Endocrine disruptors and their impact on human health and the environment

What is an endocrine disruptor?

The endocrine system is composed of all the glands producing hormones, and receptors of hormones in the body. It plays a very important role in the development of embryos and in reproduction. It also plays a role in the regulation of metabolism in general.

Some chemicals, both natural and man-made, can interfere with endocrine glands and their hormones or where the hormones act - the target tissues. These chemicals are called ‘endocrine disruptors’ or ‘endocrine disrupting chemicals’ (EDCs).

Why this growing concern about endocrine disruption and its relation to some chemicals?

Negative impacts on reproduction and development have been observed, and there is good evidence that wildlife populations can be affected. Over the last two decades, there has been evidence of increases in many endocrine-related disorders in humans.

The notion that exposure to some chemicals contributes to endocrine disorders in humans and wildlife is supported by extensive laboratory studies. Exposure during critical periods of development can cause irreversible and delayed effects that do not become evident until later in life. Nevertheless, there are significant difficulties in linking specific chemicals to endocrine disruption, especially when they do not stay for long periods in the body.

What are the main effects of endocrine disruptors that are considered?

There are four main groups of effects considered:

Impact on human reproductive health.
This is one of the key topics of human health effects of endocrine disruptors. There are effects on both male and female, ranging from incomplete sexual development to fertility problems.

Hormonal cancers in humans
A number of cancers in humans are influenced by hormones, and in those cases, endocrine disruptors can have a role in their development. However, for a number of hormonal cancers there is a lack of information on the potential role of endocrine disrupters.

Impact on development and metabolism in humans
Endocrine disruptors can have effects on a number of hormone systems, including the thyroid system. They can also have effects on immune system functions. Some evidence points to a link between chemical exposure and the ongoing obesity epidemic.

Impact on wildlife
The main endpoints that are considered when looking at animals have to do with reproduction and development. Impacts have been observed on many groups of animals, from invertebrates to mammals.

What makes endocrine disruptive chemicals (EDCs) hard to assess?

Many chemicals are capable of interacting with steroid receptors (“endocrine activity”), but whether this always leads to adverse effects is often unclear.

Endocrine disrupting chemicals can have effects at doses much lower than what is usually used in toxicological tests, and the current risk assessment methods might need to be adapted.

It is put into question whether thresholds exists for endocrine disruptors, which is a dose below which there is no effect. For example, since there is already a certain level of natural estrogen in the body, it can be argued that any amount of externally added estrogenic agent could have an effect, without any threshold.

This introduces considerable uncertainties, with the likelihood of overlooking harmful effects in humans and wildlife. Until better tests become available, hazard and risk identification has to rely also on epidemiological approaches.

What is the “State of the Science” for various families of chemical substances?

Here is a summary of the main groups of chemicals that are considered for their endocrine disrupting potential.

• Bisphenol A. Its effects are multifaceted because it can interfere with estrogen, progesterone, and thyroid hormones. Exposure during organ development has been demonstrated to produce irreversible adverse effects on reproductive organs.
• Phthlates. There is good evidence that they can cause developmental problems in male fetuses by interfering with testosterone synthesis. Some phthalates (including benzyl-butyl-phthalate (BBP) and di-ethyl-hexyl-phthalate (DEHP)) also interact with estrogen receptors. Effects on wildlife remain largely uninvestigated.
• Parabens. Epidemiological evidence in humans is very limited. There is some evidence of an effect on the density of breast tissue, but no evidence that it may increase breast cancer risk.
• PCBs (polychloro biphenyls). PCB exposure has been associated with an increased risk of breast cancer and of other cancers. They also have an effect on neural development. Effects have also been found in animal models.
• Dioxins (PCDDs and PCDFs). These have some of the effects of PCBs. They are linked to early menopause, breast cancer and thyroid cancer.
• Polybrominated biphenylethers (used notably as flame retardants). Exposure during early development can have important effects on neural development. There are also a number of potential effects on reproduction.
• Perfluorinated compounds (PFCs). There is evidence that these chemicals interfere with thyroid hormone conversion. There also is an association with increased cholesterol levels, indicating that they could create metabolic disorders. The effects of PFCs on wildlife have yet to be determined.
• Pesticides. Various families of pesticides are considered:
  
  • Dicarboxamides. Experimental evidence, but no direct evidence of exposure-disease associations exists yet for either humans or wildlife.
  • Azole fungicides (including triazoles and imidazoles). Effects on the babies of mothers exposed to these pesticides during pregnancy were proven, but no link to a specific compound.
  • Triazines (atrazine and simazine are among the most widely used herbicides). Wild frogs collected from contaminated sites showed sexual development problems. Effects in mammals remain largely undetermined.
• Heavy metals.
  • Methylmercury has multiple modes of action relating to the endocrine system.
  • Lead release of the thyroid hormone TSH by the pituitary gland.
  • Cadmium, a weak link is made by some epidemiological studies of occupational exposure and breast cancer. There is also some evidence that cadmium may have other effects on male and female health. Its effects in wildlife are understudied.
• Other chemicals. Multiple new chemicals and groups of chemicals have come to the fore over the last decade as being of potential concern. In the case of sunscreen UV filters and of artificial musks, which are present in many cosmetic and personal care products, there is not yet direct evidence on humans, but some evidence do exist for some of them from studies conducted in animals and in vitro.

What are the main recommendations of the report?

The six recommendations made in this report to the European Commission are:

1. Implement validated and internationally recognised test methods in the testing and information requirements for regulation,
2. Develop further guidance documents for the interpretation of test data;
3. Consider the creation of a separate regulatory class “Endocrine Disruptor” (ED);
4. Develop weight-of-evidence procedures that deal with the available evidence by weighing the criteria “adversity” and “mode of action” in parallel, but not by applying these criteria sequentially to exclude substances from the assessment;
5. Abandon “potency” as the only criterion, and consider potency together with other criteria such as toxicity, specificity, severity and irreversibility, in a weight-of-evidence approach.
6. Create regulatory categories that stimulate the generation of the necessary data, including test methods that are not validated, beyond the OECD Conceptual Framework for Endocrine Disrupter Testing.

References:

Highlights prepared by GreenFacts of the report “State of the Art Assessment of Endocrine Disruptors” which presents the results of a project commissioned by the European Commission, DG Environment  ec.europa.eu/environment/chemicals/endocrine/pdf/sota_edc_final_report.pdf and its updated annex on the state of the science on endocrine disrupters :  ec.europa.eu/environment/chemicals/endocrine/pdf/annex1_summary_state_of_science.pdf