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__NOTOC__
 
__NOTOC__
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= Status =
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<span style="color:#FF0000">
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This is a legacy representation of this AOP. Please see the current version here:
  
<html>
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[//{{SERVERNAME}}/aops/28 https://{{SERVERNAME}}/aops/28]
<style>
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</span>
.ui-autocomplete {
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    max-height: 100px;
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    overflow-y: auto;
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    overflow-x: hidden;
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    padding-right: 20px;
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}
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* html .ui-autocomplete {
 
    height: 100px;
 
}
 
  
.ui-menu .ui-menu-item a
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== AOP Title ==
        {
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            display: block;
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            padding: 1px 1px 1px 1px;
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            text-decoration: none;
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            cursor: pointer;
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            font-size: 13px;
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        }
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</style>
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<link type='text/css' rel='stylesheet' href='/extensions/jquery-ui-1.9.2/themes/base/jquery-ui.css'>
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<div class='Title'> Cyclooxygenase inhibition leading reproductive failure </div>
<script type="text/javascript" src="/extensions/jquery-ui-1.9.2/ui/jquery-ui.js"></script>
+
 
<script type="text/javascript" src="/extensions/EPA/MOA_Key_Event.js"></script>
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<div id='shortTitle' class='Title2'>Short name: Cyclooxygenase inhibition leading reproductive failure </div>
<script type="text/javascript" src="/extensions/EPA/MOA_Chemicals.js"></script>
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<script type="text/javascript" src="/extensions/EPA/MOA_Species.js"></script>
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== Authors ==
<script type="text/javascript" src="/extensions/EPA/MOA_Endpoint.js"></script>
+
Dan Villeneuve, US EPA Mid-Continent Ecology Division (villeneuve.dan@epa.gov)
<script type="text/javascript" src="/extensions/EPA/MOA_Life_Stage.js"></script>
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<script type="text/javascript" src="/extensions/EPA/MOA_Sex.js"></script>
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</html>
 
 
== Status ==
 
== Status ==
 +
 +
'''Please follow the link to [//{{SERVERNAME}}/aops/{{PAGENAMEE}}/snapshots snapshots page] to view and create Snapshots of this AOP.'''
 +
 +
'''Alert: The Weight of Evidence column in the Molecular Initiating Event and Key Event tables has changed to Essentiality. Consider re-evaluating the columns in these tables.'''
 +
 
'''Under development:  Do not distribute or cite.'''
 
'''Under development:  Do not distribute or cite.'''
  
Putative AOP - under development for International Workshop on Advancing AOPs for Integrated Toxicology and Regulatory Applications
+
Putative AOP
  
==  Introduction     ==
+
'''Project 1.29''': A catalog of putative AOPs that will enhance the utility of US EPA Toxcast high throughput screening data for hazard identification
 +
 
 +
 
 +
This AOP page was last modified on {{REVISIONMONTH1}}/{{REVISIONDAY}}/{{REVISIONYEAR}}.
 +
 
 +
<span id='ToggleRevision' style="text-decoration: underline;">Click here to show/hide revision dates for related pages</span>
 +
{|class="wikitable sortable" id="Revtable"
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 +
!Page
 +
!Revision Date/Time
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 +
|-
 +
 
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|}
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 +
==  Abstract     ==
  
 
== Summary of the AOP ==
 
== Summary of the AOP ==
 
[[Category:Adverse Outcome Pathway]]
 
[[Category:Adverse Outcome Pathway]]
 +
Please follow link to [//{{SERVERNAME}}/aops/{{PAGENAMEE}} widget page] to edit this section.
 +
 +
<span style="color:#FF0000">'''If you manually enter text in this section, it will get automatically altered or deleted in subsequent edits using the widgets.'''</span>
  
 
=== Molecular Initiating Event ===
 
=== Molecular Initiating Event ===
  
<html>
 
<button id="TableAdd3">Add Molecular Initiating Event to Table</button>
 
</html>
 
<div id="popbox3" title='Add a Record' style='display:none'>
 
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<span id="chosen1" style="float:left"> Action</span><span class="ui-icon ui-icon-info" title="How the event is affected"></span>
 
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<span id="chosen2" style="float:left"> Biological Process/Object</span><span class="ui-icon ui-icon-info" title="The Molecular Initiating Event for this AOP"></span>
 
</br>
 
</html>{{Template:InputBox|Molecular Initiating Event|Template:Key Event}}<html>
 
</br>
 
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<span id="chosen3" style="float:left"> Evidence</span><span class="ui-icon ui-icon-info" title="How strong the evidence is for this event"></span>
 
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{|class="wikitable sortable" id="MIEproof"
 
{|class="wikitable sortable" id="MIEproof"
  
 
!Molecular Initiating Event
 
!Molecular Initiating Event
!Evidence
+
!Support for Essentiality
  
 
|-
 
|-
  
|[[Cyclooxygenase activity, Inhibition]]||||<html><button id="edit" name="Molecular Initiating Event"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Molecular Initiating Event"><span class="ui-icon ui-icon-trash"></span></button></html>
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|[[Event:79|Cyclooxygenase activity, Inhibition]]||
  
 
|-
 
|-
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=== Key Events ===
 
=== Key Events ===
  
<html>
 
<button id="TableAdd4">Add Event to Table</button>
 
</html>
 
<div id="popbox4" title='Add a Record' style='display:none'>
 
<html>
 
<span id="chosen1" style="float:left"> Action</span><span class="ui-icon ui-icon-info" title="How the event is affected"></span>
 
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<span id="chosen2" style="float:left"> Biological Process/Object</span><span class="ui-icon ui-icon-info" title="A Key Event for this AOP"></span>
 
</br>
 
</html>{{Template:InputBox|Key Event|Template:Key Event}}<html>
 
</br>
 
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<span id="chosen3" style="float:left"> Evidence</span><span class="ui-icon ui-icon-info" title="How strong the evidence is for this event"></span>
 
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<button id="SubKE">Submit</button>
 
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{|class="wikitable sortable" id="KEproof"
 
{|class="wikitable sortable" id="KEproof"
  
 
!Event
 
!Event
!Evidence
+
!Support for Essentiality
  
 
|-
 
|-
  
|[[Prostaglandin E2 concentration, Reduction]]||||<html><button id="edit" name="Key Events"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Key Events"><span class="ui-icon ui-icon-trash"></span></button></html>
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|[[Event:243|Prostaglandin E2 concentration, Reduction]]||
  
 
|-
 
|-
  
|[[Ca and HCO3 transport to shell gland, Reduction]]||||<html><button id="edit" name="Key Events"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Key Events"><span class="ui-icon ui-icon-trash"></span></button></html>
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|[[Event:49|Ca and HCO3 transport to shell gland, Reduction]]||
  
 
|-
 
|-
  
|[[Eggshell thickness, Reduction]]||||<html><button id="edit" name="Key Events"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Key Events"><span class="ui-icon ui-icon-trash"></span></button></html>
+
|[[Event:106|Eggshell thickness, Reduction]]||
  
 
|-
 
|-
  
|[[Reproductive failure, N/A]]||||<html><button id="edit" name="Key Events"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Key Events"><span class="ui-icon ui-icon-trash"></span></button></html>
+
|[[Event:119|Gap, N/A]]||
 
+
|-
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|[[Gap, N/A]]||||<html><button id="edit" name="Key Events"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Key Events"><span class="ui-icon ui-icon-trash"></span></button></html>
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|-
 
|-
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=== Adverse Outcome ===
 
=== Adverse Outcome ===
  
<html>
 
<button id="TableAdd5">Add Adverse Outcome to Table</button>
 
</html>
 
<div id="popbox5" title='Add a Record' style='display:none'>
 
<html>
 
<span id="chosen1" style="float:left"> Action</span><span class="ui-icon ui-icon-info" title="How the event is affected"></span>
 
</br>
 
<input type=text id="describeAO" style="float:left"></input><span class="ui-icon ui-icon-circle-triangle-s"></span>
 
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</br>
 
<span id="chosen2" style="float:left"> Biological Process/Object</span><span class="ui-icon ui-icon-info" title="The Adverse Outcome for this AOP"></span>
 
</br>
 
</html>{{Template:InputBox|Adverse Outcome|Template:Adverse Outcome}}<html>
 
</br>
 
</br>
 
<span id="chosen3" style="float:left"> Evidence</span><span class="ui-icon ui-icon-info" title="How strong the evidence is for this event"></span>
 
</br>
 
<select id="weightAO">
 
  <option></option>
 
  <option>Very Strong</option>
 
  <option>Strong</option> 
 
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</br>
 
<button id="SubAO">Submit</button>
 
<button id="EditAO">Submit</button>
 
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{|class="wikitable sortable" id="AOproof"
 
{|class="wikitable sortable" id="AOproof"
  
 
!Adverse Outcome
 
!Adverse Outcome
!Evidence
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 +
|-
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|[[Event:253|Reproductive failure, N/A]]
  
 
|-
 
|-
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=== Relationships Among Key Events and the Adverse Outcome ===
 
=== Relationships Among Key Events and the Adverse Outcome ===
  
<html>
 
<button id="TableAdd">Add record to table</button>
 
</html>
 
<div id="popbox" title='Add a Record' style='display:none'>
 
<html>
 
<span id="chosen1" style="float:left"> Step </span><span class="ui-icon ui-icon-info" title="Input a step number for this relation"></span>
 
</br>
 
<input type=text id="step"></input>
 
</br>
 
</br>
 
<span id="chosen2" style="float:left"> Event</span><span class="ui-icon ui-icon-info" title="Input the upstream event that leads to/blocks the downstream event"></span>
 
</br>
 
<select id="upstream"></select>
 
</br>
 
</br>
 
<span id="chosen3" style="float:left"> Description</span><span class="ui-icon ui-icon-info" title="How the upstream event triggers the downstream event"></span>
 
</br>
 
<select id="describe">
 
  <option></option>
 
  <option>Leads to</option>
 
  <option>Blocks</option> 
 
</select>
 
</br>
 
</br>
 
<span id="chosen4" style="float:left"> Triggers</span><span class="ui-icon ui-icon-info" title="Input the downstream event triggered by the upstream event"></span>
 
</br>
 
<select id="downstream"></select>
 
</br>
 
</br>
 
<span id="chosen5" style="float:left"> Weight of Evidence</span><span class="ui-icon ui-icon-info" title="How strong the evidence is for this relationship"></span>
 
</br>
 
<select id="weight">
 
  <option></option>
 
  <option>Very Strong</option>
 
  <option>Strong</option> 
 
  <option>Moderate</option>
 
  <option>Weak</option> 
 
  <option>Very Weak</option>
 
</select>
 
</br>
 
</br>
 
</html>{{Template:InputBox|KE Relationship|Template:KE Relationship}}<html>
 
<button id="SubRel">Submit</button>
 
<button id="EditRel">Submit</button>
 
</html>
 
</div>
 
 
{| class="wikitable sortable" id="relation"
 
{| class="wikitable sortable" id="relation"
  
!Step
 
 
!Event
 
!Event
 
!Description
 
!Description
 
!Triggers
 
!Triggers
 
!Weight of Evidence
 
!Weight of Evidence
 +
!Quantitative Understanding
  
 
|-
 
|-
  
|1||[[Cyclooxygenase activity, Inhibition]]||Leads to||[[Prostaglandin E2 concentration, Reduction]]||[[Cyclooxygenase activity, Inhibition Leads to Prostaglandin E2 concentration, Reduction|Moderate]]||<html><button id="edit" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-trash"></span></button></html>
+
|[[Event:79|Cyclooxygenase activity, Inhibition]]||[[Relationship:95|Directly Leads to]]||[[Event:243|Prostaglandin E2 concentration, Reduction]]||[[Relationship:95#Weight of Evidence|Moderate]]||
  
 
|-
 
|-
  
|2||[[Prostaglandin E2 concentration, Reduction]]||Leads to||[[Gap, N/A]]||[[Prostaglandin E2 concentration, Reduction Leads to Gap, N/A|Not Specified]]||<html><button id="edit" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-trash"></span></button></html>
+
|[[Event:243|Prostaglandin E2 concentration, Reduction]]||[[Relationship:268|Directly Leads to]]||[[Event:119|Gap, N/A]]||[[Relationship:268#Weight of Evidence|Not Specified]]||
  
 
|-
 
|-
  
|3||[[Gap, N/A]]||Leads to||[[Ca and HCO3 transport to shell gland, Reduction]]||[[Gap, N/A Leads to Ca and HCO3 transport to shell gland, Reduction|Not Specified]]||<html><button id="edit" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-trash"></span></button></html>
+
|[[Event:119|Gap, N/A]]||[[Relationship:136|Directly Leads to]]||[[Event:49|Ca and HCO3 transport to shell gland, Reduction]]||[[Relationship:136#Weight of Evidence|Not Specified]]||
  
 
|-
 
|-
  
|4||[[Ca and HCO3 transport to shell gland, Reduction]]||Leads to||[[Eggshell thickness, Reduction]]||[[Ca and HCO3 transport to shell gland, Reduction Leads to Eggshell thickness, Reduction|Moderate]]||<html><button id="edit" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-trash"></span></button></html>
+
|[[Event:49|Ca and HCO3 transport to shell gland, Reduction]]||[[Relationship:59|Directly Leads to]]||[[Event:106|Eggshell thickness, Reduction]]||[[Relationship:59#Weight of Evidence|Moderate]]||
  
 
|-
 
|-
  
|5||[[Eggshell thickness, Reduction]]||Leads to||[[Reproductive failure, N/A]]||[[Eggshell thickness, Reduction Leads to Reproductive failure, N/A|Strong]]||<html><button id="edit" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-pencil"></span></button><button id="del" name="Relationships Among Key Events and the Adverse Outcome"><span class="ui-icon ui-icon-trash"></span></button></html>
+
|[[Event:106|Eggshell thickness, Reduction]]||[[Relationship:123|Directly Leads to]]||[[Event:253|Reproductive failure, N/A]]||[[Relationship:123#Weight of Evidence|Strong]]||
  
 
|-
 
|-
  
 
|}
 
|}
 +
 +
=== Network View ===
 +
<div id="cytoscapeweb">
 +
    Cytoscape Web will replace the contents of this div with your graph.
 +
</div>
 +
<div id="note">
 +
    <p>Click nodes or edges.</p>
 +
</div>
  
 
=== Life Stage Applicability ===
 
=== Life Stage Applicability ===
  
<html>
 
<button id="LifeStageList">Add Life Stage to table</button>
 
</html>
 
<div id="popbox1" title='Add a Record' style='display:none'>
 
<html>
 
<span id="chosen2" style="float:left"> Biological Process/Object</span><span class="ui-icon ui-icon-info" title="A Life Stage for this AOP"></span>
 
</br>
 
</html><div style="float:left">{{Template:InputBox|Life Stage|Template:Life Stage}}</div><html><span class="ui-icon ui-icon-circle-triangle-s"></span>
 
</br>
 
</br>
 
<span id="chosen3" style="float:left"> Evidence</span><span class="ui-icon ui-icon-info" title="How strong the evidence is for this life stage"></span>
 
</br>
 
<select id="weightLife">
 
  <option></option>
 
  <option>Very Strong</option>
 
  <option>Strong</option> 
 
  <option>Moderate</option>
 
  <option>Weak</option> 
 
  <option>Very Weak</option>
 
</select>
 
</br>
 
</br>
 
<button id="SubLife">Submit</button>
 
<button id="EditLife">Submit</button>
 
</html>
 
</div>
 
 
{|class="wikitable sortable" id="LSproof"
 
{|class="wikitable sortable" id="LSproof"
  
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=== Taxonomic Applicability ===
 
=== Taxonomic Applicability ===
 
<html>
 
<button id="SpeciesList" >Add Species from list</button>
 
</html>
 
<div id="popbox6" title='Add a Record' style='display:none'>
 
<html>
 
<span id="chosen2" style="float:left"> Biological Object</span><span class="ui-icon ui-icon-info" title="A Species for this AOP"></span>
 
</br>
 
</html>{{Template:InputBox|Species|Template:Species}}<html>
 
</br>
 
</br>
 
<span id="chosen1" style="float:left"> Scientific Name</span><span class="ui-icon ui-icon-info" title="A more scientific name for this species"></span>
 
</br>
 
<select id="scientificSpecies"><select>
 
</br>
 
</br>
 
<span id="chosen3" style="float:left"> Evidence</span><span class="ui-icon ui-icon-info" title="How strong the evidence is for this species"></span>
 
</br>
 
<select id="weightSpec">
 
  <option></option>
 
  <option>Very Strong</option>
 
  <option>Strong</option> 
 
  <option>Moderate</option>
 
  <option>Weak</option> 
 
  <option>Very Weak</option>
 
</select>
 
</br>
 
</br>
 
<button id="SubSpec">Submit</button>
 
<button id="EditSpec">Submit</button>
 
<button id="SubNext">Next</button>
 
<button id="EditNext">Next</button>
 
</html>
 
</div>
 
 
<div id="hideMsg" style='display:none'>
 
Attempting to compile scientific names.
 
This box will close when the task is complete.
 
Process time: <span>0</span>
 
</div>
 
  
 
{|class="wikitable sortable" id="Specproof"
 
{|class="wikitable sortable" id="Specproof"
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=== Sex Applicability ===
 
=== Sex Applicability ===
  
<html>
 
<button id="SexList" >Add a Sex to table</button>
 
</html>
 
<div id="popbox2" title='Add a Record' style='display:none'>
 
<html>
 
<span id="chosen2" style="float:left"> Biological Process/Object</span><span class="ui-icon ui-icon-info" title="Sexes for this AOP"></span>
 
</br>
 
<input type=text id="sexInput" style="float:left"></input><span class="ui-icon ui-icon-circle-triangle-s"></span>
 
</br>
 
</br>
 
<span id="chosen3" style="float:left"> Evidence</span><span class="ui-icon ui-icon-info" title="How strong the evidence is for this Sex"></span>
 
</br>
 
<select id="weightSex">
 
  <option></option>
 
  <option>Very Strong</option>
 
  <option>Strong</option> 
 
  <option>Moderate</option>
 
  <option>Weak</option> 
 
  <option>Very Weak</option>
 
</select>
 
</br>
 
</br>
 
<button id="SubSex">Submit</button>
 
<button id="EditSex">Submit</button>
 
</html>
 
</div>
 
 
{|class="wikitable sortable" id="Sexproof"
 
{|class="wikitable sortable" id="Sexproof"
  
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=== Graphical Representation ===
 
=== Graphical Representation ===
  
*[http://aopwiki.org/common/AOP_Graphic_Template2.pptx Click to download template for graphical representation]
+
*[https://aopkb.org/common/AOP_Graphic_Template2.pptx Click to download template for graphical representation]
  
 
[[File:Cyclooxygenase inhibition leading reproductive failure.jpg | 900px | Click to upload graphical representation]]
 
[[File:Cyclooxygenase inhibition leading reproductive failure.jpg | 900px | Click to upload graphical representation]]
  
== Assessment of the AOP ==
+
== Overall Assessment of the AOP ==
 
<em>
 
<em>
 
Consider the following criteria (may include references to KE Relationship pages):
 
Consider the following criteria (may include references to KE Relationship pages):
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</em>
 
</em>
  
== Confidence in the AOP ==
+
===Weight of Evidence Summary===
 +
[[#Relationships Among Key Events and the Adverse Outcome | Summary Table]]<br>
 +
<em>
 +
Provide an overall summary of the weight of evidence based on the evaluations of the individual linkages from the Key Event Relationship pages.
 +
</em>
 +
 
 +
===Essentiality of the Key Events===
 +
[[#Molecular Initiating Event | Molecular Initiating Event Summary]],
 +
[[#Key Events | Key Event Summary]]<br>
 +
<em>
 +
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.
 +
</em>
 +
 
 +
===Quantitative Considerations===
 +
[[#Relationships Among Key Events and the Adverse Outcome | Summary Table]]<br>
 +
<em>
 +
Provide an overall discussion of the quantitative information available for this AOP. Support calls for the individual relationships can be included in the Key Event Relationship table above.
 +
</em>
 +
 
 +
===Applicability of the AOP===
 +
[[#Life Stage Applicability | Life Stage Applicability]],
 +
[[#Taxonomic Applicability | Taxonomic Applicability]],
 +
[[#Sex Applicability | Sex Applicability]]<br>
 
<em>
 
<em>
 
Elaborate on the domains of applicability listed in the summary section above.  Specifically, provide the literature supporting, or excluding, certain domains.
 
Elaborate on the domains of applicability listed in the summary section above.  Specifically, provide the literature supporting, or excluding, certain domains.
 
</em>
 
</em>
 +
 +
== Considerations for Potential Applications of the AOP (optional) ==
  
 
== References ==
 
== References ==
  
 
<references />
 
<references />

Latest revision as of 18:39, 11 December 2016

Status

This is a legacy representation of this AOP. Please see the current version here:

https://aopwiki.org/aops/28


AOP Title

Cyclooxygenase inhibition leading reproductive failure
Short name: Cyclooxygenase inhibition leading reproductive failure

Authors

Dan Villeneuve, US EPA Mid-Continent Ecology Division (villeneuve.dan@epa.gov)

Status

Please follow the link to snapshots page to view and create Snapshots of this AOP.

Alert: The Weight of Evidence column in the Molecular Initiating Event and Key Event tables has changed to Essentiality. Consider re-evaluating the columns in these tables.

Under development: Do not distribute or cite.

Putative AOP

Project 1.29: A catalog of putative AOPs that will enhance the utility of US EPA Toxcast high throughput screening data for hazard identification


This AOP page was last modified on 12/11/2016.

Click here to show/hide revision dates for related pages

Page Revision Date/Time

Abstract

Summary of the AOP

Please follow link to widget page to edit this section.

If you manually enter text in this section, it will get automatically altered or deleted in subsequent edits using the widgets.

Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Cyclooxygenase activity, Inhibition

Key Events

Event Support for Essentiality
Prostaglandin E2 concentration, Reduction
Ca and HCO3 transport to shell gland, Reduction
Eggshell thickness, Reduction
Gap, N/A

Adverse Outcome

Adverse Outcome
Reproductive failure, N/A

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Cyclooxygenase activity, Inhibition Directly Leads to Prostaglandin E2 concentration, Reduction Moderate
Prostaglandin E2 concentration, Reduction Directly Leads to Gap, N/A Not Specified
Gap, N/A Directly Leads to Ca and HCO3 transport to shell gland, Reduction Not Specified
Ca and HCO3 transport to shell gland, Reduction Directly Leads to Eggshell thickness, Reduction Moderate
Eggshell thickness, Reduction Directly Leads to Reproductive failure, N/A Strong

Network View

   Cytoscape Web will replace the contents of this div with your graph.

Click nodes or edges.

Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

Name Scientific Name Evidence Links

Sex Applicability

Sex Evidence Links

Graphical Representation

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Overall Assessment of the AOP

Consider the following criteria (may include references to KE Relationship pages): 1. concordance of dose-response relationships; 2. temporal concordance among the key events and adverse effect; 3. strength, consistency, and specificity of association of adverse effect and initiating event; 4. biological plausibility, coherence, and consistency of the experimental evidence; 5. alternative mechanisms that logically present themselves and the extent to which they may distract from the postulated AOP. It should be noted that alternative mechanisms of action, if supported, require a separate AOP; 6. uncertainties, inconsistencies and data gaps.

Weight of Evidence Summary

Summary Table
Provide an overall summary of the weight of evidence based on the evaluations of the individual linkages from the Key Event Relationship pages.

Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.

Quantitative Considerations

Summary Table
Provide an overall discussion of the quantitative information available for this AOP. Support calls for the individual relationships can be included in the Key Event Relationship table above.

Applicability of the AOP

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains.

Considerations for Potential Applications of the AOP (optional)

References