Towards Good Read Across Practice Nicholas Ball, February 2016

State of the Art Tools Guidance

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??

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

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

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

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

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?

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…

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?

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’?

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?

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

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