Integrated skin sensitization assessment based on OECD methods (II): Hazard and potency by combining kinetic peptide reactivity and the “2 out of 3” Defined Approach

Main Article Content

Andreas Natsch
G. Frank Gerberick

Abstract

Depending on regulatory requirements, three questions on the skin sensitization risk for new chemicals with potential skin contact by consumers must be answered by experimental testing: (i) Binary hazard assessment to identify sensitizers, (ii) subclassification of sensitizers according to the Global Harmonized System (GHS), and (iii) a Point of Departure (PoD) for risk assessment. The Organisation for Economic Co-operation and Development (OECD) published a test guideline incorporating the “2 out of 3” Defined Approach (2o3 DA) for skin sensitization hazard assessment. At the same time, the kinetic direct peptide reactivity assay (kDPRA) was added to the test guidelines as a stand-alone method for GHS subclassification. For the 2o3 DA, at least two in vitro tests are conducted. The cell-based tests and the kDPRA generate, next to a binary outcome with a fixed threshold, continuous dose-response data, which can be used in quantitative regression models to derive a PoD. The 2o3 DA is flexible for the sequence of testing. Here we show different testing sequences and how they can be combined with kDPRA data to provide a PoD in parallel to hazard identification (hazard ID) and GHS subclassification. Using these different testing sequences, a set of 188 chemicals with available in vitro data was evaluated for the final PoD. The results indicate that testing can start with DPRA / kDPRA and either of the cell-based assays, and that testing can stop with two congruent tests without major impact on the final PoD for chemicals within the applicability domain of the kDPRA.

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Natsch, A. and Gerberick, G. F. (2022) “Integrated skin sensitization assessment based on OECD methods (II): Hazard and potency by combining kinetic peptide reactivity and the ‘2 out of 3’ Defined Approach”, ALTEX - Alternatives to animal experimentation. doi: 10.14573/altex.2201142.
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References

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