"Obtaining whole-animal or population-level data to evaluate the thousands of anthropogenic chemicals that exist is impractical. The U.S. National Research Council (NRC) recommended that new, predictive approaches be developed to examine toxicant effects ranging from molecular level changes in individuals to impacts on entire populations. One approach that can help meet the goals of the NRC is the adverse outcome pathway (AOP), a conceptual framework linking a single molecular initiating event to an adverse outcome at the level of the population considered relevant for risk assessment. My research is focused on the development of two AOPs; 1) Reduced fecundity in female fish due to an impairment of vitellogenin production following exposure to select neurotoxicants and 2) Reduced survival and growth of early life stage fish as a result of behavioral impairments following neurotoxicant exposure. Much of the AOP focus has been on fish reproduction, specifically the initiation of the hormonal cascade within the hypothalamic-pituitary-gonadal (HPG) axis and the formation of vitellogenin, an egg yolk precursor protein. Previous efforts modeling fish vitellogenin production were driven by gonadotropin production and did not incorporate components that influenced its release. Many end products of this hormonal cascade are controlled by the upstream production of neurotransmitters, such as gamma-aminobutyric acid and dopamine. Inclusion of a neurotransmission compartment can increase the predictive power and accuracy of the fish vitellogenin model. I hypothesized that several environmental toxicants will interact with and disrupt the function of neurotransmitter receptors and enzymes that have critical roles in vertebrate reproduction and could cause population level effects. Specifically, I explored two case studies, methylmercury (MeHg) and pulp and paper mill effluent (PPME) and their potential for neurotoxic effects on subsequent vitellogenin production. My goal was to incorporate a neurotransmission compartment into the existing fish vitellogenesis model using results from cell-free high throughput bioassays to predict adverse reproductive outcomes following exposure to contaminants. This model highlighted the importance of understanding pathway differences between species and showed a proof of principle concept for determining how perturbations to physiological systems could enhance or inhibit fish reproduction. Additionally, there is a current need for developing an AOP for fish early-life-stage toxicity as conducting traditional early-life stage tests are labor- and resource-intensive and do not provide essential information regarding a chemical's mode of action. Toxicants have been shown to cause adverse effects on larval fish behavior well below exposure concentrations that induce mortality. Behavior can be incorporated into an individual-based model (IBM) to predict how adverse effects on an individual's behavior cause ramifications at the population level. Previous research has shown that MeHg exposure can impair larval fish behavior. I hypothesized that growth rate and survival of a larval fish population will be reduced due to impaired swimming speed and reduced foraging efficiency following MeHg exposure. My approach was to adapt a previously built IBM in order to link these sublethal behavioral effects to population relevant outcomes such as survival and growth. The last chapter uses the IBM to explore several ecological factors that may explain the recent low recruitment of yellow perch in Lake Michigan. This work highlighted the importance of assessing complex mixtures of stress including both abiotic and biotic sources which can interact and adversely affect the pelagic larval fish community."--Pages ii-iii.
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