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Endocrine disruptors: Substances with harmful effects on the hormone system

A/2010, 19.04.2010

Background information for journalists

"The world is becoming more female" was the title of an article in the magazine in the Süddeutsche Zeitung and it went on "And that’s definitely not good news". It referred to studies which reported that reproduction and development disorders have been observed above all in men and male animals. Certain chemicals that can influence the hormone system are thought to be the cause. We ingest them from food and from the air. So-called endocrine disruptors are suspected of promoting the onset of specific tumours which disrupt the development of the human organism or impair reproductive ability. Substances discussed in the public domain, which are suspected of being endocrine, are bisphenol A and certain plasticisers used to manufacturer plastics. But not only synthetically produced chemicals can influence the hormone system but also specific plant ingredients which are found in our food. For instance, soya contains so-called isoflavones which can bind to the receptor for the female sexual hormone, oestrogen. However, dietary intake of substances of this kind does not automatically constitute a health risk. Endocrine disruptors are not a uniform group of substances. The structure and mechanics of the individual substances may differ greatly. Hence they must be viewed in a differentiated manner from the toxicological angle in order to estimate the health risk.

The hormone system is involved in the steering of almost all bodily functions for instance in energy production and use, regulation of blood pressure and electrolyte metabolism. Reactions to emergency situations (hunger, stress, infection) are steered by hormones as are mood, behaviour, growth, development and reproduction. The hormone system is influenced by numerous internal and external factors. Many natural and synthetic substances can impact the hormone system when they reach the body. Critical doses can on the one hand directly disrupt specific hormone-dependent body functions. Some substances can also influence the hormone system during sensitive development phases like, for instance, the unborn child during pregnancy and, in this way, cause permanent damage to health. Synthetic or natural substances of this kind, which may have harmful effects on the hormone system, are called endocrine disruptors.

Endocrine disruptors are not a defined group of substances. One of their properties is that they can have an effect on the hormone system. They may differ from one another in terms of their other properties. Potential endocrine disruptors also include natural ingredients in food like phytohormones, for instance isoflavones in soya but also environmental toxins like PCBs, pesticides like DDT, specific preservatives and components of printing inks and UV light protection substances like benzophenone, heavy metals like cadmium and plasticisers like some phthalic acid esters.

Epidemiological studies document an increase in tumours in organs regulated by hormones like breast and prostate cancer. Impairment of male reproduction ability through undescended testicles or a drop in sperm count are increasingly being observed, too. In science they are discussed as the possible consequences of the intake of endocrine active substances from the environment and food. However, no causal relationship has been proven so far.

Phytohormones - hormonally active substances in plants

Hormonal substances may occur as natural ingredients in plants. Isoflavones are one example; large levels occur particularly in the soya plant. They are also described as phyto-oestrogens as they can have an impact on the human organism similar to that of the female sexual hormone, oestrogen. They bind to cell receptors like endogenous hormones. This may have different biological consequences in the body. They can contribute to health but can also become a risk. In isolated form isoflavone capsules are available across the counter as a substitute for conventional hormone therapy for the treatment of menopausal disorders in women like hot flushes, night sweats and osteoporosis. Nonetheless, there is no clear scientific evidence that isoflavones do in fact alleviate menopausal disorders; it is far more the case that they may even have undesirable effects. Hence it cannot be ruled out that they may increase the risk of breast cancer as they have an oestrogenic impact on women’s breast tissue during menopause.

At the present time, one subject of controversial debate is whether the hormonal effect of isoflavones on the human organism is the same when isoflavones are ingested from soya-based food as when they are ingested in isolated form as food supplements. A high dose of isolated isoflavones, particularly when it is ingested over a period of several years, could constitute a risk to health.

Food packaging materials: endocrine disruptors in plastics

Many food packagings are made of plastic. Endocrine active substances either come from the building blocks (monomers) or from the additives in plastics. BfR scientists are looking at whether the chronic intake of these substances with weak hormonal action from food packaging materials constitutes a health risk for consumers. Scientific methods are needed to assess this. So far they are limited in terms of their reliability. They permit an overview of potentially endocrine active substances in materials (screening procedure) and they can clarify the hormone-like modes of action of individual substances in vitro, i.e. in the test tube. This is not sufficient for scientific risk assessment because frequently it is not clear to what extent these results can be transferred to humans. A generally accepted procedure for the detection of endocrine substance properties is not available so far in the field of food contact materials. Hence studies on the hormone-like effects do not as a rule permit any health assessment which goes beyond existing evaluations based on data from animal experiments on (sub-)chronic toxicity and/or reproduction toxicology. BfR is working on the establishment of more robust screening methods, studying the migration of endocrine active substances from food contact materials and also examining how these compounds can influence metabolism.

Bisphenol A

Bisphenol A (BPA) is an industrial chemical which is used as a starting material for the production of polycarbonate plastics and synthetic resins. For instance baby bottles, drinking beakers and the inner coating of tins are made from polycarbonate. BPA belongs to the group of substances which may have an effect similar to that of the female sexual hormone oestrogen. In the human body BPA is rapidly converted into a metabolite that no longer has any oestrogenic effect and is excreted by the kidneys.

Low levels of BPA may be released from the inner coating of cans and polycarbonate baby bottles, and migrate to food. According to the migration data available so far for these products, consumers, including children, take in far less than the tolerable daily intake (TDI: 0.05 milligram BPA per kilogram and bodyweight) which was set by the European Food Safety Authority (EFSA). The data recorded by the Federal Environmental Agency (UBA) on the BPA concentration in the urine of children likewise show that it fell considerably short of the TDI value for BPA. After careful scientific assessment of all available studies, in particular studies in the low dose range of bisphenol A, EFSA and BfR come to the conclusion that there is no health risk from bisphenol A for infants and small children when the polycarbonate bottles are used in the normal way.

In September 2009 environmental associations in Germany and Austria examined dummies for BPA and published unexpectedly high levels of BPA detected both in the protective plastic coatings of dummies and in the teats. These results prompted extensive studies of baby dummies by BfR, the Austrian Agency for Health and Food Safety (AGES) and official food control laboratories in Germany. BfR examined different brands of dummies made of latex and silicone from various manufacturers to determine how much BPA they release. In the case of 17 out of the 18 dummies examined, it could not be shown that BPA had migrated to the test saliva solution. The measured value was just below the detection limit in only one sample. The study results correlate with the measurements of the other laboratories mentioned. The only dummy with measurable migration exhausts 1% of the tolerable daily intake. This result does not give any cause for health concerns.

Phthalates

Large amounts of phthalates, i.e. up to 50% as plasticisers in plastics, in particular PVC, are used. Phthalates may separate from the plastic and - in the case of food packaging - migrate to the food. The phthalates dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP), amongst others which are classified as dangerous for reproduction, are also used. For some years now there have been regulations on the European and national levels which prohibit the use of these substances in materials in contact with fat-containing food, for instance in the seals of twist-off jar lids. Hence it can be assumed that the corresponding TDI values for phthalates can be complied with when these products are used. Phthalate measurements by UBA in the urine of children do, however, show relatively high levels which point to other intake pathways for phthalates. Toys made of PVC are a further potential source of phthalate exposure. The use of phthalates classified as dangerous for toys and baby articles has, however, been banned for several years now.

So far there are still no reliable studies available about the effects on humans of exposure to low doses of phthalates. There is a need for more research to characterise the health risk of current phthalate exposure for man in a more precise manner. The main question is whether the impact of individual substances is amplified in phthalate compounds. Animal experimental studies with individual phthalates and mixtures indicate an additive effect in the disruption of testosterone formation in animal progeny.

Endocrine disruptors in pesticides

Pesticides may only be approved when their intended, proper use does not have any harmful effects on human health. For this approval requirement to be met, active substances in pesticides must undergo comprehensive examination for potential harmful effects on health. According to internationally accepted risk assessment principles, a pesticide has no harmful effect on health when the expected exposure of humans is several orders of magnitude lower than a dose with a potentially harmful effect. In this context, harmful effects on the hormone system that have been reported so far have also been taken into account.

The new EU Regulation concerning the placing on the market of plant protection products (Regulation (EC) No. 1107/2009), which enters into force in June 2011, envisages that in future a substance may only be approved in plant protection products if it “… does not have any endocrine-disrupting properties that may cause adverse effects in humans …”. However, so far there is no concept on how to apply this provision to the testing of an active substance. After an international expert workshop, BfR drew up proposals last year for an evaluation concept of this kind.

For the assessment of pesticides with potential endocrine-disrupting properties, the concept envisages a graduated process. In the course of this process the hazard is initially characterised by identifying health effects from the data on the active substance, which could be caused by an endocrine-disrupting mechanism. The next steps involve the examination and assessment of the underlying toxicological mechanisms in order to establish whether they could be transferred from the animal experiment to humans. The final decision on the approval of an active substance in a pesticide could either be taken on the basis of the risk, i.e. taking into account the amount normally ingested by humans or on the basis of the hazard presented by the substance.

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