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Toxicology of Functionalized Nanomaterials in Fishes

  • Author / Creator
    Felix, Lindsey C
  • Engineered nanomaterials (NMs), tiny synthetic materials having at least one dimension between one and one hundred billionths of a metre, are increasingly being developed for and incorporated into a myriad of commercial, consumer, and industrial applications due to their unique and tailorable properties. Widespread and expanding production and use of engineered NMs implies that they will enter aquatic environments through accidental (e.g. down-the-drain disposal of NM-containing consumer products) or intentional (e.g. groundwater remediation efforts) anthropogenic release and thus have the potential to interact with and adversely affect living organisms like fishes. My research aimed to identify the physical and chemical properties intrinsic to the NMs themselves (e.g. surface coatings or functional groups) and extrinsic environmental factors (e.g. solar radiation) that modulate NM toxicity using fish model systems. Several functionalized and nonfunctionalized metal oxide and carbon-based NMs were characterized using appropriate analytical instruments and techniques. The information derived from these studies was used to better understand the interactions between NMs and biological systems and to accurately evaluate and interpret the toxicological effects resulting from exposure. Zebrafish (Danio rerio) embryos were exposed to a range of NM concentrations (0.1 2000 mg/L) under laboratory and more environmentally realistic conditions for up to seven days, multiple endpoints indicative of toxicity (e.g. alterations in gene expression, delayed development, incidences of malformation, increased antioxidant enzyme activity, lethality, lipid peroxidation, etc.) were assessed, and the potential mechanisms underlying noted toxicity were elucidated. Moreover, a combination of flow cytometry and laser scanning confocal microscopy was used to investigate the cellular uptake mechanisms of NMs and to determine their subsequent fate within rainbow trout (Oncorhynchus mykiss) gill epithelial cells. The work presented here represents the first comprehensive, explicit, and systematic evidence-based report on the toxicology of functionalized NMs in fishes and some of the major findings were as follows. Most NMs adsorbed to or settled on the embryonic zebrafish while some traversed the chorion and sorbed to the developing fish within the chorionic membrane. However, the NMs located on the external larval surface could not be distinguished from those that may have been internalized by the animal using in vivo methods. Further in vitro measurements demonstrated that these surface bound NMs were actively taken up into rainbow trout gill epithelial cells via clathrin mediated endocytosis and became localized within lysosomal compartments. Surface functionalization was found to affect the characteristics of certain carbon based NMs resulting in differential responses and thus played a key role in determining their toxicity at different levels of biological organization. Furthermore, the surface coating was shown to lessen the severity of reactive oxygen species induced effects of metal oxide NMs on embryo-larval zebrafish and toxicity was reported to depend on ultraviolet light exposure. Taken together, improved knowledge and understanding of the factors that modulate NM toxicity and the mechanisms by which NMs cause effects will facilitate accurate toxicological assessments by researchers and thus allow risk assessors to better predict the potential impact of engineered NMs when they are unintentionally or purposefully released into the aquatic environment.

  • Subjects / Keywords
  • Graduation date
    2016-06:Fall 2016
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3GF0N21X
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Biological Sciences
  • Specialization
    • Physiology, Cell and Developmental Biology
  • Supervisor / co-supervisor and their department(s)
    • Goss, Greg
  • Examining committee members and their departments
    • Seubert, John (Department of Pharmacology)
    • Helbing, Caren (Department of Biochemistry and Microbiology)
    • Stafford, James (Department of Biological Sciences)
    • Tierney, Keith (Department of Biological Sciences)