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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
Combustion particle in lung alveolar
Iron particle from subway
Photo: Lennart Nilsson (dn.se, Chem. Res. Toxicol., Vol. 18, No. 1, 2005)
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 airexacerbation of asthma
Particles cause inflammation?Particles can form radicals oxidize DNA (oxidative stress)
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)
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?
Cultivated lung cells
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
Analysis:Atomic Absorption Spectroscopy – graphite furnace
Separation:centrifugation, 3000 rpm, 10 min
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
Gamble’s (48h), note log-axis!
At comparable pH, the release rate may vary due to differentcomposition of the test media.
The environment influences metal release from particles
< 4 µm
Decreasing surface area
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
KTH KI SU
Sub-micron and nanosized metallic particles
metals, alloys, metal compounds
Industry (REACH)Downstream users