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The Adverse Outcome Pathways Knowledge Base
Transcript of The Adverse Outcome Pathways Knowledge Base
Studies chemicals to determine how they can be used
Assesses the probability of
to human life or the environment
Assists in establishing regulations that
humans and the environment
Limitations of current toxicology
understand mechanism of toxicity
data and data sources
To be weighed in terms of
Assess and document
Role of toxicology
AOPs help to inform regulators about the
Once regulators understand and
a mechanism, they are more inclined to accept
based on mechanistic thinking
An Adverse Outcome Pathway (AOP) is an analytical construct that describes a sequential chain of causally linked events leading to an
adverse human health
AOPs are the central element of a toxicological knowledge framework being built to support chemical risk assessment based on
AOPs are modular
AOPs are not chemical specific
to understand what a single chemical does
to describe what any chemical that perturbs "normal biology" with sufficient potency and duration is likely to do - "motifs of failure"
Adverse Outcome Pathways
Five principles of AOP development
Adverse Outcome Pathways
What is needed?
Methods to understand how
Examine how toxicity works "its way" via
* cancer, reproductive problems, death, ...
AOPs do not necessarily produce
but provide a place to collect and organise
from numerous sources
regulation of chemicals
is the legislative intent of a variety of national laws or international initiatives such as agreements, strategies or conventions.
(In the EU, REACH is the most relevant regulation)
AOPs are a pragmatic functional unit
An AOP is a
In many cases,
of AOPs are the functional unit of prediction
"objective complete AOP"
To enable the scientific community,
in one central location
, to share, develop and discuss their AOP-related knowledge, the "Adverse Outcome Pathway Knowledge Base" (AOP-KB) was created.
AOP-KB is a
platform managed by the Organisation for Economic Co-operation and Development (OECD):
Everyone across the stakeholder community (research, industry, regulatory bodies etc.)
is invited to contribute their AOP knowledge
The e.AOP. Portal is the
for all AOPs and KEs that are available currently in the other modules
The AOP Wiki provides a platform for the
formal definition and evaluation
The AOP Wiki supports the
OECD review process
Effectopedia provides a collaborative research platform for quantitative AOP development.
AOP Review Process
All AOPs aiming at
ultimately undergo review
Regulatory decision makers in all areas are
drowning in peer-reviewed journal papers
, while what they would need is
distilled from the information flood.
The success of AOP-KB clearly demonstrates there is a
to this paradox, and that people working in the overlapping areas of
are more than ready for a
in the way they gain insight into scientific issues and how they can apply the acquired knowledge to their respective areas
knowledge driven approach
to underpin the collaborative reasoning on causal relationships between the steps of a chain of events leading to an ultimate outcome (good or bad) is obviously not limited to toxicology but is waiting for its application in
The AOP concept shows that giving researchers and policy makers an
epidemic of scientific fragmentation
by inviting them to capture and share their understanding of complex phenomena in
one easy-to-handle tool
is eagerly welcomed:
Not only is knowledge aggregated and finally made
useful to all community members
, in addition informal networks are established between parties that were not even aware of each other previously,
and a common vocabulary
for the shared
Organisation for Economic
Co-operation and Development
Environment Health and Safety Division
Joint Research Centre
Health, Consumers and
Chemical Safety and
Alternative Methods Unit
Environmental Protection Agency
National Center for Computational Toxicology
US Army Corps
Numerous other organisations