PBPK model reporting template for chemical risk assessment applications

Abstract

Physiologically-based pharmacokinetic (PBPK) modeling analysis does not stand on its own for regulatory purposes but is a robust tool to support drug/chemical safety assessment. While the development of PBPK models have grown steadily since their emergence, only a handful of models have been accepted to support regulatory purposes due to obstacles such as the lack of a standardized template for reporting PBPK analysis. Here, we expand the existing guidances designed for pharmaceutical applications by recommending additional elements that are relevant to environmental chemicals. This harmonized reporting template can be adopted and customized by public health agencies receiving PBPK model submission, and it can also serve as general guidance for submitting PBPK-related studies for publication in journals or other modeling sharing purposes. The current effort represents one of several ongoing collaborations among the PBPK modeling and risk assessment communities to promote, when appropriate, incorporating PBPK modeling to characterize the influence of pharmacokinetics on safety decisions made by regulatory agencies.

A Systematic Review of Published Physiologically-based Kinetic Models and an Assessment of their Chemical Space Coverage

“…Consistent formats for publishing PBK models have been proposed previously, 28,29 with the template proposed in the recent OECD guidance 10 drawing on previous recommendations, most significantly the reporting format proposed by Tan and co-workers. 30 The use of consistent reporting formats is strongly encouraged, as this assists other researchers in re-using or re-purposing existing models.…”

A Systematic Framework for Collecting Site-Specific Sampling and Survey Data to Support Analyses of Health Impacts from Land-Based Pollution in Low- and Middle-Income Countries

“…On the other hand, biomonitoring data provides a measure of internal dose of a contaminant or its metabolite from all sources and exposure pathways [ 25 , 26 , 27 ]. In the absence of data, mathematical models are used to translate exposure doses to internal doses, including physiologically-based pharmacokinetic modeling (PBPK), as well as different statistical methods ranging from relatively simple regressions and correlations to structural equation modeling [ 28 , 29 , 30 ]. If both biomonitoring and exposure data are available, then it is possible to apply a variety of statistical and mathematical methods to explore predictors of internal dose [ 30 ].…”

“…In the absence of data, mathematical models are used to translate exposure doses to internal doses, including physiologically-based pharmacokinetic modeling (PBPK), as well as different statistical methods ranging from relatively simple regressions and correlations to structural equation modeling [ 28 , 29 , 30 ]. If both biomonitoring and exposure data are available, then it is possible to apply a variety of statistical and mathematical methods to explore predictors of internal dose [ 30 ]. Understanding exposure routes and pathways helps to inform strategies for exposure reduction, and others have called for more intensive studies to link exposures from various pathways to biomonitoring data [ 25 , 27 , 31 , 32 ].…”

Report of the Synthesis and Integration of Epidemiological and Toxicological Evidence Subgroup (SETE) of the Committee on Toxicity and the Committee on Carcinogenicity

“…144. An OECD Harmonised Template (OHT) for PBPK models providing clear guidance on the critical elements of model evaluation for regulatory application is in preparation (Tan et al, 2020). The guidance will assist public health agencies receiving PBPK model submissions.…”