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OPERA models for ADME properties and toxicity endpoints
Citation:
Mansouri, K., X. Chang, D. Allen, R. Judson, A. Williams, AND N. Kleinstreuer. OPERA models for ADME properties and toxicity endpoints. Society of Toxicology 2021 Virtual Annual Meeting, Virtual, NC, March 12 - 26, 2021. https://doi.org/10.23645/epacomptox.14470728
Impact/Purpose:
Poster presented at the Society of Toxicology 2021 Virtual Annual Meeting March 2021. Chemical safety decisions and management can be hindered by the lack of ready-access to the ever-expanding array of data, tools, and models that are relevant to the analyses. Even though many chemical safety resources are available, it may not be clear how the various sources of information might be combined in targeted, efficient workflows to address their specific questions. The current product showcases QSAR models providing predictions on toxicity endpoints and physicochemical, environmental fate, and ADME properties. This product provides regulatory scientists, students and researchers with the ability to effectively access and exploit the many in silico data streams to support different regulatory purposes and supports current Agency efforts to reduce mammal study requests by 30% by 2025, and completely eliminate all mammal study requests and funding by 2035.
Description:
OPERA is a free and open-source/open-data suite of QSAR models providing predictions on toxicity endpoints and physicochemical, environmental fate, and ADME properties. All OPERA models are built on curated data and standardized QSAR-ready chemical structures. OPERA follows the five OECD principles for QSAR modeling to provide scientifically valid, high accuracy models with minimal complexity that support mechanistic interpretation, when possible. The latest additions to OPERA include models for estrogenic activity, androgenic activity, and acute oral systemic toxicity developed through international collaborative modeling projects. Existing OPERA models are also updated regularly. Recently, the models predicting plasma protein binding and intrinsic hepatic clearance, two of the most important ADME parameters for in vitro to in vivo extrapolation, have been updated with the latest publicly available datasets to improve their predictivity and applicability domain coverage. Furthermore, models predicting physicochemical parameters such as logKow, water solubility, and vapor pressure have been updated to account for highly investigated groups of chemicals such as polyfluorinated substances (PFAS). In addition to predictive models, OPERA provides a tool for standardizing chemical structures, an estimate of prediction accuracy, an assessment of applicability domain, and experimental values when available. Technical and performance details are described in OECD-compliant QSAR model reporting format (QMRF) reports. OPERA predictions are available through the EPA CompTox Chemicals Dashboard and the National Toxicology Program’s Integrated Chemical Environment. The OPERA application can also be downloaded from the NIEHS GitHub repository as a command-line or graphical user interface for Windows and Linux operating systems. This project was funded in whole or in part with federal funds from the NIEHS, NIH under Contract No. HHSN273201500010C. The views expressed in this presentation are those of the authors and do not necessarily reflect the views or policies of the U.S. EPA.
URLs/Downloads:
DOI: OPERA models for ADME properties and toxicity endpoints
OPERA_MODELS-SOT21_KM_NCK_AJW_EPA.PDF (PDF, NA pp, 1702.192 KB, about PDF)