Thresholds and Endocrine Disruptors: An Endocrine Society Policy Perspective

Journal of the Endocrine Society
From Barbara Demeneix, Laura N Vandenberg, Richard Ivell and R Thomas Zoeller

07/09/2020

Abstract

The concept of a threshold of adversity in toxicology is neither provable nor disprovable. As such, it is not a scientific question but a theoretical one. Yet, the belief in thresholds has led to traditional ways of interpreting data derived from regulatory guideline studies of the toxicity of chemicals. This includes, for example, the use of standard “uncertainty factors” when a “No Adverse Effect Level” (or similar “benchmark dose”) is either observed, or not observed.

In the context of endocrine-disrupting chemicals (EDCs), this approach is demonstrably inappropriate. First, the efficacy of a hormone on different endpoints can vary by several orders of magnitude. This feature of hormone action also applies to EDCs that can interfere with that hormone. For this reason, we argue that the choice of endpoint for use in regulation is critical, but note that guideline studies were not designed with this in mind.

Second, the biological events controlled by hormones in development not only change as development proceeds but are different from events controlled by hormones in the adult. Again, guideline endpoints were also not designed with this in mind, especially since the events controlled by hormones can be both temporally and spatially specific. The Endocrine Society has laid out this logic over several years and in several publications. Rather than being extreme views, they represent what is known about hormones and the chemicals that can interfere with them.

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European strategy aims to rein in EDC exposures

Endocrine Today
From Regina Schaffer

10/28/2020

@Pixabay

The European Commission this month unveiled their new chemicals strategy for sustainability, designed to protect the public from exposure to endocrine-disrupting chemicals and their health effects.

The chemicals strategy, part of the European Green Deal, is designed to be the foundation for the biggest update to Europe’s chemical regulations in more than a decade. The chemical strategy commits to a hazard identification for EDCs, including strict measures to prevent their use in consumer products. The strategy also calls for stricter data requirements for EDCs across all relevant legislation and to accelerate the development and adoption of better test methods. In a statement, the Endocrine Society praised the new strategy, and urged “further details and concrete actions” to protect public health.

Healio spoke with Barbara Demeneix, PhD, DSc, chair of the Endocrine Society’s EDC advisory group, about the latest push in Europe to assess EDCs, the risks of combination chemicals and how endocrinologists can become better advocates to rein in EDC use in the United States.

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Ammonium nitrate and iodine: a look back at the explosive history of two essential substances

The Conversation
From Barbara Demeneix

@Pixabay

The horrific explosion that devastated Beirut on August 4, 2020, has receded, but the physical damage and human distress persists. Reports indicate that fireworks were also stored in the same warehouse as the fertiliser and could sparked the larger, more deadly explosion of the fertilizer.

The two faces of ammonium nitrate

Nitrogen makes up 78% of the atmosphere and is chemically and biologically inert. However, in 1908 the chemist Fritz Haber discovered that nitrogen could be fixed chemically as ammonium nitrate. As a German patriot, Haber was also interested in Germany’s preparation for what would become World War I. A problem was that the methods Haber used could not be scaled up for industrial production. It was a fellow German, Carl Bosch, who perfected the industrialisation of the method in 1913, a year before the war’s start.

Haber and Bosch were both awarded Nobel prizes for their work – Haber in 1918 and Bosch in 1931. The prizes were instituted by Alfred Nobel, who financed the prizes thanks to his patents for the explosives dynamite and gelignite. Like other explosives, these comprise a molecular mix that releases energy suddenly, most often accompanied by the production of heat, light, gases, pressure and deafening sound.

In his Nobel acceptance speech, Haber acknowledged only that his discovery would help feed the world by improving soil fertility with ammonia. And there is no doubt that it did – populations have more than tripled since then. However, the speech did not mention his the main motivation for his work, Germany’s war effort. Haber also contributed to that effort with the production of chlorine gas. What is more, Haber almost certainly did not anticipate the implications of his discovery for fixing ammonia for its contribution to climate change.

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Is the Observed Decrease in Body Temperature During Industrialization Due to Thyroid Hormone-Dependent Thermoregulation Disruption?

Frontiers in Endocrinology
From Pieter Vancamp and Barbara Demeneix

@Pixabay

Protsiv et al. used three sets of data to demonstrate that human core body temperature had decreased by 0.03°C per decade since the industrial revolution in the US (1). They proposed that a 1.6% temperature drop over a period of almost 200 birth years had occurred. Anthropometrics, gender, or race were excluded as potential factors. The authors postulated that the principle contributor to this reduction was reduced inflammation, reflecting better, healthier environments and improved hygiene measures (1). Although hygiene has increased and hence reduced death from infectious disease, other factors in our environment have also changed significantly. Here we propose another plausible and potentially testable mechanism, that of the contribution of factors interfering with thyroid hormone (TH) metabolism.

TH is an essential physiological cue that acts at central and peripheral levels to affect internal temperature in endotherms (2). Humans strive to live at thermoneutral conditions, in which peripheral muscle metabolism generates sufficient heat as a by-product to maintain temperature without the need for additional heat-generating mechanisms (3). For us, the resting metabolic rate (RMR) is thus a crude proxy for core body temperature. TH directly affects the RMR by altering mitochondrial biogenesis and oxidative phosphorylation via TRα1, the principle TH receptor isoform in muscle (Figure 1) (4). TH fluctuations within the normal range alter the RMR in humans (56), suggesting that subtle changes in TH homeostasis could have consequences for body temperature. Recent data indicate that TH also safeguards core body temperature at the central level. 

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Endocrine News Podcast 23 : EDCs and the EU

Endocrine News Podcast
By Caitlin R. Ondracek

edcnews

Caitlin talks about the European Union’s recent resolution on endocrine-disrupting chemicals. She is joined by Rémy Slama, PhD, an environmental epidemiologist and senior investigator at INSERM, France’s National Institute of Health and Medical Research, and Barbara Demeneix, PhD, professor in the Comparative Physiology Laboratory within the Natural History Museum in Paris.

>> Listen to the podcast

Eye on France: Children clobbered by chlorpyrifos!

RFI English
Michael Fitzpatrick

After glyphosate, the cancer-inducing weedkiller, the French papers look at chlorpyrifos, a commonly used pesticide suspected of pillaging our children’s IQs.

Chlorpyrifos is a pesticide which has been sprayed on European farms for the past half century, despite a staggering weight of scientific evidence suggesting that exposure to the stuff dramatically reduces the IQ of children. It also kills greenfly and caterpillars, which is why farmers like it so much.

Unfortunately, chlorpyrifos survives on our spinach leaves, lettuce, potatoes and oranges. It is to be found in our kids’ urine, and in the umbilical cords of pregnant women.  Since 1965, evidence has been accumulating that this neurotoxin causes irreversible brain damage in youngsters, knocking 13 million points off the IQ of Europe’s children every year, and causing nearly 60,000 cases of mental deficiency.

 

Chlorpyrifos – Barbara Demeneix: “Detrimental effects on IQ”

Investigative Reporting Denmark
Stéphane Horel

©Investigative Reporting Denmark 

The Cross-border investigation on chlorpyrifos was initiated by Investigative Reporting Denmark and Danwatch, and made in collaboration with journalists from Knack in Belgium, Le Monde in France, Dagbladet in Norway, Newsweek in Poland, Ostro in Slovenia, El Confidential in Spain and The Midwest Center for Investigative Reporting in US. The investigation was supported by Journalismfund.eu.

Barbara Demeneix : “Detrimental effects on IQ”

“The scientific evidence clearly shows that prenatal exposure to chlorpyrifos has detrimental effects on IQ and brain cortex thickness. Chlorpyrifos is toxic for the central nervous system, i.e. neurotoxic, and it is an endocrine disruptor, notably of thyroid signalling. Chlorpyrifos can thus interfere with brain development.”

“In 2012, it was shown that brain cortex thickness is significantly reduced as a result of prenatal chlorpyrifos exposure. Recently, French researcher Vincent Laudet has demonstrated unequivocally that chlorpyrifos is a thyroid disrupting chemicals. One can wonder why it has not already been banned.”

>> Read more

>> Read the Cross-border investigation

Is air pollution ruining your memory?

The Telegraph
By Harry de Quetteville

air pollution.jpg

©Pixabay

I have a little gadget on my kitchen shelf. It measures levels of a particle known as PM2.5 – the tiny, invisible, sooty bits of combustion that are key culprits in the air pollution health crisis.

Produced by diesel and petrol fumes, log burners and even conventional ovens, PM2.5s are small enough to make it deep into the lungs and from there into the bloodstream. They’ve been linked to diseases ranging from cancer to high blood pressure and, as the World Health Organisation (WHO) puts it, “increased mortality or morbidity”.

When I pop two slices of bread into the toaster for my six and four year old, the monitor goes bananas. The PM count in micrograms per cubic metre races up from 9 or 10 into the hundreds.

« “There’s so much data on air pollution on working memory and your capacity to think. […] It’s not just traffic. All volatile compounds, like pesticides found in rural areas, can be included.” Barbara Demeneix

>> Read the article

Endocrine disruptors drop the curtain on this European Parliament

EURACTIV
Par Gerardo Fortuna

Plenary Session © European Union 2019 – Source : EP – Marc DOSSMANN

On Thursday (18 April), the European Parliament adopted a non-binding resolution asking the European Commission to ensure a higher level of protection against endocrine disruptors (EDCs) by making a legislative proposal on the matter no later than June 2020.

It passed with 447 votes in favour, 14 against and 41 abstentions, and was actually the last text to be dealt with by this Parliament.

MEPs proposed treating EDCs or potential EDCs on an equal footing with substances classified as carcinogenic, mutagenic or toxic for reproduction, the so-called CMR substances prohibited in EU cosmetics legislation.

>> Read the full article

Endocrine Society Commends European Parliament’s EDC Resolution

Endocrine News

The Endocrine Society praised the European Parliament’s resolution calling for greater European Union action to regulate endocrine-disrupting chemicals (EDCs) that pose a serious threat to the health of current and future generations.

The resolution was adopted Thursday by an overwhelming cross-party majority during the final voting session of the current Parliament’s term and affirms the European Parliament’s commitment to shield the public from exposure to EDCs.

The Society has spent years pressing for science-based regulation of these chemicals, which mimic, block or otherwise interfere with the body’s hormones. EDCs are commonly found throughout our environment in children’s products, food containers, personal care products, pesticides and furniture.

The resolution directs the European Commission to propose legislation to regulate EDCs in toys and cosmetics and to update the regulations governing EDCs in food contact materials by June 2020. It emphasizes that EDCs pose a similar public health threat as carcinogens, substances that cause genetic mutations and reproductive toxins, and concludes that EDCs should be regulated in the same manner by the European Union.

>> Read the full article

Health risks associated with mixtures of man-made chemicals are underestimated

EDC-Mix risk

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, 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.

>> Read the EDC-MixRisk press release

Publication of the report “Endocrine Disruptors: From Scientific Evidence to Human Health Protection”

European Parliament – PETI Committee

Rapport Parlement européenThis study, commissioned by the PETI Committee of the European Parliament, presents the scientific knowledge regarding the health effects of endocrine disruptors, a class of hazards recognized in EU regulation since 1999. This report reviews the scientific evidence regarding the concept of endocrine disruption, the extent of exposure, associated health effects and costs. The existing relevant EU regulations are discussed and recommendations made to better protect human health.

 

 

Authors : Barbara DEMENEIX, PhD, UMR 7221 CNRS/MNHN, Muséum National d’Histoire Naturelle, Paris, France. Rémy SLAMA, PhD, Senior Investigator, INSERM (National Institute of Health and Medical Research), IAB Research Center, Team of Environmental Epidemiology, Grenoble, France.

>> Read the full report

Spetses Summer School 2019: applications open

spetses_2019

Our summer school aims at providing a unique meeting opportunity for young scientists (PhD students and postdocs) in the broader fields of epigenomics and nuclear receptor signaling, and in particular to cross-fertilize the fields in order to better understand diseases. Epigenomics can be described as the integrated study of components and mechanisms that regulate gene expression under physiological and pathophysiological conditions. Nuclear receptors are significant drug targets and todays best-studied signal-responsive transcription factors that in response to environmental and nutritional inputs modulate or even trigger epigenome alterations towards disease. Renowned lecturers and discussion leaders will introduce the current concepts and methodologies along with key components. This is followed by in-depth discussions of mechanisms and alterations underlying metabolic, inflammatory and proliferative diseases as well as ageing. Our course program is designed to actively encourage multiple student activities and networking during workshops, tutorial lunches and dinners, poster sessions and individual discussions every day, thereby stimulating the scientific dialogue and creating a familiar and inspiring atmosphere. All students and lecturers will stay at the Spetses Hotel offering idyllic surroundings, modern meeting facilities, excellent possibilities for recreation and exploration of Greek culture, bars and restaurants. Welcome to join us!

>> Application portal and information

Organizer:
Eckardt Treuter (Karolinska Institutet, Stockholm, Sweden)
Co-organizers:
Barbara Demeneix (CNRS, Muséum National d’Histoire Naturelle, Paris, France)
Karen Knudsen (Thomas Jefferson University, Philadelphia, USA)

Application deadline: May 6, 2019

Project EDC-MixRisk: In focus – Dr. Barbara Demeneix

EDC-Mix risk

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. 

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.

>> Read more