Species extrapolation for the 21st century

Celander, M.C., Goldstone, J.V., Denslow, N.D., Iguchi, T., Kille, P., Meyerhoff, R.D., Smith, B.A., Hutchinson, T.H., and Wheeler, J.R.
Environmental toxicology and chemistry   30(1): 52-63 (Journal)
Registered Authors
Goldstone, Jed
Species extrapolation, In silico, Predictive ecotoxicology, Aromatase, Cytochrome P45019
MeSH Terms
  • Animals
  • Aromatase/metabolism
  • Aromatase Inhibitors/toxicity
  • Brain/drug effects
  • Brain/enzymology
  • Computer Simulation
  • Environmental Monitoring/methods*
  • Environmental Pollutants/toxicity
  • Fadrozole/toxicity
  • Female
  • Fishes/metabolism
  • Fishes/physiology
  • Fungicides, Industrial/toxicity
  • Imidazoles/toxicity
  • Male
  • Ovary/drug effects
  • Ovary/enzymology
  • Species Specificity
  • Toxicity Tests/methods
  • Toxicity Tests/trends
20963850 Full text @ Environ. Toxicol. Chem.
Safety factors are used in ecological risk assessments to extrapolate from the toxic responses of laboratory test species to all species representing that group in the environment. To more accurately extrapolate species responses would be important. Advances in understanding the mechanistic basis for toxicological responses and identifying molecular response pathways can provide a basis for extrapolation across species and, in part, an explanation for the variability in whole organism responses to toxicants. We highlight potential short and medium term development goals to meet our long term aspiration of truly predictive in silico extrapolation across wildlife species' response to toxicants. A conceptual approach for considering cross species extrapolation is presented. Critical information is required to establish evidence-based species extrapolation including identification of critical molecular pathways and regulatory networks that are linked to the biological mode of action and species' homologies. A case study is presented that examines steroidogenesis inhibition in fish following exposure to fadrozole or prochloraz. Similar effects for each compound among fathead minnow, medaka, and zebrafish were attributed to similar inhibitor pharmacokinetic/pharmacodynamic distributions and sequences of cytochrome P45019A1/2 (CYP19A1/2). Rapid advances in homology modeling allow the prediction of interactions of chemicals with enzymes, for example CYP19 aromatase, making it possible to eventually allow a prediction of potential aromatase toxicity of new compounds across a range of species. Eventually, predictive models will be developed to extrapolate across species, although substantial research is still required. Knowledge gaps requiring research include defining differences in life histories (e.g., reproductive strategies), understanding tissue specific gene expression and defining the role of metabolism on toxic responses and how these collectively affect the power of inter-species extrapolation methods.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes