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Bioaccesibility of nano- and micron-sized metallic particles in simulated lung systems

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

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Bioaccesibility of nano- and micron-sized metallic particles in simulated lung systems

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

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

  6. 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). Can bioaccessibility data (metal release) reflect the toxic effect of metallic particles? Metal release Cultivated lung cells

  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 solutionpH 7.4 (neutral) simulates a normal health condition within the lung • Other simulated biological media: • PBS (phosphate buffered saline) pH 7.2 - 7.4Artificial SweatpH 6.5Artificial gastrid fluidpH 1.6

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

  9. 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). The type of material influences metal release from particles 17Cr11Ni3Mo stainless steel Cu-materials passive! pure/oxide/product! Gamble’s (168h) Gamble’s (48h), note log-axis!

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

  11. Increasing particle size 50 µm < 4 µm Decreasing surface area 0.07 m2/g 0.7 m2/g The particle size influences the metal release process. Metal releaseincreases with decreasing particle size mainly due to a larger surface area. The particle size influences metal release from particles Fe >> Cr, Ni

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

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