Physiologically Based Pharmacokinetic Models and Applications in Chemical Risk Assessments
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Because many observable health effects associated with chemical exposures are believed to be more directly related to internal measures of dose (e.g., tissue concentration) than to external ones (e.g., amount ingested), the chemical risk assessment process often involves translating applied doses or environmental exposures into internal dose metrics. Physiologically based pharmacokinetic (PBPK) models, which mathematically describe the biological processes of absorption, distribution, metabolism, and excretion, provide a means for calculating internal dose metrics. PBPK models can also be used to compare data from studies that involve different species, different dosing regimens, and different routes of exposure, and to estimate human exposures that result in the same internal doses. Thus, PBPK models can be used to support chemical risk assessments in a variety of ways. This presentation will include a description the fundamental concepts underlying PBPK modeling and a discussion of applications of PBPK models in human health chemical risk assessments, such as those conducted by the Integrated Risk Information System (IRIS) Program of the U.S. Environmental Protection Agency.