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DOI | 10.1093/toxsci/kfv171 |
Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing | |
Wetmore, Barbara A.1; Wambaugh, John F.2; Allen, Brittany1; Ferguson, Stephen S.3; Sochaski, Mark A.1; Setzer, R. Woodrow2; Houck, Keith A.2; Strope, Cory L.1; Cantwell, Katherine1; Judson, Richard S.2; LeCluyse, Edward1; Clewell, Harvey J.1; Thomas, Russell S.1,2; Andersen, Melvin E.1 | |
发表日期 | 2015-11-01 |
ISSN | 1096-6080 |
卷号 | 148期号:1页码:121-136 |
英文摘要 | We previously integrated dosimetry and exposure with high-throughput screening (HTS) to enhance the utility of ToxCast HTS data by translating in vitro bioactivity concentrations to oral equivalent doses (OEDs) required to achieve these levels internally. These OEDs were compared against regulatory exposure estimates, providing an activity-to-exposure ratio (AER) useful for a risk-based ranking strategy. As ToxCast efforts expand (ie, Phase II) beyond food-use pesticides toward a wider chemical domain that lacks exposure and toxicity information, prediction tools become increasingly important. In this study, in vitro hepatic clearance and plasma protein binding were measured to estimate OEDs for a subset of Phase II chemicals. OEDs were compared against high-throughput (HT) exposure predictions generated using probabilistic modeling and Bayesian approaches generated by the U.S. Environmental Protection Agency (EPA) ExpoCast program. This approach incorporated chemical-specific use and national production volume data with biomonitoring data to inform the exposure predictions. This HT exposure modeling approach provided predictions for all Phase II chemicals assessed in this study whereas estimates from regulatory sources were available for only 7% of chemicals. Of the 163 chemicals assessed in this study, 3 or 13 chemicals possessed AERs < 1 or < 100, respectively. Diverse bioactivities across a range of assays and concentrations were also noted across the wider chemical space surveyed. The availability of HT exposure estimation and bioactivity screening tools provides an opportunity to incorporate a risk-based strategy for use in testing prioritization. |
英文关键词 | predictive toxicology;ToxCast;in vitro-in vivo extrapolation;dosimetry;exposure assessment |
语种 | 英语 |
WOS记录号 | WOS:000365547900012 |
来源期刊 | TOXICOLOGICAL SCIENCES
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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/58999 |
作者单位 | 1.Inst Chem Safety Sci, Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA; 2.US EPA, Off Res & Dev, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA; 3.ADME, Tox Div Primary & Stem Cell Syst Business Unit, Life Technol, Durham, NC 27703 USA |
推荐引用方式 GB/T 7714 | Wetmore, Barbara A.,Wambaugh, John F.,Allen, Brittany,et al. Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing[J]. 美国环保署,2015,148(1):121-136. |
APA | Wetmore, Barbara A..,Wambaugh, John F..,Allen, Brittany.,Ferguson, Stephen S..,Sochaski, Mark A..,...&Andersen, Melvin E..(2015).Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing.TOXICOLOGICAL SCIENCES,148(1),121-136. |
MLA | Wetmore, Barbara A.,et al."Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing".TOXICOLOGICAL SCIENCES 148.1(2015):121-136. |
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