Making it more relevant! Higher-tier data and Weight of Evidence Day 2. Adam Peters and Graham Merrington 2017

What are higher-tier data? How might it be used in risk assessment? Challenges of using higher-tier data? WoE ……… What can WoE be used for? Good practice with WoE? Summary 2017

What are higher-tier data? It depends……….on the regulatory driver and jurisdiction Generally, field and meso/microcosm studies. Model ecosystems….controlling some variables. WFD: field and mesocosm data have an important role as lines of evidence in helping define the standard (through helping reduce uncertainty) but would not be regarded as ‘higher tier’ data that would replace laboratory-based ecotoxicity data (?) PPP – considered the most relevant data (in EU, not US) Might also included, refined exposure studies, multi-generational lab studies (erroneously also stated to be the use of SSDs?), targeted testing on particular species or modes of action. 2017

How might it be used in risk assessment? Gene Cell + Increasing ecological relevance Tissue + Individual +++ Population + Emphasis on demographic endpoints Survival, development, reproductive output Relate to effects on populations But, higher-tier data are population/community level Community 2017

How might it be used in risk assessment? Derivation of a limit value (EU PPP, CCME) Derivation of a local WQG (ANZECC) Derivation of an EQS in the UK (Iron, Ammonia) Supporting evidence for size of an assessment factor (one of five criteria in the EQS TDG/REACH) Validation that you have derived the right number An EQS 2017

Challenges of using higher-tier data? Increased complexity, levels of biological organisation, variability, representativity, relative uncertainty….. Interpretation of outputs and results. Big changes needed to be statistically significant. Summary statistics? Evaluation guidance (EFSA 2013, Chapter 9) Scientific reliability Score 1-3 (realistic, reporting, exposure regime, endpoints, stats, etc) Way too difficult and uncertain…. Are not many of our assessments aimed at protection IN the environment, therefore these data are probably the most relevant? 2017

WoE Weight-of-evidence, not strictly statistical (or legal) basis of term…….. Hmmmm, so subjective, non-quantitative, ambiguous? ‘the process of considering the strengths and weaknesses of various pieces of information in reaching and supporting a conclusion concerning a property of the substance’ ECHA 2010 Guidance on process to follow when undertaking WoE Allows consideration of multiple lines of information and through weighting gives support for decision making (QSAR data, Lab data, higher-tier data, semi-quantitative studies) 2017

What can WoE be used for? Allows the use of ALL the data; Derivation Iteration – focus, revision Validation/confirmation Important where individually, the lines of evidence might be limited….but when assessed together Make use of less reliable information/studies when they are pooled together with other information EDC assessments…….data from multiple sources 2017

Good practice with WoE? OECD Revised Conceptual Framework for Testing and Assessment of Endocrine Disrupters (as revised in 2012) Systematic review – identification of all relevant studies in a transparent and robust manner Study reliability – assessment of quality and reliability of studies Study relevance – evaluation of endpoint relevance to the determination of mechanism and adverse effect Balance of the weight of evidence – consistency of the evidence and biological plausibility of link between adverse effects and endocrine mode of action 2017

Summary Higher-tier data different things to different groups But, higher level of complexity and probably relevance than lab tests Can be data on hazard or exposure Assessment of reliability and relevance critical WoE – transparent assessment, repeatable, auditable process USE ALL the data – not cherry picking Be aware of the unicorns! 2017

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