Accurately predicting the toxicity and potency of compounds like N-nitrosamines is crucial. The Carcinogenic Potency Categorization Approach (CPCA) calculators, as developed by various health authorities, have been used to derive Acceptable Intake values for n-nitrosamine compounds. However, integrating read-across methodologies into the CPCA workflow offers a step forward. Here, we explore the usefulness of read-across support for N-nitrosamines and how it provides value to standard CPCA calculators.
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Read-across is a powerful technique used to predict the properties of a data-poor target compound by comparing it with known properties of structurally and biologically similar data-rich compounds, termed analogs. Local similarity (i.e. the similarity of decorated substructures in different compounds) plays a crucial role in evaluating the adequacy of the selected analogs and thus enhancing the accuracy of the corresponding read-across predictions. By focusing on the structural features of N-nitrosamines in the local chemical environment of the N-nitroso group, read-across methods can identify analogs with high relevance. This local similarity approach ensures that the predictions are based on compounds that share key structural and functional characteristics with the target compound
Value added to CPCA Calculators:
- Focused predictions: Read-across, with emphasis on local similarity, offers additional confidence in predictions for N-nitrosamines. CPCA calculators use a generalized approach, which may not fully capture the nuances of specific chemical structures.
- Data integration: Read-across methods integrate various types of data, including metabolism, phys-chem properties, and overall biological similarity. This comprehensive approach supports robust predictions.
- Context-specific assessments: While CPCA calculators rely on predefined algorithms, read-across support involves expert judgment, allowing for more nuanced and context-specific assessments.
By providing more accurate and reliable predictions, integrating diverse data types, and involving expert judgment, read-across methods are a valuable addition to standard CPCA calculators.
As part of our 2025 release, Leadscope’s CPCA tool is now integrated within the ‘Read-across’ feature!
- This expands accessible functionality to the CPCA calculator defined by health authorities worldwide to allow for deeper analysis of n-nitrosamine compounds.
- Local similarity analysis provides an additional methodology for the analysis of analogs, allowing greater confidence in the calculated acceptable intake values.
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