Lhasa Limited today announces the release of a new, free, online application of its Defined Approach for Skin Sensitisation. Use the application, alongside your in silico data and skin sensitisation assay results to get a hazard and potency prediction without the use of in vivo animal tests.
Lhasa has previously published in Regulatory Toxicology and Pharmacology on its decision tree-based defined approach. This defined approach uses:
- Exclusion criteria based on applicability domain knowledge to ensure only the most relevant information sources are used,
- An in silico tool for predicting the adverse outcome of skin sensitisation, e.g. Derek Nexus,
- Results from OECD-validated in chemico/in vitro assays covering key events 1–3 in the skin sensitisation adverse outcome pathway.
The defined approach web application begins by directing users to upload their Derek Nexus reports, or to input a structure and add their own in silico hazard prediction. The LogP is predicted based on the structure of the query compound, and the chemical is assessed against the exclusion criteria (using either information taken from Derek or provided manually by the user) to dictate which Key Event results should be used in the Defined Approach. Once sufficient information has been added, an overall hazard prediction, and potency prediction (where available), is made by the application for the query compound.
Lhasa has also added example compounds which will allow you to see a demonstration of the application without needing to add any in silico/in chemico/in vitro data.
The defined approach application can be found here, or you can read more about the general approach and performance on the webpage. We encourage you to try out Lhasa’s Defined Approach Prototype Application and get back to us with any feedback or questions.
- Macmillan, D. S. & Chilton, M. L. A defined approach for predicting skin sensitisation hazard and potency based on the guided integration of in silico, in chemico and in vitro data using exclusion criteria. Regul. Toxicol. Pharmacol. 101, 35–47 (2019).
- OECD. Test No. 442C: In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA). (OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris., 2015).
- OECD. Key Event Based Test Guideline 442D: In Vitro Skin Sensitisation Assays Addressing The Key Event On Keratinocyte Activation On The Adverse Outcome Pathway For Skin Sensitisation. (OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris., 2018).
- OECD. Key Event Based Test Guideline 442E: In Vitro Skin Sensitisation Assays Addressing The Key Event On Activation Of Dendritic Cells On The Adverse Outcome Pathway For Skin Sensitisation. (OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris., 2018).