Loading presentation...

Present Remotely

Send the link below via email or IM

Copy

Present to your audience

Start remote presentation

  • Invited audience members will follow you as you navigate and present
  • People invited to a presentation do not need a Prezi account
  • This link expires 10 minutes after you close the presentation
  • A maximum of 30 users can follow your presentation
  • Learn more about this feature in our knowledge base article

Do you really want to delete this prezi?

Neither you, nor the coeditors you shared it with will be able to recover it again.

DeleteCancel

Make your likes visible on Facebook?

Connect your Facebook account to Prezi and let your likes appear on your timeline.
You can change this under Settings & Account at any time.

No, thanks

The Adverse Outcome Pathways Knowledge Base

How crowdsourcing revolutionizes toxicology
by

Clemens Wittwehr

on 27 March 2017

Comments (0)

Please log in to add your comment.

Report abuse

Transcript of The Adverse Outcome Pathways Knowledge Base

Determines potential
harmful
effects
Studies chemicals to determine how they can be used
safely
Assesses the probability of
risk
to human life or the environment
Assists in establishing regulations that
protect
humans and the environment

Limitations of current toxicology
Depends on
animal tests
Only
observes,
does not

understand mechanism of toxicity
Risk assessment
Many
different
data and data sources
To be weighed in terms of
reliability
and
relevance
Assess and document
confidence
Acknowledge
uncertainties
Role of toxicology
Regulatory Relevance
AOPs help to inform regulators about the
mechanism
of toxicity.
Once regulators understand and
accept
a mechanism, they are more inclined to accept

non-animal tests
based on mechanistic thinking
AOPs depict
existing knowledge
Definition
An Adverse Outcome Pathway (AOP) is an analytical construct that describes a sequential chain of causally linked events leading to an
adverse human health
or
environmental effect
of
regulatory concern
.
AOPs are the central element of a toxicological knowledge framework being built to support chemical risk assessment based on
mechanistic reasoning
.
AOPs are modular
AOPs are not chemical specific
AOPs are
not trying
to understand what a single chemical does
AOPs
are trying
to describe what any chemical that perturbs "normal biology" with sufficient potency and duration is likely to do - "motifs of failure"

Toxicology
Adverse Outcome Pathways
Five principles of AOP development
Adverse Outcome Pathways
What is needed?
Methods to understand how
chemicals
affect
biological systems
Examine how toxicity works "its way" via
pathways
from an
Initiating Event
through
Key Events
towards the
Adverse Outcome
*

* cancer, reproductive problems, death, ...
AOPs do not necessarily produce
new knowledge
but provide a place to collect and organise
existing knowledge
from numerous sources
The
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
simplification
of
complex
biology
In many cases,
networks
of AOPs are the functional unit of prediction
AOPs are
living
documents
AOPs organise
existing knowledge
, but:
New methods
are developed
New experiments
are published
There is
no
"objective complete AOP"
AOP-KB
Purpose
CROWDSOURCING
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
crowdsourcing
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
.

AOP-KB modules
e.AOP.Portal
http://aopkb.org/
The e.AOP. Portal is the
search engine
for all AOPs and KEs that are available currently in the other modules
AOP Wiki
The AOP Wiki provides a platform for the
formal definition and evaluation
of AOPs.
The AOP Wiki supports the
OECD review process
https://aopwiki.org
Effectopedia
Effectopedia provides a collaborative research platform for quantitative AOP development.
http://effectopedia.org
AOP Review Process
All AOPs aiming at
regulatory relevance
ultimately undergo review
AOP Lifecycle
Lessons
learned

Regulatory decision makers in all areas are
drowning in peer-reviewed journal papers
, while what they would need is
succinct knowledge
distilled from the information flood.
The success of AOP-KB clearly demonstrates there is a
solution
to this paradox, and that people working in the overlapping areas of
applied science
and
policy formulation
are more than ready for a
quantum leap
in the way they gain insight into scientific issues and how they can apply the acquired knowledge to their respective areas
A
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
numerous disciplines
.
The AOP concept shows that giving researchers and policy makers an
antidote
to the
epidemic of scientific fragmentation
and
hyper-specialisation
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
domain emerges.
Acknowledgments
Organisation for Economic
Co-operation and Development
Environment Directorate

Environment Health and Safety Division
European Commission
Joint Research Centre
Health, Consumers and
Reference Materials
Chemical Safety and
Alternative Methods Unit
United States
Environmental Protection Agency
National Center for Computational Toxicology
US Army Corps
of Engineers
Numerous other organisations
Full transcript