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Access Type

WSU Access

Date of Award

January 2019

Degree Type

Thesis

Degree Name

M.S.

Department

Pharmaceutical Sciences

First Advisor

David K. Pitts

Abstract

Detroit, Michigan a post-industrial city, situated on the banks of the Detroit river receives contaminants from wastewater treatment plants, runoff from urban gardens and agriculture, landfill leachate, abandoned and demolished infrastructure and storm water from impervious surfaces. Contaminants found in local water that come from these sources have been termed contaminants of emerging concern (CECs) which are not regulated and/or monitored by the governing agencies. This type of water contamination is not just a local problem, but a worldwide problem commonly associated with human populations. When considering the larger global picture, we now know that these CECs can come from both urban and agricultural areas. Widespread environmental impact has been detected as effects of chemical exposure on wildlife.

A subset of the known CECs can disrupt the normal endocrine function of humans and wildlife and these are called endocrine disrupting chemicals (EDCs). Evidence of endocrine disruption in the aquatic environment has been reported in fish. This EDC activity has been observed as intersex characteristics, decreases in male to female ratios, and decreased fecundity. Although there are many known or suspected EDCs found in contaminated water, we do not yet understand their relative contribution to the effects observed on wildlife or potentially on human health. Our over-arching hypothesis is that model aquatic organisms can be used to develop a molecular identification model capable of detecting estrogenic and anti-androgenic activity in water using behavioral, morphologic, and genomic data and that this model can be used as a tool to evaluate water quality.

We previously used two model aquatic organisms, Daphnia pulex (invertebrate) and Danio rerio (vertebrate), to evaluate the toxicity of 9 known or suspected EDCs in a behavioral assay system. The 9 EDCs selected were: 4-nonylphenol, atrazine, bisphenol-A, chlorpyrifos, dieldrin, estrone, triclosan, triclocarban, and metformin. My thesis focuses on genomic responses of D. pulex and D. rerio following EDC exposure that is based on concentrations of interest previously determined in the behavioral bioassay system. This study has shown that these two model aquatic organisms are sensitive to environmentally relevant concentrations of EDCs (parts per trillion range, ppt) and a very large number of significant alterations in gene expression have been identified in both organisms. This study has clearly demonstrated the feasibility and potential utility of this two-model organism bioassay approach to studying EDC activity in water.

One of the long-term goals of this project would be to evaluate the estrogenicity and/or anti-androgenic activity of EDC mixtures typically found in sources like wastewater effluent. However, the identification of a specific gene set in Daphnia that would constitute an EDC signal representative of estrogenic and/or anti-androgenic activity in fish has not yet been verified. This would require the exposure of zebrafish to chemical concentrations identical to those used within this study and observing morphological outcomes in sexually differentiated zebrafish that demonstrate endocrine disruption (intersex, male to female ratio, etc.). A future aim of this study is to develop a qPCR plate with a subset of genes that can detect the estrogenic/anti-androgenic properties of contaminated water samples.

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