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DOI10.1016/j.scitotenv.2018.04.266
Rapid experimental measurements of physicochemical properties to inform models and testing
Nicolas, Chantel I.1,2,5; Mansouri, Kamel1,2,5; Phillips, Katherine A.3; Grulke, Christopher M.2; Richard, Ann M.2; Williams, Antony J.2; Rabinowitz, James2; Isaacs, Kristin K.3; Yau, Alice4; Wambaugh, John F.2
发表日期2018-09-15
ISSN0048-9697
卷号636页码:901-909
英文摘要

The structures and physicochemical properties of chemicals are important for determining their potential toxicological effects, toxicokinetics, and route(s) of exposure. These data are needed to prioritize the risk for thousands of environmental chemicals, but experimental values are often lacking. In an attempt to efficiently fill data gaps in physicochemical property information, we generated new data for 200 structurally diverse compounds, which were rigorously selected from the USEPA ToxCast chemical library, and whose structures are available within the Distributed Structure-Searchable Toxicity Database (DSSTox). This pilot study evaluated rapid experimental methods to determine five physicochemical properties, including the log of the octanol:water partition coefficient (known as log(K-ow) or logP), vapor pressure, water solubility, Henry's law constant, and the acid dissociation constant (pKa). For most compounds, experiments were successful for at least one property; log(K-ow) yielded the largest return (176 values). It was determined that 77 ToxPrint structural features were enriched in chemicals with at least one measurement failure, indicating which features may have played a role in rapid method failures. To gauge consistency with traditional measurement methods, the new measurements were compared with previous measurements (where available). Since quantitative structure-activity property relationship (QSAR/QSPR) models are used to fill gaps in physicochemical property information, 5 suites of QSPRs were evaluated for their predictive ability and chemical coverage or applicability domain of new experimental measurements. The ability to have accurate measurements of these properties will facilitate better exposure predictions in two ways: 1) direct input of these experimental measurements into exposure models; and 2) construction of QSPRs with a wider applicability domain, as their predicted physicochemical values can be used to parameterize exposure models in the absence of experimental data. Published by Elsevier B.V.


英文关键词Physicochemical properties;Environmental chemicals;Predictive modeling;QSAR;Chemical features
语种英语
WOS记录号WOS:000436599000087
来源期刊SCIENCE OF THE TOTAL ENVIRONMENT
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/60037
作者单位1.ScitoVation LLC, 6 Davis Dr, Durham, NC 27703 USA;
2.US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA;
3.US EPA, Natl Exposure Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA;
4.Southwest Res Inst, San Antonio, TX 78238 USA;
5.Oak Ridge Inst Sci & Educ, Oak Ridge, TN 37831 USA
推荐引用方式
GB/T 7714
Nicolas, Chantel I.,Mansouri, Kamel,Phillips, Katherine A.,et al. Rapid experimental measurements of physicochemical properties to inform models and testing[J]. 美国环保署,2018,636:901-909.
APA Nicolas, Chantel I..,Mansouri, Kamel.,Phillips, Katherine A..,Grulke, Christopher M..,Richard, Ann M..,...&Wambaugh, John F..(2018).Rapid experimental measurements of physicochemical properties to inform models and testing.SCIENCE OF THE TOTAL ENVIRONMENT,636,901-909.
MLA Nicolas, Chantel I.,et al."Rapid experimental measurements of physicochemical properties to inform models and testing".SCIENCE OF THE TOTAL ENVIRONMENT 636(2018):901-909.
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