CCPortal
DOI10.1021/acs.est.6b06230
Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology
Conolly, Rory B.1; Ankley, Gerald T.2; Cheng, WanYun1; Mayo, Michael L.3; Miller, David H.4; Perkins, Edward J.3; Villeneuve, Daniel L.2; Watanabe, Karen H.5
发表日期2017-04-18
ISSN0013-936X
卷号51期号:8页码:4661-4672
英文摘要

A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose response, and time-course predictions that can support regulatory decision-making: Herein we describe several facets of qAOPs, including (a) motivation for development, (b) technical considerations, (c) evaluation of confidence, and (d) potential applications. The qAOP used as an illustrative example for these points describe the linkage between inhibition of cytochrome P450 19A aromatase (the MIE) and population-level decreases in the fathead minnow (FHM; Pimephales promelas). The qAOP consists of three linked computational models for the following: (a) the hypothalamic-pitutitary-gonadal axis in female FHMs, where aromatase inhibition decreases the conversion of testosterone to 17 beta-esttadiol (E2), thereby reducing E2-dependent vitellogenin (VTG; egg yolk protein precursor) synthesis, (b) VTG-dependent egg development and spawning (fecundity), and (c) fecundity-dependent population trajectory. While development of the example qAQP was based on experiments with FHMs exposed to the aromatase inhibitor fadrozole, we also show how a toxic equivalence (TEQ) calculation allows use of the qAOP to predict effects of another, untested aromatase inhibitor, iprodione. While qAOP development can be resource-intensive, the quantitative predictions obtained, and TEQ-based application-to multiple chemicals, may be sufficient to justify the cost for some, applications in regulatory decision-making.


语种英语
WOS记录号WOS:000399859700057
来源期刊ENVIRONMENTAL SCIENCE & TECHNOLOGY
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/60452
作者单位1.US Environm Protect Agcy, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27709 USA;
2.US Environm Protect Agcy, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Mid Continent Ecol Div, Duluth, MN 55804 USA;
3.US Army Engn Res & Dev Ctr, Environm Lab, Vicksburg, MS 39180 USA;
4.US Environm Protect Agcy, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Mid Continent Ecol Div, Grosse Isle, MI 48138 USA;
5.Arizona State Univ, Sch Math & Nat Sci, West Campus, Glendale, AZ 85306 USA
推荐引用方式
GB/T 7714
Conolly, Rory B.,Ankley, Gerald T.,Cheng, WanYun,et al. Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology[J]. 美国环保署,2017,51(8):4661-4672.
APA Conolly, Rory B..,Ankley, Gerald T..,Cheng, WanYun.,Mayo, Michael L..,Miller, David H..,...&Watanabe, Karen H..(2017).Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology.ENVIRONMENTAL SCIENCE & TECHNOLOGY,51(8),4661-4672.
MLA Conolly, Rory B.,et al."Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology".ENVIRONMENTAL SCIENCE & TECHNOLOGY 51.8(2017):4661-4672.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Conolly, Rory B.]的文章
[Ankley, Gerald T.]的文章
[Cheng, WanYun]的文章
百度学术
百度学术中相似的文章
[Conolly, Rory B.]的文章
[Ankley, Gerald T.]的文章
[Cheng, WanYun]的文章
必应学术
必应学术中相似的文章
[Conolly, Rory B.]的文章
[Ankley, Gerald T.]的文章
[Cheng, WanYun]的文章
相关权益政策
暂无数据
收藏/分享

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。