Measuring Physicochemical Properties to Inform the Scope of Existing QSAR/QSPR Models (SOT annual meeting)
Citation:
Nicolas, C., K. Mansouri, K. Phillips, Chris Grulke, A. Richard, A. McEachran, A. Williams, J. Rabinowitz, K. Isaacs, A. Yau, AND J. Wambaugh. Measuring Physicochemical Properties to Inform the Scope of Existing QSAR/QSPR Models (SOT annual meeting). Presented at Society of Toxicology Annual Meeting, Baltimore, Maryland, March 12 - 16, 2017. https://doi.org/10.23645/epacomptox.5176699
Impact/Purpose:
This is a poster presentation to the Society of Toxicology Annual meeting. The presentation describes the initial findings of one of the ExpoCast data collection pilots. In this data collection, high throughput methods were used to measure physico-chemical properties for chemicals that are potentially poorly described by existing models for chemical properties.
Description:
Chemical structures and their properties are important for determining their potential toxicological effects, toxicokinetics, and route of exposure. These data are needed to prioritize thousands of environmental chemicals, but are often lacking. In order to fill data gaps, robust quantitative structure-activity relationship (QSAR) and quantitative structure property relationship (QSPR) models are routinely used in risk assessment for both well-known and new chemicals. However, all QSAR and QSPR models are limited in part by the “training set” of data available for model development. In order to both calibrate and inform the scope of currently available QSPR models, physicochemical measurements were attempted for 200 chemicals selected for a mix of both those with previously measured physicochemical properties as well as chemicals with moieties that were expected to be challenging to existing models from the USEPA DSSTox database. Among the properties measured are octanol:water partitioning coefficient (Kow), vapor pressure (VP), water solubility (WS), Henry’s law constant (HLC), and acid dissociation constant (pKa). The numbers of chemicals successfully measured for each property were: 176 (Kow,) 168 (VP), 129 (WS), 110 (HLC), and 100 (pKa). An analysis was performed comparing these measurements against previous experimental and prediction data, which includes those from ACD Labs, EPI SuiteTM, OPERA, and NICEATM. Results show that VP, WS, and Kow tend to have relatively similar predictive accuracies across all databases. Case studies are presented in order to demonstrate the impact of the new data on various models that depend on them. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: Measuring Physicochemical Properties to Inform the Scope of Existing QSAR/QSPR Models (SOT annual meeting)
PHYSCHEM_ANAYLSIS_ABSTRACT_SOT_011117_FINAL.PDF (PDF, NA pp, 19.626 KB, about PDF)
NICOLAS_PHYSCHEM_SOT_CIN_030717.PDF (PDF, NA pp, 896.066 KB, about PDF)