Integrated skin sensitization assessment based on OECD methods (I): Deriving a point of departure for risk assessment

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Andreas Natsch
G. Frank Gerberick


Three guidelines covering key events in the skin sensitization adverse outcome pathway are endorsed by the Organisation for Economic Co-operation and Development (OECD). A recent guideline covers Defined Approaches (DA) to combine data from these tests for regulatory (sub)-classification. These methods provide continuous data that could characterize the sensitization potency on a more granular scale beyond (sub)-classifications. We assembled a comprehensive database on in vitro and in vivo tests in OECD methods. Building on a previous approach using regression models, we provide quantitative models using input data from the kinetic Direct Peptide Reactivity Assay (kDPRA), the KeratinoSens™ (KS) assay and the human Cell Line Activation Test (h-CLAT) to calculate a point of departure (PoD) in the form of a predicted Local Lymph Node Assay (LLNA) EC3 value for use in risk assessment. Predictive models include results from either two or all three assays. Detailed analysis vs. in vivo data estimates redundancy between different tests and helps guide model selection. All models were tested on a set of case studies selected on their availability of multiple LLNA reference data in the OECD database. The predicted PoD were within or close to the area of the variation of the historical LLNA data for most of these cases studies, and overall, the models predict the in vivo value with a median fold-misprediction of a factor of around 2.5. The robustness of the models was characterized by comparing a comprehensive historical database vs. the curated dataset provided by the OECD working group on DA.

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Natsch, A. and Gerberick, G. F. (2022) “Integrated skin sensitization assessment based on OECD methods (I): Deriving a point of departure for risk assessment”, ALTEX - Alternatives to animal experimentation. doi: 10.14573/altex.2201141.

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