PowerPoint Presentation | US EPA ARCHIVE DOCUMENT · Organization EPA Airborne Particulate Matter Center, Univ. of Rochester Source Specific Health Effects of Ultrafine/Fine Particles

OrganizationEPA Airborne Particulate Matter Center, Univ. of Rochester

Source Specific Health Effects of Ultrafine/Fine Particles

Administrative CoreG.Oberdörster (Dir.) Mike Terry (Asst. Dir. Adm.)M. Utell (Co-Dir.) Judy Havalack (Adm. Asst.)

Consortia:Clarkson Univ. (Potsdam, NY);

UC-San DiegoGSF (Germany)

Scientific Advisory Committee

Executive CommitteeP.I’s of Research Cores

Scientific Info + Coordinationwith other PM Centers, EPA,

and other outside collaborating institutions

Research Cores Facility Cores

Exposure

Cardiovasc. EffectsSusceptible populationsEpidemilogy/Clinical

MechanismsAnimal models of

susceptibilityIn vitro models

Characterization &Source Apportionment

P.Hopke/K. Prather

BiostatisticsD. Oakes

Vascular & Inflammation

R. Phipps

PilotProjects

Epidemiology StudiesRisk Factors

A. Peters/ H-E. Wichmann

Clinical StudiesSusceptible Populations

M.Frampton/M. Utell

Animal ModelsG.Oberdörster/A. Elder

In vitro StudiesMolecular Mechanisms

J. Finkelstein

Aerosol Generation & Analysis

P.Hopke/R.Gelein

CardiacW. Zareba

Sources

Enrichment Programs:Seminars, EducationCommunity Outreach

Visiting Scientists

Figure 3.1

SOURCES OF FINE PM

Vapor(coating)

CoagulationNuclei Mode(UFP)

Accumulation Mode(AMP)

Inhalation

Respiratory Tract Deposition

UFP AMPpartial AMPdeaggregation and dissolution

CNS (neurodegeneration)

Translocation of UFP from NP and TB region along sensory neurons to CNS; ANS ganglia

Translocation of UFP to interstitium, capillaries, heart (direct effects)

Alveolar inflammation

Translocation tobone marrow:precursor cell effects (megakaryocytes, EPC)

Uptake by endothelium; platelets

Activation/interaction of endothelial cells, platelets and leukocytes

Increased coagulabilitythrombus formation

Plaque rupture

Cardiac eventsStroke

Acceleration of atherosclerosis

ECGmodification

Endothelial dysfunction,vasoconstriction

Release of EMP, PMP,cytokines

EMP - endothelial microparticlesPMP - platelet microparticlesEPC - endothelial precursor cellsANS - autonomic nervous systemCNS - central nervous systemTB - tracheobronchialNP - nasopharyngeal

SOURCES OF FINE PM

Vapor(coating)



Inhalation











Plaque rupture



ECGmodification




SOURCES OF FINE PM

Vapor(coating)



Inhalation











Plaque rupture



ECGmodification




SOURCES OF FINE PM

Vapor(coating)



Inhalation











Plaque rupture



ECGmodification




SOURCES OF FINE PM

Vapor(coating)



Inhalation











Plaque rupture



ECGmodification




SOURCES OF FINE PM

Vapor(coating)



Inhalation











Plaque rupture



ECGmodification




Research Core 1: Characterization of Particle-Bound ROS

Specific Aims• Aim #1. To understand the evolution of ambient

particle compositions as they are transported from the sources to the receptor site with particular emphasis on the concentrations of particle-bound reactive oxidative species.

• Aim #2. To develop methods to characterize the sources and nature of reactive oxidative species associated with the ambient PM2.5 and PM0.1 particle aerosol using high resolution EPR and LC/MS.

Characterization of Particle-Bound ROS

Rubidoux July 2003 NYC January 2004

1 10 100 10000

5

10

15

20

25

30PALAS fresh 41nmPALAS aged 41nmSevacarb 300nmPrintex-90 14nmSterling-V 70nmC-13 42nmCB+25% Fe 40nmCB Nanotubes SWNT

Noncellular ROS Summary (Carbon Particles)Particle Mass Correlation

ug

Equi

vale

nt H

2O2 c

onc.

(µM

)

1 10 100 10000

5

10

15

20

25

30

PALAS fresh 700m2/gPALAS aged 700m2/gSevacarb 7m2/gPrintex-90 300m2/gSterling-V 37m2/gC -13 ~700m2/gCB+25% Fe ~700m2/g

Noncellular ROS Summary (Carbon Particles)Particle Surface Area Correlation

cm2

Equi

vale

nt H

2O2 c

onc.

(µM

)

Research Core 2 –Epidemiological Studies

• Panel studies in potentially susceptible subgroups– Diabetics– Myocardial infarction survivors– Genetically predisposed subjects

• Associations between sources of fine and ultrafine particles and inflammation and endothelial dysfunction

• ECG-sub-study assessing associations between personal particle exposures, stress and cardiac function

Ultrafine particles Ultrafine particles and and cardiac cardiac readmission readmission in in myocardial infarction myocardial infarction

survivorssurvivors

Klot et al. Circulation 2005

A B H R S pooledRat

e R

atio

[per

10

000/

cm³]

0,9

1,0

1,1

1,2

1,3

Core 2 Studies

Cardiac Rehabilitation (Rochester) N=80

Diabetes/Myocardial Infarction (Augsburg) N=100/100

Inflammatory/Detoxification Polymorphisms/Controls (Augsburg) N=100/100

Air Monitoring

Criteria pollutants (PM2.5, SO2, CO, O3) Criteria pollutants (PM2.5, SO2, CO, O3) Criteria pollutants (PM2.5, SO2, CO, O3) Particle size distribution Particle size distribution Particle size distribution Particle composition (STN Network site) Volatile particle distributions Volatile particle distributions Indoor particle number Sulfates, Nitrates Sulfates, Nitrates

EC/OC EC/OC Surface area Surface area

Measurements Symptoms Symptoms Symptoms ECG ECG ECG BP & HR, rest & exercise BP, HR BP, HR Blood biomarkers Glycosylated hemogloblin Glycosylated hemogloblin

Genetic polymorphisms Genetic polymorphisms Blood biomarkers Blood biomarkers Endothelial dysfunction Endothelial dysfunction

Research Core 3: Human Exposures Objectives

Effects of inhaled ambient UFP in healthy and diabetic subjects:

• Blood coagulation via effects on platelets and circulating microparticles

• Cardiac output• Cardiac rhythm and repolarization• Role of reactive oxygen species• Antioxidant prevention• Comparison to carbon particles

Human Studies of Exposure to Carbon UFP

• Changes in leukocyte adhesion molecule expression

• Reduction in DLCO• Reduced brachial flow-mediated vasodilatation• Suggests both pulmonary & systemic vascular

effects• Preliminary findings: effects in type 2 diabetics,

at rest• Implications for cardiovascular disease

HUMAN EXPOSURE FACILITY

MRBx-Inhalation FacilityK

e n d r i c k R o a d

A

B

C

D

EF

GH

IJ

K

Human UFP Exposure

AnimalUFP Exposure

UF Concentrator

y

0 10000 20000 30000 40000 50000 60000 70000 800000

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

65000

70000

75000

12PM 3PM 6PM 9PM 12AM 3AM 6AM 9AM

Time (sec)

part

icle

s / c

mPa

rtic

les/

cm3

Particle Number Concentrations on Kendrick Road

(CPC counts, Mean of 4 days and nights)

Noon Midnight

Research Core 4: Animal ModelsResearch Core 4: Animal Models

Focus on: Cardiovascular Disease; CNS injury; particle biokinetics

• Exposures of diabetic rats (JCR): Concentrated UFP exposures (acute/subchronic)

On-road exposures (truck study)

Intratracheal microspray exposures to UF/Fine PM(different sites and sources)

– PM physico-chemical analyses and ROS measurements

– pulmonary and cardiovascular endpoints (inflammatory; oxidative stress, acute phase proteins,microparticles, ECG analyses)

– impact of: ultra-low sulfur fuel (less nucleation, NPs); after device (filter) + NOx catalyst

• Translocation and clearance kinetics of model and ambient UF/Fine PM(heart; platelets; bone marrow; spleen; brain)

– model particles: gold (TEM; ICPMS); 13C UFP

– neutron activation of UF/Fine PM: GeLi detector analysis; organ retention kinetics

• Neurotoxic effects of UF/Fine PM, rats and mouse model of neurodegeneration

– MPTP model; mitochondrial effects (electron transport chain function and activities;membrane potential; ROS production)

University of Minnesota Mobile Emissions Laboratory (MEL)

air-conditionedcompartment

Year 1 Year 2exhaust intake

MEL 6 hr exposure of rats on Rochester-Buffalo Thruway:

Aerosol and Atmospheric CharacteristicsAtmospheric Monitoring Data, in truck

Plume number concentration 1.6-4.3 x 106

particles/cm 3

Exposure cage number concentration 1.3-7.6 x 105 particles/cm3

NO 0.95-1.85 ppmNO2 0.05-0.15 ppmElemental carbon concentration 0-2.7 µg/m3

Organic carbon concentration 7.1-12.9 µg/m3

CO2 485-581 ppmCO 3.1-6.4 ppmParticle size (DGN) 13-19 nm

Filtered air controls (n ) <4.5 x 103 particles/cm3

Chamber temperature 19-27 ºC

Atmospheric Conditions, outsideOutside temperature (high) 10-23 ºCWind speed 3-12 mph

TNF-α and TNF-α Receptor I Gene Expressionin 21 month-old Rats Exposed for 1 Day in MEL

Lung Tissue

0

1

2

3

4

5Heart Tissue

0

1

2

3

4

5 Olfactory Bulb Tissue

0

1

2

3

4

5

Saline + Filtered AirSaline + ExhaustLPS + Filtered Air

Virus + Filtered AirVirus + Exhaust

LPS + Exhaust

Saline + Filtered AirSaline + ExhaustLPS + Filtered Air

Virus + Filtered AirVirus + Exhaust

LPS + Exhaust

Rel

ativ

e In

crea

se o

ver

Con

trol

TNF-α Receptor TNF-α Receptor TNF-α Receptor

Research Core 5: In vitro StudiesResearch Core 1

Aerosol Generationand Analysis Core

Research Core 2 Epidemiology

Research Core 3 Clinical Studies

Aim 1: ROS generationactivation of gene expressionepithelial cells microvascular

endothelial cells

Aim 5: Source dependent induction of oxidant gene

expression

Ultrafine/Fine PMLaboratory generatedConcentrated Ambient

Source Specific Aim 2: microvascular endothelium activation by PM or cytokines release

of microparticles; apoptosis

Aim 3: Altered response in aged and /or diabetic animalssensitivity to oxidant stress

Research Core 4Animal Studies

Aim 4: gene expression bone marrow precursors

neuronal cell model systems.

Vascular /Inflammation Core

Ambient UF PM stimulation of IL-6 ExpressionEndothelial and Epithelial Response (4,7ug/cm2): Source effects

0

20

40

60

80

100

120

140

160

UTAHSEATTLEPHOENIXSTERLING FORESTSOUTH BRONXHUNTER COLLEGEHETTSTETTZERBST

pg/m

l

0

100

200

300

400

500

Endothelium Epithelium

INTEGRATION OF PARALLEL AND SEQUENTIAL STUDIES

Panel Studiesdiabetes; MI;

genetic susceptibility

Clinical Studiesdiabetes

Animal StudiesDiabetic rats

(acute - subchronic)

Urban Ultrafine/fine PM(Augsburg, Rochester)(ambient concentrations)

Urban Ultrafine/fine PM(Rochester)

(ultrafine/fine concentrator)

On-road Ultrafine/fine PM(highway, NY)

(ambient concentrations)

Other ultrafine/fine PM sources

powerplants, road tunnel, toll plaza, roadside?

Chemistry, oxidativecapacity, OC/EC

deaggregation

Filter Samples

S o u r c e s

In vitro Studiesdose-response;

ranking; oxidative stress

Animal Studies

Correlating PM size, reactivity, chemistry and sources with effects

Sim

ilar B

iolo

gica

l End

poin

ts —

Rea

l Tim

e PM

Siz

e M

easu

rem

ents

Selected filter

samples

Model Particles

Input for EPA decision-makingHuman extrapolation; risk assessment; evaluation of PM standards

Concentrated Ultrafine Particles, Rochester Exposure FacilityFMPS display

5.610244287

178365560

Start + 48:00

pConcentration (#/cm³)

Par

ticle

Siz

e (n

m)

0 1e4 2e4 3e4 4e4 5e4 6e4 7e4 8e4 9e4 1e5 1.1e5 1.27e5

1510

7:11:50 AM 7:20:50 AM 7:30:50 AM 7:40:50 AM 7:50:50 AM 8:00:50 AM 8:10:50 AM

Time

CH1 CH2

Fast Scan Array of Particle Size distribution

Fast Scan Array of Particle Size distribution

Documents

PowerPoint Presentation | US EPA ARCHIVE DOCUMENT · Organization EPA Airborne Particulate Matter Center, Univ. of Rochester Source Specific Health Effects of Ultrafine/Fine Particles