Project overview

Scientific background

Bisphenols (BPs) are a group of industrial chemicals extensively utilized in the production of polycarbonate plastics and epoxy resins, representing materials that form a wide variety of products for consumers’ everyday use especially in the production of food contact materials, dental sealants, thermal paper and other paper products, medical devices, eyeglass lenses, metal can linings for food and beverages, baby bottles and children`s toys, coatings for the inside of water pipes and many other applications. Among bisphenols, bisphenol A (BPA; 2,2-Bis-(4-hydroxyphenyl)-propane) is the most widely used with an annual production that reaches over 7.7 million metric tons (in the year 2015) and is expected to reach 10.6 million metric tons by 2022. Chemically they are diphenylmethanes containing two benzene rings separated by one central carbon atom, usually with the 4-OH substituent on both benzene rings.

Starting from the late 1990s, scientific research pointed towards various adverse side effects of BPA – mainly for its disruption in the human hormone system and since then studies reporting its adverse effects to human health are accumulating. It has been identified as a substance affecting hormone systems of humans and animals and thus affecting the reproduction. Besides, more and more studies are reporting its genotoxic properties. Consequently, the questions about its safety have been raised. Due to its hazardous properties, the use of BPA has been limited in the European Union to protect human health and the environment. The first regulatory risk assessment report on BPA published by the Canadian government in 2008 has resulted in the ban of BPA in baby bottles in Canada. In 2009, the European Commission included BPA on the list of substances prohibited in cosmetic products (Regulation (EC) 1223/2009). Soon after in 2011, the EU banned to manufacture, market, and import the infant feeding bottles containing BPA and since 2018 also the packaging of food for babies and children (Regulation (EU) 2018/213). In 2017, a temporary tolerable daily intake of 4 μg/kg bw/day for BPA has been proposed by the European Food Safety Authority (EFSA), while in September 2018 EU Regulation reduced the migration limit for BPA from food packaging material into food from 0.6 mg/kg to 0.05 mg/kg and prohibited the migration of BPA into any baby food or infant formula. Since 2018 products containing BPA must be classified and labelled as toxic to reproduction. Furthermore, the use of BPA in the thermal paper has been restricted since 2020 by EU 2016/2235 regulation and REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals). National restrictions in Slovenia related to the use of BPA follow the EU legislation.

Problem identification

In 2017, the European Chemical Agency (ECHA) under REACH legislation added BPA to the Candidate List of substances of very high concern (SVHCs) due to its toxic impact on reproduction and endocrine-disrupting properties that may cause the adverse effects to humans health and the environment. All these restrictions on the use of BPA in consumer products have prompted the industry to develop and gradually replace BPA by its chemical analogues such as bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF) and many other, presumably as safer alternatives to BPA.

To date, more than 200 BPs have been identified as BPA analogues in consumer products (food packaging, toys etc.) and their global industrial production is expected to increase even more in the near future In the last two decades, the toxicity of BPA has received a lot of attention, while data for BPA analogues are scarce, despite the fact that they are threatening to become a dominant environmental pollutant. Indeed, the presence of several BPA analogues have already been reported in the environment in indoor dust, sediment, river water, soil, seawater, and sewage sludge sometimes in levels similar to or higher than that of BPA. Still, the occurrence and the internal exposure risks of BPA alternatives in the general population remain poorly understood. Due to their structural similarity and physicochemical properties with BPA, the safety of these analogues is questionable in particular as research data have shown that some of them possess very similar or even higher toxic potential among other endocrine-disrupting activity, reproductive toxicity and genotoxicity compared to BPA.

To protect human health and environment REACH regulation ((EC) No 1907/2006) requires safety assessment of chemicals and products that are intended for human use, or come into contact with food ((EU) No 10/2011). Very important is the information on genotoxic activity and endocrine-disrupting potential of chemicals in order to protect human health. Endocrine-disrupting compounds (EDCs) are exogenous chemicals or mixtures of chemicals that interfere with hormone activities or the endocrine system. They can promote hormone-sensitive disorders and cancers, produce adverse reproductive, neurological, developmental, and immune effects, as well as obesity, diabetes mellitus, and cardiovascular disease. On the other hand, genotoxic compounds interfere with the function of DNA and induce genetic alterations in somatic and germ cells that can lead to mutations with delayed effects resulting in cancers and other chronic diseases, reproductive effects, heritable diseases, and as shown by more recent studies, also neurodegenerative effects21. These effects are usually manifested years after the exposure.

So far, the majority of BPA analogues is still not regulated and they are not included in the legislation although many of them appear to be harmful to humans. In modern civilization, the products containing BPs are related to our everyday life, which means daily exposure. Due to this, the likelihood of being exposed to a combination of several bisphenols is high, which is particularly important in the case of vulnerable populations. In addition to the lack of knowledge on the toxicological properties of BPA analogues, unfortunately, the human health risk assessment is still performed on data of individual compounds where co-exposures of BPA with other BPs are not considered in the risk assessment. However, co-exposures to several BPs should not be neglected as the interactions between chemicals can occur leading to additive, synergistic, or even potentiating effects, which can have more prominent adverse health effects compared to those of single compounds. For this reason, it is very important to explore potential adverse effects of BPA analogues and to elucidate their mechanisms of action, in particular, the mechanisms of combined (geno)toxic effects of the most abundant BPA analogues. While knowledge on the endocrine-disrupting activity of BPA and its analogues is very comprehensive, data on their genotoxic activity are extremely scarce, thus the focus of the postdoctoral project will be to study the genotoxic potential of BPA analogues and the mechanisms involved.


We are open for collaborations, if you’re interested please contact dr. Martina Štampar.