What is an endocrine receptor

Endocrine disruptors and their impact on humans and the environment.

What is an endocrine disruptor?

The endocrine system is made up of all of the endocrine glands and hormone receptors in the body. It helps regulate the development, growth, reproduction and metabolism of animals and humans.

Some chemical substances, both natural and human, can affect the endocrine glands, their hormones, or the receptors they act on. These chemical substances are called "endocrine disruptors" or "endocrine disruptors" (EDCs).

Why this growing concern about endocrine disruptions from some chemicals?

Negative effects on reproduction have been observed and there is clear evidence that Wildlife populations can be affected. Over the past two decades there has been evidence that hormone levels are highdisturbances in humans increase.

Extensive laboratory studies support the view that exposure to certain chemicals contributes to endocrine disruptions in humans and wildlife. Exposure during critical developmental phases can result in irreversible and delayed effects that only emerge later in life. However, it is very difficult to link endocrine disruptions to individual chemicals, especially if they only stay in the body for a short time.

What are the main effects of endocrine disruptors being studied?

Four main groups of impacts are considered:

Influence on healthy human reproduction.

One of the key issues is the reproductive health effects for both men and women. They range from incomplete sexual development to fertility problems.

Human hormonal cancer

Certain cancers in humans are influenced by hormones, and in these cases endocrine disruptors can play a role in the development of the disease. But for many hormonal cancers, there isn't enough information about the possible role of endocrine disruptors.

Effects on development and metabolism in humans

Endocrine disruptors can affect the thyroid system and several other hormonal systems. They can also affect immune system functions. There is some evidence of a link between chemical exposure and the widespread obesity rate.

Impact on wildlife

The main effects that are studied on the animal world have to do with reproduction and development. Effects have been observed on many groups of animals, ranging from invertebrates to mammals.

What makes it difficult to evaluate endocrine disruptors?

Many chemicals can interact with steroid hormone receptors in the body ("endocrine activity") but it is often unclear whether this always leads to harmful effects.

Endocrine disrupting substances can have effects even at much lower doses than those usually tested in toxicological tests, and the current risk assessment methods may have to be adapted.

It is also questioned whether there are impact thresholds, i. H. a dose below which there is no effect. An example: Since a certain natural estrogen level is already present in the body, it can be argued that even the smallest amount of estrogenic substances supplied from outside could have an effect - without an effect threshold.

This brings with it considerable uncertainty; adverse health effects in humans and wildlife could be overlooked. Until better tests are available, hazard identification and risk assessment must also be based on epidemiological approaches.

What is the "state of the art" for different families of chemical substances?

The following is a summary of the major groups of chemicals that are being studied for their potential endocrine effects.

  • Bisphenol A. Its effects are varied due to its ability to interfere with estrogen, progesterone and thyroid hormones. It has been shown that exposure during organ development has irreversible, detrimental effects on reproductive development.
  • Phthalates. There is clear evidence that they can lead to developmental disorders in male fetuses by impairing testosterone synthesis. Certain phthalates, such as benzyl butyl phthalate (BBP) and diethylhexyl phthalate (DEHP), also interact with estrogen receptors. Effects on wildlife are largely unexplored.
  • Parabens. Epidemiological knowledge in humans is very limited. There is some evidence of effects on breast tissue density but no evidence of an increased risk of breast cancer.
  • PCB (polychlorobiphenyls). Exposure to PCBs is linked to an increased risk of breast cancer and other types of cancer. They also affect the development of the nervous system. Effects were also found in animal models.
  • Dioxins (PCDD and PCDF). They have some of the effects of PCBs and have been linked to early onset of menopause, breast cancer, and thyroid cancer.
  • Polybrominated diphenyl ethers (used, among other things, as fire retardants). The exposure during early development can have severe effects on the nervous system. There are also a number of potential reproductive effects.
  • Perfluorinated compounds (PFC). There is evidence that these chemicals interfere with thyroid hormone conversion. It is also linked to increased cholesterol, which indicates possible metabolic disorders. The effects of PCF on wildlife have yet to be determined.
  • Pesticides. Several groups of pesticides can be considered:
    • Dicarboxamides: Although there are experimental findings, there is still no direct evidence of the relationship between exposure and disease in humans and animals.
    • Azole fungicides (including triazoles and imidazoles): Effects on infants whose mothers were exposed to these pesticides during pregnancy have been proven, but no association with a specific substance.
    • Triazines. Atrazine and simazine are two of the most widely used herbicides. Wild frogs that were collected from contaminated sites showed problems in sexual development. Effects on mammals are largely unexplored.
  • Heavy metals.
    • Methyl mercury acts in multiple ways on the endocrine system.
    • lead can cause an increased release of the thyroid hormone TSH from the pituitary gland.
    • Cadmium: Some epidemiological studies find a weak link between occupational exposure and breast cancer. There is also evidence that cadmium can have other effects on both female and male health. Its effects on wildlife have not been well studied.
  • Other chemicals. Many new chemicals and groups of chemicals have come to the fore as potentially of concern over the past decade. For UV filter of sunscreens and for artificial musk fragrances, which are used in many cosmetic and personal care products, have not yet been proven to affect humans; however, some laboratory studies done on animals and in vitro indicate this.

What are the main recommendations of the report?

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

  1. Internationally recognized test methods validated for legal test and information requirements
  2. Develop further guidelines for the evaluation of the test data;
  3. Consider creating a separate Endocrine Disruptor (ED) category in the legal framework;
  4. Develop an evaluation procedure with the “evidential value of the data” approach that weights available evidence in parallel according to the criteria “harmfulness” and “mode of action.” This avoids the criteria being evaluated one after the other and substances thus being excluded from the evaluation;
  5. No longer use "potency" as a stand-alone criterion, but instead use potency together with other criteria such as toxicity, specificity, severity and irreversibility ("evidential value of the data" approach).
  6. Create categories in the legal framework that encourage the generation of the necessary data, including the development of non-validated test methods, beyond the conceptual framework of the OECD.