227
normal hormonal functions by exposure to EDCs is an area of great interest and
debate. A plethora of pollutants found in the environment may act similarly or differently, and consequently may disturb endocrine functions, thus it is very difficult
to decouple the harmful effect of a certain pollutant from others. Consequently,
many issues have arisen which are crucial to understanding the mechanism of
actions and concerns of exposure to EDCs. For example, exposure to EDCs at an
adult level may have different consequences compared with exposure at a fetal or
infancy stage. Similarly, developmental complications may not be immediately
apparent, instead may appear in adulthood or during aging. Individuals, or more
generally a population are rarely exposed to a single EDC, rather a mixture of EDCs
are present in the environment. In many instances, a synergy of chemicals may be
involved, thus making it very difficult to pin point the exact pollutant producing
negative effects on health. Dose–response is another factor that requires our attention. EDCs may evolve endocrine dysfunction at a low-dose level in certain individuals or population, and similar level of manifestations may require a high-dose
level in other individuals or population. Lastly, transgenerational effects may arise,
where the endocrine dysfunction appears in the subsequent generations [5]. Thus,
all these factors play their role in understanding endocrine disruption by EDCs.
To this end, FRs are among the EDCs that are known to be hazardous to normal
functioning hormones. Hence, we have presented a general picture of various metabolic mechanisms that are affected by the EDCs including most commonly used
FRs. To remain in the scope of this chapter, a succinct overview of various metabolic pathways that are believed to be involved in the prognosis of obesity, diabetes,
oxidative stress, and various inflammatory responses as a result of endocrine dysfunction by EDCs (particularly BFRs) is presented in the following section.
FRs Induced Obesity and Diabetes
Exposure to FRs may induce endocrinal disruption leading to specific abnormalities
such as obesity, diabetes mellitus, or the improper functioning of thyroid hormones.
Hence detailed studies are required to identify the classes of pollutant involved,
sources, route of exposure, and mechanistic pathway of such inappropriate modulation of the endocrine system [46]. Several authors in recent years suggest that these
exogenous substances potentially affect body hormonal control, causing imbalances
in the regulatory system, resulting in severe complications such as an abnormal
increase in body weight or abnormal functioning of the pancreas which leads to
obesity and diabetes mellitus, respectively [44].
Obesity has become a critical health issue and WHO declared obesity as one of
the major health issues in the world [47]. Obesity or excessive weight gain is associated with various metabolic disorders including insulin resistance, hyperinsulinemia, hypertension, and hyperlipidemia. All these problems collectively
contribute toward the development of type-2 diabetes mellitus (T2D) and coronary
heart disease. Genetics, poor diet, and insufficient exercise are considered as a
14 Role of Flame-Retardants as EDCs in Metabolic Disorders
normal hormonal functions by exposure to EDCs is an area of great interest and
debate. A plethora of pollutants found in the environment may act similarly or differently, and consequently may disturb endocrine functions, thus it is very difficult
to decouple the harmful effect of a certain pollutant from others. Consequently,
many issues have arisen which are crucial to understanding the mechanism of
actions and concerns of exposure to EDCs. For example, exposure to EDCs at an
adult level may have different consequences compared with exposure at a fetal or
infancy stage. Similarly, developmental complications may not be immediately
apparent, instead may appear in adulthood or during aging. Individuals, or more
generally a population are rarely exposed to a single EDC, rather a mixture of EDCs
are present in the environment. In many instances, a synergy of chemicals may be
involved, thus making it very difficult to pin point the exact pollutant producing
negative effects on health. Dose–response is another factor that requires our attention. EDCs may evolve endocrine dysfunction at a low-dose level in certain individuals or population, and similar level of manifestations may require a high-dose
level in other individuals or population. Lastly, transgenerational effects may arise,
where the endocrine dysfunction appears in the subsequent generations [5]. Thus,
all these factors play their role in understanding endocrine disruption by EDCs.
To this end, FRs are among the EDCs that are known to be hazardous to normal
functioning hormones. Hence, we have presented a general picture of various metabolic mechanisms that are affected by the EDCs including most commonly used
FRs. To remain in the scope of this chapter, a succinct overview of various metabolic pathways that are believed to be involved in the prognosis of obesity, diabetes,
oxidative stress, and various inflammatory responses as a result of endocrine dysfunction by EDCs (particularly BFRs) is presented in the following section.
FRs Induced Obesity and Diabetes
Exposure to FRs may induce endocrinal disruption leading to specific abnormalities
such as obesity, diabetes mellitus, or the improper functioning of thyroid hormones.
Hence detailed studies are required to identify the classes of pollutant involved,
sources, route of exposure, and mechanistic pathway of such inappropriate modulation of the endocrine system [46]. Several authors in recent years suggest that these
exogenous substances potentially affect body hormonal control, causing imbalances
in the regulatory system, resulting in severe complications such as an abnormal
increase in body weight or abnormal functioning of the pancreas which leads to
obesity and diabetes mellitus, respectively [44].
Obesity has become a critical health issue and WHO declared obesity as one of
the major health issues in the world [47]. Obesity or excessive weight gain is associated with various metabolic disorders including insulin resistance, hyperinsulinemia, hypertension, and hyperlipidemia. All these problems collectively
contribute toward the development of type-2 diabetes mellitus (T2D) and coronary
heart disease. Genetics, poor diet, and insufficient exercise are considered as a
14 Role of Flame-Retardants as EDCs in Metabolic Disorders