Institute of Epidemiology Epidemiological Evidence for Health Effects of Nanoparticles H.-Erich Wichmann GSF – Institute of Epidemiology LMU – University

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


ContentContent

Ambient concentrations Ambient concentrations Respiratory effectsRespiratory effects Cardiovascular effectsCardiovascular effects SummarySummary


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


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


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


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


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


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


Standort AugsburgBourges-Platz (LfU)

Kloster (GSF)

FH

AerosolmessstationAugsburg

Basismodul Ausbaumodul


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


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


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


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


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)


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


Particulate matter was associated with Particulate matter was associated with mortalitymortality

WHO , 1997


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.


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


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


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


Lung function reduction in Lung function reduction in asthmatic adultsasthmatic adults

Peters et al. , 1997


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)


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)


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


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


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


-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


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


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


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


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

Documents

Institute of Epidemiology Epidemiological Evidence for Health Effects of Nanoparticles H.-Erich Wichmann GSF – Institute of Epidemiology LMU – University