Bisphenol-A

1
Bisphenol-A
G. Ballon, C. Doinguez, B. Sheth and J. Stahn
2
Introduction

• Bisphenol-A (BPA)
• 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.
• BPA is exposed by leaching from plastic
  containers.
• Environmental concerns
• FDA Controversy
• Safety Precautions

• Bisphenol-A molecule
• Estrogen Molecule

3
Mechanisms and Implications of BPA toxicity in
Humans

• Bisphenol-A mimics the Estrogen Hormone
• Binds ER with moderate affinity
• Many downstream effects
• Estrogen Receptor a (NR3A1) is activated by
  estrogen and analog (BPA) (Couse)
• Nuclear Receptor located in cytosol
• Activates transcription factor
• Dimerization and nuclear localization
• Binds DNA at Hormone Response Elements
• Inactivated by phosphorlation
• Membrane associated receptor
• Complexes with Tyrosine and G-coupled protien
  kinases
• MAPK
• GSK

4
Mechanisms and Implications of BPA toxicity in
Humans

• Estrogen Receptor is highly concentrated in
• Endometrial
• Breast cancer cells
• Hypothalamus
• Ovarian stroma cells
• Adipose tissue
• Acute Hyperestrgenemia
• Increased risk of thrombosis from over-activation
  of endogenous vasodilators (Couse)
• Obesity Implications
• Increased estrogen receptor activity
• Increased receptors for fat deposition (Couse)
• Psychosocial Behavior
• Disrupted estrogen-testosterone Balance (Wise)

5
.Mechanisms and Implications of BPA toxicity in
Humans

• Breast Cancer
• 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?
6
Exposure Rate/Routes

• Leaches into food and liquids from containers.
• 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 EDCs (Endocrine Disrupting
  Chemicals)

• Source
• Baby bottles
• Lining of canned food
• Dental sealants
• Plastic laboratory equipment
• PVC pipes (water pipes)
• Refrigerator shelves
• And various household items

7
Environmental concerns

• Study
• Pharmaceutical sales are on the rise and so are
  EDCs (Endocrine Disrupting Chemicals) in the
  environment and water. (Khetan)
• Figure Fate of pharmaceuticals in the
  environment.

• 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.
• GOT BPA?

8
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.

9
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.

10
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.

11
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.

12
Removal of Bisphenol-A

• Studies
• 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.
• Micro alga Stephanodiscus hantzschii (Li)
• 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.

• BPA is considered an EDC (Endocrine disrupting
  chemical) in water reclamation.
• To remove Bisphenol-A a couple of ideas have been
  proposed
• Removal by a membrane bioreactor
• Removal by a micro alga
• BPA is hydrophobic and will associate with
  organic material. Accumulation of these and other
  estrogenic compounds could lead to long term
  toxicological effects. (Robinson)

13
Other Studies

• 960 men and womens 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 its 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.

• 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.

14
Conclusion

• From researching the effects of BPAs 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.

15
Safety Measures

• Use glass bottles
• Do not heat in microwave
• Do not use erosive cleaners
• Do not reuse water bottles
• RECYCLE!!

• Has been banned in Canada
• Baby bottles have banned the ingredient
  Bisphenol-A

16
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,
  pp139-144.

17
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
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• Khetan, Sushil K., Collins and Terrance J. Human
  Pharmaceuticals in the Aquatic Environment A
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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
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• Newbold, RR., Jefferson, W.R., Banks, E.P. 2007.
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• McDonald, R.G., Hudson, A.L., Dunn, S.M., You,
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18
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