Advancing the Development of Quality AOPs Submitted to OECD’s AOP Knowledge Base (AOP-KB) and the AOP-Wiki Rob DeWoskin1, Janet DeWoskin1, Catherine Willett2

1 etioLogic, Durham, NC, United States; 2The Humane Society of the United States (HSUS), Humane Society International, Boston, MA.

Why Develop AOPs?

Rob DeWoskin1 rdewoskin@etiologic.net 919-251-5705

Abstract: 3441 Poster: P413

AOP eLearning Course Modules

AOP HISTORY AND OVERVIEW AOP-KB AND THE AOP-WIKI The online course is intended for researchers, risk and hazard assessors from a broad array of government, public and private sectors who have an interest in submitting or using AOPs, or who are generating data that can be used to develop AOPs.

The course is designed to: •  Be a freely accessible, consolidated, centralized repository of

current and core AOP training materials and resources; •  Increase the number and quality of vetted AOPs available for

advanced research on network perturbations as well as regulatory decision making;

•  Provide an overview as well as detailed tutorials on how to create and evaluate AOPs using the AOP Wiki; and

•  Support progress towards achieving the goals of the 3Rs - Replace/Reduce/Refine the use of animals in laboratory testing and education.

A top priority to achieve TT21C objectives for predictive toxicology are the development of high quality adverse outcome pathways (AOPs) that support risk assessment research and regulatory decision-making.

To that end, the OECD (Organization of Economic Cooperation and development) launched a new program in 2012 to advance the development of Adverse Outcome Pathways (AOPs). The OECD program supports both the development and review of AOPs, and in collaboration with other international scientists, have created a suite of tools including the AOP Knowledge Base (AOP-KB), a web-based platform that brings together knowledge on the biological pathways underlying chemical-induced adverse effects. The AOP-KB provides a focal point for AOP development and dissemination.

Currently, training on the development of high quality AOPs submitted to the AOP-Wiki is contained in OECD guidance documents, and is being provided with 1-2 day in-person specialized classroom workshops or individual presentations. To compliment these trainings, the Human Toxicology Project Consortium (HTPC; https://humantoxicologyproject.org) and the US Humane Society (HSUS) sponsored the development of a widely accessible, online eLearning course.

eLearning Course Overview

A second module provides a detailed and technical step-by-step instruction on the information needed to develop and submit quality AOPs to the AOP-Wiki site.

The course includes a stand-alone module on the history and importance of the pathway approach, the OECD AOP Programme, general principles on the development and use of AOPs, and the quality criteria used to evaluate AOPs. This module can be included in a graduate or advanced undergraduate curriculum.

Additional AOP-KB tools currently under development (Effectopedia, AOP Xplorer and Intermediate Effects Database) are also discussed.

Abridged Table of Contents (~100 slides –many interactive or narrated)

1.  Course  Introduc/on  Course  Content  Who  can  benefit  Course  goals  

2.  Introduc/on  to  Toxicology  Interpre4ng  Data  for  Risk  Assessors  Current  Methods  in  Toxicology    Limita4ons  of  Current  Pathway  Approach  21st  Century  Future  of  Toxicology  Modern  research  AOP  as  knowledge  bridge  AOP  Formally  Defined  Dis4nc4on  between  MOAs  and  AOPs    

3.  AOP  Structure  AOP  Structure,  Func4on  Organiza4onal  Framework,  Benefits  Terms  and  Defini4ons  Regulatory  Context  for  Test  Methods  Benefits  of  an  AOP  Approach  Formalizing  the  AOP  Framework  Evolu4on  of  the  OECD  AOP-­‐KB    

4.  AOP  Knowledge  Base  and  Wiki    Intro  to  the  AOP-­‐KB  and  Wiki  AOP-­‐KB  -­‐  A  Collabora4ve  Effort    Components  of  the  AOP-­‐KB  The  AOP-­‐Wiki  

5.  Principles  of  AOP  development    Five  Principles  of  AOP  Development  

6.  Evalua/on  and  Review  Criteria    Assembling  and  Assessment  of  WOE  Best  Prac4ces  Modified  B/H  Considera4ons  Confidence  Analysis  

7.  Fitness  for  Use    Regulatory  Decision  Making  IATAs  QSARs  MOAs  and  tes4ng  strategies  Computa4onal  models  

8.  Current  Status  of  AOP  Development    Current  Status  of  AOP  Development  Link  to  OECD  Series  on  AOPs  

9.  List  of  Key  Resources  and  Links  

Sample Slides Highly Abridged Table of Contents (~200 step-by-step slides)

Sample Slides

1.   Intro  and  Review  of  AOPs  and  AOP-­‐KB  2.   Characteris/cs  and  Good  Prac/ces  

Assembling  Informa4on    Characteris4cs  of  KEs,  MIEs,  AOs,  KERs  

3.  Introducing  the  AOP  Wiki  4.  Development  and  Review  Process  

 OECD  AOP  Development  and  Review  Process  5.  Registering  on  the  AOP-­‐Wiki  

 Access  and  Use  of  the  AOP-­‐Wiki  Site  6.  Entering  Informa/on  -­‐  Step-­‐by-­‐Step  Training  

Quality  Criteria,  Edi4ng  &  Comments  Policy  Organizing  AOP  informa4on  in  the  AOP-­‐Wiki  Entering  Informa4on  into  the  AOP-­‐WIKI  AOP-­‐Wiki  Online  “Help”  Informa4on  Crea4ng  a  New  AOP  in  the  AOP-­‐Wiki  Title  Field,  Point  of  Contact,  Author(s),  Status  Enter  Abstract  Informa4on  Enter  Background  Informa4on  AOP  Summary  page    Adding  a  Stressor  Crea4ng  an  MIE,  KE,  AO,  KER  Suppor4ng  Informa4on  Common  to  All  Events    Adding  a  Taxonomic  Term  Adding  a  Life  Stage  Term  Adding  a  Sex  Applicability  Term  How  This  Key  Event  Works  How  it  is  Measured  or  Detected  Evidence  Suppor4ng  Taxonomic  Applicability  ....[many  addt  slides  on  MIE/AO/KERs]...  WOE  -­‐Biological  Plausibility  WOE-­‐  Empirical  Support  for  Linkage  Bradford  Hill  Considera4ons  Dose-­‐response  concordance    Temporal  concordance  WOE-­‐  Uncertain4es  or  Inconsistencies  Quan4ta4ve  Understanding  of  the  Linkage  Evidence  Suppor4ng  Taxonomic  Applicability  Network  View,  Graphical  Representa4on  Overall  Assessment  of  the  AOP  Domain  of  Applicability  Essen4ality  of  the  Key  Events  Quan4ta4ve  Understanding  Biologically-­‐based  Predic4on  Models  Poten4al  Applica4ons  of  the  AOP  Fit  for  Purpose  

7.  References  

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! !Access the AOP eLearning course at: placeholder for the URL