Developments on the identification of potential endocrine disruptors under EU legislation
As mentioned in our previous Insights document (01/07/2018), evaluation of the potential endocrine disrupting (ED) properties of all biocidal active substances and also the associated biocidal products is mandatory in the EU since 07 June 2018, as laid out in Regulation (EU) 2017/210. This is supported by notes compiled in March 2018 by the EU member state competent authorities (MSCAs) on how to apply the ED criteria (CA-March18-Doc.7.3.b-final).
On 20 October 2018, a similar requirement became applicable for plant protection products (Regulation (EU) 2018/605).
Additional regulatory EU provisions for endocrine disruptors are covered under REACH (Regulation (EC) 1907/2006), the Regulation on cosmetics ((EC) 1223/2009) and under legislation on food contact materials.
An overview of EU policy around EDs was recently published by the Commission (07 November 2018) in the form of a communication addressing the concerns of the European Parliament and the Council and following up from the 7th Environment Action Programme. The 11-page communication reviews the science of EDs, existing knowledge gaps and the development / validation of test methods. It also discusses EU policy and regulations so far, giving examples, and lays out plans for the future.
First experience with the EFSA/ECHA guidance on identification of endocrine disruptors
In support of new biocides and plant protection product requirements, the European Food Safety Authorities (EFSA) and the European Chemicals Agency (ECHA) published in June 2018 extensive guidance for the identification of EDs.
The assessment is carried out separately for human health and the environment and follows the principles laid out in the OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupters (as revised in 2012). In brief, available or newly generated in silico, in vitro and in vivo data is compiled, then evaluated to detect whether evidence of endocrine activity exists. If so, lines of evidence are built, a mode of action analysis is conducted, and conclusions on human health and/or environmental ED properties are drawn.
As experience with the new EFSA/ECHA guidance is acquired, assessors from both the authorities and industry are faced with several challenging technical issues. For example, how to evaluate very data-rich substances for which most of the available studies are not in line with the requirements of the guidance and that present often inconsistent or even contradictory results? How to link in silico or in vitro effects with a real adverse apical endpoint? How to evaluate basic substances that are known to have no ED properties (e.g. table salt) but that have no data to prove it? ED assessment for the environment may prove to be particularly difficult as the existing standard studies run in the context of a biocidal or plant protection product registration may be limited to acute toxicity, consider only few relevant species/trophic levels (e.g. Daphnia and fish) and/or do not directly address any of the required ED endpoints. At the practical level, completing the Excel table provided in Appendix E of the guidance and recommended to be used to collect available study information and build lines of evidence is a complicated and extremely time-consuming task for rich and complex data packages. It remains a difficult task for minimal data packages with little relevant information.
In conclusion, ED assessment adds a significant new step to the now well-established hazard assessment methodologies for biocides, plant protection products and all other types of substances. Significant progress has been made over the past year with regard to legislation and guidance, but experience must still be gained before the system becomes truly workable and fit for purpose.