Endocrine disrupting properties require specific evaluation under European Commission legislation, including the regulation for Plant Protection Products (PPP) (EC 1107/2009), the Biocidal Products Regulation (BPR) (EU 528/2012), REACH (EC 1907/2006) and Classification, Labelling, and Packaging (CLP) (EC 1272/2008).
Hazard based criteria for the identification of an endocrine disrupter has been accepted under the BPR (EC 2017/2100), PPP (EC 2018/605) and CLP (EU 2023/707). These criteria are based on a substance fulfilling three elements of the definition of an ED, i.e.:
a) that it shows an adverse endocrine relevant effect in an intact organism,
b) it has potential to interact with and alter the function(s) of the endocrine system (endocrine activity), and
c) a biologically plausible link between the endocrine activity and an adverse effect.
These criteria are assessed separately for effects in humans or non-target wildlife species.
An assessment of the endocrine disrupting properties of the active substance must be submitted as part of product registrations under the BPR and PPP regulations. These regulations 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. The European Food Safety Authority (EFSA) and the European Chemicals Agency (ECHA) have developed guidance for implementing these criteria.
In addition, hazard classifications have been introduced under CLP as follows:
• Known or presumed ED (category 1), or
• Suspected ED (category 2).
ECHA has published separate guidance on application of ED hazard categories for human health and the environment.
Although available guidance mainly covers endocrine disrupting substances affecting Estrogen, Androgen, Thyroid and Steroidogenesis (EATS) modalities, non-EATS modalities may also fall within scope of the above regulations.
The identification of ED substances 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. wca has considerable experience in conducting weight of evidence assessments for ED and has contributed to advancing the science in this area. We also have experience on relevant test methods for both EATS and other endocrine pathways and supported an EC workshop on this topic as well as an evaluation of proposals for potential future ED testing requirements under REACH.
We provide support for both industry and regulatory clients in the interpretation of ED effects. Our services include weight of evidence reviews of endocrine disrupting properties for substances, Mode of Action analysis, Data gap analysis (or analysis of data sufficiency), Development of testing strategies, and placement and monitoring of toxicology and ecotoxicology studies to detect endocrine disruption.
Examples of projects:
- Review and input into the development of guidance for ED assessment under CLP.
- ED assessments for substances with potential for effects via both EATS and non-EATS modalities.
- Review of vitellogenin changes in fish published as a series of papers including a decision logic for the reliability assessment and interpretation of vitellogenin measurements.
- Independent assessment of ED interpretation for Amphibian Metamorphosis Assays, Fish Short Term Reproduction Assays and Fish Life-Cycle Toxicity Tests (including the Medaka Extended One Generation Reproduction Test).
- Development of a strategy for the ED classification of substances which are UVCB (unknown or variable composition, complex reaction products, or biological materials).
- A review of in vitro estrogen and androgen methods for use in a human risk assessment for ED substances.
- Separate reviews into the application of environmental threshold levels for ED effects in fish and mammals.