Endocrine disrupting chemicals (EDCs) have been linked to serious health problems such as diabetes, obesity, and neurodevelopmental and reproductive disorders. EDC-MixRisk has studied the effects of prenatal exposure to mixtures of potential EDCs on the development and health of children. The objectives of the project were i) Identification of mixtures of EDCs that are associated with multiple adverse health outcomes; ii) Identification of molecular mechanisms and pathways underlying these associations and iii) Development of methods for risk assessment of EDC-mixtures.

EDC-MixRisk applied an integrated approach which was grounded on interdisciplinary collaboration, including epidemiology, experimental biology and regulatory toxicology. Three health domains were addressed: 1) growth and metabolism, 2) neurodevelopment and 3) sexual development. By using a whole mixture approach and epidemiology data from the Swedish pregnancy cohort SELMA, relevant EDC mixtures associated with adverse health outcomes in humans were identified. Then, reference mixtures were created to mimic real-life internal exposures, and these mixtures were tested in various cell and animal models. The experimental data were used to establish new methods and strategies for mixture risk assessment in order to complement current approaches and to better address environmental exposures. The main results and conclusions of the project are summarized in a final technical report that is available here.


We are exposed to a large number of man-made chemicals. This creates combinations of chemical mixtures, to which we are subjected during our whole lifespan. Current risk assessment and management practices, however, focus mainly on exposure to single substances. Exposure to hazardous substances, especially endocrine disrupting chemicals (EDCs), during the foetal period is of particular concern, as it can lead to irreversible changes in the development of organs and tissues and increased susceptibility to diseases later in life.

The EU Horizon 2020 EDC-MixRisk project (https://edcmixrisk.ki.se/), which has now reached its conclusion, was initiated to investigate how effects caused by real-life relevant mixtures could be studied. The project, composed by researchers from several Swedish, European and one U.S. university, developed a novel approach based on identifying and testing EDC mixtures associated with adverse health outcomes in humans.

By using epidemiology data from the Swedish pregnancy cohort SELMA (a cohort of more than 2300 pregnant women), reference mixtures were created to mimic real life exposures (at concentrations found in the pregnant women). These mixtures were tested in various experimental (cell and animal) models, and the toxicological data from these tests were used to establish new methods and strategies for mixture risk assessment in order to better account for complex environmental exposures. Professor Åke Bergman, coordinator of the project, says “the novel whole mixture approach applied in EDC-MixRisk has allowed us to assess the number of mothers in the SELMA cohort that are at risk for effects in their children, effects related to growth and metabolism, neurodevelopment and sexual development”.

Further, researchers in Prof. Testa’s laboratory in Milano spearheaded the use of human brain organoids to directly assess the impact of such mixtures on the closest available model of the developing human brain. They uncovered that even at real life concentrations, EDCs interfere with the same regulatory networks that are already involved in the genetic forms of autism spectrum disorder and intellectual disability. “This new method enables the investigation of relevant chemical exposures on equally relevant windows of sensitivity during human brain development.” Prof. Testa points out.

In Paris, the team of Prof. Demeneix investigated whether the mixtures interfered with brain development and growth through modulation of thyroid hormone signalling. Prof. Demeneix underlines that “Thyroid hormone is essential for brain development and children born to mothers that have insufficient thyroid hormone also have increased risk of autism spectrum disorder and IQ loss. Thyroid hormone signalling and numerous thyroid hormone dependent genes were disrupted by the mixture in the different models tested. These findings reveal a mechanism whereby brain development is affected by exposure to the chemicals at relevant human exposure levels.”

An overarching conclusion from the EDC-MixRisk project is that current regulations of man-made chemicals systematically underestimate health risks associated with combined exposures to EDCs or potential EDCs.

EDC-MixRisk is launching a Policy Brief which is including key results, overarching conclusions and future needs as well as some further project highlights as part of the workshop, The Chemical Cocktail Challenge, at Thon Hotel EU, Brussels, on Tuesday March 26th. The workshop is organized jointly with the EuroMix project, highlighting the main results and conclusions from the two H2020-funded projects, EDC-MixRisk and EuroMix, and their implications for future needs for chemical mixture risk assessment.

Further information:

EDC-MixRisk Policy Brief

Media contacts:

Prof. Åke Bergman, Coordinator of EDC-MixRisk,
ake.bergman@aces.su.se, Tel: +46 70 644 3861

Ass. Prof. Joëlle Rüegg, Vice-Coordinator of EDC-MixRisk
joelle.ruegg@ki.se, Tel: +46 73 712 1592

Short facts about EDC-MixRisk:

The project focuses on the effects of mixtures of endocrine-disrupting chemicals on children – with the ultimate aim of promoting safer use of chemicals.

Full name: “Integrating Epidemiology and Experimental Biology to Improve Risk Assessment of Exposure to Mixtures of Endocrine Disruptive Compounds — EDC-MixRisk”

Project period: from 2015-05-01 to 2019-05-01

Funding: EU H2020 project, EC contribution EUR 6 223 330, Grant agreement No 634880

Website: https://edcmixrisk.ki.se/


The EU-funded EDC-MixRisk research project has studied the effects of prenatal exposure to mixtures of suspected EDCs on development and health in children. The project has developed a novel whole mixture approach integrating epidemiology and experimental biology to improve risk assessment strategies for endocrine disrupting chemicals (EDCs) in mixtures.

The EDC-MixRisk approach and key results will be presented and discussed during the final scientific conference which will take place 27 March 2019 in Brussels, Belgium (DG RTD).

The conference aims at bringing together researchers and experts working in the field of endocrine disruptors and chemical mixtures to discuss the scientific results generated within the EDC-MixRisk project and the implications thereof.

The conference will be preceded by a joint stakeholder workshop “The Chemical Cocktail Challenge”, organized by EDC-MixRisk and EuroMix projects in Brussels, 26 March 2019. You may register for the meeting(s) via a single registration system:
https://matisevents.com/edc-mixrisk-and-euromix/

Deadline for the registration is 18 February 2019. The on-line registration is compulsory for all participants (NB! limited number of seats).

A draft programme of the EDC-MixRisk conference is available here.
Contact: Elina Drakvik, Project and Communications Manager, elina.drakvik@ki.se


We are pleased to invite you to register to our Joint Stakeholder Workshop entitled “Chemical Cocktail Challenge”, 26 March 2019 in Brussels, Belgium.

This is a workshop on results and conclusions from the two H2020-funded projects, EDC-MixRisk and EuroMix, and their implications for future needs for chemical mixture risk assessment”. The workshop will take place at Thon Hotel EU (address: Rue de la Loi 75) Brussels, 26 March 2019.

The meeting is organized jointly by two EU Horizon 2020 research projects working on chemical mixtures i.e. EDC-MixRisk, coordinated by Karolinska Institutet (KI) in Sweden and EuroMix, coordinated by the Netherlands National Institute for Public Health and the Environment (RIVM).

The workshop is aimed at gathering key scientists, researchers, policy makers, and stakeholders from authorities, industry and civil society. Both projects, EDC-MixRisk and EuroMix, will present key results and demonstrate new tools and approaches for risk assessment of combined exposure to multiple chemicals (mixtures) and how these could benefit future European food and chemical safety policy.

The morning part of the stakeholder workshop will focus on presenting and discussing the key results of both projects and stakeholder perspectives in a joint plenary, whereas the afternoon sessions will showcase and discuss the new approaches and tools from each of these projects. We cordially invite you to a joint dinner, in the evening of 26 March, at the restaurant Atelier 29 which is located next to the conference venue. The dinner will be at own expense.

The joint stakeholder workshop will be followed by project-specific stakeholder/scientific workshops in Brussels, 27 March 2019. Both these events are open for registration as well.

Registration
The draft programmes of all the three meetings and further details are available on the registration website. Please register for the meeting(s) through our single registration system: https://matisevents.com/edc-mixrisk-and-euromix/

Deadline for registration is 18 February 2019. The on-line registration is compulsory for all participants. Please note: registration does not guarantee participation since it is subject to availability of seats.

Click here for the invitation and further information.

 

 

 


Meet our EDC-MixRisk scientists and learn more about the work they are doing. This time in the spotlight is Barbara Demeneix, Professor at the French National Museum of Natural History. She is an internationally recognized expert on thyroid function and endocrine disruption. In the EDC-MixRisk project, her group studies how chemical mixtures affect thyroid hormone signalling. She is also the work package leader of WP4 on identification of molecular initiating events.

Hi Barbara – What are you and your research group studying in the project?

We are using an amphibian embryo to study how the different chemical mixtures affect thyroid hormone signalling. We have known for decades that thyroid hormone is essential for brain development in all vertebrates. This is why all babies born today are tested in the first few days after birth to check that they have sufficiently thyroid hormone to ensure proper brain development. More recently, we have learned from epidemiological studies that during pregnancy, especially the first few months, a mother’s thyroid hormone levels are associated with the developing child’s IQ and even the structure of their brain.

We also know that children who were born before universal screening for thyroid hormone at birth and who were not diagnosed as lacking thyroid hormone could become cretins. Such unfortunate children had very low IQs but also were small in height. This pathology was one of the first examples of the integrating role of thyroid hormone in coordinating growth and brain development, both before and after birth.

This is why we focus on the thyroid axis and how the maternal exposures found in EDC-MixRisk affect thyroid signalling. We use the frog tadpole because thyroid hormone has been conserved through 450 million years of evolution! It is exactly the same molecule in fish, amphibians, reptiles, birds, mammals – including us humans!

As tadpoles are virtually transparent, we could take the advantage of this feature in our research. We created a new line of tadpoles with a fluorescent protein under the control of thyroid-responsive gene. These tadpoles change their light emission (fluorescence) up if there is a problem with thyroid hormone signalling, making screening of chemicals and mixtures faster and easier.

What have you discovered so far?

In the beginning of the project, epidemiological data from the Swedish SELMA pregnancy cohort was used to establish relevant mixtures to be tested in the various animal and cell models and to address the three health domains (neurodevelopment, metabolism and growth, and sexual development). Many of the chemicals that were identified both in the mixture associated with language delay and the mixture associated with low birth weight are known to affect thyroid hormone signalling. This is the case for some of the phthalates and perfluorinated compounds found in the low birth weight and language delay mixtures. Also triclosan (in the low birth weight mixture) is a well characterized thyroid hormone disruptor.

Both of the mixtures (low birth weight and language delay) significantly affected thyroid hormone signalling at environmentally relevant, human exposure levels! In addition, we showed that the mixtures affected expression of key genes in the brain and slowed down tadpole behaviour.

Importantly, researchers working on other (cell and animal) models within the project also showed that thyroid hormone dependent genes were modified after exposure to the mixtures. This further strengthens the generalizability of our results.

We consider that thyroid signalling during early pregnancy is particularly vulnerable to endocrine disruption and can affect both brain development and birth weight.

What are the potential implications of your findings?

We have found that the mixtures are harmful at the levels found in mothers of the SELMA study. So some of these substances should be clearly banned from the market. Also, the combined exposures and mixture effects should be better considered in regulatory arenas.

In this sense, the implications of our findings are very much linked to the project’s expected outcomes in the end. We want to first, assess risk and second, be able to recommend new approaches as well as policy proposals for decision-makers and regulators in Europe to improve the current situation.


A joint stakeholder workshop entitled “the Chemical Cocktail Challenge”, will be held by the two H2020-funded projects, EDC-MixRisk & EuroMix, in Brussels on March 26, 2019.

The event will serve as the final conference of the two successful EU projects, EDC-MixRisk and EuroMix, bringing together key scientists, researchers, policy makers, and stakeholders from authorities, industry and civil society. Both projects will present key results and demonstrate new tools and approaches for risk assessment of combined exposure to multiple chemicals (mixtures) and how these could benefit future European food and chemical safety policy.

The Chemical Cocktail Challenge stakeholder workshop will be followed by project-specific stakeholder meetings on March 27, 2019.

Registration for public to both events will open later & more details will follow in due course.


EDC-MixRisk will organize its Steering Committee meeting in Helsinki 3-4 December. The meeting will be hosted by the Finnish project partner, the National Institute of Health and Welfare (THL), and it will gather the Principal Investigators to discuss the overall progress and highlight the key results generated within the project.

The purpose of the meeting is to present and discuss the key findings so far and to review the status of the agreed tasks. Furthermore, the meeting will facilitate coordinating the work for the remaining period, and it will provide a great forum for discussing and identifying the best strategies and solutions to deliver the expected outputs and outcomes towards the end of the project.



EU-funded EDC-MixRisk Project Highlights Importance of Considering Combined Exposure to Multiple Chemicals

19 Sep 2018

We are exposed to multiple man-made chemicals from various sources. The EDC-MixRisk research project, coordinated by Karolinska Institutet, Swetox, emphasizes the need to address the effects of chemicals as mixtures in order not to underestimate the risks they pose. The current risk assessment paradigm seems to be falling short as it is largely based on considering one chemical at a time.

The EDC-MixRisk research project studies the effects of endocrine-disrupting chemicals (EDCs), focusing on EDC-mixtures and their effects on the developing foetus. Endocrine disruptors are chemicals that interfere with our hormonal system, and they have been linked to various diseases and disorders, e.g., infertility, cancer, obesity and impaired neurodevelopment.

EDCs are ubiquitous contaminants in our environment as they can be found in everyday products, such as in plastic bottles, toys, cosmetics, electronics, textiles and even in food as pesticide residues and as additives in food contact materials. The chemicals used in various products and materials leak and migrate to the environment reaching also us, human beings.

“To study effects of these chemicals in mixtures, we used real-life exposure data from the Swedish SELMA pregnancy cohort to see which chemicals the mothers and their children were exposed to, and identified EDC mixtures in prenatal urine and blood that were associated with adverse health outcomes in the children as a first step,” explains Carl-Gustaf Bornehag, Professor in Public Health Sciences at Karlstad University, Sweden.

“Based on the chemicals measured in mothers’ serum and urine, we established reference chemical mixtures in the project. They were then tested in experimental models for potential adverse effects in terms of growth and metabolism, neurodevelopment and sexual development,” he continues.

“We observed clear effects on behavior, metabolism, and development in cell and animal models,” says Joëlle Rüegg, Associate Professor at Karolinska Institutet, Sweden and Vice-Coordinator of EDC-MixRisk project.  “We also identified common molecular targets of these mixtures, for example the thyroid hormone signaling pathway. As proper levels of thyroid hormone are essential for foetal development, interference can lead to increased susceptibility to diseases later in life,” she explains.

“We also tested selected single chemicals and compared their effects to the mixtures. In most cases, the single substances did not have an effect at concentrations comparable to the mixtures,” she adds. This points to the importance of assessing mixture effects which are often overlooked, although evidence from research is mounting.

Finally, novel approaches for a more systematic risk assessment are being developed in the project to find better models for addressing mixture effects on human health. One of the key findings by EDC-MixRisk researchers underscores that the regulatory guideline values for various single chemicals should be lower than the current ones because of the combination effects. The results suggest that the currently used chemical-by-chemical approaches underestimate risk by a factor that ranges from 1 to 100 for different chemicals. An article describing these findings was recently published in Environment International.

“We have to intensify our efforts in order to increase our understanding and most important of all, to take proper approaches and strategies that will reduce the harm and risks to human health and environment from these hazardous mixtures,” concludes Dr. Rüegg.

EDC-MixRisk has received funding from the European Union’s Horizon 2020 research and innovation programme. It has been highlighted as a success story among EU-funded research projects.

Watch a short video about the EDC-MixRisk Project here.

Media contacts:

Joëlle Rüegg,
Vice-Coordinator of EDC-MixRisk, Associate Professor
Karolinska Institutet, Swetox & Institute for Environmental Medicine, Sweden
joelle.ruegg@ki.se, Tel: +46 73 712 1592

Carl-Gustaf Bornehag
Professor, Karlstad University, Sweden and
Icahn School of Medicine at Mount Sinai, New York City, USA
carl-gustaf.bornehag@kau.se, Tel: +46 70 586 6565

Elina Drakvik,
Project and Communications Manager,
EDC-MixRisk Coordination Office
Karolinska Institutet, Swetox, Sweden
elina.drakvik@ki.se, Tel: +46 76 239 4813

 

Further information

About EDC-MixRisk: The project focuses on the effects of mixtures of endocrine-disrupting chemicals on children – with the ultimate aim of promoting safer use of chemicals.

Full name: “Integrating Epidemiology and Experimental Biology to Improve Risk Assessment of Exposure to Mixtures of Endocrine Disruptive Compounds — EDC-MixRisk”

Project period: from 2015-05-01 to 2019-05-01

Funding: EC contribution EUR 6 223 330, Grant agreement No 634880

Website: https://edcmixrisk.ki.se/

 

Recent publication by EDC-MixRisk researchers:

Gennings, C., et al. “Incorporating Regulatory Guideline Values In Analysis Of Epidemiology Data”, Env. Int. 120 (2018)

 

Overview of mixture research activities at EU-level:

Bopp, S., et al. “Current EU research activities on combined exposure to multiple chemicals”, Env. Int. 120 (2018)

 


A joint article “Current EU research activities on combined exposure to multiple chemicals” was recently published in Environment International by experts from the five EU-funded research projects, i.e. EDC-MixRisk, EuroMix, EU-ToxRisk, HBM4EU and SOLUTIONS, and European Commission Services and EU Agencies. The paper aims to map current progress, gaps and remaining challenges for the assessment of chemical mixtures.

The paper provides an overview of the various research projects’ activities, as well as the activities of European Food Safety Authority and Joint Research Centre in the area of mixture risk assessment. It describes how the ongoing projects and initiatives are bringing new knowledge and developing tools and approaches for facilitating and improving mixture risk assessment.

In addition, the paper highlights that despite the progress in the area and increased knowledge for taking combined exposures into account, several gaps prevail. These gaps are especially linked to lack of data on toxicological properties of chemical substances and realistic co-exposure scenarios hampering thus the efforts for carrying out proper mixture risk assessment.

Furthermore, different uses and different types of chemicals are regulated by different agencies and sectors, which is hindering the cross-talk and more holistic considerations of unintentional mixtures.

The paper concludes that more harmonised approaches are needed in order to make progress in combined exposure and combination effects of multiple chemicals. The needs for harmonization range from terminology, grouping, data formats, and methodology to the harmonization of regulatory approaches. Also legislative requirements are brought up in the paper.

Further information:

Bopp, S., et al. (2018):
Current EU research activities on combined exposure to multiple chemicals”,
Environment International. Vol. 120. Pages 544-562.
doi.org/10.1016/j.envint.2018.07.037