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SYMPOSIUM SESSION PROPOSAL: INCORPORATION OF MODE OF ACTION INTO MECHANISTICALLY-BASED QUANTITATIVE MODELS
Citation:
EL-MASRI, H. A. AND N. KESHAVA. SYMPOSIUM SESSION PROPOSAL: INCORPORATION OF MODE OF ACTION INTO MECHANISTICALLY-BASED QUANTITATIVE MODELS. Presented at Society of Toxicology Annual Meeting 2008, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
The following presentations will highlight the current state of the science and future directions of biologically-based quantitative modeling.
Description:
The biological processes by which environmental pollutants induce adverse health effects is most likely regulated by complex interactions dependent upon the route of exposure, dose, kinetics of distribution, and multiple cellular responses. To further complicate deciphering these interactions, the majority of toxicological data has been developed using in vitro and in vivo laboratory models, adding to the complexity of extrapolation issues. Quantitative models are the next logical step to advance the current toxicological understanding of how pollutants induce both cancer and non-cancer health effects. Mechanistically-based quantitative modeling of an environmental pollutant represents an avenue of research to identify and, in some instances, quantify uncertainties in relationship to mode of action (MOA) by which compounds elicit adverse health effects. If the MOA for an environmental pollutant is known, a model can be constructed utilizing experimentally-derived datasets that quantitatively represent the key events in the MOA. Conversely, if the MOA is unknown, a hypothesis-driven approach can be utilized to assemble the model and inform likely key events within the MOA(s) for which further experimentations can be designed to test the MOA hypothesis. An important limitation of biologically-based model development is the availability of empirical data to construct such models. It is conceivable that this type of approach would improve the efficiency of current research strategies by pointing to specific research needs and data gaps. Efforts to define the approach for creating mechanistically-based models will provide unique and useful tools for human health risk assessment. Implementation of such techniques will result in the use of science-based derivation of risk posed by exposure to environmental pollutants. The following presentations will highlight the current state of the science and future directions of biologically-based quantitative modeling. (This abstract does not reflect EPA policy)