Endocrine active substances
Endocrine active substances (EAS) are substances that can interact or interfere with normal hormonal action. When this leads to adverse effects, they are called endocrine disruptors (ED).
The endocrine system is important for human and animal health because it regulates and controls the release of hormones. Scientific knowledge in this area is still growing and, therefore, understanding of what is an EAS/ED continues to be the subject of scientific debate.
Humans and animals may be exposed to a wide range of endocrine active substances through the diet as well as other sources. EAS can be naturally-occurring (such as phytoestrogens in soya) or man-made. Examples of EAS sometimes found in food include several pesticides, environmental pollutants like dioxins and PCBs, and the food contact material , bisphenol A. Some EAS are intentionally used in medicines (birth control pills, thyroid hormone substitutes) because of their endocrine active properties.
The guidance was drafted by scientific staff from EFSA, ECHA and the European Commission’s Joint Research Centre. They were supported by a Consultation Group comprising members of ECHA’s Endocrine Disruptor Expert Group and pesticide experts selected by EFSA from EU Member States and from among its registered stakeholders.
EFSA and the European Chemicals Agency (ECHA) publish guidance on how to identify substances with endocrine disrupting properties in pesticides and biocides.
EFSA and ECHA publish an outline of the guidance they are developing on how to identify substances with endocrine disrupting properties in pesticides and biocides.
EFSA’s scientists made significant strides in addressing the issue of potential “endocrine disruptors” in the area of pesticides. Their work is a response to recent EU rules that changed, from 2014 onwards, how EFSA evaluates active substances used in pesticides.
The European Commission launched an online consultation to help define criteria for “endocrine disruptors” as required by EU regulations on biocides and plant protection products (used in pesticides).
EFSA’s Scientific Committee published a scientific opinion on the hazard assessment of endocrine disruptors. This describes scientific criteria for identification of endocrine disruptors and appropriateness of existing test methods for assessing effects mediated by these substances on human health and the environment. EFSA’s experts concluded that internationally agreed testing methods were available or soon to be available for the most important endocrine pathways in mammals and fish known to be sensitive to endocrine disruption: these relate to oestrogen, androgen, and thyroid hormones as well as steroidogenesis (the biological process for production of steroid hormones). EFSA concluded that a risk assessment approach which considers both the likelihood of exposure together with potential adverse effects of endocrine active substances makes best use of available information to regulate their use.
European Commission asks EFSA to provide, in collaboration with the Commission Scientific Committees and the other EU agencies with similar tasks (EMA, ECHA), scientific advice on the assessment and testing of endocrine active substances. EFSA agreed to take stock of existing information, current insights and scientific activities on ‘endocrine disruptors’.
EFSA’s Scientific Committee established an Endocrine Active Substances Task Force, with the support of EFSA’s Advisory Forum of national competent authorities, to clarify the state-of-play on endocrine active substances and to provide recommendations for scientific and communication issues. In a scientific report, the Task Force proposed that EFSA contributed to the work of the European Commission and OECD activities on chemical testing guidelines.
EFSA’s role in the European Union (EU) food safety system is to assess and communicate on all risks associated with the food chain. Endocrine-associated effects are amongst the toxicological endpoints (that is, the expected outcomes of a test or trial) which EFSA’s scientists take into consideration when carrying out risk assessments of chemical substances present in the food chain. The Authority’s scientific advice informs the decisions of EU risk managers (the European Commission, European Parliament and Member States) who regulate the use of these substances in a variety of areas.
- Some EFSA Scientific Panels are sometimes involved in the evaluation of substances with endocrine active properties in the course of their work: the Panel on Contaminants in the Food Chain, the Panel on Plant Protection Products and their Residues, and the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids.
- EFSA’s Scientific Committee provides scientific advice on cross-cutting issues related to the Authority’s risk assessment work. Its advice supports further development of harmonised and consistent approaches for risk assessment, including where these may be relevant to endocrine active substances.
Reliable test methods and testing strategies are needed to allow the identification and assessment of the endocrine disruptive properties of substances. In this context, the harmonisation of the testing of chemicals has been an on-going activity of the Organisation for Economic Co-operation and Development (OECD) since the 1980s. A core activity on endocrine disrupters was initiated in 1997 and under this umbrella both specific tests and a conceptual framework for such tests have been developed. EFSA provides technical support to a number of such activities of the OECD.
Between 1996 and 2000, the European Commission co-ordinated and developed together with the European Parliament, EU Member States and European scientific advisory bodies, a Community strategy for endocrine disruptors. The objectives were to identify the problem of endocrine disruption, its causes and consequences and to propose appropriate policy action in order to respond quickly and effectively to the problem, thereby alleviating public concern. This strategy set out the short, medium and long-term actions to be undertaken to address the potential environmental and health impacts of endocrine disruptors within the EU.
The Commission was called on to identify substances to be prioritised for immediate action. These lists of substances led to the development of European legislation to regulate their use in specific areas:
- Chemicals – Regulation EC 1907/2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) – substances having endocrine disrupting properties may be identified as Substances of Very High Concern (SVHC) and be made subject to authorisation.
- Pesticides – Regulation EC 1107/2009 concerning the placing of plant protection products on the market – substances regarded as having endocrine disrupting properties that may be harmful to humans or non-target organisms cannot be authorised. However, non-approval does not apply if the exposure is negligible under the conditions of use, or if the substance is necessary to control a serious danger to plant health which cannot be contained by other available means including non-chemical methods. As part of the peer review of active substances, EFSA assesses potential endocrine disrupting (ED) properties. An overview of the ED assessment of pesticide active substances in line with the criteria introduced by Commission Regulation EU 2018/605 is provided in a dedicated report, which is regularly updated and published on this website.
- Biocides – Regulation EU 528/2012 concerning the making available on the market and use of biocidal products – these substances are not approved if they have endocrine disrupting properties. However, non-approval does not apply if the risk to humans and the environment is negligible, if the substance is essential to combat a serious health risk, or if non-approval would result in disproportionate negative impacts on society relative to the risks to humans and the environment.
- Cosmetics – Regulation EC 1223/2009 on cosmetic products – endocrine disrupting substances are currently not restricted; however, this will be reviewed when EU or internationally agreed criteria for identifying substances with endocrine-disrupting properties are available.
- Water quality – Water Framework Directive (2000/60/EC) – sets out a strategy against pollution of surface waters by chemical pollutants and the substances of particular concern in the EU, including some candidate endocrine disrupting substances. In 2012, the Commission proposed to amend the list of priority substances. Although no direct reference is made, endocrine disruption could become an important criterion for sorting substances or groups of substances into this group.
Review of the EU strategy
In 2009, the Commission’s Directorate-General for the Environment commissioned a study on the ‘State of the Art of the Assessment of Endocrine Disruptors’ to provide a basis for the development of scientific criteria for the identification of endocrine disruptors; and the review and possible revision of the EU (previously ‘Community’) Strategy on endocrine disruptors. The resulting study was published in January 2012 and reviewed scientific knowledge published in the literature in the previous 10 years. Its scope followed also a review of approaches for assessment of endocrine disruptors used in selected Member States, in other countries outside the EU, and in international bodies (e.g. the World Health Organisation).
As a follow-up to this study, in June 2012, the Commission organised a conference on ‘Endocrine Disruptors: Current challenges in science and policy’. Together these two initiatives provided the platform for the review of the Strategy and also input to the Commission’s above-mentioned upcoming legislative proposal for establishing criteria for the identification of substances with endocrine disrupting properties. In addition, the European Environment Agency (EEA) published a report on ‘The Impacts of Endocrine Disrupters on Wildlife, People and their Environments – The Weybridge+15 (1996–2011)’.
In late 2014, the Commission held an on-line consultation to help define criteria for endocrine disruptors as required by EU regulations on biocides and plant protection products (used in pesticides).
On 4 July 2017 EU Member States voted in favour of the European Commission’s proposal on scientific criteria to identify endocrine disruptors in the field of plant protection products. The criteria identify known and presumed endocrine disruptors. They also specify that the identification of an endocrine disruptor should be carried out by taking into account all relevant scientific evidence including animal, in vitro or in silico studies, and using a weight-of-evidence approach.
The criteria will apply after a transitional period during which EFSA and the European Chemicals Agency (ECHA) will finalise a joint guidance document for the implementation of the criteria (see Latest). A draft of the guidance is expected to be available for public consultation in the autumn.
The endocrine system is a network of glands which regulates and controls the release and levels of hormones in the body. Hormones are chemical messengers that are essential for the body to carry out functions such as metabolism , growth and development, sleep and mood. Only a tiny amount of hormone may be needed to trigger the intended action. The endocrine system is complex and the interactions within this system which regulate hormonal release are dependent on a variety of biological and physiological factors. Scientific knowledge of this system is still growing.
Imbalances and malfunctions of the endocrine system can result in well-known diseases, such as diabetes and obesity, infertility and certain types of cancer. Also, disruption of the endocrine system can cause birth defects and learning disabilities.
Endocrine active substances are chemicals that can interact or interfere with the endocrine system. This may take place in different ways: some such substances mimic natural hormones but trigger unwarranted responses, or they may block the effects of natural hormones. Others change hormone levels in the body or alter metabolic processes that breakdown natural hormones. Importantly, these effects are not necessarily adverse. The endocrine system is capable of adjusting and adapting to these stimuli depending on factors such as the nature and dose of the substance, its timing, the type of effect and the condition of the body. This ability of the endocrine system is sometimes called adaptive response or ‘physiological modulation’. However, when this interaction or interference leads to adverse effects these substances are called endocrine disruptors.
Exposure to endocrine disruptors could increase the likelihood of harmful effects in the short-term or later in life. Concern about the possible harmful effects of endocrine disruptors has been growing in recent years because of observations in humans and wildlife. These indicate rising rates of endocrine diseases and disorders, including reproductive and developmental harm in human populations. However, the scientific basis for linking all such trends to endocrine disruptors (as opposed to other factors such as lifestyle changes and genetic background) is not conclusive.
We are potentially exposed to a wide range of endocrine active substances – these can be naturally present in the diet or be present as a result of human activity. Examples of substances naturally present in food which may exert hormonal effects are plant phytoestrogens such as isoflavones, which are often present in nuts, oilseeds and soy products. Another example is glycirrhizine in liquorice, which may disrupt the hormonal regulation of the balance of minerals and fluids (or ‘electrolytic balance’) in blood and various organs, important for the regulation of blood pressure. Examples of endocrine active substances sometimes found in food and feed include some pesticides, the food contact material bisphenol A (BPA) as well as environmental pollutants like dioxins and PCBs. Some endocrine active substances are intentionally used in medicines (birth control pills, substitutes for thyroid hormones) because of their endocrine active properties.
EFSA endorses the World Health Organization’s definition that a substance must meet three criteria to be considered an endocrine disruptor: firstly, the presence of an adverse effect; second, the presence of endocrine activity; and thirdly, a causal relationship between the two. In 2017/18 the European Commission adopted two sets of scientific criteria for identifying endocrine disruptors in biocidal products and plant protection products (PPPs). The criteria for biocidal products applied from 7 June 2018, while those for PPPs will apply from 10 November 2018. Guidance on how to implement the criteria has been developed by EFSA and the European Chemicals Agency and will be published on 7 June 2018.
The Authority neither authorises nor bans the use of substances in foods. It is the responsibility of risk managers in the European Commission, the European Parliament and the EU Member States to define and agree measures as and where required, taking into account scientific advice and other considerations.
EFSA’s role is to provide independent scientific advice to risk managers on food and feed safety and to communicate its advice to the public at large. It is in this context that EFSA’s Scientific Committee and Scientific Panels carry out safety assessments and review new evidence.
As a scientific organisation EFSA recommends that these substances – like all other substances present in the food chain – be subject to risk assessment in order to make the best use of available information in ensuring consumer safety. Such an approach considers both potential adverse effects of substances together with the likelihood of exposure to such substances. EFSA believes that scientists can clarify through expert judgement and the weight-of-evidence what may or may not be an endocrine disruptor.