Bisphenol A exposure and Prostate Cancer

1. Bisphenol A exposure
and Prostate Caner
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, 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. Risk Characterization

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. 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. 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. Possible Cancerous Cells
Centromere Defect

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. 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. 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. 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. 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. 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. 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. 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. 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. Conclusion
 More study is needed related to safe levels
 More study needed to associations with prostate
cancer