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DOI10.3109/10408444.2014.981331
Putative adverse outcome pathways relevant to neurotoxicity
Bal-Price, Anna1; Crofton, Kevin M.2; Sachana, Magdalini1; Shafer, Timothy J.2; Behl, Mamta3; Forsby, Anna4,5; Hargreaves, Alan6; Landesmann, Brigitte1; Lein, Pamela J.7; Louisse, Jochem1; Monnet-Tschudi, Florianne8,9; Paini, Alicia1; Rolaki, Alexandra1; Schrattenholz, Andre10; Sunol, Cristina11; van Thriel, Christoph12; Whelan, Maurice1; Fritsche, Ellen13
发表日期2015
ISSN1040-8444
卷号45期号:1页码:83-91
英文摘要

The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.


英文关键词adverse outcome pathway;in vitro testing;key events;molecular initiating event;pathways of neurotoxicity;predictive toxicology
语种英语
WOS记录号WOS:000348199100005
来源期刊CRITICAL REVIEWS IN TOXICOLOGY
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/61977
作者单位1.European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, Ispra, Italy;
2.US EPA, Off Res & Dev, Natl Ctr Computat Toxicol, Res Triangle Pk, NC USA;
3.Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, Res Triangle Pk, NC USA;
4.Stockholm Univ, Arrhenius Labs NaturalSci, Dept Neurochem, S-10691 Stockholm, Sweden;
5.Swedish Toxicol Sci Res Ctr, Swetox, Sodertalje, Sweden;
6.Nottingham Trent Univ, Nottingham, England;
7.Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA;
8.Univ Lausanne, Dept Physiol, Lausanne, Switzerland;
9.Univ Lausanne, SCAHT, Lausanne, Switzerland;
10.ProteoSys AG, Mainz, Germany;
11.CIBERESP, IDIBAPS, IIBB CSIC, Inst Invest Biomed Barcelona, Barcelona, Spain;
12.IfADo Leibniz Res Ctr Working Environm & Human Fa, Dortmund, Germany;
13.IUF Leibniz Res Inst Environm Med, Dusseldorf, Germany
推荐引用方式
GB/T 7714
Bal-Price, Anna,Crofton, Kevin M.,Sachana, Magdalini,et al. Putative adverse outcome pathways relevant to neurotoxicity[J]. 美国环保署,2015,45(1):83-91.
APA Bal-Price, Anna.,Crofton, Kevin M..,Sachana, Magdalini.,Shafer, Timothy J..,Behl, Mamta.,...&Fritsche, Ellen.(2015).Putative adverse outcome pathways relevant to neurotoxicity.CRITICAL REVIEWS IN TOXICOLOGY,45(1),83-91.
MLA Bal-Price, Anna,et al."Putative adverse outcome pathways relevant to neurotoxicity".CRITICAL REVIEWS IN TOXICOLOGY 45.1(2015):83-91.
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