BPA is used extensively in the manufacture of plastic tools and bottles, and in coating the inner layer of plastic food and beverage containers. The use of BPA in the manufacture of baby bottles has been banned in Europe since 2011 [32], [117] because of its suspected harmful effects on the developing body. However, it is not only infants who are at risk. According to a study by the International Endocrine Society, BPA can be detected in the urine of 93% of the American population, which can be attributed to high exposure [32]. In addition to urine, BPA can also be detected in blood, semen, and even human hair [118], [119]. In recent years, not only BPA but also its analogues with similar endocrine effects have been detected in human urine, with concentrations increasing year by year [120]. The widespread use of BPA-free water bottles and food containers, which are increasingly popular, is crucial. BPA binding to various subtypes of estrogen receptors (ERR, ER -α, ER -β) can induce hormonal alterations that may contribute to premature sexual maturation, obesity, menstrual irregularities, and implantation disorders in women. In men, it may lead to testicular and epididymal atrophy and a decrease in testosterone levels. In men, an association has also been found between urinary BPA concentration and lower sperm count, and in women, high levels of BPA in maternal urine have been associated with the incidence of preterm birth [37]. BPA may also play a role in the development of female infertility, and high urinary BPA concentration may be associated with in vitro fertilization (IVF) failure [121]. High BPA serum levels caused oxidative stress and impairment of pancreatic β-cell function in animals. Hyperinsulinemia, insulin resistance, and glucose intolerance were observed in mice. In human epidemiological studies, a positive correlation between urinary BPA concentration and the incidence of obesity and metabolic syndrome was found [37], [122]. Its immunomodulatory effect and its influence on the development of the thyroid-hypothalamic-pituitary-testicular axis have also been demonstrated. It stimulates VEGF (vascular endothelial growth factor), leading to unwanted new blood vessel formation and thickening of the interventricular septum (IVS). In this way, it may also contribute to the development of hypertension [123]. Figure 5 [123] shows the effects of BPA on living organisms. The aim of the Commission Regulation (EU) 2018/213 is to reduce BPA contamination in food. This regulation establishes a specific migration limit of 0.05 mg of BPA per 1 kg of food from varnishes or coatings applied to materials or articles that come into contact with food [124].

 

The so-called additive flame retardants are not chemically bound to the polymer but are released from it more easily thanks to weaker intermolecular interactions. Highly corrosive, toxic gaseous flame retardants released from plastic waste can bind to particulate air pollutants and be inhaled by living organisms, but these compounds can also be found in drinking water and natural waters [28]. From the point of view of environmental protection, their most important representatives are polybrominated biphenyls (PBBs) and polybrominated diphenyl(biphenyl)ethers (PBDEs), which are currently used, and polychlorinated biphenyls (PCBs), which are no longer used. Although polychlorinated biphenyls, which were once used extensively in the manufacture of electronic products, are no longer used, they are persistent molecules and can still be detected in natural waters today. Cross-sectional studies have found an association between human PCB exposure and abnormal sperm motility and morphology [133]. A meta-analysis summarizing studies that examined PCB concentrations in fetal cord blood, maternal blood, and breast milk confirmed that prenatal PCB exposure damages fetal development [134]. It was found that higher PCB concentrations in maternal serum can lead to lower birth weight. Due to their good lipid solubility, brominated flame retardants accumulate in adipose tissue and tend to bioaccumulate, have liver toxicity, can cause neurotoxicity, and are suspected carcinogens. Some substances impair thyroid function, have estrogenic and antiandrogenic effects, and negatively affect cognitive functions [33]. Polybrominated biphenyls (PBBs) and their hydroxylated metabolites bind weakly to ER -α- and ER -β-receptors, but they are effective inhibitors of estrogen sulfotransferase, one of the enzymes that converts estrogen to an inactive metabolite. By inhibiting the enzyme, they can indirectly trigger an estrogenic effect [135].

Per- and polyfluoroalkyl compounds (PFAS, e.g. perfluorooctanoic acid and perfluorooctanesulfonate) are also popular and widely used additives in the plastics industry. Due to their strong C-F bond, they are extremely resistant to thermal, chemical and biological decomposition. However, this industrially favorable property also prevents their degradation in the environment and in living organisms; they are extremely persistent and tend to bioaccumulate. Their elimination half-life in the human body is long (up to 4-7 years). They pass into breast milk and cross the placenta; they can also be detected in tissues of the pancreas, liver, lungs, and brain. Per- and polyfluoroalkyl compounds affect the expression of genes involved in cholesterol metabolism. By binding to PPAR-α and PPAR-γ receptors, they stimulate differentiation of fat cells and increase the amount of body fat. In rodents, they inhibit the enzyme 11-β-hydroxysteroid dehydrogenase 2, thereby increasing glucocorticoid concentrations, which affects growth and brain development. In animal studies, thyroid functions have also been altered [136]. They are neurotoxic and have an immunotoxic effect on the developing fetus. Male fetuses exposed to PFAS compounds in utero had lower sperm counts as adults. Perfluoroalkyl compounds have antiandrogenic and estrogen-like effects and alter male fertility [137].