Is a combination of assays really needed for non-animal prediction of skin sensitization potential? Performance of the GARD™ (Genomic Allergen Rapid Detection) assay in comparison with OECD guideline assays alone and in combination

Regulatory Toxicology and Pharmacology, Volume 98, October 2018, Pages 155-160, https://doi.org/10.1016/j.yrtph.2018.07.014. David W.Roberts Highlights Prediction of skin sensitization potential does not need multiple assays representing Key Events of the AOP. This has been argued on theoretical grounds and is now tested against published data. A single assay, GARD™, can outperform combinations of OECD test guideline […]

Regulatory Toxicology and Pharmacology, Volume 98, October 2018, Pages 155-160, https://doi.org/10.1016/j.yrtph.2018.07.014.

David W.Roberts

Highlights

  • Prediction of skin sensitization potential does not need multiple assays representing Key Events of the AOP.
  • This has been argued on theoretical grounds and is now tested against published data.
  • A single assay, GARD™, can outperform combinations of OECD test guideline assays.

Abstract
To meet regulatory requirements, and avoid or minimize animal testing, there is a need for non-animal methods to assess the potential of chemicals to cause skin sensitization. It is widely assumed that no one test will be sufficient and that combined data from several assays spanning key events from the adverse outcome pathway will be required. This paper challenges that assumption. The predictive performance of a single assay, the Genomic Allergen Rapid Detection (GARD™) assay, was compared with the performance, singly and in combination, of three formally validated non-animal approaches that appear as OECD test guidelines: the direct peptide reactivity assay (DPRA), the ARE-Nrf2 luciferase test method, and the human cell line activation test (h-CLAT).

It is shown here that GARD™ alone outperforms each of DPRA, ARE-Nrf2 luciferase or h-CLAT, alone or in any combination as a 2 out of 3 strategy, in terms of sensitivity, specificity and accuracy.

Based on the datasets analysed here, the sensitivity and specificity of GARD™ alone are 90–92% and 79–84% (“2 out of 3”, 86% and 76%). Thus, in any situation where the 2 out of 3 strategy is considered adequate, GARD™ alone could be used with equal or better performance.

Keywords
Skin sensitization potential, Non-animal assays, Integrated testing strategies, GARD™

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