1 Hype or Science? Bisphenol A Danielle Stacy January 22, 2008

1

Hype or Science?

Bisphenol A

Danielle Stacy

January 22, 2008

Burridege, E. Eur Chem News. 2003, 78, 17.

– 2 million metric tons worldwide in 2003– Monomer in epoxy resin & polycarbonates– BPA-based polymers on the market for over 50 years– Center of public health debate

Bisphenol A (BPA)

2,2-bis(4-hydroxyphenol)propane

HO OH

2

Danielle

hunt from? cite reference!

BPA Synthesis

Original Synthesis

1891 First synthesized (Alexander Dianin)

Industrial Synthesis

3

OHO

HO OH

H+

2RT

O2 OOHOH

OHO OH

H+ H+H3PO4

rad.initiator

BPA Products

CDs and DVDs Automobile partsSports safety

equipment

Coating on food and beverage cans

Water and babybottles

4

Food-storage containers

Advantages of epoxy resins – No byproducts or volatiles– Tough materials– Excellent chemical, heat, and corrosion resistance– Compatible chemically with food– Low processing cost

BPA Advantage

5

OO O

OH

n

O O O

O

n

“Ideal polymer”

Advantages of polycarbonates –Inexpensive material–High impact strength and mechanical properties–Clear AND hard plastics (anomaly)

Exposure to BPA

Hanaoka, T.; et al. Occup. Environ. Med. 2002, 59, 625-628.National Toxicology Program (NTP). http://cerhr.niehs.nih.gov/chemicals/bisphenol/BPADraftBriefVF_04_14_08.pdf. 2008.

Brotons, J. A.; et al. Environ. Health Perspect. 1995, 103, 608-612.

~4 g/kg food1 - 3 g/kg food

4.6 - 4.7 ppb in H2O

6.38 - 11.8 ng/m3

3.3 – 30 g / mL saliva

1.52 -1.95 ppm

Less than 0.1 g/kg

6

Methods to Estimate Exposure to BPA

– Must account for all routes of exposure

– Must know extent of exposure from each source

Source Based Calculation

Leaching data estimation of exposure

Pitfalls

Biomonitoring

– Must account for biotransformation– Analytic method (avoid sources of contamination)

Pitfalls

Measure concentration in urine, blood, breast milk, or tissue

7


Population BPA g / kg / day Assumption

Infant 1-11Formula from PC bottle

Formula powder in EP can

Child 0.043 – 14.7 Canned food, Dust, PC tableware

Adult 0.008 – 1.5Canned food, PC tableware, Water from PC bottles

EU and US Health Organizations: 50 g per kg / day

National Toxicology Program brief: CERHR

8NTP. http://cerhr.niehs.nih.gov/chemicals/bisphenol/BPADraftBriefVF_04_14_08.pdf. 2008.

Methods to Estimate Exposure to BPA

– Must account for all routes of exposure

– Must know extent of exposure from each source


Leaching data estimation of exposure

Pitfalls

Biomonitoring

– Analytic method (avoid sources of contamination)– Must account for biotransformation

Pitfalls

Measure concentration in urine, blood, breast milk, or tissue

9

BPA-glucuronide BPA-sulfate

BPA

HO OH

HO HO OO SO

OOO

OHOH

COOH

glucoronidase90 %

sulfatase10 %

HO

BPA metabolism

BPA half-life is less than 6 hours- more than 90 % recovered

time

BP

A (

uri

ne)

Assuming average weight

Compare to EPA regulation0.13 g / kg per day

50 g / kg per dayCalafat, A. M.; et al. Environ. Health Perspect. 2008, 116, 39-44. Dekant, W.; Volkel, W. Toxicol. Applied Pharmacol. 2008, 228, 114-134. 10

’03-’04 collection from 2,517 individuals

92.6 % had detectable BPAmean of 2.6 g / L urine

Funding Influence?

“… 90% of the government funded publications [94:104] reported significant effects of low dose BPA

while

none of the industry-funded [0:11] studies reported significant effects at similar doses.”

Maffini, M. V.; et al. Mol. Cell. Endocrinol. 2006, 254-255, 179-186. Vom Saal, F. S.; et al. Environ. Health Perspect. 2005, 113, 926-933. 11

Center of Controversy

Government Industry

BPA leaches from polymers

BPA can be found in humans

BPA causes adverse effects at

low doses

BPA causes adverse effects

only at high doses

Species-species differences– Metabolism– Bioactivity

Lack of human studies – Ethics– Finding BPA-free subjects

12Vom Saal, F. S.; et al. Reprod Toxicol. 2007, 24, 131-138.

Estrogenic Properties

13

17-estradiol

H H

H

OH

HO2,2-bis(4-hydroxyphenol)propane

HO OH

BPA

1930’s: estrogenic properties first identified

Some concernFetuses, infants, & children

Neural and behavioralprostrate, mammary gland, and early

onset of puberty in females

Also implicated in immune system & central nervous system problems

NTP. http://cerhr.niehs.nih.gov/chemicals/bisphenol/BPADraftBriefVF_04_14_08.pdf. 2008.

Legislation

Canada plans to ban PC in baby bottles and BPA leaching limits from formula cans

Investigation by US Congress found “bpa safe” results based on two industry-funded studies

Lack of consensus and proactive legislation in various countries calls for alternatives. Are there any?

14

Constructing Ideal Polymers

AmorphousDuctileAbsorbs impactTough

CrystallineBrittle

Hard & strong

linear branched network

15

Stress-Strain Behavior

Strain

Str

ess

16

stressor

experiences strain

Cowie, J. M. G. Polymers: Chemistry and Physics of Modern Materials, 2nd Edition. Stanley Thornes (Publishing) Ltd. Cheltingham, UK. 1991. McCrum, N. G.; et al. Principles of Polymer Engineering: 2nd Edition. Oxford Science Publications. New York. 1997.

http://upload.wikimedia.org/wikipedia/en/0/0a/Ductile_fracture_upd.png

http://upload.wikimedia.org/wikipedia/en/0/0a/Ductile_fracture_upd.png

Stress-Strain Behavior

Strain

Str

ess

Brittle Material (ceramic)Elastic Material (rubber band)

Ductile Material (some polymers)

17Cowie, J. M. G. Polymers: Chemistry and Physics of Modern Materials, 2nd Edition. Stanley Thornes (Publishing) Ltd. Cheltingham, UK. 1991. McCrum, N. G.; et al. Principles of Polymer Engineering: 2nd Edition. Oxford Science Publications. New York. 1997.

Glass Transition Temperature (Tg)

Cure ShrinkageCure Temperature

Critical Stress Intensity Factor (KIC)

Characterizing Polymers

18





Cowie, J. M. G. Polymers: Chemistry and Physics of Modern Materials, 2nd Edition. Stanley Thornes (Publishing) Ltd. Cheltingham, UK. 1991. McCrum, N. G.; et al. Principles of Polymer Engineering: 2nd Edition. Oxford Science Publications. New York. 1997. 18

Techniques to alter properties– Bulky side groups– Higher molecular weight– Polar side groups– Double bonds or aromatic groups– Cross-linking

100 vs -18 oC







Cl

87 vs -18 oC











thickness

KI






thickness

KI

Alloy Steel 87.4 MPaConcrete 0.2 – 1.4 MPaPolystyrene 0.7 – 1.1 MPaPolycarbonate 2.2 MPa


Epoxy Resin Synthesis

19

AmorphousDuctile

CrystallineBrittle

General techniques to improve properties– Hardening

rigidify with cross-linking– Toughening

make pliable with mixtures

HO OH

OCl

OO O

OH

n

Hardeners: use crosslinking to make intractable– Anhydrides

phthalic anhydride– Aliphatic amines

diethylene triamine triethylene tetramine

Hardening Epoxy Resin

20

O

RR'NH2

OHR

R'NH

O

R

OHR

R'N

OHR

OO O

OH

n

Toughening Epoxy Resin

OO O

OH

nNH2

H2N

21

Tougheners: elastic phase separation– moderate cross-link density resin– initial solubility– precipitates to a second phase molecule– inherently ductile additive

Varley, R. J. Polym Int. 2004, 53, 78-84.Girard-Reydet, E.; et al. J. Appl. Polym. Sci. 1997, 65, 2433-2445.

Toughening Epoxy Resin

OO O

OH

nNH2

H2N

21

Scanning Electron Microscopy (SEM) Image

Polybutadieneliquid rubber modifier

Polydimethylsiloxanepolyorganic siloxane modifier

Hyperbranched polyesterthermoplastic modifier

Tougheners: elastic phase separation– moderate cross-link density resin– initial solubility– precipitates to a second phase molecule– inherently ductile additive

Varley, R. J. Polym Int. 2004, 53, 78-84. Bucknall, C. B.; et al. Polymer. 1983. 24, 639-644. Bucknall, C. B.; et al. Polymer. 1994. 35, 353-359.

Danielle

structure?

rubber toughener

siloxane

thermoplastic

rubb

er to

ughe

ner

thermoplastic

siloxane

Enhanced Mechanical Properties

22

rubber toughener

siloxane

thermoplastic

Varley, R. J. Polym Int. 2004, 53, 78-84.

New Materials

Alternatives to BPA epoxy resins– Several already FDA approved for food packaging– Lack the versatility of BPA resins

Phenolic resins– Heat resistance– Resistance against acids, water, solvents– Flame resistant– Low cost

Disadvantages– Cures at high temperatures– Evolves volatiles– Brittle

23

OHH

HO

OH

OH

OH

HO

OH

OH

Phenolic Resins– Strategies

General modification strategies– Incorporate groups into backbone– Structure modification of OH groups– Curing with OH groups– Blend modified resin

Chemical modifications– Bismaleimide (BMI)– Bisoxazine– Polybenzoxazines

24Nair, C.P.R. Prog. Polym. Sci. 2004, 29, 401-498.

O O

OH

O O

OH OH

OH OCl

n n

OH

N

O

O

OH

N

O

O80-160 oC

N

O

O

160-220 oC

OH

N

O

ONO

O

N

O

O

225-275 oC

[4+2]

OH

N

O

ONO

O

N

O

O

O

N

O

ONO

O

N

O

O

250-300 oC

[4+2]

Bismaleimide (BMI) Strategy

max cross-linkinggood thermal stability

brittle

flexiblelow Tg

poor thermal stability

25Nair, C.P.R. Prog. Polym. Sci. 2004, 29, 401-498.

BMI Phenolic Resins

Nair, C.P.R. Prog. Polym. Sci. 2004, 29, 401-498. Yan, Y.; et al. J. Appl. Poly. Sci. 2002, 83, 1651-1657.

Property Epoxy Phenolics Toughened BMI

Cure temperature (oC) RT-180 150-190 220-300

Cure shrinkage (%) >3 0.002 0.007

Tg 150-220 170 230-380

KIC (MPa m1/2) 0.6 – 0.85

26

N

N

O

O

O

O

OH

HO

OH

OH KOH

ClOH

O

O

OH

heat

OH

HO

OH

OH heatalder-ene thermoset

BMI

BMI

BISOX Modified Phenolic Resins

Nair, C.P.R. Prog. Polym. Sci. 2004, 29, 401-498.

Property Toughened BMI Bisox-Phen

Cure temperature (oC) 220-300 175-225

Cure shrinkage (%) 0.007 < 1

Tg 230-380 160-295

KIC (MPa m1/2) 0.85 –

Commercially available as PEARTM (Poly Ether Amide Resin)

Southwest Research Institute

27

OH OH

OH

n

N

O O

N O O

OH

n

HN

O

HN

O

175-225 oC

Merger of flame retardant phenolics with the mechanical performance of epoxies

– Near zero volumetric change during curing– Low water absorption– Highest Tg

– Excellent electrical properties– Easily processed– Flame resistant

28

Polybenzoxazine (PBZ) Resins

OH

OH

2 R-NH2

NO R

N OR

OH

N OR

N

OH

OH

N

R R

NR

heat

O

H H4

Nair, C.P.R. Prog. Polym. Sci. 2004, 29, 401-498. Ishida, H.; Rodriguez, Y. Polymer, 1995, 36, 3151-3158. Ishida, H.; Sanders, D. P. Polymer, 2001, 42, 3115-3125.

PBZ Resins

Property Toughened BMI Bisox-Phen PBZ

Cure temperature (oC) 220-300 175-225 160-220

Cure shrinkage (%) 0.007 < 1 ~0

Tg 230-380 160-295 170-340

KIC (MPa m1/2) 0.85 _ 0.94

29

OH

OH

2 R-NH2

NO R

N OR

OH

N OR

N

OH

OH

N

R R

NR

heat

O

H H4

Nair, C.P.R. Prog. Polym. Sci. 2004, 29, 401-498. Ishida, H.; Rodriguez, Y. Polymer, 1995, 36, 3151-3158. Ishida, H.; Sanders, D. P. Polymer, 2001, 42, 3115-3125.

Polymer Hybrids

Nair, C.P.R. Prog. Polym. Sci. 2004, 29, 401-498. 30

NO R

N OR

O

O

N

O

O

N

R R

NR

heatR'

O O

OH OH

OHOH

NR

R' R'

R' R'

Nair, C.P.R. Prog. Polym. Sci. 2004, 29, 401-498. 31

Enhancement via Epoxy Content

O

O

N

O

O

N

R R

NR

OH OH

OHOH

NR

R' R'

R' R'

Nair, C.P.R. Prog. Polym. Sci. 2004, 29, 401-498.

Property PBZ PBZ-Epoxy Epoxy

Tg 171 219 223

KIC (MPa m1/2) 0.94 0.65 0.55

32

Enhancement via Epoxy Content

O

O

N

O

O

N

R R

NR

OH OH

OHOH

NR

R' R'

R' R'

Polycarbonate Market

33Erickson, B. E. C&ENews, 2008, 86, 36 – 39.

Polycarbonate Synthesis

34

HO OHCl Cl

O

O O O

ONaOH, R4N+

New Materials

Alternatives to polycarbonates

Polysulfone, Polyimide High Tg, $$$

35

O O SO

O

New Materials

Alternatives to BPA based polycarbonates


Polystyrene, polymethyl methacrylate (Plexiglas)

Can be transparent, lose toughness

35

O O

New Materials





Polyethylene Tg below room temperature, pliable

35

New Materials






Tritan from Eastman

Cyclohexanedimethanol and cyclobutanediol (CBDO)

Heat tolerance, resistance to hydrolysis and chemical decomposition, withstands humidity, alkalinity

35

New Materials






Tritan from Eastman

Cyclohexanedimethanol and cyclobutanediol (CBDO)

Heat tolerance, resistance to hydrolysis and chemical decomposition, withstands humidity, alkalinity

Tetramethyl-CBDO with 1,3-propanediol-dimethylterephthalates

Tough and high Tg, solvent-free synthesis, shape memory

35

Copolyterephthalates

OH

HO

OO O O O

O O O

OMe

OO

MeO

x y

Strain

Str

ess

Property PC CBDO

Peak Stress (x 108 Pa) 1.23 1.00

Elongation at Break (mm) 15.3 16.9

Stress at Break (x 107 Pa) 9.34 6.38

36

y = 40 mol %highest impact value

Booth, C. J.; et al. Polymer, 2006, 47, 6398-6405


46:54 cis:trans level (not 35:65)

OO O O O

O O O

60 40

37Booth, C. J.; et al. Polymer, 2006, 47, 6398-6405


46:54 cis:trans level (not 35:65)

OO O O O

O O O

60 40


Further Applications

Shape Memory

OO O O O

O O O

x y


BPA and Alternatives

Risk Assessment– BPA leaches from polymers– Humans exposed on g scale– Biological implications unclear

Polymer Synthesis – Characterizing polymers– Epoxy Resins

– advantages– improvements– alternatives

– Polycarbonates– advantages– alternatives

40

Choices

41

Acknowledgments

Prof. Helen Blackwell

Blackwell Research Group

Practice Talk AttendeesEmily Blanco J. P. GerdtLisa JohnsonLaura KopffMargie MattmannLauren MichaelDrew Palmer Jay SteinkrugerKat TraynorMatt Windsor

42

Toughening Mechanism

Crack-pinning:

Pearson, R. A.; Yee, A. F. Polymer. 1993, 34, 3658-3670.

Documents

1 Hype or Science? Bisphenol A Danielle Stacy January 22, 2008