Morphological and Molecular Analysis of Pharmaceutical Aquatic Contaminant Toxicity

Overview

Pharmaceuticals and personal care products (PPCPs) are aquatic contaminants that have been detected in surface water globally. However, their aquatic toxicity, especially in complex mixtures, has not been well characterized—moreover, molecular mechanisms of toxicity are not understood. To better understand PPCP toxicity, zebrafish embryos (<48 hpf) were exposed to single-chemical trials as well as binary mixtures of two cardiac-specific medications: triamterene (diuretic) and gemfibrozil (fibrate). Morphometric analysis revealed that GEM elicited a dose-dependent decrease in eye area and length (developmental delay), as well as an increase in yolk sac area, suggesting interference with lipid metabolism pathways; likewise, cardiotoxicity was observed. TRI induced a similar cardiotoxic phenotype. Mixture trials were compared to single-chemical trials using the response addition (RA) model, revealing additive toxic effects in all endpoints, with potential synergism evident in yolk sac. Thin layer chromatography coupled with flame ionization detection (TLC-FID) methodology was developed to quantify total lipid content and triglyceride/cholesterol levels in exposed embryos. Results suggest that GEM may be blocking lipid metabolism through inhibition of a lipase-mediated metabolic pathway. Further interpretation suggests that TRI+GEM may induce a distinct metabolic pathway than single-chemical exposure to produce toxicity during embryogenesis. These trends indicate that PPCPs are environmental stressors to non-target organisms and that PPCP mixtures could metabolically interact to produce greater than additive toxicity. Furthermore, novel TLC-FID method provides some of the first insight into the potential molecular mechanisms underlying PPCP toxicity and suggests that PPCPs could be inducing similar metabolic pathways in non-target organisms as they do in humans. Overall, this study highlights the need for toxicity assays to incorporate PPCP mixtures to more accurately predict environmental effects and has implications for policy development and ecotoxicological assessment.

Competition history

• AJAS 2019 Category not listed

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