The fields of toxicology and chemical risk assessment evaluate the safety of chemicals for humans the environment. Increasingly, modern methods seek to reduce the use of animals in chemical safety testing and predictive toxicology. In this context, the OECD has developed this guidance document on Physiologically Based Kinetic (PBK) models, with the goal of increasing confidence in the use of these models parameterised with data derived from in vitro and in silico methods. The document provides insights into how the data generated by such methods can be applied to construct PBK models and how these models can be validated. A series of cases studies illustrate the use of PBK models based on in vitro and in silico data, along with the application of the model assessment framework proposed herein. This guidance document provides a clear and consistent model assessment framework for facilitating the dialogue between the developers and proponents of PBK models and regulators who review and adopt the use of PBK models.