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anses

French Agency for Food, Environmental and Occupational Health & Safety

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Updated on 10/10/2017

Endocrine disruptors

Presentation and ANSES's work in the field

Keywords : Endocrine disruptors, Chemical risks, Bisphenol A (BPA)

In recent decades, various scientific studies have identified an increase in the frequency of certain diseases, mainly affecting the reproductive organs, as well as impaired fertility. Serious concerns have thus been expressed about the potential health impact of substances found in the environment or in consumer products, on the hormonal system. The understanding of the role played by these substances, known as “endocrine disruptors”, and their mechanisms of action, or the extent to which their effects are responsible for the increase in these disorders, are the subject of scientific and public controversy. ANSES has ongoing mandates on risk assessment, scientific monitoring and reference activities for endocrine disruptors. In particular, it contributes to the National Endocrine Disruptor Strategy and, since 2009, has been working on a large-scale study of some 30 substances with regard to their potential endocrine-disrupting action. It also supports research work through its National Research Programme for Environmental and Occupational Health (PNR EST).

What are endocrine disruptors?

The definition of endocrine disruptors 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 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."
 

Where do endocrine disruptors come from?

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

By disrupting the endocrine system, these substances can 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 reprotoxic effects, and may impair fertility or disrupt development of the foetus.

 

How do endocrine disruptors act?

Endocrine disruptors can:

  • mimic the action of a natural hormone, thereby causing the response due to this hormone,
  • prevent a hormone from binding to its receptor and thus prevent the transmission of the hormonal signal,
  • disrupt the production or regulation of hormones or their receptors.

 

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

Lastly, 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) to low concentration levels.

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 mixture of chemical substances and understanding their interactions in the human body over the long term, right from the period of foetal-embryonic development.

In view of this complexity, knowledge of the effects of endocrine disruptors at the concentration levels observed in the environment is 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.

 

ANSES's expert appraisal on around thirty substances

In 2009, ANSES received a formal request from the Directorate General for Health to identify and characterise exposure situations that potentially pose a risk for health, especially for the most vulnerable populations, associated with the use of everyday consumer products and/or articles containing certain chemical substances.

The request concerned around 30 substances classified as Category 2 reprotoxic (according to Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures, known as the CLP Regulation) or identified as potential "endocrine disruptors" by the European Commission.

The first two reports published in this context, in September 2011, concerned respectively the health effects and the uses of bisphenol A (BPA). In these reports, the Agency concluded that the priority should be to prevent exposure of the most susceptible populations (infants, young children and pregnant or breastfeeding women). It recommended a reduction in this exposure, mainly by replacing bisphenol A in food contact materials. The 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. This work determined the share of exposure from food (80%), and also demonstrated the existence of exposure by inhalation (via ambient air) and by the cutaneous route (skin contact with consumer products). Specific situations of exposure in the workplace, in particular associated with the handling of thermal paper (cash register receipts, credit card receipts, etc.) were also identified.

In December 2012, the French Parliament adopted a law for the suspension of the manufacture, import, export and marketing of all food packaging containing bisphenol A. Thus, since 1 January 2015, bisphenol A has been prohibited in infant feeding bottles and other food containers. This legislation is expected to lead to a very significant reduction in the level of exposure to this substance.

In July 2016, the European Commission adopted a proposal to classify BPA as toxic to reproduction Category 1B following a request from France prepared by the Agency. In addition, a proposal to restrict BPA in certain articles intended for the general public, such as receipts printed on thermal paper, was prepared by the Agency for the European Chemicals Agency (ECHA) in the framework of Regulation (EC) No 1907/2006 of 18/12/06 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACh). This proposal led to a restriction measure being published by the European Commission in December 2016.

As well as the work on bisphenol A, three other reports were published in 2013 by ANSES: a review of potential alternatives to bisphenol A, an assessment of the hazards of other compounds of the class of bisphenols, and an initial report on the uncertainties surrounding endocrine disruptors.

Since 2014, in the framework of this formal request, twelve substances likely to be found in mixtures for use by the general public (varnishes, glues, paints, etc.) have been assessed by ANSES: o-phenylphenol (OPP), toluene, n-hexane, cis-1(3-chloroallyl)-3,5,7-triaza-1-azonia adamantane chloride (cis-CTAC), methyl-tert-butyl-ether (MTBE), 4-chloro-3-methylphenol or chlorocresol, 4-nitrophenol, 4-tert-octylphenol, DEGME (or 3-methoxy ethoxy ethanol), 4-tert-butylphenol 4), 4-nonylphenol, and chloroacetamide.

In 2015, substances from the class of perfluorinated compounds and phthalates were the subject of expert appraisal work published by the Agency, particularly on the effects and uses of these substances, the sources of exposure, and the contamination of different environments.

Work of the same kind on substances from the class of polybrominated compounds was published in 2017.

These studies served as the basis for ranking the substances to be assessed in the framework of the National Endocrine Disruptor Strategy (SNPE 2014-2016).

 

The role of ANSES in the framework of the National Endocrine Disruptor Strategy

Under the National Endocrine Disruptor Strategy (SNPE), adopted in 2014, ANSES was entrusted with assessing at least five substances a year over three years. When certain substances submitted to the Agency for appraisal are suspected of having endocrine-disrupting effects and/or posing a risk to health or the environment, ANSES is asked to propose appropriate risk management measures in the framework of the European regulations (REACh, biocides, plant protection products or any other appropriate regulation). They may for example be subject to inclusion on the list of candidate substances of very high concern established by the European Chemicals Agency (ECHA) under the REACh regulation, which may lead to restrictions on use in some industrial production sectors.

In 2014, ANSES conducted an expert appraisal on five substances in the framework of the SNPE. It came to the conclusion that MTBE, DEHTP and DINCH, which were tested in many studies, do not display any endocrine-disrupting nature. For the last substance, uncertainty nevertheless persists as to possible thyroid effects on the neurocognitive development of newborn or premature babies. For BHA and methylparaben, additional studies are recommended in the context of REACh.

In 2015, ANSES conducted an analysis of six substances: ATBC (acetyl-tributyl-citrate), TBC (tributyl citrate), BHT (butylated hydroxytoluene), terephthalic acid, methyl-salicylate, and iprodione.

In 2016, ANSES analysed five substances that were the subject of a publication: TMBPF, triclocarban and RDP underwent an analysis of the best risk management options, according to the procedure in force used by ECHA and the Member States of the European Union. Dicyclopentadiene and tin sulphate were assessed under the REACh Regulation because of a suspected reprotoxic effect, and suspected carcinogenic, mutagenic and reprotoxic (CMR) properties and sensitising effects, respectively.

In 2017 five substances were added to the Agency's work programme: homosalate, trisulfuron-methyl, triphenyl phosphate, bisphenol B and BDE-47.

In addition, following a formal request from the Ministry of the Environment, in 2016 the Agency submitted a dossier to the European Chemicals Agency (ECHA) in the framework of the REACh regulation with the intention of requesting a restriction on use of bisphenol A as a substance of very high concern due to its toxicity to reproduction.

In 2017, ANSES also submitted a proposal to the European Chemicals Agency (ECHA) to classify bisphenol A (BPA) as a "substance of very high concern" (SVHC) in the context of the European REACh Regulation for its properties as an endocrine disruptor for humans. This proposal was adopted by ECHA's Member State Committee in June 2017.

 

Identification of criteria defining "endocrine disruptors"

European legislation required the European Commission to regulate endocrine-disrupting chemicals before the end of December 2013 (in the biocides and plant protection products regulations). The successive proposals for criteria defining "endocrine disruptors" presented by the European Commission since June 2016 have so far been rejected by the Member States. In July 2016, ANSES published an opinion on the proposal for criteria for identifying endocrine disruptors, in response to a request from the Ministry of the Environment.

In its conclusions, the Agency recommends retaining the definition and criteria for identifying endocrine disruptors from Option 3 of the European Commission's 2014 roadmap, which enables endocrine disruptors to be distinguished into three categories: "known", "presumed" and "suspected". In addition, the Agency advocates that classification of endocrine disruptors be performed by a single European body, to avoid any risk of divergence of classification for a given substance.

Since then, on 4 July 2017, at a meeting of the Standing Committee on the Food Chain and Animal Health (regulatory committee for plant protection products), the Member States adopted a proposal by the European Commission from June 2017 on the criteria for identifying endocrine disruptors. Similarly, this definition was formalised in July 2017 in the context of the Biocides Regulation. In September 2017, the European Parliament will examine the European Commission's proposal concerning endocrine disruptors in pesticides, with a vote due to take place in early October 2017 at the plenary session.

 

The Agency's other work on endocrine disruptors 

In 2015, the Agency published the results of an expert appraisal requested by the DGCCRF in 2011, whose aim was to assess the potential health and environmental effects of flame retardants used in upholstered furniture. For each of the 22 substances identified by the Agency among those most widely used, the available data were insufficient to rule out potential toxicity to health and/or effects on the environment.

In 2016, the Agency published its expert appraisal work in response to a formal request relating to the presence of phthalates or substitute substances in flexible plastic toys and childcare articles that can be put in the mouth by children under three years of age. The work did not identify a risk to children's health for four of the substances studied that are phthalate substitutes (DINCH, DEHTP, ATBC and TXIB). The Agency nevertheless recommended that a risk assessment be systematically carried out for any new substance found in the composition of the plastics used in toys and equipment intended for children, before they can be placed on the market.

In 2016, ANSES also published a report on dealing with uncertainty in the process of assessing the health risks of chemical substances, offering an insight into how uncertainty is characterised and taken into account in health risk assessment. This work is the result of methodological developments implemented by the Agency over the past few years to better describe the uncertainties and strengthen the weight of evidence in health risk assessment; they are based on the expert appraisal work on endocrine disruptors.

 

Other studies have been produced by the Agency in connection with the issue of endocrine disruptors:

  • Assessment of the results of the 2015 experimental plan on bisphenol A contamination of non-canned foodstuffs of animal origin, published in 2017.
  • Collection and analysis of data on the presence of pesticide residues in environmental media by the Pesticide Residues Observatory.
  • Total diet studies and in particular the one on the infant population (iTDS) published in 2016: dietary exposure of children under three years of age to substances of interest, some of which may have an endocrine-disrupting action.
  • Study of the presence of compounds in water resources and in drinking water by ANSES’s Nancy Laboratory for Hydrology.
  • French National Research Programme for Environmental and Occupational Health (PNR EST) which, over the past ten years, has helped strengthen the acquisition and development of knowledge, mainly on the hazards, potential exposure and the associated diseases. Endocrine disruptors are one of the priorities of the PNR EST's calls for research projects, in synergy with the French National Programme for Research on Endocrine Disruptors (PNRPE).