PBTK Optimizer: An Open Source Application for PBTK Model Parameter Optimization in Python

Abstract

Physiologically based toxicokinetic (PBTK) modeling in fish offers great promise in environmental risk assessment, potentially speeding up dose-response studies while minimizing animal testing. PBTK models are generally written as ordinary differential equations (ODEs) and have recently been modeled with Petri nets. Some limitations exist in the PBTK field, such as difficulty of model development and a lack of application specific software tools to help modelers. To address some of these limitations we introduce PBTK Optimizer, an open source tool for optimizing parameters of Petri net PBTK models. The software is demonstrated with a previously published and validated PBTK model of fluoranthene exposure in rainbow trout. We present case studies using PBTK Optimizer to evaluate different parameters of the model. The Python code and conclusions regarding the optimization methods used in this software may be adapted for ODE applications beyond PBTK modeling.

Keywords

• differential equations
• ode model
• physiologically based toxicokinetic modeling
• pbtk
• optimization
• petri net
• python