ANSES's work and involvement in the area of endocrine disruptors

Potential endocrine disruptors can interfere with all the major functions of living organisms, such as growth, reproduction, foetal development, behaviour, nutrition, metabolism and the nervous system.

How do endocrine disruptors act?

Multiple sources of exposure to endocrine disruptors

There are a wide variety of endocrine disruptors and numerous sources of contamination to which humans and animals are exposed. Various compounds suspected of being endocrine disruptors can be found in trace amounts in the environment.
Organisms can thus be exposed by multiple routes (ingestion, inhalation, dermal contact) to minute doses of several compounds, the effects of which can be varied and may combine.

The low-exposure dose

Usually, below a certain level of exposure, the body's defence mechanisms prevent the appearance of health effects. This is called a threshold effect. For certain hazardous substances such as carcinogenic compounds, there is sometimes no threshold effect, at least on a population scale, so effects are possible even at low doses. Endocrine disruptors are suspected of acting in the same way.

Non-monotonic dose-response relationships

Traditionally, the adverse effects of chemicals are described in toxicology studies as proportional to the dose tested. Typically, a low dose produces no effect, the median dose produces low toxic effects, while a high tested dose induces more pronounced or harmful effects. However, toxicologists have noted that some chemicals can follow inverted curves, i.e. have greater (or even opposite) effects at low doses than those observed at high doses; this is called a non-monotonic dose response.

Windows of exposure

Susceptibility to endocrine disruptors may vary with the stage of life. This applies in particular to the foetal and embryonic development period, and to infants and young children, who exhibit greater sensitivity to these substances. The onset of puberty is also a sensitive period during which a hormonal disorder can irreversibly alter certain functions of the body.

Cocktail effects

Understanding the effects of endocrine disruptors requires also taking into account the individual’s exposure to a mixture of chemicals and understanding their interactions in the human body over the long term, right from the period of foetal-embryonic development.

In view of this complexity, knowledge of the effects of endocrine disruptors at the concentration levels observed in the environment is hindered by the limitations of traditional toxicology and risk assessment methods. The challenge is therefore to develop new ones, adapted to the unique properties of these compounds. Understanding the potential environmental and human health effects requires that research projects take into account the potential synergistic effects of mixtures of environmental contaminants.

The regulation of chemicals, apart from specific uses, is governed by the REACh Regulation (for Registration, Evaluation and Authorisation of Chemicals), which applies without transposition in all EU Member States. It provides for substances with endocrine-disrupting properties and of equivalent concern to carcinogenic, mutagenic and reprotoxic substances (CMRs) to be identified as substances of very high concern, and therefore to be included in the list of substances subject to authorisation.

Plant protection products and biocides are governed by specific regulations for these uses, which are the only laws that explicitly provide for the exclusion of substances with endocrine-disrupting effects.

The CLP Regulation is a cross-cutting regulation that rules on the hazardous nature of chemicals and imposes specific labelling. For now, endocrine disruption is not a hazard class in this regulation, but the announcements made by the European Commission as part of its ambition for a toxic-free environment seek to change this.

The assessment of biocidal and plant protection substances: identification criteria now defined and implemented

A definition of endocrine disruptors for substances in plant protection and biocidal products was adopted in 2017 at European level (EU Regulations 2017/2100 and 2018/605). Consideration is being given to extending this approach to other regulated sectors (cosmetics, medical devices, food contact materials, etc.). ANSES contributed to this work on the criteria for the identification of endocrine disruptors: See our news update of July 2016 "ANSES issues its conclusions regarding criteria for the identification of endocrine disruptors" 

From now on, a plant protection or biocidal substance is identified as an endocrine disruptor if:

1. the substance has a mode of action that alters the functions of the endocrine system;
2. it produces an adverse effect in an intact organism or its descendants;
3. the adverse effect is a consequence of this mode of action.

For all plant protection and biocidal substances for which an evaluation was ongoing or due to be carried out (new substance or renewal of approval of an existing substance), the endocrine disruption assessment must be conducted in accordance with the criteria set out in the appropriate European Regulations and the methodology developed in the EFSA/ECHA Joint Guidance Document published on 5 June 2018.

> See EFSA news item of june 2018.

As soon as the European regulations were adopted, ANSES conducted an assessment of the substance epoxiconazole and confirmed its endocrine-disrupting nature.

> See our news update "ANSES announces the withdrawal of marketing authorisations for fungicidal plant protection products containing epoxiconazole in France".

France and the other Member States will assess the endocrine-disrupting properties of approximately 300 plant protection substances by 2025 and 100 biocidal substances by 2024.

ANSES, as the competent evaluation authority, will be responsible for evaluating several dozen of these.

Assessment of chemical substances

Many chemicals are suspected of having these properties: bisphenols, phthalates, parabens, brominated and perfluorinated compounds, and alkylphenols.

For nearly 10 years, ANSES has been carrying out extensive work to prioritise and then evaluate chemicals with regard to their potential endocrine-disrupting action. This work specifically contributes to identifying them as Substances of Very High Concern for their endocrine-disrupting properties under the REACh Regulation, leading to a ban on the use of the substance unless renewable authorisation is granted.  

ANSES thus identified bisphenol A as an endocrine disruptor for humans, and more recently TNPP, which contains nonylphenol and bisphenol B.

Since 2009, ANSES has assessed a number of substances liable to be found in mixtures for consumer use. It has also conducted appraisals of classes of substances such as perfluorinated compounds, phthalates and polybrominated compounds. In addition to their effects, uses and sources of exposure, the contamination of different environments by these substances was studied.
These studies served as the basis for ranking the substances to be assessed as part of the National Endocrine Disruptor Strategy (SNPE 2014-2016).

National Endocrine Disruptor Strategy

France is the first country to have had a National Endocrine Disruptor Strategy (SNPE 2014-2016) aiming to reduce exposure of the population and the environment to endocrine disruptors. In this context, ANSES has been tasked with assessing at least five substances per year; these can also include potential substitutes for substances of concern. From 2021, the number to be assessed annually is six chemicals under REACh, and three biocidal and plant protection substances.

When certain substances submitted to the Agency for appraisal are suspected of having endocrine-disrupting effects and/or posing a risk to health or the environment, ANSES is asked to propose appropriate risk management measures in the framework of the European regulations.
The experience of the SNPE1 has shown that assessing the ED nature of substances was often limited by the lack of data on these substances.

The conclusions obtained for the 22 substances evaluated in the framework of SNPE1 were as follows:

More detailed information can be found in the opinions on the assessed substances, via the links on this page. 
Following this first SNPE, the second National Endocrine Disruptor Strategy (SNPE 2) was launched in September 2019. The Agency has identified a list of 906 substances to be assessed for their potential endocrine activity and developed a methodology for assessing the ED nature of chemicals with a view to classifying them as "known, presumed or suspected". This method puts collective expert appraisal at the heart of the Agency's analysis of these issues. Read our news update on the Agency's SNPE2 reports.

> More information on the second national endocrine disruptor strategy (in French)

The Agency's other work on endocrine disruptors

ANSES has also conducted several expert appraisals:

• on the potential health and environmental effects of flame retardants used in upholstered furniture.
  
  > See the news update "Assessment of the risks associated with exposure to flame retardants used in upholstered furniture";
• on the presence of phthalates or substitute substances in flexible plastic toys and childcare articles that can be put in the mouth by children under three years of age.
  
  > See our October 2010 news update "Substitutes for phthalates in toys: no health risk detected for children under three years of age";
• collection and analysis of data on the presence of pesticide residues in environmental media by the Phytopharmacovigilance scheme;
• total diet studies and in particular the study on the infant population (iTDS), published in 2016: dietary exposure of children under three years of age to substances of interest, some of which may have an endocrine-disrupting effect;
• study of the presence of compounds in water resources and in drinking water by ANSES’s Nancy Laboratory for Hydrology.