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Author ORCID Identifier


Open Access Dissertation

Document Type


Degree Name

Doctor of Philosophy (PhD)

Degree Program

Public Health

Year Degree Awarded


Month Degree Awarded


First Advisor

Alicia R. Timme-Laragy

Second Advisor

Laura N. Vandenberg

Third Advisor

Alexander Suvorov

Fourth Advisor

Yeonhwa Park

Subject Categories

Animals | Developmental Biology | Disorders of Environmental Origin | Endocrinology, Diabetes, and Metabolism | Environmental Health | Environmental Public Health | Hepatology | Maternal and Child Health | Toxicology


The environmental pollutant 3,3’-dichlorobiphenyl (PCB-11) is a lower-chlorinated polychlorinated biphenyl (PCB) congener present in air and water samples. Both PCB-11 and its metabolite, 4-PCB-11-Sulfate, are detected in humans, including in pregnant women. The work conducted for this dissertation takes a developmental toxicology approach and uses zebrafish (Danio rerio) to investigate PCB-11’s potential impacts to the liver and pancreas. Chapter 1 introduces PCBs and the current knowledge gaps. Chapter 2 investigates PCB-11 interactions in short-term 4-day exposures with the Aryl hydrocarbon receptor (Ahr) pathway in both 0-20 mM individual and mixture exposures with other Ahr agonists. In Chapter 3, PCB-11 metabolites 4-OH-PCB-11 and 4-PCB-11-Sulfate are assessed in both 4-day and in longer-term 15-day chronic exposures. Finally in Chapter 4, the role of Nrf2, a master regulator of oxidative stress, is explored in the context of these short and long-term exposure settings. Throughout these chapters, in vivo ethoxyresorufin-O-deethylase (EROD) bioassay, RT-qPCR, RNAseq, Oil-Red-O (ORO) staining, fatty acid profiling, and fluorescence microscopy techniques, as well as the use of Tg(ins:GFP) and Tg(gut:GFP) transgenic and nrf2afh318/fh318 mutant zebrafish, were used to assess toxicity. The results from this work indicate that PCB-11 is a mild Ahr agonist, but in co-exposures can inhibit either the Ahr or downstream Cyp1a enzyme activity depending on the co-exposure, resulting in different toxicity outcomes. 4-PCB-11-Sulfate can also inhibit Cyp1a activity but does not interfere with the toxicity outcomes of co-exposures, however, chronic 15-day exposure to 4-PCB-11-Sulfate increases hepatic neutral lipids 30%, increases pancreatic β-cell cluster area in the primary Islet of Langerhans 8%, and leads to better survival at 80-85% compared to 63-75% for unexposed fish. Nrf2a seems to play a minor role in the Cyp1a enzyme inhibition and phenotypic effects observed with PCB-11 and 4-PCB-11-Sulfate 4-day exposures but plays an important role in development as well as for DHA production in the presence of 4-PCB-11-Sulfate. Chapter 5 discusses the findings from Chapters 2-4. The data presented contributes to the understanding of this sub-class of PCB compounds and provides insight into how PCB-11 could potentially impact human health.


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Creative Commons Attribution-Noncommercial 4.0 License
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