**2. Endocrine disruptors in cosmetics and PCPs**

#### **2.1 What is an endocrine disruptor?**

The World Health Organization defines an endocrine disrupting chemical (EDC) as an exogenous substance or mixture of substances that alter one or more functions of the endocrine system and consequently cause adverse effects on the health of an intact organism or its progeny [6].

The main characteristics of exposure to EDCs are as follows [7–10]:


**29**

*Endocrine Disrupting Chemicals in Cosmetics and Personal Care Products and Risk…*

• The curves that relate the exposure doses to EDCs with the adverse effect are not linear. The response does not always increase in the same proportion as the

• In general terms, individuals are not exposed to a single type of EDC but to a mixture of EDCs. Therefore, the effects are difficult to predict given the possible synergistic, additive, or antagonistic actions between chemical

• As a result of exposure to EDCs in a certain individual, consequences can be observed in subsequent generations, due to either genomic involvement or epigenetic mechanisms. There is great difficulty in establishing a causal association because the effects observed after exposure can occur after long

EDCs are distributed in the environment due to their widespread use. Depending on their resistance to physical, chemical, and biological degradation as well as their degree of liposolubility, EDCs can be divided into "persistent EDCs" and "non-persistent EDCs." In the case of persistent EDCs, low biodegradability, volatility, bioaccumulation in the trophic chain, and biomagnification are its most outstanding characteristics [11]. Furthermore, they can be transmitted to the offspring through the mother during pregnancy and lactation [12]. Since the 1970s, most countries have banned or severely restricted the production, handling, and disposal of the majority of them due to consistent evidence of their adverse effects at doses traditionally considered safe [13, 14]. Despite this, global population is suspected to be primarily exposed to these pollutants through diet, given the bioaccumulation pattern of these chemicals in

On the other hand, non-persistent EDCs are less liposoluble, and therefore, they are prone to be metabolized and excreted rapidly [15, 16]. In addition to a variety of pesticides such as glyphosate or permethrins, this group includes bisphenol-A (BPA) and its analogues, parabens (PBs) [methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butyl-paraben (BuP)], phthalates, and benzophenones (BPs). Currently, there is diverse evidence showing the presence of numerous EDC families (mainly phthalates, bisphenols, parabens, and benzophenones) in cosmetic products and PCPs [17–20]. However, contrary to most persistent EDCs, international regulation of their production, handling, and disposal is limited to a reduction in the concentrations of some specific compounds for those cosmetics in the EU market (EU 1004/2014). **Table 2** summarized the trade name, CAS number, and hormonal activity attributed to some of the most frequently used EDCs in

Phthalates are used as a plasticizer in cosmetics and PCPs. The study carried out by Gao and Kannan [17] recently revealed that phthalates were found in >90% of the 77 feminine hygiene products analyzed. Mainly, they were found in all the tested pads, panty liners, tampons, and wipes. Furthermore, phthalates were also found in bactericidal creams and solutions, deodorant sprays, and powders. In another study, Guo and Kannan [18] showed that phthalates were also present in leave-on products, such as skin lotions, hair care products, perfumes, skin toners, deodorants, and creams. In this regard, detectable levels of phthalates were found in face creams, eyeliner creams, hand creams, sunscreens, lipsticks, and nail polish. These EDCs were also detected in products for dental hygiene and rinse-off

*DOI: http://dx.doi.org/10.5772/intechopen.93091*

residues (the cocktail effect).

**2.2 Sources and routes of exposure to EDCs**

exposure dose.

latency periods.

the food chain [14].

cosmetics and PCPs.

*Endocrine Disrupting Chemicals in Cosmetics and Personal Care Products and Risk… DOI: http://dx.doi.org/10.5772/intechopen.93091*


#### **2.2 Sources and routes of exposure to EDCs**

*Endometriosis*

**Table 1.**

prevention of diseases, hygiene practices have also greatly changed through the cultures and eras, from bathing facilities in the Roman period to modern synthetic

In the last years, the variety of cosmetics and personal care products (PCPs) have greatly increased (**Table 1**), in parallel to their manufacturing and consumption volumes in developed and developing countries. For example, the consumption of cosmetics and perfumery in Spain has consecutively increased in the last years, reaching a total of 1280 million units sold of these products and 770 million units exported during 2018. To date, the USA is the leader in the consumption of cosmetics and perfumery, with an amount of 78.6 billion euros, followed by China (52 billion euros), Japan (32 billion euros), and Brazil (28 billion euros) [4]. Despite the current beauty standards are not similar along cultures and ethnicities, it is acknowledged that women have a greater use of cosmetics and personal care products (PCPs) when compared with men [5], and therefore, potential adverse effect may

**Table 1** summarizes the main types of cosmetics and PCPs commonly used

The World Health Organization defines an endocrine disrupting chemical (EDC) as an exogenous substance or mixture of substances that alter one or more functions of the endocrine system and consequently cause adverse effects on the

• There is no safe dose of EDCs. They act at low concentrations and in combination with endogenous hormones, making it difficult to establish a threshold

• Exposure to EDCs during periods of special vulnerability of the individual's development—pregnancy, lactation, puberty—causes damage with adverse

The main characteristics of exposure to EDCs are as follows [7–10]:

products such as body lotions or hair tonics [3].

*Most used cosmetics and personal care products.*

affect predominantly to this population.

**2.1 What is an endocrine disruptor?**

level of no effect.

**2. Endocrine disruptors in cosmetics and PCPs**

health of an intact organism or its progeny [6].

effects throughout their lives and descendants.

worldwide.

**28**

EDCs are distributed in the environment due to their widespread use. Depending on their resistance to physical, chemical, and biological degradation as well as their degree of liposolubility, EDCs can be divided into "persistent EDCs" and "non-persistent EDCs." In the case of persistent EDCs, low biodegradability, volatility, bioaccumulation in the trophic chain, and biomagnification are its most outstanding characteristics [11]. Furthermore, they can be transmitted to the offspring through the mother during pregnancy and lactation [12]. Since the 1970s, most countries have banned or severely restricted the production, handling, and disposal of the majority of them due to consistent evidence of their adverse effects at doses traditionally considered safe [13, 14]. Despite this, global population is suspected to be primarily exposed to these pollutants through diet, given the bioaccumulation pattern of these chemicals in the food chain [14].

On the other hand, non-persistent EDCs are less liposoluble, and therefore, they are prone to be metabolized and excreted rapidly [15, 16]. In addition to a variety of pesticides such as glyphosate or permethrins, this group includes bisphenol-A (BPA) and its analogues, parabens (PBs) [methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butyl-paraben (BuP)], phthalates, and benzophenones (BPs). Currently, there is diverse evidence showing the presence of numerous EDC families (mainly phthalates, bisphenols, parabens, and benzophenones) in cosmetic products and PCPs [17–20]. However, contrary to most persistent EDCs, international regulation of their production, handling, and disposal is limited to a reduction in the concentrations of some specific compounds for those cosmetics in the EU market (EU 1004/2014). **Table 2** summarized the trade name, CAS number, and hormonal activity attributed to some of the most frequently used EDCs in cosmetics and PCPs.

Phthalates are used as a plasticizer in cosmetics and PCPs. The study carried out by Gao and Kannan [17] recently revealed that phthalates were found in >90% of the 77 feminine hygiene products analyzed. Mainly, they were found in all the tested pads, panty liners, tampons, and wipes. Furthermore, phthalates were also found in bactericidal creams and solutions, deodorant sprays, and powders. In another study, Guo and Kannan [18] showed that phthalates were also present in leave-on products, such as skin lotions, hair care products, perfumes, skin toners, deodorants, and creams. In this regard, detectable levels of phthalates were found in face creams, eyeliner creams, hand creams, sunscreens, lipsticks, and nail polish. These EDCs were also detected in products for dental hygiene and rinse-off


*Trade name, CAS number and demonstrated hormonal activities.*

#### **Table 2.**

*Most common endocrine disrupting chemicals in cosmetics and personal care products.*

products (including body wash, shampoos, hair conditioners, face cleaners, and shaving gels).

In the case of the PB family, its main use in cosmetic products and PCPs is due to their antimicrobial properties [21]. It has been shown that the use of mixtures of paraben congeners allows the increase of their preservative capacity with the use of lower levels of each compounds [19]. Average daily application rates per women for face creams, hand or body lotions, facial cleansers, shampoos, and bath gel were 2.1, 8.7, 4.1, 12.8, and 14.5 g, respectively [22]. Yazar and Johnsson [20] carried out a study where they verified the composition of a series of 204 cosmetic products, which included shampoos, hair conditioners, liquid soap, wipes from different brands, and stores. The results showed that at least 44% of the analyzed cosmetics contained at least one PB congener. The PB that was found in the highest proportion was MeP (41% of the products), followed by PrP (25%). In the study carried out by Gao and Kannan [17], it was found that all feminine hygiene products contained at least one PB, and both MeP and EtP were found in >80% of these compounds, mainly in wipes, creams, bactericide solutions, deodorant sprays, and powders. Moreover, it has been reported that PBs were detected in 40% of the dental hygiene products analyzed and 60% in other types of daily hygiene products. MeP and PrP were the most detected compounds (40% of the analyzed samples), followed by BuP (∼20%). The highest concentrations of MeP, EtP, PrP, and BuP ranged between 1040 and 8200 μg/g, which represent approximately 0.1–0.8% per product by weight [18]. Another study carried out in China [19] found PBs in all the categories of PCPs analyzed. Almost all creams, lotions, and face cleaners contained MeP and PrP, with concentrations of MeP slightly higher than PrP (2830 and 1560 μg/g, respectively). Their presence was greater in creams and lotions than in shampoos and body soaps.

BPs are used as ultraviolet (UV) filters. As shown in the study carried out by Rastogi [23], 75 sunscreen products from Europe and the USA tested contained levels of up to three UV filters. A recent study [24] verified the presence of BP-1 and BP-3 in 19.1% of their analyzed products (283 samples analyzed), especially in makeup products, which represented 45.2% of the products with the presence of BPs.

**31**

*Endocrine Disrupting Chemicals in Cosmetics and Personal Care Products and Risk…*

In addition to these three families, the chemical composition of cosmetics and PCPs also contains many other compounds, although with a lower percentage of the presence in these products. Among them, bisphenols, camphenes, dimethicones, and oxycinnamates can be found. Within these minority families, bisphenols are the one that are usually found in the greatest presence in cosmetic products. The main use of BPA is the manufacture of epoxy resins, obtaining polycarbonate plastics, which have great mechanical and thermal stability, as well as very good transparency [25], while the main use of the families of camphenes, dimethicones, and oxycinnamates is that they are used as preservatives in the manufacture of PCPs [26, 27]. Nevertheless, the concentrations of these substances in cosmetics and

Contrary to persistent EDCs that mainly reach body internal compartments through diet, the main route of human exposure to non-persistent EDCs released from cosmetics and PCPs is mainly the dermal route [28]. Therefore, these EDCs avoid the first-pass metabolism, enhancing the bioavailability and therefore the biological effect of the parent compounds [15]. In this regard, several studies have related to the use of cosmetics and PCPs and internal levels of PB and BPs. For example, it has been recently found that levels of some PB and BPs in menstrual blood are related to the use of cosmetics [29]. Moreover, urinary concentrations of PBs were related to the use of hair products, deodorants, face, and hand creams [30]. Similarly, Larsson et al. [31] found higher levels of PBs and phthalates among

EDCs act at very different levels of complexity, interfering a variety of hormone-signaling pathways. For instance, they can modify the circulating levels of hormones by acting on their synthesis, metabolism, or degradation. They can also reduce, increase, or interfere with the specific receptors for hormonal action and therefore affect the ability to respond to natural hormones [32]. In the particular case of EDCs that interfere in steroid hormone-related signaling pathways, the observed effects seem to be linked to the activation/blocking of nuclear receptors, which are the most common modes of action responsible for dose curves with nonmonotonic response in experimental studies [33]. In fact, many EDCs released from cosmetics and PCPs have been evidenced to exert estrogenic and antiandrogenic

An increasing number of studies have also linked exposure to EDCs with epigenetic changes in humans [41, 42]. An unexposed individual may show epigenetic changes due to (1) altered ovum or sperm after EDC exposure or (2) in utero exposure to EDCs. In this regard, it has been evidenced that fetal exposure to environmental pollutants with endocrine disrupting properties such as mirex, chlordane, or *p,p´*-DDE can cause epigenetic changes with transgenerational effects [43, 44]. This is also the case of bisphenol-A (BPA), and PBs, with epigenetic changes after

Furthermore, inflammation and oxidative stress have also been recently postulated as possible mechanisms of action of EDCs [47–50]. In this regard, oxidative stress, that is, the imbalance between the production of free radicals and the antioxidant capacity, has been shown to be enhanced after exposure to a variety of EDCs, including PBs and BPs [47, 49, 50]. For instance, human exposure to PB and BP has been linked to higher levels of lipid peroxidation [50, 51]. Moreover, local disruption of the antioxidant capacity has also been reported [47]. Although the underlying mechanisms are still poorly understood, it has been suggested that,

activities in both *in vivo* and *in vitro* studies [34–40] (see **Table 2**).

prenatal and adolescence exposures to these chemicals [45, 46].

*DOI: http://dx.doi.org/10.5772/intechopen.93091*

PCPs have been poorly addressed.

**2.3 Mechanisms of action of EDCs**

those women with higher use of hygiene products.

*Endocrine Disrupting Chemicals in Cosmetics and Personal Care Products and Risk… DOI: http://dx.doi.org/10.5772/intechopen.93091*

In addition to these three families, the chemical composition of cosmetics and PCPs also contains many other compounds, although with a lower percentage of the presence in these products. Among them, bisphenols, camphenes, dimethicones, and oxycinnamates can be found. Within these minority families, bisphenols are the one that are usually found in the greatest presence in cosmetic products. The main use of BPA is the manufacture of epoxy resins, obtaining polycarbonate plastics, which have great mechanical and thermal stability, as well as very good transparency [25], while the main use of the families of camphenes, dimethicones, and oxycinnamates is that they are used as preservatives in the manufacture of PCPs [26, 27]. Nevertheless, the concentrations of these substances in cosmetics and PCPs have been poorly addressed.

Contrary to persistent EDCs that mainly reach body internal compartments through diet, the main route of human exposure to non-persistent EDCs released from cosmetics and PCPs is mainly the dermal route [28]. Therefore, these EDCs avoid the first-pass metabolism, enhancing the bioavailability and therefore the biological effect of the parent compounds [15]. In this regard, several studies have related to the use of cosmetics and PCPs and internal levels of PB and BPs. For example, it has been recently found that levels of some PB and BPs in menstrual blood are related to the use of cosmetics [29]. Moreover, urinary concentrations of PBs were related to the use of hair products, deodorants, face, and hand creams [30]. Similarly, Larsson et al. [31] found higher levels of PBs and phthalates among those women with higher use of hygiene products.

#### **2.3 Mechanisms of action of EDCs**

*Endometriosis*

shaving gels).

**Table 2.**

products (including body wash, shampoos, hair conditioners, face cleaners, and

*Most common endocrine disrupting chemicals in cosmetics and personal care products.*

*Trade name, CAS number and demonstrated hormonal activities.*

BPs are used as ultraviolet (UV) filters. As shown in the study carried out by Rastogi [23], 75 sunscreen products from Europe and the USA tested contained levels of up to three UV filters. A recent study [24] verified the presence of BP-1 and BP-3 in 19.1% of their analyzed products (283 samples analyzed), especially in makeup products, which represented 45.2% of the products with the presence of BPs.

In the case of the PB family, its main use in cosmetic products and PCPs is due to their antimicrobial properties [21]. It has been shown that the use of mixtures of paraben congeners allows the increase of their preservative capacity with the use of lower levels of each compounds [19]. Average daily application rates per women for face creams, hand or body lotions, facial cleansers, shampoos, and bath gel were 2.1, 8.7, 4.1, 12.8, and 14.5 g, respectively [22]. Yazar and Johnsson [20] carried out a study where they verified the composition of a series of 204 cosmetic products, which included shampoos, hair conditioners, liquid soap, wipes from different brands, and stores. The results showed that at least 44% of the analyzed cosmetics contained at least one PB congener. The PB that was found in the highest proportion was MeP (41% of the products), followed by PrP (25%). In the study carried out by Gao and Kannan [17], it was found that all feminine hygiene products contained at least one PB, and both MeP and EtP were found in >80% of these compounds, mainly in wipes, creams, bactericide solutions, deodorant sprays, and powders. Moreover, it has been reported that PBs were detected in 40% of the dental hygiene products analyzed and 60% in other types of daily hygiene products. MeP and PrP were the most detected compounds (40% of the analyzed samples), followed by BuP (∼20%). The highest concentrations of MeP, EtP, PrP, and BuP ranged between 1040 and 8200 μg/g, which represent approximately 0.1–0.8% per product by weight [18]. Another study carried out in China [19] found PBs in all the categories of PCPs analyzed. Almost all creams, lotions, and face cleaners contained MeP and PrP, with concentrations of MeP slightly higher than PrP (2830 and 1560 μg/g, respectively). Their presence was greater in creams and lotions than in shampoos

**30**

and body soaps.

EDCs act at very different levels of complexity, interfering a variety of hormone-signaling pathways. For instance, they can modify the circulating levels of hormones by acting on their synthesis, metabolism, or degradation. They can also reduce, increase, or interfere with the specific receptors for hormonal action and therefore affect the ability to respond to natural hormones [32]. In the particular case of EDCs that interfere in steroid hormone-related signaling pathways, the observed effects seem to be linked to the activation/blocking of nuclear receptors, which are the most common modes of action responsible for dose curves with nonmonotonic response in experimental studies [33]. In fact, many EDCs released from cosmetics and PCPs have been evidenced to exert estrogenic and antiandrogenic activities in both *in vivo* and *in vitro* studies [34–40] (see **Table 2**).

An increasing number of studies have also linked exposure to EDCs with epigenetic changes in humans [41, 42]. An unexposed individual may show epigenetic changes due to (1) altered ovum or sperm after EDC exposure or (2) in utero exposure to EDCs. In this regard, it has been evidenced that fetal exposure to environmental pollutants with endocrine disrupting properties such as mirex, chlordane, or *p,p´*-DDE can cause epigenetic changes with transgenerational effects [43, 44]. This is also the case of bisphenol-A (BPA), and PBs, with epigenetic changes after prenatal and adolescence exposures to these chemicals [45, 46].

Furthermore, inflammation and oxidative stress have also been recently postulated as possible mechanisms of action of EDCs [47–50]. In this regard, oxidative stress, that is, the imbalance between the production of free radicals and the antioxidant capacity, has been shown to be enhanced after exposure to a variety of EDCs, including PBs and BPs [47, 49, 50]. For instance, human exposure to PB and BP has been linked to higher levels of lipid peroxidation [50, 51]. Moreover, local disruption of the antioxidant capacity has also been reported [47]. Although the underlying mechanisms are still poorly understood, it has been suggested that, at least in part, EDCs might induce oxidative stress via estrogen receptor-α signaling pathways [52]. Moreover, EDC exposure has also been evidenced to trigger an inflammatory microenvironment [50, 53]. With an intimate relationship, both oxidative and inflammatory responses have also been suggested as crucial mechanisms beyond a variety of chronic diseases, as well as some gynecological conditions such as endometriosis [54, 55].
