In order to regulate so-called ‘endocrine disruptors’ the European Commission recently published a draft proposal for criteria for ‘endocrine disrupting properties’, for pesticides and biocides.
These criteria should allow regulators to identify those substances which pose real concern to health, and those that do not. Many natural and synthetic substances, like coffee or paracetamol, can interact with the endocrine system in a temporary way without causing harm.
The final criteria are of consequence for the competitiveness of EU agriculture and the supply of safe food. It is therefore essential that the criteria maintain high levels of protection for human health and the environment, while ensuring European farmers continued access to essential crop protection products.
The endocrine system consists of a set of glands which produce hormones. Hormones are chemical messengers which are released into the bloodstream to reach target organs and tissues, producing specific responses.
The endocrine system regulates processes including growth, reproduction and homeostasis.
For example, after a meal, the concentration of blood sugar increases and the pancreas starts producing a hormone known as insulin. When muscular cells detect insulin they capture the sugar from the blood, to obtain the energy required for normal cell functioning. The blood sugar concentration then decreases.
We are constantly in contact with both natural and synthetic substances that can interact with our hormone system. They are called endocrine active substances and are found everywhere in our daily life, such as in paracetamol, vitamin C, caffeine or phytoestrogens naturally present in soy.
that a lot of our body functions are controlled by hormones and that our hormonal system is in constant interaction with our environment and the substances that surround us? The endocrine system is therefore naturally dynamic and responsive as part of its normal functioning.
Endocrine disruption has been extensively researched over the last 20 years with Pubmed citing over 7,800 references. Consequently, considerable scientific understanding already exists.
The main research areas are: the effects that substances may have on the endocrine system, the main sources of exposure, testing protocols to identify endocrine disruptors and possible substitutions.
While more research may be needed - for example on the impact of endocrine disruptors in the womb and on species other than mammals and fish - existing scientific literature is enormously helpful in assessing endocrine disruption risks. We know a lot about the endocrine system, its functioning and the effects of endocrine disruption.
This knowledge is routinely applied to improve products and it is important that future regulation is based on these scientific findings.
Number of publications per year containing the key words endocrine disruptors
that in total there are already over 7,800 publications on endocrine disruption?
We are constantly in contact with substances that can interact with our endocrine system. These endocrine active substances are part of our daily lives because they are present in nature and in our food, such as in vegetables, milk, coffee 1 or soy.
Endocrine active substances are found in nature but can also be man-made 3 , like paracetamol 1, 2 , hormone replacement therapy or man-made insulin.
Our body is designed to interact with them 3, 4 . But interaction does not automatically mean disruption. There are 3 kinds of interaction between substances and the endocrine system, those that have:
• a positive effect , such as hormone replacement therapy for premenopausal women
• a neutral effect such as caffeine in coffee when consumed in reasonable amounts
• or an adverse effect , such as dystylben. These substances that go beyond a simple interaction and entail adverse health effects are called endocrine disruptors.
But the situation is not so simple. Besides the substance itself, other factors can also determine an adverse effect - such as the substance's strength and dose as well as the general health of the person.
For example, insulin is a hormone that regulates blood sugar concentration. Insulin-dependent diabetics need regular injections with man-made insulin. However, depending on the blood sugar concentration of the patient and the dose injected, the effects on the body may be beneficial or adverse. An excessive amount of insulin can induce an insulin-related coma.
Because people should not be exposed to substances that adversely affect their endocrine system, it is important that the European Commission defines regulatory criteria that identify problem substances, including factors such as the dose, potency and duration of exposure.Sources
that the intrinsic properties of a substance are not the only criteria that determine the effects it will have on the endocrine system? Potency of the substance, time and duration of exposure and physiological state of the body are also important factors that need to be taken into account.
The European regulatory requirements for the authorisation of pesticides are stringent and already provide a high level of protection for European consumers and farmers.
The pesticides approval process requires more than 300 studies to be conducted. Of these:
• 50% involve human health
• 40% involve environment
• 10% involve efficiency on crop production
The range and the level of requirements are constantly increasing with new scientific developments. Tests on human health now include many different aspects of toxicology, oncology, study of the nervous system and the immune system as well as possible endocrine related adverse effects.
European legislation is specifically designed to ensure that pesticides are authorised for use only if they are proven to be safe under realistic conditions of use.
As part of the current requirements, multi-generation tests are performed which are designed to assess all potential adverse health effects, including endocrine mediated adverse effects. The risk assessment process specifically considers vulnerable populations - such as infants and pregnant women - and applies large safety margins.
Each active substance on the market has to be reassessed roughly every 10 years, taking into account scientific advancements in testing and assessment methods. A substance that does not satisfy the regulatory requirements is either withdrawn or not authorised.
The pesticides industry recognizes the importance of strict regulatory requirements. Public health and environment are paramount for a sound framework in which growth and development is contingent.
Considering the 10-year investment required for the pesticide industry to develop and assess the safety of a new substance, it is important to have a stable regulatory framework that promotes further innovation. This way, our industry can continue to give farmers the tools they need to produce enough healthy, high-quality and affordable food to feed a growing worldwide population.
that European regulation on pesticides already ensures a high level of protection for both general public and farmers?
It is clear that people should not be exposed to substances that interact with the endocrine system in a way that will cause adverse effects. It is also important that safety regulations take sensitive subpopulations such as pregnant women and infants into account, protecting also those who need it the most.
Questioning substances based solely on the fact that they can interact with our hormonal system would implicate many substances that are part of our daily life and which are not necessarily harmful or are even useful. For example, if such criteria were applied to all endocrine active substances, products such as paracetamol, vitamin C, coffee or soy would raise the same issues 1, 5.
It is therefore of paramount importance to define criteria that identify substances that are of genuine regulatory concern, not based only on the potential to interact with the hormonal system.
Whether or not an interaction involves negative effects depends not only on intrinsic properties of the substance, but also on various other factors, such as the dose of the substance and the physiological condition of the body.
It is clear that people should not be exposed to substances that adversely affect their endocrine system. But it is also clear that we cannot ban all endocrine active substances.
To ensure the maximum level of protection of the population, it is first of all important to distinguish endocrine disruptors from endocrine active substances under normal levels of exposure.
The World Health Organisation defines an endocrine disruptor as:
"an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub) populations".6
Under this definition an endocrine disruptor is defined by 3 key criteria : 7
• an adverse effect in an intact organism or population
• interaction with the endocrine system
• a biologically plausible causal link between the first 2 points.
This definition is definitely a good scientific starting point. But additional determining factors, such as exposure and dose/potency, should be taken into account 8, 9, 10 when setting the final regulatory criteria for endocrine disruptors. Existing scientific expertise can identify the substances that are of genuine concern and set regulations on proper use for the rest. This way, the crop protection industry can continue to provide solutions to farmers and help ensure food supplies without jeopardizing public health, well-being and the environment.
Some stakeholders want to define "endocrine disruptors" solely based on their potential interaction with our hormonal system. But such a definition - which would ignore the many scientific studies done on the safety of pesticides - may have significant consequences on: public health, food supply, environment, industry, research and development and economy
Let's take the example of triazoles, which are used to prevent fungi from destroying crops before and after harvesting. In many crops such as cereals, grapes, and bananas, these fungicides prevent the development of mycotoxins, which are known to induce cancer11. Triazoles leave little or no residues in food after harvest, so there is a minimal risk to public health from their use. But the risk of not using them - the risk from mycotoxins - is high.
Triazoles are substances that are suspected of having endocrine activity. If we ban them altogether, we lose our main weapon against mycotoxins, and such common foods as cereals or bananas could become susceptible to inducing cancer. This example demonstrates that strict, inappropriate criteria on endocrine disruption will not necessarily improve protection of public health12 and may in fact make it worse.
By removing one suspected adverse effect, we may be creating a more serious threat.
Consider another example: flame-retardants are suspected of having adverse effects on the endocrine system but they actually save lives every day.
Impact assessment studies have estimated that the prohibition of certain pesticides and fungicides such as triazoles would lead to a reduction of agricultural yields of 10-15% and up to 50% during bad years13.
This reduction in agricultural productivity would pose a real threat to food security and therefore social security at a time when the global population is increasing dramatically and we will need to feed more people from fewer resources.
With globalization, pest pressure is increasing. For example, between 2000 and 2005, 41 new harmful insects have appeared in France14.
Some crops such as vineyards and trees such as pines and palm-trees require treatment to avoid the spread of deadly diseases or pests.
Global food demand is expected to double by 2050. As the land dedicated to food production is limited on a global scale, production growth must be based on productivity growth15. We need to grow more food on less land and with fewer resources.
Declining food production would significantly increase the need for food importation. This would increase food prices and could be responsible for the loss of Europe's agricultural sovereignty.
Moreover, a ban of any endocrine active substance would have a major impact on international trade between Europe and the US16. As some pesticides would still be used in the US but forbidden in Europe, many imports may be blocked. Based on a study published in November 201315, approximately $4.04 billion of US exports of raw agricultural commodities to the EU could be affected by this policy change. The largest effects would be felt in the export of tree nuts and fruit ($1.577 billion), soybeans and groundnuts ($1.516 billion) and grains ($0.586 billion). Taking into account processed food and feed products from these commodities would increase the potential amount to $4.77 billion.
Industry, Research and Development
The investment costs for developing new plant protection products have multiplied by a factor of 7 over the past 20 years; it now costs 250 million euros and 10 years to bring a product to market. Considering this investment of time and money, a stable and predictable regulatory framework is important in order to preserve the incentive to innovate.
Regulatory instability affects the innovation process: research and development in the European crop protection market is already experiencing a sharp decline, resulting in fewer resources for Europe's farmers to combat pests and diseases.
The financial resources available for R&D for crop protection products in the European market have dropped by an estimated 30% since the mid-90's17. Therefore, the potential for successful registration and commercial return is at less risk in non-EU countries. Hence, when R&D projects are being prioritised within companies, the focus for future investment is likely to be outside of the EU.Sources
that if we consider interaction with the hormonal system as the only criterion on which to define an endocrine disruptor, paracetamol, vitamin C, coffee and soy would also be considered as endocrine disruptors? If these substances were then regulated in the same way as pesticides they would be banned.