1. Institute of Epidemiology Epidemiological Evidence for Health Effects of Nanoparticles H.-Erich Wichmann GSF – Institute of Epidemiology LMU – University of Munich, Germany Conference Matform 2004 - Potentials and risks of nanoscale materials. University of Augsburg 20-21 September 2004 20-21 September 2004

2. Institute of Epidemiology Content l Ambient concentrations l Respiratory effects l Cardiovascular effects l Summary

3. Institute of Epidemiology Abbreviations: PM 10 fine and coarse particles(mass) < 10  m FPfine particles(mass)< 2.5  m UP ultrafine particles(number)< 0.1  m UP = nanoparticles

4. Institute of Epidemiology Particle distribution in Erfurt

5. Institute of Epidemiology 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.

6. Institute of Epidemiology Zhu et al (2002) Relative particle number, BC, CO concentrations versus distance from the 710 freeway

7. Institute of Epidemiology Day of week pattern of UP % Deviation from mean -40 -35 -30 -25 -20 -15 -10 -5 0 5 10 15 20 Day of Week MonTueWedThuFriSatSun

8. Institute of Epidemiology Diurnal pattern for particle number (NC 0.01-2.5 ) and mass (MC 0.01-2.5 ) concentration in 1997, showing weekends and weekdays separately

9. Institute of Epidemiology Standort Augsburg Bourges-Platz (LfU) Kloster (GSF) FH Aerosolmessstation Augsburg Basismodul Ausbaumodul

10. Institute of Epidemiology Kloster (GSF) vs. Bourges-Platz

11. Institute of Epidemiology Physical characterization of particles in Augsburg

12. Institute of Epidemiology Chemical characterization of particles in Augsburg

13. Institute of Epidemiology Additional measurements in Augsburg

14. Institute of Epidemiology Ultrafine Particles at conventional workplaces l Fumes from hot processes (e.g. smelting and refining metals; welding) l Fumes from combustion processes (e.g. diesel motor emissions, carbon black manufacture) l Bioaerosols (e.g. agriculture, biotechnology)

15. Institute of Epidemiology Who is susceptible and why?

16. Institute of Epidemiology Particulate matter was associated with mortality WHO, 1997

17. Institute of Epidemiology Role of ultrafine particles l Ultrafine particles are deposited in the alveolar region with high efficiency. l The large surface of ultrafine particles can increase toxicity. l Decreased phagocytosis allows enhanced interaction between ultrafine particles and the epithelium l Ultrafine particles are dislocated from the alveolar space and might therefore elicit systemic effects.

18. Institute of Epidemiology Mortality Study on ultrafine particles l Daily mortality counts were collected in Erfurt between summer 1995 and the end of 1998. l Particle size distributions were measured with an aerosol spectrometer between 10 nm and 2.5 µm. l Ultrafine particles were only moderately correlated with PM 2.5. Wichmann et al. HEI Report 2000

19. Institute of Epidemiology Wichmann et al. (2000) Particle and Daily Mortality, 1995 to 1998, Erfurt

20. Institute of Epidemiology Regression results by cause of death

21. Institute of Epidemiology Lung function reduction in asthmatic adults Peters et al., 1997

22. Institute of Epidemiology Medication use increased in adult asthmatics (Erfurt) 52 subjects followed for 5 months during winter 96/97 von Klot et al. (2000)

23. Institute of Epidemiology Potential mechanism leading to cardiovascular effects l Increased sympathetic activation and /or withdrawal of parasympathetic tone l Imbalance of sympathetic and parasympatetic control l Decreased heart rate variability l Increased risk for cardiac events (alteration of myocardial substrate, increased myocardial vulnerability)

24. Institute of Epidemiology Particles and Myocardial Infarction in Augsburg

25. Institute of Epidemiology Traffic and Onset of Myocardial Infarction in Augsburg l 691 MI survivors of the KORA MI Registry Augsburg l Activities were recorded 4 days before the event l Using a car, public transport or a bicycle might be a risk factor for MI Peters et al. NEJM in press

26. Institute of Epidemiology Rochester Particle Center Study in Erfurt, Germany l Panel Study in 56 patients with coronary artery disease (winter 2000/01) l Panel Study in 37 patients with chronic obstructive pulmonary disease (winter 2001/02) l Blood biomarkers and EKG recordings at 12 clinic visits l Central monitoring of ultrafine and accumulation mode particles, PM 2.5

27. Institute of Epidemiology Particle effects on normalized HF in Erfurt spontaneous breathing, 5 min recordings

28. Institute of Epidemiology Ultrafine Particle number, PM 2.5 and Temperature (CAD panel, Erfurt, winter 2000/2001)

29. Institute of Epidemiology Particle effects on T wave amplitude in Erfurt spontaneous breathing, 5 min recordings

30. Institute of Epidemiology Particle effects on T wave complexity in Erfurt spontaneous breathing, 5 min recordings

31. Institute of Epidemiology Summary l Main ambient source of UP is automobile traffic l Health effects of UP on respiratory and cardiovascular endpoints shown, but open questions l Epidemiology on technically produced nanoparticles missing (work place and environment) l Epidemiology on UP from combustion may serve as model for nanoparticles