Décryptage
Photo: Bertrand Guay / AFP

Understanding endocrine disruptors

Endocrine disruptors are being blamed for a wide range of problems nowadays, even if an exact causal link is difficult to prove. Explanation.

Endocrine disruptors can be found throughout our environment in the form of micropollution. These substances can interfere with the hormonal systems of a number of species and ultimately end up in our own food chain. They are even in the products and containers that fill our closets and bathroom drawers. Because these compounds are so diverse, they can be hard to evaluate using toxicological tests and protocols – so much so that scientists struggle to even identify them. Read on for an in-depth look at substances that are making us question the way we use products created with industrially-synthesised chemicals.

Fragile signalling pathways

An endocrine disruptor is “an exogenous substance or mixture that alters functions of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or entire sub-populations,” according to the definition of the World Health Organization published in 2002. In order to understand how these disruptors work, it’s important to first know how the endocrine system functions.

Our organs have to communicate with each other to work properly. They do so via two major transmission pathways – the nervous system and the endocrine system. The second is made up of organs, called endocrine glands, which secrete hormones into the bloodstream that are then carried to distant organs. These glands include the hypothalamus, adrenal glands, thyroid, ovaries and testicles. However, that’s not all that the endocrine system entails. Cells distributed throughout our organs have endocrine properties as well. The pancreas, stomach and placenta are just a few examples. To top it off, these two signalling pathways are interconnected. As a result, there are many opportunities for disruption. Because all our vital functions depend on our hormones, which regulate our development, sexual differentiation, behaviour, and digestive and cardiovascular systems, endocrine disruptors can cause a large variety of adverse effects.

Unattainable proof

Scientists struggle to identify these disruptive substances, which makes it difficult to ban the products that might contain them.

Thierry Buclin, Head Physician of the Clinical Pharmacology Division at Lausanne University Hospital (CHUV), reports that around 900 substances have been classified as endocrine disruptors to date.

The first such chemicals were identified in the wake of environmental disasters. “They were discovered after amphibians, alligators and fish were observed to have changed sex in the United States,” explains Nathalie Chèvre, an environmental toxicologist at Lausanne University (UNIL). In the late 1990s, studies showed these anomalies were due to substances that had an oestrogen-like effect. Oestrogen is the female sexual hormone. Exposure resulted in the feminisation of males and ultimately led to sterility. However, for most of these substances, no causal link has been identified in humans. The relevant authorities recognised the potentially dangerous nature of this phenomenon and decided to ban them based on the precautionary principle.

Today, epidemiological data is more telling. Among men, average sperm counts, which measure fertility, are declining. “It has dropped by a third in the past fifty years,” says Thierry Buclin. These data don’t just pertain to fertility. Cancer, autism, early-onset puberty, diabetes and obesity are all on the rise. Some hypotheses regarding the cause of these pathologies point to endocrine disruptors, and the corresponding mechanisms have mostly been confirmed in laboratories. Because they haven’t been tested in humans, however, bans against these substances have been slow in coming.

Why are there so many barriers to regulation, while “in any other situation, when faced with such a broad range of indirect proof, the precautionary principle would be applied and the product controlled”? It’s difficult to obtain incontrovertible proof, explains the specialist, because the effect of endocrine disruptors must be demonstrated in the clinic, which means human testing. However, this would involve administering a potentially toxic molecule for several years, which is ethically unacceptable.

Toxicology put to the test

“In conventional toxicology, the dose determines the poisonous effect,” says Thierry Buclin. An active compound like an endocrine disruptor binds with its target receptor in a dose-response relationship, which means the compound has to reach a certain concentration in the body before a measurable effect can occur. Nathalie Chèvre points out that endocrine disruptors are present in minuscule amounts and involve millions of substances, including known compounds and their degradation products. Taken separately, the compounds are never abundant enough to reach toxic levels. “However, out of millions of substances, it’s likely there are several that affect the same target.” The expert goes on to say that by simply adding their concentrations, it’s possible to achieve a biologically active dose through what’s known as the cocktail effect.

Blends of endocrine disruptors present a difficult challenge. New analytical techniques, such as the one developed by the French company WatchFrog, appear promising. Rather than try to pinpoint the toxicity of any given substance, the company created a system that uses the larva of amphibians to determine if a solution is able to alter the test subject’s hormonal system.

“Our procedure uses the endocrine system of the larva as a sensor. The larvae carry a genetic marker that becomes fluorescent once disruption has occurred,” explains Gregory Lemkine, director of WatchFrog.

The technique is currently being tested by the Lausanne Water Authority.

No to substitution – yes to pragmatism

Once a substance is declared toxic, industrial manufacturing processes simply substitute it for something else. This was the case for polychlorinated biphenyl (PCB), which was once used as an electric insulator. When its harmful effects on reproduction were discovered, it was replaced by polybrominated diphenyl ethers (PBDE), which turned out to be just as toxic and were later substituted by organophosphates. These compounds were then shown to negatively impact neuronal development. As Nathalie Chèvre explains, “Substitution is not a useful way to fight endocrine disruptors”. From a public health perspective, it’s nearly impossible to say whether the observations that have been made so far are just the tip of a deadly iceberg or if the scope of the effect will remain limited. Without a consensus or formal proof regarding these substances, Thierry Buclin suggests the most practical way to move forward is to first target the largest sources of pollutants.

Before our internal communication networks become completely disrupted, our external communication organs can be used to shed light on the topic. Immediate risks stem from the substances we ingest, breathe in, or apply to our skin. Because endocrine disruptors act over the long term, the most at-risk populations include pregnant women, children and unborn babies. Care must be taken to avoid the main sources of these toxins, namely plastics, insecticides, wood varnish and lacquer, elective drugs, and especially cosmetics. ⁄

“FRIGHTENING PEOPLE ISN'T USEFUL”

For Nathalie Chèvre, an environmental toxicologist at the University of Lausanne, it’s important to explain the effect of repeated exposure to problematic substances.

What is the current state of legislation on endocrine disruptors?

Right now, it’s crucial – for both the industry and the protection of citizens – that we define these substances. On 4 July, Europe accepted a definition that only applies to chemicals that have been identified as endocrine disruptors. The text indicates that a clear causal relationship in humans must exist in order for a substance to be labelled an endocrine disruptor. NGOs are challenging this definition because such a link is impossible to determine for most substances. The law should also cover potential disruptors to be more effective.

What are the biggest polluters?

Humans and their day-to-day lifestyles are the largest source of pollution – not agriculture. For example, with respect to the medicines that can be found in Lake Geneva, the most abundant is metformin, an anti-diabetic used in humans. After the Lausanne marathon, a rise in anti-inflammatory medication is clearly measurable at water treatment plants.

What’s the best way to raise peoples’ awareness?

It’s a tough problem. It’s important to make people critical, but frightening them isn’t useful. Fear makes people paranoid or fatalistic. Both attitudes stop people from taking concrete action. The general public doesn’t understand the concept of doses – that’s where we should start the work of awareness-raising. Repeated exposure and the cumulative effect of the substances play a critical role. It’s best to avoid repeated behaviours. It’s better to stay out of the sun rather than slather yourself with sunscreen all summer long.



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Protest in front of a Parisian supermarket in March 2014 against the use of pesticides containing toxic substances.

Products containing the most endocrine disruptors

Plastics

Plastics contain several additives that are classified as endocrine disruptors. Phthalates are added to polyvinyl chloride (PVC) to make objects more flexible. Alkylphenols like bisphenol A make them transparent. They also contain flame retardants such as PCB, PPDE and organophosphates. Most of these compounds are carcinogenic and harmful to human reproduction. They can also cause behavioural disorders.

They don’t bond to plastic polymers and rub off upon contact. PET baby bottles, toys, pipes, packaging and bottles all contain these substances.

Pesticides

The updated European definition of endocrine disruptors now includes insecticides. Glyphosate, which is found in the Monsanto herbicide Roundup, appears to be carcinogenic. Pyrethroids, which represent 30% of insecticides in the world, might lead to an accelerated onset of puberty. In addition, the French government recently published an impressive list containing the names of around 1,500 biocides and phytosanitary products that could contain endocrine disruptors.

Cosmetics

Our bathrooms are home to 400 to 500 different chemical substances. Cosmetics are no exception and contain an impressive cocktail of known endocrine disruptors. For example, parabens have antibacterial and antimycotic properties and are used as preservatives in shampoos, creams, foaming products and toothpaste. They have been shown to cause decreased fertility in men and promote the growth of certain types of tumours. The UV filters used in creams and lotions are also detrimental to human reproduction. Phthalates (see Plastics) are in most perfumes.

Medicines

The active ingredients in some medications were created to deliberately disrupt the hormonal system for therapeutic reasons. This is especially the case for the contraceptive pill and its main ingredient, ethinylestradiol. It is ten times more powerful than female oestrogen and breaks down more slowly. It accumulates in the environment and eventually ends up in our diet. Most medications also use parabens as preservatives (see Cosmetics).