An umbrella Quality Assurance Project Plan (QAPP) for PBPK models

HERO ID

4326432

Reference Type

Technical Report

Subtype

EPA Report

Year

2018

Language

English

HERO ID 4326432
Material Type EPA Report
Year 2018
Title An umbrella Quality Assurance Project Plan (QAPP) for PBPK models
Authoring Organization U.S. Environmental Protection Agency
Publisher Text U.S. Environmental Protection Agency
City Research Triangle Park, NC
Abstract The U.S. Environmental Protection (EPA) Agency requires project managers and planners to develop a Quality Assurance Project Plan (QAPP) as a tool for documenting the type and quality of data and model information that are needed for making environmental decisions. This document provides a QAPP that covers the basic data collection and modeling methodologies for physiologicallybased pharmacokinetic (PBPK) models. It is an “Umbrella” QAPP and intended to be applicable to multiple PBPK modeling projects. This QAPP conforms to EPA QA/G-5 (U.S. EPA, 2002a) and is an internal QA Project Plan in support of the U.S. EPA’s Human Health Risk Assessment (HHRA) research plan. A PBPK model is a mathematical representation that describes the disposition of one or more chemicals in the body of a human or experimental animal in which organs or tissue groups are represented as compartments linked by blood flow that carries the chemical(s) between compartments. Put another way, a PBPK model is a quantitative statement of a set of hypotheses regarding the major determinants of absorption, distribution, metabolism and excretion (ADME). A key advantage of these models is that they can be used for various types of extrapolation including cross-species (animal to human), cross-route (e.g. inhalation to oral), and among exposure scenarios (Krishnan and Andersen, 1994), all of which can be used to facilitate human health risk evaluation and the setting of regulatory exposure levels. In addition to PBPK models, simpler pharmacokinetic (PK) with more empirically derived parameters can be used for the same types of extrapolation. Either form of PK model (PBPK models being a subset of all PK models) can be linked to a model describing some level of biological response, in which the combined dosimetry-response model is referred to as a biologically-based doseresponse (BBDR) model. In this QAPP the term “PBPK” will be used since it is presently the most commonly evaluated and applied model form of model expected to be evaluated and used. However, this QAPP is intended to apply equally well to classical PK and BBDR model forms. Guidance on the use or application of PBPK models in U.S. EPA risk assessments is not the subject of this document, but can be found in U.S. EPA (2006).
Report Number ORD QAPP ID No: B-0030740-QP-1-1
Is Certified Translation No
Dupe Override No
Number Of Pages 22
Is Public Yes
Language Text English
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