW into a composite (e.g. thermoplastic or fiberglass matrix). The intermediate step of polymer coating the AP-MW is for increased dispersion in order to use less material, improve bonding to epoxy matrices for increased strength, and better handling to reduce exposure. Workers are potentially exposed at each production stage especially from dry powder handling of the AP-MW and PC-MW. Comprehensive toxicological data on AP-MW and paired PC-MW remains sparse. The aim of this study was to understand the effect of polymer coatings on the toxicity of AP-MW in vivo. Two AP-MW, with different characteristics, were chosen for this study. Each AP-MW came from a distinct manufacturer, each with the polymer coated version for toxicological analyses.;All materials used for the in vivo toxicological studies were comprehensively characterized (e.g., length, width, surface area, etc.). Male C57BL/6J mice were dosed by oropharyngeal aspiration with vehicle (physiologic dosing medium), AP-MW or PC-MW from each company at 4 microg (workplace relevant) or 40 microg (known to induce pathology) and sacrificed at 4 h, 1, 7, 28 and 84 d post-exposure. Post-exposure analyses included: bronchoalveolar lactate dehydrogenase activity (cytotoxicity), cell influx (inflammation) and inflammatory proteins, and relative mRNA expression in pulmonary tissue. Qualitative pathological endpoints such as granuloma formation and fibrosis were examined in conjunction with pulmonary biodistribution primarily to address differences due to the polymer coating. Both AP-MW induced time- and dose-dependent measures of pulmonary cytotoxicity, inflammatory cell influx, and inflammatory proteins that resolved by 84 d post-exposure. The PC-MW from Company 1 had no additional effect on induced pulmonary cytotoxicity, inflammatory cell influx, or inflammatory gene expression and inflammatory protein production as compared to the respective AP-MW. However, pulmonary cytotoxicity, inflammatory cell and inflammatory protein production were attenuated in the PC-MW exposed groups from Company 2 in comparison to the respective AP-MW. Based on qualitative observations of AP-MW and PC-MW from Company 1, particles deposited mostly within the bronchioles, were generally cleared by 84 d while a small portion was persistent in alveolar regions. There was no difference in histopathology with respect to the materials compared from Company 1. Similar distribution of particle deposition in lung compartments was observed for AP-MW and PC-MW exposed groups from Company 2, however a larger fraction deposited into alveolar regions. Small granulomas were observed in the bronchioles of AP-MW exposed groups from Company 2. In contrast, granuloma formation was absent in the PC-MW exposed groups with slightly more particle aggregation. In conclusion, the two polymer coatings studied did not increase the pulmonary toxicity compared to the AP-MW. In fact, inflammation and histopathology was attenuated in mice exposed to the polymer coating from Company 2. It is evident that pulmonary toxicity, from AP-MW to PC-MW, must be carefully considered within the occupational setting.

Download

Share

COinS