(a) pEC3 predicted based on its SNAr potential (pEC3 = -0.31*SNAr barrier + 4.90)[54] b pEC3 predicted using ACD logP
As highlighted by other researchers the prediction of skin sensitization is a highly challenging process and that the concordance between different in vivo , in vitro and in chemico based methods is often no more than 60-80% in agreement with gold-standard methods such as the LLNA assay.[8, 15, 16] This is in part due to the fact that the LLNA response is not always a result of direct sensitization the molecule itself, potentially arising as a function of reactive metabolites.[21, 64] In this case we report a purely theoretical approach to predict a diverse set of Schiff base chemicals – using just two relatively simple and interpretable descriptors. The observation that the model can explain ~50-60% of the variance in the dataset is therefore not surprising.