Fig. 4

AOP network showing all AOPs relevant to eco-neurotoxicity that are available in the AOP-Wiki (https://aopwiki.org; Accession date: April 30, 2018; AOP numbers 16, 77, 78, 79, 80, 82, 87, 88, 89, 90, 91, 93, 94, 95, 97, 98, 99, 113, 160, 161, 178, 195, 197, 203, 204; Network constructed using Cytoscape 3.6.1). Nodes in the network are key events (KEs), and edges represent key event relationships (KERs). Molecular initiating events are displayed in green, adverse outcomes in red. All other KEs are depicted in blue. Solid edges are adjacent KERs, dashed arrows are KERs that have been defined as non-adjacent (see the OECD’s users’ handbook for developing and assessing AOPs for more information, [333]). Node size represents node degree (the total number of KERs connecting the KE to the network, Villeneuve et al., and edge thickness represents the number of times a given KER is part of constituent AOPs in the network. While some of the AOPs in the network have been published, many are in early stages of development, and none have been reviewed or endorsed by the OECD. This figure and its annotations therefore merely illustrate the current focus areas of eco-neurotoxicity AOP developers in the AOP-Wiki, as well as the interrelatedness of these research topics. The AOP network does not make any inference about the scientific validity of the underlying AOPs, nor can it at this stage be used for in-depth biological interpretation or regulatory application. ACh, acetylcholine; AChE, acetylcholinesterase; 5-HTT, 5-hydroxytryptamine (serotonin) transporter; GABA, gamma-aminobutyric acid; Glu, glutamate; Na, sodium; K, potassium; Cl, chloride