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ANSES - French Agency for Food, Environmental and Occupational Health & Safety

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Updated on 14/03/2017

Endocrine disruptors

Presentation and the work of ANSES

Keywords : Endocrine disruptors

In the last few decades, various scientific studies have drawn attention to the possible effects of chemicals found in the environment on the body’s organs or reproductive function. Epidemiological studies observe in particular a change in the frequency of various diseases specifically affecting the reproductive organs or resulting in impaired fertility, leading researchers to consider a possible relationship with endocrine disruption effects. Thus, serious concerns have been expressed by some scientists, independent research organisations and associations on the possible health impact of substances, found in the environment or in consumer products, on the hormonal system. An understanding of the exact role played by these substances known as “endocrine disruptors”, and of their mechanisms of action, such as the portion attributable to their effect on the increase in these disorders, is the subject of scientific and societal controversy.  

ANSES has ongoing mandates on risk assessment, scientific monitoring and reference activities for endocrine disruptors. It has also launched a large-scale project focused on thirty substances identified as being of concern in terms of their endocrine disrupting action. In addition, it supports research work via its National Research Programme on Environmental and Occupational Health (PNR-EST).

What are endocrine disruptors?

The varying definitions for endocrine disruptors have been the subject of debate at the international level. The definition proposed by the World Health Organization in 2002 is the one most commonly accepted:

“An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or  (sub)populations."

"A potential endocrine disruptor is an exogenous substance or mixture that possesses properties that might be expected to lead to endocrine disruption in an intact organism, or its progeny, or (sub)populations."

In general, they are naturally occurring or artificial chemicals that can interfere with the functioning of the endocrine glands, the organs responsible for the secretion of hormones. This interference can occur in different ways:

  • The endocrine disruptor can mimic the action of a natural hormone and thus cause the response typical of this hormone;
  • The substance may prevent a hormone from binding to its receptor and thus prevent the transmission of the hormonal signal;
  • Lastly, the substance may disrupt the production or regulation of hormones or their receptors.

Bisphenol A, phthalates, and brominated compounds are among the substances suspected of being endocrine disruptors.

 

Where do endocrine disruptors come from?

Endocrine disruptors may be of natural origin (hormones and phyto-oestrogens) or result from human activities (chemical industry products contained in common consumer items, crop treatment products, medicines, cosmetics, etc.). They can thus be found naturally or as a result of contamination of various media (water, food, consumer products or articles, etc.).

By disrupting the endocrine system, these substances can ultimately alter various processes such as the production, use and storage of energy and, more broadly, regulation of metabolism and development. Some of these substances may also have other toxic effects, including reproductive damage, and may interfere with fertility or disrupt the development of the foetus.

 

What are the characteristics of these substances?

A number of effects attributed to endocrine disruptors have been observed in experimental studies in animals. However, in many cases they raise the issue of whether those effects can be extrapolated to humans, especially for exposure at low levels. It seems that the effects of endocrine disruptors do not all involve the ‘classic’ mechanisms of toxicity (malfunction or cell death) but are related to the phenomena of signalling and regulation of the body. Furthermore, some endocrine disrupting effects appear only at very low levels.

The work conducted shows, moreover, that susceptibility to endocrine disruptors may vary depending on the developmental phase of life. This applies in particular to the foetal and embryonic development period, and to infants and young children who exhibit an increased sensitivity to these substances. It is therefore necessary to take into account the period of exposure to these substances when analysing their effects.

Finally, various compounds suspected of being endocrine disruptors are found in trace amounts in the environment. The individual is thus exposed by multiple routes (ingestion, inhalation, dermal contact) and media (water, food, consumer products or articles, medical devices, etc.) to low levels of several compounds whose effects can be varied and can also be attributed to other causes.

Understanding the effects of endocrine disruptors thus requires adopting an integrative approach by considering humans within the context of their environment, but also by taking into account the individual’s exposure to a mix of substances and understanding their interactions in the body over the long term, from the period of foetal-embryonic development and life in utero.

In view of this complexity, knowledge of the effects of endocrine disruptors at the levels encountered in the environment is currently hindered by the limitations of traditional toxicology and risk assessment methods. The challenge is therefore to develop new ones, adapted to the unique properties of these compounds.

 

The scientific community is mobilised

According to the European Commission an endocrine disruptor is “An exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations”. Currently, no definition or criteria are common to all European legislation.

Various Community bodies (the European Food Safety Authority [EFSA], the European Chemicals Agency [ECHA], the European Commission) are working in conjunction with the Member States authorities in an attempt to identify the relevant criteria to classify these substances.

At the international level, the Organisation for Economic Co-operation and Development [OECD] has established guidelines, including protocols for toxicological and ecotoxicological testing, in order to detect effects associated with endocrine disruptors and thus help to identify the substances responsible for oestrogenic effects. Similarly, the Agency is taking part in ongoing discussions on the strategy of using these various tests in order to advance our level of knowledge on the effects associated with these chemicals. In the United States, the Tox 21 research programme was initiated on the basis of a report by the National Academy of Science. Its aim is to identify the main pathways of toxicity activated by several thousand compounds to ultimately reason in terms of activated toxicity pathways (around twenty) rather than chemical compounds taken alone (currently more than 100,000 substances).

 

Hormonal systems and endocrine disruptors

There are several types of substances that can act on the hormonal system:

  • Natural hormones produced in the body: œstrogens, testosterone, thyroid hormones, insulin, etc. Natural hormones produced by plants: phyto-oestrogens (oestrogen-like or anti-oestrogenic effects), isoflavones (soy) or resveratrol (grapes and wine).
  • Chemicals produced for their hormonal effect (oestro-progestogen birth control pills) with a structure that is similar or identical to natural hormones.
  • Chemicals used in industry, agriculture and consumer goods, or used as by-products, but whose effect on hormones is not intentional.

 

The role of ANSES

At the request of the Ministry of Health, since 2009 the Agency has been conducting broad scale expert appraisals on some thirty substances identified as category 3 reprotoxic substances and/or endocrine disruptors for reproduction and fertility. A long-term undertaking, this work illustrates the role played by ANSES in advancing the knowledge of chemical substances, their hazards and risks.The Agency’s mission are therefore to:

  • Characterise the hazards of substances.
  • Identify consumer products and articles available to the general public containing substances that are, or are likely to be, toxic for reproductive functions.
  • Characterise the exposure of the general population to these substances in these articles or products. This expert appraisal focuses in particular on vulnerable populations (especially during the gestation period) and people exposed to these substances in the workplace.
  • Assess the risks to health.
  • Identify possible substitutes for the products or substances for which health risks have been identified.

Two initial reports were published in September 2011, one on the health effects of bisphenol A and the other on its uses. In these reports the Agency was able to identify that the priority should be to prevent exposure of the most susceptible populations (infants, young children and pregnant or breastfeeding women). It recommends a reduction in these exposures to bisphenol A, mainly by replacing it in food contact materials. The final expert appraisal report on the assessment of risks associated with exposure to bisphenol A , which was published in April 2013, confirms these health effects, especially for pregnant women with regard to potential risks for the unborn child. For the first time, the report  takes into account an estimation of real population exposure to bisphenol A through the alimentary route (food), as well as by inhalation (via ambient air) and by the cutaneous route (skin contact with consumer products). It highlights the fact that food contributes to over 80% of the population’s exposure to this substance..

Three additional reports have also been published: a status report on potential alternatives to bisphenol A, an assessment of the hazards of other bisphenol-group compounds, and a report on the uncertainties surrounding endocrine disruptors. Furthermore, this work has led to the identification of other exposure situations, in particular those linked to the handling of thermal paper (cash register receipts, credit card receipts, etc.), especially in an occupational context. 

In 2014, several risk assessment reports and an opinion were published on methyl tert-butyl ether (MTBE), toluene, n-hexane, cis-CTAC and O-phenylphenol (OPP), 5 substances considered to be Category 2 reproductive toxicants and/or endocrine disruptors.

Perfluorinated and polybrominated compounds and phthalates are also being assessed by the Agency, in particular with regard to sources of exposure and the contamination of various environments. The Agency is also compiling a summary of recent toxicity data on perfluorinated compounds and phthalates. This work has been used as the basis for prioritising substances in the context of a national endocrine disruptor strategy. 

In addition to its risk assessment work, ANSES also performs monitoring, research and reference work on endocrine disruptors:

  • French Observatory for Pesticide Residues: the collection and analysis of data relating to the presence of pesticide residues in the environment.
  • Second French Total Diet Study (TDS2) published in 2011: exposure of populations over 3 years of age to substances of interest that can have some endocrine disrupting action.
  • Study of the presence of perfluorinated compounds in water resources and in drinking water by ANSES’s Nancy Laboratory for Hydrology.
  • Programme on “Drug residues and water”: prioritising substances for screening, development of detection and assaying methods in water.
  • Contribution to the implementation of the European REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) and CLP (harmonised classification) Regulations: scientific and technical assessment in its field of competence.
  • National Reference Laboratory for mycotoxins, contaminants (veterinary drug and colouring agent residues; pesticides), and physico-chemical contaminants in water.

ANSES also participates in the establishment of international cooperation (especially with its German and North American counterparts), for the purpose of developing new methodologies for the assessment of internationally recognised risks.