Browsing by Author "Jayasundara, Nishad"
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Item Embargo Connecting Environmental Exposures to Toxicology: Exposure studies using Silicon Wristbands and Whole Model Organisms(2024-04-26) Shahid, SakinaSilicone wristbands have emerged as passive sampling tools to monitor environmental contaminant exposures. They work by mimicking the skin, where SVOCs (semi volatile organic compounds) and VOCs (volatile organic compounds) can sorb onto the surface of the wristband and accumulate over time, providing time aggregated measures of chemical burden especially by dermal and inhalation routes of exposure. They are non-invasive compared to traditional techniques used to assess exposure, such as urine and serum collection, and relatively easy to transport and store, allowing for more participation. My research introduces an approach using zebrafish (Danio Rerio) to investigate biological responses to wristband extracts, focusing on neurobehavior as an endpoint. Neurobehavior is evaluated using a light/dark assay, wherein larvae respond to light and dark stimuli and deviation from the expected response to these stimuli is interpreted as indicative of potential developmental issues. After developing a protocol, I applied this methodology to explore the toxicity of chemicals captured on wristbands from a cohort based in a farming community at high risk of exposure to agrochemicals in Sri Lanka. The wristbands were worn for 7 days during a non farming season and captured varying exposures to chemical classes such as PAHs, Phthalates, Flame Retardants and Pesticides. Upon analyzing the total distance zebrafish swam in light and dark conditions, a Dunnet’s post hoc test revealed that zebrafish behavior in 7 out of 10 wristbands in the farmer group and 8 out of 10 wristbands in the non farmer group was statistically significantly different compared to the field blank. Most groups were showing hyperactivity in terms of the total distance traveled compared to the field blank, with one wristband exposure group showing hypoactivity. This was the first study to utilize wristband extracts for exposures in zebrafish, helping bridge the gap between exposure science and mixtures toxicology.Item Open Access Mitochondrial dysfunction and oxidative stress contribute to cross-generational toxicity of benzo(a)pyrene in Danio rerio.(Aquatic toxicology (Amsterdam, Netherlands), 2023-10) Kozal, Jordan S; Jayasundara, Nishad; Massarsky, Andrey; Lindberg, Casey D; Oliveri, Anthony N; Cooper, Ellen M; Levin, Edward D; Meyer, Joel N; Giulio, Richard T DiThe potential for polycyclic aromatic hydrocarbons (PAHs) to have adverse effects that persist across generations is an emerging concern for human and wildlife health. This study evaluated the role of mitochondria, which are maternally inherited, in the cross-generational toxicity of benzo(a)pyrene (BaP), a model PAH and known mitochondrial toxicant. Mature female zebrafish (F0) were fed diets containing 0, 12.5, 125, or 1250 μg BaP/g at a feed rate of 1% body weight twice/day for 21 days. These females were bred with unexposed males, and the embryos (F1) were collected for subsequent analyses. Maternally-exposed embryos exhibited altered mitochondrial function and metabolic partitioning (i.e. the portion of respiration attributable to different cellular processes), as evidenced by in vivo oxygen consumption rates (OCRs). F1 embryos had lower basal and mitochondrial respiration and ATP turnover-mediated OCR, and increased proton leak and reserve capacity. Reductions in mitochondrial DNA (mtDNA) copy number, increases in mtDNA damage, and alterations in biomarkers of oxidative stress were also found in maternally-exposed embryos. Notably, the mitochondrial effects in offspring occurred largely in the absence of effects in maternal ovaries, suggesting that PAH-induced mitochondrial dysfunction may manifest in subsequent generations. Maternally-exposed larvae also displayed swimming hypoactivity. The lowest observed effect level (LOEL) for maternal BaP exposure causing mitochondrial effects in offspring was 12.5 µg BaP/g diet (nominally equivalent to 250 ng BaP/g fish). It was concluded that maternal BaP exposure can cause significant mitochondrial impairments in offspring.Item Open Access Renal Health, Groundwater Contamination, and Water Policy in Sri Lanka(2022-04-17) O'Hara, ShannonChronic Kidney Disease of unknown (or uncertain) etiology (CKDu) is of increasing prevalence in Sri Lanka. The disease predominantly affects low-income, male agricultural workers, many of whom live in the country’s Northern Central Province and rely on groundwater for drinking water. This project took samples from wells from multiple Sri Lankan districts and analyzed them for the presence of potential contaminants. A literature review was also conducted to assess effective policies regarding alternative sources of drinking water, with a specific focus on reverse osmosis (RO) units. This project did not identify a clear association between a measured contaminant or set of contaminants and disease, suggesting that any link may involve a contaminant not measured by this project, such as agrochemicals, or a complex synergism. A series of policy recommendations were promulgated, which can be used to ensure that Sri Lankans have access to safe, sanitary drinking water and that the incidence of CKDu is reduced.Item Open Access Toxicity of an Urban Creek: Effects of developmental exposure to water from Ellerbe Creek Watershed on zebrafish (Danio rerio) swimming behavior(2023-04-28) Barbo, NadiaUrban changes in land use, such as increasing impervious surface cover and the building of stormwater pipes, result in anthropogenically manipulated water drainage into local watersheds. Along with changes in drainage patterns, urbanization introduces new chemicals into the watershed or changes existing chemical concentrations. Therefore, contaminant sources in urban watersheds, such as stormwater runoff and municipal wastewater discharge, lead to complex mixtures of chemicals entering aquatic ecosystems. Urbanization is projected to increase across the world, resulting in more changes in hydrology and more chemicals entering urban watersheds. While it is known that urban infrastructure and pollution changes the chemical and physical properties of an urban watershed, there is little known about how these changes impact the developmental health of aquatic organisms that call the watershed home. It is important to understand developmental toxicity because changes in development can impact the adult fitness of organisms, ultimately impacting the population and potentially the entire ecosystem. In Durham, North Carolina Ellerbe Creek Watershed is a highly developed watershed with 22% impervious surface by area. Ellerbe Creek (EC) cuts through Downtown Durham and has various urban pollution sources such as industrial, residential, and recreational development. Due to the exceedance of water quality standards, multiple segments of EC are considered impaired under the Clean Water Act. EC is home to many species of fish. Understanding the influence of chemical contamination on fish populations is important for estimating the broader ecosystem health. To examine the effects that EC chemical constituents may have on fish development, we conducted a series of behavioral toxicity studies following treatment with EC water using zebrafish (Danio rerio). Specifically, we raised zebrafish in urban watershed samples collected during four seasons across sixteen points along EC. Sites were selected based on their location along the main branch or tributaries of EC. Main branch sites were selected based on their spatial relationship (upstream versus downstream) to a wastewater treatment plant. Tributary sites differed in their local land cover, resulting in highly varying chemical profiles at each site. Sampling seasons roughly corresponded with seasonal variance in water quality parameters. At five days post fertilization, we assessed the swimming behavior of the zebrafish. This allowed us to determine if developing in differing urban water samples had an adverse effect on zebrafish behavior, which can ultimately have an impact on survivability and competitiveness of fish larvae. When analyzing our data, we wanted to answer four leading questions. The first was whether any effect on swimming behavior was seen between fish raised in EC samples compared to fish raised in control water. We then wanted to know if the wastewater treatment site’s effluent impacted the swimming behavior of zebrafish since we knew that the majority of water in sites downstream of the wastewater treatment plant was comprised of wastewater effluent. Similarly, we asked if fish raised in water samples from different tributaries showed differing swimming behavior. Tributaries act as a snapshot of the water that is feeding into them and the water chemistry of one does not change the water chemistry of another – allowing us to better understand the conditions that may result in urban water toxicity. Finally, we aimed to evaluate how the collection season of the water samples may influence swimming behavior. Results show spatial and temporal heterogeneity in the impacts of water samples on zebrafish larval behavior. Fish raised in EC water samples had varying responses in their swimming behavior. Among fish raised in select EC water samples, there was a change in behavior compared to fish raised in control water. This change appeared to be both spatial, varying based on collection site, and temporal, varying based on collection month. All changes in fish swimming behavior were hypoactive compared to the controls. We did not see a difference in swimming behavior between fish raised in water samples from upstream of the wastewater effluent site compared to fish raised in water samples from downstream of the wastewater effluent site. There was, however, a difference in swimming behavior among fish raised in different tributary water samples. Significant site-specific heterogeneity among tributaries appeared to be driven by one to two collection sites and varied by collection month. This study aimed to better understand how water from EC impacts the health and development of organisms living in the creek. The effects seen on swimming behavior of zebrafish raised in EC water samples suggest that the urban watershed has an adverse effect on the development of the zebrafish. Different sites and seasons had different chemical and physical properties that may have resulted in these changes and future research focused on identifying the drivers of this behavioral change is imperative for understanding and ameliorating urban watershed ecosystem health. Broadly, the impacts of urban development on watershed chemical constituents and their toxicity and on ultimate ecosystem-level consequences are an important consideration when planning future development. To this end, whole organismal toxicity assays can serve to improve ecological risk assessments.Item Embargo Zebrafish Developmental Neurotoxicity of PFMOAA – an Emerging PFAS in the Cape Fear River Watershed(2024-04-25) Davis, KalliePerfluoro-2-methoxyacetic acid (PFMOAA) is an understudied but highly detected per- and poly-fluoroalkyl substance (PFAS) in the lower Cape Fear River. Despite high environmental detection, little is known about the toxicity of this chemical. This study is the first which assesses the developmental neurotoxicity of PFMOAA at environmentally relevant concentrations (0.01 µM-1000 µM) in a zebrafish model. Neurobehavioral effects following developmental exposure to PFMOAA were assessed in larval, juvenile, and adolescent developmental stages, finding that PFMOAA is capable of significantly altering neurobehavior throughout zebrafish development. Additionally, zebrafish which were exposed to a complex environmental mixture with high PFMOAA concentrations showed similar neurobehavioral effects with individuals exposed to PFMOAA alone, suggesting the chemical is acting at environmentally relevant concentrations and warrants further investigation.