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OPERA models supporting regulatory needs
Citation:
Mansouri, K., T. Martin, X. Chang, D. Allen, A. Williams, AND N. Kleinstreuer. OPERA models supporting regulatory needs. ASCCT, RTP, NC, October 19 - 21, 2022. https://doi.org/10.23645/epacomptox.22018232
Impact/Purpose:
The goal of this product is to develop cheminformatics and computational chemistry tools and datasets to support environmental chemistry and toxicology. Prediction of key endpoints is often necessary due to the sparsity of available experimental toxicity and environmental data. Such models while less desirable than concrete measured values often provide the only quantitative or binary hazard metrics for the vast majority of chemicals in the environment. As interest in large scale evaluation and prioritization of potential toxicants increases, the development of reliable models following QSAR best practices accepted in the community for hazard endpoints is necessary to provide defensible hazard estimations to support risk–based prioritization. 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 freely accessible standalone application based on the open-source/open-data concept providing a suite of QSAR models for toxicity endpoints and physicochemical, environmental fate, and ADME properties. 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. Experimental data is thoroughly curated, and chemical structures standardized, prior to modeling. Recent additions to OPERA include models for ADME related parameters of high importance in vitro to in vivo extrapolations such as fraction unbound to plasma protein (Fu), intrinsic hepatic clearance (Clint), and Caco2 permeability (logPapp). Previously, three consensus models developed through international collaborative projects were added to the suite to support regulatory assessment processes involving estrogen and androgen pathway activity, as well as acute oral systemic toxicity. Models predicting ADME parameters (Fu, Clint and Caco2) and physicochemical parameters (logKow, water solubility, Henry’s law constant, and vapor pressure) were recently updated with the latest publicly available datasets to improve their predictivity and applicability domain coverage and to account for highly investigated groups of chemicals such as polyfluorinated substances (PFAS). OPERA also provides a tool for standardizing chemical structures and its models yield prediction accuracy estimates, applicability domain assessments, 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 EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard) and the National Toxicology Program’s Integrated Chemical Environment (https://ice.ntp.niehs.nih.gov/). The OPERA application can be downloaded from the NIEHS GitHub repository (https://github.com/NIEHS/OPERA) as a standalone command-line or graphical user interface for Windows and Linux operating systems. It is also provided as Python, C/C++ and Java libraries that can be embedded in other applications. This project was funded 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 any federal agency.
URLs/Downloads:
DOI: OPERA models supporting regulatory needs
OPERA_ASCCT.PDF (PDF, NA pp, 4562.716 KB, about PDF)