You are here:
Oral Presentation for the 2018 Total Exposure Health Conference (Bethesda, MD)
Citation:
Wetmore, B. Oral Presentation for the 2018 Total Exposure Health Conference (Bethesda, MD). 2018 Total Exposure Health Conference, Bethesda, MD, September 06 - 07, 2018.
Impact/Purpose:
Total Exposure Health is a pioneering U.S. Air Force Program that endeavors to bring exposure science into the application of precision medicine in order to improve the health of both civilians and military personnel. The meeting has been designed to Inform attendees of the state of the exposure science, the challenges, with the aim of identifyig critical R&D challenges to address knowledge gaps, in exposure science and in Total Exposure Health. This venue provides a key opportunity to interact with military scientists in other U.S. federal agencies regarding the ongoing efforts and progress of US EPA ORD scientists to advance cutting edge exposure and dosimetry modeling tools for use in exposure reconstruction and exposure assessment.
Description:
Recent advances in vitro assays, in silico tools, and systems pharmacology approaches provide opportunities to capture the exposure continuum from the external exposure space to anticipated systemic and target tissue concentrations. With the U.S. commercial and industrial chemical landscape encompassing tens of thousands of chemicals with limited safety data, efficient characterization of this continuum and its use to link internal exposures to the potential for subsequent human health effects using high-throughput toxicity data is a high priority. Ongoing efforts at the US Environmental Protection Agency (EPA) have advanced the science underlying quantitative in vitro-in vivo extrapolation (QIVIVE), a methodology that facilitates the quantitative application of in vitro experimental data and in silico modeling to predict in vivo system behaviors (e.g., toxicokinetics, toxicodynamics and population variability). To date, in vitro toxicokinetic data generated on over 500 chemicals have been employed to develop and validate IVIVE models of varying levels of complexity and have been used to predict dose and exposure metrics along this continuum. Assessments of predictivity, uncertainty and variability of these IVIVE approaches have critically evaluated the predictions to identify the appropriate use and application of these datasets across the broad chemical space requiring data. Leveraging the in vitro datasets, in silico tools predicting hepatic clearance and plasma protein binding have also been developed for broad application across the untested space. Efforts to quantitate anticipated ranges of population variability have involved incorporating physiologic and metabolic profile information with chemical toxicokinetic data, allowing assessments across the US population and different life stages. These data and models reside in the EPA’s open source CompTox Dashboard and the R-based HTTK (High-Throughput ToxicoKinetics) platform. The positioning of IVIVE at the cross-roads of new approach methodology (NAM)-based risk assessments underscores the importance of continued advances in this space. Multi-disciplinary collaboration, data and model transparency and education will be key to facilitate the application of these alternative methodologies in chemical safety assessments. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
http://www.cvent.com/events/total-exposure-health-2018/event-summary-f5ae5c586a414ceb84a7fb594789dd7b.aspx