1. Bioaccesibility of nano- and micron-sized metallic particles in simulated lung systems M.Sc. Lic. Eng. Klara Midander Inger Odnevall Wallinder, Jinshan Pan, Christofer Leygraf Div. Corrosion Science, Dept. Chemistry, KTH Hanna Karlsson, Pontus Cronholm Dept. Biosciences and Nutrition, KI MITF-seminar, Oct. 18, 2007

2. Particles in the society

3. Inhalation of airborne particles Combustion particle in lung alveolar Iron particle from subway Photo: Lennart Nilsson (dn.se, Chem. Res. Toxicol., Vol. 18, No. 1, 2005)

4. Me n+ Particles cause inflammation? Particles can form radicals  oxidize DNA (oxidative stress) 1952: ”The London Fog”  4000-12000 premature deaths 90ies: air pollution/particles  cardiovascular diseases, lung cancer High particle concentration in air  exacerbation of asthma Health effects of particles What causes toxicity? -material properties / released metal? -particle itself / surface reactivity? -is it possible to extrapolate toxicity from particle size?

5. Study of particle toxicity Exposure of cultivated lung cells to particles DNA damage comet assay (single cell gel electrophoresis) Subway particles Combustion particles (wood and pellets) Particles from tires Commersial nanoparticles street subway Composition of subway particles (SEM-EDS) Karlsson et al., Chem. Res. Toxicol., Vol. 18, No. 1, 2005)

6. Can bioaccessibility data (metal release) reflect the toxic effect of metallic particles? The metal release is influenced by particle size (surface area), shape, reactivity and material type (passive/non-passive, pure/ alloy/oxide) as well as the exposure environment (within the lung). Cultivated lung cells Metal release

7. Metal release studies of metallic particles in-vitro Simulated lung conditions: ALF (artificial lysosomal fluid) pH 4.5 - 5 (agressive) simulate conditions following an immunologic reaction in the body Gamble’s solution pH 7.4 (neutral) simulates a normal health condition within the lung Other simulated biological media: PBS (phosphate buffered saline) pH 7.2 - 7.4 Artificial Sweat pH 6.5 Artificial gastrid fluid pH 1.6

8. Experimental procedure Exposure: 37  C, darkness, gentle agitation, 10 min - 1 week Separation: centrifugation, 3000 rpm, 10 min Analysis: Atomic Absorption Spectroscopy – graphite furnace

9. The type of material influences metal release from particles The type of material strongly influences metal release from particles. Chemical and compositional material properties are crucial for the metal release mechanism (chemical dissolution and/or corrosion process). Gamble’s (168h)Gamble’s (48h), note log-axis! 17Cr11Ni3Mo stainless steelCu-materials passive! pure/oxide/product!

10. The environment influences metal release from particles The metal release rate increases with decreasing pH of the test media. At comparable pH, the release rate may vary due to different composition of the test media.

11. The particle size influences metal release from particles Fe >> Cr, Ni The particle size influences the metal release process. Metal release increases with decreasing particle size mainly due to a larger surface area. Increasing particle size < 4 µm 50 µm Decreasing surface area 0.7 m 2 /g 0.07 m 2 /g

12. Sub-micron and nanosized metallic particles metals, alloys, metal compounds Particle /aerosol generation Surface reactivity Toxicology On-going cross-disciplinary research collaboration KTH KI SU Industry (REACH) Downstream users General public Legislators