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Assessing Effects of Exposure to Complex Environmental Mixtures Using Integrated Chemical, Organismal, and Molecular Analyses.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Assessing Effects of Exposure to Complex Environmental Mixtures Using Integrated Chemical, Organismal, and Molecular Analyses./
作者:	Bertolatus, David William.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	132 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-04, Section: B.
Contained By:	Dissertations Abstracts International83-04B.
標題:	Biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28650961
ISBN:	9798538139460

Assessing Effects of Exposure to Complex Environmental Mixtures Using Integrated Chemical, Organismal, and Molecular Analyses.
Bertolatus, David William.

Assessing Effects of Exposure to Complex Environmental Mixtures Using Integrated Chemical, Organismal, and Molecular Analyses. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 132 p.

Source: Dissertations Abstracts International, Volume: 83-04, Section: B.

Thesis (Ph.D.)--University of Colorado at Denver, 2021.

This item must not be sold to any third party vendors.

Humans and wildlife are continuously exposed to complex mixtures of anthropogenic chemicals including pesticides, pharmaceuticals, personal care products, industrial chemicals and more. Exposure to many of these chemicals individually is associated with adverse outcomes at various levels of biological organization. Aquatic habitats are especially susceptible to chemical contamination from point source discharges and non-point source runoff. Much of our understanding of the effects and risk from chemical exposure comes from individual chemical exposures in laboratory settings. Much less is known about the consequences of exposure to the types of complex mixtures that occur in aquatic habitats. Here, I used integrated effects-based exposure assessments to characterize exposure to different chemical mixtures at various sites in the Shenandoah River watershed (SRW). The SRW is a heterogenous landscape with streams impacted by a diversity of human activities. Exposure sites were selected using land-use and point-source effluents to capture variation in the overall level and type of impact between sites. Over the course of three years, we conducted chemical monitoring and mobile-laboratory fish exposures at 9 different locations. Exposure water was analyzed for over 500 organic and inorganic chemicals and transcriptomic, molecular, cellular, and organismal endpoints were measured in exposed fish. Site-specific patterns of chemical occurrence and exposure effects were observed throughout the SRW and were consistent with variation in land-use and effluent impacts. Adverse organismal outcomes were observed at sites impacted by wastewater effluent and agricultural land-use practices. These outcomes included increased mortality and reproductive disruption, that may have implications for population stability in wild fish. Molecular and cellular data were used to evaluate the mechanisms involved in organismal adverse outcomes using the Adverse Outcome Pathway framework. Despite a focus on estrogenic endocrine disruption in wild fish from the SRW, we found little evidence to support an estrogenic AOP and instead gene, pathway, and cellular data suggest more complex mechanisms leading to reproductive disruption. Changes to lipid metabolism and immune processes were observed at sites with evidence of adverse survival and reproductive outcomes, suggesting these mechanisms may be important key events leading to these effects. Effective risk management of complex mixtures requires the identification of individual contaminants or sub-mixtures that are causally responsible for the observed adverse outcomes. To this end, I conducted a context likelihood of relatedness analysis to identify associations between chemical occurrence and changes to gene expression, resulting in a ranked prioritization list of contaminants that can be used to guide future research into mixture exposures.

ISBN: 9798538139460Subjects--Topical Terms:

522710
Biology.
Subjects--Index Terms:

Chemical occurrence

Assessing Effects of Exposure to Complex Environmental Mixtures Using Integrated Chemical, Organismal, and Molecular Analyses.
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500 $a Source: Dissertations Abstracts International, Volume: 83-04, Section: B.
500 $a Advisor: Vajda, Alan M.
502 $a Thesis (Ph.D.)--University of Colorado at Denver, 2021.
506 $a This item must not be sold to any third party vendors.
520 $a Humans and wildlife are continuously exposed to complex mixtures of anthropogenic chemicals including pesticides, pharmaceuticals, personal care products, industrial chemicals and more. Exposure to many of these chemicals individually is associated with adverse outcomes at various levels of biological organization. Aquatic habitats are especially susceptible to chemical contamination from point source discharges and non-point source runoff. Much of our understanding of the effects and risk from chemical exposure comes from individual chemical exposures in laboratory settings. Much less is known about the consequences of exposure to the types of complex mixtures that occur in aquatic habitats. Here, I used integrated effects-based exposure assessments to characterize exposure to different chemical mixtures at various sites in the Shenandoah River watershed (SRW). The SRW is a heterogenous landscape with streams impacted by a diversity of human activities. Exposure sites were selected using land-use and point-source effluents to capture variation in the overall level and type of impact between sites. Over the course of three years, we conducted chemical monitoring and mobile-laboratory fish exposures at 9 different locations. Exposure water was analyzed for over 500 organic and inorganic chemicals and transcriptomic, molecular, cellular, and organismal endpoints were measured in exposed fish. Site-specific patterns of chemical occurrence and exposure effects were observed throughout the SRW and were consistent with variation in land-use and effluent impacts. Adverse organismal outcomes were observed at sites impacted by wastewater effluent and agricultural land-use practices. These outcomes included increased mortality and reproductive disruption, that may have implications for population stability in wild fish. Molecular and cellular data were used to evaluate the mechanisms involved in organismal adverse outcomes using the Adverse Outcome Pathway framework. Despite a focus on estrogenic endocrine disruption in wild fish from the SRW, we found little evidence to support an estrogenic AOP and instead gene, pathway, and cellular data suggest more complex mechanisms leading to reproductive disruption. Changes to lipid metabolism and immune processes were observed at sites with evidence of adverse survival and reproductive outcomes, suggesting these mechanisms may be important key events leading to these effects. Effective risk management of complex mixtures requires the identification of individual contaminants or sub-mixtures that are causally responsible for the observed adverse outcomes. To this end, I conducted a context likelihood of relatedness analysis to identify associations between chemical occurrence and changes to gene expression, resulting in a ranked prioritization list of contaminants that can be used to guide future research into mixture exposures.
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