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Exposure Assessments and Toxicology in the 21st Century
Citation:
Price, P. AND C. Tan. Exposure Assessments and Toxicology in the 21st Century. Future Tox III, Arlington, VA, November 19 - 20, 2015.
Impact/Purpose:
This presentation will facilitate discussion on advancements in exposure science that have resulted form changes in toxicology.
Description:
It is widely recognized that the hazard and dose response portions of chemical risk assessments are being transformed by the availability of Adverse Outcome Pathways (AOPs) and in vitro and in silico data on biological activity. This transformation is also changing the exposure assessment portion of the process. Exposure assessment supports the characterization of risk by estimating the doses received by individuals and converting the doses into dose metrics defined by dosing regimes from in vivo studies (lifetime average daily doses in mg/kg/d). In contrast, the dose metrics in in vitro assays are concentrations in test solutions over short periods of time (hours or days). In addition, an AOP begins with a molecular initiating event (MIE), which is also an short-term event (e.g., binding to a receptor). As a result, exposure assessment must now characterize the time course of concentrations of chemicals, or metabolites, at the site of the MIE that occur as a result of one or more short-term exposure events. These concentrations are determined by linking longitudinal models of intake doses to pharmacokinetic models of concentrations of a chemical, or its metabolites. Such approach will require improvements in the Agency’s ability to model longitudinal exposures and produce pharmacokinetic models of internal concentrations of chemicals, and their relevant metabolites, for large numbers of substances.