Bisphenol A exposure
and Prostate Caner
Lauren Miller, Angie Moss, Michael Wallingford, Pamela
What is Bisphenol A?
 Bisphenol A has been in use for about fifty years in the
industrialized world.
 Industrial chemica...
Hazard Assessment: MSDS
(Sigma Aldrich)
4, 4’ – Isopropylidenediphenol (C15H16O2)
Health risk: 3* (*additional chronic haz...
Regulatory/Legal
 Superfunds Amendments and Reauthorization
Act, Section 313- BPA manufacturers must submit an
annual tox...
BPA Exposures
 Primary exposure is via ingestion
 BPA migrates from food/beverage containers
 Migration is increased wh...
Hazard Assessment: Estimated BPA
exposures (National Toxicology Program)
Population BPA micrograms/kg bw/day
Infant 0-6mon...
Regulatory/Legal: European
Union
 The EU currently has suggested a temporary tolerable
daily intake of 5μg/kg bw/day pend...
Regulatory/Legal: United
States
 No current TDI as defined by the FDA- current
assessment is that BPA is safe at “the ver...
Regulatory/Legal: States
 California, Maine, Maryland, Massach
usetts, New
York, Iowa, Minnesota, Connecticut, a
nd Wisco...
Risk Characterization
Risk Characterization:
Prostate Cancer
 Prostate cancer is the second leading cause of cancer-
related death in U.S. men
...
Risk Characterization:
Prostate Cancer
 BPA is a suspected endocrine disruptor
 Acts by interfering with the biosynthesi...
Prostate Cancer and BPA:
Centromeres
 Centromere region is where sister
chromatids are attached
 During mitosis/cell div...
Possible Cancerous Cells
Centromere Defect
Prostate Cancer:
Study Suggests
 BPA interacts with several different receptors and can
act as an artificial estrogen
 U...
Study Validity and Reliability
 Research was done with animal studies and cell based
model studies
 This can make it dif...
BPA and Possible Effects
On Mitosis
 Low doses of BPA promoted centrosome
amplification/altering of the centromere
 Low ...
BPA as an estrogen
 Low level exposure elicited Cancer with the greatest
effect
 This observation supports findings in o...
Urinary BPA Levels May show Correlation
with Prostate Cancer
 Stratified analyses showed
the association between
urinary ...
BPA Exposure correlated with Prostate
Carcinogenesis
Chronic BPA exposure
promotes independent
abnormal growth in cells
Re...
Study Conclusions
 “We know that stem cells help replenish our organs
throughout life. We propose that if there is exposu...
Concerns
 The effects of low-dose exposure to BPA in lab animals
are not always reproducible.
 Need to exercise caution ...
American Chemistry Council
 News Release
 For Immediate Release - Washington (Jan. 6, 2014)
 STUDY CLAIMING INCREASED P...
Conclusion
 More study is needed related to safe levels
 More study needed to associations with prostate
cancer
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Bisphenol A exposure and Prostate Cancer

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  • http://terpconnect.umd.edu/~choi/MSDS/Sigma-Aldrich/BISPHENOL%20A.pdf
  • MSDS states that this toxic chemical release report must include BPA
  • Babies: baby bottle exposures, measurements of bpa in mother’s milk, adults amounts found in canned foods, occupational: inhaled and urinary BPA
  • Assessment made by FDA scientists who have reviewed hundreds of studies
  • Didn’t want Colorado to become a “dumping ground” for BPA products since many other states are putting in bans
  • National Toxicology Program- “some concern” for prostate cancer
  • ON POINT THREE: IS THIS BECAUSE OF BPA???
  • Prostate epithelial cells treated with low dose BPA showed abnormalities.Suggests BPA may disrupt the centromere cycle in normal cellsSupports hypothesis that BPA plays role in prostate carcinogenesis
  • Bpa presentation

    1. 1. Bisphenol A exposure and Prostate Caner Lauren Miller, Angie Moss, Michael Wallingford, Pamela
    2. 2. What is Bisphenol A?  Bisphenol A has been in use for about fifty years in the industrialized world.  Industrial chemical used in the production of epoxy resins and polycarbonate plastics.  Frequently used in food and beverage containers  Inner liners of metallic food and beverage containers to prevent corrosion  Used on thermal papers like cash register and ATM receipts
    3. 3. Hazard Assessment: MSDS (Sigma Aldrich) 4, 4’ – Isopropylidenediphenol (C15H16O2) Health risk: 3* (*additional chronic hazards present) Exposure controls: Engineering: mechanical exhaust required PPE: Respirator, chemical gloves, safety googles, other protective clothing Toxicological Information: “To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated. Environmental Information: Indication of bioaccumulation
    4. 4. Regulatory/Legal  Superfunds Amendments and Reauthorization Act, Section 313- BPA manufacturers must submit an annual toxic chemical release report  Listed as an irritant in the EU and US according to MSDS
    5. 5. BPA Exposures  Primary exposure is via ingestion  BPA migrates from food/beverage containers  Migration is increased when container is heated  Other possible routes are inhalation and dermal migration  Exposure is widespread; more than 90% of Americans have been exposed to bisphenol a at some point.
    6. 6. Hazard Assessment: Estimated BPA exposures (National Toxicology Program) Population BPA micrograms/kg bw/day Infant 0-6months formula fed 1-11 Infant 0-6months breast fed 0.2-1 Infant 6-12 months 1.65-13 Child 1.5-6 years 0.043-14.7 Adult- General Population 0.008 Adult- Occupational 0.043-100
    7. 7. Regulatory/Legal: European Union  The EU currently has suggested a temporary tolerable daily intake of 5μg/kg bw/day pending further study results, a drop from the previous TDI of 50μg/kg bw/day.  European Food Safety Administration believes health risk for all population group is low because “estimates for...exposure...are 3-5 times lower than the proposed t- TDI”
    8. 8. Regulatory/Legal: United States  No current TDI as defined by the FDA- current assessment is that BPA is safe at “the very low levels that occur in some foods”  Some studies have been initiated by the National Center for Toxicological Research; findings will be published in peer-reviewed scientific literature.  Have published a rule amending food additive regulations to no longer provide for the use of BPA based epoxy resins as coatings in infant formula packaging because this use has been abandoned. (2013)
    9. 9. Regulatory/Legal: States  California, Maine, Maryland, Massach usetts, New York, Iowa, Minnesota, Connecticut, a nd Wisconsin have banned BPA in all baby bottles and sippy cups.  Washington and Vermont have both banned it in all sports bottles, reusable food/beverage containers, as well as baby bottles and sippy cups  Colorado vetoed House Bill 12-1174 in February 2012, which proposed to ban BPA in baby bottles and sippy cups.
    10. 10. Risk Characterization
    11. 11. Risk Characterization: Prostate Cancer  Prostate cancer is the second leading cause of cancer- related death in U.S. men  Approximately 15% of men will be diagnosed with prostate cancer in their lifetime  With the 1987 introduction of prostate-specific antigen testing, the newly enhanced ability to diagnose the disease caused incidence to spike to 240 age-adjusted cases per 100,000 men by 1992. After this “catch-up” period rates dropped for three years, but are now back on the rise. •Previous research has linked elevated estrogen levels during pregnancy to increased risk of prostate cancer in males.
    12. 12. Risk Characterization: Prostate Cancer  BPA is a suspected endocrine disruptor  Acts by interfering with the biosynthesis, secretion, action or metabolism of naturally occurring hormones.  In animal models, estrogens can drive carcinogenesis of the prostate and have long been suspected of playing a role in human prostate cancer  Scientists have hypothesized that prenatal exposure to estrogen-like compounds including BPA (monomeric bisphenol A) may account for recent increases in the rates of prostate cancer.
    13. 13. Prostate Cancer and BPA: Centromeres  Centromere region is where sister chromatids are attached  During mitosis/cell division spindle poles will adhere to the centromere region  Centromeres have dynamic assemblies of chromatin and have specialized functional regions Centromeres: Chromosomal Regions Essential to Mitosis/Cell Division
    14. 14. Possible Cancerous Cells Centromere Defect
    15. 15. Prostate Cancer: Study Suggests  BPA interacts with several different receptors and can act as an artificial estrogen  Urinary BPA levels are associated with PCa and may have prognostic value  BPA exposure can disrupt mitosis/cell division; specifically acting on centromeres  BPA exposure may be correlated with prostate cancer carinogenesis  PLOS (Public Library of Science) Exposure to B
    16. 16. Study Validity and Reliability  Research was done with animal studies and cell based model studies  This can make it difficult to extrapolate to humans and results should be seen as preliminary findings  Obviously, important to replicate study results and more needs to happen with this
    17. 17. BPA and Possible Effects On Mitosis  Low doses of BPA promoted centrosome amplification/altering of the centromere  Low doses of BPA had an adverse effect on centrosome numbers  Number of centrosomes per cell were scored by fluorescence microscopy  Cells with abnormal centromeres increased  Suggest BPA may disrupt the centromere’s job and long term play a role in prostate carcinogenesis
    18. 18. BPA as an estrogen  Low level exposure elicited Cancer with the greatest effect  This observation supports findings in other literature regarding interaction with receptors to affect estrogen levels. High estrogen levels are correlated with PCa.
    19. 19. Urinary BPA Levels May show Correlation with Prostate Cancer  Stratified analyses showed the association between urinary BPA levels and Prostate Cancer was highly significant among patients < 65 and that it was not significant for those >65. Perplexing- suggests that higher BPA exposure is associated with earlier onset of Prostate Cancer. However, based on theory of developmental reprogramming of cancer risk the findings do raise the possibility of early life reprogramming of Prostate Cancer in humans
    20. 20. BPA Exposure correlated with Prostate Carcinogenesis Chronic BPA exposure promotes independent abnormal growth in cells Representative of colonies after 2 weeks incubation Cells with the BPA exposure formed larger colonies compared with those grown in absence of BPA
    21. 21. Study Conclusions  “We know that stem cells help replenish our organs throughout life. We propose that if there is exposure early in life to an estrogenic compound- BPA- it reprograms our stem cells,” say Gail Prins, a University of Illinois, Chicago researcher of the study (published in Endocrinology)  This could be the latest addition to the growing field of epigenetics, linking this chemical to altered DNA in fetuses and the potential for later life disease.
    22. 22. Concerns  The effects of low-dose exposure to BPA in lab animals are not always reproducible.  Need to exercise caution when extrapolating these findings to humans; the study was derived from animal studies and cell based models.  How could an analogous study on men be done?  To obtain results of early exposure to BPA and it’s relation to prostate cancer would take 50 plus years  More research is needed- but does this justify holding out on a ban on BPA?
    23. 23. American Chemistry Council  News Release  For Immediate Release - Washington (Jan. 6, 2014)  STUDY CLAIMING INCREASED PROSTATE CANCER RISK FROM BPA EXPOSURE IS NOT SUPPORTED BY RELIABLE HUMAN EXPOSURE DATA  “The weight of scientific evidence on BPA has been extensively evaluated by government and scientific bodies around the world, which have declared it safe as used in food contact materials.”
    24. 24. Conclusion  More study is needed related to safe levels  More study needed to associations with prostate cancer
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