Developing a Tiered Framework for Extrapolation Modeling
The standard approach to extrapolating from animals to humans (inter-species) or across the human population (intra-species) in risk assessment is to apply 10X uncertainty factors. In Science and Decisions: Advancing Risk Assessment, the NAS recommends that the agency "…continue and expand use of the best, most current science to support and revise default assumptions."
EPA published its document, "Guidance for Applying Quantitative Data to Develop Data-Derived Extrapolation Factors for Interspecies and Intraspecies Extrapolation" (herein called, DDEF Guidance), in September of 2014, which provides a foundation for improving the scientific basis for inter- and intra-species extrapolation using data on pharmacokinetics (PK) and pharmacodynamics (PD).
The DDEF Guidance describes a hierarchal approach for using data and models with varying levels of sophistication to inform inter- and intra-species extrapolation. Recent advances in in vitro to in vivo extrapolation and computational modeling provide new opportunities to develop models for developing efficient and robust data-derived inter- and intra-species extrapolation factors.
As described here, to take advantages of these scientific advances, the Office of Pesticide Programs (OPP) is developing a tiered framework for extrapolation modeling. OPP is interested in beginning dialogue with interested stakeholders on this proposed tiered approach for developing efficient PBPK models using new technologies.
