Making it more relevant!
Higher-tier data and Weight of Evidence
Day 2.
Adam Peters and Graham Merrington
2017
1
 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
2
What are higher-tier data?
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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, multigenerational lab studies (erroneously also stated to be the use
of SSDs?), targeted testing on particular species or modes of
action.
2017
3
How might it be used in risk
assessment?
Gene
Cell
+
Tissue
+
Increasing ecological
relevance
Individual
+++
• Emphasis on demographic endpoints
• Survival, development, reproductive
output
• Relate to effects on populations
• But, higher-tier data are
population/community level
Population
+
Community
2017
4
How might it be used in risk
assessment?
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
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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
5
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
6
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
7
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
8
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
9
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
10
2016
11