Accelerating the assessment of endocrine disruptors
As part of France’s Second National Endocrine Disruptor Strategy (SNPE 2), ANSES has drawn up a list of substances of interest and identified a selection of priority substances to be included in its assessment programme. The Agency is also recommending a method to establish whether the substances assessed are known, presumed or suspected endocrine disruptors. The purpose of this work is to implement a shared approach in order to identify endocrine disruptors faster and more efficiently, and to promote their assessment in accordance with the objectives set by France and Europe to reduce the risks relating to chemical substances.
Endocrine disruptors (EDs) are substances that interfere with the hormonal functions of humans and animals. They lead to adverse effects on the exposed organisms or impact the survival of the species. For example, they can affect reproduction, development, metabolism and immunity, or promote the development of cancers. Launched in 2019, the Second National Endocrine Disruptor Strategy (SNPE 2), continues and expands efforts in France to reduce the exposure of the population and the environment to these substances.
To this end, the Environment and Health Ministries asked ANSES to develop two methodological tools in order to focus efforts on priority substances and to undertake a rigorous assessment of their properties as potential endocrine disruptors. These two tools are:
- a list of the substances considered to be of interest owing to their potential endocrine action, associated with a prioritisation strategy;
- an expert appraisal method to weigh the scientific evidence identifying a substance as an endocrine disruptor, in order to classify it as known, presumed or suspected.
Some of this work has been presented to the European Chemicals Agency (ECHA) and to the Member States engaged in the same approach to accelerate the assessment of endocrine disruptors. National and international scientific cooperation will play an essential role in accelerating recognition of some substances as dangerous endocrine disruptors.
From identification to prioritisation
A number of lists of potential endocrine disruptors have been drafted in different parts of the world, based on varying criteria and objectives. As a result, the number of substances on these lists varies considerably, from several dozen to several thousand. Based on the WHO definition, the hazard characterisation of EDs requires the concomitance of three characteristics (see box below). The endocrine systems of living beings are complex and can react to many substances that do not necessarily represent a health hazard. It is therefore essential to gather a large body of data and to conduct an in-depth assessment.
ANSES compared the existing lists of substances and the methods used, in order to compile a rigorous list of the substances of interest for which the data available are sufficient to consider an assessment based on the three points set out by the WHO.
Criteria for identifying endocrine disruptors
According to the WHO definition, a substance is recognised as an endocrine disruptor if it meets the three conditions below:
- adverse effects on health;
- altering one or more of the functions of the endocrine system;
- a biologically plausible link between these two findings.
It will also be necessary to show that the effects observed in animal or cell models are relevant to humans or a specific animal population.
This list of interest comprises 906 substances. These substances have multiple uses: some are used only in industrial processes, others are found in everyday consumer products, plant protection products, biocides or medicines. Some of them are already being assessed for their endocrine-disrupting properties as part of the European regulatory framework.
An in-depth assessment is essential to determine whether the substances of interest identified are endocrine disruptors. This assessment requires scientific data as well as a baseline methodology for the expert appraisal. It is essential for the resources and main focus of this assessment to be placed on priority substances. These substances will be included in the annual assessment programme, carrying on from those already conducted by ANSES in recent years, which are continuing as part of SNPE 2.
Selecting substances to be assessed: establishing a priority target
The list of 906 substances of interest drawn up by ANSES includes a number of substances that are already banned or heavily regulated in Europe, and others that are not used in European countries. ANSES therefore put in place a mechanism to prioritise the substances to which the population is exposed in Europe, and whose endocrine properties have yet to be studied as part of a planned assessment. These substances must be addressed as a matter of priority.
Through this mechanism, ANSES has identified 16 priority substances for which it considers an assessment is necessary to establish their level of hazard as endocrine disruptors. This selection will be submitted for consultation to the ANSES Thematic Steering Committee on Endocrine Disruptors. Following this consultation, the Agency will formulate its recommendations on the substances to be included in its work programme from 2021 to the ministries responsible for SNPE 2. This work thereby complements the European assessment processes already under way to assess the endocrine-disrupting nature of various substances.
An assessment methodology taking account of the sometimes fragmented knowledge of ED properties
Reflecting the recommendations made in recent years, and in particular an opinion published in 2016 on the scientific criteria for defining endocrine disruptors (PDF), ANSES underlines the need to be able to make a distinction between “known”, “presumed” and “suspected” endocrine disruptors, following an assessment.
In order to assess the priority substances identified by ANSES, a method is needed to characterise the degree of certainty of the endocrine-disrupting properties of these substances, since current scientific knowledge does not always allow us to definitively identify a substance as an endocrine disruptor.
Continuing the studies undertaken on this subject in recent years, ANSES is putting forward a methodology to establish an operational categorisation, ahead of the one to be implemented by the European Union, as announced as part of the EU Chemicals Strategy for Sustainability towards a toxic-free environment. As is currently the case for carcinogenic, mutagenic and reprotoxic substances, ANSES is implementing a graduated approach in order to take better account of uncertainties and to make it easier for experts to express their judgement.
Categories established to reflect the degree of probability of a substance being an endocrine disruptor
The categories defined by ANSES are based on the probability of a substance being an endocrine disruptor:
- known: substances that are highly probable endocrine disruptors (probability of over 90%);
- presumed: substances that are strongly suspected of being endocrine disruptors, but with no certainty (probability of between 66% and 90%);
- suspected: substances for which information received is concerning but not sufficient for clear judgement (probability of between 5% and 66%).
This methodology ensures that all the data available for a substance at given time are taken into account. By providing a graduated result, this methodology should make it possible to vary the applicable rules in accordance with the uses and population groups exposed: for example, stricter regulations for toys, with a ban on “known”, “presumed” and also “suspected” endocrine disruptors.
The proposed methodology confirms the intentions of ANSES to support changes in national and European regulations in order to take greater account of scientific uncertainty and levels of evidence, coinciding with the ambitions set out by Europe to update its regulations in order to take better account of the danger of endocrine disruptors.
Several regulations concerning endocrine disruptors
Currently, the regulations on plant protection products and biocides exclude substances assessed as endocrine disruptors from marketing authorisations (or renewals).
Other provisions take this hazard characteristic into account for other chemical substances, as part of the European REACh Regulation for the Registration, Evaluation and Authorisation of Chemicals, applied without transposition in all EU Member States. According to this regulation, substances with endocrine-disrupting properties and of an equivalent level of concern to carcinogenic, mutagenic and reprotoxic substances (CMRs), can be identified as substances of very high concern, and thus be included in the list of substances subject to authorisation.
Last, discussions are under way to create a hazard class for endocrine disruptors as part of the European CLP Regulation (Classification, Labelling and Packaging of Substances and Mixtures)