**2.2 Origin of EDCs**

There are over 140,000 man-made chemicals. In 2015, the total production of chemicals in the European Union (EU) was 323 million metric tons, 205 million metric tons of which were considered hazardous to health. The Endocrine Disruption Exchange lists approximately 1,000 agents that have been characterized as EDCs (**Figure 1**).

**369**

*Human Health Consequences of Endocrine-Disrupting Chemicals*

EDCs originate from several sources including phytoestrogens (e.g., genistein),

The exposure to EDCs is mainly unintentional. EDCs remain intact in the environment and become widely distributed geographically. They are able to travel very long distances in the air. EDCs can accumulate in the food chain and be ingested by humans. Exposure to EDCs begins before birth, and even before conception. There are several routes of exposure including air, water, food, skin, vein, breast milk, and placenta [2–8, 10–13, 15, 16, 18–21, 23, 25, 31, 39, 41]. Humans can be exposed simultaneously to several EDCs and this is a challenge for the interpretation of the epidemiological studies [14]. Professional workers (e.g., workers using pesticides)

EDCs accumulate in adipose tissue or binds to proteins. Most EDCs are highly

EDCs interfere with the action of hormones (**Figure 2**). They may interact with

or activate hormone receptors (membrane and nuclear receptors), antagonize hormone receptors, alter hormone receptor expression, alter signal transduction in hormone-responsive cells, induce epigenetic modifications in hormoneproducing or hormone-responsive cells (e.g., DNA methylation and histone modifications), alter hormone synthesis, alter hormone transport across cell membranes, alter hormone distribution or circulating hormone levels, alter hormone metabolism or clearance, and alter fate of hormone-producing or hormone-

lipophilic and are stored in adipose tissue. Non-lipophilic EDCs are bound to albumin. EDCs may have long half-lives (months or years, e.g., organochlorines) or short half-lives (minutes, hours, or days, e.g., bisphenol A) [10, 12, 14, 36]. The liver is responsible for metabolizing EDCs and may also act as a storage site for lipophilic EDCs. Lipophilic EDCs are more resistant to degradation. Detectable levels of numerous EDCs exist in human body fluids (e.g., blood and urine) and

industrial (e.g., dioxins and perchlorates), agricultural (e.g., organochlorines, organophosphates, and carbamates), residential (e.g., bisphenol A and phthalates), medical devices (e.g., bisphenol A and phthalates), and pharmaceutical (e.g.,

The EDCs can be found in our everyday lives in a variety of products including dust, soil, water, food, cosmetics, soaps, shampoos, toothpastes, plastic containers, toys, nicotine, and fertilizers. The United States (US) Environmental Protection Agency (EPA) estimates children ingest 60–100 mg of dust per day from indoor environment. Among multiple EDCs present in food, it is notable to mention monosodium glutamate (used as a flavor enhancer), genistein (found in soy-based foods), and high-fructose corn syrup (used as a sweetener). The use of plastic packaging is on the rise. The worldwide plastics production reached 380 million metric tons in 2015, with approximately 40% used for packaging. Around 60% of all plastic packaging is used for bever-

diethylstilbestrol and parabens) [1–8, 10, 11–13, 15–25, 31, 33, 44].

*DOI: http://dx.doi.org/10.5772/intechopen.94955*

ages and food.

**2.3 Routes of exposure to EDCs**

are at higher risk of exposure to EDCs.

tissues (e.g., adipose tissue and liver).

**2.5 Mechanisms of action of EDCs**

responsive cells [1, 3, 4, 9, 10, 12–21, 24, 27, 28, 33, 35].

**2.4 Metabolism of EDCs**

**Figure 1.** *EDCs are mainly man-made chemicals.*

*Human Health Consequences of Endocrine-Disrupting Chemicals DOI: http://dx.doi.org/10.5772/intechopen.94955*

EDCs originate from several sources including phytoestrogens (e.g., genistein), industrial (e.g., dioxins and perchlorates), agricultural (e.g., organochlorines, organophosphates, and carbamates), residential (e.g., bisphenol A and phthalates), medical devices (e.g., bisphenol A and phthalates), and pharmaceutical (e.g., diethylstilbestrol and parabens) [1–8, 10, 11–13, 15–25, 31, 33, 44].

The EDCs can be found in our everyday lives in a variety of products including dust, soil, water, food, cosmetics, soaps, shampoos, toothpastes, plastic containers, toys, nicotine, and fertilizers. The United States (US) Environmental Protection Agency (EPA) estimates children ingest 60–100 mg of dust per day from indoor environment. Among multiple EDCs present in food, it is notable to mention monosodium glutamate (used as a flavor enhancer), genistein (found in soy-based foods), and high-fructose corn syrup (used as a sweetener). The use of plastic packaging is on the rise. The worldwide plastics production reached 380 million metric tons in 2015, with approximately 40% used for packaging. Around 60% of all plastic packaging is used for beverages and food.

#### **2.3 Routes of exposure to EDCs**

*Environmental Issues and Sustainable Development*

**2. General characteristics of EDCs**

effects [1–5, 10, 11, 13, 16, 48].

**2.2 Origin of EDCs**

as EDCs (**Figure 1**).

**2.1 Definition and identification of EDCs**

generations.

EDCs represent a global threat for human health and cause a high cost for the society [47]. Promoting public knowledge and initiating preventive measures will help minimizing the health and economic consequences of EDCs for future

In 2002, the International Programme on Chemical Safety belonging to the World Health Organization conducted a comprehensive evaluation of EDCs and proposed the following definition: "An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse

EDCs are chemicals, mainly man-made, but also naturally occurring substances that can be found in plants or fungi, that interfere with hormonal signaling pathways. The EDCs are active at very low doses, impact health, and can have persistent

The first scientific statement of the Endocrine Society in 2009 provided a wake-up call to the scientific community on the risks of EDCs for human health. The second statement of the Endocrine Society in 2015 provided a global update on

The experimental screening process of the EDCs using animal data is timeconsuming and costly. Computer-based (*in silico*) methods have been developed to predict the effect of the EDCs on the endocrine receptor [5, 49]. One popular

There are over 140,000 man-made chemicals. In 2015, the total production of chemicals in the European Union (EU) was 323 million metric tons, 205 million metric tons of which were considered hazardous to health. The Endocrine Disruption Exchange lists approximately 1,000 agents that have been characterized

health effects in an intact organism, or its progeny, or (sub)populations."

EDCs based on the available data in the literature [10].

method is the molecular docking approach.

**368**

**Figure 1.**

*EDCs are mainly man-made chemicals.*

The exposure to EDCs is mainly unintentional. EDCs remain intact in the environment and become widely distributed geographically. They are able to travel very long distances in the air. EDCs can accumulate in the food chain and be ingested by humans. Exposure to EDCs begins before birth, and even before conception. There are several routes of exposure including air, water, food, skin, vein, breast milk, and placenta [2–8, 10–13, 15, 16, 18–21, 23, 25, 31, 39, 41]. Humans can be exposed simultaneously to several EDCs and this is a challenge for the interpretation of the epidemiological studies [14]. Professional workers (e.g., workers using pesticides) are at higher risk of exposure to EDCs.

#### **2.4 Metabolism of EDCs**

EDCs accumulate in adipose tissue or binds to proteins. Most EDCs are highly lipophilic and are stored in adipose tissue. Non-lipophilic EDCs are bound to albumin. EDCs may have long half-lives (months or years, e.g., organochlorines) or short half-lives (minutes, hours, or days, e.g., bisphenol A) [10, 12, 14, 36]. The liver is responsible for metabolizing EDCs and may also act as a storage site for lipophilic EDCs. Lipophilic EDCs are more resistant to degradation. Detectable levels of numerous EDCs exist in human body fluids (e.g., blood and urine) and tissues (e.g., adipose tissue and liver).

#### **2.5 Mechanisms of action of EDCs**

EDCs interfere with the action of hormones (**Figure 2**). They may interact with or activate hormone receptors (membrane and nuclear receptors), antagonize hormone receptors, alter hormone receptor expression, alter signal transduction in hormone-responsive cells, induce epigenetic modifications in hormoneproducing or hormone-responsive cells (e.g., DNA methylation and histone modifications), alter hormone synthesis, alter hormone transport across cell membranes, alter hormone distribution or circulating hormone levels, alter hormone metabolism or clearance, and alter fate of hormone-producing or hormoneresponsive cells [1, 3, 4, 9, 10, 12–21, 24, 27, 28, 33, 35].

**Figure 2.** *EDCs interfere with the action of hormones.*
