Endocrine disrupting chemicals in fish: Developing exposure indicators and predictive models of effects based on mechanism of action

Gerald T. Ankley; David C. Bencic; Michael S. Breen; Timothy W. Collette; Rory B. Conolly; Nancy D. Denslow; Stephen W. Edwards; Drew R. Ekman; Natalia Garcia-Reyero; Kathleen M. Jensen; James M. Lazorchak; Dalma Martinović; David H. Miller; Edward J. Perkins; Edward F. Orlando; Daniel L. Villeneuve; Rong Lin Wang; Karen H. Watanabe

doi:10.1016/j.aquatox.2009.01.013

Endocrine disrupting chemicals in fish: Developing exposure indicators and predictive models of effects based on mechanism of action

Gerald T. Ankley, David C. Bencic, Michael S. Breen, Timothy W. Collette, Rory B. Conolly, Nancy D. Denslow, Stephen W. Edwards, Drew R. Ekman, Natalia Garcia-Reyero, Kathleen M. Jensen, James M. Lazorchak, Dalma Martinović, David H. Miller, Edward J. Perkins, Edward F. Orlando, Daniel L. Villeneuve, Rong Lin Wang, Karen H. Watanabe

Research output: Contribution to journal › Article › peer-review

215 Scopus citations

Abstract

Knowledge of possible toxic mechanisms (or modes) of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, thereby 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 pathways through which these effects are elicited. 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. In this paper 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 known 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, 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.

Original language	English (US)
Pages (from-to)	168-178
Number of pages	11
Journal	Aquatic Toxicology
Volume	92
Issue number	3
DOIs	https://doi.org/10.1016/j.aquatox.2009.01.013
State	Published - May 5 2009

Keywords

EDC
Fish
Genomics
MOA
Model
Toxicity

ASJC Scopus subject areas

Aquatic Science
Health, Toxicology and Mutagenesis

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10.1016/j.aquatox.2009.01.013

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Ankley, G. T., Bencic, D. C., Breen, M. S., Collette, T. W., Conolly, R. B., Denslow, N. D., Edwards, S. W., Ekman, D. R., Garcia-Reyero, N., Jensen, K. M., Lazorchak, J. M., Martinović, D., Miller, D. H., Perkins, E. J., Orlando, E. F., Villeneuve, D. L., Wang, R. L., & Watanabe, K. H. (2009). Endocrine disrupting chemicals in fish: Developing exposure indicators and predictive models of effects based on mechanism of action. Aquatic Toxicology, 92(3), 168-178. https://doi.org/10.1016/j.aquatox.2009.01.013

Ankley, GT, Bencic, DC, Breen, MS, Collette, TW, Conolly, RB, Denslow, ND, Edwards, SW, Ekman, DR, Garcia-Reyero, N, Jensen, KM, Lazorchak, JM, Martinović, D, Miller, DH, Perkins, EJ, Orlando, EF, Villeneuve, DL, Wang, RL & Watanabe, KH 2009, 'Endocrine disrupting chemicals in fish: Developing exposure indicators and predictive models of effects based on mechanism of action', Aquatic Toxicology, vol. 92, no. 3, pp. 168-178. https://doi.org/10.1016/j.aquatox.2009.01.013

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abstract = "Knowledge of possible toxic mechanisms (or modes) of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, thereby 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 pathways through which these effects are elicited. 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. In this paper 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 known 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, 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.",

keywords = "EDC, Fish, Genomics, MOA, Model, Toxicity",

author = "Ankley, {Gerald T.} and Bencic, {David C.} and Breen, {Michael S.} and Collette, {Timothy W.} and Conolly, {Rory B.} and Denslow, {Nancy D.} and Edwards, {Stephen W.} and Ekman, {Drew R.} and Natalia Garcia-Reyero and Jensen, {Kathleen M.} and Lazorchak, {James M.} and Dalma Martinovi{\'c} and Miller, {David H.} and Perkins, {Edward J.} and Orlando, {Edward F.} and Villeneuve, {Daniel L.} and Wang, {Rong Lin} and Watanabe, {Karen H.}",

note = "Funding Information: This work was supported in part by the USEPA National Center for Computational Toxicology, a grant from the USEPA National Center for Environmental Research to the University of Florida, and the US Army Environmental Quality Installations Program. The manuscript has been reviewed in accordance with USEPA guidelines; however, the views expressed are those of the authors and do not necessarily reflect USEPA policy. Permission was granted by the Chief of Engineers to publish this information. ",

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AU - Collette, Timothy W.

AU - Conolly, Rory B.

AU - Denslow, Nancy D.

AU - Edwards, Stephen W.

AU - Ekman, Drew R.

AU - Garcia-Reyero, Natalia

AU - Jensen, Kathleen M.

AU - Lazorchak, James M.

AU - Martinović, Dalma

AU - Miller, David H.

AU - Perkins, Edward J.

AU - Orlando, Edward F.

AU - Villeneuve, Daniel L.

AU - Wang, Rong Lin

AU - Watanabe, Karen H.

N1 - Funding Information: This work was supported in part by the USEPA National Center for Computational Toxicology, a grant from the USEPA National Center for Environmental Research to the University of Florida, and the US Army Environmental Quality Installations Program. The manuscript has been reviewed in accordance with USEPA guidelines; however, the views expressed are those of the authors and do not necessarily reflect USEPA policy. Permission was granted by the Chief of Engineers to publish this information.

PY - 2009/5/5

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N2 - Knowledge of possible toxic mechanisms (or modes) of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, thereby 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 pathways through which these effects are elicited. 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. In this paper 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 known 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, 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.

AB - Knowledge of possible toxic mechanisms (or modes) of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, thereby 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 pathways through which these effects are elicited. 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. In this paper 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 known 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, 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.

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Endocrine disrupting chemicals in fish: Developing exposure indicators and predictive models of effects based on mechanism of action

Abstract

Keywords

ASJC Scopus subject areas

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