Most compounds (i.e., 88.5%) in our test set appeared to be within the applicability domain of each model. To obtain the applicability domains of these models, a 95% leverage threshold of 0.189 for amide, 0.652 for UoA, and 0.424 for cocamide was found for the training sets. For the training set the leverage values range between 0 and 1, meaning that the lower threshold for the amide model showed how similar most of the amide compounds were to each other, while for the UoA and cocamide models, the higher thresholds corresponded with the larger variety of chemical structures found in the dataset. When the leverage calculations were applied on the test sets for these models, a total of 22, 34, and 54 compounds were found to be outside of the applicability domain for the amide, UoA, and cocamide r i models, respectively. This does not necessarily mean that the predicted outcome for these cases was wrong, as can be seen in figures S4, S6, and S8. Here, most chemicals outside the applicability domain still follow the trend of the other data points. However, the outcome should be taken with care as the model might insufficiently cover the chemical space for a new compound in question, especially for leverage values > 1. It should be noted that the largest training set leverage value obtained from our applicability domain calculations was 1.