Prediction of chronic toxicity of pharmaceuticals in Daphnia magna by combining ortholog prediction, pharmacological effects, and quantitative structure-activity relationship

Abstract

To develop a method for predicting chronic toxicity of pharmaceuticals in Daphnia, we investigated the feasibility of combining the presence of drug-target orthologs in Daphnia magna, classification based on pharmacological effects, and ecotoxicity quantitative structure-activity relationship (QSAR) prediction. We established datasets on the chronic toxicity of pharmaceuticals in Daphnia, including information on therapeutic categories, target proteins, and the presence or absence of drug-target orthologs in D. magna, using literature and databases. Chronic toxicity was predicted using ecotoxicity prediction QSAR (Ecological Structure Activity Relationship and Kashinhou Tool for Ecotoxicity), and the differences between the predicted and measured values and the presence or absence of drug-target orthologs were examined. For pharmaceuticals without drug-target orthologs in D. magna or without expected specific actions, the ecotoxicity prediction QSAR analysis yielded acceptable predictions of the chronic toxicity of pharmaceuticals. In addition, a workflow model to assess the chronic toxicity of pharmaceuticals in Daphnia was proposed based on these evaluations and verified using an additional dataset. The addition of biological aspects such as drug-target orthologs and pharmacological effects would support the use of QSARs for predicting the chronic toxicity of pharmaceuticals in Daphnia.

Keywords

• Chronic toxicity
• Daphnia
• Ecological Structure Activity Relationship
• Kashinhou Tool for Ecotoxicity
• Drug-target orthologs