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