Building Prioritization Tools: Chemical Initiation of an Estrogen Receptor-mediated Toxicity Pathway
EPA seeks to use the best tools and most scientifically-sound approaches available in fulfilling its mission to protect human health and the environment. A current challenge is how to determine what specific effects data, for which chemicals, and which exposures, is essential to assess and manage risks appropriately. The goal of this research is to demonstrate how Quantitative Structure Activity Relationship (QSAR) principles are used to develop expert systems for prioritizing chemicals for further evaluation. In vitro estrogen receptor binding and gene activation assays, optimized for detecting environmentally relevant low affinity interactions, are used to determine which chemicals, with which chemical structures and properties, are capable of initiating an estrogen receptor-mediated reproductive impairment pathway.
LaLone, C., D.L. Villeneuve, J.W. Nichols, C.L. Russom, J.E. Tietge, P.K. Schmieder, and G.T. Ankley. Use of human pharmacokinetic data to aid predictions of aquatic species susceptibility to pharmaceuticals. SETAC, Boston, MA, November 13-17, 2011.
LaLone, C., D.L. Villeneuve, L. Burgoon, J.E. Tietge, C.L. Russom, and G.T. Ankley. Molecular target homology as a basis for species extrapolation to assess the ecological risk of veterinary drugs. American Chemical Society Meeting, Denver, CO, August 28-September 1, 2011.
LaLone, C., D.L. Villeneuve, L. Burgoon, J.E. Tietge, C.L. Russom, and G.T. Ankley. Molecular target homology as a basis for species extrapolation to assess the ecological risk of pharmaceuticals. 54th IAGLR Conference, Duluth, MN, May 30-June 3, 2011.
Schmieder, P.K., M.A. Tapper, J.S. Denny, B.R. Sheedy, T.R. Henry, and G.D. Veith. 2004. Use of trout liver slices to enhance mechanistic interpretation of estrogen receptor binding for cost-effective prioritization of chemicals within large inventories. Environmental Science & Technology 38: 6333-6342.
Schmieder, P.K., G.T. Ankley, O. Mekenyan, J.D. Walker, and S. Bradbury. 2003. Quantitative structure-activity relationship models for prediction of estrogen receptor binding affinity of structurally diverse chemicals. Environmental Toxicology and Chemistry 22(8): 1844-1854.
Schmieder, P.K., O. Mekenyan, S. Bradbury, and G.D. Veith. 2003. QSAR prioritization of chemical inventories for endocrine disruptor testing. Pure and Applied Chemistry 75(11-12):2389-2396.
Denny, J.S., M.A. Tapper, P.K. Schmieder, M.W. Hornung, K.M. Jensen, G.T. Ankley, and T.R. Henry. 2005. Comparison of relative binding affinities of endocrine active compounds to fathead minnow and rainbow trout estrogen receptors. Environmental Toxicology and Chemistry 24(11):2948-2953.
Research project update date
June 22, 2011