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Endocrine disrupting activity associated with unconventional oil and natural gas operations
Susan C Nagel, PhDAssociate Professor
Obstetrics Gynecology and Women’s HealthUniversity of Missouri
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Endocrine Disrupting Chemicals (EDC)
“A chemical, or mixture of chemicals, that interferes with any aspect of hormone action.”
The Endocrine Society Statement on endocrine disrupting chemicals. Endocrinology 2012
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EDCs are found in many products
MetalsIndustrial Chemicals
Personal Care
Products
PesticidesHerbicides
Pharmaceuticalchemicals
Synthetic & Natural
hormones
Endocrine Disrupting Chemicals
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EDCs disrupt hormone receptors
Estrogen Receptor
Androgen
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Steroid Receptors Are Ligand activated Transcription Factors
Estradiol Testosterone Progesterone Cortisol Aldosterone
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E2
SHBG
Albumin
ER
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Why is endocrine disruption important to
human health and disease?
• Hormones and EDCs can act at low concentrations
• Human exposure can be within the range of bioactivity
• Developmental exposure can alter adult health & disease
1 10 100 1 10 100 1 10 100 1 10 100(pg/ml) (ng/ml) (µg/ml) (mg/ml)
Parts Per trillion billion million thousand
Estradiol BPA
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Hormones are essential for normal health
and development
+ -
Fetal Testosterone
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Nutrition
Pollutants
Maternal Health and Disease
Fetal and early life exposure to EDCs is associated with adult disease
Breast CancerBone HealthEndometriosisInfertilityObesityReduced SpermHeart DiseaseDiabetesHypertensionTesticular Cancer
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Unconventional oil and natural gas extraction is a potential source of
endocrine disrupting chemicals
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Unconventional oil & gas (UOG) extraction: Hydraulic Fracturing + Horizontal Drilling
Feet
0
1000
2000
3000
4000
5000
6000
7000
8000
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Fracturing Fluid Composition
Source: FracFocus data August 2012
0.5% Chemicals
Millions of gallons
of water
Thousands of gallons of
chemicals
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Health Effects of 350 Chemicals
0
20
40
60
80
100
Per
cen
t o
f C
he
mic
als
Colborn T, Kwiatkowski C, Schultz K, and Bachran M. 2011. Natural gas operations from a public health perspective. Hum Ecol Risk Assess, 17(5):1039-56.
>37%
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Millions of gallons of wastewater• “Flowback” returns immediately to surface
• “Produced water” returns over the life of the well and contains fracking chemicals, liberated salts and radioisotopes from deep underground
• Wastewater spills and leaks
• Direct disposal into surface water
• Well casing failures
• Underground migration
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Hypothesis: Surface and ground water at natural gas drilling spill sites contain more endocrine disrupting
activity than reference sites.
Garfield County
Red = Active wells, Orange = permitted wells, Yellow = Abandoned wells
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Solid Phase Extraction & Reporter Gene Assays
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Ground Water Activity By Site
0%
20%
40%
60%
80%
100%
120%
MO Ref CO Ref Site 1 Site 2 Site 3
% A
ctiv
ity
Reference
Kassotis, et al 2014
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Surface Water Activity By Site
0%
20%
40%
60%
80%
100%
120%
MO RefCO River Site 1 Site 2 Site 3 Site 4 Site 5
% A
ctiv
ity Refer
ence
Kassotis, et al 2014
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Disposal Facility in West Virginia
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Hormone Blocking Activity Associated with Injection/Disposal Well
0%
25%
50%
75%
100%
Blank Background- 4 6 7 3
anti-thyroid
anti-progestrogenic
anti-estrogenic
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Progesterone
Thyroid
Androgen
Glucocorticoid
Estrogen
Our hypothesis: Chemicals used in hydraulic fracturing will disrupt hormone receptors
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Hydraulic Fracturing and EDCs
• Tested 24 chemicals
• Five nuclear receptors
• Measured receptor activation
• Measured receptor inhibition
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1,2,4-trimethylbenzene Ethylbenzene
2-(2-methoxyethoxy) ethanol Ethylene glycol
2-ethylhexanol Ethylene glycol butyl ether
Acrylamide Methyl-4-isothiazolin
Benzene Naphthalene
Bisphenol A Phenol
Bronopol Propylene glycol
Cumene Sodium tetraborate decahydrate
Diethanolamine Styrene
Dimethyl formamide Toluene
Ethoxylated nonylphenol Triethylene glycol
Ethoxylated octylphenol Xylenes
Fracking Chemicals We Tested
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0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%%
Inh
ibit
ion
of
Re
cep
tor
Act
ivit
yEstrogen Receptor Inhibition
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0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
% In
hib
itio
n o
f R
ece
pto
r A
ctiv
ity
Androgen Receptor Inhibition
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0%
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30%
40%
50%
60%
70%
80%
90%
100%
% In
hib
itio
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f R
ece
pto
r A
ctiv
ity
Progesterone Receptor Inhibition
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0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
% In
hib
itio
n o
f R
ece
pto
r A
ctiv
ity
Glucocorticoid Receptor Inhibition
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0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
% In
hib
itio
n o
f R
ece
pto
r A
ctiv
ity
Thyroid Receptor Inhibition
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EDC Activity of 24 Fracking Chemicals
Receptor Activation Inhibition
Estrogen 1 21
Androgen 0 21
Progesterone 1 12
Glucocorticoid 0 10
Thyroid 2 7
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Inhibitory Activity of a Mixture of 23 UOG Chemicals
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Developmental exposure to a mixture of 23 UOG chemicals via drinking water
21 70
Treatment
Prenatal
11 0
Birth
0
3000 µg/kg Mix 1300 µg/kg Mix 230 µg/kg Mix 33 µg/kg Mix 40 Vehicle
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2014 Colorado Trip: 48 Sites Sampled
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Progesterone
Thyroid
Androgen
Glucocorticoid
Estrogen
Bioassaysamples
Bioassay Guided
Fractionation Identify
unknowns Bioassay
chemicalsDirected Analysis
Identify chemicals in water responsible for EDC activity
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1,2,4-trimethylbenzene Ethylbenzene
2-(2-methoxyethoxy) ethanol Ethylene glycol
2-ethylhexanol Ethylene glycol butyl ether
Acrylamide Methyl-4-isothiazolin
Benzene Naphthalene
Bisphenol A Phenol
Bronopol Propylene glycol
Cumene Sodium tetraborate decahydrate
Diethanolamine Styrene
Dimethyl formamide Toluene
Ethoxylated nonylphenol Triethylene glycol
Ethoxylated octylphenol Xylenes
Preliminary results: Chemicals we found in wastewater
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Conclusions
1. Hormones and EDCs work at low concentrations
2. EDCs are associated with disease in people
3. Of 24 fracking chemicals tested, 23 are EDCs
4. All five hormone receptors tested were disrupted by fracking chemicals
5. Surface and ground water from hydraulic fracturing “preventable discharge” sites had greater endocrine disrupting activity than control sites
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Research Team
Nagel
Tillit
Kassotis
Lin Vengosh
Davis
Funding: The Passport Foundation, University of Missouri, EPA STAR Fellowship to Kassotis
McElroy
Balise
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Thank you
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2010 Sample Collection Sites
Site #
# of Samples
Wells within 1 mile Incident Year
Control 5 0 - -
1 8 43Natural gas upwelling 2008
2 8 78Discharge into
stream 2009
3 5 69Fuel or produced
water spill 2008
4 8 136Produced water
tank leak 2004
5 9 95Produced water line
leak 2010
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Steroid Receptor Reporter Gene assay
0
500000
1000000
1500000
2000000
2500000
3000000
1.E-10 1.E-09 1.E-08 1.E-07 1.E-06 1.E-05 1.E-04
RLU/CPRG/HOUR
[hormone]Testosterone [M]
BPA
Flutamide
0.1 µM Testosterone
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Analytical Measurement of Selected Chemicals in Produced Water
Chemicals CAS # PW1 Aqu PW1 Org PW2 PW3
Naphthalene 91-20-3 3.5 264.5 0.1 0.2Styrene 100-42-5 <LOD 52.0 <LOD <LODBenzene 71-43-2 0.9 331.5 1.8 4.6Ethylbenzene 100-41-4 7.3 1099.0 0.1 1.0Cumene 98-82-8 4.2 128.9 0.0 0.22-ethylhexanol 104-76-7 <LOD <LOD <LOD <LODtrimethylbenzene 95-63-6 78.5 5873.0 0.3 2.7Toluene 108-88-3 27.3 1410.0 4.8 11.8m-xylene 108-38-3 <LOD 885.5 1.6 8.2p-xylene 106-42-3 40.1 1172.0 (m+p) (m+p)o-xylene 95-47-6 15.0 396.4 0.9 2.72-butoxyethanol 111-76-2 77.5
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Cancer
Progesterone
Thyroid
Androgen
Glucocorticoid
EstrogenMetabolic Syndrome
Fertility
Puberty
Reproductive Tract
Behavior
Neurological Issues
Immune Health
Bone