Many chemicals are structurally similar to endogenous hormones and can disrupt the normal functioning of the endocrine system. Endocrine disruptors are present in a wide range of natural and synthetic products and can enter the body via consumption of food, drink, and air, or through the skin.
Even small quantities of endocrine disruptors may have a large impact on the natural functioning of the body’s hormones, generating a cascading disturbance due to the hormone-like effects observed in these chemicals.
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Case study: Bisphenol A
Plastics may frequently contain chemicals that induce hormone-like effects on the body, and in most developed regions the content of these plastics is controlled based on the likely end-user and frequency of exposure. For example, bisphenol A (BPA) has been utilized as a precursor to creating hard plastics for several decades and was widely used in the manufacture of water bottles and food containers, in addition to non-food contact-related applications.
More recently, however, the European Union has upheld the decision to consider BPA a “substance of very high concern” due to the growing evidence of the estrogen-mimicking effects of the chemical. The FDA currently upholds that the effects of BPA are minimal, and argues that BPA is rapidly metabolized and excreted by primates.
The FDA has ceased to recommend BPA for use in baby bottles, though only due to replacement with other materials by the market. Several states have, however, prohibited the use of the chemical in food contact items and children’s toys, including California, Delaware, Illinois, and Maine, to differing degrees.
Studies have suggested that 99% of BPA exposure could be via consumption, the chemical having leached into food products from plastic containers or during production. BPA can be effectively purged from municipal water sources, but has nonetheless been found in tap water and even in particulate matter in the air in some urban environments.
Many of the more damaging studies into the health effects of BPA tend to be based on observation of the result of large single dose administrations, and studies on human subjects are sparse, in particular towards fetuses.
The estrogenic effects of BPA occur as the molecule can bind with both of the two types of nuclear estrogen receptors that are found on the surface of cells throughout the body, acting both as an agonist and partial antagonist. At high concentrations, BPA has also been found to act as an antagonist towards androgen receptors.
Upon activation, the receptor proteins translocate to the nucleus and are involved in gene expression. The average person living in the USA is likely to have BPA present in bodily fluids in the PPB range, within the same range that is observed to generate negative outcomes in animal models.
The accumulation of hormone-like chemicals in the environment has been evident since the 1960s, and the first evidence that these chemicals could disturb the endocrine system of marine species was noted at this time.
During the 1980s an unusually high number of hermaphroditic fish and crocodiles with extremely low testosterone levels were found in marine environments surrounding industrial zones high in estrogen-mimicking pollutants, and these were the first types of endocrine disruptors recognized.
Besides estrogen, a wide range of other key hormones could be mimicked by hormone-like chemicals. Thyroxin is a thyroid hormone that is involved in metabolism homeostasis, and exposure to polychlorinated biphenyls has been shown to reduce levels of this hormone, impacting other growth-related processes.
As with BPA, the direct long-term low-dose effects of polychlorinated phenols and other hormone-like chemicals are difficult to assess in human subjects thanks to the extremely complex and cascading nature of the interactions taking place throughout the endocrine system and its peripheral components. However, identifying these chemicals and minimizing exposure to them is possible using modern techniques.
What are endocrine disruptors?
Identifying hormone-like compounds
The European Union considers a substance to be an endocrine disruptor when it shows adverse effects in an organism or its offspring through a hormonal mode of action. Many chemicals have long been suspected of disrupting the hormonal system, and most of these have or are currently being thoroughly investigated by many groups around the world.
Many additional chemicals have been added to the list of suspects both by concerns raised via observation and by active investigation. In silico methods have been used to generate probable leads for hormone-like chemicals based on structure and other chemical characteristics, supported by further in vitro, and in vivo experiments.
Traditional methods of quantitative analysis such as gas/liquid chromatography-mass spectrometry can be applied to biological or environmental samples to determine the presence of endocrine disruptors that have previously been identified.
Rapid and cost-effective enzyme-linked immunosorbent assays (ELISA) have also been developed for the detection of a wide range of endocrine disruptors. Antibodies against the chemicals can be generated, and colorimetrically or fluorimetrically indicate the presence of the chemicals in a sample in a quantitative manner, allowing quick field testing.
- Vandenberg, L. N., Hauser, R., Marcus, M., Olea, N. & Welshons, W. V. (2007) Human exposure to bisphenol A (BPA). Reproductive Toxicology, 24(2). www.sciencedirect.com/.../S0890623807002377
- Graziani, N. S., Carreras, H. & Wannaz, E. (2019) Atmospheric levels of BPA associated with particulate matter in an urban environment. Heliyon, 5(4). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454204/
- Calsolaro, V., Pasqualetti, G., Niccolai, F., Caraccio, N. & Monzani, F. (2017) Thyroid Disrupting Chemicals. International Journal of Molecular Sciences, 18(12). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751186/
- Goda, Y., Kobayashi, A., Fukuda, K., Fujimoto, S., Ike, M. & Fujita, M. (2000) Development of the ELISAs for detection of hormone-disrupting chemicals. Water Science and Technology, 42(7-8). https://pubmed.ncbi.nlm.nih.gov/11187743/
- European Chemical Agency (2012) Guidance for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009. EFSA Journal. https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2018.531