BPA Exposure - Correlation to Prostate Cancer

1. Bisphenol A exposure
and Prostate Cancer
Lauren Miller, Angie Moss, Michael Wallingford, Pamela

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. 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. 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. 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. 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. 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. 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. Regulatory/Legal: States
 California, Maine, Maryland,
Massachusetts, New York, Iowa,
Minnesota, Connecticut, and 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. Risk Characterization

11. 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. 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 may account
for recent increases in the rates of prostate cancer.

13. Study Published in
Public Library of Science
 Focus on observations in this study – Exposure to BPA
Correlates with Early-Onset Prostate Cancer and Promotes
Centrosome Amplification and Anchorage- Independent
Growth in Vitro
 Breakdown
 Centrosome Amplification is when there are two or more
centromeres/centromere defect
 Anchorage-Independent Growth is when cells grow
exponentially/out of control
 Seemed to make use of viable scientific research methods
specific for their hypothesis
 Recognized it’s limits because there are limits

14. Centromere is key to proper
cell division
 Centromeres have a dynamic and
specialized functional regions
 Centromere region is where sister
chromatids are attached
 During mitosis/cell division spindle
poles will adhere to the centromere
region
Centromeres: Chromosomal
Regions Essential to Mitosis/Cell
Division

15. Mitosis

16. Possible Cancerous Cells
Centromere Defect

17. Study Hypothesizes
 Urinary BPA levels may be associated with prostate cancer
and may have a prognostic value
 BPA exposure can disrupt mitosis/cell division; specifically
affecting the centromere region causing some cells to have
improper coding
 Proposed that if there is exposure early in life to an
estrogenic compound- BPA- it may reprograms stem cells
 Proposed this study could be an addition to the growing field
of epigenetics, linking this chemical to altered DNA in
fetuses and the potential for later life disease

18. Limits within the study
 Research was done with cell based model studies and
cannot be extrapolated to humans
 Data observed should not be considered conclusive but
rather seen as preliminary findings
 Obviously, important to replicate study results and
ultimately long term human studies need to be done

19. Observed Effects on
Centromere Regions
 Numbers of centromeres were scored using
fluorescence microscopy
 Observed increase in abnormal centromeres in cells
exposed to the BPA
 Conclusion
 Low doses of BPA promoted centrosome
amplification/altering of the centromere and causing
adverse effects thus may play a long term role in
prostate carcinogenesis

20. 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 and at face value this suggests that higher BPA exposure
is associated with earlier onset of Prostate Cancer.
However, based on theory of epigenetics the findings do raise the
possibility of early life reprogramming of prostate cancer in humans

21. 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

22. 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.”

23. Concerns Observed in the
Available Research
 The effects of low-dose exposure to BPA in lab animals
(done in determining affect on estrogen levels) 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?

24. References
 Bienkowski, Brian. "BPA Exposure Linked to Prostate Cancer." Scientific American Global
RSS. N.p., n.d. Web. 7 Apr. 2014. <http://www.scientificamerican.com/article/bpa-exposure-
linked-to-prostate-cancer/>.
 "Bisphenol A." EFSA Topic:. N.p., n.d. Web. 7 Apr. 2014.
<http://www.efsa.europa.eu/en/topics/topic/bisphenol.htm>.
 "Bisphenol A (BPA) Action Plan Summary | Existing Chemicals | OPPT | US EPA." EPA.
Environmental Protection Agency, n.d. Web. 6 Apr. 2014.
<http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/bpa.html>.
 "Bisphenol A Action Plan." EPA Existing Chemicals. N.p., n.d. Web. 29 Mar. 2010.
<http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/bpa_action_plan.pdf>.
 "Bisphenol-A." Toxics in Our Lives:. N.p., n.d. Web. 7 Apr. 2014.
<http://www.saferstates.com/toxics_in_our_lives/chemicals_of_concern/BPA.html>.
 "Colorado lawmaker proposes BPAÂ ban." KDVRcom. N.p., n.d. Web. 7 Apr. 2014.
<http://kdvr.com/2012/02/20/colorado-lawmaker-proposes-bpa-ban/>.
 "Exposure to Bisphenol A Correlates with Early-Onset Prostate Cancer and Promotes
Centrosome Amplification and Anchorage-Independent Growth In Vitro." PLOS DOI:
10.1371/journal.pone.0090332 (2014): 1-8. Print.

25. References
 "Food." FDA Regulations No Longer Authorize the Use of BPA in Infant Formula Packaging
Based on Abandonment; Decision Not Based on Safety. N.p., n.d. Web. 7 Apr. 2014.
<http://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ucm360147.htm>.
 "Google." Google. N.p., n.d. Web. 6 Apr. 2014.
<http://www.google.com/search?client=safari&rls=en&q=lowdosepeerfinalrpt-2.pdf&ie=UTF-
8&oe=UTF-8>.
 "News & Events." Bisphenol A (BPA): Use in Food Contact Application. N.p., n.d. Web. 7 Apr.
2014. <http://www.fda.gov/newsevents/publichealthfocus/ucm064437.htm>.
 "Oncocytic Renal Neoplasms A Molecular Approach To A Common ...." Eureka Alert. N.p., n.d.
Web. 7 Apr. 2014. <http://www.readanybook.com/oncocytic-renal-neoplasms-a-molecular-
approach-to-a-common-diagnostic-challenge-famonzon-et-all-pathology-case-reviews-2010-
pdf-i226647>.
 "Prostate Cancer Risk From BPA Exposure Is Not Supported By Reliable Human Exposure
Data." Prostate Cancer Risk From BPA Exposure Is Not Supported By Reliable Human
Exposure Data. N.p., n.d. Web. 7 Apr. 2014.
<http://www.americanchemistry.com/media/pressreleasestranscripts/acc-news-
releases/prostate-cancer-risk-from-bpa-exposure-is-not-supported-by-reliable-human-exposure-
data.html>.