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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 2016