1. Towards Good Read Across Practice
Nicholas Ball, February 2016

2. State of the Art
Tools
Guidance

4. OECD member states agreed with categories and read-across for these
OECD HPV program: 100 chemical categories covering over 400 substances assessed to date
Many data rich substances (high volume)
Read Across used in every category
OECD member states agreed with categories and read-across for these
So we did a good job, Right??

5. REACH Ca. 75% of REACH dossiers contain read-across
>10,000 registrations had been submitted (2010 and 2013)
Typical endpoints covered
Higher tier Animal studies – Implications for failure??
Experience with OECD HPV utilised for REACH
Pre-existing categories
New categories/analogue approaches

6. How did it go so far? Industry feeling Regulatory
Mixed – some say they have had no issues; some say failures across the board
Overall – appears to be negative – does not work
Regulatory
Some good, some bad, some (very) Ugly….
Evaluation reports to provide advice on improving
Who is at fault?
THEM or US?
The point of this is to try and bring out that both sides of the issue have similar assessments of the situation, and that we both realistically need to adapt what we are doing

7. What is the reality?
Identify cause for CC/TP; Primary focus on Read Across
But also: Exposure based waiving; QSAR use; Substance ID; Waivers; Information requirements not met; C&L; DNELS/PNECS/CSR
Review Compliance Check and Test Proposal decisions disseminated by ECHA

8. Results: Compliance Checks
Approximately one fifth (107) of all disseminated compliance check decisions involved the use of read-across
Reason for Rejection
No. of cases
Unclear Substance identity, not possible to ascertain structural similarity  48
Lack of sufficient evidence to substantiate assumptions made within read-across justifications 43
Read-across to inappropriate data   5
Lack of scientific plausibility 20
81 out of 388 testing proposals involved the use of read-across
Failures – Similar reasons to Compliance Checks

9. Substance ID Biggest issue for UVCB substances
How do we demonstrate ‘Similarity’ for these?
Can we support with other tools?
Biological similarity?
Many case studies coming
Hydrocarbons
Resins/Rosins
Others?
How will these do??
Precedents to be set?

10. Supporting Information
The ‘Easy’
Including available supporting data in dossier
Costs? Access?
Still a potential barrier
The ‘Hard’
How to effectively support arguments?
Data reliability/Applicability/Acceptability
Challenge to innovation?
Always more questions than answers
When is enough enough…
Uncertainty…

11. Scientific Plausibility
2 Aspects
Insufficient information to support hypothesis/conclusions
See earlier
Inappropriate interpretation
Scientific debate/discussion
Disagreements difficult to resolve with more data
Lions?

12. How to resolve – Short term
Opportunity: Reverse engineer RAAF
Structured approach to preparing read-across justifications
Identify ‘as you go’ gaps that need to be addressed
Challenge
Avoid ‘Just another tool’ for EU REACH
Think Globally also
Start using measures to address Uncertainty
Not simply testing
What is more important – Hazard Characterization or Risk?
What happened to ‘Exposure based testing’?

13. New tools What? How? When? Longer Term
Minimize missed opportunities vs ‘safety’ compromise
Lots of tools – but what actually works, How should we be using them (e.g. AOPs) , are they ready to go now? Or are we still developing?

14. P.s. What about everywhere else?
A Lot of Focus on EU
Are the needs of EU regulators mirrored elsewhere?
Developing and Emerging regulations – China, Korea, Taiwan, Turkey, others?
All aim to utilize REACH dossiers in some way
Unilateral acceptance of approaches?
Issues with rejection/difference in opinion?
Even within EU – REACH is just One regulation
Cosmetics, Food contact, Pesticides?
Is there acceptance of a single approach within the EU?
Same, if not worse in the US and other countries

15. Universal approach to read-across/alternative approaches Just a dream or a potential reality?