A generic avian physiologically-based kinetic (PBK) model and its application in three bird species

Physiologically-based kinetic (PBK) models are effective tools for designing toxicological studies and conducting extrapolations to inform hazard characterization in risk assessment by filling data gaps and defining safe levels of chemicals. In the present work, a generic avian PBK model for male and female birds was developed using PK-Sim and MoBi from the Open Systems Pharmacology Suite (OSPS). The PBK model includes an ovulation model (egg development) to predict concentrations of chemicals in eggs from dietary exposure. The model was parametrized for chicken (Gallus gallus), bobwhite quail (Colinus virginianus) and mallard duck (Anas pla-tyrhynchos) and was tested with nine chemicals for which in vivo studies were available. Time-concentration profiles of chemicals reaching tissues and egg compartment were simulated and compared to in vivo data. The overall accuracy of the PBK model predictions across the analyzed chemicals was good. Model simulations were found to be in the range of 22-79% within a 3-fold and 41-89% were within 10-fold deviation of the in vivo observed data. However, for some compounds scarcity of in-vivo data and inconsistencies between pub-lished studies allowed only a limited goodness of fit evaluation. The generic avian PBK model was developed following a best practice workflow describing how to build a PBK model for novel species. The credibility and reproducibility of the avian PBK models were scored by evaluation according to the available guidance docu-ments from WHO (2010), and OECD (2021), to increase applicability, confidence and acceptance of these in silico models in chemical risk assessment.

Automated summary

Physiologically-based kinetic (PBK) models are effective tools for toxicological studies and risk assessment. In this study, a generic avian PBK model for birds was developed and tested using in vivo data. The model accurately predicted the concentrations of chemicals in tissues and eggs, and its credibility and reproducibility were evaluated according to available guidance documents. This research provides a valuable reference for building PBK models for novel species.