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REACH-loaded LRI Cheminformatic system AMBIT2 supporting read-across
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Dr. Bruno HubeschCefic LRI, Programme Consultant
Ambit2 training WorkshopBrussels, Sept 29, 2017
Meeting the Global Challenge of Applying New Scientific Methods to Improve Environmental
and Human Health Risk Assessments
LRI Mission
• Advance approaches for assessing the safety of
chemicals
• Improve our understanding of the potential health and
environmental risks
• Work with partners in governmental agencies,
academia, and industry
• Build effective scientific networks linking research to
practice and policy
• Tailor its research to adapt to changing issues in
chemical risk
• Address public concerns to improve their confidence
in our products
• Leader in chemical safety assessment research
• Support high-quality science to inform effective
decision making by industry, regulators, and society.
Annual ICCA LRI Workshop
Three Regional Programs:- Europe (CEFIC)- United States (ACC)-Japan (JCIA)
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http://lri.americanchemistry.com/LRI-Research-Program/Research-Strategies/ICCA-LRI-Global-Research-Strategy.pdf
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2015-2016Innovating Chemical Testing Understanding Everyday Exposures Translating Research Outcomes for
Product Safety
CEFIC Innovate methods to link
information at the molecular
level, such as epigenetics, to
health and environmental
impacts
Support the 3Rs – replace,
reduce, and refine – for animal
testing
Develop predictive models to
estimate exposures from
biomonitoring data
Evaluate effects of cumulative
and aggregate exposures
involving dermal exposure and
consumer products
Support model development and
integration to facilitate ecological
risk assessment
Review and promote methods to
use epidemiologic data to
understand complex health
effects
ACC Advance application and
extrapolation of cell-based
testing methods for human
health risk assessments
Incorporate exposure and dose
information to advance
interpretation and modeling of
data from high-throughput
assays
Develop predictive models for
estimating consumer exposures
and screening and prioritizing
new chemicals
Improve interpretation of
biomonitoring data for
application to estimating
cumulative exposures
Translate high-throughput data
to real-world contexts and
applications, to facilitate risk-
based decision making
Advance approaches to better
understand the scientific basis of
epidemiological studies linking
health effects to chemical
exposures
JCIA Develop and evaluate new
testing methods, such as those
that use biomarkers, to improve
assessment of chemicals and
products
Innovate high-throughput and in
vitro methods to facilitate
evaluation of genotoxicity of
large numbers of chemicals
Develop predictive and practical
models for estimating
occupational exposures
Monitor and predict potential
exposures from environmental
pathways
Assess the effects of chemicals
on ecosystems and the
environment
Evaluate the safety of new
chemical substances, such as
nanomaterials, to promote
responsible industrial chemical
management
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Priorities:
7 key questions
for the next 5-10 years
Executing the long-term refocus of the
LRI Key questions (< 10y)
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1. Omics / 21st Century Toxicology: How to link information at molecular level to health impacts and interpreting results for meaningful decision making?
2. Predictive tools for health impact: What are pragmatic approaches for reducing complexity, whilst maintaining robust predictions of health effects?
3. Combination effects: How to identify combination effects scenarios of concern?
4. Eco-systems approach: Which new concepts enhance ecological relevance of risk assessment?
5. Real life Exposure: Which predictive, validated exposure scenarios apply to assessing environmental stressors?
6. Comparative assessment: How to interpret impact of health and environmental stressors?
7. Benefit to risks approaches: Can we understand societal drivers for public acceptance of innovation?
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Read-across and Category formation
Non-testing methods which are regularly applied to assess the safety of Chemicals
Used on average in 20% of the Endpoint Study Records, while QSAR is used in < 1%
Accepted by most Regulatory Bodies if the approach taken is sufficiently justified and documented
Supported by in-silico tools (see ECETOC, 2012, TR 116)
Using various methodologies like QSARs, rule-based predictions , similarity tools, etc.
Why LRI AMBIT https://ambitlri.ideaconsult.net/
An in-silico tool developed continuously since 2005 (http://ambit.sourceforge.net)
Goal of the LRI EEM9.3-IC project was enhancing the predictive power of AMBIT
Using large datasets of quality Substance data: ECHA & company DB & other sources
Implementing workflows for Assessments supporting the assessor in setting up a read across/category approach and in establishing a valid justification for the approach
Minimizing overall animal testing and resource costs by using available studies for other substances as well if appropriate 8
CEFIC LRI AMBIT Chemoinformatics System
Other
Tools
Other
Databases
Company IUCLID DB
& ECHA IUCLID DB
as
Major Data Sources
Transfer
of 14570
Dossiers
Transfer via
Web service
or *.i5z files
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Data
transfer
Data
transfer
Data
transfer
LRI AMBIT
Supporting
Read across &
Category formation
AMBIT2 ?
OpenFoodTox database from EFSA
VEGA (courtesy E.Benfenati, Mario Negri Institute,
Milano
Open source, Application Programming Interface
available
Stand alone and web versions
IUCLID6 compatible
New and better functionalities
And more…10
Acknowledgements CEFIC LRI EEM9.3-IC
Project idea for LRI EEM9.3-IC
o Volker Koch, Clariant (retired)
o Joanna Jaworska, P&G (AMBIT 2005)
Project input :
Clariant CompTox Team
o Udo Jensch (Toxicologist)
o Volker Koch (Ecotoxicologist)
o Qiang Li (Toxicologist)
o Joachim Schneider-Reigl (Ecotoxicologist)
Project implementation
o Ideaconsult Ltd. www.ideaconsult.net
Nina Jeliazkova, Nikolay Kochev
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Acknowledgement
CEFIC LRI would like to thank ECHA for providing the non-confidential IUCLID data which are accessible on the ECHA
Website
Datasets on 14570 Substances have been provided on
January 12, 2016 by ECHA in Computer readable format
allowing the import into AMBIT12
Global marketing campaign /AMBIT2
1. EU/Brussels, April 20, 2017 (Article) Chemical Watch, “|Cefic’s AMBIT software tool reaching
users around the globe”
2. EU/Helsinki, June 15-16, 2017: (Talk) ECOPA-SSCT Workshop 2017/CAAT-EU Academy,
“Tools for Read-Across”
3. US/ Seattle, August 20-24, 2017: (Poster) WC10 / 10th World Congress on Alternatives & Animal
Use
4. Launch campaign, Week Sept 4, 2017: LRI mailing list, website, Cefic Newsroom, Twitter, etc..
5. EU/Bratislava, September 11-14, 2017:(Poster) EUROTOX 2017
6. EU/Brussels, Sept 29, 2017: Hands-on Training Workshop at Cefic
7. EU/Brussels, Oct 5-6, 2017: (Talk) CAAT-EU Academy, “Use of in silico tools in chemical’s
hazard assessment”
8. EU/Milano, October 19, 2017 : (Talk) LIFE COMBASE Workshop on in silico methods and
biocides, Milan, PROSIL/LIFE project workshop (Mario Negri)
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Global marketing campaign /AMBIT
1. EU/Brussels/Jan: training WS at Cefic
2. EU/Brussels/Feb: (Talk) CAAT-EU / Cefic LRI WS
3. US/Washington/March: (Talk) CAAT-US /Cefic LRI WS
4. EU/ Finland, Helsinki, 19-20 April 2016: (Poster) Topical Scientific Workshop - New Approach
Methodologies in Regulatory Science
5. US/ Florida, Miami, 13-17 June 2016: (Poster) 17th International Conference on QSAR in
Environmental and Health Sciences
6. JP/Awaji Island, Japan, 15-16 June 2016: (Talk) Meeting the Global Challenge of Applying New
Scientific Methods to Improve Environmental and Human Health Risk Assessments
7. KO/Seoul, South Korea, 13-15 July 2016: (Talk at) 14th International Nanotech Symposium &
Nano-Convergence Expo, NANO KOREA 2016
8. EU/Helsinki, Finland, 1-2 September 2016: (Training/isntallation) ECHA
9. EU/Sevilla, Spain, 5-8 September 2016: (Poster at) EUROTOX 2016
10. EU/Milano, Italy, 21 September 2016: (Talk at) PROSIL/LIFE project workshop (Mario Negri)14