230
humans. Consequently, an increased susceptibility to insulin resistance and obesogenicity may appear; however, the exact mechanism by which BPA acts remained
poorly understood [71].
Hence detailed further investigations are required to provide substantial evidences which relate association of such health implications on exposure to environmental pollutants such as FRs [58, 72].
FRs Induced Oxidative Stress and Inflammatory Responses
In particular, polybrominated diphenyl ether and polybrominated biphenyls play a
role in endocrine dysfunction, thus result in oxidative stress and inflammatory
events [73, 74]. BFRs are produced and used extensively; accordingly, they are very
prone to contaminate the environment, and affect human and animal health and
homeostasis [75]. The human population is exposed primarily through food products, mostly from contaminated animal fats [76]. They are efficiently absorbed, distributed in the body, and deposited in adipose cells. They are bio-transformed or
metabolized in the human body by the cytochrome P450 enzyme system, in particular, by cytochrome P450-dependent monooxygenase [76]. They can readily cross
the placental barrier and are teratogenic; thus, they might have serious effects on a
fetus [16]. They also appear in the breast milk of exposed humans; therefore, they
can further affect a breast-feeding child [77, 78]. BFRs are a group of structurally
similar chemical substances, consisting of two bromine-decorated aromatic rings.
This structural similarity influences the toxic capability, and numerous congener’s
attachment to dioxin-receptor (aryl hydrocarbon receptor—AhR). In essence, most
of the highly toxic congeners play insignificant part, as they are in very minute titer.
However, some exceptions might be there which avidly bind with dioxin-receptor
and result in dioxin-receptor mediated carcinogenic property. Some other similar
consequences pertaining to structural similarity might include neuro-behavioral
effects, the imbalance in thyroid hormone homeostasis, and the effects on the
hepatic metabolic pathways [77].
Arene oxides and quinones, also known as highly reactive metabolic species, are
produced owing to biotransformation of BFRs, are genotoxic and mutagenic. The
production of reactive oxygen species (ROS), lipid peroxidation, oxidative and
alkylating gene adducts can ultimately cause genotoxicity; thereby leading to the
formation of oncogene which eventually initiates cancer. Thus, BFRs activate AhR
which is a key to open the events associated with carcinogenesis mediated by
dioxin-receptor. Due to persistent stimulation of the receptors, normal cell-cycle
control and cell proliferation are lost, apoptosis is inhibited, cell-to-cell adhesion
and signaling are impaired, and cell plasticity and invasiveness are increased [76].
From this angle, BFRs may induce tumors in rodents and cholangiocarcinomas in
mice and rats [79].
TBBPA is a relatively new FR that made its entry in the market recently. Owing
to its high efficiency, lipophilicity, and superior stability, it has been utilized as an
T. Hussain et al.
humans. Consequently, an increased susceptibility to insulin resistance and obesogenicity may appear; however, the exact mechanism by which BPA acts remained
poorly understood [71].
Hence detailed further investigations are required to provide substantial evidences which relate association of such health implications on exposure to environmental pollutants such as FRs [58, 72].
FRs Induced Oxidative Stress and Inflammatory Responses
In particular, polybrominated diphenyl ether and polybrominated biphenyls play a
role in endocrine dysfunction, thus result in oxidative stress and inflammatory
events [73, 74]. BFRs are produced and used extensively; accordingly, they are very
prone to contaminate the environment, and affect human and animal health and
homeostasis [75]. The human population is exposed primarily through food products, mostly from contaminated animal fats [76]. They are efficiently absorbed, distributed in the body, and deposited in adipose cells. They are bio-transformed or
metabolized in the human body by the cytochrome P450 enzyme system, in particular, by cytochrome P450-dependent monooxygenase [76]. They can readily cross
the placental barrier and are teratogenic; thus, they might have serious effects on a
fetus [16]. They also appear in the breast milk of exposed humans; therefore, they
can further affect a breast-feeding child [77, 78]. BFRs are a group of structurally
similar chemical substances, consisting of two bromine-decorated aromatic rings.
This structural similarity influences the toxic capability, and numerous congener’s
attachment to dioxin-receptor (aryl hydrocarbon receptor—AhR). In essence, most
of the highly toxic congeners play insignificant part, as they are in very minute titer.
However, some exceptions might be there which avidly bind with dioxin-receptor
and result in dioxin-receptor mediated carcinogenic property. Some other similar
consequences pertaining to structural similarity might include neuro-behavioral
effects, the imbalance in thyroid hormone homeostasis, and the effects on the
hepatic metabolic pathways [77].
Arene oxides and quinones, also known as highly reactive metabolic species, are
produced owing to biotransformation of BFRs, are genotoxic and mutagenic. The
production of reactive oxygen species (ROS), lipid peroxidation, oxidative and
alkylating gene adducts can ultimately cause genotoxicity; thereby leading to the
formation of oncogene which eventually initiates cancer. Thus, BFRs activate AhR
which is a key to open the events associated with carcinogenesis mediated by
dioxin-receptor. Due to persistent stimulation of the receptors, normal cell-cycle
control and cell proliferation are lost, apoptosis is inhibited, cell-to-cell adhesion
and signaling are impaired, and cell plasticity and invasiveness are increased [76].
From this angle, BFRs may induce tumors in rodents and cholangiocarcinomas in
mice and rats [79].
TBBPA is a relatively new FR that made its entry in the market recently. Owing
to its high efficiency, lipophilicity, and superior stability, it has been utilized as an
T. Hussain et al.