Endocrine disruptors, a scientific challenge
Endocrine disruptors are substances that can interfere with our hormonal system and cause adverse effects. Given the multiple sources of exposure, scientists need to understand the role played by these substances in the development of certain diseases.
What are endocrine disruptors?
Endocrine disruptors are substances that disrupt the hormonal functions of living organisms, causing harmful effects to the health of humans, animals and ecosystems.
According to the internationally agreed definition, which has been adopted at regulatory level in the CLP Regulation, an endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse effects in an intact organism, or its progeny, or (sub)populations.
What are the effects of endocrine disruptors?
These substances disrupt the hormonal system, which plays an important role in the body.
In some cases, they can alter different processes such as communication between cells or tissues and the regulation of key stages of an organism's development.
Endocrine disruptors can interfere with all the major functions of living organisms, such as growth, reproduction, foetal development, behaviour, nutrition, metabolism, the nervous system, etc. Recent studies have shown that endocrine disruptors can also have other effects, such as metabolic, neurodevelopmental or immune effects.
What is the endocrine system?
Good health depends on a well-functioning endocrine system. This system is made up of several organs called glands (composed of endocrine cells), which produce hormones and then release them into the blood. Distributed throughout the body, these hormones act as "chemical messengers". They have a variety of essential functions, such as stimulating growth and development, regulating emotions and controlling major physiological constants (body temperature, blood glucose levels, blood pressure, etc.) and systems involved in reproduction. This means that any alteration to the endocrine system can disrupt the body’s natural balance in the long term.
How do endocrine disruptors impact health and the environment?
Endocrine disruptors have an impact on wildlife, causing sex changes in certain fish populations, developmental disorders, etc. They also disrupt ecosystems, contributing to loss of biodiversity.
In addition, these substances can play a part in the development of disease in humans. Numerous studies have described, for example, fertility and reproductive disorders (reduced sperm quality, increased frequency of developmental defects in reproductive organs or reproductive function, lower age at puberty), as well as hormone-dependent cancers such as breast cancer and prostate cancer. Lastly, they affect the quality of our ageing.
Neurological disorders such as autism and reduced intelligence quotient, metabolic disorders such as diabetes and obesity, or disorders of our immune system may also be associated with exposure to endocrine disruptors.
What are the sources of exposure?
There are many different endocrine disruptors, and humans and animals are exposed to numerous sources of contamination.
Some of these substances may occur naturally in the environment. However, our exposure is compounded by the use of everyday products such as plastics, detergents and cosmetics, as well as the consumption of processed foods.
Various compounds suspected of being endocrine disruptors can be found in trace amounts in the environment: in water, air and food. Organisms can thus be exposed by multiple routes – ingestion, inhalation, dermal contact – to minute doses of several compounds simultaneously.
How do endocrine disruptors act?
The mechanisms of action of endocrine disruptors make it difficult to identify adverse effects over the long term, or over several generations. The fact that the effects potentially occur at low doses makes identification even more of a challenge.
In view of this complexity, understanding 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.
The low-exposure dose
Usually, below a certain level of exposure, the body's defence mechanisms prevent the appearance of health effects. This is referred to as the threshold effect. However, for certain substances, there is sometimes no threshold effect, at least on a population scale, so effects are possible even at low doses. This is suspected to be true of endocrine disruptors.
Non-monotonic dose-response relationships
Traditionally, the harmful effects of chemicals are described in toxicology studies as being proportional to the dose tested. Typically, a low dose produces no effect, the median dose produces mild 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 more significant (or even opposite) effects at low doses to those observed at high doses; this is called a non-monotonic dose response.
Window of exposure
Susceptibility to endocrine disruptors may vary with the stage of life. This is particularly true of exposure during pregnancy and/or early childhood, when the exposed individual is more sensitive to some of these substances. Puberty is also a sensitive period during which a hormonal disorder can irreversibly alter certain functions of the body.
What are the regulations governing endocrine disruptors?
The CLP Regulation
The CLP Regulation is a cross-cutting regulation that rules on the hazardous nature of chemicals and imposes specific labelling. Delegated Regulation 2023/707 of 19 December 2022 added the new hazard classes "endocrine disruption for human health" and "endocrine disruption for the environment". Substances and mixtures that meet the definition of endocrine disruptors will therefore have to be classified and labelled with a warning, hazard statement(s) and precautionary statements in accordance with the new rules of the CLP Regulation. This results in a cross-cutting definition that is identical regardless of how these chemicals are used. In addition, this hazard classification, which distinguishes between suspected and presumed/possible endocrine disruptors, allows varying levels of evidence to be taken into account. Lastly, the implementation of this new hazard class ensures that substance hazards are clearly identified and communicated to workers and consumers.
The REACH Regulation
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 European Union 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.
In addition, France is the first country to have had a National Endocrine Disruptor Strategy aiming to reduce exposure of the population and the environment to endocrine disruptors.a