presentation by matthew j. campen, phd_presentations.pdf · 2020. 4. 10. · eliane el hayek, phd...
TRANSCRIPT
Matthew J. Campen, PhDUniversity of New Mexico
Characterization of Chemistry and Toxicity of Ambient Particulate Matter Air Pollution Near Uranium Mine Sites on
Tribal Lands of the Southwest
Presentation by Matthew J. Campen, PhD
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Native Environmental Health Equity: Addressing the Impacts of Abandoned Mines on Native Communities
● >1/2 of Native population of US livesin 13 western US states, where161,000 abandoned hard rockmines also located
● >600,000 Native Americans livewithin 10 km of abandoned mines
● Greater reliance on local resourcescreates increased concern overpotentially greater exposure andresultant impacts
Lewis, Hoover and MacKenzie, 2017, Current Environmental Health Reports
Hot Spots in the Four-Corners Region for Environmental Lung Disease:
Silicosis and Interstitial Lung Disease/Sarcoidosis
Some images have been removed from this slide.
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Image source: Dwyer-Lindgren et al., JAMA. 318:1136-1149,2017.
Community-Based Concerns Drive Our Research
Demographics and Cardiometabolic Disease Prevalence in a Navajo Nation Cohort:
The Diné-Navajo Environmental Health Study
* self-report
VariableDiNEH Subset
(n = 252)Original DiNEH
(n = 1304) Age, years 55.3 (± 14.3) 51.5 (± 17.4)Female, % 57.5 56.4Self-reported health conditions:
Type 2 Diabetes, % 26.2 25.1Hypertension, % 38.1 35.9Heart Disease, % 6 5.4Myocardial Infarction, % 4.4 3.1Stroke, % 5.2 3.5
Body mass index (BMI), kg/m² 29.7 (26.8-33.6) 28.3 (25.1-32.6)* Obesity (BMI ≥ 30), % 47.6 41.2
Harmon et al., PLoS ONE, 2016
High prevalence of diabetes, hypertension, and obesity
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Multivariate Regression Modeling
Response variables mRNA endothelial cell responses to serum• VCAM-1• ICAM-1• CCL2
CovariatesExposure metrics:
• Water intake of metals• AUM proximity
Age, gender, BMI, HbA1c
Reduced models derived by model selection using AIC
Uranium Mine Proximity (NOT Oral Intake of Arsenic or Uranium) Correlates with Inflammatory Markers in Navajo Participants
Proximity to Uranium Mine Sites (Weighted by Surface Area of Sites)
CCL2 (Inflammatory Marker)
R = .267p < 0.0001
Harmon et al., JESEE, 2017
Ccl
2 m
RN
A Ex
pres
sion
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Community Research Interim ResultsCloser proximity to abandoned
uranium mines predicted increased serum inflammatory potential
Broader effect of overall burden of mining waste exposure
Dust from a storm in Monument Valley
Could windblown contaminated dusts negatively impact public health in affected communities?
• Other pathways windblown?• Other mining metals/mixtures
Steps in Risk Assessment:
o Hazard Identificationo Exposure Assessmento Dose-Response Assessmento Risk Characterization
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• “Dust” ranges in size greatly; respirable particles are generally<10 microns
• Size of particle determines how they deposit in the lungs• Mass mean aerodynamic diameter (“MMAD”) is used to
describe the size of particles– BASED on empirically determined particle buoyancy rather than
physical shape
Particulates
• PM toxicity is a function of:o Aerodynamic diameter
• Deposition and retentiono Chemical composition
EPA and HIS, 2010
> 500 abandoned mines4 mill sites
1,100 exposure features100s of contaminated wells
(Arsenic, Uranium)
DiNEH Study Area
New MexicoArizona
Utah Colorado
Location of Claim 28 Mine Site in the Blue Gap Tachee (BGT) Chapter of the Navajo Nation
Chinle
Gallup
Claim 28 Mine Sample Location
Blue GapTachee
*
*Background PM Sample Location
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U
V
V U
A. B. Soil
• Sediments from Claim 28 mine site contains respirable metallicmineral grains
• XANES analysis suggests many of these metallic grains are likelycarnotite, a mineral composed of uranium and vanadium
Metal Contaminants in Surface Soils
Carnotite
V
EDS spectrum of the area in Red
U
U U
C. D. ResuspendedMaterial
• Soils were resuspended in air and captured in a NextGeneration Impactor to characterize respirable fractions
• Sub-micron (respirable) PM contained significantamounts of carnotite
Metal Contaminants in Resuspended Sediments
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Carnotite Particulates Exhibit Nano-agglomerated Ultrastructure
Zychowski et al., Toxicol Sci, 2018
AsO Cr Cu Cd Co Zn Ni V Pb U103
104
105
106
107
Met
al C
onte
nt (µ
g/kg
)
Background PMClaim 28 PM
Initial Toxicity Assessments: Comparing Cardiopulmonary Toxicity of Contaminated “Claim 28” PM versus Background
PM• Dose groups (C57BL/6, male):
– Vehicle control aspiration– 100µg Claim 28 PM10
– 100µg Background PM10
• Euthanized 24h post-aspiration• Pulmonary inflammation
– Lavage Cellularity, Cytokines• Aortic vasomotor dysfunction• Cytotoxicity assay (in vitro)
Claim 28 Background
Pulmonary Endpoints
Vascular Endpoints
1
Carnotite Particulates Exhibit Nano‐Agglomerated Ultrastructure
Zychowski et al., Toxicol Sci, 2018
AsO Cr Cu Cd Co Zn Ni V Pb U103
104
105
106
107
Met
al C
onte
nt (µ
g/kg
)
Background PMClaim 28 PM
IInniittiiaall TTooxxiicciittyy AAsssseessssmmeennttss: Comparing Cardiopulmonary Toxicity of Contaminated “Claim 28” PM vs Background PM
• Dose groups (C57BL/6, male):• Vehicle control aspiration• 100µg Claim 28 PM10• 100µg Background PM10
• Euthanized 24h post aspiration• Pulmonary inflammation
• Lavage Cellularity, Cytokines• Aortic vasomotor dysfunction• Cytotoxicity assay (in vitro)
Claim 28 Background
Pulmonary Endpoints
Vascular Endpoints
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Lung Outcomes: Lavage Inflammatory Cells and Cytokines
Following particulate exposure in mice
*P<0.05; **P<0.001 by one-way ANOVA with Dunnett’s Post-Hoc test
Vehicl
e Contro
l
Backg
round PM
Claim 28
PM0.00
0.05
0.10
0.15
0.20Ne
utro
phil
coun
t (x1
05 /ml)
*
**†
Zychowski et al., Toxicol Sci, 2018
IL-12p70
IL-1β IL-6
KC/GRO
TNF-α0
50
100
150
Bron
choa
lveo
lar L
avag
eCo
ncen
tratio
n (p
g/m
l)
*
*†
**†
**
**
Claim 28 PMBackground PMVehicle Control
Relative Cytotoxicity Assessment
• Treated THP-1 cells with increasingconcentrations of Claim 28 andBackground PM10
• Dihydroethidium and caspase-1levels were both elevated in THP-1cells treated with Claim 28 PM10
Zychowski et al., Toxicol Sci, 2018
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Conclusions• Proximity to mine sites may be linked to circulating
inflammatory potential• Mine site soils contain mixed metal contaminants
– Many in respirable grains– Mine site–derived PM clearly more toxic to the pulmonary tract
than background soil PM samples• Both vanadium and uranium, key components of the ore
carnotite, have independent and complementarypulmonary toxicity
• But how realistic are these exposures . . . ?
Where Are We in Understanding the Range of Inhaled Uranium Ore Health Impacts?
Duration Pathology Exposure Risk Assessment Uranium Mine Site Ores
Acute Pulmonary TH1/2/17 Aspiration Hazard ID Carnotite/Tyayuminite(Vanadium)
Subacute, single dose Chronic Vascular Remodeling (Athero,
HTN)
Dose-Response Uraninite
Subacute/repeated Neuropathy—AD, neuroinflammation
Exposure Assessment Thucholite(pyrobitumen)
Chronic/repeated Fetal exposure/birth outcomes
Inhalation Risk Management Coffinite (Uranium Silicates)
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Steps in Risk Assessment:
o Hazard Identificationo Exposure Assessmento Dose-Response Assessmento Risk Characterization
Study Limitations, Next StepsLimitations:
● Fate and transportHow much contaminated dust is
the community actually exposedto?
Doses of mine dust administered tothe mice are much larger thananyone living near the mine wouldreceive.
Navajo residents have lived most oftheir lives near the site, receiving lowbut chronic doses over time.
The duration and extent of dustexposures are not well understood.On-site monitoring in 2017 willaddress these limitations.
Proposed next step: Mobile Laboratory
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The Long Drive . . .
Arrival at UNM Traffic in Blue Gap Tachee, AZ
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Claim 28
AirCARE1Laboratory
N
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FAPM 2.5
0.0
0.1
0.2
0.3
0.4
Mac
roph
age
Cel
ls (#
/ml)
*
FAPM 2.5
0.00
0.01
0.02
0.03
0.04
0.05
Neu
troph
ilic C
ells
(#/m
l) *
FAPM 2.5
0.0
0.5
1.0
1.5
Prot
ein
(mg/
ml)
Lung Inflammation: Pilot Study• Exposures to concentrated PM from the Blue Gap Tachee, AZ, region caused
increased levels of inflammatory cells in the lung• We will need to compare with PM2.5 from other regions
LRRI PM2.5
Time (min)
PM2.
5 (m
g/m
3 )
0 100 200 3000.00
0.05
0.10
0.15
0.20
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Overall Metals in PM from Completed Exposures, Spring 2018(Compared with Published PM Levels from Other Regions of the Planet)
Molybd
enum
Cadmium
Tung
sten
Lead
Uranium
Magne
sium
Aluminu
m
Vanad
ium Iron
Nickel
Coppe
rZinc
Arsenic
Seleniu
m0.001
0.01
0.1
1
10
100
1000
10000
100000Co
ncen
tratio
n (n
g/m
3 )
Measured Elements
Next Steps
• Move trailer to Laguna Pueblo– Jackpile mine is much larger and different ore type (uranium
silicates) for spring 2019– A “neutral” or unaffected site (TBD)– Other??
• Assay tissues• Complete wind dispersion modeling for SE Navajo region
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The Long Drive . . .
Leaving BGT, AZ Setting Up in Paguate, NM
Current Location in Paguate, NM
Jackpile mine
St. Anthony’s mine
Paguate
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Interim Conclusions
• Dusts arising from uranium mine sites are more toxic thanbackground dusts– Toxicity is either due to metal contaminants or morphology of
PM• However, even at close ranges, metal-contaminated dusts
do not seem to make up a substantial portion of the PM2.5that communities experience
• Metals data from Paguate, NM, will be very informative tofinalizing these conclusions
AcknowledgementsUNM College of PharmacyJessica Begay, MSKatie Zychowski, PhDMolly Harmon, PhDAbigail WheelerBethany SanchezSelita LucasMario Aragon, PhDBarry Bleske, PharmDGuy HerbertNitesh Kunda, PhDPavan Muttil, PhDChristina Tyler, PhDTamara YoungLauren Topper, PhDYoselin SuarezMarcus GarciaRaul SalazarBryan Villalva
Virginia Commonwealth UniversityAndrew Ottens, PhDEkaterina Mostovenko, PhDPretal Muldoon, PhD
UNM: CEHPJohnnye Lewis, PhDDebra MacKenzie, PhDEzter Erdei, PhDCarolyn Roman, PhD
Southwest Research and Information CenterChris Shuey, MPHPaul RobinsonSandy RamoneTeddy NezSarah Adiky
UNM Main Campus Jose Cerrato, PhD Adrian Brearley, PhD Sumant Avasarala, PhD Jorge Gonzalez, PhD Eliane El Hayek, PhD Johanna Blake, PhD Abdul-Mehdi Ali, PhD
Navajo Nation Partners Floyd Baldwin Jr.Triva ShirleySadie BillChris NezAaron Yazzie
Laguna Pueblo Partners Greg JojolaKyle SwimmerPat Pruitt
UTEP/OHSUHector Olvera, PhD
Funding P42 ES025589 R01 ES026673
NIOSHVamsi Kodali, PhDAaron Erdely, PhD
Michigan StateJim Wagner, PhDJack Harkema, PhDMasako Morishita, PhDRyan Lewandowski
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