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DOI | 10.1289/EHP1304 |
Application of Adverse Outcome Pathways to US EPA's Endocrine Disruptor Screening Program | |
Browne, Patience1; Noyes, Pamela D.1; Casey, Warren M.2; Dix, David J.1 | |
发表日期 | 2017-09-01 |
ISSN | 0091-6765 |
卷号 | 125期号:9 |
英文摘要 | BACKGROUND: The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. OBJECTIVES: This review describes the EDSP's use of adverse, outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. RESULTS: Pathway frameworks can facilitate a weight of evidence determination of a chemical's potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. CONCLUSIONS: A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate, alternative methods and develop predictive models for androgen and thyroid pathways. |
语种 | 英语 |
WOS记录号 | WOS:000413792800009 |
来源期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES |
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/58950 |
作者单位 | 1.US EPA, Off Chem Safety & Pollut Prevent, Washington, DC 20460 USA; 2.NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC USA |
推荐引用方式 GB/T 7714 | Browne, Patience,Noyes, Pamela D.,Casey, Warren M.,et al. Application of Adverse Outcome Pathways to US EPA's Endocrine Disruptor Screening Program[J]. 美国环保署,2017,125(9). |
APA | Browne, Patience,Noyes, Pamela D.,Casey, Warren M.,&Dix, David J..(2017).Application of Adverse Outcome Pathways to US EPA's Endocrine Disruptor Screening Program.ENVIRONMENTAL HEALTH PERSPECTIVES,125(9). |
MLA | Browne, Patience,et al."Application of Adverse Outcome Pathways to US EPA's Endocrine Disruptor Screening Program".ENVIRONMENTAL HEALTH PERSPECTIVES 125.9(2017). |
条目包含的文件 | 条目无相关文件。 |
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