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INTER-SPECIES COMPARISONS AND SAR MODELLING OF ESTROGENICITY USING RAINBOW TROUT ER BINDING DATA
Citation:
Henry, T R., J. S. Denny, M A. Tapper, Z. Nedyalkova, O. G. Mekenyan, AND P. K. Schmieder. INTER-SPECIES COMPARISONS AND SAR MODELLING OF ESTROGENICITY USING RAINBOW TROUT ER BINDING DATA. Presented at 2002 SETAC Annual Meeting, Salt Lake City, UT, November 16-20, 2002.
Description:
The U.S. EPA has been mandated to screen industrial chemicals and pesticides for potential endocrine activity. Structure-activity relationships (SARs) to predict receptor binding are being developed as a first step to rank and prioritize chemicals for testing in bioassays. First generation models developed to predict EDC activity are based on mammalian estrogen receptor (ER) binding and transcriptional activation data. A major uncertainty associated with these models is how comparable receptor binding is among mammalian and non-mammalian species and consequently, how well mammalian-based SARs predict responses in non-mammalian species. The appropriateness of extrapolating mammalian results to non-mammalian species is uncertain; primarily due to the lack of non-mammalian data from which to make such an assessment. Comparison of mammalian and rainbow trout RBAs for 80+ chemicals, including steroids, alkylphenols, chlorinated pesticides and phytoestrogens shows that differences in RBAs among the animal classes are within approximately an order of magnitude. The rainbow trout RBA data set also allows for assessment of how accurately SAR modeling based on mammalian binding data may predict activity in other species. The results of these comparisons can be used in a weight of evidence approach to screen small numbers of chemicals and as the basis for developing predictive SAR models for ranking and prioritizing large numbers of chemicals. This abstract does not necessarily reflect EPA policy.