Institute of Epidemiology
Epidemiological Evidence for Epidemiological Evidence for Health Effects of NanoparticlesHealth Effects of Nanoparticles
H.-Erich WichmannH.-Erich Wichmann
GSF – Institute of EpidemiologyGSF – Institute of EpidemiologyLMU – University of Munich, GermanyLMU – University of Munich, Germany
Conference Matform 2004 - Potentials and risks of Conference Matform 2004 - Potentials and risks of nanoscale materials. University of Augsburgnanoscale materials. University of Augsburg
20-21 September 200420-21 September 2004
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ContentContent
Ambient concentrations Ambient concentrations Respiratory effectsRespiratory effects Cardiovascular effectsCardiovascular effects SummarySummary
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Abbreviations:Abbreviations:
PMPM1010 fine and coarse particlesfine and coarse particles (mass) (mass) < 10 < 10 mm
FPFP fine particlesfine particles (mass)(mass) < 2.5 < 2.5 mm
UP UP ultrafine particlesultrafine particles (number)(number) < 0.1 < 0.1 mm
UP = nanoparticlesUP = nanoparticles
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diameter [µm]
0.01 0.1 1
number density [104 cm-3]
0
1
2
3
4
5 1991/921995/961996/971997/981998/991999/20002000/01
Particle distribution in Erfurt Particle distribution in Erfurt
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Simplified model of the coagulation dynamics in Erfurt from 1980 to 2000: In 1980, large particles have been in the air, which effectively scavenged the ultrafine particles, leading to a short halflife of UP. In 2000, mainly very small particles are in the air. They coagulate much slower and the coagulation product still are UP. In total, in the year 2000 the halflife of UP is clearly longer than in the year 1980, i.e. the measured ambient concentration of UP increases.
coagulation
0.01 0.1 1 um 0.02 0.1 1 um
1980
1990
2000
0.01 0.1 um 0.02 0.1 um
0.01 um 0.02 um
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Zhu et al (2002)
Relative particle number, BC, CO concentrations Relative particle number, BC, CO concentrations versus distance from the 710 freewayversus distance from the 710 freeway
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Day of week pattern of UPDay of week pattern of UP
% Deviationfrom mean
-40
-35
-30
-25
-20
-15
-10
-5
0
5
10
15
20
Day of WeekMon Tue Wed Thu Fri Sat Sun
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Diurnal pattern for particle number (NCDiurnal pattern for particle number (NC0.01-2.50.01-2.5) and mass (MC) and mass (MC
0.01-2.50.01-2.5) concentration in 1997, ) concentration in 1997,
showing weekends and weekdays separatelyshowing weekends and weekdays separately
0.0E+00
5.0E+03
1.0E+04
1.5E+04
2.0E+04
2.5E+04
3.0E+04
0.00 4.00 8.00 12.00 16.00 20.00 24.00
hours
NC
0.0
1_2
.5 (
1/c
m3 )
0
5
10
15
20
25
30
MC
0.0
1_2
.5 (µ
g/m
3 )
NC0.01_2.5 WEEKDAYS
NC0.01_2.5 WEEKEND
MC0.01_2.5 WEEKDAYS
MC0.01_2.5 WEEKEND
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Standort AugsburgBourges-Platz (LfU)
Kloster (GSF)
FH
AerosolmessstationAugsburg
Basismodul Ausbaumodul
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Kloster (GSF) vs. Bourges-Platz
0
10000
20000
30000
40000
50000
60000
70000
80000
11/12/00 12/12/00 13/12/00 14/12/00 15/12/00 16/12/00 17/12/00 18/12/00 19/12/00
pa
rtic
le n
um
be
r c
on
cn
etr
ati
on
[/c
m3
]
CPC at the GSF site
CPC at Bourgesplatz
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Physical characterization of particles in AugsburgPhysical characterization of particles in Augsburg
Item Unit
1a Number (volatile fraction)* d0 (1/cm3)
1b Number (non-volatile fraction)* d0 (1/cm3)
2 Total aerosol length d1 (mm/cm3)
3 Total aerosol Fuchs surface d2 (µm2/cm3)
4a Mass (volatile fraction)** d3 (µg/cm3)
4b Mass (non-volatile fraction)** d3 (µg/cm3)
* size distribution in the range 0.003 - 20 µm** PM2.5, PM10
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Chemical characterization of particles in AugsburgChemical characterization of particles in Augsburg
Item Unit
1 Sulphate (µg/m3)
1 Nitrate (µg/m3)
2 EC/OC (µg/m3)
3 Black Smoke (m-1)
4 Elemental composition* (ng/m3)
* optional
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Additional measurements in AugsburgAdditional measurements in Augsburg
Additional items Source
1 Meteorology (T, rH, p, Wind) GSF1 Meteorology (T, rH, p, Wind) DWD2 Gases (NO, NO2, CO, O3) LfU
3 PM10 LfU
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Ultrafine Particles at conventional workplacesUltrafine Particles at conventional workplaces
Fumes from hot processes (e.g. smelting Fumes from hot processes (e.g. smelting and refining metals; welding)and refining metals; welding)
Fumes from combustion processes (e.g. Fumes from combustion processes (e.g. diesel motor emissions, carbon black diesel motor emissions, carbon black manufacture)manufacture)
Bioaerosols (e.g. agriculture, Bioaerosols (e.g. agriculture, biotechnology)biotechnology)
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Who is susceptible and why?Who is susceptible and why?
System ic effectsAcute phase proteins
Cytokines
IschemiaArrhythmia
Local effectsInflam mation
Asthma AttacksAcute Bronchitis
Inhalation of am bient particles
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Particulate matter was associated with Particulate matter was associated with mortalitymortality
WHO , 1997
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Role of ultrafine particlesRole of ultrafine particles
Ultrafine particles are deposited in the Ultrafine particles are deposited in the alveolar region with high efficiency.alveolar region with high efficiency.
The large surface of ultrafine particles can The large surface of ultrafine particles can increase toxicity.increase toxicity.
Decreased phagocytosis allows enhanced Decreased phagocytosis allows enhanced interaction between ultrafine particles and interaction between ultrafine particles and the epithelium the epithelium
Ultrafine particles are dislocated from the Ultrafine particles are dislocated from the alveolar space and might therefore elicit alveolar space and might therefore elicit systemic effects. systemic effects.
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Mortality Study on ultrafine particlesMortality Study on ultrafine particles
Daily mortality counts were collected in Daily mortality counts were collected in Erfurt between summer 1995 and the end of Erfurt between summer 1995 and the end of 1998.1998.
Particle size distributions were measured Particle size distributions were measured with an aerosol spectrometer between 10 with an aerosol spectrometer between 10 nm and 2.5 µm.nm and 2.5 µm.
Ultrafine particles were only moderately Ultrafine particles were only moderately correlated with PMcorrelated with PM2.52.5..
WichmannWichmann et al. et al. HEI ReportHEI Report 20002000
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Wichmann et al. (2000)
Particle and Daily Mortality, 1995 to 1998, Erfurt
Single Fractions
Particle Fraction [nm]
30 50 100 500 1000 2500
Rel
ativ
e R
isk
1.00
1.05
1.10
1.15
Cumulative Effects
Particle Fraction [nm]
30 50 100 500 1000 2500
MCNC
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Regression results by cause of deathRegression results by cause of death
4 44 11 11 00 55 00 00
UP "PM2.5"
RR per interquartile range
0.90
0.95
1.00
1.05
1.11
1.16
1.22
1.28
total cv re other total cv re other
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Lung function reduction in Lung function reduction in asthmatic adultsasthmatic adults
Peters et al. , 1997
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Medication use increased in adult Medication use increased in adult asthmatics (Erfurt)asthmatics (Erfurt)
Ch
ang
e in
pre
vale
nce
[%
per
IQR
]
0
5
10
15
20
25
30
Beta-agonists Corticosteriods
UP FP PM10 UP FP PM10
52 subjects followed for 5 months during winter 96/97
von Klot et al. (2000)
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Potential mechanism leading to Potential mechanism leading to cardiovascular effectscardiovascular effects
Increased sympathetic activation and /or Increased sympathetic activation and /or withdrawal of parasympathetic tonewithdrawal of parasympathetic tone
Imbalance of sympathetic and Imbalance of sympathetic and parasympatetic controlparasympatetic control
Decreased heart rate variabilityDecreased heart rate variability Increased risk for cardiac events (alteration Increased risk for cardiac events (alteration
of myocardial substrate, increased of myocardial substrate, increased myocardial vulnerability)myocardial vulnerability)
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Particles and Myocardial InfarctionParticles and Myocardial Infarction in Augsburg in Augsburg
PM10
Primary MI Secondary MI Death
Ch
ang
e [%
]
-20
0
20
40
60
80
Particle number (estimated)
Primary MI Secondary MI DeathC
han
ge
[%]
-20
0
20
40
60
80
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Traffic and Onset of Myocardial Traffic and Onset of Myocardial Infarction in AugsburgInfarction in Augsburg
691 MI survivors of 691 MI survivors of the KORA MI the KORA MI Registry AugsburgRegistry Augsburg
Activities were Activities were recorded 4 days recorded 4 days before the eventbefore the event
Using a car, public Using a car, public transport or a transport or a bicycle might be a bicycle might be a risk factor for MIrisk factor for MI
Hours before MI
0 1 2 3 4
Od
ds
Rat
io
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
Peters et al. NEJM in pressPeters et al. NEJM in press
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Rochester Particle Center Study Rochester Particle Center Study in Erfurt, Germanyin Erfurt, Germany
Panel Study in 56 patients with coronary Panel Study in 56 patients with coronary artery disease (winter 2000/01)artery disease (winter 2000/01)
Panel Study in 37 patients with chronic Panel Study in 37 patients with chronic obstructive pulmonary disease (winter obstructive pulmonary disease (winter 2001/02)2001/02)
Blood biomarkers and EKG recordings at 12 Blood biomarkers and EKG recordings at 12 clinic visitsclinic visits
Central monitoring of ultrafine and Central monitoring of ultrafine and accumulation mode particles, PMaccumulation mode particles, PM2.52.5
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-30
-20
-10
0
10
20
30UFP ACP PM2.5
%ch
ang
e o
f av
erag
e H
F.N
N S
B
per
incr
ease
in IQ
R P
ollu
tan
t
0-24hrs 73-96hrs49-72hrs25-48hrs 97-120hrs 0-120hrs
Exposure to average concentrations of ambient air particlesconcurrent and prior to the 24 hr recording
Particle effects on normalized HF in ErfurtParticle effects on normalized HF in Erfurtspontaneous breathing, 5 min recordings spontaneous breathing, 5 min recordings
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Ultrafine Particle number, PMUltrafine Particle number, PM2.5 2.5 and Temperature and Temperature
(CAD panel, Erfurt, winter 2000/2001)(CAD panel, Erfurt, winter 2000/2001)U
FP
[n
/cm-
3 ]
0
10000
20000
30000
40000
50000
60000
UFP PM
2.5 [µ
g/m 3]
0
20
40
60
80
100
120
PM2.5
Air
Tem
per
atu
re [
°C]
-20
-10
0
10
20
Nov-00 Dec-00 Jan-01 Feb-01 Mar-01 Apr-01Oct-00
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Particle effects on T wave amplitude in Erfurt Particle effects on T wave amplitude in Erfurt spontaneous breathing, 5 min recordingsspontaneous breathing, 5 min recordings
-10
-8
-6
-4
-2
0
2
4Effects of 6h average Effects of 24h average
% c
han
ge o
f a
vera
ge T
wa
ve a
mp
litu
de
p
er i
ncrease
in
IQ
R p
oll
uta
nt
Ambient pollutant exposure: 6 hours and 24 hours average before the recording
UFP SO2PM2.5ACP NO2 COOC EC NO
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Particle effects on T wave complexity in Erfurt Particle effects on T wave complexity in Erfurt spontaneous breathing, 5 min recordingsspontaneous breathing, 5 min recordings
-10
-5
0
5
10
15
Effects of 6h average Effects of 24h average
% c
han
ge o
f av
era
ge T
wa
ve c
om
ple
xit
y
p
er i
ncrease
in
IQ
R p
oll
uta
nt
Ambient pollutant exposure: 6 hours and 24 hours average before the recording
UFP SO2PM2.5ACP NO2 COOC EC NO
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Summary Summary
Main ambient source of UP is automobile trafficMain ambient source of UP is automobile traffic Health effects of UP on respiratory and cardiovascular Health effects of UP on respiratory and cardiovascular
endpoints shown, but open questionsendpoints shown, but open questions Epidemiology on technically produced nanoparticles Epidemiology on technically produced nanoparticles
missing (work place and environment)missing (work place and environment) Epidemiology on UP from combustion may serve as Epidemiology on UP from combustion may serve as
model for nanoparticlesmodel for nanoparticles
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