TABLE 1.
Cheminformatics software, tools, and models used to predict UVCBs in this study.
| Cheminformatics software tool, database, or model | Commercial or open-source product | Purpose | Open-source alternative | Selected result | Results in the virtual naphthenate library |
|---|---|---|---|---|---|
| Maestro enumeration tool | Commercial (Schrödinger, LLC) | Generation of the virtual chemical library of naphthenates | RDKit’s enumeration method | NA | 11,850 naphthenate structures generated |
| KNIME analysis platform | Open source | Generation of InChi keys and CDK descriptors | NA | NA | InChi keys and CDK descriptors for all generated structures |
| Canvas cheminformatics platform | Commercial (Schrödinger, LLC) | Chemical data management for the naphthenate library | KNIME can be used as a standalone tool to manage the cheminformatics data | NA | Visualization of all structures and graphing data |
| EPA CompTox Dashboard | Open source | Allows searching of the DSSTox database | NA | NA | Identified 14 naphthenic acids in DSSTox |
| Generalized read-across web application | Open source | Read-across predictions of the naphthenate library | NA | In vivo POD predictions | POD predictions for 14 naphthenic acids, ranging from 1.7 to 4,531 mg/kg/day |
| QikProp prediction models | Commercial (Schrödinger, LLC) | Prediction of the physicochemical and pharmacokinetic properties | OPERA 2.9 also predicts many of the same properties | Octanol/water partition (log) | 1.9 to 6.8 |
| Water solubility (log mol/L) | −1.8 to −7.8 | ||||
| OPERA 2.9 | Open source | Prediction of the physicochemical properties, environmental fates, and toxicological endpoints | NA | Unbound plasma fraction | 89% of the structures in the library are predicted to have an unbound fraction <0.2 |
| Hepatic intrinsic clearance (µL/min/106 cells) | 5–30 μL/min/106 cells for most compounds | ||||
| Rat oral acute LD50 (mg/kg) | 2,000–9,011 mg/kg | ||||
| Repeat-dose POD prediction (Pradeep et al., 2020) | Open source (uses Python, NumPy, Scikit-learn, CDK, and PaDEL) | Prediction of PODs for chronic, subchronic, reproductive, developmental, and subacute studies in rats, mice, and rabbits | NA | Rat developmental POD (mg/kg/day) | 79 to 95 |
| Rat chronic POD (mg/kg/day) | 25 to 50 |