Role of Bisphenol A ( which is used in plastic materials) in Human Breast Cancer.

1. •What is Bisphenol A?
• Bisphenol A (BPA) is a carbon-basedsynthetic
compound with the
• Chemical formoula (CH3)2C(C6H4OH)2 belonging to the
group of diphenylmethane derivatives and bisphenols
Effects of the Environmental Oestrogens Bisphenol A on
Oestrogen Receptor Binding, Cell Proliferation and Regulation of
Oestrogen Sensitive Proteins in the Human Breast Cancer Cell Line MCF-
7

2. Production of epoxy resins and in the most
common form of polycarbonate plastic:
 Bisphenol A and phosgene react to give
polycarbonate under biphasic conditions; the
hydrochloric acid is scavenged with aqueous base
 Bisphenol A is used primarily to make plastics, and
products using bisphenol A-based plastics have
been in commercial use since 1957. At least 3.6
million tonnes (8 billion pounds) of BPA are used by
manufacturers yearly.

3. Uses of Bisphenol A
 Bisphenol A is used primarily to make plastics, and products
using bisphenol A-based plastics have been in commercial use
since 1957. At least 3.6 million tonnes (8 billion pounds) of BPA
are used by manufacturers yearly.

4. Health effects:
Neurological effect
Disruption of
dopaminergic
system Thyroid function
Heart & Kydney
disease in
Children
Breast cancer

5. Proposed mechanisms for the endpoints affected in
perinatally BPA-exposed females
 . BPA binds ERs, including the classical ERs (ERα and ERβ) and
mERs. This causes alterations at several levels of organization
including tissues, cells, and gene expression
 .

6. Bisphenol A act as a Xenoestogen:
 BPA, with its two benzene rings and two (4, 4′)-OH substituents, fits in
the ER binding pocket.
 BPA binds both ERα and ERβ, with approximately 10-fold higher
affinity to Erβ.
 That BPA also binds to an orphan nuclear receptor called estrogen-
related receptor-γ (ERR-γ)

7. Genomic & non genomic action of Bisphenol A

8. Non genomic pathway
 Membrane steroid receptor-mediated signals include
the activation of kinases that regulate the
phosphorylated states of important functional
proteins,membrane steroid receptors.
 a membrane-bound form of ERα (mER) that is similar
but not identical to the nuclear ERα and a
transmembrane ER called G protein-coupled receptor
30 (GPR30).
 BPA has been shown to bind to both mER and
GPR30
 These membrane-bound receptors are capable of
nongenomic steroid actions GH3/B6 pituitary cells,
which naturally express mER, respond to low level
BPA exposure (in the picomolar to nanomolar range)

9. Non genomic pathway

10. There was several effect after exposure of
bisphenol to animals listed in below the table:
Dose
(µg/kg/day)
Effects (measured in studies of mice or rat) Study Year
0.025 "Permanent changes to genital tract" 2005
0.025 ""Changes in breast tissue that predispose cells to
hormones and carcinogens"
2005
1 long-term adverse reproductive and carcinogenic
effects
2009
2 "increased prostate weight 30%" 1997
2 "lower bodyweight, increase of anogenital distance in both
genders, signs of early puberty and longer estrus."
2002
2.4 "Decline in testicular testosterone" 2004
2.5 "Breast cells predisposed to cancer" 2007
10 "Prostate cells more sensitive to hormones and
cancer"
2006
30 "Reversed the normal sex differences in brain structure and
behavior"
2003
50 Adverse neurological effects occur in non-human 2008

11. Action taken by FDA against BisphenolA:
 In 2012 the FDA banned the use of BPA in baby bottles
 A 2010 report from the US Food and Drug Administration
(FDA) identified possible hazards to fetuses, infants, and
young children.[2] Since that time numerous studies performed
at the National Center for Toxicological Research addressed
many of those issues.[3]
 .[The FDA has ended its authorization of the use of BPA in
baby bottles, sippy cups and infant formula packaging, based
on market abandonment, not safety .
 The European Union and Canada have banned BPA use in
baby bottles.
 However, FDA’s current assessment (as of 12 April 2014) is
that BPA is safe at the very low levels that occur in some
foods. This assessment is based on review by FDA scientists
of hundreds of studies including the latest findings from new
studies initiated by the agency.
 The current U.S. human exposure limit set by the EPA is

12. Controversy on BisphenolA
 As weak estrogrnic & notdeveloping cancer:
 bisphenol A, is known to be weakly estrogenic (Markey, 2001;
Wetherill, 2007).
 BPA is rapidly metabolized (converted) by the gastrointestinal
tract and the liver to a form of BPA (called conjugated BPA) (UDP-
glucronosyltransferases)produce BPA glucronide which has little
or no estrogenic activity.
 BPA is also conjugated in vivo to BPA sulfate by phenol
sulfotransferases found in the liver. to BPA glucuronide and BPA
sulfate are the metabolite of BisphenolA.
 Analysis of human urine and blood samples has led some
investigators to conclude that levels of the parent, estrogenic form
of BPA are insignificant in both blood and urine samples of
people, and that the conjugated metabolites being reported by
most scientists have no known physiological activity .

13. As imp component responsible for cancer
 pharmacokinetic studies indicate that not all BPA is
conjugated by the liver.
 In rodents, conjugated BPA is deconjugated by
enzymes in the lower intestine and colon .
 Studies also indicate that humans produce
glucuronidases in their digestive tracts, with
increasing production throughout infancy until adult
levels are reached at 4 yr of age .thus, conjugated
BPA may be deconjugated and activated by infants
during the digestive process.
 Neonatal rodents also have limited ability to conjugate
BPA to an inactive form.

14. Discussion of this controversy
 Although in early studies many researchers say
that conjugated Bpa is safe but there was enuff
evidence that tell us BisphenolA is dangerous to
our health.
 In very low dose it is safe to us but when it is
exceed 30-50ug/kg/wt it is dengerous.
 considerable data indicate that exposure of
humans to BPA is associated with increased risk
for cardiovascular disease, miscarriages,
decreased birth weight at term, breast and
prostate cancer, reproductive and sexual
dysfunctions, altered immune system activity,
metabolic problems and diabetes in adults, and
cognitive and behavioral development in young

15. BPA-Polycarbonate Plastic Alternatives (Bottles
and Containers)
 Glass and Stainless Steel
 Aluminum
 Tritan Copolyester™ (Eastman Chemical)
 High Density Polyethylene (HDPE)
 Polyethylene Terephthalate (PET)
 Epoxy Resin Alternatives (Can Liners)
 Tetra Pak

16. CONCLUSION:
 from the above studies we can ame to the dicison that
Bisphenol A is not safe to our Health.The margin level
0f this chemical is till now going to research.many
country ban bpa in producing baby bottles.we have to
use alternatives of bpa which is safe to our body.