Some potential endocrine disruptors alter ovarian function and may contribute to female infertility

A new study from FREIA, published in Environmental Research, explored the association between potential endocrine disrupting chemicals (EDCs) and female fertility in women attending fertility clinics in Sweden and Estonia.

Up to 1 in 6 women experience difficulties becoming pregnant or carrying pregnancy to term. Despite the increasing use of assisted reproductive technologies (ART), the success rates of these treatments remained the same.

Ovarian disorders are the cause for infertility in about 1 in 4 couples. The ovaries play an important role in hormone production and formation of oocytes (“eggs”). It is therefore reasonable to assume that human-made chemicals that disrupt the hormone system, i.e. endocrine disrupting chemicals or EDCs, contribute to the rates of infertility.

In this FREIA study, levels of 59 known and suspected EDCs were analysed in follicular fluid, the biological fluid surrounding oocytes, of 185 Swedish women and 148 Estonian women undergoing fertility treatment. Multiple chemicals were detected in all follicular fluids. In >90% of the follicular fluids, 3 metabolites of the phthalate DEHP, methylparaben, and 6 PFAS (PFOS, PFOA, PFHxS, PFUnDA, PFNA and PFDA) were detected and used to link with female fertility parameters.

The ovaries of women with higher levels of DEHP, methylparaben and possibly PFUnDA and PFOA responded less to fertility treatment, established by calculating the ovarian sensitivity index (OSI). There were indications that some PFAS lowered the success of fertility treatment, determined by chance of establishing a pregnancy or live birth.

Overall, this study provides additional evidence that DEHP can negatively influence female fertility. In addition, several other chemicals, i.e. methylparaben and some PFAS, were identified that may harm ovarian function and contribute to female infertility.

This study adds to the increasing evidence that EDCs can contribute to female infertility and warrants interventions to lower exposures.

Endocrine disruptors should not be assessed individually

Six chemical substances possess endocrine disrupting effects – and especially combination effects when they are assessed together. Force Technology, DHI and researchers from FREIA partners at the DTU National Food Institute have performed risk assessments for the Danish Environmental Protection Agency.

Force Technology, together with DHI and researchers at the DTU National Food Institute, has evaluated six chemical substances for their risk of exerting endocrine disrupting effect.
The six substances were:

  • Butylhydroxyanisole (BHA),
  • Butylhydroxytoluene (BHT),
  • Butyl paraben,
  • Propyl paraben,
  • Octamethylcyclotetrasiloxane (D4),
  • Bisphenol A (BPA),

The risk assessment shows that exposure to the substances individually does not constitute a risk, but that the total exposure can be a cause for concern. This conclusion is based on recent exposure assessments for the six substances, as well as a hazard assessment of the substances’ endocrine disrupting properties.

The hazard assessment shows evidence that all substances have endocrine disrupting effects. However, the evidence is stronger for some of the substances (D4, BPA, butylparaben, propylparaben) than for others (BHA and BHT).

Endocrine disruptors are suspected to contribute to the increasing incidence rate of, for example, genital malformations, reduced fertility, the development of obesity and diabetes and compromised brain development. The substances can be found in a wide range of consumer products, including foods, food contact materials and medicines.

It is not enough to evaluate chemicals individually

In recent years several major research projects at the DTU National Food Institute have shown that combination effects of endocrine disruptors exist, and that these should be taken into account when risk assessing chemicals.

If you only evaluate the substances one at a time, you will underestimate the overall risk of endocrine disrupting effects. Therefore, the risk of the combined exposure from several different chemical substances from several different sources was assessed in this project.

Threshold value or not?

In EU it has been discussed in recent years whether or not there is a threshold value for lower effect of endocrine disruptors. It is possible that, as with carcinogens, there is no lower limit for endocrine disrupting effects. The calculations in the report were therefore made both with and without assumption of threshold values.

Read more

NOTE: this message was copied from the DTU website. The original message (posted 28 June 2022) can be found here.

Why Plastic?, We The Guinea Pigs

“We the Guinea Pigs” investigates why we are still constantly – and increasingly – exposed to dangerous chemicals through our plastic use, even though researchers have warned us about the potential adverse health effects for decades. Some of the most cutting edge scientific findings on how plastic harms our health come from Danish researchers Terje Svingen and Hanna Johansson.

A recent study conducted in Denmark has revealed how endocrine disrupting chemicals affect the female reproductive system. It shows that female rats exposed to endocrine disruptors during early development end up with fewer eggs in their ovaries and are at risk of losing their ability to reproduce at an earlier age. For some time researchers have known that plastic has a negative impact on men’s sperm count. Are we involuntary participants in an enormous experiment, threatening the health of millions of people – maybe even mankind as such?

As the use of plastic has gained ground in our lives over the years, there has been an inexplicable increase in a number of diseases and disorders amongst the population. In this film as part of the Why Plastic? series, the BBC meets leading researchers looking into the reasons for these disorders and follow case studies of people suffering from various health conditions thought to be caused by exposure to certain every day materials including plastic. Are these people the victims of unfortunate coincidences – or is there an explanation?

View the episode here.

A pragmatic way forward in chemical safety assessment

In a recent paper, FREIA partners Terje Svingen (DTU) and Pauliina Damdimopoulou (KI) propose an approach to speed up the development and acceptance of mechanistic descriptions that are used by chemical safety assessors and regulators.

Adverse Outcome Pathways (AOPs) are a way to organise scientific knowledge and describe how a stressor – such as exposure to an endocrine disrupting chemical – can lead to a harmful health effect through a chain of linked events. The use of AOPs is gaining wide acceptance and will help to support chemical safety assessors and regulators.

Yet, only a few AOPs are thoroughly evaluated and endorsed by the Organisation for Economic Co-operation and Development (OECD), which clearly hampers their regulatory use. A major hurdle is the immense amount of work that has to be put into the development of an AOP. “Putting together the information for one key event relationship (the link between two sequential events in an AOP – red.) took me about three months altogether”, explains Eleftheria Panagiotou, PhD student involved in this work.

“We propose to focus more on smaller building blocks and rely more on existing common knowledge”, says lead author Terje Svingen. The approach will make it more attractive for scientists to contribute to AOPs, because in this way, they can focus on their own expertise and don’t have to be an expert on all facets of an AOP from molecular interactions to health effects.

Moreover, a description of a smaller AOP building block makes an excellent paper to be submitted for peer-review. Besides the scientific merit, publishing the building blocks has the added advantage that external peer-reviewers have already critically evaluated the information. This may stimulate faster endorsement of AOPs by the OECD. “It is our hope that our proposed approach will increase the pace at which the AOP knowledge base is populated with endorsed AOPs, which will certainly improve chemical safety assessment processes.”, according to the authors of this paper.

Reference

Terje Svingen, Daniel L. Villeneuve, Dries Knapen, Eleftheria Maria Panagiotou, Monica Kam Draskau, Pauliina Damdimopoulou, Jason M O’Brien. A pragmatic approach to Adverse Outcome Pathway (AOP) development and evaluation. Toxicological Sciences, kfab113, https://doi.org/10.1093/toxsci/kfab113 Published: 17 September 2021

Join the second FREIA webinar

EDC IDENTIFICATION: HOW DOES IT WORK?

27 October 2020, 15PM in Brussels.

In 2018, the European Commission adopted criteria to assess whether a biocide or pesticide is an endocrine disruptor. A guidance document was written on how to do this in practice. FREIA partner Julie Boberg (Technical University of Denmark) will explain the process of ED identification, using butylparaben as an example. 

Butylparaben is often used in cosmetics to prevent microbial growth. It is on the candidate list of substances of very high concern of the European Chemicals Agency for its endocrine disrupting properties.

Not only will Dr Boberg show that butylparaben has more negative effects on reproduction than previously thought. It is also a great example that current criteria and EDC identification tools may also be suitable for other chemical regulations.

This webinar is organised by the FREIA project, with support from the Health and Environment Alliance (HEAL). Participation is free. For more details, please contact info@freiaproject.eu

Participation is free. You can register here.