## BPA is not the only EDC with harmful effects

Nowadays, humans live in an environment where thousands of human-made compounds are increasingly present due to human activity. Many of them are considered potentially dangerous for human health. Special attention should be paid to EDCs, which, by influencing the function of the hormonal system, can cause the emergence of several (also civilizational) diseases. This chapter will briefly address some of them.

Phthalates are plasticizers used in the manufacturing of various products and are regarded as EDCs due to their anti-androgen effects. Phthalates are often added to vinyl products to make them more flexible but are often added to personal care products, such as perfumes, deodorants, shampoos, soaps, hair sprays, hair gels, nail polish, or body lotions, to help lubricate other substances in the formula and to carry fragrances. Despite their widespread use, phthalates can cause in vitro disruption of steroidogenesis by inducing increased estradiol synthesis. The induction of early (precocious) puberty in girls and altered gene expression in the testis caused by phthalates was also observed.There is evidence that also postnatal exposure is associated with significant decreases in sperm quality via anti-androgenic activity. Moreover, phthalates can contribute to metabolic disorders and are suspected to be associated with obesity in older European women.

Parabens are a class of synthetic chemicals commonly employed as preservatives in food, pharmaceuticals and cosmetic or personal care products. Since these products contain biodegradable ingredients, parabens are added to inhibit the proliferation of harmful bacteria and mould, thereby extending the product's shelf life. Similar to phthalates, parabens may also cause reproductive disorders. Long-term exposure of female mice and rats led to a significant decrease in serum estradiol and thyroxine concentration, a significant delay in the date of vaginal opening, and a decrease of corpora lutea, a temporary endocrine organ in female ovaries that is involved in the production of sex hormones. It is also possible that parabens may act as obesogens and contribute to the obesity epidemic.

Polychlorinated biphenyls (PCBs) were predominantly utilized as electrical insulating fluids in capacitors and transformers, as well as hydraulic, heat transfer, and lubricating fluids. Additionally, PCBs were combined with other chemicals to function as plasticizers and fire retardants, leading to their incorporation into various products such as caulks, adhesives, plastics, and carbonless copy paper. It was found that PCBs bind with relatively high affinity to the aryl hydrocarbon receptor (AhR), which is a ligand-activated transcription factor.The AhR responds to environmental, dietary, microbial, and metabolic signals to regulate complex transcriptional programs, with specificity depending on the ligand, cell type, and biological context. Exposure to PCBs results in reproductive disorders or testicular cancer, as was proven by Klenov et al., (2021) and Hardell et al., (2003). The production of PCBs was banned in many countries in the late 1970s due to their environmental persistence, bioaccumulation, and adverse health effects. However, PCBs can still be found in older equipment and materials produced before the ban, and managing these legacy sources remains an ongoing concern for environmental and public health.

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants, often found in drinking water supplies. These chemicals are environmentally-persistent, human-made compounds that are used in the manufacturing of paper, textiles, pesticides, leather, medical aids, oil, minerals, metal plating, food packaging, cosmetics and personal care products, paints, inks, non-stick cooking utensils, surfactants, firefighting foams, and several other waterproof products (reviewed in detail in Lenka et al., 2021). The PFAS family consists of two main classes which are either fully fluorinated (perfluoro) or partially fluorinated (polyfluoro). The extreme persistence of PFAS lies in the nature of the carbon-fluoride bond because of which PFAS exhibit a high resistance to degradation and heat. PFAS are well known for being non-stick as well as having both, lipophilic and hydrophilic properties. PFASs also have diverse effects on human health, particularly as endocrine disruptors. They influence multiple aspects of male and female reproductive health, alter thyroid hormone synthesis, and contribute to dyslipidemia. However, human studies often yield contrasting results, likely due to the distinct effects of individual PFAS compounds and exposure to mixtures of PFASs in the environment.