Human pharmaceuticals in the marine environment: Focus on exposure and biological effects in animal species : Fate and effects of pharmaceuticals in marine environments

Ecological risk assessors face increasing demands to assess more chemicals, with greater speed and accuracy, and to do so using fewer resources and experimental animals. New approaches in biological and computational sciences may be able to generate mechanistic information that could help in meeting these challenges. However, to use mechanistic data to support chemical assessments, there is a need for effective translation of this information into endpoints meaningful to ecological risk-effects on survival, development, and reproduction in individual organisms and, by extension, impacts on populations. Here we discuss a framework designed for this purpose, the adverse outcome pathway (AOP). An AOP is a conceptual construct that portrays existing knowledge concerning the linkage between a direct molecular initiating event and an adverse outcome at a biological level of organization relevant to risk assessment. The practical utility of AOPs for ecological risk assessment of chemicals is illustrated using five case examples. The examples demonstrate how the AOP concept can focus toxicity testing in terms of species and endpoint selection, enhance across-chemical extrapolation, and support prediction of mixture effects. The examples also show how AOPs facilitate use of molecular or biochemical endpoints (sometimes referred to as biomarkers) for forecasting chemical impacts on individuals and populations. In the concluding sections of the paper, we discuss how AOPs can help to guide research that supports chemical risk assessments and advocate for the incorporation of this approach into a broader systems biology framework.

Pharmaceuticals are biologically active and persistent substances which have been recognized as a continuing threat to environmental stability. Chronic ecotoxicity data as well as information on the current distribution levels in different environmental compartments continue to be sparse and are focused on those therapeutic classes that are more frequently prescribed and consumed. Nevertheless, they indicate the negative impact that these chemical contaminants may have on living organisms, ecosystems and ultimately, public health. This article reviews the different contamination sources as well as fate and both acute and chronic effects on non-target organisms. An extensive review of existing data in the form of tables, encompassing many therapeutic classes is presented. (c) 2009 Elsevier B.V. All rights reserved.

Pharmaceuticals are typically found in very low concentrations in the aquatic environment. Accordingly, environmental effects clearly assigned to residual drugs are consistent with high affinity interactions with conserved targets in affected wildlife species rather than with a general toxic effect. Thus, evolutionarily well-conserved targets in a given species are associated with an increased risk. In this study orthologs for 1318 human drug targets were predicted in 16 species of which several are relevant for ecotoxicity testing. The conservation of different functional categories of targets was also analyzed. Zebrafish had orthologs to 86% of the drug targets while only 61% were conserved in Daphnia and 35% in green alga. The predicted presence and absence of orthologs agrees well with published experimental data on the potential for specific drug target interaction in various species. Based on the conservation of targets we propose that aquatic environmental risk assessments for human drugs should always include comprehensive studies on aquatic vertebrates. Furthermore, individual targets, especially enzymes, are well conserved suggesting that tests on evolutionarily distant organisms would be highly relevant for certain drugs. We propose that the results can guide environmental risk assessments by improving the possibilities to identify species sensitive to certain types of pharmaceuticals or to other contaminants that act through well defined mechanisms of action. Moreover, we suggest that the results can be used to interpret the relevance of existing ecotoxicity data.