Systematic Evaluations of Physiologically-Based Pharmacokinetic Models for Human Health Risk Assessment-Poster
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Physiologically-based pharmacokinetic (PBPK) models are tools for estimating absorption, distribution, metabolism, and elimination (ADME) of chemicals in the body > Quantify internal (tissue/organ) dose vs exposure > Facilitate dose-response analysis/human extrapolation > Use chemical- and species-specific data (unlike default BW3/4 allometric scaling) Multiple alternative models or analyses in literature > “Being published is not enough”: EPA thoroughly evaluates models based on scientific and technical criteria prior to use in an assessment > IRIS uses a structures approach to evaluate quality and usability The evaluation process stresses: (1) clarity in the documentation of model purpose, structure, and biological characterization; (2) validation of mathematical descriptions, parameter values, and computer implementation; and (3) evaluation of each plausible dose metric. NAS (2014) recommendations addressed: > Develop and expand use of formal quantitative methods in data integration for dose-response assessment and derivation of toxicity values > Develop tools for assessing risk of bias in different types of studies