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DOI | 10.1093/toxsci/kfu199 |
Adverse Outcome Pathway (AOP) Development I: Strategies and Principles | |
Villeneuve, Daniel L.1; Crump, Doug2; Garcia-Reyero, Natalia3; Hecker, Markus4,5; Hutchinson, Thomas H.6; LaLone, Carlie A.1,7; Landesmann, Brigitte8; Lettieri, Teresa8; Munn, Sharon8; Nepelska, Malgorzata8; Ottinger, Mary Ann9; Vergauwen, Lucia10; Whelan, Maurice8 | |
发表日期 | 2014-12-01 |
ISSN | 1096-6080 |
卷号 | 142期号:2页码:312-320 |
英文摘要 | An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organization of regulatory relevance. Systematic organization of information into AOP frameworks has potential to improve regulatory decision-making through greater integration and more meaningful use of mechanistic data. However, for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment, it is critical that AOPs be developed in accordance with a consistent set of core principles. Based on the experiences and scientific discourse among a group of AOP practitioners, we propose a set of five fundamental principles that guide AOP development: (1) AOPs are not chemical specific; (2) AOPs are modular and composed of reusable components-notably key events (KEs) and key event relationships (KERs); (3) an individual AOP, composed of a single sequence of KEs and KERs, is a pragmatic unit of AOP development and evaluation; (4) networks composed of multiple AOPs that share common KEs and KERs are likely to be the functional unit of prediction for most real-world scenarios; and (5) AOPs are living documents that will evolve over time as new knowledge is generated. The goal of the present article was to introduce some strategies for AOP development and detail the rationale behind these 5 key principles. Consideration of these principles addresses many of the current uncertainties regarding the AOP framework and its application and is intended to foster greater consistency in AOP development. |
英文关键词 | adverse outcome pathway;regulatory toxicology;predictive toxicology;extrapolation;knowledgebase |
语种 | 英语 |
WOS记录号 | WOS:000347617800001 |
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/61784 |
作者单位 | 1.US EPA, Mid Continent Ecol Div, Duluth, MN 55804 USA; 2.Environm Canada, Ecotoxicol & Wildlife Hlth Div, Ottawa, ON K1A 0H3, Canada; 3.Mississippi State Univ, Inst Genom Biocomp & Biotechnol, Starkville, MS 39762 USA; 4.Univ Saskatchewan, Sch Environm & Sustainabil, Saskatoon, SK S7N 5B3, Canada; 5.Univ Saskatchewan, Toxicol Ctr, Saskatoon, SK S7N 5B3, Canada; 6.Univ Plymouth, Sch Biol Sci, Plymouth PL4 8AA, Devon, England; 7.Univ Minnesota, Water Resources Ctr, St Paul, MN 55108 USA; 8.Commiss European Communities, Joint Res Ctr, I-21027 Ispra, Italy; 9.Univ Houston, Dept Biol & Biochem, Houston, TX 77004 USA; 10.Univ Antwerp, Dept Vet Sci, Zebrafishlab, B-2610 Antwerp, Belgium |
推荐引用方式 GB/T 7714 | Villeneuve, Daniel L.,Crump, Doug,Garcia-Reyero, Natalia,et al. Adverse Outcome Pathway (AOP) Development I: Strategies and Principles[J]. 美国环保署,2014,142(2):312-320. |
APA | Villeneuve, Daniel L..,Crump, Doug.,Garcia-Reyero, Natalia.,Hecker, Markus.,Hutchinson, Thomas H..,...&Whelan, Maurice.(2014).Adverse Outcome Pathway (AOP) Development I: Strategies and Principles.TOXICOLOGICAL SCIENCES,142(2),312-320. |
MLA | Villeneuve, Daniel L.,et al."Adverse Outcome Pathway (AOP) Development I: Strategies and Principles".TOXICOLOGICAL SCIENCES 142.2(2014):312-320. |
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