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Endocrine disrupting chemicals in fish: developing exposure indicators and predictive models of effects based on mechanism of action
Citation:
ANKLEY, G. T., D. C. BENCIC, M. BREEN, T. W. COLLETTE, R. CONOLLY, N. DENSLOW, S. W. EDWARDS, D. R. EKMAN, K. M. JENSEN, J. M. LAZORCHAK, D. MARTINOVIC, D. H. MILLER, E. Perkins, E. F. Orlando, N. Garcia-Reyero, D. L. VILLENEUVE, R. WANG, AND K. Wantanabe. Endocrine disrupting chemicals in fish: developing exposure indicators and predictive models of effects based on mechanism of action. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, 92(3):168-178, (2009).
Impact/Purpose:
We provide an overview and illustrative results from a large, integrated project that assesses the effects of EDCs on two small fish models, the fathead minnow (Pimephales promelas) and zebrafish (Danio rerio). For this work a systems-based approach is being used to delineate toxicity pathways for 12 model EDCs with different nown or hypothesized toxic MOA. The studies employ a combination of state-of-the-art genomic (transcriptomic, proteomic, metabolomic), bioinformatic and modeling approaches, in conjunction with whole animal testing protocols, to develop response linkages across biological levels of organization. This understanding forms the basis for predictive approaches for species, endpoint and chemical extrapolation. Although our project is focused specifically on EDCs in fish, we believe that the basic conceptual approach has utility for systematically assessing exposure and effects of chemicals with other MOA across a variety of biological systems.
Description:
Knowledge of possible toxic mechanisms/modes of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, such as reducing uncertainties related to extrapolation across species, endpoints and chemical structure. However, MOA-based testing seldom has been used for assessing the ecological risk of chemicals. This is in part because past regulatory mandates have focused more on adverse effects of chemicals (reductions in survival, growth or reproduction) than the MOA through which these effects are caused. A recent departure from this involves endocrine-disrupting chemicals (EDCs), where there is a need to understand both MOA and adverse outcomes. To achieve this understanding, advances in predictive approaches are required whereby mechanistic changes caused by chemicals at the molecular level can be translated into apical responses meaningful to ecological risk assessment.