A mechanistic reinterpretation of the AOP for skin sensitisation

David W Roberts, Liverpool John Moores University, Liverpool Introduction – Non-Animal Prediction: the 21st Century Consensus Because of the biological complexity of the skin sensitisation process no single in chemico or in vitro assay will be an appropriate replacement for an animal-based assay such as LLNA or GPMT… …to ensure a mechanistic basis and cover the […]

David W Roberts, Liverpool John Moores University, Liverpool

Introduction – Non-Animal Prediction: the 21st Century Consensus
Because of the biological complexity of the skin sensitisation process no single in chemico or in vitro assay will be an appropriate replacement for an animal-based assay such as LLNA or GPMT…
…to ensure a mechanistic basis and cover the complexity, multiple methods should be integrated into a testing strategy, in accordance with the adverse outcome pathway that describes all key events in skin sensitisation.

We need an ITS based on the KEs of the AOP…but
Is that what we really need?

Conclusion

A single assay, GARD™, predicts sensitisation potential and absence of sensitisation potential better than any of, or combinations of, the OECD guideline assays DPRA, KeratinosensTM (ARE-Nrf2 ) and h-CLAT.

We do not really need an ITS covering all KE’s of the AOP.

Link to poster