Regulatory provisions

Classification, labelling and identification of endocrine disruptors

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The CLP Regulation governs the classification and labelling of hazardous substances and mixtures in the EU. In accordance with the criteria specified in this regulation, all chemical substances and mixtures placed on the market in the EU must be assigned to hazard classes and hazard categories according to their hazardous properties (physical hazards, health hazards, environmental hazards).

New hazard classes requiring labelling were added to the regulation in April 2023. These include endocrine disruptors (EDs) that are harmful to human health (ED HH: human health) and to organisms in the environment (ED ENV: environment).

When a substance is classified as an endocrine disruptor, other parties in the supply chain must be made aware of the hazards identified. These parties include consumers. Hazard labels and the corresponding statements in Section 2 of the safety data sheets inform those using a substance or mixture of its hazard classification and draw their attention to the hazard and the need to reduce the associated risks.

The new ED hazard classes and transition periods

Whereas the hazard classes set out to date in the CLP Regulation define actual health hazards (e.g. specific target organ toxicity, reproductive toxicity, carcinogenicity), the new regulatory classification of certain hazardous substances as "endocrine disruptors" describes these substances’ toxicological mechanism of action. Accordingly, double classifications are also possible: for example, substances that have been classified as EDs based on their mechanism of action may at the same time be reprotoxic or carcinogenic.

Transition periods have been in place since Delegated Regulation (EU) 2024/197 amending Annex VI to the CLP Regulation entered into force on 20 April 2023. New substances placed on the market by companies since 1 May 2025 must be classified and labelled in accordance with the new hazard classes. For substances placed on the market before this date, a deadline of 1 November 2026 applies.

Separate transition periods apply to mixtures. For newly labelled and packaged mixtures, the rules apply as of 1 May 2026. For existing mixtures, the updates need not be made until 1 May 2028.

Whether a substance has been classified in one of the new hazard classes must be indicated (on the safety data sheet and hazardous substance label) at the latest when the transition periods expire.

All chemical substances or mixtures of substances manufactured or imported in quantities of one ton or more per year must be registered by manufacturers and importers with the European Chemicals Agency (ECHA). A part of this process involves use of the IUCLID (International Uniform ChemicaL Information Database) software application to create a registration dossier. The new hazard classes were added to IUCLID at the end of April 2024, thereby enabling registration dossiers to be created for the substances concerned.

These hazard classes have not yet been adopted in the United Nations Globally Harmonised System of Classification and Labelling of Chemicals (GHS). They therefore apply at present only within the scope of the CLP Regulation.

1. Classification

When substances are assigned to hazard classes, a distinction is made between endocrine disruptors that harm human health (ED HH) and those that harm environmental organisms (ED ENV).
Two categories are distinguished in each hazard class. "Known or presumed" EDs are assigned to ED Category 1, "suspected" EDs to ED Category 2.

Categories

Table: ED HH – Definition of categories (Hazard categories for endocrine disruptors for human health, Table 3.11.1, from Delegated Regulation (EU) 2024/197 amending Annex VI to the CLP Regulation

Categories	Criteria
Category 1	Known or presumed endocrine disruptors for human health The classification in Category 1 shall be largely based on evidence from at least one of the following: a) human data; b) animal data; c) non-animal data providing an equivalent predictive capacity as data in points a or b. Such data shall provide evidence that the substance meets all the following criteria: a) endocrine activity; an adverse effect in an intact organism or its offspring or future generations; c) a biologically plausible link between the endocrine activity and the adverse effect. However, where there is information that raises serious doubt about the relevance of the adverse effects to humans, classification in Category 2 may be more appropriate.
Category 2	Suspected endocrine disruptors for human health A substance shall be classified in Category 2 where all the following criteria are fulfilled: a) there is evidence of: i) an endocrine activity; and ii) an adverse effect in an intact organism or its offspring or future generations b) the evidence referred to in point (a) is not sufficiently convincing to classify the substance in Category 1; c) there is evidence of a biologically plausible link between the endocrine activity and the adverse effect.
Where there is evidence conclusively demonstrating that the adverse effects are not relevant to humans, the substance shall not be considered an endocrine disruptor for human health. The same criteria apply by analogy to ED ENV.

Both categories are based on the scientifically established criteria of the World Health Organization (WHO)/the IPCS definition for the identification of EDs (i.e. adverse effects in an intact organism, endocrine activity, and a biologically plausible link between the two).

Classification approach

Classification is based on assessment of the weight of evidence from the available data. Data sources include the results of in vivo, in vitro and in silico studies from which the activity, the harmful effects and the biologically plausible link between them are determined. Data on analogue substances (structure-activity relationships) are evaluated, and consideration is given to evaluations of chemically related substances and any additional relevant and acceptable scientific data. Data already collected (e.g. from substance or dossier evaluation performed under REACH or from another active substance approval procedure) are used for classification.
Adverse effects that are solely non-specific consequences of other toxic effects are not to be considered for the purpose of ED classification. Adverse effects that are referred to for ED classification may also be relevant in their own right for classification in another hazard class. Accordingly, double classifications are also possible (e.g. harmful reproductive effects with an endocrine mechanism of action may be classified as both ED HH and Repr/reproductive toxicity).
The criteria and derogations for ED ENV are formulated similarly.

2. Labelling

Since the new classifications are initially limited to the EU, they are not included in the UN GHS. For this reason, EUH statements, which apply only in the EU, are assigned to these classifications rather than H statements.

The following applies to mixtures:
If a mixture contains at least one ingredient that has been classified as a Category 1 or Category 2 endocrine disruptor for human health and is present at or above the appropriate generic concentration limit for Category 1 or Category 2, it is classified as an endocrine disruptor for human health. If a Category 2 endocrine disruptor for human health is present in the mixture as an ingredient at a concentration ≥ 0.1%, a safety data sheet is to be available for the mixture upon request.

Label elements

Table: Label elements of endocrine disruption for human health or the environment and generic concentration limits that trigger classification of a mixture

Classification	Category 1	Category 2
GHS pictogram	-*	-*
Signal word	Danger	Warning
Hazard statement	ED HH 1 EUH380: May cause endocrine disruption in humans ED ENV 1 EUH430: May cause endocrine disruption in the environment	ED HH 2 EUH381: Suspected of causing endocrine disruption in humans ED ENV 2 EUH431: Suspected of causing endocrine disruption in the environment
Generic concentration limits that trigger classification of a mixture	≥ 0.1%	≥ 1%
Precautionary Statement Prevention	P201: Obtain special instructions before use P202: Do not handle until all safety precautions have been read and understood P263: Avoid contact during pregnancy and while nursing P280: Wear protective gloves/protective clothing/eye protection/face protection
Precautionary Statement Response	P308+P313: If exposed or concerned: Get medical advice/attention
Precautionary Statement Storage	P405: Store locked up
Precautionary Statement Disposal	P501: Dispose of contents/container to ...
*New pictograms for these hazard classes will not be created for the time being.
Notes: The concentration limits in this table apply both to solids and liquids (w/w units) and to gases (v/v units). If a Category 2 endocrine disruptor for human health or a Category 2 endocrine disruptor for the environment is present in the mixture as an ingredient at a concentration ≥ 0.1%, a safety data sheet for the mixture is to be made available upon request.
For ED ENV, P phrase 273, "Avoid release to the environment", applies instead of P263 and P280, and P phrase P391, "Collect spillage", applies for the response.

3. Further regulatory aspects

With the introduction of the new ED hazard classes, the CLP Regulation is now a key instrument for specifying a substance’s or mixture’s status as an endocrine disruptor. In future, ECHA’s Committee for Risk Assessment (RAC) will conduct ED assessment of substances by means of the harmonised classification and labelling process (CLH process). This process yields a legally binding classification in Annex VI to the CLP Regulation by means of an "Adaptation to Technical Progress" (ATP) and an EU regulation.
To date, application and use of EDs in the EU has been governed on a sectoral basis by way of the registration procedure under the relevant EU legislation.
The legislation governing plant protection and biocidal products, and chemicals in general under the REACH Regulation, the Cosmetic Products Regulation, the Medical Devices Regulation and the Water Framework Directive, set out specific measures and means of identifying, assessing and dealing with endocrine disruptors.

4. Identification of endocrine disruptors – guidelines and lists

To ensure uniform assessment (consistent with the principle of "one substance, one assessment"), harmonised criteria for the identification of EDs across all regulatory frameworks are being developed at European level. Guidance on the identification of endocrine disruptors can be found in the updated ECHA Guidances on the Application of the CLP criteria, which was published in November 2024 and comprises five documents. Information on applying the ED criteria during self-classification can be found in Part 3.11 for ED HH and in Part 4.2 for ED ENV.

A number of lists are available containing information on the current status of the assessment of substances. These substances either have already been identified as endocrine disruptors or are currently being studied as such. The lists also contain information on the endocrine activity of substances and on standardised OECD detection methods for identifying endocrine disruptors. An overview is provided below.

Endocrine disruptor assessment list
In the "Endocrine disruptor assessment list", ECHA publishes the substances that are undergoing ED assessment and have been submitted to ECHA’s ED expert group for discussion. Following the latest update on 25 February 2025, this list currently contains 129 individual substances.
Endocrine Active Substances Information System (EASIS)
(European Commission database)
EASIS is a European Commission database of information on the endocrine effects of chemicals. It currently contains data on over 600 substances, derived from 10,000 studies, including animal tests and human data. The data are derived from scientific studies that have been reviewed independently, and are presented in a standardised format with use of the OECD harmonised templates (OHTs). This ensures compatibility with other international surveys of data.
Endocrine Disruptor Lists I-III - Edlists.org (Member States)
In June 2020, the "Endocrine Disruptor Lists" were introduced by Belgium, Denmark, France, the Netherlands and Sweden; Spain followed in 2021. The lists serve as a harmonised source of information on the status of substances identified or tested as endocrine disruptors (EDs) in the EU.
- List I: Substances identified as endocrine disruptors at EU level
- List II: Substances under evaluation for endocrine disruption under an EU legislation
- List III: Substances considered, by the evaluating National Authority, to have endocrine disrupting properties

The lists are updated at least every six months.

OECD identification methods
This OECD summary lists standardised methods for identifying EDs. In addition to animal models (in vivo), these include cell culture systems (in vitro) and computer-assisted calculation methods (in silico). In future, animal testing is to be replaced progressively by alternative methods. Owing to the absence of mechanistic tests and the complexity of the endocrine system, however, this will continue to be a challenge.