243
predominant phthalate metabolites while the daily intake of DEHP, DBP, and DEP
was 5, 3.8, and 12.2 μg/Kgram body weight/day, respectively [12]. According to
one such study in New Delhi, India, researchers analyzed dust, in- and outdoor air
samples, food items, and drinking water using sophisticated technique like GC-MS
and found DEHP as the major toxic compound approximately 70 μg/Kg body
weight/d along with others like BBP, DMP, and DnBP with detectable limits.
Further, they concluded edibles and drinking water are the major source (more than
75%) of these residual phthalates [13].
Such studies have raised the alarms about the so common exposures, existence,
and detection of phthalates in humans in developing as well as in developed countries. Considering the gravity of situation, researchers have developed a number of
biomonitoring parameters using biological fluids like blood serum, breast milk, and
mainly urine for the detection of body burden of phthalates and their primary and
secondary metabolites. Correspondingly, a number of risk assessment strategies
have been evolved over the years to avoid toxicant-mediated illness [14, 15].
Transformation
In general, the high molecular phthalates first get converted into hydrolytic monoesters and subsequent enzyme-mediated oxidation of alkyl chain produces more
hydrophilic metabolites readily excreted through feces, sweat, and urine. These
monoesters are excreted as such or they do experience phase-II biotransformation
and get converted into more water soluble and easily excretable glucuronide conjugates (Fig. 15.3). The oxidative metabolites of DEHP (Fig. 15.4) namely mono(2ethyl- 5-hydroxylhexyl) phthalates (MEHHP) and mono(2-ethyl-5-oxylhexyl)
phthalates (MEOHP) mainly undergo glucuronidation before excretion in human
(Scheme 2). Similarly, the monoester metabolite of DEHP, the mono(2-ethylhexyl)
phthalates (MEHP) gets transformed into glucuronide conjugates before its final
excretion. The low molecular weight phthalates undergo hydrolysis of one of the
ester in phase-I biotransformation [16, 17]. So the hydrolytic monoesters, oxidative
metabolites, and biotransformed glucuronide conjugates should precisely be
detected for the determination of body burden of phthalates for accurate risk assessment especially in human beings.
Phthalates as Endocrine Disrupting Chemicals
The glands located in thyroid, testes, ovaries, pancreas, kidneys, gastrointestinal
system, and brain in human control a number of physiological functions through
hormone secretions directly in circulatory system. These hormones do act as chemical messengers (Fig. 15.5) in the nature of steroids (secosteroids, glucocorticoids,
15 Role of Phthalates as EDCs in Metabolic Disorders
predominant phthalate metabolites while the daily intake of DEHP, DBP, and DEP
was 5, 3.8, and 12.2 μg/Kgram body weight/day, respectively [12]. According to
one such study in New Delhi, India, researchers analyzed dust, in- and outdoor air
samples, food items, and drinking water using sophisticated technique like GC-MS
and found DEHP as the major toxic compound approximately 70 μg/Kg body
weight/d along with others like BBP, DMP, and DnBP with detectable limits.
Further, they concluded edibles and drinking water are the major source (more than
75%) of these residual phthalates [13].
Such studies have raised the alarms about the so common exposures, existence,
and detection of phthalates in humans in developing as well as in developed countries. Considering the gravity of situation, researchers have developed a number of
biomonitoring parameters using biological fluids like blood serum, breast milk, and
mainly urine for the detection of body burden of phthalates and their primary and
secondary metabolites. Correspondingly, a number of risk assessment strategies
have been evolved over the years to avoid toxicant-mediated illness [14, 15].
Transformation
In general, the high molecular phthalates first get converted into hydrolytic monoesters and subsequent enzyme-mediated oxidation of alkyl chain produces more
hydrophilic metabolites readily excreted through feces, sweat, and urine. These
monoesters are excreted as such or they do experience phase-II biotransformation
and get converted into more water soluble and easily excretable glucuronide conjugates (Fig. 15.3). The oxidative metabolites of DEHP (Fig. 15.4) namely mono(2ethyl- 5-hydroxylhexyl) phthalates (MEHHP) and mono(2-ethyl-5-oxylhexyl)
phthalates (MEOHP) mainly undergo glucuronidation before excretion in human
(Scheme 2). Similarly, the monoester metabolite of DEHP, the mono(2-ethylhexyl)
phthalates (MEHP) gets transformed into glucuronide conjugates before its final
excretion. The low molecular weight phthalates undergo hydrolysis of one of the
ester in phase-I biotransformation [16, 17]. So the hydrolytic monoesters, oxidative
metabolites, and biotransformed glucuronide conjugates should precisely be
detected for the determination of body burden of phthalates for accurate risk assessment especially in human beings.
Phthalates as Endocrine Disrupting Chemicals
The glands located in thyroid, testes, ovaries, pancreas, kidneys, gastrointestinal
system, and brain in human control a number of physiological functions through
hormone secretions directly in circulatory system. These hormones do act as chemical messengers (Fig. 15.5) in the nature of steroids (secosteroids, glucocorticoids,
15 Role of Phthalates as EDCs in Metabolic Disorders