Transcript Bisphenol-A

Bisphenol-A
G. Ballon, C. Doinguez, B. Sheth and J. Stahn
Introduction
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Bisphenol-A (BPA)
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Bisphenol-a is a polycarbonate
compound with two phenol
functional groups. It is majorly
used in the production of plastic
ware.
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Mimics the estrogen hormone by
attaching to the estrogen receptor.
Bisphenol-A molecule:
Estrogen Molecule:
•
BPA is exposed by leaching from
plastic containers.
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Environmental concerns
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FDA Controversy
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Safety Precautions
Mechanisms and Implications of BPA toxicity in Humans
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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
•
•
ii.
B.
Dimerization and nuclear localization
Binds DNA at Hormone Response Elements
Inactivated by phosphorlation
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.
ii.
iii.
iv.
v.
3.
Endometrial
Breast cancer cells
Hypothalamus
Ovarian stroma cells
Adipose tissue
Acute Hyperestrgenemia
i.
4.
Obesity Implications
i.
ii.
5.
Increased risk of thrombosis from over-activation of endogenous
vasodilators (Couse)
Increased estrogen receptor activity
Increased receptors for fat deposition (Couse)
Psychosocial Behavior
i.
Disrupted estrogen-testosterone Balance (Wise)
….Mechanisms and Implications of BPA toxicity in
Humans
6.
Breast Cancer
i.
ii.
Can support estrogen-receptor (+) cancers (Santen)
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
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Leaches into food and liquids
from containers.
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Rate of leaching increases with
increasing temperature
Rate of leaching increases if
liquids are acidic or erosive
cleaner is used.
Leaches into waterways

Leaves behind EDC’s (Endocrine
Disrupting Chemicals)
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Source:
 Baby bottles
 Lining of canned food
 Dental sealants
 Plastic laboratory equipment
 PVC pipes (water pipes)
 Refrigerator shelves
 And various household items
Environmental concerns
Waterways
 BPA is entering waterways such
as streams, lakes across the world
 By being carried through
sewage into rivers.
 Recycled waste water often
becomes drinking water.
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Study:
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Pharmaceutical sales are on the rise
and so are EDC’s (Endocrine
Disrupting Chemicals) in the
environment and water. (Khetan)
GOT BPA?
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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.
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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.
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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
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In rodents it has shown to induce oxidative stress.
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In rodents BPA has shown to have an effect on the
brain and their behaviors.
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In women, BPA blood levels have shown a relationship
with ovarian disease and recurrent miscarriages.
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BPA has shown to block the beneficial effects of
estradiol on neuronal synapse formation.
Long term effects of BPA exposure
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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.
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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
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BPA is considered an EDC
(Endocrine disrupting chemical) in
water reclamation.
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To remove Bisphenol-A a couple of
ideas have been proposed:
 Removal by a membrane
bioreactor
 Removal by a micro alga
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Studies:
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Membrane Bioreactor (Chen)
 A membrane bioreactor (MBR)
and conventional activated sludge
reactor (CASR) were used to
absorb BPA. Initially BPA was
removed but decreased over time
suggesting that a microorganism
was needed.
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Micro alga Stephanodiscus hantzschii
(Li)
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BPA is hydrophobic and will
associate with organic material.
Accumulation of these and other
estrogenic compounds could lead to
long term toxicological effects.
(Robinson)
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A diatom that showed to
accumulate and biodegrade BPA
in low concentrations. At higher
concentrations of BPA
Stephandosicus hantzschii growth
and ability to biodegrade was
inhibited.
Other Studies
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960 men and women’s urine levels
were measured for several different
environmental chemicals and their
effect on oxidative stress by the use
of biomarkers. (Hong)
 The study went a step further to
associate the measured levels of
BPA and it’s affect on the
increased sensitivity of insulin.
 Insulin resistance increases the
chance of developing Type II
diabetes.
 Results showed that BPA was
related to increased blood
sugar levels.
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Neonatal mice were injected with
levels of Bisphenol-A for 5
consecutive days with doses of 10,
100 and 1000 (mg/kg/day). Control
mice received corn oil. (Newbold)
 Uterine Leimyomas were more
common in BPA treated mice and
none were found in control.
 This study suggested that
exposure to BPA at critical periods
of development can result in
adverse effects of growth.
 The two lower doses are projected
to be what we are exposed to.
Conclusion
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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).
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FDA is full of it!
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Removal of Bisphenol-A should be researched more to provide
clean water, food and environment.
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Focus on removal of BPA by microorganisms.
In the meantime use precaution with use of BPA products.
Safety Measures
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Has been banned in Canada
Baby bottles have banned the
ingredient Bisphenol-A
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Use glass bottles
Do not heat in microwave
Do not use erosive cleaners
Do not reuse water bottles
RECYCLE!!
References
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Ahmada Firoz, Ansari A. Rizwan, Bhatiab Kanchan, Islam Fakhrul, Kaur Manpreet,
Rahman Shakilur, Raisuddin Sheikh, 2008. Iron deficiency augments bisphenol Ainduced oxidative stress in rats. Toxicology 256: 7-12.
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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 ERalphaknockout mouse. Endocrinology 138; 4613-4621, 1997.
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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)
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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.
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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
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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.
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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
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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.
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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.
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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
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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,
Jul2009, Vol. 74 Issue 7, p586-594, 9p; DOI: 10.1016/j.steroids.2008.11.020
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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
Scotia, Canda. 2009. Environmental Toxicology and Chemistry. Vol 28, No.1,p18-25.
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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.
Appl. Pharmacol. 168, 225−234.
http://www.sriconsulting.com/CEH/Public/Reports/619.5000/
http://www.environmentalhealthnews.org/newscience/2007/20070802newboldetal.html
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
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