**2.3 Cosmetics (UV filters)**

Cosmetics include all non-pharmaceutical substances consumed or applied to improve personal health, hygiene, or appearance. These products contain many components such as phthalates, parabens, UV filters, polycylic musks, antimicrobials, formaldehyde, which are used different purposes. In addition, many cosmetic products contain heavy metals such as lead, cadmium, antimony, chromium, arsenic, mercury, nickel as ingredient or impurities [18, 67]. The main route of exposure is through the skin and through inhalation. The main endpoint of exposure is endocrine disruption. This is because of the many substances in cosmetics and UV filters that have endocrine active properties that affect directly damaging the testicular tissue. Recently, Peterson et al. [18] investigated the cosmetic exposure and associations with measures of semen quality in young Danish men. Despite the widespread use of multiple products, they found little an association with semen quality.

UV filters are used not only in cosmetic products such as skin lotion, beauty creams, lipsticks, and hair sprays, but also as additives in plastics, printing inks, shampoos, perfumes, and other products. Although UV filters are applied to the body surface, there is information that they are absorbed, metabolized, bio accumulated, and/or excreted from the skin. There is not much information about the metabolism of the UV filter in humans in the literature [68–70].

UV filters are new environmental pollutants that could potentially affect a large proportion of the population [71]. Men's exposure to these substances is likely due to contact with products containing these chemicals [72]. In fact, *in vitro* and *in vivo* studies in different species of mammals showed that some of these UV filters exhibit hormonal activity and are able to interact with estrogen, androgen, and thyroid signaling [68]. However, epidemiological studies on the relationship between hormonedisrupting effects of organic UV filters and infertility are very limited. Therefore, more research is needed to determine the health risks of these substances [73]. Frederiksen et al. [72] investigated the degree of exposure of human spermatozoa to UV filters in Danish men. They found that almost half of the men had measurable concentrations in their seminal fluid of at least one of the selected UV filters.

In recent studies, the mechanism of action of UV filters on sperm has been evaluated. Some processes in sperm depend on calcium ion channels opened in the cell membrane. CatSper ion channel, which is specifically expressed in spermatozoa, controls intracellular Ca2+ concentration and sperm motility. CatSper activation

mediates an increase in intracellular Ca2+ levels in the sperm tail. The presence of an inactive CatSper protein in male mice has been reported to cause infertility [74, 75]. Schiffer et al. [74] investigated the effect of 96 different EDCs including UV filters (4-MBC, BP3, 3-BC, HMS, OD-PABA) on human sperm. Researchers reported that structurally diverse EDCs activate the sperm-specific CatSper channel, thereby inducing intracellular Ca2+ increase, motility response, and acrosomal exocytosis. Rehfeld et al. [76] also revealed that organic UV filters have been shown to induce a Ca2+ influx through CatSper. As a result, authors argue that EDCs (selected UV filters) interfere with various sperm functions and thus may impair human fertility. Sperm cell dysfunction is a common cause of infertility. Progesterone is a known inducer of acrosomal reaction in sperm cells, and suboptimal induction of acrosomal reaction in response to progesterone is correlated with fertility. Rehfeld et al. [77] examined the effects of organic UV filters on the human sperm cell function acrosomal reaction, sperm penetration into a viscous medium and hyperactivation, as well as on sperm viability. The result of these study showed that selected UV filters mimic the effects of progesterone on the activation of the CatSper Ca2+ channel in human spermatozoa.

Adoamnei et al. [78] investigated whether there are associations between urinary concentrations of BP-type UV filters and semen quality and reproductive hormone levels in young men. They found a significant positive association between urinary BP-type (BP1 and BP3) concentrations and some reproductive hormones (FSH, T/E2). They suggest that further research is needed in other male populations. When the relationship between semen parameters and reproductive hormones is evaluated in other studies with BP-type UV filters, it is reported that there is a significant relationship [79] and found no association between urinary concentrations of BP3 and idiopathic male infertility [80]. As a result, human exposure to these organic UV filters can interfere with sperm and impair fertility.
