Bisphenol A exposure

and Prostate CanerLauren 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 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

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

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

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.

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

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”

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)

Regulatory/Legal: States California, Maine, Maryland, Massach

usetts, 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.

Risk Characterization

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.

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.

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

Possible Cancerous Cells

Centromere Defect

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

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

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

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.

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

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

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.

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?

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.”

Conclusion More study is needed related to safe levels

More study needed to associations with prostate

cancer