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

Abstract

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.