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Challenges Associated With Applying Physiologically Based Pharmacokinetic Modeling for Public Health Decision-Making
Tan, C., R. Worley, J. Leonard, AND J. Fisher. Challenges Associated With Applying Physiologically Based Pharmacokinetic Modeling for Public Health Decision-Making. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 162(2):341-348, (2018).
PBPK modeling will remain a vital research, screening, and regulatory tool within our federal agencies. Searches of both the FR and the EPA IRIS database for the use of PBPK modeling clearly demonstrate a growing interest in the incorporation of computational models at EPA. Computational modeling and simulation is also a large enterprise across the FDA. In a non-regulatory capacity, ATSDR has incorporated PBPK modeling in its evaluation of environmental exposures to chemicals to promote public health. There are demonstrated barriers to the acceptance of PBPK modeling in both regulatory and non-regulatory arenas because of challenges in identifying independent peer reviewers with appropriate experience in applying PBPK modeling in regulatory risk assessment, lack of confidence in PBPK models for which no data exist for model evaluation, and a lack of consensus on computing platforms.
The development and application of physiologically based pharmacokinetic (PBPK) models in chemical toxicology have grown steadily since their emergence in the 1980s. However, critical evaluation of PBPK models to support public health decision-making across federal agencies has thus far occurred for only a few environmental chemicals. In order to encourage decision-makers to embrace the critical role of PBPK modeling in risk assessment, several important challenges require immediate attention from the modeling community. The objective of this contemporary review is to highlight 3 of these challenges, including: (1) difficulties in recruiting peer reviewers with appropriate modeling expertise and experience; (2) lack of confidence in PBPK models for which no tissue/plasma concentration data exist for model evaluation; and (3) lack of transferability across modeling platforms. Several recommendations for addressing these 3 issues are provided to initiate dialog among members of the PBPK modeling community, as these issues must be overcome for the field of PBPK modeling to advance and for PBPK models to be more routinely applied in support of public health decision-making.