Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP5297 |
Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches | |
Noyes, Pamela D.1; Friedman, Katie Paul2; Browne, Patience3; Haselman, Jonathan T.4; Gilbert, Mary E.5; Hornung, Michael W.4; Barone, Stan, Jr.6; Crofton, Kevin M.2; Laws, Susan C.5; Stoker, Tammy E.5; Simmons, Steven O.2; Tietge, Joseph E.4; Degitz, Sigmund J.4 | |
2019-09-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES |
ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2019 |
卷号 | 127期号:9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; France |
英文摘要 | BACKGROUND: Extensive clinical and experimental research documents the potential for chemical disruption of thyroid hormone (TH) signaling through multiple molecular targets. Perturbation of TH signaling can lead to abnormal brain development, cognitive impairments, and other adverse outcomes in humans and wildlife. To increase chemical safety screening efficiency and reduce vertebrate animal testing, in vitro assays that identify chemical interactions with molecular targets of the thyroid system have been developed and implemented. OBJECTIVES: We present an adverse outcome pathway (AOP) network to link data derived from in vitro assays that measure chemical interactions with thyroid molecular targets to downstream events and adverse outcomes traditionally derived from in vivo testing. We examine the role of new in vitro technologies, in the context of the AOP network, in facilitating consideration of several important regulatory and biological challenges in characterizing chemicals that exert effects through a thyroid mechanism. DISCUSSION: There is a substantial body of knowledge describing chemical effects on molecular and physiological regulation of TH signaling and associated adverse outcomes. Until recently, few alternative nonanimal assays were available to interrogate chemical effects on TH signaling. With the development of these new tools, screening large libraries of chemicals for interactions with molecular targets of the thyroid is now possible. Measuring early chemical interactions with targets in the thyroid pathway provides a means of linking adverse outcomes, which may be influenced by many biological processes, to a thyroid mechanism. However, the use of in vitro assays beyond chemical screening is complicated by continuing limits in our knowledge of TH signaling in important life stages and tissues, such as during fetal brain development. Nonetheless, the thyroid AOP network provides an ideal tool for defining causal linkages of a chemical exerting thyroid-dependent effects and identifying research needs to quantify these effects in support of regulatory decision making. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000488971900009 |
WOS关键词 | MICROSOMAL-ENZYME INDUCERS ; UDP-GLUCURONOSYLTRANSFERASE INDUCERS ; TYPE-2 IODOTHYRONINE DEIODINASE ; POLYBROMINATED DIPHENYL ETHERS ; FOLLICULAR CELL-PROLIFERATION ; INFLATION FOLLOWING EXPOSURE ; BROMINATED FLAME RETARDANTS ; MODERATE IODINE DEFICIENCY ; THYROXINE-BINDING GLOBULIN ; SMALL-MOLECULE AGONISTS |
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/186587 |
专题 | 资源环境科学 |
作者单位 | 1.US EPA, Natl Ctr Environm Assessment, ORD, Washington, DC 20460 USA; 2.US EPA, Natl Ctr Computat Toxicol, ORD, Res Triangle Pk, NC 27711 USA; 3.OECD, Environm Directorate, Environm Hlth & Safety Div, Paris, France; 4.US EPA, Midcontinent Ecol Div, NHEERL, ORD, Duluth, MN USA; 5.US EPA, Tox Assessment Div, NHEERL, ORD, Res Triangle Pk, NC 27711 USA; 6.US EPA, Off Pollut Prevent & Tox, Off Chem Safety & Pollut Prevent, Washington, DC 20460 USA |
推荐引用方式 GB/T 7714 | Noyes, Pamela D.,Friedman, Katie Paul,Browne, Patience,et al. Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2019,127(9). |
APA | Noyes, Pamela D..,Friedman, Katie Paul.,Browne, Patience.,Haselman, Jonathan T..,Gilbert, Mary E..,...&Degitz, Sigmund J..(2019).Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches.ENVIRONMENTAL HEALTH PERSPECTIVES,127(9). |
MLA | Noyes, Pamela D.,et al."Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches".ENVIRONMENTAL HEALTH PERSPECTIVES 127.9(2019). |
条目包含的文件 | 条目无相关文件。 |
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。
修改评论