Understanding the impacts of environmental factors on uptake and effects of ionizable organic chemicals in aquatic organisms

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Chemical contamination of the aquatic environment often occurs in combination with environmental stressors that follow complex spatiotemporal patterns. Unlike for neutral organic chemicals, the impacts of environmental factors on uptake and effects of ionizable organic chemicals (IOCs), i.e. chemicals that are fully or partially dissociated depending on ambient conditions, are poorly understood. More than half of all industrial chemicals, and approximately 85% of pharmaceuticals are IOCs. Consequently, knowledge of the mechanisms that govern these impacts is critical to adequately assess the risks of IOCs to aquatic ecosystems in an era of unprecedented environmental change. The overall goal of this proposed research is to identify environmental factors that control the availability and consequently the effects of IOCs, and their interactions with molecular, biochemical and physiological processes in aquatic organisms, specifically fish. We will use an integrative approach combining biological, chemical and computational techniques to achieve this goal. To test the direct influence of physicochemical parameters on the availability and uptake of IOCs by controlling the fraction of uncharged, permeable species (Objective 1), we will perform in vitro permeation experiments using gill cells, and in vivo experiments with rainbow trout. Concentrations of individual IOCs found in municipal waste water effluents (MWWEs), mixtures of IOCs, and representative MWWEs will be studied. Chemical analyses will be complemented by gene expression analyses (qPCR, RNAseq) to determine the impacts of environmental factors on uptake and effects of IOCs. To test whether active transport and biotransformation of charged species are relevant processes (Objective 2), we will characterize the effects of selected environmental factors on the expression and activity of transport and biotransformation proteins. Recently, we discovered that the barrier function of the fish gill can be disrupted by pathogen-induced inflammation. To improve our understanding of the effects of inflammation on the uptake of IOCs from MWWEs (Objective 3), we will conduct experiments with bacterial lipopolysaccharides to mimic pathogen-induced inflammation in exposed fish. Finally, a toxicokinetic model will be amended with sub-models for active transport, biotransformation, and epithelial integrity to estimate the individual contribution of each of these processes (Objective 4). Overall, this innovative and integrated research will result in a mechanistic understanding of the impacts of environmental factors on uptake and effects of IOCs in aquatic organisms and will inform regulators that develop water quality guidelines to protect aquatic ecosystem health. This will facilitate solving the key environmental issue of surface water contamination and help to prepare for water threats in an era of unprecedented global change.