An exchange standard for FAIR PBK models in chemical risk assessment – A PARC community effort

Summary

In next-generation risk assessment (NGRA), there is a growing need for physiologically-based kinetic (PBK) models to extrapolate external doses to internal concentrations in biological matrices and vice versa. PBK models are used in different scientific contexts, including chemical risk assessment. As they are commonly developed for specific chemicals, effects, and populations, a wide range of PBK models is available. However, because PBK models are developed and implemented by different researchers using varying concepts, programming languages, and coding standards, they are often difficult to find, access and reuse across platforms or contexts. Improving their findability, accessibility, interoperability, and reusability (i.e., FAIR) is essential to gain acceptance of PBK models in risk assessment for regulatory purposes. Although many elements to enhance the FAIRness of PBK models are available, a standardised good modelling practice has yet to be established. This paper presents a practical strategy for implementing the FAIR principles for PBK models through a proposed FAIR PBK standard designed to promote interoperability and reusability. The standard builds upon the existing Systems Biology Markup Language (SBML), the dedicated physiologically-based pharmacokinetic ontology (PBPKO) for semantic annotation, and guidelines and tools to combine these to create FAIR PBK models. The standard aids both model developers and (re-)users. It is accompanied by a dedicated software tool, the FAIR PBK inspector, to aid model developers in creating PBK models compliant with the standard. Also, support for PBK models compliant with the standard was implemented in the Monte Carlo Risk Assessment (MCRA) software, enabling their reuse in chemical risk assessment. More broadly, the SBML basis enables reuse in other environments, including R, MATLAB, and Python. A proof-of-principle application within the EU Partnership for the Assessment of Risks from Chemicals (PARC) demonstrates the use and potential of the standard.