Next generation risk assessment for skin allergy: Decision making using new approach methodologies

Area of Science:

• Toxicology
• Dermatology
• Risk Assessment

Background:

• Advancements in New Approach Methodologies (NAMs) provide non-animal testing alternatives for skin sensitization assessment.
• Focus is shifting towards utilizing NAMs for deriving potency information essential for Next Generation Risk Assessment (NGRA).

Purpose of the Study:

• To develop and implement advanced approaches for skin allergy risk assessment (SARA) that eliminate the need for animal testing and improve uncertainty quantification.
• To apply the SARA model within a weight-of-evidence NGRA framework for skin allergy using case studies.
• To demonstrate how to structure risk assessments, utilize NAMs for deriving points of departure, and conclude on consumer safety.

Main Methods:

• Utilized the SARA model, a Bayesian statistical approach, to infer human-relevant sensitizer potency and risk metrics.
• Integrated data from various NAMs including human repeat insult patch test, local lymph node assay, direct peptide reactivity assay, KeratinoSens™, h-CLAT, and U-SENS™.
• Applied the SARA model within an NGRA framework to three case study materials across four consumer products.

Main Results:

• The SARA model successfully inferred sensitizer potency and risk for consumer exposures using a combination of NAM data.
• The application of NGRA based on NAMs in case studies proved to be at least as protective as historical risk assessment methods for the evaluated exposures.
• The study successfully highlighted the structure for risk assessment, NAM application for point of departure derivation, and consumer safety risk conclusions.

Conclusions:

• The SARA model and NGRA framework provide a robust, animal-free approach to skin allergy risk assessment.
• Confidence in utilizing NAMs for skin allergy risk assessment is increasing through successful application in case studies.
• NGRA utilizing NAMs demonstrates comparable or superior protection compared to traditional methods for consumer product safety evaluations.