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Nov. 26, 2011Congress reports

Endocrine disruptors: a first sum up of the current scientific knowledge Add to my portfolio
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The 9th Congrès Parfums et Cosmétiques of the Cosmetic Valley (Conferences on Perfumes and Cosmetics), held in Chartres on 23 and 24 November 2011, is the time for professionals to look at the regulatory environment. A wide topic: the regulatory environment includes very different points, such as animal tests, the registration of raw materials on the European level, marketing claims, packaging ingredients or the sanitary and toxicological safety of products … Many of the topics regularly in the headlines of media have been talked about during two days; among them, endocrine disruptors.

Reading time : ~ 10 minutes

Endocrine disruptors, especially Bisphenol A, are said to be dangerous for the human health, in our food or in baby bottles.
Cosmetics are not exempt from this problem. Parabens or phthalates are also questioned about their harmfulness. Legislators and scientists shall provide consumers with, for the former, a regulatory frame assuring the consumers of their safety, for the latter, elements to support political and legislative actions.

It is a major project, yet far from finished. Nevertheless, the due date is already given by the European Cosmetics Regulation, which will apply in lieu of the current Directive in July 2013. In its Article 15, it is written, “when Community or internationally agreed criteria for identifying substances with endocrine-disrupting properties are available, or at the latest on 11 January 2015, the Commission shall review this Regulation with regard to substances with endocrine-disrupting properties.”

Nowadays, the problem is to agree on a definition of endocrine disruptors, needed to write a thorough regulation. Indeed, very different substances are involved, with different and poorly known actions and effects on the human body. Nevertheless, our knowledge is increasing, as Robert Barouki, the Manager of the UMR-S 747 (Toxicology, Pharmacology and Cellular Signals) Department of the French Inserm (the French Institute for Health and Medical Research) has shown in Chartres.

What is an endocrine disruptor?

In a didactic manner, Pr Barouki first gave some basics to let us understand better what endocrine disruptors are. He reminded us that, when toxicology is the “science of poisons”, there are poison and poison:
• “historical” poisons: some groups of substances, with acute, easy-to-see and dramatic effects, which are efficient at high doses,
• “modern” poisons: many different groups of substances, which induce chronic and often not very specific effects, and that are efficient at low doses or when mixed together.

It is often quite easy to find the cause for acute pathologies (infections, poisoning…). It is far more difficult with chronic pathologies (allergies, cancers, fertility modification, neurologic or metabolic diseases, fetal or infant development impairment…). Thus, a proof of the link between an exposure to a given substance and a pathology is of the utmost importance. This is the topic of many scientific studies currently performed on endocrine disruptors.

Brought up as soon as 1962 in a book by the biologist Rachel Carson, Silent Spring, these substances have been more and more understood along the second half of the 20th century. In 1991, Theo Colborn, a specialist of environmental health, quoted, “a large number of man-made chemicals as well as a few natural ones have the potential to disrupt the endocrine system of animals, including humans.”
In 1995, the American Environmental Protection Agency (EPA) gave another definition: “an exogenous agent that interferes with the synthesis, secretion, transport, biding, action and elimination of natural hormones in the body that are responsible for the maintenance of homeostasis, reproduction, development and/or behavior”.

Complex, but better known

In the ‘90s and 2000s, many papers, especially from Europe, began to increase our knowledge on the effects due to endocrine disruptors on fertility or on testicles deformities during the period of embryonic development.  

Gradually, we know more.
Nowadays, scientists know more about what is disrupted by these substances: hormones and receptors of steroids, thyroid hormones, neurotransmitters receptors and carriers, signals between endocrine excretions and metabolism, signals implied in the development… This makes Pr Barouki think it would be more exact to say “physiological disruption”, which deals with more than only endocrine disruption, as metabolism, development and neurology are also implied…  

The groups of substances are also better known now. Thus, those that mimic or disrupt oestrogens (steroids and female sexual hormones) functions come from organo-chlorinated pesticides, plasticizers, persistent organic pollutants and flame retardants, natural phyto-œstrogens or even some drugs.
The many action mechanisms of endocrine disruptors are also better understood: activation or inhibition of steroids receptors, hormone synthesis, metabolism, transport and action impairment … are only some of them.

Distilben, BPA and Parabens

Every study on an endocrine disruptor has enlarged our knowledge of the effects on all similar products, the way they work and the doses at which they are the most important concerns. Indeed, it is very difficult to generalize, as every product is peculiar and different from the others.

Studies on DiEthylStilbestrol (DES, better known as distilben), a drug given pregnant women until the early 80s to prevent miscarriages or premature birth, have shown that a prenatal exposure may induce effects when adult on carcinogenesis, may induce metabolic disorders, even on the progeny. Some endocrine disruptors may have effects until the 4th generation.
Further, what has been shown is that DES has different effects if in low or high doses, an effect duplicated by many other endocrine disruptors.

Bisphenol A (BPA), for its part, modifies the oestrogens receptors action. Its effects vary with the involved tissues, development, the presence or the absence of the natural hormone. A perinatal exposure to BPA may have effects on the weight when adult, and on the breast structure (this could predispose to cancer.)
Once again, the topic of the dose of exposure is essential. In fact, BPA seems to be more harmful at a low dose. A toxicologic study, during which an adult was exposed to BPA at 50 µg/kg/day for 28 days led to an accumulation of triglycerides in the liver … far more important than in adults exposed to 5000 µg/kg/day. Indeed, as Pr Barouki said, 50 µg/kg/day is the acceptable daily intake (ADI) for Bisphenol A … and at the same time a figure close to the dose, we are all exposed to daily.

Phthalates and alkylphenols have been also studied. Studies have shown yet other different actions and effects.

Obviously, Parabens have been talked about. Some of them may have an oestrogen-like action that could even, at high doses lead to a utero-trophic effect. Pr Barouki thinks that “they are obviously endocrine disruptors, which require vigilance. Nevertheless, with our current data, we have few elements to know about their harmfulness due to the doses at which they are currently used.” To sum it up, the evidence is not as clear as for other endocrine disruptors … in spite of the media and political responses they have induced.

Cocktail effect

Pr Barouki has also emphasized a very peculiar characteristic of endocrine disruptors: the cocktail effect that he explained in one sentence. “One disruptor, it’s OK; it is when there are several of them…”. Implying: " …that troubles begin".
In fact, with these substances, the concept of harmfulness threshold figure makes almost o sense.

It is a given that, when exposed to a dose of an endocrine disruptor lower than its harmfulness threshold level, one has no risk. However, when in contact with several endocrine disruptors, which have similar effects, each one being respectively at a dose lower than its threshold level, it is not the sum of the theorical effects that shall be considered, but the total of the doses of the endocrine disruptors.
A Danish female researcher had given an equation: 0 (effect) + 0 + 0 = … 7! In other words: an endocrine disruptor, which in itself is not a danger +  an endocrine disruptor, which in itself is not a danger + an endocrine disruptor, which in itself is not a danger + an endocrine disruptor, which in itself is not a danger = a dangerous cocktail.

“How, in such a situation, could the legislator push for the principle of precaution?”, Anne Dux, the Manager or the Scientific and Regulatory Affairs of the FEBEA (the French Federation of Beauty  Companies) asked at the end of Robert Barouki’s conference.
The scientist answers, “endocrine disruptors are true questions for the public health that need to be answered… even if it is not only the duty for researchers”. He adds that the legislator, before enhancing a regulation or a ban about a substance, shall think about its replacement by another one… more or less harmful. Further, the socioeconomic consequences shall be assessed.

LW

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