You are here:
INTEGRATING TOXICITY PATHWAY-SPECIFIC IN VITRO TESTING WITH ADVANCED CHEMICAL SELECTION STRATEGIES FOR ENVIRONMENTAL QSAR DEVELOPMENT
Citation:
INTEGRATING TOXICITY PATHWAY-SPECIFIC IN VITRO TESTING WITH ADVANCED CHEMICAL SELECTION STRATEGIES FOR ENVIRONMENTAL QSAR DEVELOPMENT. Presented at 11th International Workshop on Quantitative Structural Activity Response in Human Health and Environmental Science, Liverpool, England, May 9-13, 2004.
Description:
Environmental risk assessments often require the evaluation of large numbers of untested chemicals. Chemical assessment protocols that include QSARs have been widely applied for endpoint prediction as well as chemical ranking and prioritization. Approaches are needed to strategically select and test chemicals, to provide sufficient information to develop robust assessment protocols that adequately predict potential toxicity of numerous diverse chemicals. The challenge of developing adequate models and assessment protocols, with minimal testing, is significant. An approach is described which integrates advancements in chemical selection strategies for QSAR development with toxicity pathway-specific in vitro testing to develop mechanistically-sound and robust screening protocols. Criteria used to evaluate the competitive nature of binding to the estrogen receptor of rainbow trout, particularly for low affinity industrial chemicals is presented. The biological relevance of low affinity binding is further assessed as chemicals are evaluated for their ability to induce vitellogenin mRNA in metabolically-competent trout liver tissue. Integrating testing with strategic chemical selection in an iterative approach for QSAR development is presented to illustrate efficient use of testing resources.
Disclaimer:This abstract does not necessarily reflect EPA policy.
Environmental risk assessments often require the evaluation of large numbers of untested chemicals. Chemical assessment protocols that include QSARs have been widely applied for endpoint prediction as well as chemical ranking and prioritization. Approaches are needed to strategically select and test chemicals, to provide sufficient information to develop robust assessment protocols that adequately predict potential toxicity of numerous diverse chemicals. The challenge of developing adequate models and assessment protocols, with minimal testing, is significant. An approach is described which integrates advancements in chemical selection strategies for QSAR development with toxicity pathway-specific in vitro testing to develop mechanistically-sound and robust screening protocols. Criteria used to evaluate the competitive nature of binding to the estrogen receptor of rainbow trout, particularly for low affinity industrial chemicals is presented. The biological relevance of low affinity binding is further assessed as chemicals are evaluated for their ability to induce vitellogenin mRNA in metabolically-competent trout liver tissue. Integrating testing with strategic chemical selection in an iterative approach for QSAR development is presented to illustrate efficient use of testing resources.
Disclaimer:This abstract does not necessarily reflect EPA policy.