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 Watanabe-Sailor

Research output: Contribution to journalArticle

180 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)168-178
Number of pages11
JournalAquatic Toxicology
Volume92
Issue number3
DOIs
StatePublished - May 5 2009

Fingerprint

Endocrine Disruptors
endocrine-disrupting chemicals
mechanism of action
Fishes
Poisons
Zebrafish
fish
Pimephales promelas
Pharmacologic Actions
endpoints
Danio rerio
Cyprinidae
Metabolomics
Computational Biology
Proteomics
Uncertainty
Reproduction
environmental assessment
metabolomics
transcriptomics

Keywords

  • EDC
  • Fish
  • Genomics
  • MOA
  • Model
  • Toxicity

ASJC Scopus subject areas

  • Aquatic Science
  • Health, Toxicology and Mutagenesis

Cite this

Ankley, G. T., Bencic, D. C., Breen, M. S., Collette, T. W., Conolly, R. B., Denslow, N. D., ... Watanabe-Sailor, K. (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

Endocrine disrupting chemicals in fish : Developing exposure indicators and predictive models of effects based on mechanism of action. / Ankley, Gerald T.; Bencic, David C.; Breen, Michael S.; Collette, Timothy W.; Conolly, Rory B.; Denslow, Nancy D.; Edwards, Stephen W.; Ekman, Drew R.; Garcia-Reyero, Natalia; Jensen, Kathleen M.; Lazorchak, James M.; Martinović, Dalma; Miller, David H.; Perkins, Edward J.; Orlando, Edward F.; Villeneuve, Daniel L.; Wang, Rong Lin; Watanabe-Sailor, Karen.

In: Aquatic Toxicology, Vol. 92, No. 3, 05.05.2009, p. 168-178.

Research output: Contribution to journalArticle

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-Sailor, K 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
Ankley, Gerald T. ; Bencic, David C. ; Breen, Michael S. ; Collette, Timothy W. ; Conolly, Rory B. ; Denslow, Nancy D. ; Edwards, Stephen W. ; Ekman, Drew R. ; Garcia-Reyero, Natalia ; Jensen, Kathleen M. ; Lazorchak, James M. ; Martinović, Dalma ; Miller, David H. ; Perkins, Edward J. ; Orlando, Edward F. ; Villeneuve, Daniel L. ; Wang, Rong Lin ; Watanabe-Sailor, Karen. / Endocrine disrupting chemicals in fish : Developing exposure indicators and predictive models of effects based on mechanism of action. In: Aquatic Toxicology. 2009 ; Vol. 92, No. 3. pp. 168-178.
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