Presentation Abstract

Pharmaceutical chemicals, a subset of pharmaceuticals and personal care products (PPCPs), are aquatic contaminants of emerging concern (CECs) that have been detected at elevated concentrations in surface water globally, entering waterways primarily through sewage discharges containing unmetabolized drugs and improper drug disposal. However, the aquatic toxicity of these contaminants, especially in complex mixtures, is poorly understood; moreover, biomarker frameworks have not been largely applied to this class of contaminants. Here, the toxicity of two cardiac-specific medications, triamterene (diuretic) and gemfibrozil (fibrate), was examined both singly and in mixture concentrations in order to better understand the toxicological implications of PPCP mixtures and develop a biomarker framework. Zebrafish embryos (<48 >hpf) were exposed to single-chemical trials as well as binary mixtures. Morphometric measurements were extracted for various toxicological endpoints (eye area, length, yolk sac size, and cardiac abnormalities) and results from mixture trials were compared to single-chemical trials using the response addition model. Follow-up qPCR was conducted to inform molecular mechanisms of toxicity and identify potential biomarker responses. Gemfibrozil elicited a dose-dependent decrease in eye area and length (developmental delay), as well as an increase in yolk sac area, suggesting possible interference with lipid metabolism pathways; likewise, increased cardiac abnormalities were observed in a dose-dependent manner, indicating potential cardiotoxicity. Triamterene induced a similar dose-dependent increase in cardiac abnormalities, suggesting possible cardiotoxicity. Additive toxic effects were observed in multiple endpoints, with potential synergism evident in yolk sac and cardiotoxicity. These trends indicate that complex mixtures of PPCPs in the environment could interact in waterways to produce increased toxic effects and highlight the need for toxicity assays to take into account the effect of complex PPCP mixtures in order to more accurately predict environmental effects. This study also points to the need for increased policy regulating the disposal of pharmaceutical waste.

Session Title

Posters: Fate, Transport, & Toxicity of Chemicals

Keywords

pollution, ecotoxicology, gemfibrozil, triamterene, zebrafish

Conference Track

SSE18: Posters

Conference Name

Salish Sea Ecosystem Conference (Seattle, WA : 2018)

Document Type

Event

SSEC Identifier

SSE18-55

Start Date

5-4-2018 11:30 AM

End Date

5-4-2018 1:30 PM

Type of Presentation

Poster

Contributing Repository

Digital content made available by University Archives, Heritage Resources, Western Libraries, Western Washington University.

Geographic Coverage

Salish Sea (B.C. and Wash.)

Rights

This resource is displayed for educational purposes only and may be subject to U.S. and international copyright laws. For more information about rights or obtaining copies of this resource, please contact University Archives, Heritage Resources, Western Libraries, Western Washington University, Bellingham, WA 98225-9103, USA (360-650-7534; heritage.resources@wwu.edu) and refer to the collection name and identifier. Any materials cited must be attributed to the Salish Sea Ecosystem Conference Records, University Archives, Heritage Resources, Western Libraries, Western Washington University.

Type

text

Language

English

Format

application/pdf

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Apr 5th, 11:30 AM Apr 5th, 1:30 PM

Morphological and molecular analysis of the toxicity of pharmaceutical-derived aquatic contaminants (PPCPs)​ in zebrafish

Pharmaceutical chemicals, a subset of pharmaceuticals and personal care products (PPCPs), are aquatic contaminants of emerging concern (CECs) that have been detected at elevated concentrations in surface water globally, entering waterways primarily through sewage discharges containing unmetabolized drugs and improper drug disposal. However, the aquatic toxicity of these contaminants, especially in complex mixtures, is poorly understood; moreover, biomarker frameworks have not been largely applied to this class of contaminants. Here, the toxicity of two cardiac-specific medications, triamterene (diuretic) and gemfibrozil (fibrate), was examined both singly and in mixture concentrations in order to better understand the toxicological implications of PPCP mixtures and develop a biomarker framework. Zebrafish embryos (<48>hpf) were exposed to single-chemical trials as well as binary mixtures. Morphometric measurements were extracted for various toxicological endpoints (eye area, length, yolk sac size, and cardiac abnormalities) and results from mixture trials were compared to single-chemical trials using the response addition model. Follow-up qPCR was conducted to inform molecular mechanisms of toxicity and identify potential biomarker responses. Gemfibrozil elicited a dose-dependent decrease in eye area and length (developmental delay), as well as an increase in yolk sac area, suggesting possible interference with lipid metabolism pathways; likewise, increased cardiac abnormalities were observed in a dose-dependent manner, indicating potential cardiotoxicity. Triamterene induced a similar dose-dependent increase in cardiac abnormalities, suggesting possible cardiotoxicity. Additive toxic effects were observed in multiple endpoints, with potential synergism evident in yolk sac and cardiotoxicity. These trends indicate that complex mixtures of PPCPs in the environment could interact in waterways to produce increased toxic effects and highlight the need for toxicity assays to take into account the effect of complex PPCP mixtures in order to more accurately predict environmental effects. This study also points to the need for increased policy regulating the disposal of pharmaceutical waste.