There are currently many intense global activities on adverse outcome pathways (AOP). Much of this activity is focused on endocrine disruption (ED). There is a risk that AOPs will be used to conclude on ED without sufficient substantiation. AOPs may be used for prediction of Adverse Outcomes (AOs) based on limited mechanistic data. Or be used to extrapolate from AOs to the preceding key events in the absence of sufficient evidence from Mode of Action (MoA). As a result some chemicals may be labelled as being endocrine disruptors and consequently face severe restrictions.
Terms of Reference
What do we want to achieve: Based on the current state of the science, to develop guidance on the robust use of AOPs while preventing the misuse of AOPs when applied to the field of ED.
- There are currently intense global activities on AOPs. Much of this activity is focused on ED. There is a temptation to use AOPs to predict Adverse Outcomes based on limited mechanistic data, similarly to extrapolate from adverse outcomes to the preceding events in the absence of sufficient evidence from MoA.
- There is a concern that the state of the science in understanding AOPs does not support the wide used of AOPs for either of the purposes above. Inappropriate use of incomplete AOPs as they refer to ED could result in misleading identification of substances as having endocrine disrupting properties.
- The purpose of this TF is to elaborate clear guidance on how to establish the minimum scientific standards that allow the use of AOPs to either predict an AO or to explain a known AO.
- The elaboration of the guidance document should be aligned with the previous ECETOC endocrine disruption task force work in the framework of AOPs and will underline important principles of causality, adversity, population relevance, specificity, weight-of-evidence and potency.
06 December 2016
The Task Force published Technical Report no.128: Guidance on Assessment and Application of Adverse Outcome Pathways (AOPs) Relevant to the Endocrine System
Various European chemical regulations do not allow the marketing or use of substances known to have endocrine disrupting properties – chemicals that induce adverse effects in humans and/or wildlife as a result of interaction with the endocrine system.
Adverse outcome pathways (AOPs) have the potential to be important tools for the assessment of endocrine disrupting properties as they can help identify if an adverse effect observed in an in vivo (animal based) study can be plausibly linked to a change in the endocrine system. AOPs could potentially be used to help predict the potential for an adverse effect in humans and/or wildlife from the results of in vitro (non-animal based) assays, potentially reducing the requirement for animal testing.
However, if AOPs are to be used to identify and/or predict endocrine disrupting properties, it must be ensured that they are sufficiently robust and fit for purpose. To this end, this Technical Report provides guidance on identifying the basic requirements and how to establish the minimum scientific standards that allow the use of AOPs. The guidance is centred on the different contexts of AOP use such as hazard identification, read-across (predicting potential effects for a chemical based on data for other, similar, chemicals) and risk assessment. These requirements are described as ‘Key Elements in Assessment of AOP Utility’ and cover factors such as ensuring that AOPs are consistent with the current scientific knowledge (Biological Plausibility) and ensuring that any potential differences amongst species are considered (Taxonomic Applicability/Species Concordance).
This guidance will be a useful tool for 1) those looking to develop new AOPs helping to identify the key elements that need to be considered during construction, and 2) those considering applying existing AOPs by providing a list of key elements to be considered to facilitate a critical review and ensure it is fit for the intended purpose.
The document has been published as ECETOC Technical Report no.128: Guidance on assessment and application of Adverse Outcome Pathways (AOPs) relevant to the Endocrine System. The Executive Summary and free PDF of the report are available at http://bit.ly/ecetoc-tr128