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THE USE OF STRUCTURE-ACTIVITY RELATIONSHIPS IN INTEGRATING THE CHEMISTRY AND TOXICOLOGY OF ENDOCRINE DISRUPTING CHEMICALS
Citation:
Schmieder, P. K., S P. Bradbury, AND G T. Ankley. THE USE OF STRUCTURE-ACTIVITY RELATIONSHIPS IN INTEGRATING THE CHEMISTRY AND TOXICOLOGY OF ENDOCRINE DISRUPTING CHEMICALS. Presented at 21st SETAC Annual Meeting, Nashville, TN, November 12-16, 2000.
Description:
Structure activity relationships (SARs) are based on the principle that structurally similar chemicals should have similar biological activity. SARs relate specifically-defined toxicological activity of chemicals to their molecular structure and physico-chemical properties. To develop toxicologically-credible approaches for predicting potency and biological character from chemical structure requires the establishment of a knowledge base that contains training sets of chemicals whose mode of action (MOA) and potency are well defined in terms of a biological model, toxic endpoint, and exposure regime. With appropriate knowledge bases, a variety of classification techniques can be employed to assign untested chemicals to MOA and to predict potency. In environmental toxicology and ecological risk assessment, SARs have developed as scientifically credible tools for predicting the acute toxicity of industrial organic chemicals. The models have typically been used in the U.S. and Europe to screen and prioritize chemicals for toxicity testing. Consistent with this approach, SARs are being developed to predict the potential for compounds to moderate endocrine function, in terms of specific MOA, when rigorous in vitro toxicological knowledge bases have been established. The presentation will describe the application of structure-activity models to predict binding of chemicals to androgen, estrogen and retinoid receptors. Considerations in the development of such models will be discussed, as well as application of such models to more biologically complex endpoints.