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Endocrine disruptors

Definitions

The endocrine system plays an essential part in the maintenance of the biological equilibriums that are necessary for life. This is the reason for today’s questioning about the consequences of a potential breaking of these equilibriums by environmental contaminating agents.

Except in the case of DIETHYLSTILBESTROL and pesticides such as DDTDichlorodiphenyltrichloroethane or CHLORDECONE, which have been known as factors of infertility for a long time and the modus operandi of which (probably for DESDiethylstilbestrol and pesticides mentioned above) relates to an endocrine disruption, there are only few reliable data about the link between EDS and human health. Moreover, it is also important to mention that the situations of exposure are hardly transposable to the whole population, even with substances such as DES and pesticides mentioned above.

Nevertheless, the matter of the small doses, as it appears today with BISPHENOL A or the toxicity of some mixtures of EDS (with the same dose of every component being harmless) requires vigilance.

The endocrine system is made of the set of glands secreting hormones, and acts on the development, the growth, the reproduction and the behavior of animals and human beings.

The WHO has defined an EDS as an exogenous substance or mixture that alters the functions of the endocrine system and generates noxious effects onto the health of a safe body, of its descendants or of its sub-population.

Since December 2006, REACH regulation identifies EDS as some very worrying substances, to which some specific management measures may apply. As biological, physical or chemical alterogens, EDS match the normalized definition of the word “pollutant” as accepted by AFNOR in France.

So EDS are substances of either natural or artificial origin that interfere with the hormone system. There are several classes of EDS:

  • Hormones that are naturally secreted by the human body (such as oestrogens, testosterone, androgens…)
  • Hormones that are naturally produced by plants (phytoestrogens) that can cause “estrogenic effects” after consumption.
  • Substances chemically produced for their hormonal effect (for instance, birth-control pills…), with a structure making them similar or identical to natural hormones.
  • Substances chemically used in industry, agriculture or consumption goods or as sub-products but with unwanted effects onto hormones. Their structures may be similar to the ones of natural hormones. This group of EDS is a subject of controversy and is on the list of the substances requiring further evaluation. In order to achieve this, the EU and the USA have set up some programs of fast hierarchized tests.

In order to select the substances requiring testing, the EU has made the inventory of 553 substances that are priorities because of their persistence, environmental exposure, production volume and because of the evidence of their EDS character. The EU has classified them into 3 classes:

  • class 1: 60 compounds for which there is an evidence of EDS character and that are top priority because of their exposure
  • class 2: 55 potentials EDS that are medium priority because of their exposure
  • class 3: 438 substances for which the evidence of EDS character is not sufficient and that are no priority because of their exposure

Please note that most of those substances are also classified as CMR (carcinogenic, mutagenic and toxic for reproduction).

Inside the body, EDS may operate in different ways:

  • Effects that are similar to the ones of hormones (agonistic)
    Inside the body, the substance binds to a hormone receptor and activates it in the same way as a body hormone would.
  • Blocking of the hormonal effect (antagonistic)
    The substance binds to a hormone receptor then blocks it, so that the body hormones cannot bind to the receptor anymore.
  • Influence on the availability of body hormones (agonistic or antagonistic)
    The substance disrupts the synthesis or degradation of body hormones, and thus changes the available quantity of hormones. The substance may also alter the hormone circulation into the blood.
  • Side effect
    Inside body cells, EDS modify some mechanisms which interact with the hormone system in one way or another. Therefore EDS end up altering hormones.

EDS generate various body reactions:

  • In specific conditions, some regulation mechanisms of the hormone system can compensate exposure in adulthood. There is no perceptible functional damage, but a true molecular disruption.
  • During the development of a body, the regulation mechanisms cannot compensate exposure, so that lasting abnormalities and damages may occur. Therefore, the development mechanisms are more vulnerable.
  • Alterations occur when the effect of EDS cannot be counterbalanced anymore.
    Abnormalities can occur, for example, during reproduction, metabolism or cause the apparition of tumors.

How important is the EDS matter?

In animals

The action of EDS on living bodies has been observed in animals:

  • Thinning of the eggshell of birds exposed to DDT,
  • Alteration of the reproduction of seals exposed to PCB,
  • Alteration of the sexual development of alligators exposed to pesticides in Florida,
  • Effects on the reproduction of some fishes exposed to the effluents of waste waters released by paper and chemical industries,
  • Masculinization of snakes exposed to TBT (TRIBUTYLTIN which is a powerful biocide).
  • Those are only few examples but this list proves the importance of EDS in our environment.

In humans

EDS impact the body in different ways depending on the age or the development phase of the affected body. In utero exposure is by far the most severe. Because the « right hormone » must be present during the formation of every organ, the date of exposure is more important for a developing body.

An absence of hormonal signal at a specific stage of development may cause serious consequences for the whole life of the body. Health problems due to in utero exposures may arise anytime, from birth to adulthood.

Regular exposure over long periods, even to very small doses, may also generate big damages. Moreover, exposure to a combination of several EDS at the same time may have a much stronger effect than exposure to a single product, which demonstrates the “synergy” effect of EDS.

The following sanitary changes are considered as being directly or indirectly due to EDS:

  • The decrease of the number of spermatozoons by more than 40 % in blood donations in some countries. In France, a large number of couples have troubles to conceive a child (14 % couples get advice from a specialist for this problem at least once in their life, according to a 1988-89 survey).
  • The increase of the incidence of testicular cancer in Europe since the —- according to M. GERIN and al, up to 50 % in Scotland from 1959 to 1984, by 350 % in Denmark from 1943 to 1989 and by 5 % per year in Germany and Poland.
  • The increase of breast cancers in developed countries (in France, their number has almost doubled between 1980 and 2000)
  • The increase of the number of congenital malformations (in Paris, for 150 000 births a year, their frequency went from 2 % in 1981 to 3.7 % in 2000)
  • In 2002, a study in Belgium highlighted a delayed sexual maturity in teenagers living in areas contaminated by PCB and DIOXINE (Den HOND and al, 2002)

In workers

Several researches have highlighted infertility problems and prostate cancers in farmers and people handling pesticides.

In the field of pharmaceutical industry producing drugs with hormonal action, production workers are affected by several abnormalities such as gynecomastiae, breast nodules, decrease of the number of spermatozoons… Effects suggesting abnormalities of the suprarenal glands, in workers producing a corticosteroid agent, have also been reported.

Workers producing pesticides (chlordecone) have developed a syndrome combining neurological disorders and infertility. The toxicity of chlordecone has been associated with its estrogenic activity. In addition, several researches have associated infertility, in both women and men, with farming work and pesticides handling (International Program on Chemical Safety, 2002).

To be honest, it has to be said that the trends described herein may be due to other factors non related to EDS: diagnosis advances (for cancers), increase of the age of pregnancy and better antenatal detection (for congenital malformations), evolution of the frequency of ejaculation before a sperm donation (for the declining quality of sperm) etc…

Therefore the link between EDS and health problem is more a subject of suspicions then one of certitudes. It then requires the listing of priority substances, the harmful effects of which must be thoroughly tested and studied.

Implemented on June 2006, the European environment and health strategy, named SCALE (Science, Children, Awareness, Legislation, Evaluation), includes priority actions on EDS. In 2003, a European working group, called CREDO (Cluster of Research into Endocrine Disruption in Europe) was set up by gathering 60 European laboratories doing research into EDS.

In France, the “fertility observatory” was set up in 2006 by INSERM as a tool of observation of the reproductive function of couples living in France.

In this article, we will only deal with EDS from work environment and of chemical origin. It has to be said that EDS to be found in the environment have only been detected since the 90’s. Various EDS have been identified in streaming waters and sediments: alkylphenol polyethoxylates (APEOs), DDT, lindane, PCB, phthalates, whereas organostannic compounds have been detected in harbors.

Moreover some substances from the environment also penetrate into man’s food chain, like dioxines or PCB, commonly found in milk, meat and fish. And even if this contamination decreases on the whole, the concentrations of these substances in some aliments are above the desirable values (OFSP 2008, Swiss Federal Public Health Office).

EDS and professional risks

The lack of consensus among scientists about this issue and the absence of a directly applicable regulatory frame do not help the set up of a preventive practice focusing on the actual EDS risks. But, nevertheless, that must not be a good reason for inaction and the first action is to better appreciate chemical hazards. Only few tests can highlight the EDS character of a substance:

  • Uterotrophic test on rodents,
  • Reproduction test on rats and mice,
  • Ecotoxicological test on daphnia (planktonic crustaceans).

Those two last tests must be incorporated into the « biocide » directive and then into REACH regulation, in order to be finally included into the specifications required from manufacturers willing to commercialize a substance.

In order to make it clearer to everybody, 11 classes of industrial products suspected of being EDS will be dealt with later:

  • Alkylphenols
  • Bisphenol A
  • Phtalates
  • Chloroorganic compounds (polychlorobiphenyls and dioxine)
  • Diphenyls and diphenyl brome ethers
  • Pesticides
  • Trialkyltin compounds
  • Uv filters
  • Heavy metals
  • Solvents
  • Professional steroid hormones

Dr Danièle Henny – Occupational health doctor

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