Weight of Evidence Reviews for Endocrine Disrupting Properties
Endocrine disrupting properties require specific evaluation under the European regulation on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH; 1907/2006) and the regulations on plant protection (Regulation [EC] 1107/2009) and biocidal (Regulation [EC] 528/2012) products.
Specific criteria to identify endocrine disrupting properties, which enable hazard‐based regulation, has been accepted under the BPR (EC 2017/2100) and PPP Regulation (EC 2018/605). These regulations and the criteria only support the marketing and use of chemicals on the basis that they do not meet these criteria in humans or non-target wildlife species.
Scope of guidance
To enable the implementation of the scientific criteria for the determination of endocrine-disrupting properties pursuant to the BPR and PPP, EFSA/ECHA has developed guidance.The guidance (like the ED criteria) is based on the WHO/IPCS definition of an endocrine disrupter (WHO/IPCS 2002): ‘an endocrine disrupter is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations’. The guidance is further based on the OECD Conceptual Framework for testing and assessment of endocrine disrupters (OECD GD 150) which lists the OECD TGs and aids interpretation of the results. It covers modes of action caused by estrogen, androgen, thyroid and steroidogenic (EATS) modalities, and focuses on ED effects in vertebrates i.e. mammals (incl. humans), fish, amphibians, birds and reptiles.
Assessment strategy: OECD GD 150
The assessment strategy groups the ED parameters investigated in the available studies according to the information they provide (grouping base on OECD GD 150 and JRC screening methodology to identify potential EDs):
- In vitro mechanistic: parameters measured in vitro, that provide information on the mechanism through which a substance could be considered endocrine active. OECD Conceptual Framework level 2.
- In vivo mechanistic: parameters measured in vivo that provide information on endocrine activity that are usually not considered adverse. OECD CF level 4 and 5 assays.
- EATS-mediated: parameters measured in vivo that may contribute to the evaluation of adversity, also considered indicative of an EATS MoA and thus also imply underlying in vivo mechanistic.
- Sensitive to, but not diagnostic of, EATS: parameters measured in vivo that may contribute to the evaluation of adversity, however, these effects cannot be considered diagnostic on their own of any one of the EATS modalities.
- Non-EATS modalities: While currently available OECD test guidelines can detect apical effects potentially relevant for ED identification through non-EATS modalities, there are currently no OECD test methods to elucidate the potential non-EATS mechanism eliciting those apical effects. However, there are methods described in scientific literature which could provide mechanistic information for non-EATS modalities.
An evaluation of data quality (relevance and reliability) according to the provisions of PPP and BPR is required for all studies. Available information is then assembled into lines of evidence based on grouping and the evidence analysed resulting in three possible outcomes:
- Conclude ‘ED criteria not met’ if: e.g.EATS mediated parameters sufficiently investigated and no EATS mediated adversity observed or Endocrine activity sufficiently investigated and no endocrine activity observed (and also no EATS mediated adversity).
- Move to MoA analysis if: EATS mediated adversity observed or Endocrine activity observed.
- Generate information if: No EATS mediated adversity and no endocrine activity observed but endocrine activity not sufficiently investigated.
Mode of action analysis
MoA analysis is necessary to demonstrate the biologically plausible link between adverse effects and endocrine activity. The IPCS MoA framework has been considered in the guidance to address additional considerations which are necessary for ED assessment.
Conclusion on the ED criteria
If the MoA analysis supports the biological plausibility of the link between the observed adverse effects and endocrine activity for at least one MoA among the postulated, the substance is considered to meet the ED criteria. If the biological plausibility of the link between the endocrine activity and the adverse effect(s) is not demonstrated for any of the postulated MoA(s), the substance is considered not to meet the ED criteria.
The identification of endocrine disrupters requires a review of all relevant information on the adverse effects and endocrine activity of a substance, mode of action analysis and application of a weight of evidence approach to determine if a substance fulfils the criteria.
Enviresearch has considerable expertise in the area of endocrine disruption and have supported several governmental programmes contributing to advancing science in this field.
Our services extend to:
- Weight of evidence evaluation of endocrine disrupting properties for substances (Explore our other related articles:Endocrine Disrupters and Plant Protection Products, Endocrine Disrupters and Biocides)
- Mode of Action analysis
- Data gap analysis (or analysis of data sufficiency)
- Development of testing strategies
- Placement and monitoring of specific studies to detect endocrine disruption
Guidance for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009 (7 June 2018). EFSA Journal 2018;16(6):5311. Question Number: EFSA-Q-2016-00825. DOI: 10.2903/j.efsa.2018.5311