S13-04 Skin sensitization potency assessment: Make full use of NAM data to conduct quantitative risk assessment

Abstract

Great progress has been made over the last 15 years in the development, validation and regulatory acceptance of New Approach Methods for skin sensitization hazard assessment . However, even in the hazard-assessment driven regulatory landscape of Europe, toxicology remains a quantitative science and determining safe use levels is the cornerstone of any toxicological assessment. Thus in the past years, the focus has shifted to use NAM data in a more granular way and to harness quantitative dose-response data to derive a Point of Departure (PoD) for risk assessment. This requires on the one hand a high-quality set of in vivo reference data and a comprehenisve set of NAM data on the other hand. Thus, a brief summary of recent data curation efforts is given. Different approaches for data integration can then be used to predict a point of departure based on NAM data, and both a deterministic linear regression approach and a probabilistic Bayesian approach have been proposed and submitted to OECD approval. These approaches will be reviewed and compared along with other emerging approaches. Overall similar outcomes with different mathematical approaches are achieved when the same input data are used, and key differences are often in the prediction target and the treatment of missing input data. All these NAM approaches indicate a significant progress in potency assessment and it is now possible to derive a PoD without animal testing. Often the different NAM approaches are even better correlated to each other than to the in vivo data. This can both indicate (i) insufficient coverage of the Adverse Outcome Pathway or (ii) similar gaps in the applicability domain of different methods or (iii) significant residual uncertainty in the in vivo dataset, which cannot be overcome with further NAM development. These different possibilities wil be briefly discussed to give a status for NAMs for skin sensitization potency assessment and an outlook for potential improvements.