The movement of toxicology away from an observational-based paradigm and towards a mechanism-based one is ongoing. One pertinent question is how to combine data across mechanistic pathways to derive an overall assessment of hazard and what level of confidence should be placed in such a result. Further, where data gaps exist, how could in silico tools be used to support an assessment.
The area of skin sensitization is exemplary. Hinging on knowledge of the adverse outcome pathway (AOP) for skin sensitization, key events across the AOP could be assessed and integrated to derive an overall assessment. But what if information is missing? Could I utilize the power of existing knowledge- stored in a database- to analyze reactive features, statistical correlations, chemical and mechanistic similarity to facilitate an assessment? Could I really ‘pull out all the stops’ as they say? And if I did (congrats to you on getting this far!), and managed to standardize reporting for the various assessments, would I be able to reproducibly justify the overall conclusion across hundreds of chemicals and effectively (don’t forget reproducibly) communicate the confidence in the results?
There is so much to unravel here. A major plus is that we have a starting point. Documents such as the OECD’s Guidance Document on the Reporting of Defined Approaches and Individual Information Sources to Be Used within Integrated Approaches to Testing and Assessment (IATA) for Skin Sensitization1 are an excellent resource. The recently published skin sensitization in silico protocol2 is also a good resource for expert review considerations and guidelines on how to assess the reliability and confidence of an in silico assessment. If you would like to talk more about implementing the principles outlined in the skin sensitization in silico protocol, we would like to hear from you. Together, we could explore the solutions to many of the questions above.
- OECD. Guidance Document on the Reporting of Defined Approaches and Individual Information Sources to Be Used within Integrated Approaches to Testing and Assessment (IATA) for Skin Sensitisation. OECD; 2017. doi:10.1787/9789264279285-en
- Johnson C, Ahlberg E, Anger LT, et al. Skin sensitization in silico protocol. Regul Toxicol Pharmacol. 2020;116:104688. doi:https://doi.org/10.1016/j.yrtph.2020.104688