The OECD Framework forAOP Development and ApplicationMagda Sachana

NC3Rs: Pathways-based approaches across the biosciences: Towards application in practiceThursday 28 April 2016, London

• OECD AOP Development Programme• OECD Survey to explore the utility of

AOPs for regulatory assessment of chemicals and to identify development priorities

• Use of AOPs in developing Integrated Approaches to Testing and Assessment (IATA)

2

Presentation Outline

OECD AOP Development Programme

This is a sample text.Insert your desired text

here.

Sample text

AOP’s central role in OECD work on predictive toxicology

AOPs

OECD Hazard Assessment activities

Development of IATA for defined hazard endpoints

Selection of methods for Test Guideline development/refinement

This is a sample text.Insert your desired text

here.

Sample text

AOP’s central role in OECD work on predictive toxicology

AOPs

OECD Hazard Assessment activities

Development of IATA for defined hazard endpoints

Development of (Q)SARs

This is a sample text.Insert your desired text

here.

Sample text

AOP’s central role in OECD work on predictive toxicology

AOPs

OECD Hazard Assessment activities

Development of IATA for defined hazard endpoints

2013 Guidance document on developing and assessing

AOPs

2014 AOP-KB and Users' Handbook supplement to the guidance document for AOPs

2015 External review of AOPs and training material for

AOP development

2016 Endorsement of 5 AOPs by WNT

Future: Increase the AOP-KB content and facilitate the use of AOPs in a regulatory context

2012OECD AOP

Development Programme

Main milestones achieved since the launch of the OECD AOP Development

Programme

e.AOPPortal

Shared chemical, biological and toxicological ontologies

AOP-KB

AOP Xplorer

Visualize attribute networks to

discover & explore AOPs

in a broader context

Effectopedia(in beta testing)

Collaborative development of quantitative AOPs in

graphical environment

AOP Wiki

Collaborative development of AOP

descriptions & evidence

Intermediate Effects DBChemical-relateddata derived from

non-apical endpoint methods Third party

Applications, plugins

Interlinkages between systems - data exchange

Electronic PesticideSubmission Package

MetaPathh

AOP-KBHub

Intermediate Effects DB

AOP Xplorer

EffectopediaAOP Wiki

OECD Survey to explore the utility of AOPs for regulatory

assessment of chemicals and to identify development priorities

Experience with the AOP framework (familiarity)

0

2

4

6

8

10

12

14

16

Not at all (1) To a small extent(2)

To a moderateextent (3)

To a fairly greatextent (4)

To a great extent(5)

0

1

9

16

9

0

5

10

15

20

25

30

OECD activities Scientificliterature/meetings

Colleague(s) Other

26

18

15

2

Experience with the AOP framework (source of experience)

Experience with the AOP framework (participation in development or review of AOPs)

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

Author Co-author Reviewer No experience

2.70%

13.51%

29.73%

54.05%

AOPs in AOP-Wiki and coverage of toxicological endpoints

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

Not at all (1) To a small extent (2) To a moderateextent (3)

To a fairly greatextent (4)

8.57%

25.71%

54.29%

11.43%

• Endocrine disruption• Carcinogenicity• Genotoxicity• Reproductive and developmental toxicity

Other toxicological endpoints to be addressed by AOPs in the AOP-Wiki (1)

• Repeated dose toxicity• Respiratory toxicity• Immunotoxicity• Ecotoxicological endpoints

• There is need for a systematic review of regulatory needs and the pathways involved

• A call for AOPs relating to the identified pathways

Other toxicological endpoints to be addressed by AOPs in the AOP-Wiki (2)

Is the information provided in the AOPs useful for your regulatory needs?

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

40.00%

Not at all (1) To a small extent (2) To a moderate extent(3)

To a fairly greatextent (4)

8.57%

34.29%37.14%

20.00%

Use of the information available in the AOP-Wiki by agencies/organisations

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

Not at all (1) To a small extent (2) To a moderate extent(3)

To a fairly greatextent (4)

24.24%

54.55%

18.18%

3.03%

Use of AOP concept by agencies/organisations

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

Not at all (1) To a small extent(2)

To a moderateextent (3)

To a fairly greatextent (4)

To a great extent (5)

14.29%

31.43%

34.29%

17.14%

2.89%

Regulatory need(s) in which the AOP concept was used

20%

21%

10%5%

25%

13%

6%

Prioritisation

Grouping of chemicalsand subsequent ReadacrossIATA development

Classification andLabelling

Hazard Assessement

Risk assessment

• Quantitative AOPs • Linking of AOPs to regulatory endpoints and

test guidelines• Development of guidance/framework for

reporting and applying AOPs for regulatory applications

• Training in interpreting AOPs and applying in a weight of evidence approach.

Suggestions on how to improve AOPs’ usability

Use of AOPs in developing Integrated Approaches to Testing

and Assessment (IATA)

Framework for how an AOP can be applied to inform and structure IATA

Reporting Defined approaches

For Official Use ENV/JM/HA(2016)11 Organisation de Coopération et de Développement Économiques Organisation for Economic Co-operation and Development ___________________________________________________________________________________________

English - Or. English ENVIRONMENT DIRECTORATE JOINT MEETING OF THE CHEMICALS COMMITTEE AND THE WORKING PARTY ON CHEMICALS, PESTICIDES AND BIOTECHNOLOGY

Task Force on Hazard Assessment

Guidance Document on the Reporting of Defined Approaches to Testing and Assessment for Skin Sensitisation

This is a draft document, the work is still in progress. This document is intended for the use of ECHA MSC/RAC members only and for no further circulation.

Complete document available on OLIS in its original format This document and any map included herein are without prejudice to the status of or sovereignty over any territory, to the delimitation of international frontiers and boundaries and to the name of any territory, city or area.

ENV

/JM/H

A(2016)11

For Official U

se

English - O

r. English

For Official Use ENV/JM/HA(2016)10 Organisation de Coopération et de Développement Économiques Organisation for Economic Co-operation and Development ___________________________________________________________________________________________

English - Or. English ENVIRONMENT DIRECTORATE JOINT MEETING OF THE CHEMICALS COMMITTEE AND THE WORKING PARTY ON CHEMICALS, PESTICIDES AND BIOTECHNOLOGY

Task Force on Hazard Assessment

Guidance Document on the Reporting of Defined Approaches to be used within Integrated Approaches to Testing and Assessment

This is a draft document, the work is still in progress. This document is intended for the use of ECHA MSC/RAC members only and for no further circulation.

Complete document available on OLIS in its original format This document and any map included herein are without prejudice to the status of or sovereignty over any territory, to the delimitation of international frontiers and boundaries and to the name of any territory, city or area.

ENV

/JM/H

A(2016)10

For Official U

se

English - O

r. English

THANK YOU