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science in ACTION
INNOVATIVE RESEARCH FOR A SUSTAINABLE FUTURE
ADVERSE OUTCOME PATHWAY
Background
The same way you might piece
together a jigsaw puzzle, scientists at
the EPA are working hard to piece
together information about the
potential biological effects caused by
chemicals in the environment. Their
aim is to collect and connect
biological information to create a
fuller picture of how toxicity may be
expressed in the body. The approach
is helping to develop a consistent
way for scientists worldwide to
organize biological information— a
priority for the EPA. The science
behind this approach is called
Adverse Outcome Pathways, or
"AOPs." An AOP is a framework for
organizing these data, thereby
creating context to help better
understand the bigger picture.
Currently, only a relatively small
percentage of chemicals we are
exposed to everyday have been
evaluated in traditional toxicity
tests. The good news is that we have
massive amounts of information
from various sources that can help us
understand potential effects of the
remaining chemicals in the market.
And, we have the additional benefit
of newer high-throughput screening
methodologies which can be used to
inform the potential effects of
chemical exposure. But until AOPs,
there was no consistent way to pull
all this data together to understand it
in context.
Macro-Molecular Cellular
Chemical Interactions Responses
Organ	Individual
Responses Responses
Population
Response
/
II
Increasing level of biological organization
AOPs enable us to better use all
existing information to evaluate
"data poor" chemicals, even though
they have not gone through the time
intensive and expensive traditional
toxicity tests. They allow scientists
and decision-makers to access the
latest scientific information to
efficiently and effectively evaluate
the safety of chemicals.
Here's how it works
An AOP maps out how a stressor (e.g.
chemical) interacts within an
organism to cause adverse effects. If
the amount of the chemical is
sufficient, then cells can be affected,
which can then affect tissues (which
are collections of cells), organs
(which are collections of tissues),
and, ultimately, the health of the
organism or even the population as a
whole. By understanding the
individual key events, one can better
understand what the health outcome
will be. Information used to develop
AOPs can come from in vitro assays,
animal studies and computational
models. AOPs allow scientists to
connect the in vitro results generated
from rapid screening protocols to
actual adverse outcomes.
Standardizing the Adverse
Outcome Pathway Approach
The AOP approach requires
coordination and consistency among
scientists worldwide to ensure their
ability to inform chemical risk
assessments and regulatory
decisions. The EPA, in collaboration
with the international scientific
community, the European Joint
Research Center, the US Army Corp
of Engineers, the Organization of
Economic Cooperation and
Development (OECD), and others are
developing standardized approaches
and tools to facilitate consistent
development of AOPs. These
collaborations enable global "crowd
sourcing" of information and
establish common standards for
mutual acceptance of data across
borders.
1
U.S. Environmental Protection Agency
Office of Research and Development
February 2018

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Adverse Outcome Pathway Databases and Tools
The AOP Knowledge Base is an internationally accessible and searchable web-based resource for AOP information. The
AOP Knowledge Base was designed to bring together comprehensive knowledge on how chemicals can result in adverse
outcomes. This platform serves as a portal to share AOP tools and resources as they become publicly available.
The AOP Wiki is an interactive and virtual encyclopedia for AOP development intended to help the international
scientific community recognize and agree on AOPs. The AOP Wiki is maintained as part of the AOP Knowledge Base.
•	The AOP Wiki allows users to develop new AOPs and take advantage of AOPs already developed. The easy-to-
use tool stimulates open, crowd-sourced knowledge to capture and use AOPs.
•	The Wiki uses templates to make it easy for users to include the information needed for proper evaluation of an
AOP. These templates are based on OECD guidance so that fully developed AOPs from the Wiki can be used in a
regulatory context.
•	A controlled vocabulary promotes consistent terminology, avoiding unnecessary duplication of information in
the Wiki.
•	To be granted Wiki editing rights, interested users should request access and provide a summary of how they
can contribute expertise to the development and evaluation of AOPs.
More information
•	EPA's AOP Research Brief: https://www.epa.gov/chemical-research/adverse-outcome-pathwav-aop-research-
brief
•	AOP Knowledge Base: http://aopkb.org/background.html
•	AOP Wiki: http://aopwiki.org/
•	EPA's chemical safety research: https://www.epa.gov/chemical-research
•	Organization of Economic Cooperation and Development:
http://www.oecd.org/chemicalsafetv/testing/adverse-outcome-pathwavs-molecular-screening- and-
toxicogenomics.htm
•	For technical assistance/access: aopwiki(5)googlegroups.com
2
U.S. Environmental Protection Agency
Office of Research and Development
February 2018

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