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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
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