The VERA software: Implementation of the acute fish toxicity endpoint and its application to pharmaceutical compounds

The Virtual Extensive Read-Across software (VERA) is a new tool for read-across using a global similarity score, molecular groups, and structural alerts to find clusters of similar substances; these clusters are then used to identify suitable similar substances and make an assessment for the target substance. A beta version of VERA GUI is free and available at vegahub.eu; the source code of the VERA algorithm is available on GitHub. In the past we described its use to assess carcinogenicity, a classification endpoint. The aim here is to extend the automated read-across approach to assess continuous endpoints as well. We addressed acute fish toxicity. VERA evaluation on the acute fish toxicity endpoint was done on a dataset containing general substances (pesticides, industrial products, biocides, etc.), obtaining an overall R² of 0.68. We employed the VERA algorithm also on active pharmaceutical ingredients (APIs). We included a portion of the APIs in the training dataset to predict APIs, successfully achieving an overall R² of 0.63. VERA evaluates the assessment's reliability, and we reached an R² of 0.78 and Root Mean Square Error (RMSE) of 0.44 for predictions with high reliability.