SaferWorldbyDesign: Tiered testing strategy for evaluating kinetics of compounds in chemical risk assessment

Chemical risk assessment is a rigorous process that requires the integration of in silico, in vitro, and any other existing data to evaluate the potential hazards of a compound. Various modelling approaches, leveraging structure-activity and property-property relationships, are deployed to predict toxicity and assess chemical safety of a compound. A tiered approach can be employed in risk assessment, where initial screening relies on in silico and high-throughput in vitro methods, followed by more complex testing strategies if further evaluation is needed. This approach enhances efficiency by prioritizing compounds based on potential risk, reducing reliance on animal testing while maintaining scientific robustness.

Physiologically based pharmacokinetic (PBPK) modelling is used in risk assessment to predict internal exposure following administration of a compound at a relevant route. In silico models are widely used to estimate key parameters necessary for PBPK modelling, enabling accurate predictions of internal dosimetry. Additionally, in silico models are employed to predict metabolite formation, providing insights into potential bioactivation and detoxification pathways that may influence toxicity outcomes. In this presentation, I will discuss how a tiered approach can be used in PBPK modelling of compounds to enhance efficiency, predictive power and decision-making in chemical risk assessment. I will also discuss how existing data can be used to predict off-target effects of the compounds using Certara’s Secondary intelligence software.

Speaker: Barira Islam (Certara)