Use of Structure–Activity Relationship (SAR) Evaluation as a Critical Tool in the Evaluation of the Genotoxic Potential of Impurities
Andrew J. Teasdale · 2021
Computational toxicology includes approaches to predict the toxicity of a chemical based solely on its chemical structure. The predictions are generated using computational models that encode complex structure–activity (toxicity) relationships (SAR). This chapter provides an overview of (Quantitative) SAR ((Q)SAR) methodologies related to International Council on Harmonization (ICH) M7 and outlines the process of assigning and documenting impurities to the five ICH M7 classes, including an expert review. The implementation of (Q)SAR assessments for impurities has shown that computational methods have a significant role to play in the assessment of chemicals. It has also led to improvements in science around the SAR knowledge for chemicals of particular concern in impurities assessment, such as aromatic amines. The predictivity of the (Q)SAR methods has improved as more data become available for building models.