bioaccesibility of nano- and micron-sized metallic particles in simulated lung systems m.sc. lic....
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Bioaccesibility of nano- and micron-sized metallic particles in simulated lung systems
M.Sc. Lic. Eng. Klara MidanderInger 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
Particles in the society
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)
Men+
Men+
Men+
Men+
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?
Study of particle toxicity
Exposure of cultivated Exposure of cultivated lung cells to particleslung cells to particles
DNA damageDNA damagecomet assaycomet assay(single cell gel electrophoresis)(single cell gel electrophoresis)
Subway particlesCombustion particles (wood and pellets)Particles from tiresCommersial nanoparticles
street
subwayComposition of subway particles
(SEM-EDS)
Karlsson et al., Chem. Res. Toxicol., Vol. 18, No. 1, 2005)
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
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 lungOther simulated biological media:
PBS (phosphate buffered saline) pH 7.2 - 7.4
Artificial Sweat pH 6.5 Artificial gastrid fluid pH 1.6
Experimental procedure
Exposure:37C, darkness, gentle agitation, 10 min - 1 week
Separation:centrifugation,
3000 rpm, 10 min
Analysis:Atomic Absorption
Spectroscopy – graphite furnace
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 steel Cu-materials
passive!
pure/oxide/product!
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 differentcomposition of the test media.
The particle size influences metal release from particles
Fe >> Cr, Ni
The particle size influences the metal release process. Metal releaseincreases with decreasing particle size mainly due to a larger surface area.
Increasing particle size
< 4 µm 50 µm
Decreasing surface area
0.7 m2/g 0.07 m2/g
Sub-micron and nanosized Sub-micron and nanosized metallic particlesmetallic particles
metals, alloys, metal compoundsmetals, alloys, metal compounds
Particle/aerosol
generationSurface
reactivity
Toxicology
On-going cross-disciplinary research collaboration
KTH KI SU
Industry (REACH)Industry (REACH)Downstream usersDownstream users
General General publicpublic
LegislatorsLegislators