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Poll: What do you drink out of?
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Poll: What do you drink out of?
What’s all this racquet about BPA?
National Institute of Environmental Health Sciences:Bisphenol A (BPA) is a chemical produced in large quantities for use primarily in the production of
polycarbonate plastics and epoxy resins.
Why Do We Care?• “Specifically, select environmental estrogens (bisphenol A, etc.) effectively lowered
total serum cholesterol in an estrogen-dependent animal model, the ovariectomized rat.”– Dodge et al., 1996
• “BPA and BPA-DM increased cell proliferation above the control to a level equivalent to that seen with 10-9M of estradiol…”*– Schafer et al., 1999
• “There is a concern that BPA has potential endocrine-disrupting properties, which may adversely impact physical, neurological and behavioural development. BPA is considered as a weak oestrogen-like agent, and a multitude of biological effects has been postulated for BPA”– European Food Safety Authority, 2010
• BPA has been detected in 95% of human urine samples.– Wolstenholme et al., 2010
*For BPA concentrations of 10-6
BPA Known to be Estrogenic
• Estrogenic properties discovered in 1930
Estradiol
Wolstenholme et al., 2010
The Discrepancy
• “BPA's binding to ER and hormonal activity is extremely weak, 1000–10,000 times lower than for natural hormones”– Takayanagi S. Et al, 2006
• National Toxicology Program, 2001• Safe et al., 2002• Gray et al., 2004• vom Saal and Hughes, 2005
• “The binding affinity of BPA to the ER-α and β is approximately 10,000 to 100,000 fold lower than that of E2”– Wolstenholme J. Et al, 2010
• Barkhem et al. 1998• Andersen et al. 1999
Delving into the Estrogenic Effect of BPA
Units: IC50 is a measure of binding affinity, or more accurately, ability to inhibit a given biological process.
Takayanagi S. Et al. Toxicology Letters. Vol 167, Issue 2, 2006, 95–105.
Binding Affinities for Various Receptors
Takayanagi S. Et al. Toxicology Letters. Vol 167, Issue 2, 2006, 95–105.
Unraveling the Estrogenic Effects
Baker M. Et al. 2012
Molecules on Estrogen Receptor
BPA EstrodiolMBP
Baker M. Et al. 2012
Other Effects of BPA
• Acts as Androgen Receptor antagonist
• BPA reduces aromatase enzyme activity
• Exposure to BPA during fetal development may impact cardiovascular fitness
Chapalamadugu KC. Et al, 2014
Wolstenholme et al., 2010
BPA as a DNA Methylation Inhibitor
Wolstenholme et al., 2010
The FDA Says:
• Level of BPA passed from mothers to offspring too low to be measured
• Eating BPA results in rapid metabolism to inactive form
• Primates get rid of BPA faster than rodents
Note: The FDA banned the use of BPA in plastic bottles for infants in 2012
popsci.com
Introducing a New Player
Bisphenyl S
What is BPS?
• Bisphenol S (BPS) is an alternative to BPA in plastic consumer products and thermal paper– BPS replaced BPA because it is thought to be more resistant to
leaching
• BPS was detected in 81% of 315 urine samples
• Second highest Concentrations of BPS found in samples from United States
Liao C. Et al, 2012Jenna Bilbrey, Scientific American
Watson and Viñas, 2013• First study to examine BPS for at the low
concentration– Concentrations present in foods, environmental
samples, or humans
• “Our results show that BPS is active at femtomolar to picomolar concentrations, and can alter a variety of E2-induced nongenomic responses in pituitary cells, including pERK and pJNK signaling and functions (e.g., cell number, PRL release).”
Viñas R and Watson C. 2013
Another in Vitro Study
E2 BPA and BPS
Takeaway: BPS has similar potency of estrogenic effects to BPAGrignard E. Et al, 2012
Estrogenic Effects in BPA Free• “Almost all commercially available plastic products
leached chemicals having reliably detectable estrogenic activity”
Yang C. Et al, 2011
Concern: Antimony (Sb) (EPA Limit: 6ppb)
• PET Resin Association:– Very small amounts of antimony leached,
poses no health concern• Literature:– Average concentration 0.195±0.116 ppb and
0.226±0.160 ppb 3 months later–
Temp °C 60 65 70 75 80 85Days to exceed 6 ppb 176.0 38.0 12.0 4.7 2.3 1.3
Westerhoff P. Et al, 2008
Concern: None
• Dow Chemical:– Low toxicity if swallowed– Plastics can contain residual or unreacted
quantities of monomers and process additives
DOW Product Safety Assessment
Concern: Phthalates, dioxins, BPA– Plasticizers used to make plastics more flexible– Byproduct produced during PVC manufacturing
• National Institute of Medicine:– Dioxins can cause reproductive, developmental, and other
health problems– At least one dioxin is classified as a carcinogen– Dioxins, phthalates, and BPA are suspected to be endocrine disruptors
• Literature:– di-butyl, di-(2-ethylhexyl) and butyl benzyl phthalates have been shown
to produce a syndrome of reproductive abnormalities• malformations of the epididymis, vas deferens, seminal vesicles,
prostate, external genitalia etc. Tox Town (NLM, NIH)Foster P. 2005
Concern: None
• Dow Chemical:– Low toxicity if swallowed
• Literature:– Migration of antioxidants from the LDPE has been
reported• Very small quantities released
Halden R. 2010DOW Product Safety Assessment
Concern: None
• Literature:– Migration of additives into surrounding media is
limited
Halden R. 2010
Concern: Styrene– Neurotoxic, carcinogenic, cytogenetic, hematological, effects
• EPA:– Chronic exposure: Effects on Central Nervous System
• headache, fatigue, weakness, depression, CNS dysfunction (reaction time, memory, visuomotor speed and accuracy, intellectual function), peripheral neuropathy
– Reproductive• Lung tumors have been observed in the offspring of orally exposed mice.• Human studies have not reported an increase in developmental effects
– Cancer• increased risk of leukemia and lymphoma• EPA does not have a carcinogen classification for styrene• IARC has classified styrene as a Group 2B, possibly carcinogenic to humans
• Literature:– Known to release styrene oligomers, exhibit estrogen-like activity
Halden R. 2010EPA
Concern: BPA
• Typically Polycarbonate, with BPA, BPS or other monomers
Questions?
• Comments?• Discussion?
ReferencesBisphenol A (BPA). http://www.niehs.nih.gov/health/topics/agents/sya-bpa/index.cfm (accessed Jan 27, 2015)
Dodge JA, Glasebrook AL, Magee DE, Phillips DL, Sato M, Short LL, Bryant HU. J Steroid Biochem Mol Biol. 1996; 59(2):155-61.
Schafer TE, Lapp CA, Hanes CM, Lewis JB, Wataha JC, Schuster GS. J Biomed Mater Res. 1999; 45(3):192-7.
Scientific Opinion on Bisphenol A. EFSA Journal 2010; 8(9):1829
Jennifer T. Wolstenholme, Emilie F. Rissman, Jessica J. Connelly. Horm Behav. 2011 Mar; 59(3): 296–305.
Sayaka Takayanagi, Takatoshi Tokunaga, Xiaohui Liu, Hiroyuki Okada, Ayami Matsushima, Yasuyuki Shimohigashi Toxicology Letters December 2006, 167, Issue 2, 1, Pages 95–105
Michael E. Baker, Charlie Chandsawangbhuwana. PLOS ONE. Oct 2012 DOI: 10.1371/journal.pone.0046078
Bisphenol A (BPA): Use in Food Contact Application. http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm064437.htm (accessed Jan 28, 2015)
Are BPA-Free Bottles Just As Bad? http://www.popsci.com/article/science/are-bpa-free-bottles-just-bad (accesssed Dec, 2014)
Liao C, Liu F, Alomirah H, Loi VD, Mohd MA, Moon HB, Nakata H, Kannan K. Environ Sci Technol. 2012 Jun 19;46(12):6860-6
Bilbrey J, BPA-Free Plastic Containers May Be Just as Hazardous. Scientific American. August 11, 2014
Viñas R, Watson C. Environ Health Perspect. 2013 Vol 121, Issue 3
Grignard E, Lapenna S, Bremer S. Toxicol In Vitro. 2012 Aug;26(5):727-31
Chun Z. Yang, Stuart I. Yaniger, V. Craig Jordan, Daniel J. Klein, and George D. Bittner. Environ Health Perspect. 2011 Jul 1; 119(7): 989–996.
Westerhoff P, Prapaipong P, Shock E, Hillaireau A. Water Res. 2008 Feb;42(3):551-6.
Polyvinyl Chloride (PVC). http://toxtown.nlm.nih.gov/text_version/chemicals.php?id=84 (accessed Feb 1, 2015)
Foster, P. . International Journal of Andrology, 2010 29:1, 140–147.
Halden R. Annual Review of Public Health 2010. Vol. 31: 179-194
Styrene. http://www.epa.gov/airtoxics/hlthef/styrene.html (accessed Feb 1, 2015)
