Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP408 |
Comparison of Points of Departure for Health Risk Assessment Based on High-Throughput Screening Data | |
Sand, Salomon1,2; Parham, Fred3; Portier, Christopher J.4; Tice, Raymond R.3; Krewski, Daniel2,5 | |
2017-04-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES
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ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2017 |
卷号 | 125期号:4 |
文章类型 | Article |
语种 | 英语 |
国家 | Sweden; Canada; USA; Netherlands |
英文摘要 | BACKGROUND: The National Research Council's vision for toxicity testing in the 21st century anticipates that points of departure (PODs) for establishing human exposure guidelines in future risk assessments will increasingly be based on invitro high-throughput screening (HTS) data. Objectives: The aim of this study was to compare different PODs for HTS data. Specifically, benchmark doses (BMDs) were compared to the signal-to-noise crossover dose (SNCD), which has been suggested as the lowest dose applicable as a POD. METHODS: Hill models were fit to >10,000 invitro concentration-response curves, obtained for >1,400 chemicals tested as part of the U.S. Tox21 PhaseI effort. BMDs and lower confidence limits on the BMDs (BMDLs) corresponding to extra effects (i.e., changes in response relative to the maximum response) of 5%, 10%, 20%, 30%, and 40% were estimated for >8,000 curves, along with BMDs and BMDLs corresponding to additional effects (i.e., absolute changes in response) of 5%, 10%, 15%, 20%, and 25%. The SNCD, defined as the dose where the ratio between the additional effect and the difference between the upper and lower bounds of the two-sided 90% confidence interval on absolute effect was 1, 0.67, and 0.5, respectively, was also calculated and compared with the BMDLs. RESULTS: The BMDL40, BMDL25, and BMDL18, defined in terms of extra effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. Similarly, the BMDL25, BMDL17, and BMDL13, defined in terms of additional effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. CONCLUSIONS: The SNCD may serve as a reference level that guides the determination of standardized BMDs for risk assessment based on HTS concentration-response data. The SNCD may also have application as a POD for low-dose extrapolation. |
领域 | 资源环境 |
收录类别 | SCI-E ; SSCI |
WOS记录号 | WOS:000397904400024 |
WOS关键词 | BENCHMARK DOSE CONCEPT ; OF-DEPARTURE ; TOXICITY ; SCIENCE ; FRAMEWORK ; EXPOSURE |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/23272 |
专题 | 资源环境科学 |
作者单位 | 1.Natl Food Agcy, Dept Risk Benefit Assessment, Uppsala, Sweden; 2.Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON, Canada; 3.NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA; 4.Maastricht Univ, Dept Toxicogen, Maastricht, Netherlands; 5.Risk Sci Int, Ottawa, ON, Canada |
推荐引用方式 GB/T 7714 | Sand, Salomon,Parham, Fred,Portier, Christopher J.,et al. Comparison of Points of Departure for Health Risk Assessment Based on High-Throughput Screening Data[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2017,125(4). |
APA | Sand, Salomon,Parham, Fred,Portier, Christopher J.,Tice, Raymond R.,&Krewski, Daniel.(2017).Comparison of Points of Departure for Health Risk Assessment Based on High-Throughput Screening Data.ENVIRONMENTAL HEALTH PERSPECTIVES,125(4). |
MLA | Sand, Salomon,et al."Comparison of Points of Departure for Health Risk Assessment Based on High-Throughput Screening Data".ENVIRONMENTAL HEALTH PERSPECTIVES 125.4(2017). |
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