Technical Report 130

Draft Commission Delegated Regulation setting out scientific criteria for the determination of endocrine-disrupting properties pursuant to the BP Regulation

The following excerpts from the Draft Commission delegated Regulation setting out scientific criteria for the determination of endocrine-disrupting properties pursuant to Regulation (EU) No 528/2012 (Commission, 2016c) describe which criteria for the identification of ED properties are currently stipulated (for BPs):

Section A - Endocrine disrupting properties with respect to humans

(1) An active substance shall be identified as having endocrine disrupting properties that may cause adverse effect in humans if, based on points (a) to (d) of point (2), it is a substance that meets all of the following criteria, unless there is information demonstrating that the adverse effects identified are clearly not relevant to humans:

(a) it shows an adverse effect in an intact organism or its progeny, which is a change in the morphology, physiology, growth, development, reproduction, or, life span of an organism, system, or (sub)population that results in an impairment of functional capacity, an impairment of the capacity to compensate for additional stress, or an increase in susceptibility to other influences;

(b) it has an endocrine MoA, i.e. it alters the function(s) of the endocrine system;

(2) The identification of an active substance as having endocrine disrupting properties that may cause adverse effect in humans in accordance with point (1) shall be based on all of the following:

(a) all available relevant scientific data:

(i) scientific data generated in accordance with internationally agreed study protocols (in vivo studies or adequately validated alternative test systems predictive of adverse effects in humans or animals; as well as in vivo or in vitro studies informing about MoA). In particular, ECHA guidance on the implementation of the BP Regulation shall be considered;

(ii) other relevant scientific data selected applying a systematic review methodology.

(b) an assessment of the available relevant scientific data based on a WoE approach in order to establish whether the criteria set out in point (1) are fulfilled.

(c) in applying the WoE determination, the assessment of quality, reliability, reproducibility and consistency of the scientific evidence shall, in particular, consider all of the following factors:

both positive and negative results.
the relevance of the study designs for the assessment of adverse effects and of the endocrine MoA.
the biological plausibility of the link between the adverse effects and the endocrine MoA.
the quality and consistency of the data, considering the pattern and coherence of the results within and between studies of a similar design and across different species.
the route of exposure, toxicokinetic and metabolism studies.
the concept of the limit dose, and international guidelines on maximum recommended doses and for assessing confounding effects of excessive toxicity.

(d) adverse effects that are non-specific secondary consequences of other toxic effects shall not be considered for the identification of the substance as ED.

Section B - Endocrine disrupting properties with respect to non-target organisms

(1) An active substance shall be considered as having endocrine disrupting properties that may cause adverse effects on non-target organisms if, upon the application of points (a) to (d) of point (2), it is a substance that meets all of following criteria, unless there is information demonstrating that the adverse effects identified are not relevant at the (sub)population level for non-target organisms:

(a) it shows an adverse effect in non-target organisms, which is a change in the morphology, physiology, growth, development, reproduction, or, life span of an organism, system, or (sub)population that results in an impairment of functional capacity, an impairment of the capacity to compensate for additional stress, or an increase in susceptibility to other influences, considered relevant at the (sub)population level;

(b) it has an endocrine MoA, i.e. it alters the function(s) of the endocrine system;

(2) The identification of an active substance as having endocrine disrupting properties that may cause adverse effects on non-target organisms in accordance with point (1) shall be based on all of the following:

(a) all available relevant scientific data:

scientific data generated in accordance with internationally agreed study protocols (in vivo studies or adequately validated alternative test systems predictive of adverse effects in humans or animals; as well as in vivo or in vitro studies informing about endocrine MoA). In particular, ECHA guidance on the implementation of the BP Regulation shall be considered.  
other relevant scientific data selected applying a systematic review methodology.

(b) an assessment of the available relevant scientific data based on a WoE approach in order to establish whether the criteria set out in point 1 are fulfilled.

(c) in applying the WoE determination, the assessment of quality, reliability, reproducibility and consistency of the scientific evidence shall consider all of the following factors:

both positive and negative results, discriminating between taxonomic groups (e.g. mammals, birds, fish) where relevant.
the relevance of the study designs for the assessment of the adverse effects and its relevance at the (sub)population level, and for the assessment of the endocrine MoA.  
the adverse effects on reproduction and growth/development, as these are the effects most likely to impact on (sub)populations. Adequate, reliable and representative field or monitoring data and/or results from population models shall be considered where available.  
the biological plausibility of the link between the adverse effects and the endocrine MoA.  
the quality and consistency of the data, considering the pattern and coherence of the results within and between studies of a similar design and across different taxonomic groups.  
the concept of the limit dose and international guidelines on maximum recommended doses and for assessing confounding effects of excessive toxicity.

(d) adverse effects that are non-specific secondary consequences of other toxic effects shall not be considered for the identification of the substance as endocrine disruptor with respect to non-target organisms.