science in ACTION
INNOVATIVE RESEARCH FOR A SUSTAINABLE FUTURE
&EPA
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www.epa.gov/research
ADVERSE OUTCOME PATHWAY (AOP) WIKI (http://aopwiki.org/)
Chemicals
Receptors / Enzymes I etc.
Direct Molecular Interaction
Pathway Regulation I
Genomics
Cellular Processes
Tissue I Organ I Organism Tox Endpoint
Background
An adverse outcome pathway
(AOP) is a conceptual framework
that portrays existing knowledge
concerning the linkage between a
direct molecular initiating event
and an adverse outcome, at a
level of biological organization
relevant to risk assessment. The
goal of an AOP is to provide the
framework that connects those
two events.
AOPs are important for
expanding the use of mechanistic
toxicological data for risk
assessment and regulatory
applications. Information can be
derived from in vitro, in vivo, or
computational systems. AOPs
allow scientists to connect results
from the use of in-vitro tools and
rapid screening protocols to
actual adverse outcomes.
AOP Wilvi
The wiki-based tool "AOPWiki"
provides a user-friendly and
open-source interface for rapid,
widely accessible, and
collaborative sharing of
established AOPs and building
new AOPs. The goals are to
structure information and to
provide a shared space to
facilitate collaboration. This
design will help to avoid
duplicated efforts. In addition, it
will initiate scientific discussions
early in order to build consensus
on the evidence supporting the
biological information
underlying each AOP as well as
the relevance of that AOP for
supporting regulatory decision
making.
AOPWiki is being developed by
multiple organizations - EPA
Office of Research and
Development, Chemical Safety
U.S. Environmental Protection Agency
Office of Research and Development
for Sustainability program, the
European Commission's Joint
Research Centre, the
Organization of Economic
Cooperation and Development
(OECD), the US Army Engineer
Research and Development Center,
and the international scientific
community at large.
Coordination among these
organizations will help with
international recognition and
consensus. AOPWiki is an
implementation of the OECD
"Guidance on Developing and
Assessing AOPs"*, and thereby
lets users both develop new
AOPs and make the most of
already developed AOPs. The
easy-to-use tool will stimulate
open, crowd-sourced knowledge
capture and use.
AOPWiki uses templates to
make it easy for users to include
the information needed for
proper evaluation of an AOP.
These templates are based on the
OECD guidance* so that fully
developed AOPs from the wiki
should be suitable for use in a
regulatory context. The general
idea is to develop the AOP using
user-friendly widgets instead of
requiring users to learn a wiki
markup language. This
simplifies the process for
scientists and users who may not
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Con tin ued from fron t
Macro-
Molecular
Interactions
Cellular
Responses
Organ
Responses
Organism
Responses
Population
Responses
Toxicant
Gene
activation
Receptor/Ligand
Interaction
Altered
physiology
Lethality
Structure
Recruitment
Extinction
Chemical
Properties
Impaired
Development
Protein
production
DNA Binding
Protein Oxidation
Disrupted
homeostasis
Altered
signaling
Impaired
Reproduction
Altered tissue
development/
function
Toxicity Pathways
Adverse Outcomes
have extensive experience with
editing in a wiki environment. In
addition, a controlled vocabulary
promotes consistent terminology,
thereby avoiding unnecessary
duplication of information in the
wiki.
AOPWiki represents the initial
phase in a larger effort to build a
complete AOP knowledgebase
(AOP KB). In addition to the
AOP wiki to capture textual
knowledge, the AOP KB will
contain additional modules. A
gi-ciphic module will support
AOP development and highlight
the interconnections among
AOPs via network viewing tools.
An Intermediate Effects module
will provide AOP information in
a format acceptable for
regulatory purposes (OECD
Harmonised Templates).
Together, these modules will
form a comprehensive collection
of AOP knowledge - based on
internationally accepted
standards
Timeline
•	June, 2013 - Beta release for
OECD AOP development
teams
•	December, 2013 - Broader
access based on OECD EAG
recommendations
•	2014 and beyond -
-	Integrate wiki with other
components of the AOP KB
-	Focus on formalizing AOP
information to facilitate
computational modeling
More information:
www.epa.gov/research/
*http://www.oecd.org/env/ehs/t
esting/molecularscreeningandt
oxicogenomics.htm
For technical assistance access:
aouwiki(a),soosIesroiws.com
Contact: Stephen Edwards,
edwards. Stephen®, epa. gov.
919-541-0514.
June 2013
AOP Knowledgebase
Contributors:
•	US EPA
•	European Commission's
Joint Research Centre
•	US Army Corps of Engineers
Engineer Research &
Development Center
•	International QSAR
Foundation
•	International Organizations
-	OECD External Advisory
Group on AOPs
-	IPCS/WHO Mode of Action
Steering Committee
Collaboration
In addition to the international
collaborators working together to
build the AOP KB, EPA Program
Offices, EPA Regions, and
external stakeholders have
participated in the AOP wiki
planning process. Collaboration
is vital for the success of the
AOP wiki, and EPA will
continue to seek input to
continuously enhance AOP wiki
development.
2
U.S. Environmental Protection Agency
Office of Research and Development

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