Adverse outcome pathway networks I: Development and applications

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usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="xVUu0ACaO0B62VAgswKTWpMKOaslNNQNTF71A4oJzSi6RZ4TYVojukVyAFCwsSrx"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="xVUu0ACaO0B62VAgswKTWpMKOaslNNQNTF71A4oJzSi6RZ4TYVojukVyAFCwsSrx"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="xVUu0ACaO0B62VAgswKTWpMKOaslNNQNTF71A4oJzSi6RZ4TYVojukVyAFCwsSrx"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="xVUu0ACaO0B62VAgswKTWpMKOaslNNQNTF71A4oJzSi6RZ4TYVojukVyAFCwsSrx"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="29488651"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" 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value="xVUu0ACaO0B62VAgswKTWpMKOaslNNQNTF71A4oJzSi6RZ4TYVojukVyAFCwsSrx"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio" id="collections-action-dialog-new" class="collections-new" name="collections" value="new" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio" id="collections-action-dialog-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="collections_button" data-ga-action="click" data-ga-label="add"> Add </button><button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="collections_button" data-ga-action="click" data-ga-label="cancel"> Cancel </button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" 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class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Environ+Toxicol+Chem%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22Environ+Toxicol+Chem%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=Environ Toxicol Chem" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Environ Toxicol Chem"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Environ+Toxicol+Chem%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="Environ Toxicol Chem"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"Environ Toxicol Chem"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"Environ Toxicol Chem"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2018 Jun;37(6):1723-1733.</span> </div> <span class="citation-doi"> doi: 10.1002/etc.4125. </span> <span class="secondary-date"> Epub 2018 May 7. </span> </div> <h1 class="heading-title"> Adverse outcome pathway networks I: Development and applications </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Knapen+D&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Dries Knapen">Dries Knapen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Zebrafishlab, Veterinary Physiology and Biochemistry, University of Antwerp, Wilrijk, Belgium." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Angrish+MM&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Michelle M Angrish">Michelle M Angrish</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="National Center for Environmental Assessment, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Fortin+MC&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Marie C Fortin">Marie C Fortin</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Katsiadaki+I&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Ioanna Katsiadaki">Ioanna Katsiadaki</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Centre for Environment, Fisheries and Aquaculture Science, Weymouth, United Kingdom." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Leonard+M&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Marc Leonard">Marc Leonard</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="L'Oréal Advanced Research, Aulnay-sous-Bois, France." href="#full-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Margiotta-Casaluci+L&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Luigi Margiotta-Casaluci">Luigi Margiotta-Casaluci</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Environment, Health and Societies, Brunel University London, London, United Kingdom." href="#full-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Munn+S&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sharon Munn">Sharon Munn</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Joint Research Centre, European Commission, Ispra, Italy." href="#full-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=O%27Brien+JM&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jason M O'Brien">Jason M O'Brien</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="National Wildlife Research Centre, Environment and Climate Change Canada, Ottawa, Ontario, Canada." href="#full-view-affiliation-8" ref="linksrc=author_aff"> 8 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Pollesch+N&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Nathan Pollesch">Nathan Pollesch</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Mid-Continent Ecology Division, US Environmental Protection Agency, Duluth, Minnesota, USA." href="#full-view-affiliation-9" ref="linksrc=author_aff"> 9 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Smith+LC&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="L Cody Smith">L Cody Smith</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida, USA." href="#full-view-affiliation-10" ref="linksrc=author_aff"> 10 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Zhang+X&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Xiaowei Zhang">Xiaowei Zhang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China." href="#full-view-affiliation-11" ref="linksrc=author_aff"> 11 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Villeneuve+DL&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Daniel L Villeneuve">Daniel L Villeneuve</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Mid-Continent Ecology Division, US Environmental Protection Agency, Duluth, Minnesota, USA." href="#full-view-affiliation-9" ref="linksrc=author_aff"> 9 </a></sup></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/29488651/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> <div class="expanded-authors" id="full-view-expanded-authors"> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="full-view-affiliation-1" id="full-view-affiliation-1" ><sup class="key">1</sup> Zebrafishlab, Veterinary Physiology and Biochemistry, University of Antwerp, Wilrijk, Belgium.</li> <li data-affiliation-id="full-view-affiliation-2" id="full-view-affiliation-2" ><sup class="key">2</sup> National Center for Environmental Assessment, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA.</li> <li data-affiliation-id="full-view-affiliation-3" id="full-view-affiliation-3" ><sup class="key">3</sup> Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.</li> <li data-affiliation-id="full-view-affiliation-4" id="full-view-affiliation-4" ><sup class="key">4</sup> Centre for Environment, Fisheries and Aquaculture Science, Weymouth, United Kingdom.</li> <li data-affiliation-id="full-view-affiliation-5" id="full-view-affiliation-5" ><sup class="key">5</sup> L'Oréal Advanced Research, Aulnay-sous-Bois, France.</li> <li data-affiliation-id="full-view-affiliation-6" id="full-view-affiliation-6" ><sup class="key">6</sup> Institute of Environment, Health and Societies, Brunel University London, London, United Kingdom.</li> <li data-affiliation-id="full-view-affiliation-7" id="full-view-affiliation-7" ><sup class="key">7</sup> Joint Research Centre, European Commission, Ispra, Italy.</li> <li data-affiliation-id="full-view-affiliation-8" id="full-view-affiliation-8" ><sup class="key">8</sup> National Wildlife Research Centre, Environment and Climate Change Canada, Ottawa, Ontario, Canada.</li> <li data-affiliation-id="full-view-affiliation-9" id="full-view-affiliation-9" ><sup class="key">9</sup> Mid-Continent Ecology Division, US Environmental Protection Agency, Duluth, Minnesota, USA.</li> <li data-affiliation-id="full-view-affiliation-10" id="full-view-affiliation-10" ><sup class="key">10</sup> Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida, USA.</li> <li data-affiliation-id="full-view-affiliation-11" id="full-view-affiliation-11" ><sup class="key">11</sup> State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China.</li> </ul> </div> </div> </div> <ul class="identifiers" id="full-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">29488651</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC6004608&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6004608/" data-ga-category="full_text" data-ga-action="PMCID" > PMC6004608 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1002/etc.4125&id_type=DOI" href="https://doi.org/10.1002/etc.4125" data-ga-category="full_text" data-ga-action="DOI" > 10.1002/etc.4125 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> <div class="short-view" id="short-view-heading"> <h1 class="heading-title"> Adverse outcome pathway networks I: Development and applications </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">Dries Knapen</span><span class="citation-separator"> et al.</span></span> </span> <span class="citation-journal"> Environ Toxicol Chem<span class="citation-separator">.</span> </span> <span class="date"> <span class="citation-year">2018 Jun</span><span class="citation-separator">.</span> </span> </div> <div class="more-article-details-section with-display-settings"> <button class="more-article-details" id="toggle-article-details" data-alt-text="Hide details" ref="linksrc=toggle_article_details" aria-controls="full-article-details" aria-expanded="false" data-fetch-url="/29488651/long-authors/" data-id-prefix=""> <span class="title">Show details</span> </button> <div class="display-options" data-format-key="format" data-default-format-value="abstract" 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href="/?term=Knapen+D&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Dries Knapen">Dries Knapen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Zebrafishlab, Veterinary Physiology and Biochemistry, University of Antwerp, Wilrijk, Belgium." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Angrish+MM&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Michelle M Angrish">Michelle M Angrish</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="National Center for Environmental Assessment, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Fortin+MC&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Marie C Fortin">Marie C Fortin</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Katsiadaki+I&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Ioanna Katsiadaki">Ioanna Katsiadaki</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Centre for Environment, Fisheries and Aquaculture Science, Weymouth, United Kingdom." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Leonard+M&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Marc Leonard">Marc Leonard</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="L'Oréal Advanced Research, Aulnay-sous-Bois, France." href="#short-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Margiotta-Casaluci+L&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Luigi Margiotta-Casaluci">Luigi Margiotta-Casaluci</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Environment, Health and Societies, Brunel University London, London, United Kingdom." href="#short-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Munn+S&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sharon Munn">Sharon Munn</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Joint Research Centre, European Commission, Ispra, Italy." href="#short-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=O%27Brien+JM&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jason M O'Brien">Jason M O'Brien</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="National Wildlife Research Centre, Environment and Climate Change Canada, Ottawa, Ontario, Canada." href="#short-view-affiliation-8" ref="linksrc=author_aff"> 8 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Pollesch+N&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Nathan Pollesch">Nathan Pollesch</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Mid-Continent Ecology Division, US Environmental Protection Agency, Duluth, Minnesota, USA." href="#short-view-affiliation-9" ref="linksrc=author_aff"> 9 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Smith+LC&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="L Cody Smith">L Cody Smith</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida, USA." href="#short-view-affiliation-10" ref="linksrc=author_aff"> 10 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Zhang+X&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Xiaowei Zhang">Xiaowei Zhang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China." href="#short-view-affiliation-11" ref="linksrc=author_aff"> 11 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Villeneuve+DL&cauthor_id=29488651" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Daniel L Villeneuve">Daniel L Villeneuve</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Mid-Continent Ecology Division, US Environmental Protection Agency, Duluth, Minnesota, USA." href="#short-view-affiliation-9" ref="linksrc=author_aff"> 9 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Zebrafishlab, Veterinary Physiology and Biochemistry, University of Antwerp, Wilrijk, Belgium.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> National Center for Environmental Assessment, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA.</li> <li data-affiliation-id="short-view-affiliation-3" id="short-view-affiliation-3" ><sup class="key">3</sup> Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.</li> <li data-affiliation-id="short-view-affiliation-4" id="short-view-affiliation-4" ><sup class="key">4</sup> Centre for Environment, Fisheries and Aquaculture Science, Weymouth, United Kingdom.</li> <li data-affiliation-id="short-view-affiliation-5" id="short-view-affiliation-5" ><sup class="key">5</sup> L'Oréal Advanced Research, Aulnay-sous-Bois, France.</li> <li data-affiliation-id="short-view-affiliation-6" id="short-view-affiliation-6" ><sup class="key">6</sup> Institute of Environment, Health and Societies, Brunel University London, London, United Kingdom.</li> <li data-affiliation-id="short-view-affiliation-7" id="short-view-affiliation-7" ><sup class="key">7</sup> Joint Research Centre, European Commission, Ispra, Italy.</li> <li data-affiliation-id="short-view-affiliation-8" id="short-view-affiliation-8" ><sup class="key">8</sup> National Wildlife Research Centre, Environment and Climate Change Canada, Ottawa, Ontario, Canada.</li> <li data-affiliation-id="short-view-affiliation-9" id="short-view-affiliation-9" ><sup class="key">9</sup> Mid-Continent Ecology Division, US Environmental Protection Agency, Duluth, Minnesota, USA.</li> <li data-affiliation-id="short-view-affiliation-10" id="short-view-affiliation-10" ><sup class="key">10</sup> Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida, USA.</li> <li data-affiliation-id="short-view-affiliation-11" id="short-view-affiliation-11" ><sup class="key">11</sup> State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">29488651</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC6004608&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6004608/" data-ga-category="full_text" data-ga-action="PMCID" > PMC6004608 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1002/etc.4125&id_type=DOI" href="https://doi.org/10.1002/etc.4125" data-ga-category="full_text" data-ga-action="DOI" > 10.1002/etc.4125 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/29488651/citations/" data-citation-style="nlm" data-pubmed-format-link="/29488651/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> Based on the results of a Horizon Scanning exercise sponsored by the Society of Environmental Toxicology and Chemistry that focused on advancing the adverse outcome pathway (AOP) framework, the development of guidance related to AOP network development was identified as a critical need. This not only included questions focusing directly on AOP networks, but also on related topics such as mixture toxicity assessment and the implementation of feedback loops within the AOP framework. A set of two articles has been developed to begin exploring these concepts. In the present article (part I), we consider the derivation of AOP networks in the context of how it differs from the development of individual AOPs. We then propose the use of filters and layers to tailor AOP networks to suit the needs of a given research question or application. We briefly introduce a number of analytical approaches that may be used to characterize the structure of AOP networks. These analytical concepts are further described in a dedicated, complementary article (part II). Finally, we present a number of case studies that illustrate concepts underlying the development, analysis, and application of AOP networks. The concepts described in the present article and in its companion article (which focuses on AOP network analytics) are intended to serve as a starting point for further development of the AOP network concept, and also to catalyze AOP network development and application by the different stakeholder communities. Environ Toxicol Chem 2018;37:1723-1733. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. </p> </div> <p> <strong class="sub-title"> Keywords: </strong> Adverse outcome pathway; Adverse outcome pathway network; Network development; Network topology; Predictive toxicology; Risk assessment. </p> </div> <p class="copyright" id="copyright"> © 2018 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. </p> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37fa/6004608/5e16f4f5000f/nihms972624f1.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="800" data-image-height="249" data-image-alt="Figure 1" data-pmc-id="PMC6004608" data-figure-id="F1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37fa/6004608/3e10aa0c31f1/nihms972624f1.gif" alt="Figure 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="249"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><p> Graphical representation of the AOP… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><p> Graphical representation of the AOP network derivation – refinement – analysis workflow. A… </p></div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 1 </strong> <div class="figure-caption-contents">Graphical representation of the AOP network derivation – refinement – analysis workflow. A primary AOP network is constructed by querying the AOP knowledgebase (AOP-KB). Filters are then applied to derive a filtered network containing AOPs of interest for a given application or research question. Layers can be added in a next step to add data relevant to the application. Finally, the AOP network can be analyzed to produce metrics related to the topology and other properties of the network.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37fa/6004608/b4a162483472/nihms972624f2.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="800" data-image-height="645" data-image-alt="Figure 2" data-pmc-id="PMC6004608" data-figure-id="F2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37fa/6004608/4b4b2d7818b6/nihms972624f2.gif" alt="Figure 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="645"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><p> Examples of AOP network analysis… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><p> Examples of AOP network analysis concepts and approaches. (A) Network topology analysis can… </p></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2 </strong> <div class="figure-caption-contents">Examples of AOP network analysis concepts and approaches. (A) Network topology analysis can reveal converging, diverging, or mixed patterns. A mixed pattern can take the shape of a bow tie motif. (B) Two different examples of network metrics calculated for the same hypothetical AOP network. The degree of a node (key event, KE) in the network is equal to the number of edges (key event relationships, KERs) connecting the node to the network and is one way of expressing how connected that node is to the network. The path occurrence is the number of times a node (KE) occurs in a path connecting a molecular initiation event (MIE) to an adverse outcome (AO) after evaluating all possible paths between the MIEs and AOs of the network. The path occurrence may be an indication of the relative importance of a node within the overall network.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37fa/6004608/9af7219298ce/nihms972624f3.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="800" data-image-height="782" data-image-alt="Figure 3" data-pmc-id="PMC6004608" data-figure-id="F3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37fa/6004608/749172c14800/nihms972624f3.gif" alt="Figure 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="782"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><p> AOP network for steatosis. The… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><p> AOP network for steatosis. The high level of crosstalk between the different receptors… </p></div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 3 </strong> <div class="figure-caption-contents">AOP network for steatosis. The high level of crosstalk between the different receptors and associated signaling pathways complicates the use of existing high-throughput screening data as predictors of a steatotic outcome. This challenge was overcome by identifying a network topology converging into four key events (i.e., lipogenesis, and fatty acid uptake, efflux and oxidation) that were viewed as critical paths leading to steatosis. Assays measuring these points of convergence integrate the complex interplay of upstream events and translate them into measures that are more directly related to the adverse outcome. FA: fatty acid, TAG: triacylglycerol, PI3K: phosphatidylinositol-3-kinase, AKT: protein kinase B, PPAR: peroxisome proliferator-activated receptor, LXR: liver X receptor, CAR: constitutive androstane receptor, PXR: pregnane X receptor, FXR: farnesoid X receptor, RXR: retinoid X receptor.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37fa/6004608/579bbeb9a99f/nihms972624f4.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="800" data-image-height="825" data-image-alt="Figure 4" data-pmc-id="PMC6004608" data-figure-id="F4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37fa/6004608/1a8d4d17b784/nihms972624f4.gif" alt="Figure 4" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="825"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><p> AOP networks related to disruption… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><p> AOP networks related to disruption of the thyroid axis. (A) Multi-taxon thyroid hormone… </p></div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 4 </strong> <div class="figure-caption-contents">AOP networks related to disruption of the thyroid axis. (A) Multi-taxon thyroid hormone disruption AOP network including mammalian, amphibian and teleost endpoints. The blue regions illustrate how a taxonomic applicability layer may be used to add relevant data to the primary network representation. The key events highlighted in yellow indicate two major points of convergence/divergence in the network, resembling the “knot” of a bow tie motif. (B) Filtered thyroid AOP network only containing key events that are relevant to fish. The dashed brown area illustrates how additional filtering might be used to further refine the network, e.g. to only include key events that are relevant to specific life stages. The blue area illustrates the use of a layer to indicate the presence of a feedback loop acting on an AOP in the network, and the interaction between the feedback loop and one of the molecular initiating events in the network. IYD: iodotyrosine deiodinase, NIS: sodium-iodide symporter, TPO: thyroperoxidase, DIO: iodothyronine deiodinase, TH: thyroid hormone, T4: thyroxine, T3: triiodothyronine, TRH: thyrotropin-releasing hormone, TSH: thyroid stimulating hormone, thyrotropin, SB: swim bladder. Red negative sign: inhibition processes. Red arrow: DIO inhibition decreases conversion of T4 into T3, thereby inhibiting the feedback inhibition of T3 on TRH and TSH synthesis.</div> </figcaption> </figure> </div>  <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog">  <div class="pswp__bg"></div>  <div class="pswp__scroll-wrap">  <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div>  <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar">  <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" title="Toggle fullscreen"></button> <button class="pswp__button pswp__button--zoom" title="Zoom in/out"></button>   <div class="pswp__preloader"> <div class="pswp__preloader__icn"> <div class="pswp__preloader__cut"> <div class="pswp__preloader__donut"></div> </div> </div> </div> </div> <div class="pswp__share-modal pswp__share-modal--hidden pswp__single-tap"> <div class="pswp__share-tooltip"></div> </div> <button class="pswp__button pswp__button--arrow--left" title="Previous (arrow left)"> </button> <button class="pswp__button pswp__button--arrow--right" title="Next (arrow right)"> </button> <div class="pswp__caption"> <div class="pswp__caption__center"></div> </div> </div> </div> </div> <div class="figure-dialog-caption"> <div class="figure-caption-link-container"> <a class="figure-caption-link" href="#">See this image and copyright information in PMC</a> </div> <div class="figure-caption-center" data-expand-title="click to show full caption" data-collapse-title="click to hide full caption"> </div> <button class="figure-caption-toggle-btn" aria-label="show full caption" data-expand-text="show full caption" data-collapse-text="hide full caption">  </button> </div> </div> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/29492998/" ref="article_id=29492998&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="29492998" data-ga-label=""> Adverse outcome pathway networks II: Network analytics. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Villeneuve DL, Angrish MM, Fortin MC, Katsiadaki I, Leonard M, Margiotta-Casaluci L, Munn S, O'Brien JM, Pollesch NL, Smith LC, Zhang X, Knapen D.</span> <span class="docsum-authors short-authors">Villeneuve DL, et al.</span> <span class="docsum-journal-citation full-journal-citation">Environ Toxicol Chem. 2018 Jun;37(6):1734-1748. doi: 10.1002/etc.4124. 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Tipping the Balance: Hepatotoxicity and the 4 Apical Key Events of Hepatic Steatosis. Toxicol Sci. 2016;150(2):261–268. - <a class="reference-link" href="/26980302/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="26980302" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Angrish MM, McQueen CA, Cohen-Hubal E, Rooney JP, Bruno M, Ge Y, Chorley BN. Mechanistic Toxicity Tests Based on an Adverse Outcome Pathway Network for Hepatic Steatosis. Toxicol Sci. 2017;159(1):159–169. - <a class="reference-link" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8130650/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="PMC8130650" > PMC </a> - <a class="reference-link" href="/28903485/" ref="linksrc=references_link&ordinalpos=2" data-ga-category="reference" data-ga-action="28903485" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrrano JA, Tietge JE, Villeneuve DL. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem. 2010;29(3):730–741. - <a class="reference-link" href="/20821501/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="20821501" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Bell SM, Angrish MM, Wood CE, Edwards SW. Integrating Publicly Available Data to Generate Computationally Predicted Adverse Outcome Pathways for Fatty Liver. Toxicol Sci. 2016;150(2):510–20. - <a class="reference-link" href="/26895641/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="26895641" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Cavallin JE, Ankley GT, Blackwell BR, Blanksma CA, Fay KA, Jensen KM, Kahl MD, Knapen D, Kosian PA, Poole ST, Randolph EC, Schroeder AL, Vergauwen L4, Villeneuve DL. Impaired swim bladder inflation in early life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid. 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Adverse outcome pathway networks I: Development and applications - PubMed