## Bisphenol A is a potentially hazardous substance

One of the many endocrine disruptors is bisphenol A (BPA), which is a polyphenolic, synthetically produced substance used in the manufacture of many plastic products and epoxy resins, from which it can enter the environment. For example, BPA can be found in some plastic bottles, the inner lining of cans, disposable plastic products, certain sports protection equipment, medical aids or dental fillings. Epoxy resins are used as industrial adhesives or building materials. However, there are several restrictions on the use of BPA in the European Union. In 2011, the European Commission banned the use of BPA in the manufacture of polycarbonate infant feeding bottles. Then, in 2018, BPA was also banned in all plastic bottles and packaging containing food for babies and children under three years, and since 2020, the use of BPA has been banned in thermal paper receipts (https://www.efsa.europa.eu/en/topics/topic/bisphenol). In addition, recent 2023 EFSA regulations have reduced the tolerable daily intake (TDI) of BPA from 4 µg per kilogram of body weight per day (kg/bw/day) to 0.2 ng/kg/bw/day, which represents a 20,000-fold lowering of TDI.

Nevertheless, since BPA can be released from the material, it is detected in all environmental matrices (soil, water, air) as well as in food and drinking water. Therefore, BPA is considered an “ubiquitous compound” and is an environmental pollutant. We can be exposed to BPA from various sources such as food (especially food wrapped in plastic film or cans), heat-sensitive paper used to make cash receipts, as well as some toys, cosmetic products or dust particles. BPA can also enter the body through the digestive system, the skin and by inhalation. Other sources of exposure are from industry (the chemical industry, which produces BPA, and the textile industry, which produces synthetic fibres) as well as waste and sewage. People from the chemical and textile industries and salespeople who handle hundreds of tills every day are therefore particularly exposed to the effects of BPA. Furthermore, it should be considered that not only humans, but also microorganisms, plants and animals that are part of our food chain are exposed to BPA.

After BPA enters the body, there are several ways it can get into the cells themselves. Probably the easiest way for BPA to enter the cell is by free passage through the lipid bilayer of the membrane. This is possible because of the lipophilic character of the chemical, i.e., the ability of BPA to bind to lipids. BPA is also able to bind to oestrogen receptors on the surface of cells, of which there are several types. Binding to each of these receptors affects signalling pathways and the expression of genes involved in regulating the cell cycle, growth and development. Consequently, the presence of BPA alters the cascades of biochemical reactions in the cell, modulating normal cell behaviour. This leads to various undesirable reactions that do not occur in the cell under physiological conditions. As described in the following subsections, scientific evidence of BPA's harmful effects on humans is accumulating.

BPA may promote the development of some cancers

BPA can trigger the transition of cells from an epithelial to mesenchymal form (Figure 12.8), which is characteristic of the progression of cancer. This is a process in which the epithelial cells of the primary tumour lose cell polarity and intercellular contacts, change the structure of the cytoskeleton (cell skeleton) and take on a mesenchymal form. Cells that have undergone such a transition have increased motility and can migrate into the blood or lymph vessels where they take on the typical characteristics of tumour stem cells. Furthermore, it was found that BPA can be responsible for triggering the process of tumorigenesis in ovarian cells, even at low (environmental) doses.

BPA promotes metabolic changes in the body

BPA is also known as an adipogenic substance, which can cause or increase the risk of obesity and metabolic syndrome. This is because BPA, due to its lipophilic nature, is deposited in adipose tissue where it binds extensively to the nuclear hormone receptor (Figure 12.9). This receptor is a protein that enters the nucleus from the nuclear membrane and binds to the regulatory regions of genes. It then triggers the expression of genes responsible for the formation and development of adipocytes (fat cells), the regulation of blood glucose levels and the formation of proteins that bind fatty acids. Thus, on the one hand, BPA deregulates the formation of fat cells, but on the other hand, it also has a negative effect on sugar and fat metabolism in the blood.

Recently, BPA has been shown to decrease testosterone production in the testes, with the effect depending on the dose and duration of exposure. At the same time, BPA increases the production of the hormone INSL-3 (insulin-like factor 3) in the Leydig cells of the testes, which is responsible for the descent of the testes from the abdominal cavity during intrauterine development of the foetus. Premature descent of the testes at a time when they are not yet sufficiently developed can contribute to reproductive disorders in adulthood.

In young men (aged 18-23 years old) BPA levels were measured in their urine, and this was found to correlate to a reduced amount of luteinising hormone, which stimulates the production and maintenance of testosterone levels. In addition, higher levels of BPA in the urine of these men also corresponded with reduced sperm concentration and total sperm count. These results thus support the hypothesis that BPA can reduce the capacity of Leydig cells, which are responsible for testosterone production, which in turn can reduce fertility.

In females, BPA can impact fertility via multiple pathways. The chemical is able to alter the levels of reproductive hormones, as well as impacting the ovary and there is evidence that exposure to BPA causes follicle loss and decreased oocyte survival. More recent evidence has suggested a link between BPA and PCOS (polycystic ovarian syndrome), although a causal link has yet to be proven.

BPA can be removed from the environment

The first way to remove BPA (as well as other environmental pollutants) from the environment is through the process of biodegradation. Here, microorganisms can use BPA as a carbon source i.e., a food source, which breaks BPA down into less toxic and simpler compounds. Since the entire organic world is made up of carbon and its compounds, microorganisms (e.g., some bacteria from the genera Pseudomonas and Methylomonas) degrade BPA into basic components of organic chemistry and benefit from this process through the production of energy. It is not so important what molecules are made up in the process of BPA degradation, but that bacteria can do it relatively efficiently and in a relatively short time.

Phytoremediation is generally a sustainable method of removing pollutants from the environment. Phytoremediation is based on the fact that plants absorb substances from the environment through their root systems, and some plants can also extract substances that are toxic to us (heavy metals, bisphenols, etc.) from the soil in this way. Examples include Cannabis sativa (hemp) or Panicum virgatum (millet), which can remove even relatively high concentrations of BPA from the soil. In this way, a specific pollutant can be removed relatively quickly and efficiently from the affected area, and the soil can then be used for agricultural purposes without concern of contamination.