Access Type

Open Access Thesis

Date of Award

January 2017

Degree Type

Thesis

Degree Name

M.S.

Department

Pharmaceutical Sciences

First Advisor

David K. Pitts

Abstract

Thousands of chemicals have introduced into the environment as a result of human activity since the industrial revolution, and the U.S. Government Accountability Office has estimated that as many as 1,500 new chemical entities are synthesized each year ("Key Issues: Toxic Chemicals - High Risk Issue," 2017). Many of these chemicals are now found in surface water and ground water and can have detrimental effects on environmental health and on human health. This anthropogenic contamination has resulted in the labeling of the diverse array of chemicals found in water, which are not routinely monitored or regulated, as contaminants of emerging concern or CECs. Some of the CECs of greatest concern are those capable of disrupting endocrine system function.

The endocrine system of humans and wildlife is designed to be very sensitive to endogenous signaling molecules we call hormones. Exogenous chemicals that can mimic or augment the signaling by hormones are capable of disrupting the normal function of endocrine systems, and this subset of CECs has been called endocrine disrupting chemicals or EDCs. EDCs can have a broad range of deleterious impacts on biological function and can affect development and reproduction, and cause cancer. Although EDC effects have been reported in the literature, the number of newly released and existing chemicals in the environment underscores the need for better EDC detection tools. Some of the most commonly observed evidence for endocrine disruption in the environment comes from the observation of feminized male fish or altered sex ratios with fewer males downstream of wastewater effluent outfalls. Evidence strongly suggests that these EDC effects are due to the estrogenic and/or anti-androgenic influence of chemical contaminants in the water. Some of the known or suspected EDCs fall into the category of pharmaceuticals and personal care products (PPCPs).

We proposed that two aquatic model organisms, one invertebrate – Daphnia pulex (waterflea), and one vertebrate - Danio rerio (zebrafish), can be used to detect the estrogenicity and anti-androgenic effects of known or suspected PPCPs in water. The hypothesis was that known or suspected EDCs have detectable behavioral effects, and that the characterization of these behavioral effects, when combined with developmental and gene expression data, will enable the creation of a mathematical model that can identify chemicals contributing to the estrogenicity or ant-angdrogenic qualities of contaminated water. Furthermore, the study of the impact of EDCs on the behavior of two different aquatic organisms can increase the discriminating power of the behavioral results and broaden the application of these results to the assessment of potential ecological impact.

This study of behavioral effects is one component of a larger EDC project, and it focused on selected PPCPs suspected or known to be endocrine disrupting chemicals: estrone, triclosan (TCS), triclocarban (TCC), and metformin. A novel optical bioassay examined the effects of these four chemicals on the swimming behavior of the two different aquatic species. Significant concentration-dependent differences in responses were found across the series of chemicals and between species for a given chemical (metformin, estrone), and similar responses to one chemical were found for both species (TCS). These behavioral studies in conjunction with the planned morphological evaluation of development will provide the foundation for interpreting the effects of EDCs on gene expression in the last phase of the project, and the creation of the initial prototype of a mathematical model to predict the nature of the chemical entities contributing to the estrogenic or anti-androgenic qualities of water samples. This new bioassay approach will compliment and expand the power of existing analytical chemistry techniques and enable more efficient evaluation of the complex issues associated with the contamination of aquatic systems by CECs.

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