The regression based defined approach for skin sensitization potency assessment based on NAM data from OECD accepted...

Area of Science:

• Toxicology
• Computational Chemistry

Background:

• New Approach Methodologies (NAMs) are increasingly used for skin sensitization hazard assessment.
• The focus has shifted towards predicting sensitization potency using these methods.
• Previous models used Local Lymph Node Assay (LLNA) data or combined EC3 values with human evidence.

Purpose of the Study:

• To describe a Defined Approach (DA) for skin sensitization potency prediction.
• To evaluate the predictivity and reproducibility of this DA using extensive chemical data.
• To highlight best practices for integrating the kinetic DPRA and address technical limitations.

Main Methods:

• Development of regression models for potency prediction using various input data combinations.
• Integration of these models into a fixed workflow to establish a single point-of-departure.
• Validation of the DA with data from 203 chemicals and ring trial data for reproducibility.

Main Results:

• The DA demonstrated predictivity across 203 chemicals.
• Ring trial data indicated good reproducibility for NAM-based potency predictions.
• The approach offers a transparent evaluation of NAM data and utilizes existing hazard identification data.

Conclusions:

• The described Defined Approach provides a transparent and efficient method for skin sensitization potency assessment.
• This DA is being validated by the OECD for potential inclusion in TG 497.
• The approach maximizes the utility of existing toxicological data for hazard identification and classification.