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Bisphenol-A

G. Ballon, C. Doinguez, B. Sheth and J. Stahn


Introduction

• Bisphenol-A (BPA)
Bisphenol-A molecule:
• Bisphenol-a is a polycarbonate
compound with two phenol
functional groups. It is majorly
used in the production of plastic
ware.

• Mimics the estrogen hormone by


attaching to the estrogen receptor.
Estrogen Molecule:
• BPA is exposed by leaching from
plastic containers.

• Environmental concerns

• FDA Controversy

• Safety Precautions
Mechanisms and Implications of BPA toxicity in Humans

 Bisphenol-A mimics the Estrogen Hormone


 Binds ER with moderate affinity
 Many downstream effects

1. Estrogen Receptor α (NR3A1) is activated by estrogen and analog (BPA)


(Couse)

A. Nuclear Receptor located in cytosol


i. Activates transcription factor
• Dimerization and nuclear localization
• Binds DNA at Hormone Response Elements
ii. Inactivated by phosphorlation

B. Membrane associated receptor


i. Complexes with Tyrosine and G-coupled protien kinases
• MAPK
• GSK
…Mechanisms and Implications of BPA toxicity in
Humans
2. Estrogen Receptor is highly concentrated in:
i. Endometrial
ii. Breast cancer cells
iii. Hypothalamus
iv. Ovarian stroma cells
v. Adipose tissue

3. Acute Hyperestrgenemia
i. Increased risk of thrombosis from over-activation of endogenous
vasodilators (Couse)
4. Obesity Implications
i. Increased estrogen receptor activity
ii. Increased receptors for fat deposition (Couse)
5. Psychosocial Behavior
i. Disrupted estrogen-testosterone Balance (Wise)
….Mechanisms and Implications of BPA toxicity in
Humans
6. Breast Cancer
i. Can support estrogen-receptor (+) cancers (Santen)
ii. BPA affects chemotherapeutics for anti-estrogen (Santen,Toolson)
• Can affects Tamoxifen dosage regimine

BPA is an agonist

What is the
Appropriate dose?
Exposure Rate/Routes

 Leaches into food and liquids  Source:


from containers.  Baby bottles
 Rate of leaching increases with  Lining of canned food
increasing temperature
 Dental sealants
 Rate of leaching increases if
liquids are acidic or erosive  Plastic laboratory equipment
cleaner is used.  PVC pipes (water pipes)
 Leaches into waterways  Refrigerator shelves
 Leaves behind EDC’s (Endocrine  And various household items
Disrupting Chemicals)
Environmental concerns

Waterways  Study:
 BPA is entering waterways such  Pharmaceutical sales are on the rise
as streams, lakes across the world and so are EDC’s (Endocrine
Disrupting Chemicals) in the
 By being carried through environment and water. (Khetan)
sewage into rivers.
 Recycled waste water often
becomes drinking water.
 GOT BPA?

 Figure: Fate of pharmaceuticals in the environment.


FDA Controversy
BPA approved by the FDA

 FDA supports that BPA has an impact on


humans when administered over the “safe”
dose, while the EFSA panel supports that it does
not cause an impact on humans.

 Levels of BPA are considered safe when the


amount a person is exposed to does not harm
him/her.

 Studies have shown that low doses of BPA


throughout their lifespan have an impact on their
health.
Low doses of BPA are enough to cause effects
 In efforts to disprove the FDA and the
“safe“ dose of BPA a study conducted by
Fredrick S. vom Saala and others proved
that low doses of BPA have profound
effects on humans.

 Studies have been funded by the


government in efforts to find a safe intake
of BPA.

 There is still controversy between those


that say it does not have an effect in
humans because we have a faster way of
eliminating the toxin compared to rodents.
Long term effects of BPA exposure

 In rodents it has shown to induce oxidative stress.

 In rodents BPA has shown to have an effect on the


brain and their behaviors.

 In women, BPA blood levels have shown a relationship


with ovarian disease and recurrent miscarriages.

 BPA has shown to block the beneficial effects of


estradiol on neuronal synapse formation.
Long term effects of BPA exposure

 However, chemistry industries


who have conducted studies have
found in 100% of their cases that
BPA leaves the body rapidly. But
because we are exposed to it
daily it is common.

 There are currently studies being


done with women, to prove that
there are long term effects for
constant low amounts of BPA.
Removal of Bisphenol-A

 Studies:
 BPA is considered an EDC  Membrane Bioreactor (Chen)
(Endocrine disrupting chemical) in
 A membrane bioreactor (MBR)
water reclamation. and conventional activated sludge
 To remove Bisphenol-A a couple of reactor (CASR) were used to
ideas have been proposed: absorb BPA. Initially BPA was
removed but decreased over time
 Removal by a membrane
suggesting that a microorganism
bioreactor was needed.
 Removal by a micro alga  Micro alga Stephanodiscus hantzschii
(Li)
 A diatom that showed to
 BPA is hydrophobic and will accumulate and biodegrade BPA
associate with organic material. in low concentrations. At higher
Accumulation of these and other concentrations of BPA
estrogenic compounds could lead to Stephandosicus hantzschii growth
long term toxicological effects. and ability to biodegrade was
(Robinson) inhibited.
Other Studies
 960 men and women’s urine levels  Neonatal mice were injected with
were measured for several different levels of Bisphenol-A for 5
environmental chemicals and their consecutive days with doses of 10,
effect on oxidative stress by the use 100 and 1000 (mg/kg/day). Control
of biomarkers. (Hong)
mice received corn oil. (Newbold)
 The study went a step further to
associate the measured levels of  Uterine Leimyomas were more
BPA and it’s affect on the common in BPA treated mice and
increased sensitivity of insulin. none were found in control.
 Insulin resistance increases the  This study suggested that
chance of developing Type II exposure to BPA at critical periods
diabetes. of development can result in
 Results showed that BPA was adverse effects of growth.
related to increased blood  The two lower doses are projected
sugar levels.
to be what we are exposed to.
Conclusion
 From researching the effects of BPA’s toxicity in animals and
human we assume that there is negative consequences.
Although, some research tries to imply that there is no direct
correlation with pathologies and BPA contamination, there is
over-whelming evidence that it causes the disruption of dynamic
processes, most notably, endocrine disruption (Saala).

 FDA is full of it!

 Removal of Bisphenol-A should be researched more to provide


clean water, food and environment.
 Focus on removal of BPA by microorganisms.

 In the meantime use precaution with use of BPA products.


Safety Measures

 Has been banned in Canada  Use glass bottles


 Baby bottles have banned the  Do not heat in microwave
ingredient Bisphenol-A  Do not use erosive cleaners
 Do not reuse water bottles
 RECYCLE!!
References
 Ahmada Firoz, Ansari A. Rizwan, Bhatiab Kanchan, Islam Fakhrul, Kaur Manpreet,
Rahman Shakilur, Raisuddin Sheikh, 2008. Iron deficiency augments bisphenol A-
induced oxidative stress in rats. Toxicology 256: 7-12.
 Couse JF, Lindzey J, Grandien K, Gustafsson JA, Karach KS. Tissue distrubution
and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen
receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-
knockout mouse. Endocrinology 138; 4613-4621, 1997.
 Dana D. Wise, Angela Felker and Stephen M. Stahl. Tailoring treatment of
depression for women acreoss the reproductie lifecycle: the importance of
pregnancy, vasomotor symptoms, and other estrogen-related events in
psychompharmacology. Psychopharmacology Education Updates (PsychEdUp) 5.1
(Jan 2009)
 Gioiosa Laura,Palanza Paola, Frederick S. vom Saal Frederick S. vom , Parmigiani
Stefano, 2008. Effects of developmental exposure to bisphenol A on brain and
behavior in mice. Environmental Research 180: 150-157.
 Hong, Yun-Chul. 2009. Community Level Exposure to Chemicals and Oxidative
Stress in Adult Population. Toxicology Letters. Vol 158, Issue 2, pp:139-144.
References
 Saala vom S. Frederick, Welshons V. Wade, 2004. Large effects from small
exposures. The importance of positive controls in low-dose research on
bisphenol A. Environmental Research 100: 50-76.
 Khetan, Sushil K., Collins and Terrance J. Human Pharmaceuticals in the
Aquatic Environment: A Challenge to Green Chemistry. Chemistry Reviews.
2007. Vol 107, Issue 6, pp: 2319-2364. DOI: 10.1021/cr020441w
 Li, Rui., Chen, Gui-Zhu., Fung Yee Tam, Nora., Luan, Tian-Gang., Paul, K.S.,
Cheung, S.G. and Lui, Yu. 2009. Toxicity of Bisphenol-A and its
bioaccumilation and removal by a marine micro alga Stephanodiscus
hantzschii. Ecotoxicology and Envirnomental Safety. Vol 72, Issue 2, pp:321-328.
 Newbold, RR., Jefferson, W.R., Banks, E.P. 2007. Longterm adverse effects on
Neonatel Exposure to Bisphenol-A on Murine Female Reproductive Tract.
Reproductive Toxicology. Vol 24, pp:253-258.
 McDonald, R.G., Hudson, A.L., Dunn, S.M., You, H., Baker, G.B., Whittal, R.M.,
Martin, J.W., Jha, A., Edmondson, D.E. and Holt, A. 2008. Bioactive
Contaminants Leach from Disposable Laboratory Plasticware. Science. Vol 7,
p:917.
References
 Santen, Richard J.; Fan, Ping; Zhang, Zhenguo; Bao, Yongde; Song, Robert X.-D.;
Yue, Wei. Estrogen signals via an extra-nuclear pathway involving IGF-1R and
EGFR in tamoxifen-sensitive and -resistant breast cancer cells. Steroids,
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 Robinson, Brian J., Hui, Joseph H.I., Soo, Evelynn, C. and Hellou, Jocelyne.
Estorgenic Compounds In Seawater And Sediment From Halifax Harbour, Nova
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 Snyder, R. W., Maness, S. C., Gaido, K. W., Welsch, F., Sumner, S. C., and Fennell,
T. R. (2000) Metabolism and disposition of bisphenol A in female rats. Toxicol.
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 http://www.sriconsulting.com/CEH/Public/Reports/619.5000/
 http://www.environmentalhealthnews.org/newscience/2007/2007-
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 http://www.thefatherlife.com
 http://www.steadyhealth.com/articles/FDA_Urged_to_Ban_BPA_Found_In_Plastics_
Due_to_Its_Links_To_Heart__Diabetes_and_Liver_Problems_a748.html
 http://www.indoorquality.org/pollutants/bisphenolA.cfm