In the EU Commission's "Chemicals Strategy for Sustainability - Towards a toxic-free environment" from 2020, one of the goals is to introduce a generic approach to risk management, where the most harmful substances, including endocrine disruptors, are not allowed in consumer products. Until this generic approach is implemented, the aim is to prioritize broad restrictions encompassing groups of these substances.
Following up on this, several activities are ongoing to identify groups of substances as endocrine disruptors. One example is the European Commission’s "Restrictions Roadmap under the Chemicals Strategy for Sustainability" from 2022, which identifies several priority substances and groups of substances that are in the process towards regulation or under discussion in the EU, including groups of endocrine disruptors. Another example is the continuous development of "Assessment of Regulatory Needs" (ARNs) prepared by ECHA on groups of substances with the purpose of helping authorities conclude on the most appropriate way to address the identified concerns and any intermediate steps, such as data generation, needed to initiate and introduce regulatory measures. Several of the ARNs contain (sub)groups of substances suspected of being endocrine disruptors.
The ED hazard classes are new in the harmonized classification and labelling system (EU 1272/2008; EU 2023/707), enabling harmonized hazard classification of EDs, which will trigger risk assessment and/or management in other relevant legislation and labelling requirements along the supply chain.
There are examples of harmonized classification for groups of substances from the past. Nickel and its compounds, comprising a total of ~ 140 substances, have an array of harmonized classifications, including for carcinogenicity. Nickel (and nickel powder) are classified as suspected human carcinogens (Carc. 2), as is nickel tetracarbonyl; all other nickel compounds have harmonized classifications as known human carcinogens (Carc. 1A) (EC 2018). Further, smaller groups of Boron compounds have a harmonized classification due to reproductive toxicity (Repr. 1B) (EC 2018; EC 2021).
Assigning harmonized classifications for a whole group of substances can be an efficient regulation approach if the whole group is found to possess one or more hazardous properties and a possible means to avoid regrettable substitution (i.e. one substance with a harmonized classification is substituted with another structurally very similar substance, which is later found to have similar hazardous effects).
It can be foreseen that, in the coming years, groups of endocrine disruptors will be identified and regulated, including under the CLP Regulation. Work has just started, and the methods and their regulatory acceptability, which will set a precedent for many years to come, are under development.
In this project, we explored approaches and developed recommendations for formation of (sub-) groups of substances with the ultimate aim of filling data gaps by read-across. Some of the case examples did not in their objectives aim at data gap filling, but their category formation approaches were still found to provide valuable learnings generally applicable for forming (sub-)groups with this purpose.
Additional broad grouping approaches in regulatory contexts, without an aim of data gap filling by read across, can be exemplified by the EFSA Cumulative Assessment Group (CAG) approach (EFSA 2012; EFSA 2014; EFSA 2019) and the proposal for a restriction of PFAS substances under REACH (ECHA 2023b). None of these are analysed in detail in this report, but their potential use and relevance for EDs is put into perspective in the discussion.
The OECD Guidance Document (GD) 194 on the Grouping of Chemicals is under revision. It provides guidance, stepwise procedures and reporting formats for different types of grouping approaches. The guidance aims to support the development of grouping and read-across for use in hazard or risk assessment of substances. It draws on approaches known to have been accepted by regulators or have been developed by regulators or registrants under voluntary programs (OECD 2014)
ECHAs Read-Across Assessment Framework (RAAF) is a tool for examining predictions, based on read-across, of the human health, environmental fate and environmental hazard properties of chemical substances in the context of the REACH Regulation. It can be used as guidance for consistent evaluation of the scientific aspects of a proposed read-across case (ECHA 2017).
Under REACH, registrants are responsible for ensuring that the chemicals they place on the EU market do not pose a risk to human health and the environment. Registrants are also obliged to consider and, where they can, use appropriate alternative approaches to fulfil the REACH information requirements on vertebrate animal studies. Read-across approaches are often used by Registrants to fulfil legal information requirements for toxicological endpoints and to avoid testing on animals. According to the 5th report on the use of alternatives to testing on animals for the REACH Regulation, 22,8% of the substances registered under REACH rely on read-across for at least one endpoint to comply with the standard information requirements, making read-across the most commonly used adaption if experimental data are not available (ECHA 2023). Although REACH registrants are responsible for the safety of the chemicals, they place on the EU market, the EU authorities are obligated to check whether a certain number of the registration dossiers are in compliance with the legal requirements. REACH was amended in 2020 to raise the minimum percentage of registration dossiers selected for compliance checks defined in Article 41(5) from 5% to 20% (EC 2020). Other regulatory actions such as substance evaluation, restriction proposals and testing proposals can also lead to authorities evaluating read-across cases. The RAAF provides guidance for evaluating whether the applied read-across is valid, or if testing of the specific registered substance is needed to fulfil the standard information requirements.
By including both the OECD GD 194 and the ECHA RAAF as frameworks for our analyses, we sought to examine and discuss as many aspects of the case examples as possible.
This report aims to analyse existing examples of groupings of endocrine disruptors (or other relevant substances using a relevant methodology), identify advantages and challenges in the case examples and develop recommendations for (sub-)grouping of endocrine disruptors for regulatory purposes with the ultimate aim of filling data gaps by read-across and/or regulate groups of substances, hereunder assign harmonized classifications.